A B ICCTF BSTRACTS

ICCTF
International Cognition and
Cancer Task Force Conference
March 15-17th, 2012
PARIS - FRANCE
A BSTRACTS B OOKLET
This event is supported by :
Espace Saint Martin
199 bis, rue Saint-Martin - 75003 Paris FRANCE
Phone : +33 (0)1 44 54 38 54
website : ww.espacesaintmartin.com
SUMMARY
EDITORIAL
p
3
PROGRAM ICCTF 2012
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4-6
ORAL COMMUNICATIONS :
- Plenary sessions ............................................................................. p
7 - 10
- Abstracts selected for an Oral Communication......................................... p
11 - 28
- Posters Session
Abstracts in alphabetical order..............................................
29 - 88
p
The Cognitive meeting in Paris has been organized in close collaboration with
the Canceropole Nord-Ouest :
•
•
•
Cancéropôle Nord-Ouest
1, avenue Oscar lambret - BP 90 005
59008 Lille Cedex
www.canceropole-nordouest.org
2
Florence Joly, medical oncologist, Centre François Baclesse
Hélène Castel-Gandolfo, biologist/researcher, Université de Rouen
Bénédicte Giffard, neuropsychologist, Université de Caen Basse Normandie
EDITORIAL
International Cognition and Cancer Task Force
In 2003, a multidisciplinary group of neuropsychologists, clinical and experimental
psychologists, neuroscientists, imaging experts, physicians and patient advocates
gathered in Banff (Canada) to participate in a workshop on cognition and cancer.
Subsequently, a second workshop was organized in Venice in October 2006 during
the 8th World Congress of Psycho-Oncology. The success of these two workshops led
to the formation of the International Cognition and Cancer Task Force (ICCTF). The
recognition of the expansion of the number of investigators involved in research in this
area during a third workshop, held in Amsterdam, lead to the decision to organize the
Cognition and Cancer Conference. The first of these was held in New York in 2010.
We are very pleased to welcome you to the 2012 conference in the beautiful city of
Paris.
Mission statement
The mission of the ICCTF is to advance our understanding of the impact of cancer and
cancer-related treatment on cognitive and behavioral functioning in adults with noncentral nervous system cancers. Members of the ICCTF conduct local, national and
international research to help elucidate the nature of the cognitive and neurobehavioral sequelae associated with cancer and cancer therapies, the mechanisms that underlie these changes in function, and interventions to prevent or manage these undesired
symptoms and/or their side effects.
Steering Committee members are:
Dr
Dr
Dr
Dr
Tim Ahles
Sanne Schagen
Janette Vardy
Jeffrey Wefel
Psychologist
Neuropsychologist
Medical Oncologist
Neuropsychologist
Memorial Sloan Kettering Cancer Center, New York
Netherlands Cancer Institute, Amsterdam
Sydney Cancer Centre, Australia
MD Anderson Cancer Center, Houston
The Advisory Board is comprised of:
Dr
Dr
Dr
Dr
Dr
Patricia Ganz
Ian Tannock
Jimmie Holland
Christina Meyers
Frits van Dam
Medical Oncologist
Medical Oncologist
Psychiatrist
Neuropsychologist
Psychologist
UCLA, Los Angeles
Princess Margaret Hospital, Toronto
Memorial Sloan Kettering Cancer Center, New York
MD Anderson Cancer Center, Houston
Netherlands Cancer Institute, Amsterdam
Conference Committee:
The ICCTF Cognition and Cancer conference has been organized by the Steering
committee members and Dr Florence Joly, Medical Oncologist from Caen, France.
We are indebted to the help received from Cancéropôle Nord-Ouest in France and
acknowledge the sponsorship that they have obtained.
3
ICCTF
International Cognition and
Cancer Task Force Conference
March 15-17th, 2012
PARIS - FRANCE
Scientific Agenda
Day One: Thursday 15th March 2012
1.00 - 2.00
REGISTRATION & COFFEE
2.00 - 2.30
Introduction and Welcome : Introduction to Cognition and Cancer
(Florence Joly)
PLENARY N°1
2.30 - 3.30
CHAIRS : TIM AHLES
The relationship between aging, cognition and cancer
(Arti Hurria)
3.30 - 4.00
Plenary N°1 Discussion
4.00 - 4.30
REFRESHMENT BREAK
4.30 - 5.30
Abstract Presentations
8.00
4
CHAIRS : BAUKE BUWALDA
4.30 - 4.50
Cognitive dysfunctions and cerebral plasticity in mice after chemotherapy : Influence of cognitive reserve in young and aged mice
(Martine Dubois)
4.50 - 5.10
The presence of cancer influences blood-brain barrier permeability to
docetaxel and cognitive function of mice
(Joanna Fardell)
5.10 - 5.30
 Corticosteroids impair glial progenitor function in the central nervous
system
(Jorg Dietrich)
Boat Cruise and dinner
http://www.melodyblues.com/uk/index.php
Day two: Friday 16th March 2012
PLENARY N°2
9.00 - 9.40
CHAIRS : ANDREW SAYKIN
Neuroimaging techniques : applications and pitfalls
(Michiel De Ruiter)
9.40 - 10.20
Neuroimaging Studies of the Post-Chemo Brain : an overview
(Daniel Silverman)
10.20 - 10.50
Plenary N°2 Discussion
10.50 - 11.20
REFRESHMENT BREAK
11.20 - 12.20
Abstract Presentations
CHAIRS : ANDREW SAYKIN
11.20 - 11.40

Longitudinal assessment of chemotherapy-induced structural
changes in cerebral white matter and its correlation with impaired cognitive functioning in breast cancer patients
(Sabine Deprez)
11.40 - 12.00
Effects of adjuvant chemotherapy for breast cancer on brain structure
more than 20 years post-treatment
(Vincent Koppelmans)
12.00 - 12.20
 Disrupted Large-Scale Functional Brain Networks in Breast Cancer
Survivors
(Shelli Kesler)
12.20 - 1.20
LUNCH
PLENARY N°3
1.20 - 2.20
CHAIRS : FLORENCE JOLY
Memory and Self: Theoretical Approaches and Implications for
Cancer Patients
(Francis Eustache and Bénédicte Giffard)
2.20 - 2.50
Plenary N°3 Discussion
2.50 - 4.40
Abstract Presentations
2.50 - 3.10
3.10 - 3.40
CHAIRS : JANETTE VARDY
Radiation-Induced Cognitive Impairment in Postmenopausal Female
Nonhuman Primates
(Mike Robbins)
REFRESHMENT BREAK
3.40 - 4.00
 Cognitive Complaints in Breast Cancer Patients: Associations with
Therapy and Cytokine Markers
(Patricia A. Ganz)
4.00 - 4.20
Longitudinal Assessment of Cognitive Changes Associated with Adjuvant treatment for Breast Cancer: The Impact of APOE and Smoking
(Tim A. Ahles)
4.20 - 4.40
Preliminary Evidence of a Genetic Association Between an Interleukin
6 Promoter Polymorphism and the Severity of Self-Reported Attentional
Fatigue
(John D. Merriman)
4.40 - 6.00
Poster Session (Wine and Cheese Provided)
5
Day three : Saturday 17th March 2012
PLENARY N°4
9.00 - 10.00
CHAIRS : JEFFREY WEFEL
Modern Approaches to Longitudinal Data Analysis
(Brent Small)
10.00 - 10.30
Plenary N°4 Discussion
10.30 - 11.50
Abstract Presentations
CHAIRS : JEFFREY WEFEL
10.30 - 10.50
 Study of the Cognitive Effects of Chemotherapy: How Choice of
Control Group Affects Outcome
(Barbara Collins)
10.50 - 11.10
 Effects of Co-morbid Disease on Pre-treatment Neurobehavioral
Functioning
(Sunita K. Patel)
11.10 - 11.30
Cognitive function in colorectal cancer patients: a longitudinal
prospective study
(Janette Vardy)
11.30 - 11.50
The Influence of Sleep on Cognition in Breast Cancer
(Sonia Ancoli-Israel)
11.50 - 1.30
POSTER SESSION AND LUNCH
PLENARY N°5
1.30 - 2.30
CHAIRS : SANNE SCHAGEN
Neuropsychology in everyday functioning
(David Loewenstein)
2.30 - 3.00
Plenary N°5 Discussion
3.00 - 3.20
Patient Advocate and discussion
3.20 - 4.20
Abstract Presentations
3.20 - 3.40
CHAIRS : SANNE SCHAGEN
Improving the Ecological Validity of Cognitive Assessments : Virtual
Reality Testing of Prospective Memory Following Chemotherapy Treatments for Breast Cancer
(Heather J. Green)
3.40 - 4.00
 Group Cognitive Rehabilitation for Cancer Survivors: Enhancing Cognitive Function and Quality of Life
(Heather J. Green)
4.00 - 4.20
A randomized trial of Cognitive Rehabilitation in Cancer Survivors
(Monique Cherrier)
4.20 - 4.30
6
Closing Comments
FLORENCE JOLY
PLENARY
SESSIONS
7
PLENARY N°1 (Thursday 15
th
March 2012 : 2.30 - 4.00)
The relationship between Aging, Cognition and Cancer
Arti HURRIA
Arti Hurria, MD ; Director, Cancer and Aging Research Program
Editor-in-Chief, Journal of Geriatric Oncology
City of Hope Comprehensive Cancer Center
1500 E. Duarte Road
Duarte, CA 91010
The loss of cognitive function is one of the most feared consequences of aging, potentially impacting an older adult’s
ability to live independently and their overall quality of life. Furthermore, cognitive decline is associated with emotional
and economic burden for the patient, the family, and the healthcare system. There is a dearth of literature regarding the
association of cancer and/or cancer therapeutics with the trajectory of cognitive aging, partly because of concerns that
a multitude of factors may affect cognitive function (in addition to cancer and cancer therapy). Hence, in the midst of
this complexity, the effect of cancer or cancer therapeutics may be diluted. However, these studies are especially critical, given the aging of the worldwide population and the association of cancer with aging. From 2000 to 2030, there is
a projected doubling of the number of individuals age 65 and older in the United States, secondary to the aging of the
baby boomer population and rises in life expectancy. Because cancer is a disease associated with aging, there will be a
67% increase in cancer incidence in adults age 65 and older during this time frame. Therefore, understanding the potential risks and benefits of cancer therapy in an older adult is paramount. In this session, we will review risk factors for
cognitive decline in older adults (including the role of genetics, comorbid medical conditions, and lifestyle activities) and
review the current level of evidence regarding cancer therapy and cognitive function in older adults. Gaps in knowledge
will be discussed, as well as strategies to help address these gaps.
Dr. Arti Hurria is a geriatrician and oncologist, focusing on care of the older patient with cancer. She completed a
geriatric fellowship in the Harvard Geriatric Fellowship Program, followed by a hematology-oncology fellowship at
Memorial Sloan-Kettering Cancer Center (MSKCC). She subsequently joined the faculty at MSKCC, where she served as co-Principal Investigator on the institutional NIH P20 grant “Development of an Aging and Cancer Center at
MSKCC.” In the fall of 2006, Dr. Hurria joined the City of Hope as Director of the Cancer and Aging Research Program.
Dr. Hurria is a cadre member of the Cancer and Leukemia Group B, Cancer in the Elderly Committee and is a recipient of the Paul Beeson Career Development Award in Aging Research (K23 AG026749-01) and American Society of
Clinical Oncology-Association of Specialty Professors-Junior Development Award in Geriatric Oncology. In 2010, she
was named Editor-in Chief of the Journal of Geriatric Oncology and chair of the NCCN Senior Adult Oncology Panel.
She serves as PI on a U13 grant in collaboration with the NIA and NCI to identify and develop research methodology
that will lead evidence based recommendations to improve clinical care for older adults with cancer. She also serves
as PI on an R01 funded grant evaluating clinical and biological predictors of chemotherapy toxicity in older adults with
breast cancer. These grants are executed in collaboration with members from the Cancer and Aging Research Group,
which Dr. Hurria founded and leads.
PLENARY N°2 (Friday 16
th
March 2012 : 9.00 - 10.50)
Neuroimaging techniques : applications and pitfalls
Michiel DE RUITER
Michiel de Ruiter, PhD, Fellow of the Dutch Cancer Society
The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital (NKI-AVL),
Department of Psychosocial Research and Epidemiology/Academic Medical Center,
University of Amsterdam, Department of Radiology, Amsterdam, the Netherlands
Neuroimaging techniques like magnetic resonance imaging (MRI) offer powerful tools to peek into the living brain. This
non-technical and non-exhaustive presentation will give some examples of applications of neuroimaging techniques within and outside the field of cancer and cognition. The rationale of functional methods (electroencephalography, positron
emission tomography and functional MRI) will be explained and subsequently the focus will be on various non-functional
MRI techniques. Pitfalls in acquiring, analysing and interpreting neuroimaging data will be discussed.
Dr. M.B (Michiel) de Ruiter is a psychologist trained in cognitive neuroscience. He obtained his PhD at the University
of Amsterdam in 2005. In 2007 and 2008 he carried out a pilot study into late neurotoxicity of high-dose chemotherapy in breast cancer survivors. In 2009 he obtained a 4 year personal development grant from the Dutch Cancer
Society to explore the applicability of neuroimaging methods in the study of cognitive dysfunction in cancer patients.
He is currently affiliated with the Netherlands Cancer Institute and the Academic Medical Center of the University of
Amsterdam. In the past, Dr. de Ruiter has investigated fundamental attention processes, pathological gambling and
dissociative tendencies with event-related brain potentials and functional MRI. He was a visiting scientist at the Uniformed Services University (USUHS) in Bethesda, USA, the Technical University of Dresden, Germany, the Max Planck
Institute in Cologne, Germany and the University of Oxford, UK.
8
PLENARY N°2 (Friday 16
th
March 2012 : 9.00 - 10.50)
Neuroimaging Studies of the Post-Chemo Brain : an overview
Daniel H.S. SILVERMAN
Daniel H.S. Silverman, M.D., Ph.D.*, Steven A. Castellon, Cheri L. Geist, Kelsey L. Pomykala, Patricia A. Ganz
David Geffen School of Medicine, University of California, Los Angeles
While a substantial proportion of patients who have undergone systemic therapy for cancer subsequently experience
cognitive difficulties that persist even after chemotherapy has been concluded, as documented by self-report and/or formal neuropsychological testing, the mechanisms and the specific neurologic substrates underlying these difficulties are
only beginning to be understood. Studies with brain tissue performed ex vivo, and non-human animal studies performed
in vivo can bring to bear a variety of methodologic approaches with which to provide a window to understanding regional
cerebral changes associated with chemotherapy, as well as potential mechanisms leading to those changes. There are,
however, substantial qualitative and quantitative differences between human and other animals with respect to both
cognition and functional neuroanatomy -- as well as between brain tissue in vivo and brain tissue ex vivo with respect to
many physiologic aspects -- which limit the precision with which these questions concerning human cognitive problems
can be addressed using any methods other than those suited for studying brain tissue in living humans as it is functioning. Electroencepalography (EEG) studies can in principle provide information about human cerebral function with high
temporal resolution, but spatial resolution is relatively poor, and the type of data yielded are inherently phenomenologic.
To date (and continuing into the forseeable future), the methods used to elucidate affected biochemistry and intracerebral structures at the level of human brain regions that provide the greatest spatial resolution at the lowest degree of
invasiveness, have involved applications of positron emission tomography (PET) and magnetic resonance (MR) imaging.
Following Dr. Ruiter’s presentation covering the basis and limitations of these imaging methods, this presentation will
focus on providing an overview of findings that have so far emerged concerning alterations that have been documented
in human brain chemistry and structure through application of a variety of PET and MR-based methods aimed at measuring processes such as regional cerebral metabolism and blood flow changes, changes in volumes of specific brain
regions, and disruptions of white matter integrity and functional connections between regions of human brain. Some
animal studies will also be considered, in the context of further illuminating the findings of the human-based studies
described above.
PLENARY N°3 (Friday 16
th
March 2012 : 1.20 - 2.50)
Memory and Self: Theoretical Approaches and Implications for Cancer Patients
Francis EUSTACHE and Bénédicte GIFFARD
Francis Eustache, Professor EPHE and Bénédicte Giffard, University lecturer
INSERM U1077 «Neuropsychology and functional neuroanatomy of Human memory»
Université de Caen-Basse/Normandie, France
Autobiographical memory (AM) refers to information and memories of personal life events, accumulated since childhood,
which enable the construction of a feeling of identity and continuity. AM retrieval is a dynamic and reconstructive process,
as mental representations change with the passage of time. This flexible aspect of memory is linked to one’s changing
self and aspirations over time, that evolve according to our personal status and environment.
Hence, any breakdown in the continuity of life involves a distortion of memory. Such distortions can be observed in
stress-related psychiatric disorders, such as major depression or post-traumatic stress disorder, where AM retrieval is
characterized by over-generality (i.e., the tendency to recall repeated events rather than specific events in response to
cue words).
Such memory disorders can be observed at different degrees in cancer patients. We will report studies focusing on such
psychiatric disorders and cancer, and will attempt to establish a relation with AM dysfunction. The better understanding
of such memory deficits will permit new pathophysiological hypotheses to emerge which could be tested in neuroimaging
studies.
Pr Francis Eustache is head of a neuropsychology and functional neuroimaging team working in Caen (France) within
an Inserm (Institut National de Santé et de la Recherche Médicale – National Health and Medical Research Institute),
EPHE (Ecole Pratique des Hautes Etudes) and UCBN (Université de Caen/Basse-Normandie) Unit. He is Director of
this research Unit (U1077), which is specialized in the study of the mechanisms of human memory functioning and
its disorders (Alzheimer’s disease, amnesic syndromes...) by implementing novel cognitive protocols and a range of
brain imaging and electrophysiological techniques.
Dr Bénédicte Giffard is a senior lecturer in neuropsychology at the University of Caen (France). She is affiliated with
the INSERM-EPHE-University of Caen unit (“Neuropsychology and functional neuroanatomy of Human memory”)
directed by Francis Eustache. Her researches focused on semantic memory and episodic memory in neurodegenerative diseases (Alzheimer’s disease, fronto-temporal dementia) and schizophrenia. Since a few years, she develops
projects on memory dysfunction in cancer patients with the collaboration of the Clinical research unit of Baclesse
Centre directed by Pr Florence Joly. These projects are conducted within the “Canceropole Nord-Ouest”.
9
PLENARY N°4 (Saturday 17
th
March 2012 : 9.00 - 10.30)
Modern Approaches to Longitudinal Data Analysis
Brent J. SMALL
Brent J. Small, PhD, Professeur, School of Aging Studies, University of South Florida.
Senior Member, Health Outcomes and Behavior Program, Moffitt Cancer Center
Senior Member, Biostatistical Resource Core, Moffitt Cancer Center
Longitudinal data is critical to our ability better understand how the diagnosis of cancer and subsequent treatment
impacts short-term and long-term cognitive functioning. However, traditional statistical methods, such as repeated
measures analysis of variance have important limitations, especially in cases of missing data and unequal spaced measurement intervals. The goal of this presentation is to provide a non-technical overview of modern methods of longitudinal
data analysis. In particular, the presentation will describe the advantages of random effects models of change, which
allow greater flexibility in the spacing of measurement occasions, as well as fewer penalties for missing data. Using this
method as a basis, an introduction to growth mixture models and latent change score models will be provided and the
potential application of these methods to the analysis of change in cognitive performance associated with cancer treatment will be highlighted. Throughout the presentation, the application of these methods to outcome data from cancer
survivors, as well as older adults will be presented and statistical code and resources will be discussed.
Dr. Small’s research examines cognitive performance among persons treated for cancer, as well as in normal aging
and preclinical Alzheimer’s disease. His recent work has shown that breast cancer survivors possessing the val allele
of the Catechol-O-Methyltransferase gene who were treated with chemotherapy were at greatest risk for cognitive
deficits. Dr. Small’s applied statistics research has focused on the use of advanced statistical techniques to longitudinal data. This includes the application of logistic and survival models, random effects models of change, growth
mixture models of change, and structural equation modeling. Dr. Small has been funded by the National Cancer
Institute and the National Institute on Aging and has authored more than 150 publications. Finally, Dr. Small serves
on the editorial boards of Aging, Neuropsychology and Cognition, Journal of Gerontology: Psychological Sciences,
and Psychology and Aging and is a member of the NIA-S, Social and Behavioral Science study section of the National
Institutes of Health.
PLENARY N°5 (Saturday 17
th
March 2012 : 1.30 - 3.00)
Neuropsychology in everyday functioning
David LOEWENSTEIN
David Loewenstein PhD Professor of Psychiatry and Behavioral
Sciences Miller School of Medicine,
University of Miami, Miami, Florida
Neuropsychological assessment plays an important role in the detection of deficits in areas such as memory, language,
attention, visuospational skills and executive function. However, there is increasing evidence that many commonly used
neuropsychological measures may lack ecological validity. Different aspects of ecological validity such as verisimilitude
and veridicality as it relates to optimal prediction of real-world functional outcomes will be examined. In addition, the
advantages and disadvantages of collateral informant judgments versus performance measures of functional performance in different clinical populations will be explored. Issues such as cognitive reserve, developing effective cognitive
stress tests and use of measures that capture real world impacts of remediation and other therapeutic interventions will
be discussed.
Dr. Loewenstein is Professor of Psychiatry and Behavioral Sciences at the Miller School of Medicine at the University
of Miami. Dr. Loewenstein has a number of research interests centering on the early detection of early cognitive
impairment in neurodegenerative and other brain disorders, development of novel cognitive and functional measures, examining relationships between neuropsychological measures and neuroimaging and other biomarkers of
early Alzheimer’s disease (AD) and other cognitive disorders. Further, Dr. Loewenstein and other investigators in his
laboratory have been involved in developing cognitive and functional interventions for normal elderly patients as well
as those with mild cognitive impairment (MCI) and early dementia.
Dr. Loewenstein has been Principal Investigator on several large NIH and state funded grants and has a number of
ongoing longitudinal investigations with new cognitive instruments developed in his laboratory. The Direct Assessment of Functional status Scale (DAFS) was one of the first performance-based scales for Alzheimer’s disease and
has been translated into multiple languages The scale has also been used in the study of schizophrenia and other
neurocognitive disorders. The Semantic Interference Test (SIT) and the Miami Semantic Memory Test (MSMT) have
shown considerable promise in the early detection and prediction of progression in patients with early Alzheimer’s
disease and other neurodegenerative disorders.
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ABSTRACTS SELECTED
FOR AN ORAL
COMMUNICATIONS
eligible for Young Investigator Awards
11
Thursday 15
th
March 2012
Oral Communications
1) Cognitive dysfunctions and cerebral plasticity in mice after chemotherapy: Influence of cognitive reserve in young and aged mice (Martine DUBOIS)
Authors: Martine Dubois 1, Nicolas Lapinte 1, Vincent Roy 2, Venceslas Villier
Pierrick Gandolfo 1, Florence Joly 3,4, Pascal Hilber 2 and Hélène Castel 1
, Tonon Marie Christine
2
,
1
Institutional Affiliations:
1
U982 Inserm, Laboratoire DC2N, Equipe Astrocyte et Niche Vasculaire, IFRMP 23, Université de Rouen, France;
2
EA 4306, Laboratoire PSY NCA, IFRMP 23, Université de Rouen, France;
3
Centre François Baclesse, Caen, France;
4
Centre Hospitalo-Universitaire, Caen, France.
E-mail of the corresponding author: [email protected]
Purpose: Evidence is emerging that cancer and treatments can induce cognitive impairments such as deficits of attention/concentration and memory, and psychomotor processing slowing, referred to as “chemofog” or “chemobrain”. The
objective of the current project is to explore the direct role of chemotherapy on cognitive disorders among elderly patients with treatment for a breast or colon cancer by means of young and aged mice models and to study the underlying
biological and physiological mechanisms.
Methods: We investigated the middle-term effects of a chronic administration of 5-Fluorouracil (5-FU) or a combination
of 5-FU/oxaliplatin in young and aged C57/Bl6 mice on cognitive functions and cerebral plasticity.
Results: 5-FU alone or in combination with oxaliplatin neither altered emotional reactivity, nor spatial learning and
memory performances, in young and aged mice. However, 5-FU-treated mice were impaired in a spatial cognitive flexibility-dependent task, and exhibited a hyper-reactivity to novelty. Moreover, 5-FU reduced the hippocampal neurogenesis,
and induced alteration of metabolic activity in selective brain regions, both in young and aged mice. Co-administration
of glucose with 5-FU alone or in combination with oxaliplatin, protected animals against chemotherapy-evoked cognitive
impairments and neurogenesis inhibition. In vitro, increasing concentrations of 5-FU and/or oxaliplatin evoked direct
neurotoxicity on neural stem cells (NSC). Quiescence induced by high glucose concentration likely protected NSC from
chemotherapy-induced death.
Conclusions: 5-FU provokes, at distance, selective impairment of behavioural flexibility and inhibitory control processes
in both young and aged mice. These deficits are associated to selective cerebral metabolic modifications, and may be
consecutive to the reduced number of adult generated hippocampal neurons. However, the age associated cognitive
declines may be responsible for a long-term chemotherapy-induced altered quality of life. The observed neuroprotective
role of co-administered glucose opens new clinical perspectives in the modality of chemotherapy administration.
NOTES
12
Thursday 15
th
March 2012
Oral Communications
2) The presence of cancer influences blood-brain barrier permeability to docetaxel
and cognitive function of mice ( Joanna FARDELL)
Authors : Joanna Fardell
, Ji Zhang 2, Raquel De Souza 2, Ian Johnston 1, Janette Vardy
1,3
, Micheline Piquette-Miller
3,4,5
2
Institutional Affiliations :
1
School of Psychology, The University of Sydney, Australia;
2
Faculty of Pharmacy, The University of Toronto, Canada;
3
Cancer Institute New South Wales, Australia;
4
Sydney Medical School, The University of Sydney, Australia;
5
Sydney Cancer Centre, Concord Repatriation General Hospital, Australia.
E-mail of the corresponding author : [email protected]
Purpose : A subset of cancer patients treated with adjuvant chemotherapy experience cognitive dysfunction long after
treatment completion. It is unclear how chemotherapy treatment and the presence of cancer interact to cause these
cognitive impairments. This study investigates the level of brain exposure to docetaxel (DTX) in the presence of cancer or
not, and the resultant effect on cognition. DTX is a substrate of the blood-brain barrier efflux transporters P-glycoprotein
(encoded by mdr1a) and MRP7. As such changes in these transporters were investigated.
Methods : Female C57BL/6 mice were inoculated with ID8 tumour cells (murine ovarian cancer cells), and then treated
at day 14 with a single injection of Taxotere (8mg/kg). Cognition was assessed 48h post-treatment using the Morris
water maze (MWM) and novel object recognition (NOR). Brain samples were collected 24h post treatment and post
cognitive-behavioural testing.
Results : There was a non-significant trend for ID8-DTX mice to perform worse than either ID8 or DTX alone and healthy untreated controls during MWM training. No differences were observed during MWM testing. There was a significant
effect of cancer on NOR with ID8 mice performing worse than mice without cancer (p<.05), and a significant interaction
between the presence of ID8 cancer and Taxotere (p<.05). As compared to healthy controls, mdr1a mRNA was significantly downregulated in the brains of ID8 tumor bearing mice (p<.05), while levels of mrp7 were unchanged post-behavioural testing. Accordingly, DTX accumulation in brain tended to be greater in ID8 mice (ID8: 7.1+/-0.9; controls:
3.4+/-1.9ng/g) at 24h post-treatment, no DTX was detected in-brain post-testing.
Conclusions : The presence of cancer increases the level of brain exposure to DTX. Further, this interaction has a negative impact on cognition. This suggests the level of brain exposure to chemotherapy may be instrumental in causing
subsequent cognitive impairment. These results have important implications for patients.
NOTES
13
Thursday 15
th
March 2012
Oral Communications
3) Corticosteroids impair glial progenitor function in the central nervous system
(Jörg DIETRICH)
Authors: Jörg Dietrich
, Yannis Kalogirou-Valtis 1, Ina Ly 1, Chris Proschel 3, David Scadden 1 & Margot Mayer-Proschel
1,2
3
Institutional Affiliations:
1
Center for Regenerative Medicine and Harvard Stem Cell Institute, Boston, MA, USA;
2
Massachusetts General Hospital Cancer Center, Division of Neuro-Oncology, Harvard Medical School, Boston, MA, USA;
3
Department of Biomedical Genetics, University of Rochester School of Medicine, Rochester, NY, USA.
E-mail of the corresponding author: [email protected]
Purpose: Corticosteroids have been used for decades in the treatment of cancer patients. Both short-term and longterm administration can be associated with neurotoxicity, such as cognitive decline, behavioral changes and brain atrophy. The cell-biological basis for such neurotoxicities has been poorly defined. While it is known that steroids may impair
neurogenesis, little is known of their effects on glia cells, the most abundant cell type in the central nervous system
(CNS). The purpose of the present study was to determine the effects of corticosteroids on self-renewal and differentiation of oligodendrocyte precursor cells (OPCs), the myelin forming cells of the CNS.
Methods: We used in vitro cell culture systems, clonal studies and in vivo mouse models to assess the effects of corticosteroids on glial progenitors and myelin forming cells of the CNS.
Results: Corticosteroid treatment was associated with a dose-dependent impairment of cell survival of OPCs and postmitotic oligodendrocytes. Clonal studies revealed that corticosteroids were shifting the balance between self-renewal
and differentiation towards progenitor cell differentiation. In vitro studies were predictive of in vivo studies showing
impairment of glial progenitor proliferation in subcortical white matter tracts of mice systemically exposed to corticosteroids. Impairment of progenitor cell proliferation was in part reversed by the powerful anti-oxidant N-Acetylcysteine,
suggesting a redox-dependent steroid effect on neural progenitor cells.
Conclusions: Given the critical importance of neural progenitor cells for endogenous repair mechanisms and myelin
maintenance, corticosteroid-associated glial progenitor cell function appears to be an important component of steroidinduced neurotoxicity. We further hypothesize that steroid-induced cognitive dysfunction could be explained by a combination of impaired neurogenesis and subcortical white matter dysfunction.
NOTES
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th
Oral Communications
March 2012
4) Longitudinal assessment of chemotherapy-induced structural changes in cerebral
white matter and its correlation with impaired cognitive functioning in breast cancer
patients (Sabine DEPREZ)
Authors :
S. Deprez 1, F. Amant 2, A. Smeets 2, R. Peeters 1, M-R. Christiaens
J. Vandenberghe 4 , M. Vandenbulcke 4 , S. Sunaert 1
2
, J. Verhoeven 1, A. Leemans
3
, W. Van hecke 1,
Institutional Affiliations :
Department of Radiology, University Hospital Gasthuisberg, K.U. Leuven, Leuven, Belgium;
2
Multidisciplinary Breast Center, University Hospital Gasthuisberg, K.U. Leuven, Belgium;
3
Image Sciences Institute, Department of Radiology, University Medical Center Utrecht, The Netherlands;
4
Department of psychiatry, University Hospital Gasthuisberg, K.U. Leuven.
1
E-mail of the corresponding author : [email protected]
Purpose : To uncover the neural substrate of cognitive impairment related to adjuvant chemotherapy, we studied cerebral white matter (WM) integrity before and after chemotherapy using magnetic resonance diffusion tensor imaging
(DTI) in combination with detailed cognitive assessment.
Methods : Thirty-four women with early-stage breast cancer exposed to chemotherapy underwent neuropsychological
testing and DTI before the start of chemotherapy (t1) and 4 months after treatment (t2). Sixteen patients not exposed
to chemotherapy, and 19 age-matched healthy controls underwent the same assessment at matched intervals. In all
groups, we used paired-T-tests to study changes in neuropsychological test scores and whole-brain voxel-based-paired-T-tests to study changes in WM fractional anisotropy (FA, a DTI-measure reflecting WM tissue organization), with
depression scores and IQ as included covariates. Changes of neuropsychological test scores were correlated with the
mean change of FA for regions that survived the paired-T-test in chemotherapy-treated patients.
Results : In contrast to controls, the chemotherapy-treated group performed significantly worse on attention tests,
psychomotor speed and memory at t2 compared to t1 (p<0.05). In the chemotherapy-treated patient group, we found
significant decreases of FA in frontal, parietal and occipital WM tracts after treatment (pFWE <0.05), whereas for both
control groups FA-values were the same between t1 and t2. Furthermore, performance changes in attention and verbal
memory correlated with mean regional FA changes in chemotherapy-treated patients (p<0.05).
NOTES
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March 2012
Oral Communications
5) Effects of adjuvant chemotherapy for breast cancer on brain structure more than
20 years post-treatment (Vincent KOPPELMANS)
Authors:
Vincent Koppelmans 1,2, MSc.; Michiel B. de Ruiter 2, PhD; Marius de Groot 3, MSc.; Willem Boogerd 4, MD, PhD; Caroline
Seynaeve 7, MD, PhD; Henri Vrooman 3, PhD; Aad van der Lugt 6, MD, PhD; Wiro J. Niessen 3, PhD; Monique M.B. Breteler
1
, MD, PhD; Sanne B. Schagen 2,*, PhD
Institutional affiliations:
1
Erasmus MC, University Medical Center, department of Epidemiology, Rotterdam, the Netherlands;
2
Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, department of Psychosocial Research & Epidemiology,
Amsterdam, the Netherlands;
3
Erasmus MC, University Medical Center, department of Medical Informatics;
4
Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, department of Neuro-oncology, Amsterdam, the
Netherlands;
5
Erasmus MC, University Medical Center, Daniel den Hoed Cancer Center, department of Medical Oncology, Family Cancer Clinic, Rotterdam, the Netherlands;
6
Erasmus MC, University Medical Center, department of Radiology, Rotterdam, the Netherlands.
* Corresponding author: email: [email protected]
Purpose: Adjuvant chemotherapy has been associated with cognitive dysfunction and brain structural changes up till
several years post-treatment. Not much is known about the potential long-term effects of adjuvant chemotherapy on
brain structure. We investigated whether adjuvant chemotherapy for breast cancer is associated with brain structure on
average 21 years post-treatment.
Methods: Female breast cancer survivors (n=187, mean age=64.2 years, sd=6.5) treated with adjuvant CMF (Cyclophosphamide-Methotrexate-Fluorouracil) chemotherapy were compared on several MRI measures with an age matched
population-based sample of women (n=374, mean age=64.2 years, sd=6.5) without a history of cancer. Survivors were
on average 21.2 years post-treatment (sd=4.4). Outcome measures of the MRI (1.5T) were total brain volume, gray and
white matter volume, hippocampal volume, focal gray matter volume, and focal and global white matter integrity. We
used voxel based morphometry to compare groups on focal gray matter volume. Focal and global white matter integrity
was examined using tract based spatial statistics.
Results: Chemotherapy-exposed survivors had significantly smaller total brain volume (-3.5 ml, p=.019) and gray matter volume (-2.9 ml, p=.003) than reference subjects. No significant differences were observed in white matter volume,
hippocampal volume, focal gray matter volume, or focal and global white matter integrity.
Discussion : This study shows that adjuvant CMF chemotherapy is associated with small reductions in overall gray
matter volume in the long term in the absence of focal gray matter reductions or deteriorated white matter integrity.
This is an important message for the survivor community as studies shortly after cessation of treatment have reported
larger adverse effects of standard- cytotoxic regimens on brain structure. Prospective studies are needed to confirm our
findings.
NOTES
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th
March 2012
Oral Communications
6) Disrupted Large-Scale Functional Brain Networks in Breast Cancer Survivors
(Shelli KESLER)
Authors : Shelli Kesler, PhD, Jennifer Bruno, PhD, Hadi Hosseini, PhD and Della Koovakkattu, MS
Institutional Affiliations :
Stanford University
E-mail of the corresponding author : [email protected]
Purpose : Breast cancer (BC) survivors often experience cognitive impairments, particularly following chemotherapy.
These women show regional brain impairments as well as reduced global brain efficiency evidenced by over-activation
of distributed regions. These deficits suggest potential disruption of large-scale brain networks. Therefore, we aimed to
examine the organization of functional brain networks following BC and chemotherapy.
Methods : We acquired functional magnetic resonance images during resting state from 34 chemotherapy-treated BC
survivors who were at least 6 months off-therapy and 27 age, education and IQ matched healthy females. We constructed a model of the intrinsic functional brain networks using coactivation patterns among 90 cortical and subcortical
regions. We then measured network properties using graph theory analyses controlled for psychiatric symptoms (depression, fatigue, anxiety) and menopausal status. We assessed cognitive function using standardized tests.
Results : Compared to controls, the BC group demonstrated decreased network clustering (p = 0.03) and path length
(p = 0.05) as well as a marginally significant decrease in small-worldness (p = 0.06), significantly decreased nodal
degree in frontal, temporal, caudate and amygdala regions (p < 0.05), fewer frontal and temporal integrative hubs and
reduced executive function (p = 0.02). Declarative memory and executive function were reduced in the breast cancer
group (p < 0.05). Higher executive function was associated with higher clustering (r2 = 0.42), path length (r2 = 0.43)
and small-worldness (r2 = 0.51) across the groups.
Conclusions : BC and/or chemotherapy may disrupt both local and global brain network properties such that specialized
regions subserving executive function, memory and emotion regulation, as well as their dynamic coordination for parallel
processing, are impaired. Certain network characteristics may represent biomarkers of deficits in executive function
skills. These results provide novel insights regarding the neurobiologic mechanisms of cognitive dysfunction in chemotherapy-treated breast cancer survivors.
NOTES
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th
Oral Communications
March 2012
7) Radiation-Induced Cognitive Impairment in Postmenopausal Female Nonhuman
Primates (Mike ROBBINS)
Authors: Mary Lou Voytko 1, Rhonda S. Murray 1, J. Daniel Bourland
, Mike E. Robbins
2,3
2,3
Institutional Affiliations:
Departments of Neurobiology & Anatomy 1 and Radiation Oncology 2, Brain Tumor Center of Excellence 3, Comprehensive
Cancer Center, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
E-mail of the corresponding author: [email protected]
Purpose : Although postmenopausal females usually have their hormonal therapy (HT) stopped when diagnosed with
breast or gynecological cancers, most older women diagnosed with other cancers continue HT. Thus, thousands of
female metastatic brain cancer patients receive fractionated partial or whole-brain irradiation (fWBI) each year, with or
without HT. Essentially no information is available regarding the cognitive effects of fWBI in postmenopausal females.
Using a cohort of cognitively trained, postmenopausal nonhuman primates (NHP) with or without HT, we conducted a
pilot project to start to test the hypothesis that HT will prevent/ameliorate fWBI-induced memory and attention deficits.
Methods : Six cognitively trained ovariectomized older female NHP (23-25 years) were divided into 3 groups; 2 shamirradiated + placebo, 2 fWBI (40 Gy; 5 Gy fractions 2/week for 4 weeks) + placebo (PL), and 2 fWBI + estrogen therapy
(ET); sham-irradiated NHPs were anesthetized 2/week for 4 weeks. Cognitive function was assessed monthly for 9
months after fWBI using the tasks of Delayed Match-to-Sample (DMS; visual memory), Delayed Response (DR; spatial
memory), and the Wisconsin Card Sort (WCS; executive function).
Results : Group differences were found on DMS at 1 m post-fWBI and on WSC at 6 m post-fWBI. In both tasks, monkeys receiving fWBI + placebo showed worse performance than the other groups. The differences in DMS resolved by 2
m post-fWBI but reappeared at the short delays at 4 m post-fWBI. There were no group differences on DR.
Conclusions : These findings suggest that, i] visual memory and executive function may be more sensitive to fWBI than
spatial memory in older female monkeys, and ii] ET may mitigate these harmful cognitive effects of fWBI. The older
female monkey represents a unique model in which to investigate the effects of fWBI + HT and other forms of therapy
in postmenopausal women.
NOTES
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th
March 2012
Oral Communications
8) Cognitive Complaints in Breast Cancer Patients: Associations with Therapy and
Cytokine Markers (Patricia GANZ)
Authors: P.A. Ganz, L. Kwan, S. A. Castellon, J.E. Bower, D.H.S. Silverman, M.R. Irwin, S.W. Cole.
Institutional Affiliations:
UCLA Schools of Medicine & Public Health, Jonsson Comprehensive Cancer Center, and Cousins Center for Psychoneuroimmunology, University of California, Los Angeles, CA, USA.
E-mail of the corresponding author: [email protected]
Purpose: Breast cancer (BC) patients commonly have cognitive complaints (CC) after completing initial therapy. We
prospectively studied stage 0-IIIA BC patients, beginning post-initial therapy and before endocrine treatment, and present their baseline data here.
Methods: BC patients ≤65 y.o. without neurologic conditions, uncontrolled depression, diabetes, or inflammatory conditions, were recruited and assessed for self-reported QOL, fatigue, CC, mood; 120 minute neuropsychologic (NP) testing;
blood for genotyping, plasma cytokines. CC assessed with Patient’s Assessment of Own Functioning Inventory (PAOFI)
subscales for memory (M) and executive function (EF), dichotomized into low-complainer and high-complainer groups.
Results: N=190, mean age 51.8 years, 6.6 months since diagnosis, 1.2 months post-treatment, 52% college graduates,
65% early stage (0 or I); 74% received radiation (55% of whom also had chemotherapy); 11% had chemotherapy
only, 15% surgery only. Compared with the low-M-complainers, high-M-complainers (n=97) were significantly younger
(50.5±8.6 vs. 53.1±7.9, p=0.03), while high-EF-complainers (n=36) were more likely to have received previous HRT
(51% vs 24%, p=0.001), and both high complainer groups were more likely to have received combined chemo/radiation
therapy than single agent or none (p= 0.0002, p=0.02). QOL and fatigue were worse in high-complainers (p<0.0001).
High-M-complainers had worse NP verbal memory (-0.14 vs. 0.13, p=0.02), while high-EF-complainers had worse NP EF
and psychomotor performance (-0.29 vs. 0.08, p=0.003; -0.23 vs. 0.07, p=0.03). In multivariable regression analyses,
more high-M-complainers than low-complainers had depressive symptoms (p<0.0001), chemo/radiation (p=0.006),
and diminished verbal memory (p=0.04); more high-EF-complainers than low-complainers had depressive symptoms
(p=0.001), and diminished EF (p=0.002). High-M-complainers also had significant elevations of plasma sTNFrII (p=.02)
and significantly greater likelihood of GG allele of TNFα-308 SNP.
Conclusions: Memory complaints are associated with chemo/radiation therapy, as well as TNFα biomarkers, while both
high memory and executive function self-reported CC are associated with complaint-specific NP relative deficits and
depressive symptoms.
Supported by NCI/NIH R01 CA 109650 and the BCRF
NOTES
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th
March 2012
Oral Communications
9) Longitudinal Assessment of Cognitive Changes Associated with Adjuvant Treatment for Breast Cancer: The Impact of APOE and Smoking (Tim A. AHLES)
Authors : Tim A. Ahles 1, 2 , Yuelin Li 1, Brenna C. McDonald 3, Charlotte T. Furstenberg 2, Brett S. Hanscom 5, Gary N.
Schwartz 6, Peter A. Kaufman 6 , C. Harker Rhodes Gregory J. Tsongalis, Andrew J. Saykin 3
Institutional Affiliations :
1
Department of Psychiatry and Behavioral Sciences, Memorial Sloan-Kettering Cancer Center, New York, NY;
2
Department of Psychiatry and Center for Psycho-Oncology Research, the Norris Cotton Cancer Center, DartmouthHitchcock Medical Center Lebanon, NH;
3
Department of Psychiatry (Neuropsychology Program), Dartmouth-Hitchcock Medical Center, Lebanon, NH and Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine Indianapolis, IN;
4
Department of Community and Family Medicine, Dartmouth Medical School and the Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center Lebanon, NH;
5
Department of Orthopedics, Dartmouth-Hitchcock Medical Center, Lebanon, NH;
6
Department of Medicine (Medical Oncology), Dartmouth-Hitchcock Medical Center Lebanon, NH.
E-mail of the corresponding author : [email protected]
Purpose: The goal of this study was to examine the association of post-treatment changes in Processing Speed and
APOE and smoking in breast cancer patients treated with adjuvant chemotherapy.
Methods: Breast cancer patients treated with chemotherapy were evaluated with a battery of neuropsychological tests
prior to chemotherapy and at 1, 6, and 18 months post-chemotherapy Matched groups of breast cancer patients not
exposed to chemotherapy (N=79, age=57.5+/-9.8, education=14.8+/-2.3) and healthy controls (N=57, age=53.3+/9.8, education=15.2+/-2.1) were evaluated at similar intervals. APOE genotyping was done with Taqman and smoking
history was collected by self-report.
Results: Mixed-effects modeling for Processing Speed revealed no significant group by APOE interaction (p=0.57), but
a significant APOE by smoking history interaction ( p=0.01) and a stong trend for three way interaction of treatment,
APOE status and smoking history (p=0.07). Specific contrasts between the fixed effects were calculated and tested via
the best linear unbiased predictions (BLUP). A statistical contrast between the never- and ever-smokers across the
ApoE4 status showed that, within patients treated with chemotherapy, never-smokers were significantly worse than
ever-smokers if they were ApoE4 positive than if ApoE4 negative (BLUP estimate = – 0.4504, 95% CI: – 0.771, – 0.130,
p = 0.006). Using the non-cancer group as the reference, another contrast showed that the smoking by ApoE4 effect of
the chemotherapy group was more pronounced (– 0.6199, 95% CI: – 1.152, – 0.088, p = 0.023).
Conclusions: These results support previous research suggesting that the association between APOE status and cognitive functioning is moderating by smoking history. The putative mechanism is that smoking corrects a deficit in nicotinic
receptor functioning and dopamine levels in APOE4+ individuals.
NOTES
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th
March 2012
Oral Communications
10) Preliminary Evidence of a Genetic Association Between an Interleukin 6 Promoter Polymorphism and the Severity of Self-Reported Attentional Fatigue (John D.
MERRIMAN)
Authors: John D. Merriman, RN, MS1; Bradley E. Aouizerat, PhD1,2; Bruce A. Cooper, PhD1; Dale J. Langford, PhD1;
Marylin Dodd, RN, PhD1; Kathryn Lee, RN, PhD1; Claudia West, RN, MS1; Steven M. Paul, PhD1; Patrick S. Swift, MD4;
William Wara, MD5; Laura Dunn, MD3; Christine Miaskowski, RN, PhD1
Institutional Affiliations:
School of Nursing,1 Institute for Human Genetics,2 School of Medicine,3 University of California, San Francisco;
Alta Bates Comprehensive Cancer Center, Berkeley, California;4 Kaiser Permanente, San Francisco5.
This study was supported by F31 (NR012604) and R01 (NR04835) grants funded by the National Institute of Nursing
Research. Additional support was provided by the American Cancer Society Doctoral Degree Scholarship in Cancer Nursing (DSCN-10-087).
E-mail of the corresponding author: [email protected]
Purpose: The purposes of this study were to identify latent classes of attentional fatigue and determine the relationship
between the IL6 c.C-174G (rs1800795) promoter polymorphism and these classes.
Methods: Attentional fatigue was evaluated in 242 patients and family caregivers using the Attentional Function Index
before radiation therapy and at additional assessments over six months. Growth mixture modeling was used to identify
latent classes with distinct symptom trajectories. Because 65% of participants were in patient-caregiver dyads, models
were estimated with dyad as a clustering variable. Using an additive model (CC versus CG versus GG) controlling for
ethnicity, patient/caregiver status, and functional status, logistic regression was used to determine the impact of genotype on the odds of attentional fatigue class membership.
Results: Three latent classes of attentional fatigue were identified: none (15.5%), low levels (48.0%), and moderate
levels (36.5%). Participants in the moderate symptom class were younger with more comorbidities and lower functional
status than other participants. They had more anxiety and depressive symptoms, sleep disturbance, physical fatigue,
and pain. The overall logistic regression model explained 13.1% of the variance in class membership (McFadden’s
pseudo R-squared), with genotype explaining 3.9% of the variance. Each additional copy of the G minor allele (frequency=35.5%) was associated with a 2.6-fold increase in the odds of belonging to a higher attentional fatigue class
(95% CI: 1.3-5.1, p=.006).
Conclusions: These findings provide preliminary evidence of distinct groups of oncology patients and family caregivers
who experience different levels of attentional fatigue over the course of radiation therapy. These findings also provide
preliminary evidence of a genetic association between an IL6 promoter polymorphism and the severity of the symptom.
Future studies should confirm these latent classes and the effects of c.C-174G so that this and other genomic markers
could be used to identify persons at risk for attentional fatigue.
NOTES
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th
March 2012
Oral Communications
11) Study of the Cognitive Effects of Chemotherapy: How Choice of Control Group
Affects Outcome (Barbara COLLINS)
Authors : Barbara Collins, Ph. D., Joyce MacKenzie, M. Ps
Institutional Affiliations :
The Ottawa Hospital, Ottawa, Canada
E-mail of the corresponding author : [email protected]
Purpose: Studies of the cognitive effects of chemotherapy have yielded inconsistent results. We analyzed the same data
three different ways to determine if choice of control group might be contributing to this confusion.
Methods: A Reliable Change Index (RCI) plus practice effects model was applied to neuropsychological data from 28
breast cancer patients tested before and shortly following chemotherapy. These data were analyzed repeatedly using a
local disease control group, a local healthy control group, and published norms, respectively. Reliable cognitive decline
for a given subject was defined as an RCI of –2.0 or lower on ≥ 2 of 16 cognitive measures. Chi-square was used to
determine group differences in frequency of decline.
Results: The frequency of decline in the chemotherapy and control groups was as follows: 21% versus 0% using local
healthy controls (p = .01); 21% versus 4% using published norms (p=.04); and 29% versus 7% using a disease control
group (p=.04). In all cases, the frequency of decline in the chemotherapy group was significantly higher than in the
control group. The rate of decline in the chemotherapy group did not differ significantly from one analysis to another
(p = .77).
Conclusions: Regardless of the control group used, the frequency of cognitive decline was significantly greater in the
chemotherapy treated patients than in the control subjects. We conclude that whether published norms or a local control
group is used is not as critical as careful matching of the normative group to the treatment group on potentially confounding variables. Agreement on a standardized protocol for cancer and cognition studies would allow us to establish a large
normative database that would provide accurate estimates of reliability and practice effects for a battery of relevant tests
and allow for more efficient and economical study in this field.
NOTES
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th
March 2012
Oral Communications
12) Effects of Co-morbid Disease on Pre-treatment Neurobehavioral Functioning
(Sunita K. PATEL)
Authors : Sunita K. Patel, Arpine Davtyan, Francesca Hernandez, Ellis Beier, Krystle Barrera, Andrew Wong, Lennie
Wong, Arti Hurria, & Smita Bhatia.
Institutional Affiliations :
City of Hope Medical Center and Beckman Research Institute, Department of Population Sciences, Outcomes Division,
Behavioral Science Section.Duarte, California.
E-mail of the corresponding author : [email protected]
Purpose: Neurobehavioral dysfunction in breast cancer patients is primarily attributed to the effects of chemotherapy;
however, recent studies suggest these symptoms are present even prior to adjuvant treatments. Given the literature
on neurobehavioral effects and various non-cancer health conditions, we hypothesized that cancer patients’ co-morbid
health status is associated with lowered neurobehavioral functioning prior to initiation of cancer treatment.
Methods: A sample of 154 post-menopausal women newly diagnosed with non-metastatic breast cancer and without
serious neurological or psychiatric disorder were seen for neurobehavioral assessments prior to any treatment, including
surgery. The validated Charlson Comorbidity Index was calculated for each patient using medical records to represent
baseline con-comitant disease conditions. Statistical analyses were conducted using the presence versus absence of a
qualifying comorbid condition as the independent variable, and neurobehavioral scores as dependent variables.
Results: Forty-two women had co-morbid disease (Group1), while 112 did not (Group 2). From the 42, 17 had diabetes,
16 had chronic pulmonary disease, 8 had cardiovascular disease, 7 had significant connective tissue disease, etc. Group1
and Group2 were similar in age, education, social support, cancer stage, and functional activity scores.
On performance measures of neurocognitive functioning, a pattern of significantly lowered executive functioning emerged in Group1 relative to Group2, including on the DKEF Trail Making Test, F(1, 137) = 4.51, p = .03, and the Verbal
Fluency Switching Test, F (1, 126) = 5.77, p = .018. This finding was supported by self-report where Group 1 reported
significantly more executive dysfunction on the BRIEF, F (1, 141) = 6.97, p=.009. While there were no differences in
depression or anxiety, Group 1 had significantly higher self-reported fatigue and somatic symptoms.
Conclusion: Comorbid health conditions impact neurobehavioral symptoms such as executive functioning and fatigue,
even prior to any treatment, and should be methodologically considered in cognition-related cancer research.
NOTES
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th
Oral Communications
March 2012
13) Cognitive function in colorectal cancer patients: a longitudinal prospective study
(Janette VARDY)
Authors : Janette Vardy 1, Haryana Dhillon 1, Wei Xu 2, Sean Rourke 3, Anna Dodd 2, Corrinne Renton 1, Xin Qiu 2, Stephen
Clarke 1, Ian F. Tannock 2
Institutional Affiliations :
1
Sydney Cancer Centre, University of Sydney, Australia;
2
Princess Margaret Hospital, University of Toronto, Canada
3
St Michael’s Hospital, University of Toronto, Canada
E-mail of the corresponding author :
[email protected]
Purpose: A subset of cancer patients has cognitive impairment after chemotherapy (CTh). We evaluate cognitive function and potential mechanisms in CRC patients.
Methods: Cognitive function was evaluated in localized CRC patients at baseline (pre-CTh), 6, and 12 months. Group 1A
(Stage II/III) received CTh and group 1B (Stage I/II) received no CTh. Group 2 patients had limited metastatic/recurrent CRC. Group 3 were healthy controls (HC). All patients completed neuropsychological (NP) assessment with classical
tests and CANTAB, with impairment defined using global deficit scores (GDS) and ICCTF criteria. Subjects completed
concurrent questionnaires for fatigue, QOL, anxiety/depression, and perceived cognitive function. Blood tests evaluated
cytokine levels, clotting factors, sex hormones, CEA and apolipoprotein genotyping as potential causal factors. Primary
endpoint: cognitive function (classical tests) comparing Groups 1A and 1B at 12 months. Associations between results,
demographic and disease-related factors were sought.
Results: Baseline 359 pts: 169 Group 1A, 118 Group 1B, 72 Group 2 and 72 HC (presented separately); follow-up currently for 6 and 12 months for 270 and 225 CRC patients respectively. Median age 59 (23-75 years); 64% male. Preliminary 12 month data: using GDS criteria for cognitive impairment: classical tests 20% in Group 1A vs 12% Group 1B,
and 27% Group 2; CANTAB Group 1A 19% vs Group 1B 16%, and Group 2 18%. Self-reported cognitive impairment:
18% Group 1A vs 8% Group 1B, and Group 2 13%. Fatigue: 46% Group 1A vs 28% Group 1B and 62% Group 2. There
was no difference in QOL or anxiety/depression.
The final subject will be tested in January 2012. Longitudinal data and blood test results for all CRC patients and 72 HC
will be available for presentation at the meeting in March.
Conclusions: Cognitive impairment occurs in a subset of CRC patients prior to, during and after chemotherapy.
NOTES
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th
March 2012
Oral Communications
14) The Influence of Sleep on Cognition in Breast Cancer (Sonia ANCOLI-ISRAEL)
Authors : Sonia Ancoli-Israel, Loki Natarajan, Lianqi Liu, Barton W. Palmer, Barbara A. Parker
Institutional Affiliations :
University of California San Diego
E-mail of the corresponding author : [email protected]
Purpose: Examine the influence of sleep, fatigue and mood on cognition in breast cancer.
Methods: 74 women(mean age=51.8y) diagnosed with stage I-III breast cancer, undergoing chemotherapy and 66
age- and education-matched controls(mean age=51.6y) with no cancer were recruited. Neuropsychological (NP) tests,
questionnaires (fatigue, sleep, mood, Patient’s Assessment of Own Function [PAOF]) were administered pre-chemotherapy (baseline), after cycle4 and one-year post-chemotherapy. Actigraphs were worn for 72-hours at same time points
to objectively measure sleep.
Results: At baseline, patients had worse sleep, more naptime, depressive symptoms and fatigue(all p<0.001); there
were no differences between groups in measures of cognition. After cycle4, compared to baseline and controls, patients
had significantly worse sleep quality and more depressive symptoms, fatigue and naptime(all p<0.001) and patients
reported more deterioration of language(p=0.001) and of overall cognitive function on PAOF(p=0.005) while controls
reported no change. At cycle-4 vs. baseline and at year-1 vs. cycle4, there was no significant change in NP tests in
patients; however, controls improved(p=0.0006).
Relationships with change in cognition were tested with models adjusted for baseline NP, age, and
gree. Decline in sleep quality(Beta=-0.0235; p=0.043), PAOF Memory(Beta=0.0134;p=0.036),
language(Beta=0.0185;p=0.0023) predicted decline in cognition from baseline to cycle4. Decline in sleep
-0.0310;p=0.003) and PAOF Sensory(Beta=0.0229;p=0.023) predicted decline in cognition from cycle4
Fatigue and mood did not predict change in cognition.
college deand PAOF
quality(Beta
to one-year.
Conclusions: Decrease in cognitive ability was associated with low baseline NP scores, not having a college degree
and worse sleep quality as well as a perception of cognitive deficits, but not fatigue or mood. The model which included
baseline NP, age, college degree and sleep explained 16.5% of the variance of change of cognition at cycle 4 and 27%
at year one. Treatment for sleep should begin early in the diagnosis and treatment of cancer.
NOTES
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th
March 2012
Oral Communications
15) Improving the Ecological Validity of Cognitive Assessments : Virtual Reality Testing of Prospective Memory Following Chemotherapy Treatments for Breast Cancer
(Heather J. GREEN)
Authors : Mary E. Mihuta 1, Heather J. Green 1, David W. K. Man 2, & David H. K. Shum
1
Institutional Affiliations :
1
School of Psychology & Behavioural Basis of Health Program, Griffith Health Institute, Griffith University, Gold Coast,
Australia
2
Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, People’s Republic of China
E-mail of the corresponding author : [email protected]
Purpose: The current study aimed to improve the ecological validity of objective cognitive assessment in two ways: (1)
by testing prospective memory, a type of cognition that involves remembering to carry out an action when there are
distracting ongoing tasks, and (2) by using a virtual reality environment that is more similar to participants’ everyday
cognitive challenges than standard neuropsychological tests. The study examined whether prospective memory (PM)
performance among breast cancer survivors (BCS) exposed to chemotherapy differed from that seen in a demographically matched control group.
Methods: Approximately 30 female survivors of breast cancer who received chemotherapy that finished 0.5-5 years ago
will be compared with 30 age- and education-matched women who have no history of cancer. Participants will complete
event-, time- and activity-based PM measures; standardised neuropsychological tests assessing attention and concentration, executive function and verbal memory; and self-report measures of cognitive dysfunction and PM failures. Preliminary results are available from 24 survivors of breast cancer (age M = 52.8, SD = 6.8 years) and 18 healthy women
with no history of cancer or chemotherapy treatment (age M = 50.3, SD = 6.9).
Results: Preliminary results show that the BCS group performed significantly worse on the test of attention and concentration. Furthermore, there were trends towards poorer performance by the BCS group on both measures of executive
function and all four PM tasks. The BCS group reported significantly more cognitive complaints and PM failures than the
control group on five of six measures. PM tasks appear to correlate with both neuropsychological tasks and with selfreported PM failures in everyday life.
Conclusions: The results provide some evidence that cognitive impairment following chemotherapy treatment is seen
in PM, which supports a need for further research into PM performance in this clinical group.
NOTES
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March 2012
Oral Communications
16) Group Cognitive Rehabilitation for Cancer Survivors: Enhancing Cognitive Function and Quality of Life (Heather J. GREEN)
Authors : Alana Schuurs & Heather J. Green
Institutional Affiliations :
School of Psychology & Behavioural Basis of Health Program, Griffith Health Institute, Griffith University, Gold Coast,
Australia
E-mail of the corresponding author : [email protected]
Purpose: This research aimed to address the gap in evidence-based treatment available for cancer survivors who are
experiencing cognitive dysfunction. The research aim was to test the feasibility and effectiveness of a group cognitive
rehabilitation intervention designed to improve cognitive function and quality of life for people who have completed
cancer treatment.
Methods: Three groups of adults were recruited: an intervention group of 23 cancer survivors who completed a 4-week
group cognitive rehabilitation treatment, a comparison group of 9 cancer survivors, and a community sample of 72
adults who had never experienced cancer. The manualised « ReCog » intervention was developed by the authors for this
study and was delivered by a clinical health psychologist and a provisionally registered psychologist, in small groups
of 4-8 participants. The two comparison groups completed assessments but did not receive the intervention. Measures
of objective and subjective cognitive functions, quality of life, psychosocial distress and illness perceptions were used.
Results: The results indicated that the intervention was effective in improving overall cognitive function, visuospatial/
constructional performance and delayed memory beyond practice effects alone. It was helpful in reducing participants’
perceptions of cognitive impairment and psychosocial distress, as well as promoting social functioning and understanding
of cognition. The improvements were maintained at three months after the intervention. Participants reported a high
level of satisfaction with the treatment.
Conclusions: The results provided evidence for the use of a brief group-based cognitive rehabilitation intervention to
treat cognitive problems experienced by cancer survivors.
NOTES
27
Saturday 17
th
Oral Communications
March 2012
17) A randomized trial of Cognitive Rehabilitation in Cancer Survivors (Monique
CHERRIER)
Authors : M. Cherrier 1 , C. Higano
2
, H. Gray
3
, A. Church
1
, K. Anderson
1
, A. Tattersall
1
S. Willis
1
Institutional Affiliations :
1
Department of Psychiatry and Behavioral Sciences;
2
Department of Medicine- Division of Oncology;
3
Department of Obstetrics and Gynecology-Division of Gynecologic Oncology, University of Washington Medical School,
Seattle, WA 98195
E-mail of the corresponding author : [email protected]
Purpose: The second most frequently reported post treatment symptom in cancer survivors is concerns about impaired cognition. Despite numerous studies demonstrating significant impairments in a portion of survivors, very little is
known about the effectiveness of cognitive rehabilitation in this population. Millions of cancer survivors live with residual
symptoms of impaired cognition severe enough to interfere with basic activities of daily living. Although some studies in
brain injured patients have shown efficacy of cognitive rehabilitation, the effectiveness of various methods of treatment
in cancer survivors is a new area of investigation. This study examined the effectiveness of a cognitive rehabilitation
intervention in cancer survivors.
Methods: This study was a double-blind, randomized, wait-list controlled study of cognitive rehabilitation in cancer survivors. The intervention was a 7-week cognitive rehabilitation intervention delivered in group format and participants
were evaluated with a comprehensive cognitive battery prior to and following treatment. Participants with depression or
more severe cognitive impairments and on active treatment were excluded.
Results: Participants (mean age 67 yrs) were men and women with median 3 years (+/- 6 yrs) post primary/adjuvant
treatment and various cancer sites (breast, bladder, prostate, colon, uterine). All participants reported subjective cognitive difficulties (FACT-Cog). Compared to baseline, cancer survivors in the treatment group demonstrated a significant
improvement in the number of words recalled after a short delay on a word list task (p<.05), with a trend for better
performance on a sustained attention task (CPT). Other abilities such as executive functions or spatial abilities did not
change.
Conclusions: Participants were satisfied with the intervention and endorsed increased confidence in their cognitive abilities as indicated on a questionnaire. Overall, these results suggest that group-based cognitive rehabilitation may be an
effective intervention for treating cognitive dysfunction in cancer patients and should be further studied in a larger trial.
NOTES
28
POSTER
SESSION
eligible for Young Investigator Awards
29
Abstracts in alphabetical order
NAME
First name
Ahles
Tim A.
Amidi
Ali
Ancoli-Israel
Sonia
Beadle
Geoffrey
Number of the
poster or oral
com.
page
NAME
First name
Number of the
poster or oral
com.
page
Oral Com. 9
20
JOHNSTON
I
27
57
1
31
Kemperman
M
28
58
Oral Com. 14
25
Kesler
Shelli
2
32
Kobus
M
Oral Com. 6
17
29
59
Bernstein
Lori J.
3
33
Koppelmans
Vincent
Oral Com. 5
16
Boone
Mathieu
4
34
Lange
Marie
30
60
Chambers
Annabelle
5
35
Le Fel
Johan
31
61
Chen
Wenhong
6
36
Léger
Isabelle
32
62
Cherrier
Monique
Oral Com. 17
28
Libert
Yves
33
63
CHEUNG
Yin Ting
7
37
Maqbool
Ayesha
34
64
CHEUNG
Yin Ting
8
38
McDonald
Brenna C.
35
65
Christie
Lori-Ann
9
39
Menning
Sanne
36
66
Cohen
Jonathan
10
40
Mereuta
Onana C.
37
67
Collins
Barbara
Oral Com. 11
22
Merriman
John D
Collins
Barbara
11
41
Morel
N
Oral Com. 10
21
38
68
Conroy
Susan K
12
42
Moyers Ruiz
Liliana
39
69
Correa
DD
13
43
Noal
Sabine
40
70
Couture-Lalande
Marie-Eve
14
44
Patel
Sunita K.
Oral Com. 12
23
Das
Enny
15
45
Pérès
Elodie
41
71
Deprez
Sabine
Oral Com. 4
15
Pomykala
Kelsey L.
42
72
Dietrich
Jörg
Oral Com. 3
14
Pullens
Marleen JJ
43
73
Dubois
Martine
Oral Com. 1
12
Pullens
Marleen JJ
44
74
Dubois
Martine
16
46
Quittet
Marie-Sophie
45
75
Edelstein
Kim
17
47
Ribi
Karin
46
76
Ercoli
LM
18
48
Robbins
Mike
Oral Com. 7
18
Fardell
Joanna
Oral Com. 2
13
Root
JC
47
77
Fardell
Joanna
19
49
Scherling
Carole
48
78
Fleishman
Stewart
20
50
Schrauwen
W
49
79
Ganz
Patricia
Oral Com. 8
19
Schrauwen
W
50
80
Green
Heather
Oral Com. 15
26
Seigers
R
51
81
Green
Heather
Oral Com. 16
27
Smith
Andra
52
82
53
83
Oral Com. 13
24
Hardt
M
21
51
Tattersall
A
Höhn
Gabriela
22
52
Vardy
Janette
Hubbard
Karen
23
53
Vardy
Janette
54
84
Janelsins
Michelle C.
24
54
Virani
Shamsuddin
55
85
Jim
Heather
25
55
Wagner
Lynne I
56
86
Jim
Heather
26
56
Winocur
Gordon
57
87
Wu
Lisa
58
88
30
1) Self-reported Cognitive Failure in Breast Cancer Survivors: Preliminary Results
from a Danish Nationwide Cohort Study (Ali AMIDI)
Authors :Ali Amidi 1, Mimi Mehlsen 1, Robert Zachariae 1, Søren Christensen
1
Institutional Affiliations :
1
Psycho-Oncology Research Unit, Dept. Oncology, Aarhus University Hospital and Department of Psychology, Aarhus
University, Aarhus, Denmark
E-mail of the corresponding author : [email protected]
Purpose: Self-reported cognitive impairment after chemotherapy has instigated the colloquial use of the term “chemobrain”. There is, however, uncertainty related to the cognitive impairments observed following cancer treatment, both in
terms of the potential causes and long term status. The aim of the current study was to investigate: a) the long-term
prevalence of self-reported cognitive failures in a large population based sample of breast cancer survivors, and, b)
whether such reports differ between survivors treated with or without chemotherapy.
Methods: Data originated from a large Danish nationwide cohort study including 3343 women treated for primary breast
cancer. Follow-up data 7-10 years after initial surgery include questionnaires from 2061 recurrence-free breast cancer
survivors (34-80 years). Of these, 870 (42.2%) had received chemotherapy. Self-reported cognitive failure was assessed
with the Cognitive Failure Questionnaire (CFQ), which consists of 25 items related to daily cognitive functioning rated on
a five-point Likert scale (0-4), with higher scores indicating higher levels of perceived cognitive failures.
Results: Mean CFQ score in all survivors was 31.32 (SD=12.56). Univariate analysis showed that the chemotherapy
group (M=32.63, SD=13.12) reported significantly more cognitive complaints than the non-chemo group (M=30.37,
SD=12.05), (t(2059) = -3.76, p<.001). A significant inverse association was found between age and CFQ (r = -0.132,
p<0.01) When adjusting for age, no group differences in CFQ scores were found (F(1,2058) = 0.61, p>.05).
Conclusions: Breast cancer patients, 7-10 years post-surgery, did not report high levels of cognitive failures. Furthermore the present study did not detect long-term chemotherapy induced cognitive impairments following breast cancer
when the effect of age was accounted for. Our results therefore indicate that any initial cognitive complaints may have
diminished seven to ten years after treatment, and that younger breast cancer patients are slightly more susceptible to
report cognitive failures.
NOTES
31
2) Perceived cognitive impairment after adjuvant chemotherapy for operable breast
cancer: Patterns of change and associations. (Geoffrey BEADLE)
Authors : Geoffrey Beadle
Mengersen 2
, Margaret Rolfe
1,4
, Brooke Andrew
2,5
, Katharine Vearncombe
1,2
, Margaret Wright 4, Kerrie
1,3
Institutional Affiliations :
1
The Wesley Research Institute, Brisbane, Australia
2
Queensland University of Technology, Brisbane, Australia
3
The University of Queensland, Brisbane, Australia
4
Queensland Institute of Medical Research, Brisbane, Australia
5
Southern Cross University, Lismore, Australia
6
Queensland Institute of Medical Research, Brisbane, Australia
E-mail of the corresponding author : [email protected]
Purpose: This research investigated the utility of the Functional Assessment of Cancer Therapy- Cognition (FACT-Cog),
a self-report measure of perceived cognitive functioning. We examined the associations between FACT-Cog ratings and
performance on objective tests of neuropsychological functioning and other self-report measures of psychological health.
Methods: One hundred and twenty three breast cancer patients were assessed pre-chemotherapy, and at one, six, and
eighteen months post-chemotherapy completion on a battery of neuropsychological tests and self-report measures of
psychological functioning.
Results: Perceived cognitive functioning as measured by the self-report FACT-Cog scale showed a significant decline
over the treatment period, with some recovery evident at eighteen months post-chemotherapy. FACT-Cog ratings were
highly correlated with other self-report measures of anxiety, depression, and quality of life across all time points. In
contrast, perceived cognitive functioning did not correlate with performance on the objective neuropsychological tests.
Conclusions: The FACT-Cog appears to be a valid and reliable measure of perceived cognitive functioning in this population. In line with other studies, there was a lack of association between perceived impairment and performance on
neuropsychological tests. This may reflect the fact that perceived impairment can be attributed to factors other than true
loss of cognitive capacity, or perhaps an inability of the objective tests to pick up subtle cognitive change.
NOTES
32
,
f
e
e
n
n
e
3) Cognitive function and quality of life in head and neck cancer patients before and
after chemo/bio-radiotherapy. (Lori J. BERNSTEIN)
Authors: Lori J. Bernstein 1,4, Lillian L. Siu 2,4 , Andrew Chan 3,4, Greg R. Pond 5, Kattleya Tirona 1, Eric Chen 2,4, Andrew
Hope 3,4, Jolie Ringash 3,4, Brian O’Sullivan 3,4, John Waldron 3,4, Kelvin Chan 2,4, Hui Gan 6, Albiruni R. Abdul Razak 2
Institutional Affiliations:
1
Psychosocial Oncology and Palliative Care;
2
Medical Oncology;
3
Radiation Oncology, Princess Margaret Hospital;
4
University of Toronto;
5
McMaster University;
6
Austin Hospital, Melbourne, Austria.
Email of the corresponding author: [email protected]
Purpose: To assess performance on neuropsychological tests, self-reported cognitive function, and quality of life (QoL)
in head and neck cancer (HNC) patients before and after chemo/bio-radiotherapy treatment.
Methods: Patient demographics and disease and treatment characteristics were collected. All patients underwent a
2-hour battery of NCF testing at baseline and one year later. Domains evaluated included intelligence, attention, memory, language, processing speed, executive function, and motor skills. Performances on the various tests were transformed to Z-scores using normative data. NCF decline was defined as a Z-score decrease of > -1 and improvement as
a Z-score increase of > +1. Patients also had subjective assessments of anxiety, depression, NCF and QoL using the
Hospital Anxiety and Depression Scale and FACT questionnaires.
Results: Patient demographics (n= 24) were M:F= 19:5, mean age= 61.2, CRT(cisplatin):BRT(panitumumab):RT=
14:6:4, oropharynx:other= 21:3. At one year, six patients (25%) had NCF decline in at least one cognitive domain, with
memory and attention most frequently affected (n= 3 each). Three of these six patients had multiple domains affected,
most frequently in memory, attention and executive function. One patient with NCF declines in intelligence, memory and
attention received the highest RT dose to the frontal and temporal lobes. Five patients had NCF improvements, albeit
only in a single domain each. Although 96% of patients did not report severe levels of anxiety or depression, more
patients self-reported lower NCF (46%) and QoL (33%) than those self-reporting higher NCF or QoL (17% and 8% respectively) at 1-year. There was no association between changes in objective NCF and changes in subjective NCF or QoL.
Conclusions: Treatment for HNC may be associated with NCF decline at 1-yr and can affect multiple domains. Subjective declines in NCF and QoL were more frequent than objective NCF declines. Longer-term follow up will further characterize these findings.
NOTES
33
4) Prevalence and descriptive analysis cognitive disorders and adult grade I to III
gliomas (Mathieu BOONE)
Authors : Boone M.1,3, Roussel M.2, Chauffert B.3, Le Gars D.4, Godefroy O.1,2.
Departement of Neurology, University Hospital of Amiens, France
Laboratory of Functional Neurosciences, University Hospital of Amiens, France
Departement of Medical Oncology, University Hospital of Amiens, France
4
Departement of Neurosurgery, University Hospital of Amiens, France
Address correspondence to Dr. Boone, Service de Neurologie, CHU Nord 80054, Amiens cedex France.
1
2
3
E-mail: [email protected]
Background: In glioma follow-up, cognitive disorders are reported with variable prevalence (from 47% to 100%) and
profile. This study aims at determining the prevalence of cognitive deficits and their profile in patients with primary brain
tumor below WHO’s grade IV.
Patients and methods: this single-center cross sectional study examined 27 patients (mean age: 43 years; sex male:
63%) fitting this criterion (mean delay: 36 months) using a comprehensive neuropsychological battery assessing general intellectual efficiency, language, visuospatial and constructive abilities, long and short term memory, psychomotor
speed, behavioural and cognitive dysexecutive disorders. In addition scales assessed the severity of neurological deficit
(NIHSS) and disability (Karnofsky Index, Barthel Index, Modified Rankin Scale). Cognitive impairment was defined by a
deficit of at least one domain, each domain being assessed using 2 tests.
Results: it showed that (1) cognitive deficit was observed in 70% [95%IC = 53.1-87.6]; (2) 31% patients had one
domain impaired, 16%, 2 domains, and 23% more than 2 domains; (3) the cognitive profile was characterized by prominence of memory deficit (46%) followed by disorders of language (42%), executive functions (31%) and visuo-spatial
abilities (23%), (4) a correlation was showed between number of impaired cognitive domains and severity of neurological deficit (R = 0.61; p = 0.001) and disability indexed by Karnofski (R = -0.56, p = 0.002).
Conclusion: this study supports that about 2/3 of survivors with primary brain tumor below grade IV suffers from
cognitive impairment, mostly due to memory, language and executive disorders and that it is associated with disability.
Keywords: brain neoplasm - glioma - cognitive disorders - prevalence - neuropsychological tests
NOTES
34
5) 5-Fluorouracil causes a prolonged reduction in neurogenesis in the rat hippocampus. (Annabelle CHAMBERS)
Authors : Annabelle Chambers 1, Maha ElBeltagy 2, Ayesha Maqbool 1, Maria Toledo-Rodriguez
1
and Peter Wigmore
1
Institutional Affiliations :
1
School of Biomedical Sciences, University of Nottingham, Queen’s Medical Centre, Nottingham, NG7 2UH, UK
2
Department of Anatomy, Menoufiya University, Egypt
E-mail of the corresponding author : Annabelle Chambers: [email protected]
Purpose: 5-Fluorouracil is a commonly used chemotherapy treatment for breast, prostate and bowel cancer, yet has
been shown to cause long term cognitive and memory deficits in patients, which continue for years after treatment
ceases. We are conducting ongoing studies to determine what effects 5FU chemotherapy treatment has on the survival
and proliferation of neural cells in the dentate gyrus, at short term and long term intervals.
Methods: Male Lister Hooded rats were injected with 5FU and Leucovorin, or 0.9% saline every other day for two weeks.
BrdU (150mg/kg, i.p.) was administered twice on consecutive days, before chemotherapy treatment. Animals were killed either immediately; 2 weeks or 6 weeks post-treatment. Their brains were processed for immunohistochemistry to
detect BrdU and Ki67. Statistical analysis was performed using two way ANOVA with Bonferroni post hoc test.
Results: Two weeks 5FU treatment caused a significant reduction in cell survival (BrdU detection) immediately after
treatment, which continued for 2 and 6 weeks post-treatment, compared to controls . Although 5FU caused no significant
decrease in cell proliferation (Ki67 detection) immediately after treatment, proliferation was considerably less 2 and 6
weeks post-treatment, compared to controls.
Conclusions: Results presented here show cell survival is initially, and continually decreased after 5FU treatment. Cell
proliferation however is only affected several weeks after treatment has ceased, indicating a delay. Together, this data
indicates that 5FU continues to negatively affect neurogenesis for a considerable time after treatment.
Further experiments will look at the effects of acute and chronic doses of 5FU on neurogenesis, to determine what stage
of neural cell development is targeted. We also aim to find the cellular mechanisms by which this decrease in neurogenesis occurs, as well as considering ways to investigate epigenetic factors that also alter this process.
NOTES
35
6) Astaxanthin Enhances Recognition Memory in a Rat Model of Brain Metastasis
(Wenhong CHEN)
Authors : Wenhong Chen, Valerie Payne, Keith D. Barlow, Anne Sanders, Christine McMahan, Michael E. Robbins and
Linda J. Metheny-Barlow
Institutional Affiliations : Department of Radiation Oncology, Wake Forest School of Medicine
E-mail of the corresponding author : [email protected]
Purpose: Metastasis to the brain is a common complication of metastatic cancer. The treatment for brain metastases
currently usually includes fractionated partial or whole brain irradiation (fWBI). However, patients who receive fWBI
frequently are afflicted with therapy-induced progressive, irreversible cognitive impairment that significantly impacts
their quality of life. Astaxanthin (AST), an antioxidant carotenoid, reportedly crosses the blood-brain barrier, prevents
oxidative stress-associated neurodegeneration in vitro, and may improve age-related cognitive decline. In this pilot
study we evaluated the ability of AST to alleviate WBI-induced cognitive impairment in a rat model of breast cancer
brain metastasis.
Methods: Fischer344 rats implanted with MATBIII mammary tumor cells and treated with fWBI (5 Gy fractions delivered 2x/week for 4 weeks) were fed a control diet or an Astaxanthin diet (100mg/kg diet) that was initiated prior to
or after completion of fWBI. Rats surviving 26 weeks following completion of fWBI were subjected to the Novel Object
Recognition (NOR) Test to measure recognition memory.
Results: In our model, 77% of rats receiving control diet and 100% of rats receiving AST diet after fWBI survived
until endpoint NOR test. In contrast, only 63% of rats consuming AST during fWBI survived until 26 weeks; pairwise
comparison with the AST after fWBI group suggests that AST consumed after fWBI completion provides a survival
advantage. Although the rats in this model did not show a decrease in cognition following fWBI as measured by NOR,
the consumption of AST diet resulted in a statistically significant enhancement of recognition memory.
Conclusions: These data suggest that consumption of AST following the completion of fWBI may enhance recognition
memory in a model of breast cancer brain metastasis without compromising therapeutic response. In contrast, administration of AST during fWBI does not provide survival or cognitive benefit.
Supported by the U.S.A.M.R..M.C under W81XWH-10-1-044
NOTES
36
7) Cognitive Changes in Multiethnic Asian Breast Cancer Patients – A Focus Group
Study (Yin Ting CHEUNG )
Authors : Yin Ting CHEUNG 1, Maung SHWE@Ham Guo 1, Yee Pin TAN 2, Gilbert Kam Tong FAN 2, Raymond Chee Hui NG 3,
Alexandre CHAN 1, 4
Institutional Affiliations :
1
Department of Pharmacy, National University of Singapore, Singapore
2
Department of Psychosocial Oncology, National Cancer Centre Singapore, Singapore
3
Department of Medical Oncology, National Cancer Centre Singapore, Singapore
4
Department of Pharmacy, National Cancer Centre Singapore, Singapore
E-mail of the corresponding author : [email protected]
Purpose: To gather in-depth descriptions from multiethnic Asian breast cancer patients on (1) their perception and
experience of cognitive changes, (2) the impact of cognitive changes on their family, working and social life, and (3)
their coping strategies.
Methods: Forty-three early-stage breast cancer patients (mean age: 52 years; > 80% Chinese) who had received chemotherapy participated in eight 60-minute English or Chinese structured focus group discussions, conducted by trained
psychosocial oncologists. Each group discussion consisted of 4 to 6 patients. Thematic analysis was performed to distill
themes from transcripts through open coding by a team of independent coders.
Results: Patients were unfamiliar and averse to both English and Chinese-translated equivalent of the term “chemobrain”. Patients viewed this phenomenon holistically as a by-product of the physical (fatigue and aging) and psychosocial
(anxiety and mood changes) adverse effects associated with chemotherapy. Most patients have encountered short-term
memory loss, difficulty in decision making and speech problems upon completion of chemotherapy. Married patients
expressed disappointment and frustration as cognitive deterioration limited their conservative roles as homemakers.
Despite knowing the potential neurocognitive effects, majority of the patients still valued the benefits of chemotherapy.
Identified coping strategies included playing mahjong and utilising multimedia for mind stimulation. Other strategies
involved managing psychosocial factors that contribute to cognitive changes, such as practicing qi-gong to regulate their
moods and taking complementary alternative medicines to reduce the severity of their fatigue.
Conclusions: «Chemobrain” is foreign to most Asian cancer patients but post-chemotherapy cognitive changes have
significantly impacted their daily lives. Our results suggested that a culturally-relevant approach (eg. cultural adaptation
of subjective neuropsychological tools) should be adopted to evaluate and manage perceived cognitive changes in these
patients.
NOTES
37
8) Oncology Practitioners’ Perceptions of Cognitive Changes in Asian Cancer Patients
(Yin Ting CHEUNG )
Authors : Yin Ting CHEUNG 1, Earl Hsien Jie TAN 1, Raymond Chee Hui NG 2, Alexandre CHAN
1, 3
Institutional Affiliations :
1
Department of Pharmacy, National University of Singapore, Singapore
2
Department of Medical Oncology, National Cancer Centre Singapore, Singapore
3
Department of Pharmacy, National Cancer Centre Singapore, Singapore
E-mail of the corresponding author : [email protected]
Purpose: To gather information from Asian oncology practitioners on the (1) relevance and impact of chemotherapyassociated cognitive impairment in Asian cancer patients, (2) perception of the causes for cognitive changes, and (3)
awareness of coping strategies.
Methods: A self-administered cross-sectional survey was designed and conducted among oncology practitioners. Practitioners were recruited from 3 major cancer centres in Singapore and Thailand, and through a regional cancer meeting
that took place in Singapore in September 2011.
Results: A total of 159 practitioners completed the survey. Respondents consisted of oncologists (42.1%), nurses
(38.4%), pharmacists (15.1%), and patient advocates (4.4%). Majority interacts with breast (75.5%), colorectal
(70.4%) and lung (67.3%) cancer patients. Cognitive changes were frequently observed among cancer patients, particularly in the domains of memory (76.7%) and concentration (76.1%). Majority (86.1%) agreed that cognitive changes
have adversely impacted patients’ quality of life. However, only a small number of practitioners agreed the necessity
to implement routine neuropsychological assessments in the clinical setting. Perceived causative factors of cognitive
changes include ageing (79.9%), cancer-related fatigue (62.9%) and chemotherapy (32.1%). Fewer oncologists perceived chemotherapy as the main causative factor of cognitive changes, comparing to other health care professionals.
(56.4% vs. 83.3%, p=0.008). Psychosocial support and usage of complementary alternative medicines (CAM) were
identified as coping strategies of cognitive changes.
Conclusions: This is the first survey in the literature that has evaluated practitioners’ perception of chemotherapy-associated cognitive impairment. Asian cancer patients are affected by this phenomenon, however, perceived causative
factors remain debatable among practitioners of different professions. Future studies should evaluate the role of nonpharmacological interventions and CAM to manage these cognitive changes.
NOTES
38
9) Chronic exposure to chemotherapeutic drugs impairs cognitive function and neurogenesis (Lori-Ann CHRISTIE)
Authors : Lori-Ann Christie; Munjal M. Acharya; Vipan K. Parihar; Anna Nguyen; Vahan Martirosian; Charles L. Limoli
Institutional Affiliations :
Department of Radiation Oncology, University of California, Irvine, Irvine, USA
E-mail of the corresponding author : [email protected] (Lori-Ann Christie)
Purpose: A substantial proportion of breast cancer survivors report significant, long-lasting impairments in cognitive
function, often referred to as ‘chemobrain’. Advances in early detection and treatment mean that many more patients
are surviving long-term following a diagnosis of invasive breast cancer. Thus, it is becoming increasingly important to
define the types, extent and persistence of cognitive impairments following treatment with cytotoxic cancer drugs. In the
present study, we examined the effects of chronic treatment with two agents commonly used in breast cancer patients,
cyclophosphamide and doxorubicin (Adriamycin).
Methods: Athymic nude rats were given 50mg/kg cyclophosphamide, 2mg/kg doxorubicin or saline injections once per
week for 4 weeks. A battery of cognitive tasks was employed to characterize learning and memory ability, including a
novel place recognition task and contextual and cued fear conditioning. Dual immunofluorescence staining for immature
and mature neurons was used to assess changes in hippocampal neurogenesis.
Results: Cyclophosphamide-treated rats showed significantly impaired performance on both the novel place recognition
task and the contextual fear conditioning task compared to untreated controls, suggesting disrupted hippocampal-based
memory function. Similarly, doxorubicin-treated animals explored the novel spatial position less than expected by chance
during novel place recognition testing, and showed disrupted contextual memory as assessed by the fear conditioning
task. Chemotherapy-treated animals showed a significant decline in neurogenesis (>80% drop), and the number of
newly born neurons was also significantly reduced by ~50% in treated groups. Moreover, the morphology of immature
neurons in treated animals was characterized by abnormal dendritic arborization.
Conclusions: Our results demonstrate that chronic treatment with two commonly-used chemotherapeutic agents induces lasting impairments in a range of cognitive abilities that are coincident with altered neurogenesis. Our findings
suggest that strategies to prevent or repair unintended disruption of hippocampal neurogenesis may be effective in
ameliorating this serious, currently untreated side effect in cancer survivors.
NOTES
39
10) Emotional brain rhythms and their impairment in post-traumatic patients
(Jonathan E. Cohen)
Authors: Jonathan E. Cohen
Ilan Shelef 4, Talma Hendler
, Hadar Shalev 2, Roee Admon 3, Shy Hefetz 1, Christopher J. Gasho 4, Lavi J. Shachar 1,
& Alon Friedman 1
1,4
3
Institutional Affiliations:
Departments of 1Physiology and Neurobiology, 2Psychiatry and 4Radiology, Soroka University Medical Center and Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, POB 653, Beer-Sheva 84105, Israel
3
Functional Brain Imaging Unit, Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
4
Sharett Institute of Oncology, Hadassah Medical Organization, Jerusalem, Israel.
E-mail of the corresponding author: [email protected]
Purpose: Patients with post-traumatic stress disorder (PTSD) suffer from a failure of cognitive control over emotional
distracters. The physiological substrates of cognitive-emotional interactions and their breakdown in disease are, however, unknown.
Methods: Here, we studied brain activity in PTSD patients and healthy controls in response to emotion-provoking pictures using electroencephalography and functional magnetic resonance imaging (fMRI).
Results: We demonstrate that in healthy individuals, emotion-induced frontal theta rhythm modulates activity in the
beta rhythm mainly in sensory-motor regions. In contrast, in PTSD patients, beta activity is elevated irrespective of
emotion, and is not modulated by frontal theta activity in response to negative emotion. EEG source localization and
fMRI findings suggest that theta activity is localized to the pre-frontal and anterior cingulate cortices while beta activity
is localized to sensory-motor regions. We further found that beta activity in sensory-motor regions is related to the emotion-induced slowing of the motor response in healthy controls while the excess frontal theta activity in PTSD is related
to the intensity of negative emotional experience.
Conclusions: These findings reveal for the first time the importance of brain electrical oscillations and coherence in
emotional top-down modulation and point to specific failure of these mechanisms in PTSD. The methods and findings
described herein may have implication for the study of cancer, emotion and cognition.
NOTES
40
11) Cognition Declines as a Function of Number of Chemotherapy Cycles in Breast
Cancer Patients (Barbara COLLINS)
Authors : Barbara Collins, Ph. D.†, Joyce MacKenzie, M. Ps.†, Giorgio Tasca, Ph. D. †, Carole Scherling, M. Sc.*, Andra
Smith, Ph. D.*
Institutional Affiliations : † Ottawa Hospital, Canada; * University of Ottawa, Psychology, Canada
E-mail of the corresponding author : [email protected]
Purpose: The purpose of this study was to determine if cognition worsens with cumulative chemotherapy exposure.
We reasoned that the demonstration of such a “dose-response” relationship would help to establish whether cognitive
changes are caused by neurotoxic effects of chemotherapy or other confounding factors such as mood and fatigue.
Methods: 60 women with early stage breast cancer, aged 65 or younger with no previous history of cancer or chemotherapy, were matched to 60 healthy women on age and education. Neuropsychological assessment was conducted
after surgery but prior to commencing chemotherapy and then again following each chemotherapy cycle in patients and
at equivalent intervals in healthy controls. We used hierarchical linear modeling to compare change over time between
the groups in an overall Cognitive Summary score as well as domain-specific cognitive scores.
Results: After controlling for baseline performance, baseline depression, age, and education, there was a significant
group difference in change over time in the Cognitive Summary score, as well as in a Working Memory score and a Processing Speed score (p ≤ .001 in each case). This gap between the groups widened with each successive treatment.
While increases over time in depression, physical symptoms, and, especially, fatigue were correlated with decline in
overall cognitive function, they did not entirely explain the progressive worsening of neuropsychological performance
over time in the chemotherapy group.
Conclusions: These results show that cognitive function progressively worsens with cumulative chemotherapy exposure. While depression, physical symptoms and, particularly, fatigue were all related to declining neuropsychological
performance, these variables did not entirely account for the adverse effects of chemotherapy on cognition, suggesting
a more direct biochemical mechanism.
NOTES
41
12) Brain structure and function in breast cancer survivors: Relation to cognitive
complaints, oxidative DNA damage and time since chemotherapy (Susan K. CONROY)
Authors: Susan K. Conroy 1,2, Brenna C. McDonald 1*, Dori J. Smith 1, Lyndsi R. Moser 3, John D. West 1, Lisa M. Kamendulis 4*, James E. Klaunig 4*, Susan M. Perkins 5*, Victoria L. Champion 6*, Fred W. Unverzagt 3*, Andrew J. Saykin 1*
Institutional Affiliations:
1
Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana USA
2
Medical Scientist Training Program and Medical Neurosciences Graduate Program, Indiana University School of Medicine, Indianapolis, Indiana USA
3
Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana USA
4
Environmental Health Department, Indiana University School of Health, Physical Education, and Recreation, Bloomington, Indiana USA
5
Department of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana USA
6
Center for Research and Scholarship, Indiana University School of Nursing, Indianapolis, Indiana USA
*
Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana USA
E-mail of the corresponding author : [email protected]; [email protected]
Purpose: The purpose of this study was to 1) compare brain structure and function in breast cancer survivors (BCS) to
healthy controls; 2) assess the effect of time since chemotherapy on brain structure and function; and 3) evaluate the
association of these neural changes with neuropsychological testing, self-reported cognition, and DNA damage.
Methods: Structural and functional 3.0T MRI scans were acquired on 25 BCS treated with chemotherapy and 23 healthy
controls. Gray matter (GM) density was examined with voxel-based morphometry (VBM). Working memory-related fMRI
brain activation was assessed during a 3-back task. Neurocognitive testing results were summarized using composite
domains. The FACT-COG and MASQ assessed self-reported cognition. Comet assays were performed on blood samples
to measure DNA damage.
Results: Between-group VBM indicated decreased BCS GM density in left substantia nigra/thalamus, left middle frontal
gyrus, and right cerebellum. Decreased GM density in the substantia nigra/thalamus and cerebellum was associated
with increased oxidative DNA damage and cognitive complaints; decreased left frontal GM density was associated with
decreased psychomotor function. Brain activation was decreased in BCS in frontal, parietal, cerebellar, and basal ganglia
regions. Decreased left precentral gyrus activation was correlated with increased cognitive complaints and decreased
psychomotor function.
Within BCS, a longer post-chemotherapy interval was associated with increased GM density in the right basal ganglia
and decreased working memory activation, most pronounced within right cingulate and frontal regions. Within a right
inferior parietal lobule cluster, decreased activation was associated with decreased psychomotor function and increased
direct DNA damage and cognitive complaints.
Conclusions: Our results suggest brain changes associated with both breast cancer and its treatment. Self-report,
neuropsychological, and DNA damage correlates suggest both functional effects and pathophysiological underpinnings
of such changes. These neural changes in BCS associated with post-treatment interval warrant replication but are
consistent with the limited prior literature.
NOTES
42
13) Structural Neuroimaging and Cognitive Functions in Adult Stem Cell Transplant
Recipients (DD CORREA)
Authors: Correa DD 1, Peck KK 3, Root J 2, Moore D 4, Relkin N 5, Lis E 6, Jakubowski A
7
Institutional Affiliations:
1
Departments of Neurology; 2 Psychiatry & Behavioral Sciences; 3,6 Radiology; 7 Medicine,
Memorial Sloan-Kettering Cancer Center; Department of Neurology 1 4 5, Weill Cornell Medical College
E-mail of the corresponding author: [email protected]
Purpose: Hematopoietic stem cell transplantation (HSCT) is often used in the treatment of hematologic disorders.
Although it can be curative, the pre-transplant conditioning regimen may be associated with neurotoxicity. In this prospective study, we assessed brain structure and cognitive functions before and one year after HSCT.
Methods: Twenty-eight patients with hematologic disorders participated in the study. Nineteen patients received conditioning treatment with high-dose (HD) chemotherapy and nine received full dose total body irradiation (fTBI) and HD
chemotherapy prior to undergoing an allogeneic or autologous HSCT. Brain magnetic resonance imaging and neuropsychological evaluations were conducted before the conditioning treatment and one year following HSCT. We assessed
changes in brain structure using voxel-based morphometry (VBM), brain ventricular quantification (BVQ), and diffusion
tensor imaging (DTI); standardized neuropsychological measures were used to assess cognitive functions.
Results: In patients who received conditioning treatment with fTBI and HD chemotherapy, there was an 8% increase in
ventricular volume and a significant decrease in white matter fractional anisotropy (FA) in the corpus callosum (p=0.01)
one year post-HSCT; there was a trend toward a decline in visual recognition memory (p=0.051). In patients who
received conditioning treatment with HD chemotherapy, there was a 5% increase in ventricular volume, a significant
reduction in dorsolateral prefrontal cortex volume bilaterally (left side p=0.046; right side p=0.047), and a significant
decrease in whole white matter mean diffusivity (MD; p=0.001), radial diffusivity (RD; p=0.002) and axial diffusivity
(AD; p=0.009) one year post-HSCT; there was a trend toward a decline in attention (p=0.053) and significant improvements in memory (p<0.04).
Conclusions: This prospective study used multiple modalities to document brain structural changes one year following
HSCT, including ventricular enlargement, alterations in white matter integrity, and reduction in regional gray matter
volume. There was no significant cognitive decline, and memory function improved in patients treated with HD chemotherapy.
NOTES
43
14) Profile of Cortisol Secretion in Long-Term Breast Cancer Survivors (Marie-Eve
COUTURE-LALANDE)
Authors: Couture-Lalande, Marie-Ève, & Bielajew, Catherine
Institutional Affiliations:
University of Ottawa
E-mail of the corresponding author: [email protected]
Purpose: Atypical cortisol secretion rhythm (e.g. flatter diurnal slope and blunted cortisol response to acute stressors)
is seen in many breast cancer survivors. However, no study has investigated if these patterns persist in breast cancer
survivors with no evidence of disease long after diagnosis.
Methods: Nineteen cancer-free breast cancer survivors (mean time since diagnosis = 6 years, ranging from 1 to 21
years) and 24 women in the comparison group took part in this study. Participants supplied saliva samples over two days
in order to evaluate their cortisol diurnal rhythm. Shortly thereafter, they underwent exposure to a brief psychosocial
stressor using the Trier Social Stress Test. This task is a standardized protocol developed two decades ago for inducing a
moderate stress response in the laboratory. On test day, serial saliva samples were collected for cortisol analyses before
and after stress administration in order to obtain a profile of recovery function. In addition, we included a number of
self-report measures related to stress experience, psychosocial questions and medical history.
Results: Preliminary analyses indicated no group differences in the diurnal pattern but a blunted cortisol response to
the acute stressor in breast cancer survivors relative to control participants. Trend analysis revealed a significant linear
effect (p=.015) in the period following the stressor in breast cancer survivors but not in the control group participants.
In the latter, cortisol concentrations were higher overall and peak levels almost twice that of the cancer group (p=.023).
Time since diagnosis was not a significant covariate indicating that the HPA axis response to stress does not normalize
even years after the cancer diagnosis.
Conclusions: These data suggest that breast cancer survivors display a maladaptive glucocorticoid system in response
to stressors and that this pattern persists long after diagnosis. This may have implications for the long-term health of
these women.
NOTES
44
15) Priming cognitive problems following chemotherapy: The influence of stigma
consciousness (Enny DAS )
Authors : Enny Das
1
Wendy Jacobs
1, 2
Simone Monster
1
Sanne Schagen
2
Institutional Affiliations :
1
VU University, Amsterdam
2
Netherlands Cancer Institute, Amsterdam
E-mail of the corresponding author: [email protected]
Purpose: Recent studies suggest that informing patients about the relation between chemotherapy and cognitive problems may contribute to the occurrence of cognitive problems in cancer patients. The present study examined the conditions under which ‘stereotype priming’-effects occur and mediating processes.
Methods: In an online experiment, the influence of informing patients about the association between cognitive problems
and chemotherapy was investigated among126 female breast cancer patients. Half of the patients received the introduction that ‘some patients treated with chemotherapy experience cognitive problems’; the other half received a neutral
introduction. Self-reported cognitive complaints were measured with the Dutch version of the Cognitive Failure Questionnaire. Cognitive performance was assessed with the Groningen Fifteen Words Test. Stereotype activation was measured
by asking patients to complete word fragments, e.g., BR… can be completed as BRAIN or BROWN. Stigma consciousness
was measured by 8 items for the Stigma Consciousness Questionnaire, e.g. ‘the fact that I am a cancer patient influences
how people act with me’. Data were analyzed with regression analyses, controlling for confounding factors.
Results: Priming differentially affected cognitive complaints and test scores depending on the level of consciousness of
cancer patient stigma. Priming increased cognitive complaints for patients high in stigma consciousness and decreased
cognitive complaints for patients low in stigma consciousness (β = .199, t = 2.40, p= .02). In contrast, priming increased
cognitive test scores for patients high in stigma consciousness, and decreased test scores for patients low in stigma
consciousness (β = .184, t = 2.05, p<.05).
Conclusions: Patient information may increase the activation of cognition-related concepts, which differentially affects
self-reported cognitive function and neuropsychological test performance depending on stigma-consciousness. Patients
who are aware of patient stigma appear motivated to fight stereotypes, which may be successful in the short run but
hard to sustain over time.
NOTES
45
16) Evaluation of the cancer targeted therapy Everolimus on cognitive functions,
cerebral plasticity and brain metabolism in a mice model (Martine DUBOIS)
Authors: Martine Dubois 1, Vadim LeJoncour 1, Nicolas Lapinte 1, Marie-Christine Tonon 1, Pierrick Gandolfo 1, Florence
Joly 3,4, Pascal Hilber 2 and Hélène Castel 1
Institutional Affiliations:
1
U982 Inserm, Laboratoire DC2N, Equipe Astrocyte et Niche Vasculaire, IFRMP 23, Université de Rouen, France;
2
EA 4306, Laboratoire PSY NCA, IFRMP 23, Université de Rouen, France;
3
Centre François Baclesse, Caen, France;
4
Centre Hospitalo-Universitaire, Caen, France.
E-mail of the corresponding author: [email protected]
Purpose: Cancer and treatments can induce cognitive impairments in patients, called “chemofog”. Although direct
effect of chemotherapy on cognitive functions and neurogenesis has been demonstrated in animal models, the impact
of targeted therapies has never been investigated. Everolimus (Afinitor®), which blocks the mTOR pathway, alters cell
proliferation, metabolism and neoangiogenesis. Thus, we used a validated behavioral animal model to evaluate the
potential cognitive troubles induced by Everolimus. In addition, ex vivo analyses were conducted on neural cell plasticity,
endothelial architecture in hippocampus and cerebral metabolism.
Methods: During two weeks, adult C57BL/6J Rj males mice daily received Everolimus (5 mg/kg) by gavage, before to
be subjected, one week later, to behavioral tests. Ex vivo cerebral cytochrome oxidase activity and hippocampal neurogenesis, and in vitro neural stem cells and endothelial cells survival were investigated.
Results: Everolimus-treated mice displayed reduced weight gain from the last day of the treatment period. The treatment did not alter neither emotional reactivity, nor learning and memory performances, nor behavioral flexibility. Alterations of metabolic activity in brain regions involved in energy balance, food intake, reward, learning and memory
modulation, sleep/wake and arousal were detected after two weeks of treatment. Everolimus did not alter hippocampal
neurogenesis and neural stem cells viability in culture whereas it reduced the density of vascular niches and the number
of cultured endothelial cells.
Conclusions: Everolimus did not induce alterations of cognitive performances evaluated in hippocampal and prefrontal
cortex-dependent tasks sensitive to chemotherapy. Selective modifications of cerebral activity in brain areas involved in
feeding behavior likely associated to weight gain reduction, and/or the sleep/wake cycle, would suggest that hypothalamus represents the key target of Everolimus. As revealed by this animal model, symptoms (weight loss and fatigue) of
patients receiving targeted therapies may be directly consecutive to the treatment.
NOTES
46
t
t
17) Relation between self reported neurocognitive concerns and neuropsychological
test performance in adult brain tumor patients: Does tumor location matter?
(Kim EDELSTEIN)
Authors : Kim Edelstein
, Brenda Spiegler
1,2
, Lori Bernstein
3,4
1,2
Institutional Affiliations :
1
Psychosocial Oncology and Palliative Care, Princess Margaret Hospital;
2
Psychiatry and 3 Pediatrics, University of Toronto;
4
Psychology, The Hospital for Sick Children
E-mail of the corresponding author : [email protected]
Purpose: To examine self-reported neurocognitive difficulties, symptoms of anxiety and depression, and performance
on standardized neuropsychological tests in adult brain tumor patients.
Methods: Participants were 15 brain tumor patients (20-62 years old; mean±SD: 43.4±14.0) diagnosed between
the ages of 16 and 56 (37.8±12.1). Time since diagnosis ranged from 0.3-23 years (5.7±6.2). Participants completed
standardized neuropsychological tests and questionnaires about mood (BDI-2, STAI). Self-reported neurocognitive difficulties were measured using the Neurocognitive Questionnaire (NCQ), developed to monitor neurocognitive functioning
in adult survivors of childhood cancers across four domains: Task Efficiency, Emotional Regulation, Memory, and Organization. The NCQ has good psychometric properties with factor scores discriminating between healthy survivors and
survivors at risk for neurocognitive impairment due to CNS-directed treatment.
Results: Full scale IQ (WASI) was average (103.3±11.4; range 80-118). All four NCQ domains showed some association with Anxiety (Task Efficiency, r=.65, p=.008; Emotional Regulation, r=.53, p=.044; Memory, r=.49, p=.07;
Organization, r=.73, p=.002). Two of the domains were correlated with performance on standardized verbal tasks (Task
Efficiency, r=.56, p=.03; Memory, r=.53, p=.04) but not other neuropsychological performance domains. Task Efficiency
was also correlated with longer time since diagnosis (r=.65, p=.009).
r
Next, we split the sample based on tumor location. Patients with subcortical tumors (n=7) endorsed more Organization
problems (t(13)=2.35,p=.04) and symptoms of anxiety (t(13)=-2.15, p=.05) than did patients with cortical tumors
(n=8), perhaps reflecting damage to limbic brain regions. Patients with cortical tumors performed more poorly on tests
measuring speed (t(13)=2.10, p=.06) and executive function (t(13)=2.25, p=.04), which may reflect lack of insight,
tumor burden, or both.
f
Conclusions: We are continuing to explore the role of tumor factors (location, prognosis, time since diagnosis), adjustment (anxiety, depression) and test sensitivity/specificity in a larger cohort of brain tumor patients to better understand
the relation between performance and subjective concerns in adult brain tumor patients.
NOTES
47
18) Effects of a Cognitive Rehabilitation Pilot Program for Breast Cancer Survivors
(LM ERCOLI)
Authors: Ercoli LM
, Castellon SA 3, Kwan L 4, Cernin PA 1, Hunter AM 1, Leuchter AF
1,2
, Ganz PA
1,2
1,2,4
Institutional Affiliations:
1
UCLA Semel Institute for Neuroscience and Human Behavior;
2
UCLA David Geffen School of Medicine;
3
Veteran’s Administration Greater Los Angeles Healthcare System;
4
Jonsson Cancer Center
E-mail of the corresponding author: [email protected]
Purpose: Many breast cancer survivors (BCS) exposed to adjuvant chemo and hormonal therapy complain of cognitive
difficulties, known as ‘chemobrain’, and approximately 25% show reductions on neuropsychological (NP) tests. Our team
developed a cognitive rehabilitation intervention for BCS. We report results of a phase-II single-arm study evaluating the
efficacy of the intervention on cognitive complaints and NP functioning.
Methods: The manualized, small group intervention of 5 once-weekly, 2-hour sessions included psycho-education,
in-class and at-home cognitive exercises, and goal setting. Eligibility: Disease free BCS with cognitive complaints that
interfere with daily activity; diagnosed with stage I, II or III breast cancer; completed primary treatment 18-months to
5 years earlier; current endocrine therapy allowed. NP Tests: Standardized and computerized tests of memory, executive, psychomotor, attention/processing speed and other domains. Subjects completed the Patient’s Assessment of Own
Functioning Inventory (PAOFI) covering cognitive complaints of Memory, Communication, Motor-Sensory, Executive, and
Total score. Assessments occurred at baseline, immediately, 2-months and 4-months post-intervention. Nine of the
subjects underwent resting state quantitative electroencephalography EEG (QEEG) at baseline and immediately postintervention to assess the relationship of brain function with complaints.
Results: 28 subjects [Mean Age (SD) = 53.7 (6.2)] completed 4-month post-testing. At immediate post-intervention,
motor and psychomotor speed tests, PAOFI Memory and Total differed significantly from baseline (p-values range:
0.0001 to 0.0391). All, except for motor speed, remained significant at 2-and 4-month post-intervention (p-value range
<0.0001 to 0.0361). Executive tests showed late improvement. Improvement on PAOFI Memory and Total were positively associated with increases in QEEG absolute alpha power (r range = .81 to .88, p-value range .007 to .002).
Conclusions: Cognitive complaints and NP performances in BCS improve immediately following a 5 week intervention.
Some improvements were sustained up to 4 months. The correlation of QEEG measures with improved PAOFI scores
suggests a biological basis for cognitive complaints.
NOTES
48
A
19) Long-term effects of oxaliplatin on cognitive function and the association with
peripheral neuropathy in laboratory rodents (Joanna E FARDELL)
Authors : Joanna E Fardell
, Janette Vardy
1, 2
, Ian N Johnston
2, 3, 4
1
Institutional Affiliations :
1
School of Psychology, The University of Sydney, Australia
2
Cancer Institute New South Wales, Australia
3
Sydney Medical School, The University of Sydney, Australia
4
Sydney Cancer Centre, Concord Repatriation General Hospital, Australia
E-mail of the corresponding author : [email protected]
Purpose: A subset of cancer survivors experience long-term cognitive impairments due to chemotherapy treatment.
The aetiology and risk factors of this impairment are unknown. Our aim was to examine the impact of oxaliplatin dose
on long-term cognitive outcomes in an animal model, and to determine if there was an association with peripheral neuropathy (PN).
Methods: Healthy male Sprague-Dawley rats (N=38) were treated with oxaliplatin (0.6, 2, or 6mg/kg) or physiological
saline (control) weekly for 3 weeks. Cognitive function was assessed 1 week and 1, 4, 6 and 11 months post-treatment
using object location recognition (OLR), a measure of spatial memory, and novel object recognition (NOR), a measure of
object memory. Mechanical sensitivity, an indicator of PN, was assessed using von Frey filaments. Repeated measures
ANOVA were conducted on each variable.
Results: There was a significant effect of dose on NOR performance (F(3,33)=4.762, p<.05); rats treated with high dose
oxaliplatin (6mg/kg) displayed poor object recognition compared to controls up to 11 months post-treatment. Similarly,
there was a significant effect of dose (F(3,33)=7.690, p<.05), and time (F(4,132)=3.109, p<.05) on OLR performance,
but no interaction effect was seen. Two weeks after treatment completion, rats treated with oxaliplatin had poor OLR
regardless of dose, while rats treated with 6mg/kg OX displayed lasting impairment at 11 months post OX. There was
a significant interaction between time since treatment and dose and the extent of PN (F(21,231)=5.066, p<.05); rats
treated with higher doses of OX displayed greater PN, but this resolved after treatment completion.
Conclusions: This study demonstrates that, in the absence of cancer and other anti-cancer treatments, oxaliplatin
continues to impair both object and location memory in healthy rodents long after treatment. The type and severity of
cognitive impairment was determined by oxaliplatin dose and was associated with PN experienced during chemotherapy.
NOTES
49
20) Research Design of TRIMc: Testosterone Replacement in Men with Cancer: Effect
of Physiologic Testosterone Replacement on Functional Status and Quality of Life and
in Male Patients with Cancers Unrelated to Androgens (Stewart FLEISHMAN)
Authors: Fleishman, Stewart, MD; Rosenwald, Victoria, RN MPH
Institutional Affiliations:
Continuum Cancer Centers of New York: Beth Israel & St. Luke’s-Roosevelt, 10 Union Square East , 4th Floor, New York,
NY 10003, USA
E-mail of the corresponding author: [email protected]
Purpose: The proposed study investigates whether replacement of testosterone (T) to physiologic levels will improve
overall quality of life (QoL) including cognitive function, functional status, and sexual function due to hypogonadism. The
complaint of « chemobrain » is well-known in women. An investigation of the prevalence of and potential for treatment
of cognitive symptoms in male cancer patients and survivors has not been done.
Methods: We designed a multi-site randomized double-blind placebo-controlled trial to assess effectiveness of androgen replacement in 305 male cancer patients age <71. Eligibility : score >1 on FACT-P for at least 1 “lack of energy, I
feel sad, or I feel ill” questions AND at least 1 sexual function question . Baseline Total T < 300 ng/dl, or free T < 50 pg/
dl ,and PSA < 4 ng/ml. Subjects will be randomly assigned to 12 weeks of treatment with 50 mg transdermal testosterone or matching placebo with possible dose escalation to maintain physiologic levels, T = 300-1000 ng/dL. Cognitive
function will be assessed at baseline and end of treatment by High-Sensitivity Cognitive Screen. Clinically significant
improvement in cognitive function is defined as 0.5 SD above baseline.
Results: The sample is calculated to have 90% power to detect 20% improvement in functional and overall QoL.
Conclusions: Our large epidemiological survey (Fleishman SB, Khan H, Homel P et al, Testosterone Levels and Quality
of Life in Diverse Male Patients with Cancers Unrelated to Androgens, J Clin Oncol 28:5054-5060, 2010) documented a
high incidence (48% by Total T, 66% by Bioavailable T) of hypogonadism. In addition, men were physically, functionally,
and sexually symptomatic. Using functional outcomes, cognitive testing and QoL assessments will determine whether
symptoms of hypogonadism are reversed with testosterone replacement, and demonstrate that the intervention does
not simply correct low T levels.
NOTES
50
21) The Association Between Aromatase Inhibition (AI), Cognitive Function, and PET
Metabolism (M HARDT)
Authors : M Hardt 1, D Silverman 2, S Patel 1, C Geist 2, G Somlo 1, J Mortimer 1, T Luu 1, R Ramani 1, V Katheria 1,
K Hansen 1, J Brown 1, R Jayani 1, C Chuang 1, A Hurria 1
Institutional Affiliations :
1
City of Hope National Medical Center, Duarte, CA
2
UCLA David Geffen School of Medicine, University of California, Los Angeles, CA
E-mail of the corresponding author : [email protected]
Purpose: To understand the association between AI therapy and change in cognitive function, and correlate these
changes with regional cerebral metabolism
Methods: Sixty-seven participants [35 with stage I-III breast cancer (BC),32 age-matched controls], age 60+, enrolled
in this longitudinal study. The patients with BC completed a neuropsychological battery (7 domains) and Squire selfreported memory questionnaire prior to initiation of AI therapy and 6 months later. The control group completed the
assessments at the same timepoints. Ten patients and 10 controls underwent FDG PET scans at both timepoints. Cerebral activity was analyzed by standardized volume of interest (sVOI) and statistical parametric mapping (SPM).
Results: Patients had a mean age of 71 (SD 7, range 60-85) and controls had a mean age of 72 (SD 7, range 62-89).
At baseline, controls scored higher than patients on WAIS Digit Symbol (p<0.05) and Boston Naming Test (p<0.05).
Longitudinal change in performance (p<0.05) was seen between the 2 groups on Block Design (patients improved) and
WRAT-Reading Test (controls declined). Within the imaging cohort, controls demonstrated longitudinal improvement
on Rey-Osterrieth Complex Figure Test (ROCF), while patients receiving AI did not (p=0.01). sVOI analysis revealed
longitudinal differences between groups in right posterior cingulate (p<0.01), right caudate (p=0.03), and midbrain
(p=0.04) metabolism. Increased metabolism was observed in left medial temporal and cerebellar regions after AI relative to controls (SPM; p<0.01). Change in ROCF z-scores correlated with change in left primary visual cortex metabolism in controls (sVOI; p=0.014), but not in patients (p=0.5). Controls reported greater perceived longitudinal decline
in memory than patients.
Conclusions: In the overall cohort, there were no significant longitudinal declines in the cognitive performance of
patients relative to controls. In the PET cohort, however, changes in visual memory were noted by both neuropsychological testing and PET. Additional longitudinal follow-up is needed to understand the clinical significance of these findings.
NOTES
51
22) Time-Limited Neurocognitive Psychoeducational Workshop for Cancer Survivors
(Gabriela HÖHN)
Authors : Gabriela Höhn, Ph.D., Stewart B. Fleishman, M.D. & Victoria Rosenwald, RN, MPH
Institutional Affiliations :
Continuum Cancer Centers of New York: Beth Israel & St. Luke’s-Roosevelt, New York, NY USA
E-mail of the corresponding author: Victoria Rosenwald, RN, MPH: [email protected]
Purpose: This workshop provided information to participants, helped build an evidence-based intervention for future
participants, and piloted management strategies for neurocognitive limitations for those affected by cancer and cancerrelated treatment.
Methods: A four-week semi-structured psychoeducational workshop was developed. Participants attended as many
sessions as they were able, referred by oncology staff, or self-referral. Groups were limited to 8 to allow for individualized attention and participation. Sessions lasted 1.5 hours, and were facilitated by a neuropsychologist who was also a
cancer survivor. A specific topic was selected for each week: “Memory”, “Attention and Concentration”, “Planning”, and
“Everyday Thinking.” Each workshop included a short presentation. Patients reported cognitive problems, shared personal experiences and discussed difficulties encountered. Strategies to assist or compensate for self-reported decline in
function were discussed, with participants sharing their own coping strategies, or exploring their own solutions with the
group’s input and facilitator’s guidance.
Results: Participants gave feedback at the end of each group, as well as at the end of the series, on surveys using a five
point Likert Scale, ranging from: 1=Not at all Helpful, to 5= Extremely Helpful. Six of the eight workshop components
surveyed were assessed as “very helpful” or “extremely helpful.” These included information provided, support received
from other members, effectiveness of the facilitator, cognitive strategies discussed, handouts given at each workshop,
and “usefulness for my daily life.” The format and structure of the group, as well as the time and day it was offered were
ranked as “adequately helpful” to “very helpful.” Participants expressed feelings of relief, validation, and appreciation
for the workshops. Many indicated that they had not been told to expect cognitive changes, or that cognitive functions
could persist after treatment ended.
Conclusions: Education and compensation strategies can successfully address both the psychosocial and cognitive
impact of cancer and cancer-related treatment.
NOTES
52
23) Mechanisms of Cyclophosphamide and Doxorubicin Induced Cognitive Decline
(Karen HUBBARD)
Authors : 1 Hubbard Karen, 1 Ragnauth Andre,
1
Levitt Jonathan and
2
Ahles Tim
Institutional Affiliations :
The City College of New York
Memorial Sloan Kettering Cancer Center
1
2
E-mail of the corresponding author : [email protected]
Purpose: We have employed a transdisciplinary approach to identify mechanisms involved in chemotherapy-induced
cognitive changes observed in cancer patients through the use an animal model system.
Methods: Ovariectomized Long-Evans rats were tail vein injected with a combination of cyclophosphamide and doxorubicin once a week for three weeks followed by cognitive studies using the Y maze behaviorial assay. The localization and
quantification of specific neuronal and cell cycle proteins were assesed in brain slices from control and treated animals
using immunohistochemical assays.
Results: We have found that animals treated with cyclophosphamide and doxorubicin exhibited impaired cognitive behavior in the Y maze assay consistent with other behavorial studies. We also found a significant decrease in NeuN positive
cells in the hippocampus, a biomarker for neurons, whereas GFAP, a biomarker for glia, was unchanged. This decrease
was more pronounced in the dentate gyrus. We also measured the number of cells expressing p16 and ARF, which are
growth inhibitors as well as tumor suppressors. We found a decrease in the number of p16 positive cells but not ARF
positive cells. This decrease was similiar to NeuN and also had a more pronounced decrease in the dentate gyrus. We are
currently using Western and RT-PCR analyses to determine the protein and mRNA levels of all of the biomarker studied
in control and treated animals.
Conclusions: While there was no gross alterations in the rat brains treated with cyclophosphamide and doxorubicin,
we observed significant decreases in the neuronal numbers of specific hippocampal regions. In addition, there was a
decrease in p16 positive neurons but not ARF. P16 regulates the Rb pathway, while ARF modulates p53. Thus, further
examination of the Rb and p53 pathways are warranted and may contribute to the loss of cognitive function observed
following chemotherapy.
NOTES
53
24) Chemotherapy-Related Cognitive Impairment (CRCI) Among Cancer Patients and
Quality of Life (QOL): A University of Rochester Cancer Center Clinical Community
Oncology Program (URCC CCOP) Study of 439 Patients (Michelle C. JANELSINS)
Authors: Michelle C. Janelsins*, Karen M. Mustian, Shelli R. Kesler, Katie A. Devine, Gary R. Morrow
Institutional Affiliations:
University of Rochester Cancer Center – Janelsins, Mustian, Devine, Morrow, Stanford University, Kesler
E-mail of the corresponding author*: [email protected]
Purpose: CRCI, including impairments in memory and concentration, affects up to 75% of cancer patients during chemotherapy, and can linger for years after chemotherapy has ended. The extent to which CRCI affects QOL is not wellunderstood.
Methods: Levels of memory and concentration impairments were measured in 439 patients undergoing chemotherapy
who were enrolled in a nationwide URCC CCOP randomized trial. Memory and concentration were assessed via the
Fatigue Symptom Checklist (FSCL) from those that completed the measure at cycles 2, 3, and 4 of chemotherapy. QOL
(i.e., general activity, mood, normal work, and enjoyment of life) items were assessed by the Brief Fatigue Inventory
(BFI). Spearman’s rho correlations were used to determine the strength of the relationship between cognitive function
and QOL. Logistic regression was used to predict associations between memory and concentration at cycle 2 and 3 with
cycle 4 and to predict memory and concentration difficulty at cycle 2 with interference in QOL at cycle 4.
Results: Concentration and memory impairments at cycles 2 and 3 were both significant predictors of concentration
and memory difficulty at cycle 4 (OR range=1.94 to 9.08; all p <0.05). At cycles 2, 3, and 4, problems with memory
and concentration were significantly correlated with interference in all QOL items assessed (r values range=.16 to .37,
all p <0.05). Concentration difficulty at cycle 2 was significantly predictive of interference in all QOL items at cycle 4 (OR
range=2.23 to 3.34; all p <0.05). Memory difficulty at cycle 2 was only significantly predictive of interference in mood
at cycle 4 (OR=2.05, p <0.05) and not other items (OR range=1.33 to 2.13; p >0.05).
Conclusions: Memory and concentration impairments in cancer patients receiving chemotherapy are associated with reductions in QOL. Further research on the long-term effects of CRCI on QOL is needed. NCIR25CA01618 and U10CA37420
NOTES
54
25) Changes in Cognition in Men Treated with Androgen Deprivation Therapy For
Prostate Cancer: A Controlled Comparison (Heather JIM)
Authors: Heather Jim
1
, Kristin Phillips
1
Laura Mayhew
2
, Heather McGinty
2
, Brent Small
2
and Paul Jacobsen
1
Institutional Affiliations:
1
Moffitt Cancer Center, Tampa, FL;
2
University of South Florida, Tampa, FL
E-mail of the corresponding author: [email protected]
Purpose: Studies suggest that androgen deprivation therapy (ADT) for prostate cancer is associated with reduced
cognition, particularly in visuospatial domains. Most of these studies were cross-sectional or have not included matched
control groups. Thus, well-controlled studies of change in cognition following initiation of ADT are scarce. The goal of
the current study was to examine changes in cognition in prostate cancer patients starting ADT compared to a matched
sample of men without cancer.
Methods: As part of a larger study, prostate cancer patients (n=55, mean age 66, range 49-90) completed standardized
neuropsychological testing prior to initiation of ADT and six months later. Men without cancer (n=46, mean age 69,
range 55-90) matched to patients on age, education, and geographic location were assessed at comparable time points.
Results: ANOVAs indicated a significant group-by-time interaction for spatial attention (p=.05), controlling for age and
estimated IQ. Prostate cancer patients displayed a significant decline in spatial attention (p<.05), while there was no
change over time in non-cancer controls. While there was no group difference in spatial attention at time 1 (p=.39), at
time 2 prostate cancer patients performed significantly worse than non-cancer controls (p=.01).
Conclusions: Results from the current study suggest that ADT for prostate cancer is associated with deficits in spatial
attention. Future studies should examine the efficacy of behavioral interventions to improve spatial attention in this
population.
NOTES
55
26) A Meta-Analysis of Cognitive Functioning in Adult Survivors Previously Treated
with Standard-Dose Chemotherapy (Heather JIM)
Authors: Heather Jim 1 , Kristin Phillips
Hussin 1 , Paul Jacobsen 1 , Brent Small
1
6
, Sari Chait
2
, Leigh Anne Faul
3
, Mihaela Popa
4
, Yun-Hsiang Lee
5
, Mallory
Institutional Affiliations:
1
Moffitt Cancer Center, Tampa, FL, USA;
2
VA Boston Healthcare Center, Jamaica Plain, MA, USA;
3
Georgetown University, Washington D.C., USA;
4
Biovest International Inc., Tampa, FL, USA;
5
National Taiwan University, Taipei, Taiwan; 6University of South Florida, Tampa, FL, USA
E-mail of corresponding author: [email protected]
Purpose: Evidence is mixed regarding longer-term cognitive deficits in patients treated with chemotherapy. Previous
meta-analyses have not focused on the post-chemotherapy period and have not incorporated several recent studies. The
goal of the current study was to conduct a meta-analysis of cognitive functioning in cancer survivors who were treated
with chemotherapy six or more months previously.
Methods: A search of PubMed, PsycInfo, CINAHL, and Cochrane Library yielded 2,751 abstracts. Meta-analysis was
conducted on 21 studies of 963 patients previously treated with standard-dose chemotherapy for solid, non-central
nervous system tumors. Neuropsychological tests were categorized according to eight cognitive domains: attention,
executive functioning, information processing, motor speed, verbal ability, verbal memory, visual memory, and visuospatial ability.
Results: Cognitive deficits were observed in patients treated with chemotherapy relative to controls or pre-chemotherapy baseline in verbal ability (g=-.14, p=.02) and visuospatial ability (g=-.23, p=.01). Study design (i.e., comparator)
was a significant moderator; patients treated with chemotherapy performed worse than non-cancer controls in verbal
ability and worse than patients treated without chemotherapy in visuospatial ability (ps<.05).
Conclusions: Meta-analysis indicates that on average, observed cognitive deficits in cancer patients previously treated
with chemotherapy are small in magnitude and limited to the domains of verbal ability and visuospatial ability. This
information can be used to educate patients regarding the long-term impact of chemotherapy on cognitive functioning.
NOTES
56
27) Juvenile rats treated with the chemotherapy agent methotrexate display impairments in reversal learning, and spatial recognition and working memory as adults.
(I. JOHNSTON)
Authors : I. Johnston 1, A. Price 1, J. Fardell 1, J. Vardy 2;
Institutional Affiliations :
School of Psychology, The University of Sydney, Australia;
Sydney Cancer Centre., University of Sydney, Australia
1
2
E-mail of the corresponding author : [email protected]
Purpose: Methotrexate is used both as a single agent drug and as part of multiagent chemotherapy regimens to treat
malignancies in children and adults. However, there are concerns that these protocols may be associated with both short
and long-term cognitive impairments in survivors, including impairments in memory and executive function.
Methods: Juvenile rats (Post-natal day [PND] 21) were treated with either methotrexate (2mg/kg i.p. twice weekly for
3 weeks) or with saline. Beginning PND60 (adults), the rats were tested for performance in a battery of learning and
memory tests.
Results: Methotrexate treated rats demonstrated impairments in the object location recognition but not the novel object
recognition test of short-term memory. Methotrexate treated rats did not show deficits in an ability to learn a Go-No
Go discrimination (a test of behavioural inhibition), but were impaired in learning to reverse this learning. Methotrexate
treated rats were not impaired in long-term memory in the water maze, but were impaired in delayed matching to place
and also in reversal learning in the water maze.
Conclusions: Taken together, this pattern of results suggests that paediatric administration of methotrexate induces
focal deficits in short-term spatial recognition and working memory, and in behavioural flexibility that persist into adulthood.
NOTES
57
28) The very late neurotoxic effects of chemotherapy in breast cancer survivors on
white matter integrity and brain function are dose dependent: preliminary results of
a multimodality MRI study (M.M. KEMPERMAN)
Authors : M.M. Kemperman
Schagen 1, PhD.
, MS; M.B. de Ruiter
1,2
, PhD; W. Boogerd 3, MD, PhD; L. Reneman 2, MD, PhD and S.B.
1,2
Institutional Affiliations :
1
Department of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands
2
Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
3
Department of Neuro-oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands
E-mail of the corresponding author: [email protected]
Purpose: Adjuvant chemotherapy for breast cancer (BC) is associated with cognitive problems and alterations in brain
structure and function. In a previous study, multimodality MRI was acquired in BC survivors who either received highdose chemotherapy (FEC-CTC) or radiotherapy (RT) ten years earlier.
In the current study, we extended our measurements to BC survivors who received conventional-dose chemotherapy
(FEC) ten years earlier and healthy controls (HC) without a history of cancer. This enables us to examine whether our
previous findings of very long-term neurotoxicity are generalizable to other chemotherapeutic regimens and types of
treatment for BC.
Methods: Fifteen FEC breast cancer survivors (58,6±4 yrs) and nineteen HC ( 58,4±3,7 yrs) were assessed by means
of neuropsychological testing and 3Tesla multimodal MRI (FLAIR, T1-weighted imaging, Diffusion Tensor Imaging, fMRI,
MR spectroscopy [1H-MRS]). Executive functioning and memory were also measured with an fMRI-adapted version of
the Tower of London (TOL) and a Paired-Associate Learning paradigm (PAL). These data were compared to previously
obtained and reported data in nineteen FEC-CTC (55.8 yrs±5,6) and fifteen RT subjects (57,7±5,8 yrs) (de Ruiter et al.).
Results: Only FEC+CTC was associated with a reduction of N-acetyl aspartate in parietal white matter, suggestive of
axonal injury.
Interestingly, both FEC+CTC and FEC were associated with reduced performance on the TOL and faster reaction times
on the TOL and the PAL compared to the RT and HC group. However, on both tasks, FEC+CTC was associated with hyporeactivity of frontoparietal regions whereas FEC was associated with hyperreactivity.
Conclusions: Our preliminary findings suggest that the very late neurotoxic effects of chemotherapy in breast cancer
survivors on white matter integrity and brain function are dose dependent. The other outcome measures have not yet
been analyzed. Inclusion of FEC and HC subjects will continue until December 2011.
NOTES
58
29) Executive functioning and stress regulation in breast cancer patients following
chemotherapy (M KOBUS)
Authors : Kobus M.
1
, Kieffer J.M.1 , Van den Berg E
2
, Schagen. S.B
1
Institutional Affiliations :
1
The Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Department of Psychosocial Research and Epidemiology ;
2
Utrecht University, Department of Psychology, division of Experimental Psychology.
E-mail of the corresponding author : [email protected]
Purpose: Studies have demonstrated cognitive dysfunction (e.g. memory, executive functioning, attention) in breast
cancer patients after chemotherapy. This study examines the effects of chemotherapy on aspects of executive functioning (EF), on stress regulation and stress experience in breast cancer patients, and on potential relationships between
factors.
Methods: Forty-two women (age M=49.2; SD=6.6), who were treated with different adjuvant cytotoxic regimens up to
five years ago (M=24.4 months), underwent an extensive neuropsychological assessment, which consisted of 10 EF tests
(12 test results) and questionnaires measuring coping style, stress experience and personality. Furthermore, objective
stress levels were measured by means of cortisol concentrations in hair strings, allowing for the assessment of chronic
stress. The results were matched to appropriate normative data, based on z-scores and analyzed by means of binomial
tests and correlation analysis.
Results: In breast cancer patients, 48% of women exhibited significant impaired EF profiles (z-scores of ≤-1.5 SD on at
least 2 tests, or ≤-2 SD on at least a single test; p ≤.001). EF was significantly impaired on three tasks (WCST, PASAT
and category fluency; all p’s ≤.0001). Performance on the Tower Test was reduced, although not statistically significant.
Avoidant and emotional coping styles were used less frequently in breast cancer survivors compared to norms, while
no difference was observed in task-oriented coping style. No difference was found between impaired and not impaired
breast cancer patients with respect to coping styles, personality, stress experience and cortisol levels. In addition, no
relation was found between EF performance and stress (cortisol levels or self-report).
Conclusions: Results suggest that multiple aspects of EF were impaired in our breast cancer group, involving set shifting, updating and fluency. No support was found for the use of less adaptive coping strategies and elevated stress levels
in impaired breast cancer patients.
NOTES
59
30) Cognitive function of elderly patients treated for a localized breast cancer: preliminary results of a French multicenter, prospective longitudinal study (Marie LANGE)
M. Lange 1,2, B. Giffard 1, A. Daireaux 2, C. Rieux 2, N. Heutte
F. Eustache 1, F. Joly 2,4,8
, S. Noal 2, J. Le Fel 5, O. Rigal 6, J.E. Kurtz 7,
2,3,4
Institutional Affiliations:
1
U923 Inserm-EPHE-Université de Caen Basse-Normandie, Caen, France
2
Unité de Recherche Clinique, Centre François Baclesse, Caen, France
3
UFR des Sciences Pharmaceutiques, Université de Caen Basse-Normandie, Caen, France
4
Equipe « Cancers et Populations » ERI3 INSERM, UFR de Médecine, Université de Caen Basse-Normandie, Caen
5
EA4306, Université de Rouen, Rouen, France
6
Département d’oncologie médicale, Centre Henri-Becquerel, Rouen, France
7
Département d’hématologie et d’oncologie, Hôpitaux universitaires de Strasbourg, Strasbourg
8
CHU Côte de Nacre, Caen, France
E-mail of the corresponding author: [email protected]
Purpose: Very few studies have been conducted among elderly patients although cancer mainly appears among seniors
and elderly are vulnerable to develop cognitive dysfunctions. Our goal was to clarify the incidence and nature of cognitive
disorders among elderly breast cancer patients and to evaluate the impact of adjuvant chemotherapy and the influence
of anxio-depressive factors and fatigue.
Methods: Episodic memory, working memory, executive functions, information processing speed, cognitive complaint,
anxiety, depression and fatigue were assessed with neuropsychological tests and self-reported quality of life questionnaires before (T0) and after (T6) adjuvant treatment. Cognitive impairment was defined as a score less than 1.5 standard deviation (SD) of normative data on >2 tests, or less than two SDs on >1 test. Preliminary results of this longitudinal study are presented.
Results: Results concern the first 87 elderly patients (71±4 years) with localized breast cancer already included: 33
treated with chemotherapy (CT) and radiotherapy and 54 without CT. Before any adjuvant treatment (T0), cognitive
impairments were observed for 67% of patients with CT (working and episodic memory mainly impaired) and 46% of
patients without CT (mainly impaired executive functions). Fatigue was reported for 27% and 42% of patients with
and without CT, respectively. For both groups, less than 10% of patients had anxio-depressive symptoms at baseline.
Anxiety, depression and fatigue were related to cognitive complaint but not to objective cognitive scores. Cognitive
complaint did not appear related to objective cognitive scores. These longitudinal results will be further developed at the
symposium in March 2012.
Conclusions: Almost half of elderly breast cancer patients were found to present objective cognitive impairment before
any adjuvant therapy. This proportion is higher among patients with CT indication. Consistent with previous studies,
anxiety, depression and fatigue were related to cognitive complaint but not to objective cognitive scores.
NOTES
60
31) Support of patients with cognitive disorders: interests of a “memory consultation” (Johan LE FEL)
Johan Le Fel
1
2
3
*, Aurélie Daireaux 2, Marie Lange 2, Florence Joly 2, Rovira Katia 1, Vincent Roy 1, Olivier Rigal
1,3
3
EA 4306, PSY-NCA, IFRMP 23, University of Rouen, France
Cancer Center François Baclesse and CHU, Caen, France.
Cancer Center Henri Becquerel, Rouen, France.
* Corresponding author: [email protected]
Purpose: Cancer and chemotherapy can have adverse effects on cognitive functions and quality of life of patients. To
date, no specific prevention or treatments have been developed despite a large number of patients who report subjective
cognitive changes related to cancer and its treatment. In 2010, a survey was conducted in three cancer day care departments and results show that 39% of the patients declared having memory disorders during and after their treatment.
Furthermore, 85% of the patients reported that the evaluation and the support of these troubles was one of the priorities
in the management of the treatment of side effects. Therefore, we proposed the creation of a “memory consultation” in
the supportive care service in order to assess and deal with the patients cognitive impairments.
Consultations implementation: First, we have developed informative documents distributed to the medical staff and
in waiting rooms of the different cancer day care departments. At their request, patients can meet a neuropsychologist
to conduct an assessment, which is composed of scales and tests to assess fatigue, emotional disorders and cognitive
functions (e.g. verbal memory, episodic memory, working memory, executive functions and attention).
Results since January 2011: 47 patients (46 women, 1 man), consulted for cognitive function complaints. Of these
patients, 70% were treated for breast cancer, 15% for ovarian cancer, 10% for lung cancer and 5% for a brain tumor.
The majority of these patients were consulted at the end of chemotherapy (80%). The assessments show that 25% of
patients had mild cognitive impairments, 50% had subtle disorders, and 25% didn’t have cognitive functions problems.
Concerning the orientation of these patients, approximately 35% were referred to psycho-oncologists to treat psychoemotional difficulties, 20% to a neurologist or to a pain support and 45% to neuropsychological support (20% to a neuropsychological follow-up, and 25% to “Memory workshops”). We will present at the conference all the data and results
of the « Memory workshops » support.
Conclusions: The “memory consultation” implementation in our various centers seems to have become a necessary
supportive care and responds to a growing demand from patients receiving chemotherapy treatments. The support proposed would improve cognitive function and hopefully, patient’s quality of life.
NOTES
61
32) Memory Consultation for patients treated for cancer: Psycho-Social Support
(Isabelle LEGER)
Authors: I. Léger
Institutional Affiliations:
Institut de cancérologie Gustave Roussy, 94805 VILLEJUIF Cedex, France
E-mail of the corresponding author: [email protected]
Purpose: Cognitive disorders after chemotherapy (chemofog) are frequently reported by patients. They are subtle and
transient. However, after treatment, for some patients these disturbances subjective or objectified by neuropsychological
tests persist and have a negative impact on their quality of life. Today very few structures offer a scheme of management
of these patients making a cognitive complaint. Thus in January 2009, with 25% of time neuropsychologist week, we
opened the first consultation in oncology to identify, to deal with the cognitive symptoms when possible, and to try to
improve the quality of life for patients.
Methods: A consultation Memory pamphlet is given to every patient who complained of cognitive impairment after
treatment during a medical or para-medical consultation. A neuropsychologist receives patients 3 weeks maximum after
taking up appointment. Consultation has 3 stages: a clinical interview including anamnesis and a clinical appreciation of
the patient’s psychological state. Next, a standardized neuropsychological assessment lasting 45 minutes and finally, a
restitution of results and a proposal supported if necessary.
Results: 101 patients have been received by the neuropsychologist and 20 retests have been done. The tests results
showed weakening performance in restitution memory, speed of information processing and on the executive functions.
For most patients is observed a depressive syndrome. Most patients accept the rehabilitation exercises. Depressed
patients recognize their fragile psychological state: 1 / 3 of them agreed to take a psychotropic treatment, and 2 / 3
agreed to meet at least once a psychologist.
Conclusion: At first glance, the reception of cognitive complaints of patients treated for cancer appears to participate in
improving their quality of life. This seems to be perceptil in the efficiency of daily activities through rehabilitation sessions
and good management of depressive symptoms.
A subsequent evaluation of this consultation is planned to refine its content and form
NOTES
62
33) How much is cognitive functioning related to the psychological adaptation of
elderly cancer patients: a longitudinal prospective multicentre study (Yves LIBERT)
Authors : Libert Y *1,2, Merckaert I
Bron D 5, Razavi D 1,2
, Dubruille S
1,2
, Etienne AM 3, Jonius B 3, Vandenbossche S
1,2
, Reynaert C 4,
1,2
Institutional Affiliations :
1
Clinique de Psycho-Oncologie, Université Libre de Bruxelles-Institut Jules Bordet, Bruxelles, Belgium.
2
Faculté des Sciences Psychologiques et de l’Education, Université Libre de Bruxelles, Bruxelles, Belgium.
3
Faculté de Psychologie et des Sciences de l’Education, Université de Liège, Liège, Belgium.
4
Service de Médecine Psychosomatique, Université Catholique de Louvain-CHU Mont-Godinne, Yvoir, Belgium.
5
Service d’Hématologie Clinique, Université Libre de Bruxelles-Institut Jules Bordet, Bruxelles, Belgium.
E-mail of the corresponding author : [email protected]
Purpose: The relations between subjective and objective cognitive functioning and psychological adaptation of patients
facing cancer treatment remain poorly understood. Increasing knowledge about this relation is especially relevant for
elderly cancer patients. This study aims to assess the impact of subjective and objective cognitive functioning on the
psychological adaptation of elderly patients starting a cancer treatment for a hematologic malignancy.
Methods: Consecutive elderly patients with a hematologic malignancy were included in the study. Patients’ medical characteristics, psychological distress (HADS), cognitive complaints (FACT-Cog) and functional autonomy (ADL and IADL)
were assessed during the first two days of treatment (T1). Patients also underwent a battery of neuropsychological tests
aiming at assessing cognitive functioning (Backward Memory Span test, Stroop test, Gröber and Buschke test and Trail
Making Test). Thirty days later, patients underwent the same assessment (T2). All medical critical events were recorded.
Results: Relations between objective and subjective cognitive functioning assessed during the first two treatment days
(T1) and self-reported psychological distress (HADS) assessed 30 days later (T2) will be presented (N=100). Moreover,
regression models will be performed in order to assess the predictive value of objective and subjective cognitive functioning assessed during the first two treatment days (T1) on patients’ self-reported psychological distress (HADS) assessed
30 days later (T2).
Conclusions: This longitudinal prospective study will allow a better understanding of the relations between subjective
and objective cognitive functioning and psychological adaptation in a population of elderly patients with cancer. The usefulness of the neuropsychological assessment in the understanding of psychological adaptation of elderly patients with
cancer will be discussed.
NOTES
63
34) The effects of Fluotexine; on the cognitive and cellular effects of chemotherapy.
(Ayesha MAQBOOL)
Authors : Ayesha Maqbool, Laura Lyons, Annabelle Chambers, Maria Toledo-Rodriguez, Peter Wigmore.
Institutional Affiliations :
School of Biochemical Sciences, University of Nottingham.
University of Health Sciences, Lahore, Pakistan.
E-mail of the corresponding author : Ayesha Maqbool
E mail: [email protected]
Purpose: The chemotherapy drug 5-FU has been used for over 40 years to treat various cancers but can have a deleterious effect on cognition. Antidepressant drugs, of the selective serotonin reuptake inhibitor class (e.g., fluoxetine),
increases generation of new neurons in the dentate gyrus of the adult brain and can be neuroprotective and increase
cognition. The present study was designed to investigate whether fluoxetine prevents or enables recovery from the
cognitive decline and reduced neurogenesis caused by 5-FU.
Methods: Male Lister-hooded rats received 5 injections of 5-FU over 2 weeks. Some rats were co-administered with
fluoxetine for 3 weeks before and during or after 5-FU treatment or both time periods. Spatial memory was tested using
the novel location recognition test and proliferation and survival of hippocampal cells was quantified using immunohistochemistry.
Results: 5-FU-treated rats showed cognitive impairment in the NLR task and a reduction in cell proliferation and survival
in the subgranular zone of the dentate gyrus, compared to saline treated controls. These impairments were still seen for
rats administered fluoxetine after 5-FU treatment, but were not present when fluoxetine was administered both before
and during 5-FU treatment. The results demonstrate that fluoxetine is able to prevent but not reverse the cognitive and
cellular effects of 5-FU.
Conclusions: Results of the present study showed that fluoxetine co treatment with chemotherapy is a viable treatment
to prevent the cognitive effect of chemotherapy.
NOTES
64
35) Breast cancer and treatment effects on brain structure and function in a prospective longitudinal cohort: A replication and extension study (Brenna C. McDONALD)
Authors: Brenna C. McDonald, Susan K. Conroy, Dori J. Smith, John D. West, Andrew J. Saykin
Institutional Affiliations:
Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine and
Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN
E-mail of the corresponding author: [email protected]
Purpose: Cross-sectional and longitudinal neuroimaging has shown neural correlates of cognitive changes related to
cancer and its treatment, which can persist in some patients for years post-treatment. We recently reported on the first
longitudinal cohort of breast cancer patients. Decreased frontal gray matter density was seen shortly after chemotherapy, which partially recovered over the next year. Functional MRI showed frontal hyperactivation during working memory processing prior to chemotherapy which significantly decreased one month post-treatment, followed by increases
over the next year. These findings suggested correlates to the cognitive symptoms demonstrated in prior studies, which
most commonly involve executive and memory processes in which the frontal lobes are a critical component of underlying neural circuitry. While intriguing, such findings require replication. This study attempted to replicate prior findings
at higher magnet field strength, and extended this line of inquiry to a more heterogeneous cohort.
Methods: Participants were female breast cancer patients treated with and without chemotherapy and healthy demographically matched controls. Subjects completed all study measures at baseline (after surgery but before systemic
treatment), one month after chemotherapy completion, and one year later (or yoked intervals for the nonchemotherapy-treated and control groups). MRI analyses included examination of gray matter with voxel-based morphometry and
investigation of working memory-related brain activation using fMRI.
Results: Chemotherapy-treated patients showed decreased frontal lobe gray matter and altered working memory-related activation post-treatment.
Conclusions: These data from a second, larger, independent cohort show frontal lobe alterations in brain structure and
function consistent with those we recently reported in an initial prospective longitudinal study. The current cohort is more
demographically diverse, and more generalizable to the larger breast cancer population in overall health status (e.g.,
other medical conditions, mental health treatment). Ongoing research into individual risk factors for such changes will
be critical to their future treatment and prevention.
NOTES
65
36) Prospective multimodality MRI study into cognitive dysfunction in breast cancer
patients – preliminary baseline results (Sanne MENNING)
Authors : Sanne Menning, MSc 1,2, Michiel de Ruiter
, Willem Boogerd 3, Liesbeth Reneman 2, Sanne Schagen
1,2
1
Institutional Affiliations :
1
Dept. Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands
2
Dept. Radiology, Academic Medical Center, Amsterdam, The Netherlands
3
Dept. Neuro-oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
E-mail of the corresponding author: [email protected]
Purpose: The majority of neuroimaging studies into cognitive dysfunction after chemotherapy are cross-sectional. In
this study, we prospectively investigate structural and functional properties of the brain with MRI in relation to cognition.
Here we report on potential functional and structural MRI differences at baseline between breast cancer (BC) patients
who will receive chemotherapy, BC patients that will not undergo cytotoxic treatment and healthy controls, mid-study.
Methods: 60 BC patients who will be treated with chemotherapy (CT+ group) will be compared to 60 women with BC
who do not require adjuvant chemotherapy (CT- group) and with 60 healthy controls (HC group).
All subjects are assessed at baseline, following surgery and before the start of adjuvant treatment, and a second time
at six months following chemotherapy, or at equivalent time points. Each assessment consists of questionnaires, neuropsychological tests and multimodality MRI scanning. In addition, data on hair cortisol, genetic factors, sex hormones
and cytokines is collected.
Results: Currently, 27 CT+, 36 CT- and 20 HC subjects completed baseline assessments. Age (CT: 50±11 yrs, BC:
53±8 yrs, HC: 48±14 yrs) and education level (CT: 5.8±0.8, BC: 5.5±1.0, HC: 5.9±0.7) were not significantly different
between groups.
Baseline performance data obtained in the scanner (memory and executive function) showed no significant differences
between the groups. 1H-MRS in cerebral white matter and the hippocampus revealed no significant differences on common markers of brain metabolism. Finally, no differences in gray and white matter volume were found.
Discussion: To our knowledge, the potential effect of BC (diagnosis) on brain structure and function has not been
assessed previously. We expect that this study will contribute to our understanding of the impact of cancer and cancer
treatment on cognition and brain functioning by examining BC patients longitudinally with multimodality MRI, neuropsychological testing and by studying potential moderating and mediating processes.
NOTES
66
37) Chemotherapy-induced cognitive changes: A meta-analysis (Oana C. MEREUTA)
Authors: Oana C. Mereuta, Martin McCabe, Andrew Mayes, Deborah Talmi
Institutional Affiliations:
School of Psychological Sciences, University of Manchester, United Kingdom
E-mail of the corresponding author: [email protected]
Purpose: Qualitative reviews estimate that between 13 and 70% of cancer survivors suffer from cognitive impairments
(Wefel et al., 2011). This variability, which is due to inherent treatments and patient characteristics, severely limits the
extent to which qualitative reviews can illuminate the underlying nature and causes of specific impairments. By contrast,
quantitative analysis can formally assess the sources of this variability.
Methods: We used meta-analytic techniques adhering, wherever possible, to the Cochrane standards for quality assessment, data extraction, and publication bias analysis. Our meta-analysis focused on the evidence from animal, adult, and
child studies investigating cognitive impairments related to chemotherapy. We analyzed the data available from studies
on these three types of populations in terms of the affected cognitive domains, and the specific participant and design
related conditions in which these cognitive changes appear.
Results: In animal models, chemotherapy drugs cause significant impairments in spatial learning. In humans, chemotherapy had the largest effects on overall cognitive functioning and spatial abilities and moderate effects were found for
executive function. Memory effects were found when specific aspects of memory were analyzed separately.
Conclusions: Meta-analysis is a useful technique for determining the effects of chemotherapy drugs on psychological
function to support optimal interventions. Our findings highlight the usefulness of employing reliable and sensitive instruments to assess each cognitive domain in addition to the standard neuropsychological testing as they would more
clearly differentiate the types of impairments suffered by chemotherapy-treated patients.
NOTES
67
38) Characteristics of autobiographical memory before adjuvant chemotherapy for
breast cancer (N. MOREL)
Authors : N. Morel 1, J. Dayan
, P. Piolino
1,2
, D. Allouache 4, S. Noal
1,3
, C. Levy
4,5
4
, F. Joly
, F. Eustache 1, B. Giffard
4,5,6
1
Institutional Affiliations :
1
Unité U923, Inserm – EPHE – Université de Caen/Basse-Normandie, Caen
2
Département de Psychiatrie de l’Enfant et de l’Adolescent, CHU Guillaume Régnier, Rennes
3
Laboratoire Psychologie et Neuropsychologie Cognitive, CNRS FRE 3292, Université Paris Descartes
4
Département d’oncologie médicale, Centre François Baclesse, Caen,
5
Unité de recherche clinique, Centre François Baclesse, Caen
6
CHU Côte de Nacre, Caen, France
E-mail of the corresponding author : [email protected]
Purpose: Announcement of breast cancer may be associated with increased stress-related psychiatric disorders. These
disorders, such as Post Traumatic Disorder Stress or Major Depression, have been shown associated with episodic autobiographical memory retrieval deficits1,2. Nillson-Ihrfelt et al. (2004)3 revealed autobiographical specificity impairment in
remitted breast cancer patients (patients who had lived cancer diagnosis, treatments and remission period). However,
the specific factors responsible for these memory impairments remain unknown. The aim of this study was to investigate
the ability to retrieve specific autobiographical memories immediately after announcement of cancer and surgery but
before adjuvant treatment to better understand putative autobiographical memory impairment.
Methods: 16 patients newly diagnosed with breast cancer (53.6 ± 5.4 years) and 26 matched healthy subjects without
any history of cancer (58 ± 8.6) were tested for autobiographical memory using a semi-structured interview4, which
assesses each specific detail of memory (factual, spatial, temporal and emotional) for three life periods: 18-30 years
old, the last 2 years (before cancer period) and the last 6 months (cancer period). Psychopathological assessment (STAI,
Beck) was also administered.
Results: Compared to controls, the number of patients recalling factual details is greater for cancer period (p=0.02)
and before cancer period (tendency p = 0.06). The reverse is observed for emotional details recall for before cancer
and cancer periods (tendency p = 0.07). Contrary to our hypothesis, any psychological distress was observed in these
patients between cancer diagnosis and adjuvant treatment (note that they also carried out neuroimaging exams).
Conclusions: Higher factual scores and lower emotional scores after cancer diagnosis were observed. These results suggest an active adaptation process following the announcement of a life-threatening illness. This overlappes with results
of previous research showing existence of transient alexithymia in severe disease diagnosis.
1
2
3
4
Dalgleish et al. (2008)- J Abnorm Psychol 117: 236–241
Lemogne et al. (2006)- Conscious Cogn 15: 258–268
Nilsson-Ihrfelt et al. (2004)- J Psychosom Res. 57: 363–266.
Piolino et al. (2009)- Neuropsychologia 47:2314-29
NOTES
68
39) Investigation of prospective and working memory decline and the impact of
impaired sleep and/or glucose metabolism in rencently diagnosed breast cancer
patients undergoing chemotherapy : a longitudinal study (Liliana MOYERS RUIZ)
Liliana Moyers Ruiz (PhD Student)
Bournemouth University and Royal Bournemouth & Christchurch Hospitals
Supervisory Team:
Dr Simon Thompson, Associate Professor of Clinical Psychology & Neuropsychology (First Supervisor)
Professor Tamas Hickish, Consultant in Oncology (Second Supervisor)
Background: Some patients present memory deficits after experiencing chemotherapy. However, the aetiology of this
phenomenon remains unknown. It is proposed that Working Memory and Prospective Memory are being affected by
chemotherapy on breast cancer patients. Biological factors such as sleep, sleepiness and glucose metabolism are altered
during chemotherapy treatment and may be playing a role in the cognitive impairment of cancer patients.
Aims: Analyse Working and Prospective Memory by using a neuropsychological battery and try to identify if the battery
Cambridge Prospective Memory Test, is more sensitive to the mild cognitive changes presented in chemo-brain patients.
Identify if alterations on biological factors such as sleep, sleepiness, and glucose metabolism impair memory processes.
Methods: A nine-month longitudinal study will be conducted. A comprehensive neuropsychological battery, along with
measures of sleep and sleepiness, will be administered at 4 time-points during the 9-month period. Additionally, blood
samples will be analised.
The study groups will comprise 30 breast cancer patients scheduled for chemotherapy treatment; 30 breast cancer
patients not receiving chemotherapy; 30 healthy participants. They will be required to wear a Sensewear armband. A
measure of their pupil aperture will be taken, along with a blood sample.
Discussion: It is important to analyze subjective and objective measures, as well as more ecological and sensitive measures such as those of specific neuropsychological batteries in order to detect the mild cognitive impairment as sequelae
of chemotherapy treatment. Other factors such as sleep, sleepiness, and glucose metabolism, should also be considered.
NOTES
69
40) Impact of antiangiogenic treatment on cognitive functions and fatigue among
metastatic renal cancer patients (Sabine NOAL)
S. Noal 1,2, I. Léger 3, N. Heutte 1,4,5, B. Duclos 6, B. Clarisse 1, A. Daireaux 1, S. Dauchy 3, B. Escudier 3, C. Rieux 1, M.
Lange 1,5, N. Longato 6, F. Joly 1,2,5,7
Institutional Affiliations:
1
Unité de Recherche Clinique, Centre François Baclesse, Caen, France
2
Département d’oncologie médicale, Centre François Baclesse, Caen, France
3
Institut Gustave Roussy, Villejuif
4
UFR des Sciences Pharmaceutiques, Université de Caen Basse-Normandie, Caen, France
5
Equipe « Cancers et Populations » ERI3 INSERM, UFR de Médecine, Université de Caen Basse-Normandie, Caen
6
Département d’hématologie et d’oncologie, Hôpitaux universitaires de Strasbourg, Strasbourg
7
CHU Côte de Nacre, Caen, France
E-mail of the corresponding author: [email protected]
Purpose: Antiangiogenic treatments recently developed in metastatic renal cancer are nowadays the standard treatment. Nevertheless, these therapies can induce some important adverse effects such as fatigue, concentration and
attention disorders. Our goal was to assess the incidence of fatigue and cognitive impairments induced by antiangiogenic
treatment and their evolution over time among metastatic renal cancer patients.
Methods: Episodic memory, working memory, executive functions, information processing speed, cognitive complaint,
anxiety, depression and fatigue were assessed with neuropsychological tests and self-reported questionnaires before
antiangiogenic treatment (T0) and 3 months later (T3). Cognitive impairment was defined as a score less than 1.5 standard deviation (SD) of normative data on >2 tests, or less than 2 SDs on >1 test. Preliminary results of this longitudinal
study are presented.
Results: Results concern the first 59 patients (64±10 years): male/female ratio was 40/19 and WHO=0 concerns 69%
of patients. Antiangiogenic treatment was the first metastatic line for 43 patients (73%). It was mostly sunitinib (38
patients, 64%). At baseline, 31 (53%) patients had cognitive disorders (episodic memory and executive functions mainly
impaired). 35 patients (59%) expressed fatigue. Only 2 and 1 patients experienced anxiety and depression, respectively.
Among the 41 patients with evaluations at T0 and T3, 16 (39%) had >1 domain of cognitive functions that became
pathological over antiangiogenic treatment (principally executive functions and episodic memory). Fatigue was reported
by 28 patients (68%) at T3. Cognitive complaint was not related to objective cognitive performances but was associated
to fatigue, particularly in case of fatigue at baseline.
Conclusions: Our study is the first to prospectively describe the incidence of both cognitive impairments and fatigue
and their deterioration over antiangiogenic treatment. More than half of metastatic renal cancer patients experienced
cognitive impairments and fatigue before antiangiogenic treatment. Moreover, antiangiogenic treatment induces cognitive impairment.
NOTES
70
41) Erythropoietin and brain tumors: a paradigm of Yin-Yang (Elodie PERES)
Authors: Elodie Pérès 1,2,3; Claire Leconte 1,2,3, Samuel Valable 1,2,3, Armelle Calipel 1,2,3, Jean-Sébastien Guillamo 4, Simon
Roussel 1,2,3, Emmanuèle Lechapt-Zalcman 5, Michel Boulouard 5, Pascale Schumann-Bard 6, Edwige Petit 1,2,3, Myriam
Bernaudin 1,2,3
Institutional Affiliations:
1
CNRS, UMR 6232 CERVOxy group, F-14074 Caen, France
2
Université de Caen Basse-Normandie, UMR 6232 CERVOxy group, F-14074 Caen, France
3
CEA, UMR 6232 CERVOxy group, F-14074 Caen, France
4
CHU de Caen, service de neurologie, F-14000 Caen, France
5
CHU de Caen, Laboratoire d’Anatomie Pathologique, F-14000 Caen, France
6
Université de Caen Basse-Normandie, EA 4259, GMPc, F-14032 Caen, France
E-mail of the corresponding author: [email protected]
Purpose: Erythropoietin (EPO) is a haematopoietic growth factor widely used as a standard therapy to treat chemotherapy-related anaemia. Interestingly, the cognitive status is improved by chronic EPO treatment in patients. This latter
beneficial effect of EPO has been first attributed to its haematopoietic action leading to an improved cerebral oxygenation. However, the detection of EPO and EPO receptor (EPOR) in the brain suggested a direct effect onto the central
nervous system. Accordingly, EPO has been recently reported to exert an antidepressant-like effect in human and to
improve hippocampus-dependent memory. Nevertheless, further studies are needed to better understand the mechanisms underlying these beneficial effects on cognition. On another hand, we and others have obtained data attesting that
EPOR present on glioma cells could promote glioma growth. Accordingly the purpose of this study was 1/ to investigate
the effects of EPO on memory performances as well as on depressive- and anxiety-related and 2/ to evaluate the role of
EPOR of glioma cells in tumor growth as well as in the hypoxia-dependent chemo-and radioresistance.
Methods: Effects of EPO have been studied on memory- and emotion-related behavior in the adult healthy mouse. Locomotor activity, memory performances, anxiety and despair-like behaviors were assessed over 6 weeks of repeated EPO
(40 μg/kg, twice a week). Effects of EPO on neurogenesis have been studied in the dentate gyrus. To study the impact of
EPOR on glioma growth human glioma cells (U87, U251) were genetically modified by a RNAi strategy and injected in the
striatum of nude mice. Tumor growth was followed by MRI. In vitro, the effect of the down-regulation of EPOR expression
was studied in response or not to irradiation or temozolomide (TMZ) treatments, in presence or not of hypoxia.
Results: Our results showed that EPO treatment improved spatial and non-spatial recognition memory in adult healthy
mice and increased the number of NeuN/BrdU double-labeled cells in the dentate gyrus field of the hippocampus suggesting that neurogenesis might be related to those effects. In glioma, we showed that EPOR contributes to glioma growth
as well as to the hypoxia-dependant chemo- and radioresistance.
Conclusions: Collectively, on one hand, our results reinforce the interest of using EPO for improving the quality of life for
glioma suffering patients but on another hand suggest the need to explore in more details the biology of EPO and EPOR
as well as its clinical application for cancer patients.
This work was realized as part of the Interreg program TC2N « Trans Channel Neuroscience Network and supported by
the French Centre National de la Recherche Scientifique (CNRS) and the French Ministère de l’Enseignement Supérieur
et de la Recherche and by a grant from l’ARC.
NOTES
71
42) Cerebral Function after Breast Cancer Treatment (Kelsey L. POMYKALA)
Authors : Kelsey L. Pomykala, Cheri L. Geist, Patricia A. Ganz, Iris Cheng, Lorna Kwan, Steven A. Castellon, Elizabeth C.
Breen, Julienne E. Bower, Michael R. Irwin, Johannes Czernin, Michael E. Phelps, Daniel H. S. Silverman
Institutional Affiliations :
David Geffen School of Medicine at UCLA, Jonsson Comprehensive Cancer Center, Greater Los Angeles VA Healthcare
System, Los Angeles, CA, USA.
E-mail of the corresponding author : [email protected]
Purpose: Explore effects of adjuvant cancer therapy on cerebral function in breast cancer patients(BCP).
Methods: 190 BCP completed standardized questionnaires and neuropsychological assessments at the end of primary
treatment(baseline), and were followed a year. A subset of 33 women(23 chemotherapy, 10 no chemotherapy) obtained PET/CT brain imaging at baseline and one year later, to examine the association between cognitive functioning and
cerebral metabolism. Lastly, mechanisms by which cancer therapy influences cerebral functioning were explored by examining changes in cognitive functioning and brain metabolism, and their relationship to immune and endocrine function,
mood and symptoms between the baseline, 6 and 12 month assessments.
Results: At baseline, subjects in the chemotherapy group(CG) had less metabolism in the hindbrain. Consequently,
areas of the hindbrain, including the cerebellum, significantly increased in metabolism after one year(t=4.66, p<0.0005).
Baseline frontal metabolism in the CG also negatively correlated with baseline cytokine levels(IL1RA, sTNFR2, CRP, IL6),
and a subsequent increase in metabolism over one year in the frontal and anterior temporal cortex of the CG positively
correlated with baseline IL6 levels(p<0.0005). Furthermore, lower baseline metabolism in the bilateral frontal cortex
and higher metabolism in the inferior temporal and medial cerebellar cortex correlated to slower performance of Trail
Making Test B(TMTB) in chemotherapy treated subjects. These correlations were not found in untreated subjects.
Conclusions: Chemotherapy was associated with regionally specific changes in resting metabolism in brains of newly
diagnosed BCP. Baseline levels of inflammatory cytokines correlated with decreased baseline metabolism and predicted
subsequent increases in metabolism over the ensuing year. Correlations between TMTB completion time and regions of
cerebral metabolism were seen in the CG. These changes in brain metabolism may underlie cognitive effects reported
by the patients following therapy. We are currently exploring interactions of these observed associations with age, BMI,
and endocrine therapies.
Supported by NCIR01CA109650 and BCRF
NOTES
72
43) Chemotherapy and cognitive complaints in patients in women with breast cancer
(Marleen J.J. PULLENS)
Authors : Marleen J.J. Pullens 1, Jolanda De Vries
A. Roukema 1 , 5
, Laurence J.C. Van Warmerdam 3, Marieke A. Van De Wal 4, & Jan
12
Institutional Affiliations :
¹
CoRPS Center of Research on Psychology in Somatic Diseases, Department of Medical Psychology, Tilburg University ;
2
Department of Medical Psychology, St. Elisabeth Hospital, Tilburg ;
3
Department of Internal Medicine, Catharina Hospital, Eindhoven ;
4
Department of Medical Psychology, Maxima Medical Centre, Veldhoven/Eindhoven ;
5
Department of Surgery, St. Elisabeth Hospital, Tilburg.
E-mail of the corresponding author : [email protected]
Purpose: Results of existing studies are inconclusive concerning the relationship between systemic therapy and subjective cognitive functioning (SCF). The first aim of this study was to evaluate SCF of breast cancer (BC) patients before
and three months after chemotherapy in comparison with patients with a benign breast problem (BBP). The second aim
was to find predictors of impaired SCF.
Methods: Women with BC who were about to receive chemotherapy and women with a benign breast problem (BBP)
participated in the study. Before chemotherapy started (Time 1) and three months after ending chemotherapy (and at
comparable moments for the BBP group) (Time 2) women completed validated questionnaires concerning the frequency
of complaints and satisfaction with SCF and fatigue, perceived stress, anxiety, and depressive symptoms.
Results: Seventy-four women with BC and 63 women with a BBP participated in the study. Women with BC or BBP did
not score differently on the frequency of complaints about SCF. The frequency of complaints about SCF did significantly
change over time (except for the subscale Social recklessness). This effect for time did not remain significant after
controlling for state anxiety and perceived stress. An interaction effect between satisfaction with SCF and time was
found, even after controlling for state anxiety and perceived stress. Satisfaction with SCF decreased over time in BC
patients, but remained stable over time in BBP patients. Depressive symptoms before the start of chemotherapy predicted the frequency of complaints about SCF. Satisfaction with SCF was predicted by state anxiety, fatigue, psychologist/
psychiatrist counseling in the past, and the interaction between anxiety and diagnosis.
Conclusions: BC patients do not differ in the frequency of complaints about SCF compared to BBP patients, but their
satisfaction with SCF decreased after chemotherapy. Psychologica factors predicted frequency of complaints and satisfaction with SCF.
NOTES
73
44) No effect of treatment on objective cognitive functioning in breast cancer patients (Marleen J.J. PULLENS)
Authors : Marleen J.J. Pullens 1, Jolanda De Vries
1 ,2
& Jan A. Roukema1 , 3
Institutional Affiliations :
¹ CoRPS Center of Research on Psychology in Somatic Diseases, Department of Medical Psychology, Tilburg University ;
2
Department of Medical Psychology, St. Elisabeth Hospital, Tilburg ;
3
Department of Surgery, St. Elisabeth Hospital, Tilburg.
E-mail of the corresponding author : [email protected]
Purpose: Recent studies suggest that chemotherapy may induce cognitive decline in women treated for breast cancer.
However, evidence for this chemotherapy-induced cognitive decline is inconclusive. Therefore, the purposes of this multicenter, prospective longitudinal study was to examine the effect of chemotherapy on objective cognitive functioning in
breast cancer patients three months after chemotherapy administration. The data presented is part of a study on the
course of objective/subjective cognitive functioning after cytostatic treatment and the effect on patients’ quality of life.
Methods: Post-operative breast cancer patients who were about to receive chemotherapy participated in this study. The
control group consisted of women who were diagnosed with a benign breast problem. Before the chemotherapy started
and three months after completion of chemotherapy (and at comparable moments for the benign breast problem group),
a neuropsychological test battery was administered covering the following domains: verbal memory, visual memory,
information processing speed, executive functioning, verbal fluency, motor speed and reaction speed.
Results: At the moment of analysis 52 breast cancer patients (mean age 51, range: 28-69) and 50 patients with a
benign breast problem (mean age 47, range 21-71) had completed both neuropsychological assessments. General linear
model analyses for repeated measures with age and verbal intelligent quotient as covariates revealed no interaction
effects (p≥ .145) and no significant effects for time on the neuropsychological domains (p≥ .270), indicating that objective cognitive functioning remained stable over time. In addition, no significant differences between the breast cancer
patients and the patients with a benign breast problem were found on any of the neuropsychological domains (p≥.232).
Conclusions: Three months after ending chemotherapy no effect was found on objective cognitive functioning in breast
cancer patients.
NOTES
74
45) Effects of targeting VEGF signalling on sensorimotor and cognitive functions in
the healthy adult rat (Marie-Sophie QUITTET)
Authors: Marie-Sophie Quittet 1,2,3,5, Léna Marteau 1,2,3, Samuel Valable 1,2,3,
Simon Roussel 1,2,3, Myriam Bernaudin 1,2,3, Pascale Schumann-Bard 5, Edwige Petit 1,2,3
Jean-Sébastien
Guillamo
,
4
Institutional Affiliations:
1
CNRS, UMR 6232 CERVOxy group, F-14074 Caen, France
2
Université de Caen Basse-Normandie, UMR 6232 CERVOxy group, F-14074 Caen, France
3
CEA, UMR 6232 CERVOxy group, F-14074 Caen, France
4
CHU de Caen, service de neurologie, F-14000 Caen, France
5
Université de Caen Basse-Normandie, EA 4259, GMPc, F-14032 Caen, France
E-mail of the corresponding author: [email protected]
Purpose: It is well known that the development of tumor vascularization is a key event for tumor growth. Because VEGF
(vascular endothelial growth factor) is the main actor of angiogenesis, molecules targeting this factor or its signalling
have been developed as new cancer therapeutic strategies. Accordingly, Sunitinib which inhibits several receptor tyrosine
kinases, including VEGF receptors, was approved to treat renal cell carcinoma or gastrointestinal stromal tumors and
more recently Sunitinib has been introduced for brain tumors. However, it is becoming clear that these anti-angiogenic inhibitors can induce side effects in patients like hypertension, fatigue, behavioural or mnesic troubles that justify
a treatment adaptation. These cognitive effects might be due to the important role of endogenous VEGF on the brain.
Indeed, beside its angiogenic properties, VEGF displays neurotrophic and neurogenic effects that can modulate the
mnesic and emotional state of patients1. In this context, the aim of this work was to evaluate the impact of a Sunitinib
treatment on the normal brain.
Methods: We administered Sunitinib to healthy rats (20mg/kg with 5days ON and 2days OFF, close to clinic regimen)
and evaluated the effect of this treatment on animals performances at different sensorimotor and cognitive tests: spatial (Morris water maze) and emotional (passive avoidance test) long term memory, working memory (spontaneous
alternation test), anxiety-like behaviour (elevated plus maze), depressive-like behaviour (forced swimming test) and
sensorimotor capacities (grip test). Magnetic resonance imaging (MRI) and positron emission tomography (PET) studies
allowed characterizing the cerebral vascularization as well as glucose metabolism.
Results: Our results showed no functional perturbation of brain vascularization and metabolism when the rats were
treated with Sunitinib. In addition, no difference was observed between treated and control groups in sensorimotor and
cognitive tests. However, at the used regimen, the treatment caused an important loss of weight associated with a low
recuperation rate after an acute stress.
Conclusions: Collectively, our results suggest that, in our experimental conditions, Sunitinib displays no apparent toxicity on healthy rat brain functions.
1 Ruiz de Almodovar et al. (2009) Physiological Reviews 89(2):607-48.
This work was realized as part of the Interreg program TC2N « Trans Channel Neuroscience Network and supported by the French Centre National de la Recherche Scientifique (CNRS) and the French Ministère de l’Enseignement Supérieur et de la Recherche.
NOTES
75
46) Subjective cognitive complaints one year after ceasing adjuvant endocrine treatment for early-stage breast cancer: results from the BIG 1-98 randomised trial
(Karin RIBI)
Authors : Karin Ribi 1, Julie Aldridge 2, Kelly-Anne Phillips 3, Alastair Thompson 4, Vernon Harvey 5 , Beat Thürlimann 6, Fatima Cardoso 7,
Olivia Pagani 8, Alan S. Coates 1,9, Aron Goldhirsch 10, Karen N. Price 11, Richard D. Gelber 2,11, Jürg Bernhard 1,12
Institutional Affiliations :
1
IBCSG Coordinating Center, Bern, Switzerland ;
2
IBCSG Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA ;
3
Peter MacCallum Cancer Centre and the University of Melbourne, Melbourne, Victoria, Australia ;
4
Dundee Cancer Centre, University of Dundee, Dundee, Scotland, UK ;
5
Auckland City Hospital, Auckland, New Zealand and Australian New Zealand Breast Cancer Trials Group ;
6
Breast Center, Kantonsspital, St. Gallen, Switzerland, Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland ;
7
Department of Medical Oncology; Jules Bordet Institute, Brussels, Belgium ;
8
Oncology Institute of Southern Switzerland, Ospedale Italiano, Viganello, Lugano, Switzerland and Swiss Group for Clinical Cancer
Research (SAKK), Bern, Switzerland ;
9
International Breast Cancer Study Group, Bern, Switzerland and University of Sydney, Australia ;
10
European Institute of Oncology, Milan, Italy and Oncology Institute of Southern Switzerland, Bellinzona, Switzerland ;
11
International Breast Cancer Study Group Statistical Center and Frontier Science and Technology Research Foundation, Boston, MA ;
12
Inselspital, Bern University Hospital, Department of Medical Oncology, Bern, Switzerland.
E-mail of the corresponding author : [email protected]
Purpose: The BIG 1-98 trial showed an improvement in objective cognitive function in postmenopausal women one year
after cessation of adjuvant endocrine therapy for breast cancer. This report evaluates whether there are similar changes
in subjective cognitive function (SCF) and other patient-reported outcomes.
Methods: One hundred postmenopausal women, who were randomized to receive five years of adjuvant tamoxifen,
letrozole, or sequences of the two, completed self-reported measures on SCF, psychological distress, fatigue and quality
of life (QOL) during the fifth year of trial treatment (year 5) and one year after treatment completion (year 6). The Wilcoxon signed-rank test was used to evaluate changes in these factors between years 5 and 6; the Wilcoxon rank-sum
test was used to test the difference in changes between treatment groups. SCF and its correlates were explored.
Results: At year 5, no differences were found for SCF, fatigue, psychological distress or QOL between women taking
tamoxifen or letrozole. SCF and the other patient-reported outcomes did not significantly change after cessation of
endocrine therapy (except for hot flushes, which improved; p=0.0005), and no difference in changes was found between
the two treatment groups. SCF was the only psychosocial outcome with a substantial correlation between year 5 and 6
(Spearman’s R=0.80). Among women who reported the highest 33% of SCF scores at year 5 and 6 (higher scores reflecting poorer cognition), the most bothersome complaints pertained to few but specific memory problems. Correlations
between SCF and the other patient-reported outcomes were generally low.
Conclusions: Although objective cognitive function improved after cessation of adjuvant endocrine therapy in the BIG
1-98 trial, improvement in SCF was not evident. The substantial correlation of SCF scores over time may represent a
stable feature.
NOTES
76
47) Changes in dlPFC recruitment Associated with Breast Cancer Treatment: A Longitudinal fMRI Study of Changes in Brain Function Associated with Chemotherapy
Treatment (JC ROOT)
Authors : Root JC 1, Morris L 1, Ryan E 1, Pan H 3, Silbersweig D 3, Stern E 3, Orlow I 2, Ahles T
1
Institutional Affiliations :
1
Department of Psychiatry and Behavioral Sciences; Memorial Sloan-Kettering Cancer Center, New York, NY ;
2
Department of Epidemiology-Biostatistics; Memorial Sloan-Kettering Cancer Center, New York, NY ;
3
Department of Psychiatry; Brigham and Women’s Hospital/Harvard Medical School, Boston, MA.
E-mail of the corresponding author : [email protected]
Purpose: This is a prospective, longitudinal study to examine neurocognitive changes in breast cancer patients receiving
chemotherapy. Several studies have provided evidence for chemotherapy-induced cognitive changes in breast cancer
survivors, although little is known about the underlying mechanisms. We are recruiting patients with breast cancer
undergoing treatment for the first time and will test the effects of chemotherapy on patients’ cognitive function utilizing
structural and functional MRI (fMRI) pre-and post-treatment.
Methods:
Subjects: Treatment-naïve breast cancer patients (chemotherapy, n=9; no chemotherapy, n=4) were included. While
these are preliminary findings based on a subset of subjects analyzed, the full processed and analyzed dataset will be
presented during the poster session.
Image acquisition and processing: Images are acquired with a GE 3Tesla MRI scanner (max gradient strength 40 mT/
m;max slew rate 150 T/m/s). Blood Oxygenation Level-Dependent (BOLD) contrast imaging is used and collected with
a gradient echo EPI sequence.
Behavioral Task: Subjects perform a visual n-back task consisting of a block presentation of a series of letters with a
three second ISI. Four conditions are used: 0-back, 1-back, 2-back, and 3-back. The subject is instructed to press a
button to indicate recognition of a match as defined by each condition. Each condition is presented in 27-s epochs. There
are 12 epochs during each scan.
Results: Patients who have received chemotherapy demonstrate increased dorsolateral prefrontal cortex recruitment
from pre- to post-treatment, as indicated by a more distributed pattern of activity in regions subserving sustained and
selective attention. These findings were especially pronounced in the 1-back and 2-back tasks.
Conclusions: Relative prefrontal cortex functional activation is consistent with voluntary, compensatory recruitment of
more diffuse dlPFC sites suggesting more effortful processing post-treatment. Regional activations are consistent with
previous morphometric data (McDonald, 2010) that found dlPFC gray matter reductions in these same regions.
NOTES
77
48) Does Chemotherapy Alter Visuospatial Working Memory: An fMRI Study (Carole
SCHERLING)
Authors : Carole Scherling, Andra Smith, Joyce MacKenzie, Nancy Wallis, Rocio Lopez, Barbara Collins
Institutional Affiliations :
University of Ottawa, Psychology and The Ottawa Hospital, Neuropsychology
E-mail of the corresponding author : [email protected]
Purpose: Chemotherapy-treatment has been associated with working memory deficits. Previous neuropsychological and
neuroimaging research have revealed impairments in processing speed and executive functioning, essential for successful working memory capacities. The current study examines neurofunctional differences related to visuospatial working
memory between breast cancer (BC) patients and controls, after chemotherapy treatment.
Methods: Twenty female early-stage BC patients, scanned prior to treatment and after completing chemotherapy treatment, were sex-, age- and education-matched to non-cancer controls. fMRI data collected during performance of a Visuospatial 2-back task were analyzed by whole brain and region of interest (ROI) group comparisons with reaction times,
error rates, neuropsychological tests, hospital records and salivary biomarkers used as potentially contributing variables.
Results: Independent t-tests revealed more left medial frontal, right insula and right superior temporal activity in
patients following chemotherapy, compared to controls. These differences were significantly modified when considering
depression, anxiety, reaction time, errors of commission, and time since surgery values. Within group t-tests revealed
that patients had more neural activity post-chemotherapy compared to pre-chemotherapy in the right frontal lobe, while
controls revealed more activity in the left frontal lobe at the second scanning session. Depression, days since surgery and
reaction times were the variables that significantly impacted neural processing during the visuospatial working memory
task.
Conclusions: This multifaceted imaging study focused on visuospatial working memory and uncovered neural processing differences between BC patients after chemotherapy and well matched controls. Results were modified by the
addition of variables such as depression scores and fMRI task reaction times. This study revealed post-chemotherapy
neurophysiological group differences, and highlights the need to better understand contributing variables and their
effects on cognition in this post-treatment patient population.
NOTES
78
49) Cognitive impairment and perseverative cognitions during treatment for breastcancer: preliminary results (W SCHRAUWEN)
Authors : Schrauwen W., Dillen L., Cornelis S., Vingerhoets G., VanHeule S., Denys H., Van den Broecke R., Cocquyt V.
Institutional Affiliations :
Medical Oncology and Palliative Care, Ghent University Hospital; Oncology Centre, Ghent University Hospital; Laboratory For Neuropsychology Ghent University; Department Of Psychoanalysis And Clinical Consulting, Ghent University;
Department Of Gynaecology, Ghent University Hospital
E-mail: [email protected]
Purpose: A challenge in the research on cognitive difficulties after cancer is the identification of variables, - other than
objective cognitive impairment - related to cognitive complaints found in breast cancer patients. Depression/anxiety
are thought to be correlated with cognitive self-ratings, but some of their core features, worry and rumination, increase
negative affect and interfere with cognitive functioning and problem-solving. More worry/rumination should predict
higher self-reported cognitive problems, and may mediate between mood and experienced cognitive functioning.
Methods: Women with stage I-III breast carcinoma were recruted and tested following surgery but before the start of
adjuvant treatment. Inclusion criteria were primary invasive breast cancer, age between 25-65 years, no drug/alcoholabuse and no previous neuropsychological impairment. A control group of healthy women performed the same tests. A
standardized neuropsychological battery was administered to each patient in a set order. Questionnaires were administered at the same time. A blood sample was taken to measure hormonal factors and cytokines.
Results,Conclusions: We compared patients with /without chemotherapy. Patients of both groups showed better
performance on verbal memory, information processing speed and inhibition/switching tasks. Chemotherapy was
found to have a specific negative impact on verbal fluency while patients without chemotherapy performed significantly
better. Mediational analyses indicated that perseverative cognitions, measured by worry and rumination, mediate the
relationship between negative emotions and subjective cognitive functioning.
NOTES
79
50) Effects of Perseverative Cognitions and Personality on Subjective Cognitive Functioning (W SCHRAUWEN)
Authors : Schrauwen W., Dillen L., Belsack R., Vingerhoets G., VanHeule S., Denys H., Van den Broecke R., Cocquyt V.
Institutional Affiliations :
Medical Oncology and Palliative Care, Ghent University Hospital; Oncology Centre, Ghent University Hospital; Laboratory For Neuropsychology Ghent University; Department Of Psychoanalysis And Clinical Consulting, Ghent University;
Department Of Gynaecology, Ghent University Hospital
E-mail of the corresponding author : [email protected]
Purpose: Getting back on track after cancer is a multidimensional construct that includes physical health, functional status, emotional adjustment, cognitive functioning and social engagement. Cognitive complaints after cancer are frequent,
although there are questions unanswered concerning the nature of these complaints. Subjective cognitive complaints
(SCC) are known to be associated with other non-cognitive variables, such as anxiety and depression. Williams (2009)
suggests a ruminative self-focus effects attention and concentration. In this explorative study we investigated the
relation between perseverative cognitions and SCC, and questioned personality factors as vulnerable/protective for the
development of cognitive complaints.
Methods: A total of 198 patients with invasive breast carcinoma, between 1.5 and 5 years after diagnosis, were invited
to participate in a cross-sectional study. Participants were women with stage I-III breast carcinoma treated with chemotherapy followed by radiotherapy and hormonal therapy at the Breast Clinic of Ghent University Hospital. Following
informed consent, participants were mailed a packet of questionnaires with a self-adressed stamped return envelope. 87
participants completed self-report questionnaires on cognitive functioning, perseverative cognitions, negative emotions
and personality.
Results,Conclusions: Disease-related factors such as time since diagnosis and main surgery were not associated with
subjective measures of cognitive functioning, anxiety/depression or repetitive thought, ie worry/rumination. Patients
who received FEC scored (non-significant) higher on cognitive measures, anxiety/depression and worry/rumination than
patients who received a combination with Docetaxel. Especially conscientiousness seems to be a protective personality
factor and perseverative thought is likely to be a mediator between anxiety/depression and cognitive complaints.
NOTES
80
51) Cognitive impact of multiple cytotoxic agents in mice (R. SEIGERS)
Authors: R. Seigers 1, M. Loos 2, O. Van Tellingen 3, W. Boogerd 4, A.B. Smit 5, S.B. Schagen
1
Institutional Affiliations :
1
Department of Psychosocial Research and Epidemiology, Department of Psychosocial Research and Epidemiology,
Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands ;
2
Sylics (Synaptologics BV), Amsterdam, the Netherlands ;
3
Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience
Campus Amsterdam, VU University, Amsterdam, The Netherlands ;
4
Department of Neuro-Oncology, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam ;
5
Division of Molecular Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
E-mail of the corresponding author: [email protected]
Purpose: Adjuvant chemotherapy is associated with cognitive impairment in patients. Since chemotherapy is generally
given as a cocktail of multiple cytotoxic agents, it is impossible to state which agents are responsible for the observed
cognitive impairment. Therefore, in this study, we examined the effect of several cytotoxic agents on cognition in a mice
model.
Methods: Male C57Bl6 mice (n=12 per group) were treated with one of the following agents: cyclophosphamide (CYC,
150 mg/kg ip), docetaxel (DOC, 33 mg/kg iv), doxorubicine (DOX, 10 mg/kg iv), 5-fluorouracil (5-FU, 75 mg/kg ip),
methotrexate (MTX, 250 mg/kg iv), or topotecan (TOP, 25 mg/kg ip). A control group received saline ip. Behavioral
testing started two weeks after treatment and included the following tasks: general behavior in an automated home
cage, open field, novel location recognition (NLR), Barnes maze, fear conditioning, and simple choice reaction time task
(SCRTT).
Results: CYC and DOX treatment decreased activity during the dark phase, as measured in an automated home cage.
CYC, DOC, DOX, and MTX treated animals were not able to learn the NLR task. All cytotoxic agents affected learning
behavior in the Barnes maze. Performance in the SCRTT was affected in animals treated with CYC, DOC, 5-FU, and TOP.
Conclusions: CYC, DOC, or DOX treatment decreased general activity in an automated home cage. However, this did
not result in less activity in the other behavioral tasks. All cytotoxic agents affected spatial memory as measured in the
NLR and Barnes maze. 5-FU treated animals showed a slower response time in the SCRTT. And also in the SCRTT, impairment in response control was seen in animals treated with CYC, DOC, or TOP. These results show that, in mice, single
treatment with several cytotoxic agents causes impairment in various cognitive domains.
NOTES
81
52) Effects of Chemotherapy on Response Inhibition: An fMRI Study (Andra SMITH)
Authors : Andra Smith, Carole Scherling, Joyce MacKenzie, Nancy Wallis, Rocio Lopez, Barbara Collins
Institutional Affiliations :
University of Ottawa, Psychology and The Ottawa Hospital, Neuropsychology
E-mail of the corresponding author : [email protected]
Purpose: Cognitive impairment is often a side-effect of chemotherapy. To understand the neural mechanisms of this
consequence and provide empirical evidence of a neurological impact of chemotherapy on cognitive functioning, the current study examined neurofunctional processing during response inhibition in breast cancer (BC) patients and controls,
before and immediately following chemotherapy. Neuropsychological, neuroimaging and biomarker measures contributed to this investigation.
Methods: Twenty female early-stage BC patients, studied prior to treatment and after completing all cycles of chemotherapy treatment, were sex-, age- and education-matched to non-cancer controls. Functional magnetic resonance
imaging (fMRI) data collected during performance of a Go-No Go task were analyzed by whole brain and region of interest (ROI) group comparisons with reaction time, error rates, neuropsychological tests, hospital records and salivary
biomarkers used as experimental variables of interest.
Results: Independent t-tests revealed significantly less right precuneus activity in patients post-chemotherapy, compared to controls. Within group t-tests revealed differential changes over time in patients compared to controls, with
controls showing more task activity at the second scan and patients showing more neural activity prior to chemotherapy.
Regression analyses for each group along depression, anxiety, errors of commission and reaction time revealed more
within-group variability for patients compared to controls. These variables contributed significantly to the neural processing of patients during response inhibition challenge.
Conclusions: This multifaceted fMRI study revealed differences in neural processing during response inhibition before
and after chemotherapy in BC patients. Results were modified by the addition of such factors as depression and anxiety,
reaction time and errors of commission. This study contributes to the literature by providing empirical evidence that
chemotherapy affects neural processing during response inhibition and by highlighting that many factors need to be
considered when studying the impact of chemotherapy on cognition.
NOTES
82
53) Companion ratings of emotions, quality of life, and cognitive functioning in prostate cancer patients undergoing androgen deprivation therapy. The view from the
other side. (A. TATTERSALL)
Authors : A. Tattersall
, M. Cherrier
1,3
, A. Church
1,3
, K. Andersen
1,3
, C. Higano 2, C. Moinpour 4, B. Kurland 4, S. Chai
1,3
4
Institutional Affiliations :
1
Department of Psychiatry and Behavioral Sciences ;
2 Department of Medicine- Division of Oncology, University of Washington Medical School, Seattle, WA 98195 ;
3
VAPSHCS, Seattle, WA 98109
4
Fred Hutchinson Cancer Research Center, Seattle, WA 98109
E-mail of the corresponding author: [email protected]
Purpose: Men who undergo androgen deprivation therapy (ADT) often experience depressed and anxious mood, low
energy, and cognitive decrements. Studies examining the extent of these changes over treatment have used self-reports
from patients to measure change. However, the incidence of self-reported symptoms is 5-25% lower in men and 1040% lower for patients over the age of 65. Companion report of patient symptoms has been widely used as a tool in
oncology when the patient is unable to self-report, and may be more accurate to true patient condition when involving
non-physiological symptoms. This study examined self-reports of patients about the effects of ADT compared to the
reports of companions.
Methods: ADT patients currently enrolled as part of a larger study examining treatment effects were approached to
participate with a companion (spouse, partner, family member or friend). Companions were contacted via mail and completed questionnaires that the ADT patients had also completed. Measures used included the POMS, FACT-cog, FACIT-F,
SF-36, and PHQ9.
Results: The majority of participants (mean age 68 years) were women and the spouses of patients. The areas of assessment analyzed for agreement were mood, fatigue, cognitive difficulties, depression, pain, and emotional difficulties.
The companion scores for most measures were higher, indicating a more severe endorsement of symptoms than those
of patients. There was a trend for more deviation in dyad scores with lower cognitive test performance.
Conclusions: Some patients undergoing ADT may under-report their symptoms in comparison to companion views.
Companion assessment may be a valuable tool for assessing non-physiological variables in patients, particularly if ability
to self-evaluate is affected by mild or marked cognitive decline.
NCI#: CA120933
NOTES
83
54) Cognitive function in colorectal cancer (CRC) patients: Baseline data from a large
longitudinal prospective study (Janette VARDY)
Authors : Janette Vardy 1, Haryana Dhillon 1, Wei Xu 2, Sean Rourke 3, Anna Dodd 2, Corrinne Renton 1, Xin Qiu 2, Stephen
Clarke 1, Ian F. Tannock 2
Institutional Affiliations :
1
Sydney Cancer Centre, University of Sydney, Australia;
2
Princess Margaret Hospital, University of Toronto, Canada
3
St Michael’s Hospital, University of Toronto, Canada
E-mail of the corresponding author :
[email protected]
Purpose: Cancer patients may have cognitive impairment at diagnosis, and this may increase after chemotherapy. Here
we evaluate baseline cognitive function and potential mechanisms in CRC patients.
Methods: Chemotherapy-naïve patients with stage I-III CRC (Group 1), patients with limited metastatic CRC prior to
chemotherapy (Group 2) and healthy controls (HC) were evaluated. Group 1A had subsequent chemotherapy and group
1B did not; comparisons during treatment are reported elsewhere. Neuropsychological (NP) evaluation included classical
and computerized tests with impairment defined using global deficit scores (GDS). Participants completed concurrent
questionnaires for fatigue & quality of life (FACT-F), anxiety/depression (GHQ), and perceived cognitive function (FACTCOG). Groups 1 and 3 donated blood to evaluate 10 cytokines, clotting factors, sex hormones, CEA and apolipoprotein
E genotype. The primary endpoint was cognitive function assessed by classical tests. Associations between test results,
demographic and disease-related factors were sought.
Results: We evaluated 359 patients (169 Group 1A, 118 Group 1B, 72 Group 2), median age 59 (23-75 years); 64%
male; and 72 HC. Using GDS criteria 8% of HC had cognitive impairment on classical tests vs Group 1 32% (p=.0002),
Group 2 26% (p=.006); with no difference between Group 1A and 1B, or those evaluated pre- and post-surgery. Men
had greater cognitive impairment (p<.004). Self-reported cognitive symptoms: Group 1 10% vs HC 6%. Fatigue: 54%
Group 1, 68% Group 2 and 26% HC (p<0.0001). Fatigue, QOL, anxiety/depression & self-reported cognitive symptoms
were associated with each other (r=.44-.70, p<.0001) but not with NP performance. Cytokines were significantly elevated compared to HC. There was no association with cognitive function and: cytokines, sex hormones, clotting factors,
CEA or apoE genotype.
Conclusions: Cognitive impairment occurs in ~1/3 of CRC patients pre-chemotherapy, with men having higher rates.
Cytokine levels were elevated, but not associated with baseline cognitive function.
NOTES
84
55) Pilot Study Utilizing Fluorine-18 fluorodeoxyglucose (F-18 FDG) Positron Emission Tomography - Computed Tomography scan (PET-CT scan) to Investigate Brain
Metabolic Changes during Treatment in Women with Breast Cancer (Shamsuddin
VIRANI)
Authors: Shamsuddin Virani 1,
Rachel Lagos
Govardhanan Nagaiah 4 and Jame Abraham 4
,
2
Gerald Hobbs
,
3
Gary Marano
,
2
Quoc Truong
,
4
Institutional Affiliations:
Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States, 53226 ;
Department of Radiology, West Virginia University, Morgantown, West Virginia, United States, 26506 ;
3
Department of Statistics, West Virginia University, Morgantown, West Virginia, United States, 26506 ;
4
Mary Babb Randolph Cancer Center, Section of Hematology and Oncology, West Virginia University, Morgantown, West
Virginia, United States, 26506.
1
2
E-mail of the corresponding author: [email protected]
Purpose: Approximately 25% of the patients undergoing chemotherapy and some of those undergoing endocrine therapy develop neurocognitive changes. Though extensively studied, specific changes in the brain associated with cognitive dysfunction remain unclear. We performed an IRB-approved retrospective pilot study utilizing brain images from
standard PET-CT scans in patients being treated for breast cancer. Comparison was made between patients initial and
follow-up scans to look for metabolic changes.
Methods: Thirty-nine patients with a diagnosis of breast cancer were identified from radiology database of West Virginia
University Hospitals, who underwent at least two PET-CT scans during their treatment for breast cancer from 2004-2009.
Patients with brain metastasis were excluded. NeuroMIM® software analysis program was used to compare a comprehensive database of physiologic brain anatomy and metabolism with F-18 FDG perfusion brain images from the patients.
Comparison was made in sixty-three defined brain regions. For each patient, two scans at approximately twelve month
intervals were analyzed. The data sets from initial scans were compared with the follow up.
Results: A total of 37 patients received cytotoxic chemotherapy, 2 patients received only endocrine therapy. Data
analysis using the signed-rank test shows that the collective Z-score values change between the initial and follow up
scans. When data analysis is applied to the individual brain regions, the Lingual Gyrus (p=0.012) and the Angular Gyrus
(p=0.056)show statistically significant and near significant decreases in brain metabolism respectively. These regions
are attributed with language, mathematics and cognition. Several additional regions such as the fusiform gyrus and the
primary visual cortex show p-values between 0.05 and 0.10, which indicate «trending» . These regions may demonstrate
statistically significant decrease in metabolism if the sample size is increased.
Conclusions: The Lingual and the Angular Gyrus show a statistically significant and near significant decrease in glucose
metabolism respectively, in patients receiving treatment for breast cancer. Limitations of this study include lack of baseline brain imaging and its clinical correlation with cognitive function. Based upon these preliminary findings prospective
studies are being planned.
NOTES
85
56) Patient-reported cognitive impairments among women with breast cancer randomized to hormonal therapy alone versus chemotherapy followed by hormonal therapy : Results from the TAILORx trial (PACCT-1) (Lynne I. WAGNER)
Authors : 1 Lynne I. Wagner, 2 Robert Gray, 3 George Sledge,
Geyer ; 8 Elizabeth Claire Dees ; 9 Joseph Sparano
4
Tim Whelan,
5
JoAnne Zujewski,
6
Daniel Hayes,
7
Charles
Institutional Affiliations :
1
Northwestern University Feinberg School of Medicine ;
2
Eastern Cooperative Oncology Group Statistical Center ;
3
Indiana University Simon Cancer Center ;
4
McMaster University ;
5
National Cancer Institute ;
6
University of Michigan Comprehensive Cancer Center ;
7
Allegheny Cancer Center ;
8
University of North Carolina ;
9
Montefiore Medical Center.
E-mail of the corresponding author : [email protected]
Purpose: To prospectively assess patient-reported cognitive impairments among women with breast cancer randomized
to hormonal therapy alone versus chemotherapy followed by hormonal treatment.
Methods: Patients registered on the Eastern Cooperative Oncology Group and Breast Cancer Intergroup clinical trial
Trial Assigning IndividuaLized Options for Treatment: The TAILORx Trial (PACCT-1) after January 2010 were eligible to
participate in the patient-reported outcomes (PRO) assessment component of this trial. Based on OncoType DX Recurrence Score (RS), TAILORx participants were assigned to receive hormonal treatment alone (RS > 11), chemotherapy
followed by hormonal treatment (RS < 25), or were randomized to hormonal treatment +/- chemotherapy (RS 11-25).
Participants completed patient-reported outcomes measures to assess: (1) perceived cognitive function (Functional
Assessment of Cancer Therapy – Cognitive Function; FACT-Cog version 3), (2) fatigue (FACT-Fatigue and PROMIS-Fatigue 7-item short form), (3) endocrine symptoms (FACT-Endocrine Symptoms), (4) fears about recurrence and health
(Assessment of Survivor Concerns), and (5) health-related quality of life (FACT-General). Assessments were administered at baseline and 3, 6, 12, 24, and 36 months after registration.
Results: 1105 patients were eligible for the PRO component of the TAILORx trial. As of September 30, 2011, PRO data
are available for 978 patients. FACT-Cog scores measuring patient-reported cognitive impairment will be presented for
307 participants randomized to hormonal treatment alone and 268 randomized to chemotherapy + hormonal treatment.
Results from baseline, 3, 6 and 12 months will be presented. FACT-Cog scales demonstrated excellent internal consistency (Cronbach’s alphas 0.88 – 0.97).
Conclusions: This trial provides the first opportunity to examine patient-reported cognitive impairments among women
with breast cancer randomized to hormonal treatment +/- chemotherapy. Findings will be used to evaluate the psychometric properties of the FACT-Cog. Findings will provide valuable insights on the trajectory of this prevalent symptom
prospectively throughout and following treatment.
NOTES
86
57) Chemotherapy and Cognitive Function in a Mouse Model (Gordon WINOCUR)
Authors : Gordon Winocur
1
& Ian Tannock
2
Institutional Affiliations :
1
Rorman Research Institute, Baycrest Centre ;
2
University of Toronto ; Princess Margaret Hospital, Departments of Medical Oncology and Medical Biophysics, University
of Toronto.
E-mail of the corresponding author : [email protected]
The study of chemotherapy-induced cognitive impairment has been advanced by the use of animal models that enable
greater control over the biological and psychosocial effects of living with a serious disease, as well as the challenges of
coping with a difficult treatment. In this presentation, we report a prospective study in which normal adult mice were
treated with a combination of methotrexate (MTX) + 5- fluorouacil (5-FU) and administered a series of cognitive tests
that assessed various aspects of learning and memory. Relative to controls, the chemotherapy-treated group exhibited
poor memory for tasks acquired before treatment as well as impaired learning and memory for tasks introduced after
treatment. Impairment was especially pronounced on tests of hippocampus-dependent memory and tests of frontal
lobe-controlled executive function. Over a 3-month period there was some recovery but continuing deficits on some
tests provided evidence of long-term impairment. In a second study, donepezil, a cholinergic drug used to treat cognitive
disorders in other clinical populations (e.g., Alzheimer disease), was found to be effective in reducing cognitive impairment in mice injected with MTX + 5-FU. Finally, a third study evaluated the neuroprotective value of increased physical
activity against the adverse effects of MTX + 5-FU on cognitive performance. This study is ongoing at the time of writing
and the results will be presented at the conference. Possible mechanisms underlying cognitive impairment associated
with chemotherapy (e.g., reduced neurogenesis, neuroinflammation) will be discussed.
NOTES
87
58) Moving beyond ‘chemobrain’: Understudied neurobehavioral changes following
hematopoietic cell transplant (Lisa WU)
Authors: Lisa Wu, PhD 1*, Jane Austin, PhD 2, Heiddis Valdimarsdottir, PhD
William Redd, PhD 1, Christine Rini, PhD 6
, Luis Isola, MD 4, Scott Rowley, MD 5,
1,3
Institutional Affiliations:
1
Department of Oncological Sciences, Mt. Sinai School of Medicine, NY ;
2
Department of Psychology, William Paterson University, NJ ;
3
Department of Psychology, Reykjavik University, Iceland ;
4
Department of Medicine, Mt. Sinai School of Medicine, NY ;
5
John Theurer Cancer Center, Hackensack University Medical Center, NJ;
6
Department of Health Behavior & Health Education, University of North Carolina, Chapel Hill, NC
*E-mail of the corresponding author:[email protected]
Purpose: Although survivors of hematopoietic cell transplant (HCT) may experience neurocognitive impairment, there is
little research examining survivors’ neurobehavioral functioning (i.e., behavioral symptoms associated with neurological
dysfunction, such as apathy). The purpose of this preliminary study is to describe survivors’ neurobehavioral functioning
pre- and post-HCT.
Methods: Forty-two survivors 9-months to 3-years post-HCT used the Frontal Systems Behavior Scale to report preHCT and post-HCT apathy, disinhibition and executive dysfunction. Descriptive statistics were examined to determine the
frequency with which each behavior was endorsed. Paired t-tests and McNemar tests were used to explore differences
in neurobehavioral functions.
Results: Executive dysfunction was most frequently reported pre-HCT (28.6%). Post-HCT, apathy was most frequently
reported (35.7%) followed by executive dysfunction (31.0%). Survivors reported greater post-HCT apathy (p= .001)
and higher total impairment (p= .005) than pre-HCT. There was a trend toward survivors being more likely to endorse
borderline levels of apathy post-HCT than pre-HCT (p=.07).
Conclusions: Although studies have noted neurocognitive difficulties among HCT survivors, results suggest that neurobehavioral symptoms (apathy and executive dysfunction), may also be present. Furthermore, apathy may increase
significantly following HCT. Since apathy and executive dysfunction are often confused with other diagnoses, including
depression, understanding the nature of these symptoms has implications for intervention. Longitudinal research in this
area is indicated.
NOTES
88
Abstracts in alphabetical order
NAME
Ahles
First name
Tim A.
Number of the
poster or oral
com.
page
Oral Com. 9
20
JOHNSTON
I
1
31
Kemperman
M
Oral Com. 14
25
Kesler
Shelli
NAME
First name
Amidi
Ali
Ancoli-Israel
Sonia
Beadle
Geoffrey
2
32
Kobus
M
Bernstein
Lori J.
3
33
Koppelmans
Vincent
Boone
Mathieu
4
34
Lange
Chambers
Annabelle
5
35
Le Fel
Chen
Wenhong
6
36
Cherrier
Monique
Oral Com. 17
28
CHEUNG
Yin Ting
7
CHEUNG
Yin Ting
8
Number of the
poster or oral
com.
page
27
57
28
58
Oral Com. 6
17
29
59
Oral Com. 5
16
Marie
30
60
Johan
31
61
Léger
Isabelle
32
62
Libert
Yves
33
63
37
Maqbool
Ayesha
34
64
38
McDonald
Brenna C.
35
65
Christie
Lori-Ann
9
39
Menning
Sanne
36
66
Cohen
Jonathan
10
40
Mereuta
Onana C.
37
67
Collins
Barbara
Oral Com. 11
22
Merriman
John D
Oral Com. 10
21
Collins
Barbara
11
41
Morel
N
38
68
Conroy
Susan K
12
42
Moyers Ruiz
Liliana
39
69
40
70
Oral Com. 12
23
Correa
DD
13
43
Noal
Sabine
Couture-Lalande
Marie-Eve
14
44
Patel
Sunita K.
Das
Enny
15
45
Pérès
Elodie
41
71
Deprez
Sabine
Oral Com. 4
15
Pomykala
Kelsey L.
42
72
Dietrich
Jörg
Oral Com. 3
14
Pullens
Marleen JJ
43
73
Dubois
Martine
Oral Com. 1
12
Pullens
Marleen JJ
44
74
Dubois
Martine
16
46
Quittet
Marie-Sophie
45
75
Edelstein
Kim
17
47
Ribi
Karin
46
76
Ercoli
LM
18
48
Robbins
Mike
Oral Com. 7
18
Fardell
Joanna
Oral Com. 2
13
Root
JC
47
77
Fardell
Joanna
19
49
Scherling
Carole
48
78
Fleishman
Stewart
20
50
Schrauwen
W
49
79
Ganz
Patricia
Oral Com. 8
19
Schrauwen
W
50
80
Green
Heather
Oral Com. 15
26
Seigers
R
51
81
Green
Heather
Oral Com. 16
27
Smith
Andra
52
82
53
83
Oral Com. 13
24
Hardt
M
21
51
Tattersall
A
Höhn
Gabriela
22
52
Vardy
Janette
Hubbard
Karen
23
53
Vardy
Janette
54
84
Janelsins
Michelle C.
24
54
Virani
Shamsuddin
55
85
Jim
Heather
25
55
Wagner
Lynne I
56
86
Jim
Heather
26
56
Winocur
Gordon
57
87
Wu
Lisa
58
88
89
Notes
90
Notes
91
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