memoire EGFR NSCLC version finale WK

Université basse Normandie
CAEN
Faculté de médecine
MEMOIRE
DES oncologie option radiothérapie
Présenté par
KAO William
Né le 11 novembre 1986
Evaluation du score GPA chez des patients suivis pour un
adénocarcinome bronchique avec métastases cérébrales
mutés pour l’EGFR
Sous la direction du Dr GERVAIS
Présenté publiquement le 24 juin 2016

Résumé
Evaluation of lung specific GPA in adenocarcinoma patients with brain
metastasis and EGFR activating mutation
Objective: The lung specific GPA is an index, commonly used for patients with non-small cell lung
carcinoma (NSCLC) and brain metastasis (BM) in order to predict overall survival (OS), with the help
of four easy-to-use items: Age at the diagnosis of BM; Karnofsky Performance Status, Presence of
extra cranial metastasis and Number of BM. A score of 0.0 corresponds with the worst prognosis
whereas 4.0 correlates with the best prognosis. However, this tool might not be appropriate to
patients harboring EGFR activating mutations, which are known to have a better prognosis.
The goal of our study was to determine if the Lung specific GPA is adapted to population with these
mutations.
Materials & Methods: We retrospectively analyzed 108 caucasians patients diagnosed with NSCLC
between 2000 and 2014. Clinical features, systemic treatments (chemotherapy or EGFR tyrosine
kinase inhibitors) and previous local brain treatment were examined. OS were compared to the
expected OS according to the lung specific GPA score (Sperduto, JCO, 2012)
Results: Ninety-eight patients (91%) had EGFR activating mutations, whereas the status was
unknown for 10 (9%) patients. Among these mutations, we found 63% of deletion exon 19, 30% of
mutation L858R (exon 21) and 7% of minor mutations (L851Q and L861G in exon 21, G719C in exon
18)
9% of them were nonsmokers. 77/108 patients (71.3%) were women. 53/108 patients (49%) had BM:
30 patients had synchronous BM whereas 23 patients had metachronous. 20/53 patients (38%) were
treated with WBRT.
OS was significantly superior in patients with EGFR activating mutations, compared to the referred
OS in accordance with Sperduto’s GPA score: in GPA 0.0-1.0 (median of 11.5 months IC 95% [8.5-
25.7] vs 3.02 months IC 95% [2.63-3.84]) and in GPA 1.5-2.0 (28 months IC 95% [24.3-NR] vs 5.49
months IC 95% [4.83-6.40]).

Among EGFR activating mutations, OS were also significantly longer in group 1.5-2 than group 0-1 (28
vs 11.5 months) (p = 0.026)
Despite better prognosis for patients with lung cancer and EGFR activating mutations, BM is still a
burden with worse OS, compared with patients without BM (median of 41.9 vs 25.5 months) (p =
0.0007).
Conclusion: Currently, Lung specific GPA is not accurate enough to estimate survival time for EGFR
mutant patients. However, this tool is still reliable to distinguish different prognosis for patient with
EGFR activating mutations, according to their GPA score.
In conclusion, EGFR status modifies OS of patients and should be integrated in the items of the GPA
score. These results should be validated in further prospective studies.
Keywords
EGFR mutation; GPA score; Brain Metastasis; Lung Cancer; Adenocarcinoma

Abréviations
ALK: Anaplastic Lymphoma kinase
ASO PCR: Allele Specific Oligonucleotide Polymerase Chain Reaction
ASTRO: American Society for Radiation Oncology
CK: Cyber Knife
IET: Irradiation Encéphalique in Toto
EGFR: Epidermal Growth Factor Receptor
GPA: Grade Prognostic Assessment (score)
HER: Human Epidermal Growth Factor Receptor
ITK : Inhibiteur de Tyrosine kinase
IC95% : Intervalle de confiance à 95%
KPS : Karnofsky Performance Status
MEC : Métastases Extra-Cérébrales
MC : Métastases Cérébrales
NA : Non Atteinte (limite IC)
NS : Non Significatif
RCP : Réunion de Concertation Pluridisciplinaire
RTOG : Radiation Therapy Oncology Group
SNC : Système Nerveux Central
SSP : Survie Sans Progression
SG : Survie Globale
RPA : Recursive Partitioning Analysis

Figures
Figure 1 : Incidence cancer du poumon chez hommes et femmes âgés de 20 à 44 ans en France
Figure 2 : Taux de mortalité par cancer chez la femme et chez l’homme en 2015
Figure 3 : Courbes de survie en fonction des différentes classes du RPA
Figure 4 : Estimation de la survie au diagnostic des métastases cérébrales en fonction du score GPA
spécifique à l'histologie initiale
Figure 5 : Tableau des médianes de survie, en fonction de l'histologie de la tumeur et des différents
groupes : pronostiques GPA
Figure 6 : Courbe de survie (Kaplan-Meier) des patients avec cancer bronchique EGFR muté
Figure 7 : Courbes de survie (Kaplan-Meier) en fonction de la présence ou non de métastases
cérébrales
Figure 8 : Courbes d'incidence cumulée de métastases cérébrales en fonction du temps, sur
l'ensemble de la population, et sur la population sans métastases cérébrales synchrones
Figure 9 : Courbes de survie (Kaplan-Meier) des différents groupes GPA
Figure 10 : Test de l’hypothèse de proportionnalité
Figure 11 : Courbes de survie (Kaplan-Meier) des patients traités par IET d’emblée puis par ITK EGFR
et des patients traités par ITK de l'EGFR avant IET