IS#THERE#A#ROLE#FOR## INTRA-ARTERIAL#THERAPY##OR## ISOLATED#LIVER#PERFUSION?! Pr!Olivier!Detry! Department!of!Abdominal!Surgery!&!Transplanta;on! CHU!Liège,!Université!de!Liège! ! IS#THERE#A#ROLE#FOR## INTRA-ARTERIAL#THERAPY##OR## ISOLATED#LIVER#PERFUSION?# YES!! Pr!Olivier!Detry! Department!of!Abdominal!Surgery!&!Transplanta;on! CHU!Liège,!Université!de!Liège! ! Disclosure!statement! • No!ﬁnancial!rela;onships!to!disclose!!! CRC!Liver!Mets! • 25%!of!pa;ents!with!CRC!have!synchronous!liver! Mets!at!;me!of!diagnosis! • 50%!of!pa;ents!will!develop!metachronous!Mets!! • R0!resec;on!remains!the!standard!of!treatment! and!the!only!hope!for!cure!and!longOterm!survival! • Survival!aPer!resec;on:!25!to!50%!at!5!years! • 50%!of!recurrences!within!2!years! • 25!to!50%!of!recurrences!are!intrahepa;c!only!! CRC!Liver!Mets! Liver!vascularisa;on:! 66!%!Portal!vein! 33!%!Hepa;c!artery! ! MTST!vascularisa;on:! >!80!%!Hepa;c!artery! ! CRC!Liver!Mets!! and!intraarterial!therapy! • Intra!arterial!chemotherapy! • Radioembolisa;on!YXrium! • Isolated!liver!perfusion! IntraOarterial!chemotherapy! • Adjuvant!IA!chemotherapy! • Irresectable!MTST! ! !O!pallia;ve!(1st!or!2nd!line)! ! • BeXer!compared!to!old!style!chemotherapy! • Discussed!compared!to!modern!iv!therapy! ! !! Goere,!Ann!Surg!2013;!257:114O120.! Pallia;ve!IA!chemotherapy! IntraOarterial!chemotherapy! • ideal!for!mul;ple!CRC!MTST!isolated!to!the! liver! O!irresectable! O!aPer!resec;on!>!4!lesions! • Technically!challenging! O!thrombosis! O!infec;on! • Placement:!surgical!or!radiological! Surgical!placement! IntraOarterial!chemotherapy! • Need!for!beXer!prospec;ve!studies!comparing! modern!IV!and!IA!chemotherapy!both!in! pallia;ve!and!postopera;ve!condi;ons! YXriumO90!radioemboliza;on! • TheraSpheres!(20O30!microns)! • SIRSpheres!(20O60!microns)! • First!line!therapy! • Second!or!third!line!chemotherapy! • Salvage!for!chemorefractory!pa;ents! Selec;ve!treatmetn!of!the!right!liver!MTST! +!5!months! +!15!months! Isolated!liver!perfusion! • High!concentra;on!of!chemotherapy! • High!temperature! • melphalan!+!TNFOα! • oxalipla;n! • Ocular!melanoma!MTST! • NeuroOendocrine!MTST! • CRC!MTST! Isolated!liver!perfusion! Ann Surg Oncol (2009) 16:385–394 DOI 10.1245/s10434-008-0179-5 ORIGINAL ARTICLE – HEPATOBILIARY AND PANCREATIC TUMORS A Phase I Study of Hyperthermic Isolated Hepatic Perfusion with Oxaliplatin in the Treatment of Unresectable Liver Metastases from Colorectal Cancer Herbert J. Zeh III, MD1, Charles K. Brown, MD, PhD1, Matthew P. Holtzman, MD1, Merrill J. Egorin, MD2,3, Julianne L. Holleran, BS2, Douglas M. Potter, PhD4, and David L. Bartlett, MD1 1 Division of Surgical Oncology, Department of Surgery, University of Pittsburgh School of Medicine, Suite 417 UPMC Cancer Pavilion, 5150 Center Ave., Pittsburgh, PA 15232, USA; 2Molecular Therapeutics/Drug Discovery Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232, USA; 3Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15232, USA; 4Biostatistics Department, Graduate School of Public Health and Biostatistics Facility, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA Isolated Hepatic Perfusion with Oxaliplatin 387 years). We conclude that 1hyperthermic with oxaABSTRACT perfusion (IHP) a proven bypass hadIsolated beenhepatic established, the isIHP circuit([4was conTABLE OxaliplatinIHP dose escalation scheme 2 liplatin was safe and feasible at a dose of 40 mg/m approach for regional delivery of chemotherapy in patients . The structed. The GDA was ligated distally. The inflow cannula Planned Actual number of Dose vascular Oxaliplatin with unresectable primary and metastatic tumors of the ability to obtain complete isolation with open IHP number 2 for perfusion was positioned in the proximal GDA, and, ) of patients patients enrolled level dose (mg/m liver. Most trials of IHP have utilized melphalan as the was confirmed. The response rate in this small phase I study once secured, a cross was placed the entire active drug in the perfusate. We clamp performed a phase I trial across to was encouraging. 1 5 1 1 evaluate the efficacy, safety, and maximum tolerated dose porta hepatis, including the common hepatic artery, bile (MTD) of oxaliplatin delivered by hyperthermic isolated 2 10 1 1 duct, and portal vein. The perfusion outflow cannula was hepatic perfusion. A phase I dose-escalation trial of Cancer of the colon and rectum20 is the third most frequent 1 1 inserted into the retrohepatic IVC via percutaneous can-in the 3USA, and accounts hyperthermic IHP with oxaliplatin in patients withaunresite of cancer for approximately a 4 40 3–6 6 sectable metastatic colorectal scheduled undergo nulation of the right cancer femoral veintoand a tourniquet was 150,000 new cases annually.1 Hepatic metastases as the sole placement a hepaticthe arterial infusion pump was 3–6 1b dominant site of 5 life-limiting 60 disease occur in approxiplaced ofaround cannula at (HAI) the level of theorsuprarenal carried out. Thirteen patients were enrolled between mately 20–50% of patients with colorectal cancer.2 Median 6 90 3–6 0 infrahepatic IVC. The suprahepatic IVC was then crossNovember 2003 and September 2006. Dose-limiting venosurvival of patients with untreated colorectal cancer hepatic 2 7 120 3–6 0 clamped, and thisat had been vascular occlusive disease wasonce observed 60 mg/m . Ataccomplished, the MTD metastases ranges from 4 to 12 months.3 Complete surgical 2 3–6 0 of isolation 40 mg/m only minor transient liver dysfunction was resection of isolated8colorectal 150 cancer hepatic metastases of the liver was considered complete, and perfuobserved. Ultrafilterable platinum area under the curve and results in 5-year survival rates between 32% and a sion was initiated. The perfusate consisted of overall MTD maximum concentration delivered by IHP increased non58%.4–8 Unfortunately, only 10–20% of patients with b approximately 500platinum ml Ringer’s lactate to which 9 linearly with dose as did concentrations in liver of grade V VOD and fulminant hepatic failure colorectalwere metastases toDLT the liver are eligible for resection. biopsies at the of the red 60 min IHP. cells. Seventy-Once addedobtained 2 units of end packed blood perfusion Systemic chemotherapy is the predominant treatment for seven percent of patients had a [50% decrease in serum patients with unresectable liver metastases from colorectal IS#THERE#A#ROLE#FOR## INTRA-ARTERIAL#THERAPY##OR## ISOLATED#LIVER#PERFUSION?# YES!! Pr!Olivier!Detry! Department!of!Abdominal!Surgery!&!Transplanta;on! CHU!Liège,!Université!de!Liège! ! Thanks!!