Clinical Study Received: October 17, 2014 Accepted after revision: December 19, 2014 Published online: March 7, 2015
Oncology DOI: 10.1159/000371745
Resection of Borderline Resectable and Locally Advanced Pancreatic Adenocarcinomas after Neoadjuvant Chemotherapy Pietro Addeo a Edoardo Rosso a Pascal Fuchshuber c Elie Oussoultzoglou a Vito De Blasi a Gael Simone a Christine Belletier b Patrick Dufour b Philippe Bachellier a
a
Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Pôle des Pathologies Digestives, Hépatiques et de la Transplantation, Hôpital de Hautepierre-Hôpitaux Universitaires de Strasbourg, and b Department of Medical Oncology, Paul Strauss Cancer Center, University of Strasbourg, Strasbourg, France; c Department of Surgery, The Permanente Medical Group, Kaiser Medical Center, Walnut Creek, Calif., USA
Abstract Objective: To report the outcomes of surgical resection of borderline resectable (BL) and locally advanced (LA) ‘unresectable’ pancreatic cancer after neoadjuvant chemotherapy. Methods: A review of a prospectively maintained database for pancreatic resections was undertaken to identify patients undergoing resection for BL and LA pancreatic cancer after neoadjuvant chemotherapy between January 2007 and December 2012. Clinicopathological, surgical and survival outcomes were analyzed. Results: A total of 45 patients with LA (n = 34) or BL cancer (n = 11) underwent surgery after a mean (± SD) of 7 ± 4 preoperative chemotherapy cycles. Ninety-day mortality was 6.7%, and overall morbidity was 33.3%. An R0 resection was achieved in 34 patients, and 4 patients showed a complete pathological response. Overall median postoperative survival was 17 months (21 after the start of neoadjuvant treatment). Overall and disease-free survival was 74.9 and 43.6% at 1 year and 21.2 and 10.3% at 3 years, respectively. In BL cancer patients, the 3-year sur-
© 2015 S. Karger AG, Basel 0030–2414/15/0000–0000$39.50/0 E-Mail [email protected] www.karger.com/ocl
vival was significantly higher compared to that of LA cancer patients (p = 0.02). Conclusions: Curative intent resection in BL and LA cancer patients after neoadjuvant chemotherapy can be achieved with reasonable mortality and morbidity and an encouraging 3-year survival. After neoadjuvant therapy, resection provides a better overall survival for BL compared to LA cancer patients. © 2015 S. Karger AG, Basel
Introduction
Multimodal neoadjuvant therapy for advanced disease is being used in the preoperative management of patients affected by several digestive malignancies. The main goals of preoperative chemotherapy and/or radiotherapy in this setting are (1) the downstaging and downsizing of bulky local disease and (2) the optimization of patient selection for surgery by excluding paP.A. and E.R. contributed equally to this study. Part of this work was presented at the 99th Annual Congress of The American College of Surgeons, Washington, DC, in October 2013, and at the 11th World Congress of the International Hepto-Pancreato-Biliary Association, Seoul, in March 2014.
Prof. Philippe Bachellier Pôle des Pathologies Digestives, Hépatiques et de la Transplantation Hôpital de Hautepierre-Hôpitaux Universitaires de Strasbourg 1, Avenue Molière, FR–67098 Strasbourg (France) E-Mail philippe.bachellier @ chru-strasbourg.fr
Downloaded by: University of Tokyo 157.82.153.40 - 5/17/2015 10:39:18 PM
Key Words Pancreatic cancer · Borderline resectable tumors · Locally advanced tumors · Neoadjuvant chemotherapy · Extended pancreatectomies · Vascular resection
2
Oncology DOI: 10.1159/000371745
Patients and Methods The prospective database for pancreatic resections maintained at the Department of Hepato-Pancreato-Biliary Surgery and Liver Transplantation of the University of Strasbourg was reviewed to identify patients undergoing surgical resection for PDA between January 2007 and December 2012. According to the classification provided by the MD Anderson Cancer Center [4], resectable pancreatic cancers were defined as tumors without extension to the superior mesenteric artery or celiac axis and without invasion of the superior mesenteric vein or the superior mesenteric vein-portal vein confluence. BL pancreatic cancers were defined as those (1) abutting the superior mesenteric artery and/or the common hepatic artery, (2) abutting, occluding or encasing the superior mesenteric and/or the portal vein, and (3) abutting the celiac trunk. LA pancreatic cancers were defined as tumors presenting with non-reconstructable superior mesenteric vein invasion and/or encasement of the superior mesenteric artery and/or of the celiac trunk. Patients with LA and BL tumors undergoing surgery after neoadjuvant chemotherapy were identified through our database and constituted the study population. Demographic and clinical data, cancer type, duration and type of preoperative chemotherapy, intraoperative and postoperative outcomes were retrospectively analyzed. Mortality and morbidity were defined as events occurring within the first 90 postoperative days. Morbidity was stratified according to the Dindo-Clavien classification [12]. Pancreatic fistula (PF) was classified using the International Study Group for Pancreatic Fistula (ISGPF) system. The severity of PF was recorded according to the ISGPF grading system using grades A, B and C, with grades B and C being clinically significant [13]. Medical complications were defined as septic shock, deep vein thrombosis and other medical complications originating from cardiac, pleuropulmonary, neurological and hepatic sources. Pretreatment Staging In all cases, the preoperative evaluation included multidetector contrast-enhanced computed tomography (CT) of the abdomen and chest with 3D reconstruction of the hepatic and superior mesenteric vessels. A histological diagnosis of PDA was obtained in all patients through endoscopic ultrasonography-guided cytological aspiration. Jaundiced patients underwent placement of a short metallic endoscopic biliary stent. Serum carbohydrate antigen 19-9 (CA 19-9, normal values
Oncology DOI: 10.1159/000371745
Resection of Borderline Resectable and Locally Advanced Pancreatic Adenocarcinomas after Neoadjuvant Chemotherapy Pietro Addeo a Edoardo Rosso a Pascal Fuchshuber c Elie Oussoultzoglou a Vito De Blasi a Gael Simone a Christine Belletier b Patrick Dufour b Philippe Bachellier a
a
Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Pôle des Pathologies Digestives, Hépatiques et de la Transplantation, Hôpital de Hautepierre-Hôpitaux Universitaires de Strasbourg, and b Department of Medical Oncology, Paul Strauss Cancer Center, University of Strasbourg, Strasbourg, France; c Department of Surgery, The Permanente Medical Group, Kaiser Medical Center, Walnut Creek, Calif., USA
Abstract Objective: To report the outcomes of surgical resection of borderline resectable (BL) and locally advanced (LA) ‘unresectable’ pancreatic cancer after neoadjuvant chemotherapy. Methods: A review of a prospectively maintained database for pancreatic resections was undertaken to identify patients undergoing resection for BL and LA pancreatic cancer after neoadjuvant chemotherapy between January 2007 and December 2012. Clinicopathological, surgical and survival outcomes were analyzed. Results: A total of 45 patients with LA (n = 34) or BL cancer (n = 11) underwent surgery after a mean (± SD) of 7 ± 4 preoperative chemotherapy cycles. Ninety-day mortality was 6.7%, and overall morbidity was 33.3%. An R0 resection was achieved in 34 patients, and 4 patients showed a complete pathological response. Overall median postoperative survival was 17 months (21 after the start of neoadjuvant treatment). Overall and disease-free survival was 74.9 and 43.6% at 1 year and 21.2 and 10.3% at 3 years, respectively. In BL cancer patients, the 3-year sur-
© 2015 S. Karger AG, Basel 0030–2414/15/0000–0000$39.50/0 E-Mail [email protected] www.karger.com/ocl
vival was significantly higher compared to that of LA cancer patients (p = 0.02). Conclusions: Curative intent resection in BL and LA cancer patients after neoadjuvant chemotherapy can be achieved with reasonable mortality and morbidity and an encouraging 3-year survival. After neoadjuvant therapy, resection provides a better overall survival for BL compared to LA cancer patients. © 2015 S. Karger AG, Basel
Introduction
Multimodal neoadjuvant therapy for advanced disease is being used in the preoperative management of patients affected by several digestive malignancies. The main goals of preoperative chemotherapy and/or radiotherapy in this setting are (1) the downstaging and downsizing of bulky local disease and (2) the optimization of patient selection for surgery by excluding paP.A. and E.R. contributed equally to this study. Part of this work was presented at the 99th Annual Congress of The American College of Surgeons, Washington, DC, in October 2013, and at the 11th World Congress of the International Hepto-Pancreato-Biliary Association, Seoul, in March 2014.
Prof. Philippe Bachellier Pôle des Pathologies Digestives, Hépatiques et de la Transplantation Hôpital de Hautepierre-Hôpitaux Universitaires de Strasbourg 1, Avenue Molière, FR–67098 Strasbourg (France) E-Mail philippe.bachellier @ chru-strasbourg.fr
Downloaded by: University of Tokyo 157.82.153.40 - 5/17/2015 10:39:18 PM
Key Words Pancreatic cancer · Borderline resectable tumors · Locally advanced tumors · Neoadjuvant chemotherapy · Extended pancreatectomies · Vascular resection
2
Oncology DOI: 10.1159/000371745
Patients and Methods The prospective database for pancreatic resections maintained at the Department of Hepato-Pancreato-Biliary Surgery and Liver Transplantation of the University of Strasbourg was reviewed to identify patients undergoing surgical resection for PDA between January 2007 and December 2012. According to the classification provided by the MD Anderson Cancer Center [4], resectable pancreatic cancers were defined as tumors without extension to the superior mesenteric artery or celiac axis and without invasion of the superior mesenteric vein or the superior mesenteric vein-portal vein confluence. BL pancreatic cancers were defined as those (1) abutting the superior mesenteric artery and/or the common hepatic artery, (2) abutting, occluding or encasing the superior mesenteric and/or the portal vein, and (3) abutting the celiac trunk. LA pancreatic cancers were defined as tumors presenting with non-reconstructable superior mesenteric vein invasion and/or encasement of the superior mesenteric artery and/or of the celiac trunk. Patients with LA and BL tumors undergoing surgery after neoadjuvant chemotherapy were identified through our database and constituted the study population. Demographic and clinical data, cancer type, duration and type of preoperative chemotherapy, intraoperative and postoperative outcomes were retrospectively analyzed. Mortality and morbidity were defined as events occurring within the first 90 postoperative days. Morbidity was stratified according to the Dindo-Clavien classification [12]. Pancreatic fistula (PF) was classified using the International Study Group for Pancreatic Fistula (ISGPF) system. The severity of PF was recorded according to the ISGPF grading system using grades A, B and C, with grades B and C being clinically significant [13]. Medical complications were defined as septic shock, deep vein thrombosis and other medical complications originating from cardiac, pleuropulmonary, neurological and hepatic sources. Pretreatment Staging In all cases, the preoperative evaluation included multidetector contrast-enhanced computed tomography (CT) of the abdomen and chest with 3D reconstruction of the hepatic and superior mesenteric vessels. A histological diagnosis of PDA was obtained in all patients through endoscopic ultrasonography-guided cytological aspiration. Jaundiced patients underwent placement of a short metallic endoscopic biliary stent. Serum carbohydrate antigen 19-9 (CA 19-9, normal values
