Curr Oncol Rep (2014) 16:388 DOI 10.1007/s11912-014-0388-y
GASTROINTESTINAL CANCERS (B CZITO, SECTION EDITOR)
Management Options in Locally Advanced Pancreatic Cancer Omar Y. Mian & Ashwin N. Ram & Richard Tuli & Joseph M. Herman
Published online: 17 April 2014 # Springer Science+Business Media New York 2014
Abstract Pancreatic ductal adenocarcinoma is a highly lethal cancer that is rarely curable at the time of presentation. Unfortunately, most patients are diagnosed with either metastatic or locally advanced disease, which is not amenable to surgery owing to the high likelihood of incomplete resection. Given the generally poor prognosis with propensity for metastatic failure greater than that for local failure, treatment options are variable, and include chemotherapy, radiotherapy, targeted therapies, and combinations thereof. This review summarizes the current evidence for definitive management of locally advanced pancreatic adenocarcinoma, as well as the role of palliative therapies. Future directions, including the development of predictive biomarkers and novel systemic agents, are also discussed.
Keywords Pancreatic cancer . Cancer . Oncology . Gastrointestinal cancers . Locally advanced pancreatic cancer . Chemotherapy . Radiotherapy . Targeted therapies . Predictive biomarkers . Novel systemic agents . Pancreatic ductal adenocarcinoma
Omar Y. Mian and Ashwin N. Ram, both contributed equally. This article is part of the Topical Collection on Gastrointestinal Cancers O. Y. Mian : A. N. Ram : J. M. Herman (*) Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, 401 North Broadway, Weinberg Suite, 1440, Baltimore, MD 21231, USA e-mail: [email protected]
R. Tuli Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Introduction Pancreatic ductal adenocarcinoma is the fourth leading cause of cancer mortality in the United States, accounting for more than 38,000 deaths in 2013 alone. Despite aggressive combined modality treatment approaches, 5-year mortality remains dismal at less than 5%. Of the current treatment options, only margin-negative (R0) surgical resection is thought to have curative potential. Unfortunately, only 10-15% of patients have resectable disease at presentation. Tumor interface with the superior mesenteric artery (SMA), celiac axis, and superior mesenteric and portal veins predicts the likelihood of performing a margin-negative resection. Tumor encasement of greater than 180° of the SMA, any celiac artery involvement, or involvement of the superior mesenteric and portal veins that is not amenable to reconstruction is considered surgically unresectable and locally advanced pancreatic cancer (LAPC) according to the most recent consensus guidelines from the National Comprehensive Cancer Network (NCCN). Removal of tumors with these features is either technically unfeasible owing to the overriding risks of surgery, or would likely result in a margin-positive (R1/R2) resection. Because completeness of resection is generally associated with longterm survival, margin-positive resections are associated with significantly worse outcomes relative to margin-negative resections, while subjecting patients to a considerably morbid procedure [1–5]. Because survival rates for patients with LAPC are generally poor, with median overall survival ranging from 8 to 12 months [6, 7], treatment recommendations often involve aggressive multimodal therapies, which should be based on patient performance status and the goals of care. A multidisciplinary approach involving surgical oncologists, medical oncologists, and radiation oncologists is strongly recommended for a balanced discussion of management options [8–10].
388, Page 2 of 12
It is equally imperative to properly select patients for aggressive multimodal treatment versus quality-of-life (QOL)directed measures. At present, treatment options for LAPC include chemotherapy alone, induction chemotherapy followed by chemoradiotherapy (CRT), or definitive CRT. Herein, we summarize current evidence with a look forward to future directions, vis-à-vis personalization of treatment and novel systemic agents.
Surgical Treatment of LAPC Surgical treatment of LAPC is controversial. In part, this is reflected by the evolving criteria for tumor resectability. Indeed, definitions of resectability can vary as a function of institutional experience, radiographic interpretation, and surgeon skill. For example, a subgroup of patients with LAPC involving the celiac axis or proximal common hepatic artery with adequate collateral blood flow from the SMA may be eligible for the Appleby procedure, which involves a distal pancreatectomy with en bloc resection of the celiac axis and dissection of the retroperitoneal tissue, stomach, colon, and adrenal gland. Although appropriate only in wellselected patients who are generally younger and have a high performance status, this procedure has been shown to improve survival compared with survival of patients who did not undergo resection of locally advanced disease [11, 12]. However, extended pancreatic resections remain controversial, as arterial resection has been associated with a significantly increased risk of perioperative mortality (odds ratio 5.04, p
GASTROINTESTINAL CANCERS (B CZITO, SECTION EDITOR)
Management Options in Locally Advanced Pancreatic Cancer Omar Y. Mian & Ashwin N. Ram & Richard Tuli & Joseph M. Herman
Published online: 17 April 2014 # Springer Science+Business Media New York 2014
Abstract Pancreatic ductal adenocarcinoma is a highly lethal cancer that is rarely curable at the time of presentation. Unfortunately, most patients are diagnosed with either metastatic or locally advanced disease, which is not amenable to surgery owing to the high likelihood of incomplete resection. Given the generally poor prognosis with propensity for metastatic failure greater than that for local failure, treatment options are variable, and include chemotherapy, radiotherapy, targeted therapies, and combinations thereof. This review summarizes the current evidence for definitive management of locally advanced pancreatic adenocarcinoma, as well as the role of palliative therapies. Future directions, including the development of predictive biomarkers and novel systemic agents, are also discussed.
Keywords Pancreatic cancer . Cancer . Oncology . Gastrointestinal cancers . Locally advanced pancreatic cancer . Chemotherapy . Radiotherapy . Targeted therapies . Predictive biomarkers . Novel systemic agents . Pancreatic ductal adenocarcinoma
Omar Y. Mian and Ashwin N. Ram, both contributed equally. This article is part of the Topical Collection on Gastrointestinal Cancers O. Y. Mian : A. N. Ram : J. M. Herman (*) Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, 401 North Broadway, Weinberg Suite, 1440, Baltimore, MD 21231, USA e-mail: [email protected]
R. Tuli Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Introduction Pancreatic ductal adenocarcinoma is the fourth leading cause of cancer mortality in the United States, accounting for more than 38,000 deaths in 2013 alone. Despite aggressive combined modality treatment approaches, 5-year mortality remains dismal at less than 5%. Of the current treatment options, only margin-negative (R0) surgical resection is thought to have curative potential. Unfortunately, only 10-15% of patients have resectable disease at presentation. Tumor interface with the superior mesenteric artery (SMA), celiac axis, and superior mesenteric and portal veins predicts the likelihood of performing a margin-negative resection. Tumor encasement of greater than 180° of the SMA, any celiac artery involvement, or involvement of the superior mesenteric and portal veins that is not amenable to reconstruction is considered surgically unresectable and locally advanced pancreatic cancer (LAPC) according to the most recent consensus guidelines from the National Comprehensive Cancer Network (NCCN). Removal of tumors with these features is either technically unfeasible owing to the overriding risks of surgery, or would likely result in a margin-positive (R1/R2) resection. Because completeness of resection is generally associated with longterm survival, margin-positive resections are associated with significantly worse outcomes relative to margin-negative resections, while subjecting patients to a considerably morbid procedure [1–5]. Because survival rates for patients with LAPC are generally poor, with median overall survival ranging from 8 to 12 months [6, 7], treatment recommendations often involve aggressive multimodal therapies, which should be based on patient performance status and the goals of care. A multidisciplinary approach involving surgical oncologists, medical oncologists, and radiation oncologists is strongly recommended for a balanced discussion of management options [8–10].
388, Page 2 of 12
It is equally imperative to properly select patients for aggressive multimodal treatment versus quality-of-life (QOL)directed measures. At present, treatment options for LAPC include chemotherapy alone, induction chemotherapy followed by chemoradiotherapy (CRT), or definitive CRT. Herein, we summarize current evidence with a look forward to future directions, vis-à-vis personalization of treatment and novel systemic agents.
Surgical Treatment of LAPC Surgical treatment of LAPC is controversial. In part, this is reflected by the evolving criteria for tumor resectability. Indeed, definitions of resectability can vary as a function of institutional experience, radiographic interpretation, and surgeon skill. For example, a subgroup of patients with LAPC involving the celiac axis or proximal common hepatic artery with adequate collateral blood flow from the SMA may be eligible for the Appleby procedure, which involves a distal pancreatectomy with en bloc resection of the celiac axis and dissection of the retroperitoneal tissue, stomach, colon, and adrenal gland. Although appropriate only in wellselected patients who are generally younger and have a high performance status, this procedure has been shown to improve survival compared with survival of patients who did not undergo resection of locally advanced disease [11, 12]. However, extended pancreatic resections remain controversial, as arterial resection has been associated with a significantly increased risk of perioperative mortality (odds ratio 5.04, p
