Pathologic response with neoadjuvant chemotherapy and stereotactic body radiotherapy for borderline resectable and locally-advanced pancreatic cancer

Malolan S Rajagopalan,Annette E Quinn,Steven A Burton,Randall Brand,Herbert J Zeh,Dwight E Heron,Alyssa M Krasinskas,Barry Lembersky,Nathan Bahary,A James Moser,Rodney E Wegner

doi:10.1186/1748-717x-8-254

Abstract

BackgroundNeoadjuvant stereotactic body radiotherapy (SBRT) has potential applicability in the management of borderline resectable and locally-advanced pancreatic adenocarcinoma. In this series, we report the pathologic outcomes in the subset of patients who underwent surgery after neoadjuvant SBRT.MethodsPatients with borderline resectable or locally-advanced pancreatic adenocarcinoma who were treated with SBRT followed by resection were included. Chemotherapy was to the discretion of the medical oncologist and preceded SBRT for most patients.ResultsTwelve patients met inclusion criteria. Most (92%) received neoadjuvant chemotherapy, and gemcitabine/capecitabine was most frequently utilized (n = 7). Most were treated with fractionated SBRT to 36 Gy/3 fractions (n = 7) and the remainder with single fraction to 24 Gy (n = 5). No grade 3+ acute toxicities attributable to SBRT were found. Two patients developed post-surgical vascular complications and one died secondary to this. The mean time to surgery after SBRT was 3.3 months. An R0 resection was performed in 92% of patients (n = 11/12). In 25% (n = 3/12) of patients, a complete pathologic response was achieved, and an additional 16.7% (n = 2/12) demonstrated <10% viable tumor cells. Kaplan-Meier estimated median progression free survival is 27.4 months. Overall survival is 92%, 64% and 51% at 1-, 2-, and 3-years.ConclusionsThis study reports the pathologic response in patients treated with neoadjuvant chemotherapy and SBRT for borderline resectable and locally-advanced pancreatic cancer. In our experience, 92% achieved an R0 resection and 41.7% of patients demonstrated either complete or extensive pathologic response to treatment. The results of a phase II study of this novel approach will be forthcoming.

Highlights

Neoadjuvant stereotactic body radiotherapy (SBRT) has potential applicability in the management of borderline resectable and locally-advanced pancreatic adenocarcinoma
Patient population Patients with biopsy-proven borderline resectable or locally-advanced pancreatic adenocarcinoma who were treated with neoadjuvant SBRT from 2008–2011 and completed surgical resection were included in this retrospective analysis
Patient characteristics One-hundred and five patients were treated at our institution with SBRT for pancreatic cancer for primary or definitive intent

Summary

Introduction

Neoadjuvant stereotactic body radiotherapy (SBRT) has potential applicability in the management of borderline resectable and locally-advanced pancreatic adenocarcinoma. Pancreatic cancer is the fourth leading cause of death from cancer in both men and women in the United States [1] It is a highly aggressive entity with approximately 40% presenting as locally-advanced but unresectable disease and an additional 40% presenting with metastatic disease [2]. Based upon this study and ESPAC-1, which does have a number of flaws with design but found a deleterious effect of adjuvant chemoradiation, the use of adjuvant radiation has fallen out of favor in Europe and is controversial in North America [5,6]. A number of studies including CONKO-001 and RTOG 9704 began to shed light that gemcitabine-based adjuvant chemotherapy may be more efficacious than previous regimens [7,8]. It must be noted that the recent update to ESPAC-3 found that adjuvant gemcitabine may be equivalent to adjuvant 5FU [9]

Methods

Results

Discussion

Conclusion