Focal Radiation Therapy Dose Escalation Improves Overall Survival in Locally Advanced Pancreatic Cancer Patients Receiving Induction Chemotherapy and Consolidative Chemoradiation

Abstract

Purpose To review outcomes of locally advanced pancreatic cancer (LAPC) patients treated with dose-escalated intensity modulated radiation therapy (IMRT) with curative intent. Methods and Materials A total of 200 patients with LAPC were treated with induction chemotherapy followed by chemoradiation between 2006 and 2014. Of these, 47 (24%) having tumors >1 cm from the luminal organs were selected for dose-escalated IMRT (biologically effective dose [BED] >70 Gy) using a simultaneous integrated boost technique, inspiration breath hold, and computed tomographic image guidance. Fractionation was optimized for coverage of gross tumor and luminal organ sparing. A 2- to 5-mm margin around the gross tumor volume was treated using a simultaneous integrated boost with a microscopic dose. Overall survival (OS), recurrence-free survival (RFS), local-regional and distant RFS, and time to local-regional and distant recurrence, calculated from start of chemoradiation, were the outcomes of interest. Results Median radiation dose was 50.4 Gy (BED = 59.47 Gy) with a concurrent capecitabine-based (86%) regimen. Patients who received BED >70 Gy had a superior OS (17.8 vs 15.0 months, P = .03), which was preserved throughout the follow-up period, with estimated OS rates at 2 years of 36% versus 19% and at 3 years of 31% versus 9% along with improved local-regional RFS (10.2 vs 6.2 months, P = .05) as compared with those receiving BED ≤70 Gy. Degree of gross tumor volume coverage did not seem to affect outcomes. No additional toxicity was observed in the high-dose group. Higher dose (BED) was the only predictor of improved OS on multivariate analysis. Conclusion Radiation dose escalation during consolidative chemoradiation therapy after induction chemotherapy for LAPC patients improves OS and local-regional RFS.

Demonstration of Safety and Feasibility of Hydrogel Marking of the Pancreas–Duodenum Interface for Image Guided Radiation Therapy (IGRT) in a Porcine Model: Implications in IGRT for Pancreatic Cancer Patients

“…Existing preliminary data support optimism for the possibility of improving outcomes for patients with unresectable pancreatic cancer with dose-escalated RT (13–15). The opportunity to deliver a higher prescription dose, however, has largely been restricted to only those with >1 cm of separation between the pancreas and the closest gastrointestinal mucosa (<25% of patients in the published series) (13) or to centers with a magnetic resonance imaging—guided linear accelerator (14, 15).…”

“…The opportunity to deliver a higher prescription dose, however, has largely been restricted to only those with >1 cm of separation between the pancreas and the closest gastrointestinal mucosa (<25% of patients in the published series) (13) or to centers with a magnetic resonance imaging—guided linear accelerator (14, 15). …”

Current and emerging radiotherapy strategies for pancreatic adenocarcinoma: stereotactic, intensity modulated and particle radiotherapy

“…However, with IMRT, the total dose to the tumor can be increased while ensuring the dose constraints of normal tissues are respected. The MD Anderson Cancer Center group had showed improved outcomes in terms of OS and locoregional relapse free survival in patients who received escalated dose (biological equivalent dose >70 Gy) compared to those who had standard radiation dose or biological equivalent does of <70 Gy (22). Only 1 out of 200 patients in the cohort developed Grade 3 acute toxicity.…”

A Novel Absorbable Radiopaque Hydrogel Spacer to Separate the Head of the Pancreas and Duodenum in Radiation Therapy for Pancreatic Cancer

“…The feasibility of dose escalation, however, has been limited owing to the sensitivity of the surrounding gastrointestinal organs, in particular, the small bowel, which is directly adjacent to the head of the pancreas (HOP). Advances in image guidance have provided the opportunity to safely deliver greater biologically effective doses (BEDs) of RT using IMRT of >70 Gy (57.25 Gy in 25 fractions; BED 70.36 Gy) compared with standard fractionation regimens (50.40 Gy in 28 fractions or 50 Gy in 25 fractions; BED of 59.47 Gy and 60 Gy, respectively) resulting in improved overall survival (17). However, candidates for dose escalation were restricted to those with >1 cm of separation between the pancreas and the closest gastrointestinal mucosa, restricting the therapy to <25% of patients in reported series of LAPC patients (17).…”