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.

Copyright © 2016 Elsevier Inc. All rights reserved.

Figures

Fig. 1

A representative plan of a patient treated with radiation dose escalation (biologically effective dose >70 Gy). (a) Axial isodose plots and (b) dose-volume histogram corresponding to a planned course of treatment. The patient was aligned daily by mapping soft-tissue anatomy and isodose lines between (c) a reference computed tomography scan obtained at simulation and (d) a computed tomography scan obtained on the day of treatment. Black contours are vertebral bodies; red isodose lines indicate 67.5 Gy, blue 45 Gy, and green 40 Gy. As noted here, alignment to bony landmarks would have resulted in an increased dose to the stomach wall. Abbreviations: GTV Z gross tumor volume; PTV Z planning target volume. A color version of this figure is available at www.redjournal.org.

Fig. 2

Kaplan- Meier plots. (a) overall survival, (b) recurrence-free survival, (c) local-regional recurrence-free survival, (d) time to local-regional recurrence, (e) distant recurrence-free survival, and (f) time to distant recurrence by biologically effective dose (BED).

Fig. 3

Weighted Kaplan-Meier plots. (a) Overall survival, (b) recurrence-free survival, (c) local-regional recurrence-free survival, (d) time to local-regional recurrence, (e) distant recurrence-free survival, and (f) time to distant recurrence by biologically effective dose (BED) (after adjustment).