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

Int J Radiat Oncol Biol Phys. 2016 Mar 15;94(4):755-65. doi: 10.1016/j.ijrobp.2015.12.003. Epub 2015 Dec 11.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Breath Holding
  • Chemoradiotherapy / methods*
  • Disease-Free Survival
  • Dose Fractionation, Radiation
  • Female
  • Humans
  • Induction Chemotherapy / methods
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Pancreatic Neoplasms / diagnostic imaging
  • Pancreatic Neoplasms / mortality*
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / therapy*
  • Radiography
  • Radiotherapy Dosage
  • Radiotherapy, Image-Guided
  • Radiotherapy, Intensity-Modulated / methods*
  • Retrospective Studies
  • Treatment Outcome
  • Tumor Burden / radiation effects