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Title: A Phase 1/2 and Biomarker Study of Preoperative Short Course Chemoradiation With Proton Beam Therapy and Capecitabine Followed By Early Surgery for Resectable Pancreatic Ductal Adenocarcinoma

Purpose: To evaluate the safety, efficacy and biomarkers of short-course proton beam radiation and capecitabine, followed by pancreaticoduodenectomy in a phase 1/2 study in pancreatic ductal adenocarcinoma (PDAC) patients. Methods and Materials: Patients with radiographically resectable, biopsy-proven PDAC were treated with neoadjuvant short-course (2-week) proton-based radiation with capecitabine, followed by surgery and adjuvant gemcitabine. The primary objective was to demonstrate a rate of toxicity grade ≥3 of <20%. Exploratory biomarker studies were performed using surgical specimen tissues and peripheral blood. Results: The phase 2 dose was established at 5 daily doses of 5 GyE. Fifty patients were enrolled, of whom 35 patients were treated in the phase 2 portion. There were no grade 4 or 5 toxicities, and only 2 of 35 patients (4.1%) experienced a grade 3 toxicity event (chest wall pain grade 1, colitis grade 1). Of 48 patients eligible for analysis, 37 underwent pancreaticoduodenectomy. Thirty of 37 (81%) had positive nodes. Locoregional failure occurred in 6 of 37 resected patients (16.2%), and distant recurrence occurred in 35 of 48 patients (72.9%). With median follow-up of 38 months, the median progression-free survival for the entire group was 10 months, and overall survival was 17 months. Biomarker studies showed significant associations between worse survivalmore » outcomes and the KRAS point mutation change from glycine to aspartic acid at position 12, stromal CXCR7 expression, and circulating biomarkers CEA, CA19-9, and HGF (all, P<.05). Conclusions: This study met the primary endpoint by showing a rate of 4.1% grade 3 toxicity for neoadjuvant short-course proton-based chemoradiation. Treatment was associated with favorable local control. In exploratory analyses, KRAS{sup G12D} status and high CXCR7 expression and circulating CEA, CA19-9, and HGF levels were associated with poor survival.« less
Authors:
 [1] ; ; ; ;  [2] ;  [1] ; ;  [3] ; ;  [1] ; ; ; ; ;  [2] ;  [4] ;  [5] ; ; ;  [1] more »; « less
  1. Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States)
  2. Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States)
  3. Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States)
  4. Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States)
  5. Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, Massachusetts (United States)
Publication Date:
OSTI Identifier:
22420369
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 89; Journal Issue: 4; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ASPARTIC ACID; BIOLOGICAL MARKERS; BIOPSY; BLOOD; CARCINOMAS; CHEST; GENE MUTATIONS; GLYCINE; PAIN; PANCREAS; PATIENTS; PROTON BEAMS; RADIATION DOSES; RADIOTHERAPY; SURGERY; TOXICITY