title: Phase 2 multi-institutional trial evaluating gemcitabine and stereotactic body radiotherapy for patients with locally advanced unresectable pancreatic adenocarcinoma.
abstract: BACKGROUND
  This phase 2 multi-institutional study was designed to determine whether gemcitabine (GEM) with fractionated stereotactic body radiotherapy (SBRT) results in acceptable late grade 2 to 4 gastrointestinal toxicity when compared with a prior trial of GEM with single-fraction SBRT in patients with locally advanced pancreatic cancer (LAPC).
  
  
  METHODS
  A total of 49 patients with LAPC received up to 3 doses of GEM (1000 mg/m(2)) followed by a 1-week break and SBRT (33.0 gray [Gy] in 5 fractions). After SBRT, patients continued to receive GEM until disease progression or toxicity. Toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0] and the Radiation Therapy Oncology Group radiation morbidity scoring criteria. Patients completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) and pancreatic cancer-specific QLQ-PAN26 module before SBRT and at 4 weeks and 4 months after SBRT.
  
  
  RESULTS
  The median follow-up was 13.9 months (range, 3.9-45.2 months). The median age of the patients was 67 years and 84% had tumors of the pancreatic head. Rates of acute and late (primary endpoint) grade ≥ 2 gastritis, fistula, enteritis, or ulcer toxicities were 2% and 11%, respectively. QLQ-C30 global quality of life scores remained stable from baseline to after SBRT (67 at baseline, median change of 0 at both follow-ups; P>.05 for both). Patients reported a significant improvement in pancreatic pain (P = .001) 4 weeks after SBRT on the QLQ-PAN26 questionnaire. The median plasma carbohydrate antigen 19-9 (CA 19-9) level was reduced after SBRT (median time after SBRT, 4.2 weeks; 220 U/mL vs 62 U/mL [P<.001]). The median overall survival was 13.9 months (95% confidence interval, 10.2 months-16.7 months). Freedom from local disease progression at 1 year was 78%. Four patients (8%) underwent margin-negative and lymph node-negative surgical resections.
  
  
  CONCLUSIONS
  Fractionated SBRT with GEM results in minimal acute and late gastrointestinal toxicity. Future studies should incorporate SBRT with more aggressive multiagent chemotherapy.
authors.affiliation: Department of Radiation Oncology & Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Herman
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Chang
authors.forename: Karyn A
authors.initials: KA
authors.lastname: Goodman
authors.forename: Avani S
authors.initials: AS
authors.lastname: Dholakia
authors.forename: Siva P
authors.initials: SP
authors.lastname: Raman
authors.forename: Amy
authors.initials: A
authors.lastname: Hacker-Prietz
authors.forename: Christine A
authors.initials: CA
authors.lastname: Iacobuzio-Donahue
authors.forename: Mary E
authors.initials: ME
authors.lastname: Griffith
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Pawlik
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Pai
authors.forename: Eileen
authors.initials: E
authors.lastname: O'Reilly
authors.forename: George A
authors.initials: GA
authors.lastname: Fisher
authors.forename: Aaron T
authors.initials: AT
authors.lastname: Wild
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Rosati
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Wolfgang
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Laheru
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Columbo
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Sugar
authors.forename: Albert C
authors.initials: AC
authors.lastname: Koong
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018450:Disease Progression; D019583:Dose Fractionation, Radiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D011379:Prognosis; D011446:Prospective Studies; D011788:Quality of Life; D016634:Radiosurgery; D015996:Survival Rate; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D000093542:Gemcitabine
keywords: chemoradiation; locally advanced; pancreatic cancer; positron emission tomography; stereotactic body radiotherapy; unresectable