title: Duodenal toxicity after fractionated chemoradiation for unresectable pancreatic cancer.
abstract: OBJECTIVE
  Improving local control is critical to improving survival and quality of life for patients with locally advanced unresectable pancreatic cancer (LAPC). However, previous attempts at radiation dose escalation have been limited by duodenal toxicity. In order to guide future studies, we analyzed the clinical and dosimetric factors associated with duodenal toxicity in patients undergoing fractionated chemoradiation for LAPC.
  
  
  METHODS
  Medical records and treatment plans of 106 patients with LAPC who were treated with chemoradiation between July 2005 and June 2010 at our institution were reviewed. All patients received neoadjuvant and concurrent chemotherapy. Seventy-eight patients were treated with conventional radiation to 50.4 Gy in 28 fractions; 28 patients received dose-escalated radiation therapy (range, 57.5-75.4 Gy in 28-39 fractions). Treatment-related toxicity was graded according to Common Terminology Criteria for Adverse Events, version 4.0. Univariate and multivariate analyses were performed to assess prognostic influence of clinical, pathologic, and treatment-related factors by using Kaplan-Meier and Cox regression methods.
  
  
  RESULTS
  Twenty patients had treatment-related duodenal toxicity events, such as duodenal inflammation, ulceration, and bleeding. Four patients had grade 1 events, 8 had grade 2, 6 had grade 3, 1 had grade 4, and 1 had grade 5. On univariate analysis, a toxicity grade ≥2 was associated with tumor location, low platelet count, an absolute volume (cm(3)) receiving a dose of at least 55 Gy (V(55 Gy) > 1 cm(3)), and a maximum point dose >60 Gy. Of these factors, only V(55 Gy) ≥1 cm(3) was associated with duodenal toxicity on multivariate analysis (hazard ratio, 6.7; range, 2.0-18.8; P=.002).
  
  
  CONCLUSIONS
  This study demonstrates that a duodenal V(55 Gy) >1 cm(3) is an important dosimetric predictor of grade 2 or greater duodenal toxicity and establishes it as a dosimetric constraint when treating patients with unresectable pancreatic cancer with concurrent chemoradiation.
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Kelly
authors.forename: Prajnan
authors.initials: P
authors.lastname: Das
authors.forename: Chelsea C
authors.initials: CC
authors.lastname: Pinnix
authors.forename: Sam
authors.initials: S
authors.lastname: Beddar
authors.forename: Tina
authors.initials: T
authors.lastname: Briere
authors.forename: Mary
authors.initials: M
authors.lastname: Pham
authors.forename: Sunil
authors.initials: S
authors.lastname: Krishnan
authors.forename: Marc E
authors.initials: ME
authors.lastname: Delclos
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Crane
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D059248:Chemoradiotherapy / Q000009:adverse effects; D019583:Dose Fractionation, Radiation; D004386:Duodenum / Q000528:radiation effects*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D016016:Proportional Hazards Models; D011832:Radiation Injuries / Q000473:pathology*; D011879:Radiotherapy Dosage