Duodenal Toxicity After Fractionated Chemoradiation for Unresectable Pancreatic Cancer

Published:November 30, 2012DOI:


      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 and Materials

      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.


      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 (cm3) receiving a dose of at least 55 Gy (V55 Gy > 1 cm3), and a maximum point dose >60 Gy. Of these factors, only V55 Gy ≥1 cm3 was associated with duodenal toxicity on multivariate analysis (hazard ratio, 6.7; range, 2.0-18.8; P=.002).


      This study demonstrates that a duodenal V55 Gy >1 cm3 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.
      To read this article in full you will need to make a payment
      ASTRO Member Login
      ASTRO Members, full access to the journal is a member benefit. Use your society credentials to access all journal content and features.

      Purchase one-time access:

      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Krishnan S.
        • Rana V.
        • Janjan N.A.
        • et al.
        Induction chemotherapy selects patients with locally advanced, unresectable pancreatic cancer for optimal benefit from consolidative chemoradiation therapy.
        Cancer. 2007; 110: 47-55
        • Crane C.H.
        • Varadhachary G.R.
        • Yordy J.S.
        • et al.
        Phase II trial of cetuximab, gemcitabine, and oxaliplatin followed by chemoradiation with cetuximab for locally advanced (T4) pancreatic adenocarcinoma: correlation of Smad4(Dpc4) immunostaining with pattern of disease progression.
        J Clin Oncol. 2011; 29: 3037-3043
        • Li C.P.
        • Chao Y.
        • Chi K.H.
        • et al.
        Concurrent chemoradiotherapy treatment of locally advanced pancreatic cancer: gemcitabine versus 5-fluorouracil, a randomized controlled study.
        Int J Radiat Oncol Biol Phys. 2003; 57: 98-104
        • Desai S.P.
        • Ben-Josef E.
        • Normolle D.P.
        • et al.
        Phase I study of oxaliplatin, full-dose gemcitabine, and concurrent radiation therapy in pancreatic cancer.
        J Clin Oncol. 2007; 25: 4587-4592
        • Chauffert B.
        • Mornex F.
        • Bonnetain F.
        • et al.
        Phase III trial comparing intensive induction chemoradiotherapy (60 Gy, infusional 5-FU and intermittent cisplatin) followed by maintenance gemcitabine with gemcitabine alone for locally advanced unresectable pancreatic cancer. Definitive results of the 2000-01 FFCD/SFRO study.
        Ann Oncol. 2008; 19: 1592-1599
        • Ceha H.M.
        • van Tienhoven G.
        • Gouma D.J.
        • et al.
        Feasibility and efficacy of high dose conformal radiotherapy for patients with locally advanced pancreatic carcinoma.
        Cancer. 2000; 89: 2222-2229
        • Willett C.G.
        • Del Castillo C.F.
        • Shih H.A.
        • et al.
        Long-term results of intraoperative electron beam irradiation (IOERT) for patients with unresectable pancreatic cancer.
        Ann Surg. 2005; 241: 295-299
        • Schellenberg D.
        • Kim J.
        • Christman-Skieller C.
        • et al.
        Single-fraction stereotactic body radiation therapy and sequential gemcitabine for the treatment of locally advanced pancreatic cancer.
        Int J Radiat Oncol Biol Phys. 2011; 81: 181-188
        • Murphy J.D.
        • Christman-Skieller C.
        • Kim J.
        • et al.
        A dosimetric model of duodenal toxicity after stereotactic body radiotherapy for pancreatic cancer.
        Int J Radiat Oncol Biol Phys. 2011; 78: 1420-1426
        • Nakamura A.
        • Shibuya K.
        • Matsuo Y.
        • et al.
        Analysis of dosimetric parameters associated with acute gastrointestinal toxicity and upper gastrointestinal bleeding in locally advanced pancreatic cancer patients treated with gemcitabine-based concurrent chemoradiotherapy.
        Int J Radiat Oncol Biol Phys. 2012; 84: 369-375
        • Schisterman E.F.
        • Perkins N.J.
        • Liu A.
        • et al.
        Optimal cut-point and its corresponding Youden Index to discriminate individuals using pooled blood samples.
        Epidemiology. 2005; 16: 73-81
        • Emami B.
        • Lyman J.
        • Brown A.
        • et al.
        Tolerance of normal tissue to therapeutic irradiation.
        Int J Radiat Oncol Biol Phys. 1991; 21: 109-122
        • Kavanagh B.D.
        • Pan C.C.
        • Dawson L.A.
        • et al.
        Radiation dose-volume effects in the stomach and small bowel.
        Int J Radiat Oncol Biol Phys. 2010; 76: S101-S107
        • Huang J.
        • Robertson J.M.
        • Hong Y.
        • et al.
        Dose-volume analysis of predictors for gastrointestinal toxicity after concurrent full dose gemcitabine and radiotherapy for locally advanced pancreatic adenocarcinoma.
        Int J Radiat Oncol Biol Phys. 2012; 83: 1120-1125
        • Cosset J.M.
        • Henry-Amar M.
        • Burgers J.M.
        • et al.
        Late radiation injuries of the gastrointestinal tract in the H2 and H5 EORTC Hodgkin's disease trials: emphasis on the role of exploratory laparotomy and fractionation.
        Radiother Oncol. 1988; 13: 61-68
        • Kim H.
        • Lim do H.
        • Paik S.W.
        • et al.
        Predictive factors of gastroduodenal toxicity in cirrhotic patients after three-dimensional conformal radiotherapy for hepatocellular carcinoma.
        Radiother Oncol. 2009; 93: 302-306
        • Crane C.H.
        • Abbruzzese J.L.
        • Evans D.B.
        • et al.
        Is the therapeutic index better with gemcitabine-based chemoradiation than with 5-fluorouracil-based chemoradiation in locally advanced pancreatic cancer?.
        Int J Radiat Oncol Biol Phys. 2002; 52: 1293-1302
        • Loehrer Sr., P.J.
        • Feng Y.
        • Cardenes H.
        • et al.
        Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative Oncology Group trial.
        J Clin Oncol. 2011; 29: 4105-4112
        • Taub S.J.
        • Hurley A.
        Metallic stents for the treatment of malignant and benign strictures of the biliary system.
        Am J Gastroenterol. 1997; 92: 724-725
        • Bentzen S.M.
        • Constine L.S.
        • Deasy J.O.
        • et al.
        Quantitative analyses of normal tissue effects in the clinic (QUANTEC): an introduction to the scientific issues.
        Int J Radiat Oncol Biol Phys. 2010; 76: S3-S9

      Linked Article

      • In Regard to Kelly et al
        International Journal of Radiation Oncology • Biology • PhysicsVol. 88Issue 1
        • Preview
          To the Editor: We read with interest the study by Kelly et al (1) and compliment the authors for giving guidelines on an important dose constraint in pancreatic cancer management. However, we believe that their correlation of duodenal toxicity with radiation dose needs to be interpreted, keeping in mind the following: in their analysis, 70% of the patients underwent three-dimensional conformal radiation therapy. The radiation portals and beam energy used in these patients are not mentioned in the study.
        • Full-Text
        • PDF


      Commenting Guidelines

      To submit a comment for a journal article, please use the space above and note the following:

      • We will review submitted comments as soon as possible, striving for within two business days.
      • This forum is intended for constructive dialogue. Comments that are commercial or promotional in nature, pertain to specific medical cases, are not relevant to the article for which they have been submitted, or are otherwise inappropriate will not be posted.
      • We require that commenters identify themselves with names and affiliations.
      • Comments must be in compliance with our Terms & Conditions.
      • Comments are not peer-reviewed.