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Duodenal Toxicity After Fractionated Chemoradiation for Unresectable Pancreatic Cancer

Published:November 30, 2012DOI:https://doi.org/10.1016/j.ijrobp.2012.09.035

      Purpose

      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.

      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 (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).

      Conclusions

      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.
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      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.
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