PURPOSE: To use a high-quality multicenter trial dataset to determine dose-volume effects for gastrointestinal (GI) toxicity following radiation therapy for prostate carcinoma.
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Influential dose-volume histogram regions were to be determined as functions of dose, anatomical location, toxicity, and clinical endpoint.
METHODS AND MATERIALS: Planning datasets for 754 participants in the TROG 03.04 RADAR trial were available, with Late Effects of Normal Tissues (LENT) Subjective, Objective, Management, and Analytic (SOMA) toxicity assessment to a median of 72 months. A rank sum method was used to define dose-volume cut-points as near-continuous functions of dose to 3 GI anatomical regions, together with a comprehensive assessment of significance. Univariate and multivariate ordinal regression was used to assess the importance of cut-points at each dose.
RESULTS: Dose ranges providing significant cut-points tended to be consistent with those showing significant univariate regression odds-ratios (representing the probability of a unitary increase in toxicity grade per percent relative volume). Ranges of significant cut-points for rectal bleeding validated previously published results. Separation of the lower GI anatomy into complete anorectum, rectum, and anal canal showed the impact of mid-low doses to the anal canal on urgency and tenesmus, completeness of evacuation and stool frequency, and mid-high doses to the anorectum on bleeding and stool frequency. Derived multivariate models emphasized the importance of the high-dose region of the anorectum and rectum for rectal bleeding and mid- to low-dose regions for diarrhea and urgency and tenesmus, and low-to-mid doses to the anal canal for stool frequency, diarrhea, evacuation, and bleeding.
CONCLUSIONS: Results confirm anatomical dependence of specific GI toxicities. They provide an atlas summarizing dose-histogram effects and derived constraints as functions of anatomical region, dose, toxicity, and endpoint for informing future radiation therapy planning.
Ebert MA, Foo K, Haworth A, Gulliford SL, Kennedy A, Joseph DJ, Denham JW. Are you the author?
Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia; School of Physics, University of Western Australia, Perth, Western Australia, Australia; Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia; Department of Physical Sciences, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia; Joint Department of Physics, Institute of Cancer Research and Royal Marsden National Health Service Foundation Trust, Sutton, Surrey, United Kingdom; Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia; School of Surgery, University of Western Australia, Perth, Western Australia, Australia; School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia.
Reference: Int J Radiat Oncol Biol Phys. 2015 Mar 1;91(3):595-603.