Gastrointestinal dose-histogram effects in the context of dose-volume-constrained prostate radiation therapy: Analysis of data from the RADAR Prostate Radiation Therapy trial - Abstract

PURPOSE: To use a high-quality multicenter trial dataset to determine dose-volume effects for gastrointestinal (GI) toxicity following radiation therapy for prostate carcinoma.

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.

Written by:
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.
doi: 10.1016/j.ijrobp.2014.11.015

PubMed Abstract
PMID: 25596108 Prostate Cancer Section