Prostate external beam radiotherapy combined with high-dose-rate brachytherapy: dose-volume parameters from deformably-registered plans correlate with late gastrointestinal complications.

Derivation of dose-volume correlated with toxicity for multi-modal treatments can be difficult due to the perceived need for voxel-by-voxel dose accumulation. With data available for a single-institution cohort with long follow-up, an investigation was undertaken into rectal dose-volume effects for gastrointestinal toxicities after deformably-registering each phase of a combined external beam radiotherapy (EBRT)/high-dose-rate (HDR) brachytherapy prostate treatment.

One hundred and eighteen patients received EBRT in 23 fractions of 2 Gy and HDR (TG43 algorithm) in 3 fractions of 6.5 Gy. Results for the Late Effects of Normal Tissues - Subjective, Objective, Management and Analytic toxicity assessments were available with a median follow-up of 72 months. The HDR CT was deformably-registered to the EBRT CT. Doses were corrected for dose fractionation. Rectum dose-volume histogram (DVH) parameters were calculated in two ways. (1) Distribution-adding: parameters were calculated after the EBRT dose distribution was 3D-summed with the registered HDR dose distribution. (2) Parameter-adding: the EBRT DVH parameters were added to HDR DVH parameters. Logistic regressions and Mann-Whitney U-tests were used to correlate parameters with late peak toxicity (dichotomised at grade 1 or 2).

The 48-80, 40-63 and 49-55 Gy dose regions from distribution-adding were significantly correlated with rectal bleeding, urgency/tenesmus and stool frequency respectively. Additionally, urgency/tenesmus and anorectal pain were associated with the 25-26 Gy and 44-48 Gy dose regions from distribution-adding respectively. Parameter-adding also indicated the low-mid dose region was significantly correlated with stool frequency and proctitis.

This study confirms significant dose-histogram effects for gastrointestinal toxicities after including deformable registration to combine phases of EBRT/HDR prostate cancer treatment. The findings from distribution-adding were in most cases consistent with those from parameter-adding. The mid-high dose range and near maximum doses were important for rectal bleeding. The distribution-adding mid-high dose range was also important for stool frequency and urgency/tenesmus. We encourage additional studies in a variety of institutions using a variety of dose accumulation methods with appropriate inter-fraction motion management.

NCT NCT00193856 . Retrospectively registered 12 September 2005.

Radiation oncology (London, England). 2016 Oct 31*** epublish ***

Calyn R Moulton, Michael J House, Victoria Lye, Colin I Tang, Michele Krawiec, David J Joseph, James W Denham, Martin A Ebert

School of Physics (M013), University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009, Australia. ., School of Physics (M013), University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009, Australia., Radiation Oncology, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, WA, 6009, Australia., School of Medicine and Population Health, University of Newcastle, University Drive, Callaghan, NSW, 2308, Australia.

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