Optimal Hypofractionated Rectal Dose-Volume Constraint From The Prostate Cancer Patients of The PCS V Trial

Hypofractionated radiotherapy (HF RT) is now a standard of care management option for prostate cancer (PCa). However, existing recommendations on dose volume constraints from phase III trials have not been correlated with toxicity. There is a need to better understand how HF RT to the prostate could be planned to minimize gastrointestinal (GI) toxicity. Through a retrospective analysis of a phase III trial that implemented HF RT, we sought to elucidate accurate rectal dose-volume constraints. Dose volume histogram (DVH) data was collected for patients enrolled in PCS V, a randomized Phase III trial that compared conventional fractionation (CF; 76 Gy in 38 fractions) and HF (68 Gy in 25 fractions) RT regimens in PCa patients. PCS V’s prospective reports of GI toxicity, defined as per Common Terminology Criteria for Adverse Events (CTCAE) version 4, were classified as either acute or late; acute if they arose between zero to six months or late if six to 24 months after RT’s start. We extracted the V50, V60, V65 V70, V75, Dmax, and Dmean values for the rectal wall and the whole rectum from both CF and HF RT plans. Receiver operating characteristic (ROC) analysis was conducted to identify the optimal dose constraint thresholds that would predict toxicity. Only the ROC curves with an area under the curve (AUC) of ≥0.6 were reported. Of the 155 patients for which full dosimetric data was obtained, 24 acute and 8 late Grade 2+ GI toxicity events were prospectively reported. For CF, the threshold dose constraints for acute GI toxicity obtained with the rectal wall V50, V60, V65, V70, V75, and Dmean were 41%, 26%, 23%, 19%, 14%, and 47 Gy, respectively. Using the whole rectum, the V60, V65, V70, and Dmean thresholds were 26%, 21%, 16%, and 50 Gy respectively. For late toxicity, only the ROC analysis with Dmax yielded an AUC of over 0.6, and the threshold was 78 Gy for both the rectal wall and the whole organ. For HF regimen, the threshold dose constraints for acute GI toxicity obtained with the rectal wall and the whole organ were both a Dmean of 44 Gy. Late GI toxicity for the rectal wall V50, V60, V65, and Dmean were 38%, 18%, 13% and 44 Gy, respectively. Using the whole rectum, the V50, V60, and Dmean points were 38%, 24%, and 45 Gy, respectively. ROC analyses of PCS V’s DVH and toxicity data for CF were similar to the dose constraints reported by QUANTEC, supporting this study’s methodology. Application of the same methods to the HF RT toxicity data generated several threshold dose constraints that can guide the production of even more tolerable PCa treatments with HF. The proposed HF dose constraints for the rectal wall and whole rectum are tabulated below.Abstract 2711; Table 1Hypofractionated dose volume constraintsWallWholeV5038%38%V6018%24%V6513%Dmean44Gy44Gy Open table in a new tab