Purpose: This is a secondary analysis examining a six-month home-based Prostate Cancer-Patient Empowerment Program (PC-PEP) on patient-reported urinary, bowel, sexual, and hormonal function in men with curative prostate cancer (PC) against standard of care. Methods: In a crossover clinical trial, 128 men scheduled for PC surgery (n = 62) or radiotherapy with/without hormones (n = 66) were randomized to PC-PEP (n = 66) or waitlist-control and received the standard of care for 6 months, and then PC-PEP to the end of the year. PC-PEP included daily emails with video instructions, aerobic and strength training, dietary guidance, stress management, and social support, with an initial PFMT nurse consultation. Over 6 months, participants in the PC-PEP received optional text alerts (up to three times daily) reminding them to follow the PFMT video program, encompassing relaxation, quick-twitch, and endurance exercises; compliance was assessed weekly. Participants completed baseline, 6, and 12-month International Prostate Symptom Score (IPSS) and Expanded Prostate Cancer Index Composite (EPIC) questionnaires. Results: At 6 months, men in the PC-PEP reported improved urinary bother (IPSS, p = 0.004), continence (EPIC, p < 0.001), and irritation/obstruction function (p = 0.008) compared to controls, with sustained urinary continence benefits at 12 months (p = 0.002). Surgery patients in the waitlist-control group had 3.5 (95% CI: 1.2, 10, p = 0.024) times and 2.3 (95% CI: 0.82, 6.7, p = 0.11) times higher odds of moderate to severe urinary problems compared to PC-PEP at 6 and 12 months, respectively. Conclusions: PC-PEP significantly improves lower urinary tract symptoms, affirming its suitability for clinical integration alongside established mental health benefits in men with curative prostate cancer.

Background: Although survival rates for newly diagnosed prostate cancer patients are very high, most of them will likely suffer significant treatment-related side effects, depression, or anxiety, affecting their quality of life. Objective: The aim of this study was to examine the effects of a 6-mo online home-based physical, mental, and social support intervention, the Prostate Cancer Patient Empowerment Program (PC-PEP), on preventing psychological distress among men undergoing curative prostate cancer treatment. Design, setting, and participants: In a crossover randomized clinical trial of 128 men aged 50-82 yr scheduled for curative prostate cancer surgery or radiotherapy (+/- hormone treatment), 66 received the 6-mo PC-PEP intervention and 62 were randomized to a waitlist-control arm and received the standard of care for 6 mo, and then PC-PEP to the end of the year. The PC-PEP intervention consisted of daily e-mails with video instructions providing education, patient activation, and empowerment on healthy living including physical and mental health, dietary recommendations, social support, physical and pelvic floor fitness, stress reduction using a biofeedback device, social connection and intimacy, and social support. Outcome measurements and statistical analysis: The primary outcome was nonspecific psychological distress (clinical cutoff >= 20) measured at baseline, and at 6 and 12 mo using the Kessler Psychological Distress Scale (K10). Results and limitations: At 6 mo, patients in the waitlist-control group had 3.59 (95% confidence interval: 1.12-11.51) times higher odds for nonspecific psychological distress and need for psychological treatment than men who received the PC-PEP intervention.

INTRODUCTION:The total mesorectal excision (TME) significantly improved rectal cancer outcomes. Radiotherapy's benefit in T3N0 rectal cancer patients managed with TME has not been clearly demonstrated. A systematic review and meta-analysis were undertaken to determine whether radiotherapy altered the risk of locoregional recurrence (LR) in T3N0 rectal cancer patients managed with a TME.MATERIALS AND METHODS:Studies indexed on PubMed or Embase were systematically searched from inception to October 18, 2020. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were observed for the literature search, study screening, and data extraction; the Newcastle Ottawa Scale evaluated bias; Grades of Recommendation, Assessment, Development, and Evaluation Working Group system evaluated certainty; and all were performed independently by at least two investigators. Studies that reported LR data specific to T3N0 rectal cancer patients managed with TME, treated with and without radiotherapy, were included. Data was pooled using a random-effects model. Meta-analyses of the relative risk of local recurrence were conducted.RESULTS:Five retrospective cohort studies involving 932 unique patients reported LR outcomes; no prospective studies met eligibility criteria. Median follow-up ranged from 38.4-78 months. Adjuvant radiotherapy was provided in 3 studies. Chemotherapy was delivered and reported in 4 studies, providing both concurrent and adjuvant chemotherapy. A non-significant LR reduction with radiotherapy alongside TME was estimated, mean relative risk (RR) 0.63 (95% Confidence Interval 0.31-1.29; I2 = 41.8%).CONCLUSIONS:A non-significant LR benefit with radiotherapy's addition was estimated. Meta-analysis of exclusively retrospective cohort studies was concerning for biased results. Adequately powered randomized trials are warranted.

Tumor biology may play an important role as an effective predictive biomarker that is complementary to functional imaging for metastatic hormone-sensitive prostate cancer.

3604 Background: Total mesorectal excision (TME) significantly improved rectal cancer outcomes. Radiotherapy (RT) is recommended for T3N0 rectal cancers, though benefit has not been demonstrated in combination with TME for this specific population. This meta-analysis could provide evidence to ameliorate toxicities from treatment. Methods: Randomized clinical trials and observational studies published until October 18, 2020 were identified via PubMed and Embase. Objective: To determine whether RT decreased the risk of local recurrence (LR) in T3N0 rectal cancer managed with TME. Study Selection and Extraction: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were observed for literature search, extraction, and screening. Studies with LR data specific to T3N0M0 rectal cancer, treated with and without RT, were included. Reviews, non-English articles, and non-TME studies were excluded. Newcastle Ottawa Scale (NOS) evaluated quality. Meta-analysis was done with a random-effects model. Main outcome: Meta-analysis of the relative risk of LR was conducted. Results: 7,246 studies were screened, 134 full-text studies assessed for eligibility, 5 studies were included in the final analysis. No randomized data reported results specific to our study population. Five retrospective cohort studies involving 932 participants reported LR outcomes. The median follow-up ranged from 38.4 months up to 71 months. Four studies took place in Asia (797 participants) and one in North America (135 participants) (Table). Quality according to NOS ranged from 7–9. The estimated average relative risk for LR at 5 years was 0.63 (95% CI 0.31–1.29; I 2 =41.8%) when RT was used. Conclusions: This meta-analysis’ supports that there is no clear benefit to LR with the addition of RT in T3N0 patients with rectal adenocarcinoma undergoing TME. As meta-analysis was limited to retrospective cohort studies, there is concern for bias. Registration Prospero number CRD42020216058 .[Table: see text]

The management of prostate cancer (PCa) is dependent on biomarkers of biological aggression. This includes an invasive biopsy to facilitate a histopathological assessment of the tumor’s grade. This review explores the technical processes of applying magnetic resonance imaging based radiomic models to the evaluation of PCa. By exploring how a deep radiomics approach further optimizes the prediction of a PCa’s grade group, it will be clear how this integration of artificial intelligence mitigates existing major technological challenges faced by a traditional radiomic model: image acquisition, small data sets, image processing, labeling/segmentation, informative features, predicting molecular features and incorporating predictive models. Other potential impacts of artificial intelligence on the personalized treatment of PCa will also be discussed. The role of deep radiomics analysis-a deep texture analysis, which extracts features from convolutional neural networks layers, will be highlighted. Existing clinical work and upcoming clinical trials will be reviewed, directing investigators to pertinent future directions in the field. For future progress to result in clinical translation, the field will likely require multi-institutional collaboration in producing prospectively populated and expertly labeled imaging libraries.

The initial management of potentially oligometastatic hormone sensitive prostate cancer has been complicated by rapid advances in the field. Clinically, subgroup analyses of two randomized control trials have suggested that a specific synchronous oligometastatic prostate cancer state may be predictive for benefit from radiation to the primary. Further exploration of metastasis-directed therapy has been supported for various prostate cancer populations among three phase II clinical trials. There are numerous caveats in applying this evidence, a dilemma being addressed by present and upcoming clinical trials. Despite existing clinical equipoise and an avenue to address this uncertainty, the temptation to combine this evidence off-trial exists. Matters have become more complex as our ability to evaluate metastatic disease and tumour biology have also matured. This paper synthesizes our understanding of prostate cancer's natural history into a model which rationalizes both the theoretical benefits and limitations of metastasis directed therapy. We postulate that a metastatic prostate cancer's total disease activity is primarily driven by the combination of its burden of disease and underlying biology, namely genomic instability, then highlight the numerous remaining questions that challenge this hypothesis. This review focuses on harmonizing the language used to describe the disease, the current efforts exploring this hypothesis, and the need for clinical trial participation to appropriately advance patient care.

Convolutional neural networks (CNNs) require large amounts of data for training, beyond what can be acquired for current radiomics models. We hypothesize that deep entropy features (DEFs) derived from existing CNNs can be applied to MRI images of prostate cancers (PCa) to reliably predict the Gleason score (GS) of PCa lesions. In this study, we analyzed 112 lesions acquired from 99 PCa patients, either pre-biopsy or pre-treatment, their associated GS, and multi-parametric MRI (mpMRI) sequences. Our approach is based on the extraction of DEF features produced in individual layers of 9 pre-trained CNN models. We first analyze DEFs from separate CNNs using the Wilcoxon test and Spearman correlation to find significant features associated with GS. In a multivariate analysis, we then use the combined DEFs of all CNNs as input to a random forest (RF) classifier for predicting the Gleason grade group of patients. Among the 9 pre-trained CNNs, the NASNet-mobile architecture offered the features most correlated to GS ($\rho =0.47$ ; p <; 0.05). From the 7,857 combined features, 11 DEFs could differentiate GS <; 8 from GS ≥8 (corrected p <; 0.05). Moreover, the RF classifier discerned GS of 6, 3+4, 4+3, 8 and ≥9 with an AUC (%) of 80.08, 85.77, 97.30, 98.20, and 86.51, respectively. Our results suggest that the DEFs can be used to differentiate GS of PCa lesions with the highest accuracy of GS ≥8 based on mpMRI. DEFs could improve diagnosis accuracy, reduce the risks of misclassification, help to better assess prognosis, and individualize patient care approaches.

Purpose: Following radical prostatectomy, prostate bed radiotherapy (PBRT) has been combined with either long-term androgen deprivation therapy (LT-ADT) or short-term ADT with pelvic lymph node radiotherapy (PLNRT) to provide an oncological benefit in randomized trials. McGill 0913 was designed to characterize the efficacy of combining PBRT, PLNRT, and LT-ADT. It is the first study to do so prospectively. Methods: In a single arm phase II trial conduced from 2010 to 2016, 46 post-prostatectomy prostate cancer patients at a high-risk for relapse (pathological Gleason 8+ or T3) were assessed for treatment with combined LT-ADT (24 months), PBRT, and PLNRT. Patients received PLNRT and PBRT (44 Gy in 22 fractions) followed by a PBRT boost (22 Gy in 11 fractions). The primary endpoint was progression-free survival (PFS). Toxicity and quality of life (QoL) were evaluated using CTCAE V3.0 and EQ-5D-3L questionnaires, respectively. Results: Among the 43 patients were treated as per protocol, median PSA was 0.30 μg/L. On surgical pathology, 51% had positive margins, 40% had Gleason 8+ disease, 42% had seminal vesicle involvement, and 19% had lymph node involvement. At a median follow-up of 5.2 years, there were no deaths or clinical progression. At 5 years, PFS was 78.0% (95% Confidence Interval 63.7–95.5%). Not including erectile dysfunction, patients experienced: 14% grade 2 endocrine toxicity while on ADT, one incident of long-term gynecomastia, 5% grade 2 acute urinary toxicity, 5% grade 2 late Urinary toxicity, and 24% long-term hypogonadism. No comparison between the average or minimum self-reported QoL at baseline, during ADT, nor after ADT demonstrated a statistically significant difference. Conclusions: Combining PBRT, PLNRT, and LT-ADT had an acceptable PFS in patients with significant post-operative risk factors for recurrence. While therapy was well-tolerated, long-term hypogonadism was a substantial risk. Further investigations are needed to determine if this combination is beneficial. Trial registration: NCT01255891.

Stereotactic body radiotherapy (SBRT) is a highly ablative local therapy which has emerged as part of the treatment paradigm for patients with oligometastatic (OM) breast cancer (defined by 5 or fewer sites). This patient group has demonstrated improved prognosis in some cases and may therefore, benefit from aggressive local treatment. The role of upfront SBRT in newly diagnosed OM breast cancer in addition to systemic therapy is not clear, yet it is being increasingly utilized within the oncology community. The Canadian medical system is an ideal platform in which to investigate SBRT into the OM breast cancer setting, as it is not routinely implemented across centers at this time, as there is potential for robust collaboration between oncologists in the small community to investigate SBRT, and there is limited financial or industry motivation for early SBRT uptake compared with other countries. It is critical therefore to define the optimal patient population and scenarios for which SBRT should be investigated, as well as offered in the interim to Canadian patients. We therefore conducted a survey of Canadian Medical Oncologists, the primary physicians and gatekeepers of patients with OM breast cancer, to characterize their beliefs, opinions, and areas of controversy in the use of SBRT for OM breast cancer.

Radiation-induced gastrointestinal (GI) toxicity is an important complication of prostate cancer (PCa) radiotherapy (RT) that radiation oncologists seek to minimize by respecting dose constraints for the rectum. It remains unclear whether dose to the rectal wall or whole rectum better predicts GI toxicity. This study used prospectively collected toxicity data from a registered phase III randomized trial to address this question. Dose-volume histogram (DVH) data was extracted from patients enrolled in PCS V, a multi-institutional phase III trial that compared conventionally fractionated (76 Gy in 38 fractions) to hypofractionated RT (68 Gy in 25 fractions) in PCa patients. Acute and late GI toxicity was assessed at 0-6 months and 6-24 months, respectively, using the Common Terminology Criteria for Adverse Events (CTCAE v.4). Rectal wall and whole volumes were collected prospectively. Dosimetric values evaluated were the whole rectum and rectal wall V50, V60, V60, V65, V70, V75, Dmax, and Dmean. Spearman’s rho (ρ) was used to correlate each DVH point of both rectum contours to acute and late GI toxicity. A Fisher’s z-transformation was then performed to test the significance of the difference between the rectal wall and whole rectum ρ’s for individual DVH points. Wilcoxon signed rank test was used to determine whether paired differences of the GI toxicity grade associated with rectal wall vs. whole rectum were significant. In total, DVH data was obtained from 155 patients, with 83 patients having been treated conventionally and 72 with hypofractionation. Spearman’s ρ correlation test revealed a strong association between the whole rectum DVH points and acute GI toxicity, namely for V60 (p=0.04), V65 (p=0.01), V70 (p=0.01) and Dmax (p=0.04). When the same analysis was conducted for late toxicity, only the V50 and Dmean points yielded a marginally significant correlation (p=0.049 and 0.042, respectively). These findings were not observed in the hypofractionated arm. There was no significant association between the rectal wall’s DVH points with either acute nor late GI toxicity in both arms. While the Fisher’s z-transformation analysis did not reveal any significant differences between the correlations of individual DVH points obtained from the rectal wall and whole rectum with acute or late GI toxicity, the distribution of Spearman’s ρ was significantly higher for the whole rectum, compared to its wall for acute toxicity (p=0.047) in the conventional arm. Our data suggests that the whole rectum DVH profile better correlates with acute GI toxicity than that of the rectal wall. Furthermore, the whole rectum’s DVH distribution rather than individual DVH points correlated more reliably with acute GI toxicity. Set-up protocols aiming to minimize rectal wall inter- and intra-fractional movement to improve the accuracy of rectal wall dosimetric values to predict toxicity are thus worthy of future study.

After radical prostatectomy (RP), pathological features of high-risk prostate cancer (PCa) and a detectable prostate-specific antigen (PSA) signify a higher risk of recurrence. Such high risk cohorts benefitted from adding long-term androgen deprivation therapy (LTADT) or pelvic nodal radiotherapy (PNRT) to prostate bed radiotherapy (PBRT) at the cost of increased toxicity in RTOG 9601 and SPPORT. McGill 0913 quantified the safety and efficacy of intensifying PBRT in high risk patients by combining LTADT and PNRT. Following RP, patients with high-risk PCa (pT3 or Gleason 8) were enrolled in this single-arm prospective phase II trial. Patients received 24 months of LTADT and radiotherapy commenced 8-12 weeks into LTADT. Image guided intensity modulated radiotherapy provided 44Gy in 22 fractions of PNRT then a 22 Gy in 11 fraction boost to complete PBRT. Primary endpoints were freedom from biochemical failure (FFBF) (PSA nadir + 0.3 μg/L) or clinical progression. Secondary endpoints included local and distant failure rates, toxicity as per Common Toxicity Criteria, and Quality of Life (QOL) as per the EORTCQL30’s visual analog score. Statistical methods employed included a Kaplan-Meier analysis for FFBP, a Wilcoxon signed rank test for ordinal data, an unpaired t-test for continuous data, and a chi-square proportion test for binary data. From August 2010 to May 2015, 46 patients were enrolled, 43 were treated as per protocol and 2 were lost to follow-up. The median PSA was 0.30 μg/L (IQR 0.20-0.47), 52% had positive margins, 40% had at least Gleason 8 disease, and 19% had lymph node involvement. At a median follow-up of 5.2 years, there was no clinical progression and FFBF was 97.1, 90.3, and 71.0% at 3, 4, and 5 years, respectively. Of the 7 patients with biochemical failure, only 2 completed 2 years of LTADT and 3 maintained castrate levels of testosterone (<0.7 nM) on LTADT, with no statistically significant differences (p = 0.24 & p = 0.23, respectively). Univariate analysis appreciated no statistical relationship between FFBP and baseline variables, including Gleason score, PSA, T stage, or N stage. Adverse effects (AEs) and severity included sexual dysfunction for all men on ADT, 14% grade 2 endocrine AEs while on ADT, 1 incident of long term gynecomastia, 5% grade 2 acute urinary AEs, 5% grade 2 late urinary AEs, and no grade 3 AEs. The average and minimum QOL reported during LTADT were statistically similar, though the minimum QOL was more heterogeneous (baseline = 8.2, σ=1.2; average = 8.1, σ=1.5; minimum = 7.6, σ = 2.0). PBRT intensified with PNRT and LTADT in patients at a high risk of relapse produced a robust FFBP with few AEs and only minor decreases in QOL. McGill 0913's limitations included its small heterogeneous population and single arm design. While intensifying PBRT with PNRT and LTADT in high risk PCa patients appeared to be both efficacious and well tolerated, ongoing randomized evidence is awaited to prove if a benefit exists.

Radiomics analysis has had remarkable progress along with advances in medical imaging, most notability in central nervous system malignancies. Radiomics refers to the extraction of a large number of quantitative features that describe the intensity, texture and geometrical characteristics attributed to the tumor radiographic data. These features have been used to build predictive models for diagnosis, prognosis, and therapeutic response. Such models are being combined with clinical, biological, genetics and proteomic features to enhance reproducibility. Broadly, the four steps necessary for radiomic analysis are: 1) image acquisition, 2) segmentation or labeling, 3) feature extraction, and 4) statistical analysis. Major methodological challenges remain prior to clinical implementation. Essential steps include: adoption of an optimized standard imaging process, establishing a common criterion for performing segmentation, fully automated extraction of radiomic features without redundancy, and robust statistical modeling validated in the prospective setting. This review walks through these steps in detail, as it pertains to high grade gliomas. The impact on precision medicine will be discussed, as well as the challenges facing clinical implementation of radiomic in the current management of glioblastoma.

Purpose: Long-term androgen deprivation therapy has been associated with decreased bone mineral density in men with prostate cancer. Some evidence suggests that there is no impact on fracture risk despite this bone mineral density loss. Our study aimed to quantify changes in bone mineral density in men with high risk prostate cancer on long-term androgen deprivation therapy and calcium and vitamin D supplementation. Materials and Methods: Bone mineral density analysis was conducted for localized high risk prostate cancer patients enrolled in the phase III randomized trial PCS-V (Prostate Cancer Study 5), comparing conventional and hypofractionated radiation therapy. Patients received 28 months of luteinizing hormone-releasing hormone agonist and calcium and vitamin D supplementation (500 mg calcium BID+400 IU vitamin D3 BID). The areal density and T-scores (spine, femoral neck and total femur) at baseline and 30 months of follow-up were extracted, and the absolute change was calculated. Clinical bone density status (normal, osteopenia, osteoporosis) was monitored. Results: The lumbar spine, femoral neck and total femoral bone mineral density were measured for 226, 231, and 173 patients, respectively. The mean percent change in bone mineral density was -2.65%, -2.76% and -4.27% for these respective sites (p <0.001 for all). The average decrease in bone mineral density across all sites was -3.2%, with no decline in bone mineral density category in most patients (83%). Eight patients (4%) became osteoporotic. Conclusions: Despite a mild decline in bone mineral density, the change in clinical bone mineral density category remained low with long-term androgen deprivation therapy. Consequently, calcium and vitamin D supplementation alone may suffice for most localized prostate cancer patients on long-term androgen deprivation therapy.

Purpose: In this prospective phase II study, we investigated whether cone beam computed tomography scan was a superior method of image-guided radiotherapy relative to 2D orthogonal kilovoltage images in the post-radical prostatectomy setting. Methods: A total of 419 treatment fractions were included in this analysis. The shifts required to align the patient for each treatment were performed using 3D matching between cone beam computed tomography scans and the corresponding computed tomography images used for planning. This was compared with the shifts obtained from 2D orthogonal kilovoltage images, matching with the corresponding digitally reconstructed radiographs. Patients did not have fiducials inserted to assist with localization. Interfractional changes in the bladder and rectal volumes were subsequently measured on the cone beam computed tomography images for each fraction and compared to the shift differences between orthogonal kilovoltage and cone beam computed tomography scans. The proportion of treatment fractions with a shift difference exceeding the planning target volume of 7 mm, between orthogonal kilovoltage and cone beam computed tomography scans, was calculated. Results: The mean vertical, lateral, and longitudinal shifts resulted from 2D match between orthogonal kilovoltage images and corresponding digitally reconstructed radiographs were 0.353 cm (interquartile range: 0.1-0.5), 0.346 cm (interquartile range: 0.1-0.5), and 0.289 cm (interquartile range: 0.1-0.4), compared to 0.388 cm (interquartile range: 0.1-0.5), 0.342 cm (interquartile range: 0.1-0.5), and 0.291 cm (interquartile range: 0.1-0.4) obtained from 3D match between cone beam computed tomography and planning computed tomography scan, respectively. Our results show a significant difference between the kilovoltage and cone beam computed tomography shifts in the anterior–posterior direction ( P = .01). The proportion of treatment fractions in which the differences in kilovoltage and cone beam computed tomography shifts between exceeded the 7 mm planning target volume margin was 6%, 2%, and 3% in the anterior–posterior, lateral, and superior–inferior directions, respectively. Conclusion: We prospectively demonstrated that the daily use of volumetric cone beam computed tomography for treatment localization in post-radical prostatectomy patients demonstrated an increased need for a shift in patient position. This suggests that in post-radical prostatectomy patients the daily cone beam computed tomography imaging improved localization of the prostate bed and may have prevented a limited number of geographic misses, compared to daily kilovoltage imaging that was not assisted with fiducials.

Background Prostate cancer (pca) is the most common non-dermatologic cancer and the 3rd leading cause of male cancer mortality in Canada. In patients with high-risk localized or recurrent pca, management typically includes the combination of long-term androgen deprivation therapy (ADT) and radiotherapy (RT). New androgen-receptor-axis targeted therapies (ARATS), which await validation, offer an option to intensify therapy. Methods In this narrative review, we report the relevant history that has supported combining ADT with RT. The literature in PubMed was searched for studies involving pca and novel ARATS (abiraterone acetate, enzalutamide, apalutamide, darolutamide) published between 1995 and 2019. Literature discussing clinical trials in which those modalities were combined was extracted and synthesized into a combined molecular and clinical discussion. Potential treatment intensification mechanisms and rationales are explored. Results Early results from three phase I/II trials demonstrated that concurrent abiraterone acetate, ADT, and RT is safe, improves the extent of chemical castration, and is associated with limited treatment failures. A single in vitro study implies synergy for radiosensitization beyond that facilitated by conventional ADT. Studies investigating the combination of other ARATS with RT are under way, including multiple phase III trials, but short-term results are not yet available.

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