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Purpose Hypofractionated radiation therapy (HFRT) for localized prostate cancer is safe and effective. The question that remains is which hypofractionation schedule to implement. We compared 2 different HFRT regimens in the present study. Methods and Materials From June 2013 to July 2016, 160 patients with prostate cancer were randomly assigned (1:1), within this single-center phase III trial, to 56 Gy (16 fractions of 3.5 Gy; arm A) or 67 Gy (25 fractions of 2.68 Gy; arm B). Randomization was performed using computer-generated permuted blocks, stratified by previous transurethral resection of the prostate and the presence of a dominant intraprostatic lesion. Treatment allocation was not masked, and the clinicians were not blinded. The primary endpoint was acute gastrointestinal (GI) toxicity, assessed using the Common Terminology Criteria for Adverse Events, version 4.0, and Radiation Therapy Oncology Group toxicity scale. An interim analysis of acute toxicity was planned at 160 patients to prove the safety of both treatment regimens. If ≥22 of 72 patients had grade ≥2 GI toxicity, the study arm would be rejected. The study is registered at ClinicalTrials.gov ( NCT01921803 ). Results In arm A, 20 patients (26%) and 1 patient (1%) developed acute grade 2 and grade 3 GI toxicity. In arm B, 16 patients (20%) reported acute grade 2 GI toxicity. In arm A, 42 (55%) and 5 (6%) patients developed acute grade 2 and grade 3 urinary toxicity. In arm B, 40 (49%) and 7 (9%) patients reported acute grade 2 and grade 3 urinary toxicity. Toxicity peaked during radiation therapy and resolved in the months after radiation therapy. Conclusions With acute grade ≥2 GI toxicity reported in 21 of 77 patients in arm A and 16 of 82 patients in arm B, both treatment arms can be considered safe.

PURPOSE: REQUITE aimed to establish a resource for multi-national validation of models and biomarkers that predict risk of late toxicity following radiotherapy. The purpose of this article is to provide summary descriptive data. METHODS: An international, prospective cohort study recruited cancer patients in 26 hospitals in eight countries between April 2014 and March 2017. Target recruitment was 5300 patients. Eligible patients had breast, prostate or lung cancer and planned potentially curable radiotherapy. Radiotherapy was prescribed according to local regimens, but centres used standardised data collection forms. Pre-treatment blood samples were collected. Patients were followed for a minimum of 12 (lung) or 24 (breast/prostate) months and summary descriptive statistics were generated. RESULTS: The study recruited 2069 breast (99% of target), 1808 prostate (86%) and 561 lung (51%) cancer patients. The centralised, accessible database includes: physician- (47,025 forms) and patient- (54,901) reported outcomes; 11,563 breast photos; 17,107 DICOMs and 12,684 DVHs. Imputed genotype data are available for 4223 patients with European ancestry (1948 breast, 1728 prostate, 547 lung). Radiation-induced lymphocyte apoptosis (RILA) assay data are available for 1319 patients. DNA (n = 4409) and PAXgene tubes (n = 3039) are stored in the centralised biobank. Example prevalences of 2-year (1-year for lung) grade ≥2 CTCAE toxicities are 13% atrophy (breast), 3% rectal bleeding (prostate) and 27% dyspnoea (lung). CONCLUSION: The comprehensive centralised database and linked biobank is a valuable resource for the radiotherapy community for validating predictive models and biomarkers. PATIENT SUMMARY: Up to half of cancer patients undergo radiation therapy and irradiation of surrounding healthy tissue is unavoidable. Damage to healthy tissue can affect short- and long-term quality-of-life. Not all patients are equally sensitive to radiation "damage" but it is not possible at the moment to identify those who are. REQUITE was established with the aim of trying to understand more about how we could predict radiation sensitivity. The purpose of this paper is to provide an overview and summary of the data and material available. In the REQUITE study 4400 breast, prostate and lung cancer patients filled out questionnaires and donated blood. A large amount of data was collected in the same way. With all these data and samples a database and biobank were created that showed it is possible to collect this kind of information in a standardised way across countries. In the future, our database and linked biobank will be a resource for research and validation of clinical predictors and models of radiation sensitivity. REQUITE will also enable a better understanding of how many people suffer with radiotherapy toxicity. ispartof: RADIOTHERAPY AND ONCOLOGY vol:138 pages:59-67 ispartof: location:Ireland status: published

The risk of developing acute radiotherapy(RT)-induced side effects may increase with hypofractionated RT. To detect treatment-related side effects, patient-reported outcomes (PROs) might be more reliable than physician-reported outcomes. Therefore, we tried to evaluate the rate of agreement between urinary and gastrointestinal (GI) side effects and the prevalence of side effects reported by patients and by physicians. Data from a randomized controlled trial (RCT) comparing two hypofractionated RT schedules were used. Urinary (nocturia, incontinence, frequency, dysuria, and urgency) and GI (obstruction, diarrhea, vomiting, nausea, bloating, hemorragia, and incontinence) symptoms measured by the EORTC QLQ-C30 and PR-25 were used for PROs. The same symptoms were scored by the physician using the Common Terminology Criteria Adverse Events v4.0. Outcomes were reported at baseline, end of treatment, month 1, and month 3. PROs and physician-reported outcomes were converted in two categories (0 = no symptoms; 1 = symptoms of any severity) and were correlated using the kappa (κ) correlation statistics. Values below 0.40 were considered low agreement. In addition, the prevalence of symptoms was calculated. Data from 160 patients were used. The mean value for Cohen’s κ was 0.31 (ranging between 0.04 and 0.55) and 0.23 (ranging between 0.04 and 0.47) for urinary and GI symptoms, respectively. Except for three symptoms at baseline, all symptoms reported by patients were higher than those reported by physicians. There is low agreement between symptoms reported by patients and physicians, with high rates of underreporting by the physician.

Neo-adjuvant chemotherapy followed by radical cystectomy with extended pelvic lymph node dissection is considered to be the treatment of choice for patients with muscle invasive bladder cancer (MIBC). Despite this aggressive treatment the outcome is poor and ultimately, 30% of the patients with ≥pT3 tumors develop a pelvic recurrence. We hypothesize that postoperative adjuvant external beam radiotherapy (EBRT) might prevent local and lymph node recurrence and improve disease free- and overall survival as loco-regional recurrence is linked to the development of distant metastasis. We plan to perform a multicentric prospective phase two study including 76 patients. Eligible patients are patients with MIBC, treated with radical cystectomy and presenting with ≥1 of the following characteristics: Patients will have a 18F–FDG PET-CT to rule out the presence of distant metastasis prior to EBRT. A median dose of 50 Gy in 25 fractions is prescribed to the pelvic lymph node regions with inclusion of the operative bladder bed in case of a positive surgical margin. Patients with suspected lymph nodes on PET- CT can still be included in the trial, but a simultaneous integrated boost to 74Gy to the positive lymph nodes will be delivered. Blood and urine samples will be collected on day-1 and last day of EBRT for evaluation of biomarkers. The primary endpoint is evaluation of acute ≥Grade 3 intestinal or grade 4 urinary toxicity, in case of a neo-bladder reconstruction, within 12 weeks after EBRT. Secondary endpoints are: assessment of QOL, late RTOG toxicity, local control, disease free survival and overall survival. Biomarkers in urine and blood will be correlated with secondary survival endpoints. This is a prospective phase 2 trial re-assessing the feasibility of adjuvant radiotherapy in high-risk MIBC. The Ethics committee of the Ghent University Hospital (EC2014/0630) approved this study on 31/07/2014. Trial registration on Clinicaltrials.gov ( NCT02397434 ) on November 19, 2014.