Patient- versus physician-reported outcomes in prostate cancer patients receiving hypofractionated radiotherapy within a randomized controlled trial.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: There is low agreement between symptoms reported by patients and physicians, with high rates of underreporting by the physician.

Adjuvant radiotherapy after radical cystectomy for patients with muscle invasive bladder cancer: a phase II trial.

BACKGROUND: 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. METHODS: 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: Pathological (p)T3 stage + presence of lymphovascular invasion on pathological examination pT4 stage <10 lymph nodes removed positive lymph nodes positive surgical margins 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. DISCUSSION: This is a prospective phase 2 trial re-assessing the feasibility of adjuvant radiotherapy in high-risk MIBC. TRIAL REGISTRATION: 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.

4 Weeks Versus 5 Weeks of Hypofractionated High-dose Radiation Therapy as Primary Therapy for Prostate Cancer: Interim Safety Analysis of a Randomized Phase 3 Trial.

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.

Intensity-modulated radiotherapy for early-stage glottic cancer.

BACKGROUND: The purpose of this study was to report on treatment outcome of intensity-modulated radiotherapy (IMRT) for early-stage (cT1-2 cN0 M0) squamous cell carcinoma of the glottis, as compared with patients treated with conventional radiotherapy. METHODS: Between November 2007 and December 2011, 40 consecutive patients were treated with IMRT with daily cone-beam CT position verification. The median prescription to the planning target volume (PTV) was 63 Gy/28 fractions and 67.5 Gy/30 fractions for T1 and T2 tumors, respectively. The historical control comprised 81 consecutive patients treated with conventional radiotherapy to total doses of 66 Gy/33 fractions (66 patients) and 70 Gy/35 fractions (15 patients) for T1 and T2 tumors, respectively. RESULTS: The median follow-up of living patients was 3.8 years (range, 1.0-5.0 years) in the IMRT group and 9.0 years, (range, 5.2-12.7 years) in the conventional group. Five-year actuarial local control was equal compared to the conventional group: 83% versus 74% (p = .64). Five-year actuarial ultimate local control was 100% in the IMRT group and 95% in the conventional group (p = .17). Five-year actuarial overall and disease-specific survival was 85% after IMRT versus 65% after conventional radiotherapy (p = .15) and 97% versus 89% (p = .31), respectively. Incidence and severity of acute dermatitis was significantly less during IMRT than in the control group (p < .001). Two patients receiving IMRT had late grade 3 hoarseness. CONCLUSION: IMRT is as efficient as conventional radiotherapy in terms of disease control and overall survival. It has the potential to reduce toxicity as compared to conventional radiotherapy. © 2015 Wiley Periodicals, Inc. Head Neck 38: E179-E184, 2016.