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Background: Smoking status at point of diagnosis is not used in defining risk groups for human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) despite its prognostic value in head and neck cancer. Methods: Retrospective analysis of consecutive patients treated with chemoradiotherapy between January 2005 and July 2017 was performed with multivariable analysis to explore the impact of smoking status at diagnosis (current/former/never) on overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS). Results: Median follow-up was 61 months. Four hundred and four patients were included. Current smokers had inferior OS versus never and former smokers [adjusted HR 2.37 (95% CI 1.26–4.45, p < 0.01) and 2.58 (95% CI 1.40–4.73, p < 0.01), respectively] and inferior PFS versus never smokers [adjusted HR 1.83 (95% CI 1.00–3.35, p = 0.04)]. Smoking status did not predict for CSS. Conclusion: Detailed smoking behavior should be considered in refining risk groups in HPV-associated OPC treated with radiotherapy and in future trial design eligibility and stratification.

Purpose To explore site- and clinician-level factors associated with protocol violations requiring real-time-review (RTR) resubmission in a multicenter clinical trial to help tailor future quality assurance (QA) protocols. Methods and Materials RAVES (Radiation Therapy–Adjuvant vs Early Salvage) (Trans-Tasman Radiation Oncology Group 08.03) is a randomized trial comparing adjuvant with early salvage radiation therapy in men with positive surgical margins or pT3 disease after prostatectomy. Quality assurance in RAVES required each clinician and site to submit a credentialing dummy run (DR) and for each patient's radiation therapy plan to undergo external RTR before treatment. Prospectively defined major violations from trial protocol required remedy and resubmission. Site and clinician factors associated with RTR resubmission were examined using hierarchical modeling. Results Data were collected from 171 consecutive patients, treated by 46 clinicians at 32 hospitals. There were 47 RTR resubmissions (27%) due to 65 major violations. The relative rate of resubmission decreased by 29% per year as the study progressed (odds ratio OR. 0.71, P =.02). The majority of resubmissions were due to contouring violations (39 of 65) and dosimetric violations (22 of 65). For each additional patient accrued, significant decreases in RTR resubmission were seen at both clinician level (OR 0.75, P =.02) and site level (OR 0.72, P =.01). The rate of resubmission due to dosimetric violations was only 1.6% after the first 5 patients. Use of IMRT was associated with lower rates of resubmission compared with 3-dimensional conformal radiation therapy (OR 0.38, P =.05). Conclusion Several low- and high-risk factors that may assist with tailoring future clinical trial QA were identified. Because the real-time resubmission rate was largely independent of the credentialing exercise, some form of RTR QA is recommended. The greatest benefit from QA was derived early in trial activation and clinician experience.

Introduction We aimed to quantify a relationship between radiotherapy dose and freedom from biochemical failure (FFBF) in low- and intermediate-risk prostate cancer. To reduce confounding we used data with a standardised end–point, mature follow-up, low competing risk of metastatic failure, conventional fractionation and separate reporting for outcomes with hormonal therapy (HT). Methods A systematic review of the literature was carried out. Studies that reported the use of radiotherapy alone in 1.8–2 Gy fractions in low- and intermediate-risk prostate cancer were included. The primary end–point was Phoenix definition 5-year FFBF. A logistic regression was used to quantify the dose–response relationship. Results Data from eight studies with 3037 patients met the inclusion criteria. The data from 810 low-risk patients and 2245 intermediate-risk patients were analysed. A strong association between radiotherapy dose and FFBF was found in low- and intermediate-risk patients managed with radiotherapy alone. In low-risk patients not treated with HT the dose required to achieve 50% biochemical tumour control (TCD50) is 52.0 Gy and the slope of the dose–response curve at TCD50 (γ50) is 2.1%/Gy. At 78 Gy this represented a FFBF of 90.3%. In intermediate-risk patients not treated with HT the TCD50 is 64.7 Gy and γ50 is 3.2%/Gy. At 78 Gy this translated into a FFBF of 84.3%. HT had a small effect for low-risk patients and an inconsistent effect for intermediate-risk men. Conclusion A strong association was found between radiation dose and biochemical outcome in both low- and intermediate-risk patients. Standardised reporting of results from future studies will make future analyses more robust.