p16+ Oropharyngeal Cancer Radiation Optimization Trial Reducing Elective Treatment Volumes (PROTEcT)

Measured by the Xerostomia Questionnaire (XQ), which is an 8 item self-reported xerostomia specific questionnaire. Patients rate each item on an 11 point ordinal Likert scale from 0 to 10, with higher scores indicating greater dryness or discomfort due to dryness. Item scores are added and the sum is transformed linearly to a final summary score ranging between 0 and 100, with higher scores representing greater levels of xerostomia. Based on existing literature, the mean XQ score for patients treated with standard dose and volume radiotherapy is estimated to be 52 (null hypothesis). To detect a clinically meaningful reduction of 11 points in patients treated with volume and dose de-intensified radiotherapy, with a resulting mean XQ score of 41 (alternative hypothesis), with an alpha of 0.05 and 80% power using a one-sided Wilcoxon test assuming normal distribution, 28 patients are required. Accounting for 10% dropout a total sample size of 32 patients is required.

Measured by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0

Time from treatment initiation to death from any cause

Time from treatment initiation to disease progression or death from any cause

Time from treatment initiation to local, regional, and distant failure

Measured by fibre-optic endoscopic evaluation of swallowing (FEES) or modified barium swallow (MBS)

The primary study endpoint is the Xerostomia Questionnaire (XQ), an 8 item self-reported xerostomia specific questionnaire. Patients rate each item on an 11 point ordinal Likert scale from 0 to 10, with higher scores indicating greater dryness or discomfort due to dryness. Item scores are added and the sum is transformed linearly to a final summary score ranging between 0 and 100, with higher scores representing greater levels of xerostomia.

Measured by the MD Anderson Symptom Inventory - Head & Neck (MDASI-HN); a questionnaire used to assess the severity of head and neck cancer-related symptoms and their impact on six daily activities (general activity, mood, work, relations with others, walking, and enjoyment of life). Severity of symptoms are assessed on a 0-10 numerical scale, with 0 being "not present" and 10 being "as bad as you can imagine." The ratings can be averaged into several subscale scores: mean core symptom severity (13 core symptom items), mean module symptom severity (additional module symptom items if using a module), mean total symptom severity (13 core symptom items plus additional module symptom items if using a module), and mean interference (6 interference items only). The interference with daily activities is rated on a 0-10 numerical scale, 0 being "did not interfere" and 10 being "interfered completely." The mean of the interference items can be used to represent overall symptom distress.

Measured by the MD Anderson Dysphagia Inventory (MDADI), which is a 20 item self-administered questionnaire designed for evaluating the impact of dysphagia on the QOL of patients with head and neck cancer. Five responses (strongly agree, agree, no opinion, disagree, and strongly disagree) are available to each question and are scored on a scale of 1 to 5. The MDADI quantifies an individual's global (G), physical (P), emotional (E), and functional (F) perceptions of their swallowing ability. Two summary scores can be obtained: 1) global and 2) composite. The global scale is a single question, which is scored individually to assess the overall impact that swallowing abilities have on QOL. The composite MDADI score summarizes overall performance on remaining 19 items of the MDADI, as a weighted average of the P, E, and F subscales. MDADI scores are normalized to range from 20 (extremely low functioning) to 100 (high functioning).