Optimum Radiation Dose for Palliation in Head and Neck SCC: A Phase III Randomized Controlled Trial (OPRAH)

Abstract

Palliative radiotherapy has been used to alleviate symptoms in locally advanced (T4b) head and neck Squamous cell carcinoma, but optimum dose is still debated. The trial has been designed to determine if high palliative radiation dose (30 Gy/ 5#/ 5 days) improves progression free survival compared to low palliative dose (20 Gy/ 5# 5 days). The secondary objective was to compare toxicity rates profile between the two radiation doses (CTCAE version 5) and compare Quality of life between the two arms with QOL - HN35 questionnaire. This is a prospective randomized phase III randomized controlled trial. We hypothesized that by increasing the dose per fraction and total dose there would be an improvement in PFS without difference in late toxicity and QOL. The present study will also perform an exploratory analysis of effect of palliative radiotherapy on immune function and its effect on survival. Considering median PFS 2.5 months in 20 Gy arm we assumed that PFS will improve by 1.25 months (total PFS 3.75 months) in 30 Gy arm. To reach the hypothesis with 90% power and alpha error of 0.05, attrition rate of 10% sample size calculated was 286. Patients with cT4b disease of larynx/ Hypopharynx/ Oropharynx/ Oral cavity not amenable to surgery, Carotid encasement > 180 degree, histologically proven squamous cell carcinoma, Age > 18 years and < 75 years ECOG PS 0-2 were eligible. Until December 2022, we completed accrual of 239 patients. Median age: 53 years (Range: 29-70 years); Gender: Male: Female = 9: 1 (214: 25). 145 patients had history of smoking, 87 had additional history of tobacco chewing. 67 patients had history of alcohol consumption, 13 patients had history of smoking, tobacco and alcoholism. All patients had stage IVA or Stage IVB disease. Primary site was oral cavity in 58%, Oropharynx in 19%, larynx in 10% and hypopharynx in 8% cases. 72.3% patients had a PS of 1, 21.7% had PS 2 at presentation. Prior to RT requirement of analgesic was: No pain medicine: 5; WHO step I:173, WHO step II: 52, WHO step III:14. All patients received conformal radiation with 6 MV linear accelerator. Target volume was GTV plus 1 cm margin to form CTV and 5 mm expansion to generate PTV. Out of 239 patients 67 patients had a disease progression. Mucositis is the commonest side effect affecting most of the patients and improve with best supportive care. High dose palliation appears to be equally well tolerated. However, the impact of such dose escalation will be established if final analysis reaches the pre-defined endpoint.