HYPCON trial: A phase II randomized study evaluating hypofractionated versus conventional adjuvant radiation therapy in head and neck malignancies.

143 Background: Hypofractionated RT has been established as standard of care at many cancer sites but there is limited data on use of hypofractionated RT for head and neck carcinomas (HNC). The HYPCON trial (CTRI/2023/02/049804) tested to reduce 10 fractions of PORT by delivery of hypofractionated PORT. Methods: Patients of HNC after radical surgery, with intermediate risk factors, were randomized based on site, T and N stage to either standard fractionation arm A (60Gy/30 fractions/6 weeks) or hypofractionated arm B (50Gy/20 fractions/4 weeks) in a 1:2 manner. The minimum sample size for the study was estimated based on a non-inferiority trial design as 120 considering a 10% clinical effectiveness margin and 5% attrition. Treatment allocation was done based on T stage, N stage & HNC subsite. Target delineation included tumour bed with adequate margins (CTV_P) and microscopic lymph nodal (CTV_N) basin at risk. Organ delineation included all DARS. A double arc swallowing-sparing IMRT was used in both arms. The primary endpoint was locoregional control (LRC) at 1 year. Compliance, RT time (RTT), overall treatment time (OTT), progression-free survival (PFS) and overall survival (OS) were calculated in all patients. Acute & late toxicities were recorded as per RTOG scale. Results: 135 patients were enrolled, 45 in Arm A & 90 in Arm B. Majority of patients (96.9%) had oral cavity primary. Most of patients 74.8 % had early-stage disease. Compliance to PORT was 91.1% in Arm A versus 100% in Arm B. Median RTT for Arm A was 43 days (25-73 days) and 28 days (25-43 days) for Arm B (p<0.0001). Median OTT in Arm A was 91 days (70-126 days) and 77 days (57-119 days) in Arm B (p<0.0001). Median follow-up was 12.7 (2.73-23.87) months. One year, LRC was 72.9% vs 91.6% (p=0.007); PFS was 70.6% vs 90.5% (p=0.009) and OS was 88.7% vs 94.5% (p 0.02) Arm A versus Arm B respectively. Grade 3 or higher acute toxicity was seen in 39% in Arm A and 31.1% in Arm B (p=0.374). Grade 3 or higher late toxicity events were noted in 29.2% and 32.2% in arms A and B respectively (p= 0.671). Conclusions: Hypofractionated PORT reduced RTT & OTT and was associated with improved treatment compliance, treatment outcomes (LRC, PFS, OS), and similar acute and late toxicity profile. This is the first study to demonstrate the superiority of hypofractionated compared to conventional PORT delivery for HNC. Clinical trial information: CTRI/2023/02/049804 .