255 - The HYPCON Trial 2: A Phase II Randomized Study Evaluating Hypofractionated vs. Conventional Adjuvant Concurrent Chemoradiation in Head and Neck Malignancies

12:30pm - 12:39pm ET

Room 157

Presenter(s)

Aarcha Ramadas, MBBS - AIIMS New Delhi, New Delhi, Delhi

A. Ramadas¹, A. Sharma², A. Maiti², A. Ghosh², J. Meena³, A. Dagar⁴, J. Sharma², S. Panda⁵, S. Mallick⁶, A. Thakar⁷, and S. Bhasker⁴; ¹AIl India Institute of Medical Sciences, New Delhi, Delhi, India, ²National Cancer Institute, All India Institute of Medical Sciences, New Delhi, India, ³National Cancer Institute, AIIMS,Delhi, Jhajjar, India, ⁴All India Institute of Medical Sciences, New Delhi, India, ⁵National Cancer Institute, AIIMS-Jhajjar, Jhajjar, India, ⁶National Cancer Institute, Jhajjar, Haryana, India, ⁷All India institute of Medical Sciences, New Delhi, India

Purpose/Objective(s):

The HYPCON trial conducted at our department demonstrated superior outcomes while delivering postoperative radiotherapy in Head and Neck Squamous Cell Carcinoma (HNSCC) with intermediate risk factors. In light of this background, we conducted the HYPCON II aimed to reduce two weeks of adjuvant chemoradiation(CRT) in high risk HNSCC.

Materials/Methods:

Resected HNSCC patients with positive margin and/or extra capsular extension were randomized 1:2 to receive conventional radiation (RT) 60Gy in 30 fractions over 6 weeks (Arm A) vs hypofractionated RT 50Gy in 20 fractions over 4 weeks (Arm B) with concurrent cisplatin at 40mg/m2.Sample size was estimated with equivalence trial design. Primary endpoint was 1-year locoregional control (LRC). Secondary endpoints were disease free survival (DFS), overall survival (OS), acute and late toxicity (RTOG, LENT SOMA), quality of life (QOL) (EORTC QLQ-C30& HN35) and swallowing function (MDADI). OS, DFS and LRC were analyzed using Kaplan-Meier and compared using log rank test

Results:

A total of 63 patients were included in the study and was randomized from 2023 to 2025 into arm A(n=21) and arm B(n=42), where 2 patients who received maintenance methotrexate was eliminated from Arm A. Hence 61 patients were analyzed. Majority of patients had oral cavity cancer (89.4%) where bulk of the patients had buccal mucosa primary (44.3%) followed by tongue (21.3%). Median RTT (29 days) and OTT (77days) in arm B was significantly reduced (p<0.001). Compliance was more in arm B (95.2% vs 73.7%, p=0.04). One-year LRC was 84.2% in arm A and 87.8% in arm B, p=0.761. One-year DFS was 57.9% in arm A and 80.9% in arm B which was statistically significant (p=0.037). Mean OS was 338.2 days in Arm A and 455.6 days in Arm B (p=0.095). Significant acute hematological toxicity =grade 3 was seen in 10.5% patients (p=0.04) in arm A and none in arm B. Arm B had fewer grade 3 skin reactions (4.9% vs 26.3%, p=0.01). Acute mucositis was significantly severe in arm A(p=0.04) where 57.9% patients had = grade 3 mucositis.Acute pharyngeal,laryngeal and salivary toxicity remained nonsignificant. Arm A showed higher ear toxicity (p=0.04) but after 6 months it was similar in both arms.Hypothyroidism was more in Arm A (42.1%) than Arm B, p= 0.03.Arm B consistently did better in QLQ domains like social (p=0.001) salivary (p=0.001), pain (p=0.011), cough (p=0.031), and communication (p=0.015). Cognitive function(p=0.006) and financial difficulty(p=0.008) showed a significant improvement in 3 months in arm B (p = 0.006). Social function (p = 0.001) was significantly higher at 3, 6, 12 months in arm B. Arm B showed significantly better swallowing-related QOL during first six months but long-term outcomes were similar in both arms.

Conclusion:

Hypofractionated adjuvant CRT maintained non-inferiority between two arms with regards to LRC and OS. Improved DFS, compliance, acute toxicity and early QOL outcomes supports this regimen as a practical approach to high-risk HNSCC.