De-intensification of adjuvant therapy based on ctDNA based risk stratification in operated advanced oral squamous cell carcinoma with intermediate risk factors– A Phase III Randomised Control Trial

This Phase III randomized control trial investigates whether ctDNA-based risk stratification can guide adjuvant treatment de-intensification without compromising overall survival in patients with operated advanced oral squamous cell carcinoma (OSCC) having intermediate risk factors. Standard care involves concurrent chemoradiotherapy (CTRT), known to reduce recurrence but linked with substantial toxicities. The study addresses the need to balance treatment efficacy with toxicity, aiming to identify OSCC patients who may benefit from a reduced-intensity adjuvant approach, specifically guided by post-operative ctDNA levels.

Patients in the control arm will receive standard CTRT, while those in the experimental arm will undergo ctDNA-based stratification, receiving radiotherapy alone or CTRT based on ctDNA levels indicating minimal residual disease. Primary outcomes focus on overall survival, with secondary objectives examining disease-specific survival, quality of life, and adverse effects. The trial’s innovative approach includes ctDNA as a non-invasive prognostic biomarker, facilitating personalized treatment and potentially minimizing unnecessary toxicities associated with chemoradiation.

This trial represents a significant step toward personalized oncology by testing the viability of liquid biopsy (ctDNA) as a determinant for treatment intensity in OSCC, potentially improving patient outcomes while preserving quality of life. Through stratified randomization, the study intends to recruit 300 patients and conduct an interim analysis after enrolling 100 patients. This trial will take place in the Head and Neck Surgical Oncology department at HBCHRC, Muzaffarpur, with the goal of setting new standards for tailored adjuvant therapy in OSCC.