Selective Treatment Deintensification by Reducing Radiation Dose and Omitting Concurrent Chemotherapy Based on Response to Induction Chemotherapy in Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma: A Single-Arm, Phase 2 Trial (IChoice-01)
Tingting Xu, Chunying Shen, Xin Zhou, Lin Zhu, Jun Xiang, Yulong Wang, Yongxue Zhu, Xiayun He, Hongmei Ying, Yu Wang, Qinghai Ji, Chaosu Hu, Xueguan Lu
Abstract
PurposeTo demonstrate the feasibility of de-intensification regimen in the light of the response to induction chemotherapy (IC) in human papillomavirus (HPV)associated oropharyngeal squamous cell carcinoma (OPSCC).Methods and MaterialsPatients with p16+ OPSCC, T1-2/N1-3M0 (excluding T1N1M0 with single and ≤3cm lymph node) or T3-4N0-3M0 were enrolled between January 2019 and July 2021. All patients received two cycles IC with docetaxel 75mg/m2 d1 and cisplatin 75mg/m2 d1 every 3 weeks. Those with major responses (≥50% decrease in both primary and lymph nodes) to IC entered the de-intensification cohort (Cohort D), in which intensity modulated radiation therapy (IMRT) alone was given to a reduced dose of 60Gy/30fractions. For those failed to meet major responses, as concurrent chemoradiotherapy cohort (Cohort C), dose was simultaneously integrated boosted to a standard 70Gy/35fractions to non-major response sites, concurrently with cisplatin 80mg/m2 d1,22. Patient-reported swallow function was documented using MD Anderson Dysphagia Inventory (MDADI). The primary endpoint was 2-year progression-free survival (PFS) using Simon's twostage design.ResultsA total of 26/48 (54.2%) participants met the criteria of treatment deintensification while 22/48 (45.8%) patients entered Cohort C. With a median follow-up time of 29.7 months (6.9-48.0 months), two-year PFS and OS rates were 85.4% and 93.6%, respectively for all enrolled patients. In cohort D, two-year PFS and OS rates were both 100%. Grade 3/4 IC-related toxicities included leukopenia/neutropenia occurring in 41.7% and hyponatremia in 4.2% of patients. A higher incidence of grade 3/4 mucositis (61.9% vs 23.1% P=0.022) was observed in cohort C. Consistent decline in longitudinal MDADI scores were observed at month 3 after radiotherapy between cohorts and both were found to recover to baseline at month 12.ConclusionsSelective radiotherapy dose reduction and concurrent chemotherapy removal based on IC response in HPV+ OPSCC was feasible and promising. Further study of this strategy to balance the efficacy and toxicity is warranted in a prospective controlled trial.