CCTG HN11: SPECT-CT guided elective contralateral neck treatment (SELECT) for patients with lateralized oropharyngeal cancer—A phase III randomized controlled trial.
John R. de Almeida, Wendy R. Parulekar, Apostolos Christopoulos, Isabelle Gauthier, Rosemary Martino, Andrea McNiven, Anthony C. Nichols, Ambika Parmar, Eitan Prisman, Jolie Ringash, Martin Smoragiewicz, Rathan M. Subramaniam, John Waldron, Steven B. Chinn, James E. Bates, Kate Whelan, Wei Tu, Ali Hosni
Abstract
TPS6114 Background: Lymphatic mapping identifies neck lymph nodes at risk for cancer spread in patients with lateralized oropharyngeal (OPC) squamous cell carcinoma. We hypothesize that a lymphatic mapping guided approach to radiotherapy (RT) treatment of the contralateral neck will enable safe de-escalation of therapy with acceptable disease control with potential benefits in RT related toxicity, QOL, swallowing function and economics. Methods: HN.11 is a Canadian Cancer Trials Group international multi-centre, non-inferiority randomized phase III trial comparing a lymphatic mapping-guided approach for management of the contralateral neck (experimental) vs. bilateral neck radiation therapy (RT) (control). The primary objective is to determine if a lymphatic mapping-guided approach for management of the contralateral neck has a non-inferior disease-free survival (DFS) compared to bilateral neck RT. Secondary objectives: To compare swallowing related QOL, xerostomia, isolated contralateral neck failure, overall survival, loco-regional failure, distant metastases, RT-related toxicities, patient reported adverse events (PRO CTCAE), gastrostomy tube usage, and economics indicators (resource utilization, lost productivity, financial toxicity, EQ5D). Exploratory objectives: Swallowing function using video fluoroscopic swallow studies, head and neck-cancer specific QOL, patterns of lymphatic drainage, radiomic prediction of contralateral lymphatic drainage, correlation of tumour somatic mutations and ctDNA with disease recurrence. Statistical Design: The target sample size is 510 patients. The experimental arm will be considered non-inferior if the upper limit of the one sided 95% confidence interval (CI) of the estimated hazard ratio (HR) does not exceed 1.46 (non-inferiority margin of 6.5% for 2-year DFS). In the primary intention-to-treat (ITT) analysis, the study has 81% power, with a one-sided type I error rate of 5%, assuming 5 years of accrual, 3-years of follow up to observe 178 DFS events, and a 5% loss to follow up. If non-inferiority is demonstrated in the ITT analysis, a secondary per-protocol analysis will be performed, analyzing those patients treated as per their allocation, with 80% power to detect non-inferiority of the experimental arm assuming a conservative 10% cross-over from the experimental to the control arm (i.e. failed lymphatic mapping). Conduct to Date: Study activation September 29, 2022. First enrollment was February 10, 2023. Supported by Canadian Cancer Society, Canadian Institutes of Health Research, National Cancer Trials Network (NCTN). Clinical trial information: NCT05451004 .