Postoperative SBRT and Severe Late Toxic Effects in Early-Stage Oropharyngeal and Oral Cavity Cancers: The STEREOPOSTOP-GORTEC 2017-03 Nonrandomized Clinical Trial.

Importance: Postoperative radiotherapy (mainly fractionated intensity-modulated radiotherapy) is indicated after surgery for early-stage oral cavity squamous cell carcinoma (OCSCC) and oropharyngeal squamous cell carcinoma (OPSCC) in the presence of high-risk margins. Postoperative brachytherapy is a treatment option, but it is not always feasible; stereotactic body radiotherapy (SBRT) may offer a noninvasive alternative. Objective: To evaluate late toxic effects and 2-year local control after postoperative SBRT to the primary tumor bed in patients with early-stage OCSCC or OPSCC and high-risk resection margins. Design, Setting, and Participants: This national, multicenter, single-arm, phase 2 nonrandomized clinical trial was conducted across 18 academic centers in France in the Groupe d'Oncologie Radiothérapie Tête et Cou (GORTEC) network. Adults with pT1 to pT2 OCSCC or OPSCC and R1 or smaller than 5 mm margins, pN0 or pN1 without extracapsular extension, no indication for neck irradiation, and not planned for adjuvant chemotherapy were enrolled between April 2018 and August 2021. Final analysis was conducted from February to May 2024. Intervention: SBRT to the surgical bed, 36 Gy in 6 fractions over 2 weeks, using volumetric modulated arctherapy (VMAT) or CyberKnife, with image guidance and quality assurance protocols. Main Outcomes and Measures: The primary outcome was the 2-year rate of grade 3 or greater late toxic effects (>90 days after treatment), per Common Terminology Criteria for Adverse Events version 4.03. The key secondary end point was 2-year local control. Quality of life (QoL) was assessed using European Organization for Research and Treatment of Cancer (EORTC) core Quality of Life Questionnaire (QLQ-C30) and EORTC Quality of Life Questionnaire Head and Neck Module (QLQ-HN35). Results: Among 90 patients (median [range] age, 64 [31-87] years; 51 [56.5%] male), at 2 years, 2 patients (2.2%) had grade 3 late toxic effects, while 13 patients (14.6%) experienced at least 1 grade 3 late toxic effect during the 2-year follow-up period, mainly soft-tissue necrosis and osteoradionecrosis, most of which were transitory. The 2-year local control rate was 92.0% (95% CI, 84.6%-96.4%). Acute grade 3 or greater toxic effects were limited to mucositis (28.9%; 95% CI, 19.8%-39.4%), mostly resolving by 3 months. Median follow-up was 25 months (range, 3-31 months). Disease-free and overall survival at 2 years were 73.3% (95% CI, 63.4%-81.7%) and 88.8% (95% CI, 80.9%-94.2%), respectively. QoL scores showed a transient decline at 1 month followed by recovery and improvement at 12 and 24 months. Conclusions and Relevance: In this phase 2 nonrandomized clinical trial, postoperative primary tumor bed SBRT for early-stage OCSCC and OPSCC with high-risk margins was associated with manageable toxic effects and high rates of local control. These findings support SBRT as a promising approach in carefully selected patients, but confirmatory randomized trials are needed. Trial Registration: ClinicalTrials.gov Identifier: NCT03401840.