Mechanisms Underlying an Enhanced Navigation-Based Intervention to Improve Timely Adjuvant Therapy: A Secondary Analysis of the NDURE Randomized Clinical Trial.

Importance: Initiation of postoperative radiation therapy (PORT) within 6 weeks of surgery is part of National Comprehensive Cancer Network guidelines for head and neck squamous cell carcinoma (HNSCC), yet more than 50% of patients experience a delay. In a randomized clinical trial of patients with locally advanced HNSCC undergoing surgery, Navigation for Disparities and Untimely Radiation Therapy (NDURE), an enhanced navigation-based intervention that targets PORT-related care steps, improved timely PORT relative to usual care (UC) navigation. Objectives: To examine the mechanisms by which NDURE improved timely PORT relative to UC navigation among patients with HNSCC. Design, Setting, and Participants: This randomized clinical trial was conducted at a single US academic medical center and enrolled adults with locally advanced HNSCC undergoing surgery and PORT. Data were collected from May 2020 to January 2024, and data were analyzed from May 2025 to January 2026. Main Outcomes and Measures: The primary end point was initiation of PORT within 6 weeks of surgery. Five PORT-related care steps were evaluated as mediators: (1) preoperative radiation oncology consultation, (2) preoperative dental evaluation, (3) timely postoperative radiation oncology evaluation (within 21 days of surgery), (4) timely computed tomography (CT) simulation (within 7 days after the radiation oncology appointment), and (5) timely radiation planning (CT simulation to PORT start within 14 days). Causal mediation analysis was performed to determine the effect of the PORT-related care steps, individually and as a group, on timely PORT. Results: Of 145 included patients, 51 (35.2%) were female and 94 (64.8%) were male; 30 (20.7%) were Black and 115 (79.3%) were White; and the median (IQR) age was 63.0 (54.0-69.0) years. A total of 67 patients were randomized to NDURE and 78 to UC. NDURE improved preoperative radiation oncology consultation (odds ratio [OR], 4.9; 95% CI, 2.3-10.3), preoperative dental evaluation and extractions (OR, 27.6; 95% CI, 3.6-213.0), timely postoperative radiation oncology evaluation (OR, 5.0; 95% CI, 2.4-10.7), and timely radiation planning (OR, 2.1; 95% CI, 1.1-4.2). Timely postoperative radiation oncology evaluation mediated 24% (95% CI, 8-65) and completion of more than half of the PORT-related care steps mediated 53% (95% CI, 28-95) of the effect of NDURE on improving timely PORT relative to UC. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, NDURE improved timely PORT relative to UC primarily by enhancing early postoperative evaluation by radiation oncology and completion of a greater number of PORT-related care steps. PORT-related care steps, including preoperative evaluation by radiation oncology, preoperative dental evaluation, timely postoperative radiation oncology evaluation, timely CT simulation, and timely radiation planning, are important intervention targets to improve timely PORT. Trial Registration: ClinicalTrials.gov Identifier: NCT04030130.