Timing of postoperative chemoradiotherapy and survival outcomes in high-risk locally advanced head and neck squamous cell carcinoma: A supplementary analysis of JCOG1008.

6015 Background: For patients with post-operative high-risk locally advanced head and neck squamous cell carcinoma (LA-HNSCC), initiation of chemoradiotherapy (CRT) within 6 weeks after surgical resection is recommended based on previous reports. However, the guideline-defined 6-week threshold for initiating post-operative radiotherapy (PORT) is derived mainly from data in patients treated with PORT alone. Therefore, its relevance in patients receiving post-operative CRT remains uncertain. Methods: This supplementary analysis used data from the JCOG1008 trial (jRCTs031180135), which compared post-operative CRT with weekly cisplatin versus 3-weekly cisplatin. Associations between the surgical-to-PORT interval (S-PORT) and locoregional relapse-free survival (LRFS), overall survival (OS), and relapse-free survival (RFS) were evaluated using restricted cubic spline analyses, Kaplan–Meier methods, and Cox proportional hazards models. Treatment package time (TPT), defined as the sum of S-PORT and radiotherapy duration, was also assessed. Results: Among 261 enrolled patients, 251 were eligible for this analysis (median age, 62 years; 16.3% female; 45.8% with oral cavity primaries). The median S-PORT and TPT were 7.0 weeks (range, 2.9–10.0) and 13.9 weeks (range, 7.6–16.9), respectively. Restricted cubic spline analyses demonstrated minimal variation in risk across the observed S-PORT range, with hazard ratios (HRs) remaining close to 1 for LRFS, OS, and RFS. Kaplan–Meier analyses using the guideline-defined 6-week cutoff showed similar 5-year LRFS between patients with S-PORT ≤6 weeks and >6 weeks (64.0% vs 64.9%; HR 0.91, 95% CI 0.60–1.37; Table), with no significant differences in OS or RFS. In multivariable Cox models adjusting for clinical covariates, S-PORT was not independently associated with outcomes. Findings for TPT closely paralleled those for S-PORT, with no significant associations observed between TPT and treatment. Conclusions: In this supplementary analysis of JCOG1008, no prognostic disadvantage was observed when PORT was initiated within the range observed in this trial (6–10 weeks after surgery) among patients receiving post-operative CRT. These findings support individualized S-PORT timing rather than rigid cutoff-based decision-making in contemporary standardized CRT. Clinical trial information: jRCTs031180135. Kaplan–Meier analyses according to guideline-defined 6-week surgical-to-postoperative radiotherapy interval (S-PORT) cutoff. S-PORT ≤ 6 weeks S-PORT > 6 weeks 5y LRFS (95% CI) 64.0% (52.1%–73.7%) 64.9% (57.3%–71.5%) HR (95% CI), p-value 1 0.91 (0.60–1.37), 0.65 5y OS (95% CI) 65.3% (53.4%–74.9%) 66.6% (59.1%–73.1%) HR (95% CI), p-value 1 0.88 (0.58–1.34), 0.54 5y RFS (95% CI) 60.0% (48.0%–70.1%) 60.2% (52.6%–67.0%) HR (95% CI), p-value 1 0.98 (0.66–1.46), 0.93