The effect of time from surgery to commencing adjuvant radiotherapy for patients with head and neck squamous cell carcinoma

Introduction: Studies reported inferior outcomes when radiotherapy starts >6-8 weeks post-surgery for head and neck squamous cell carcinoma (HNSCC) but are limited due to time variable dichotomization. We assessed the relationship between survival and the time between surgery and radiotherapy as a continuous variable, hypothesising there would be no change in patients' survival at 6-8 weeks post-surgery.

Methods/materials: Inclusion criteria: patients with HNSCC who underwent surgery and adjuvant (chemo)radiotherapy, Jan 2014-Dec 2020. A sub-cohort included patients with oral cavity squamous cell carcinoma (OCSCC) treated at the same institution, Jan 2016-Dec 2020. The primary endpoint was overall survival (OS); a multivariable Cox model was fitted. For the OCSCC sub-cohort, the endpoint of interest was progression-free survival (PFS); a multivariable competing risk regression model was fitted.

Results: 386 patients with HNSCC were included (main cohort). The median time between surgery and radiotherapy was 44 days (IQR: 14 days). Plotting time intervals vs log(hazard) did not demonstrate a threshold time where risk of death increases. The time interval between surgery and radiotherapy was not associated with OS (HR 1.00; 95 % CI 0.99-1.02; p = 0.4). In the sub-cohort of 208 patients with OCSCC, the time interval between surgery and radiotherapy was not associated with increased risk of cancer vs competing events (HR 1.01; 95 % CI 0.99-1.03; p = 0.5).

Conclusion: Increasing time interval between surgery and radiotherapy was not associated with inferior survival outcomes. We suggest patients are considered for radiotherapy >6-8 weeks post-surgery and that no threshold is considered for patient selection.