Aims: To determine the impact of interruptions/suspensions of radiotherapy in relation to the stage and histopathological features in patients with Non-Metastatic Head and Neck Squamous Cell Cancer (NMHNSCC), undergoing chemotherapy and Intensity-Modulated Radiation Therapy (IMRT).

Materials and methods: We retrospectively analyzed patients with T3-T4 N+ NMHNSCC treated with IMRT in our department from January 2014 to December 2023, matching the following inclusion criteria: age > 18 years, availability of 18F-FDG CT/PET before and after the treatment, T3-4 N+ disease, adjuvant or exclusive Concurrent Chemoradiation Therapy (cCTRT) +/- Induction Chemotherapy (ICT). The patients were divided into two groups according to the nodal disease stage: Group A with limited (N1-N2b) and group B (N2c-N3) with extensive nodal involvement. Prescribed doses and Treatment volumes extension were determined according to international guidelines. Data concerning time of treatment, interruptions, dose prescriptions, sites of progression, and histopathological features were collected.

Results: A total of 107 eligible patients were collected. Median age was 68.6 years (range 53-78 years). Median time of follow-up 36.7 months (range 12-60 months).
Group A included 79 patients; of these, 62.02% (49) achieved a complete response, 12.66% (10) showed no response to treatment; 25.32% (20) showed loco-regional progression. Median End of Treatment Delay (EoTD) for patients experiencing recurrences was 9.05 days, being > 5 days in 85% (17) of them.
Group B included 28 patients. Of these, only 14.29% (4) achieved a complete metabolic response. 21.43% (6) showed no response to treatments. 60.71% (17) showed loco-regional progression.
Median EoTD for these patients experiencing pathologic relapses was 7.4 days, being > 5 days in 71.43% (20) of them. LC for all patients was 49.53% (53). Cumulative 1 year-PFS was 71.1%. Cumulative 3 years-PFS was 55.4%.
The PFS analysis was also performed in relation to patients’ HPV status confirming worse clinical outcomes in those with HPV-unrelated tumors.

Conclusion: This study shows the role of a correctly timed radiotherapy. It was also confirmed that patients, not achieving complete remission, experience disease progression in sites located outside the areas where higher radiation doses were delivered, but still included in the treatment field. Thus, patients with tumor progression after chemoradiation should be included in clinical trials testing immunotherapy, alone or combined with chemotherapy.