Defining failure patterns and dynamics in locally advanced pharyngeal and laryngeal SCC following radiotherapy: Real-World Insights in the modern Era!

Introduction: We aimed to evaluate the prevalence and patterns of locoregional recurrence (LRR), outcome and prognostic factors in patients with locally advanced squamous cell carcinoma of the oropharynx, hypopharynx, and larynx treated with intensity-modulated or volume-modulated arc therapy definitive radiotherapy (RT) with or without systemic therapy.

Methods: Of the 213 reviewed patients treated between 2016 and 2023, 177 met the inclusion criteria. LRR was defined as recurrence in the primary tumor region or regional nodes. Failure patterns were classified based on a recurrence model, including central high-dose (A), peripheral high-dose (B), central elective(C), peripheral elective (D), and out-of-field recurrence (E).

Results: LRR was observed in 50/177 (28.2%) patients and 81 recurrent lesions. Most recurrences occurred within the first year after RT (39/177, 22.0%), predominantly in HPV-negative patients. The majority of failures were within the high-dose target volume (65% type A, 14% type C), with marginal recurrences (types B and D) occurring in 22% of cases and type E in 5% of patients. HPV-positive patients had fewer LRR (16.0% vs. 34.4% in HPV-negative patients).Multivariate analysis identified HPV status as a significant prognostic factor for OS, PFS and LRR. The occurrence of distant metastases showed a negative impact on OS, PFS and LRR. LRR showed a trend toward worse OS (p = 0.072). Chemotherapy had a significant effect on PFS and LRR.

Conclusion: LRR remains a challenge, especially in HPV-negative patients. Most failures occurred centrally, but marginal and extra-field recurrences highlight the need for improved target delineation and adaptive RT strategies. Further research is needed to optimize treatment in high-risk patients.