Does severe mucositis impair oncological outcome in head and neck cancer patients? A pooled analysis of two prospective studies with long-term follow-up

• DOI: 10.1186/s12885-025-14293-8
• Publication Date: 2025-05-21T16:53:04Z
• Authors: Tanja Sprave; Jörg Sahlmann; Andreas R. Thomsen; Diana Klein; Henning Schäfer; Raluca Stoian; Vivek Verma; Anca-Ligia Grosu; Elsa Beatriz Monr...

Abstract

Background Oral mucositis (OM) is a frequently reported radiotherapy (RT)-induced acute toxicity in head and neck (H&N) cancer patients. Severe OM may be a dose-limiting condition, which can affect oncological outcomes. Therefore, we conducted a pooled analysis of two prospective studies with long-term follow-up to evaluate the impact of grade ≥3 OM on outcomes.

Methods This pooled analysis included 253 H&N cancer patients who received primary definitive or adjuvant chemoradiotherapy at the University of Freiburg Medical Center. Kaplan–Meier analyses with log-rank tests stratified for the presence of grade 3 OM were performed for overall survival (OS), local recurrence-free survival (LRFS), and distant-metastasis free survival (DMFS). Univariate Cox proportional hazards regression was performed to identify prognostic factors for OS, LRFS, and DMFS.

Results The majority of participants had locally advanced disease: UICC stage IVA in 157 (62.1%) and IVB in 31 (12.3%). During treatment, 168 (66.4%) participants developed grade 3 OM. After a median follow-up of 73.6 months, the median OS was 64.6 months (95% CI, 47.6–83.7), and the median LRFS and DMFS had not yet been reached. Advanced disease stages had a significant impact on OS as follows: UICC IVb vs. I, HR 4.62 (95%-CI: 1.364–5.637, SE 0.6, p = 0.014) and UICC IVc vs. I, HR 9.01 (95%-CI: 1.500–54.1643, SE = 0.9, p = 0.016). Previous surgery also has a significant impact on OS with an HR 0.65 (95% CI: 0.440–0.948, SE 0.2, p = 0.026). RT duration also showed a significant impact on OS with HR 1.03 (95% CI: 1.002–1.067, SE = 0, p = 0.040). For LRFS, prior surgery had a significant impact with an HR of 0.46 (95% CI: 0.247–0.857, SE 0.3, p = 0.014). Furthermore, the cumulative RT dose had a measurable impact on LRFS with HR 1.10 (95% CI: 1.022–1.189, SE = 0.03, p = 0.012). Smoker status showed a significant effect on DMFS with an HR 3.29 (95% CI: 1.090–9.872, SE 0.561, p = 0.034). The presence of grade 3 OM has no significant impact on LRFS, OS, or DMFS.

Conclusions Severe acute grade 3 OM shows no long-term impact on oncological endpoints. Validation in larger multicenter cohorts is recommended.