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

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 studie...

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Main Authors: Tanja Sprave, Jörg Sahlmann, Andreas R. Thomsen, Diana Klein, Henning Schäfer, Raluca Stoian, Vivek Verma, Anca-Ligia Grosu, Elsa Beatriz Monroy Ordonez
Format: Article
Language:English
Published: BMC 2025-05-01
Series:BMC Cancer
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Online Access:https://doi.org/10.1186/s12885-025-14293-8
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author Tanja Sprave
Jörg Sahlmann
Andreas R. Thomsen
Diana Klein
Henning Schäfer
Raluca Stoian
Vivek Verma
Anca-Ligia Grosu
Elsa Beatriz Monroy Ordonez
author_facet Tanja Sprave
Jörg Sahlmann
Andreas R. Thomsen
Diana Klein
Henning Schäfer
Raluca Stoian
Vivek Verma
Anca-Ligia Grosu
Elsa Beatriz Monroy Ordonez
author_sort Tanja Sprave
collection DOAJ
description 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.
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spelling doaj-art-a0bc9257d4834ef1b1e99fc0b9102c712025-08-20T01:53:12ZengBMCBMC Cancer1471-24072025-05-0125111210.1186/s12885-025-14293-8Does severe mucositis impair oncological outcome in head and neck cancer patients? A pooled analysis of two prospective studies with long-term follow-upTanja Sprave0Jörg Sahlmann1Andreas R. Thomsen2Diana Klein3Henning Schäfer4Raluca Stoian5Vivek Verma6Anca-Ligia Grosu7Elsa Beatriz Monroy Ordonez8Department of Radiation Oncology, University Hospital of FreiburgInstitute for Medical Biometry and Statistics, Medical Center - University of Freiburg, Faculty of Medicine, University of FreiburgDepartment of Radiation Oncology, University Hospital of FreiburgInstitute for Cell Biology (Cancer Research), University Hospital Essen, University of Duisburg-EssenDepartment of Radiation Oncology, University Hospital of FreiburgDepartment of Radiation Oncology, University Hospital of FreiburgDepartment of Radiation Oncology, The University of Texas MD Anderson Cancer CenterDepartment of Radiation Oncology, University Hospital of FreiburgDepartment of Radiation Oncology, University Hospital of FreiburgAbstract 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.https://doi.org/10.1186/s12885-025-14293-8Head and neck cancerRadiation therapyMucositis
spellingShingle Tanja Sprave
Jörg Sahlmann
Andreas R. Thomsen
Diana Klein
Henning Schäfer
Raluca Stoian
Vivek Verma
Anca-Ligia Grosu
Elsa Beatriz Monroy Ordonez
Does severe mucositis impair oncological outcome in head and neck cancer patients? A pooled analysis of two prospective studies with long-term follow-up
BMC Cancer
Head and neck cancer
Radiation therapy
Mucositis
title Does severe mucositis impair oncological outcome in head and neck cancer patients? A pooled analysis of two prospective studies with long-term follow-up
title_full Does severe mucositis impair oncological outcome in head and neck cancer patients? A pooled analysis of two prospective studies with long-term follow-up
title_fullStr Does severe mucositis impair oncological outcome in head and neck cancer patients? A pooled analysis of two prospective studies with long-term follow-up
title_full_unstemmed Does severe mucositis impair oncological outcome in head and neck cancer patients? A pooled analysis of two prospective studies with long-term follow-up
title_short Does severe mucositis impair oncological outcome in head and neck cancer patients? A pooled analysis of two prospective studies with long-term follow-up
title_sort does severe mucositis impair oncological outcome in head and neck cancer patients a pooled analysis of two prospective studies with long term follow up
topic Head and neck cancer
Radiation therapy
Mucositis
url https://doi.org/10.1186/s12885-025-14293-8
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