European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2026
Impact of radiotherapy dosimetry and acute toxicity on pharyngocutaneous fistula after salvage total laryngectomy.
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Sánchez-Llanos Ernesto, Cerrolaza-Pascual María, Fernández-Liesa Rafael, Vicente-González Eugenio A
Аннотация
OBJECTIVE: To analyze the characteristics of patients undergoing total laryngectomy (TL) and to evaluate the influence of previous radiotherapy on the development of pharyngocutaneous fistula (PCF). Additionally, radiotherapy-related characteristics, treatment-associated complications, and their potential impact on PCF occurrence were assessed.
MATERIALS AND METHODS: Clinical and surgical variables were retrospectively collected from the medical records of patients who underwent TL between 2010 and 2025. The association between PCF development and several radiotherapy-related factors was analyzed, including prior chemotherapy, interval between radiotherapy and surgery, radiation dose, irradiated fields, radiotherapy technique (IMRT/VMAT vs. 3D-CRT), fractionation schedule, and early radiation-related complications according to the EORTC/RTOG classification.
RESULTS: A total of 194 patients who underwent TL were included. The incidence of PCF was 47.9%. Previous radiotherapy had been administered in 108 patients (56.3%), among whom 66 developed PCF (61.1%). Prior radiotherapy was significantly associated with PCF development (p = 0.005; OR 2.31, 95% CI 1.29-4.14). Radiation dose differed according to the target volume, with a median dose of 69.3 Gy (58-72.1; IQR 4) delivered to the primary tumor and 59.4 Gy (50-70.2; IQR 9.5) delivered to nodal fields. Radiation dose to the primary tumor was not significantly associated with PCF development (p = 0.572), whereas dose delivered to nodal fields showed a significant association (p = 0.018). Patients presenting acute radiation toxicity greater than grade 1 according to the RTOG/EORTC scale had a significantly higher risk of developing PCF (p = 0.012; OR 3.02, 95% CI 1.26-7.25). Multivariate analysis identified maximum dose to nodal areas (p = 0.016) and acute radiation toxicity RTOG > 1 (p = 0.034) as independent predictors of PCF. When disaggregated by anatomical subsite, this association was specifically attributable to mucosal toxicity (p = 0.045), while skin, glandular, and dysphagia toxicity showed no significant relationship with PCF.
CONCLUSIONS: Previous radiotherapy was confirmed as a significant associated factor of PCF development after TL. In addition, radiation dose delivered to surrounding healthy tissues, rather than to the tumor volume itself, and the presence of acute radiation toxicity (RTOG >1) were independently associated with increased PCF risk. Although these associations remained statistically significant after adjustment, the retrospective nature of the study and the limited number of patients included in the multivariable model warrant cautious interpretation. Notably, this toxicity-related risk was specifically attributable to mucosal toxicity (G>1), whereas skin, glandular, and dysphagia toxicity showed no significant association with PCF.
MATERIALS AND METHODS: Clinical and surgical variables were retrospectively collected from the medical records of patients who underwent TL between 2010 and 2025. The association between PCF development and several radiotherapy-related factors was analyzed, including prior chemotherapy, interval between radiotherapy and surgery, radiation dose, irradiated fields, radiotherapy technique (IMRT/VMAT vs. 3D-CRT), fractionation schedule, and early radiation-related complications according to the EORTC/RTOG classification.
RESULTS: A total of 194 patients who underwent TL were included. The incidence of PCF was 47.9%. Previous radiotherapy had been administered in 108 patients (56.3%), among whom 66 developed PCF (61.1%). Prior radiotherapy was significantly associated with PCF development (p = 0.005; OR 2.31, 95% CI 1.29-4.14). Radiation dose differed according to the target volume, with a median dose of 69.3 Gy (58-72.1; IQR 4) delivered to the primary tumor and 59.4 Gy (50-70.2; IQR 9.5) delivered to nodal fields. Radiation dose to the primary tumor was not significantly associated with PCF development (p = 0.572), whereas dose delivered to nodal fields showed a significant association (p = 0.018). Patients presenting acute radiation toxicity greater than grade 1 according to the RTOG/EORTC scale had a significantly higher risk of developing PCF (p = 0.012; OR 3.02, 95% CI 1.26-7.25). Multivariate analysis identified maximum dose to nodal areas (p = 0.016) and acute radiation toxicity RTOG > 1 (p = 0.034) as independent predictors of PCF. When disaggregated by anatomical subsite, this association was specifically attributable to mucosal toxicity (p = 0.045), while skin, glandular, and dysphagia toxicity showed no significant relationship with PCF.
CONCLUSIONS: Previous radiotherapy was confirmed as a significant associated factor of PCF development after TL. In addition, radiation dose delivered to surrounding healthy tissues, rather than to the tumor volume itself, and the presence of acute radiation toxicity (RTOG >1) were independently associated with increased PCF risk. Although these associations remained statistically significant after adjustment, the retrospective nature of the study and the limited number of patients included in the multivariable model warrant cautious interpretation. Notably, this toxicity-related risk was specifically attributable to mucosal toxicity (G>1), whereas skin, glandular, and dysphagia toxicity showed no significant association with PCF.