放疗剂量学及急性毒性对挽救性全喉切除术后咽皮瘘的影响

文献信息

中文摘要

目的： 分析接受全喉切除术（TL）患者的特征，并评估既往放疗对咽皮瘘（PCF）发生的影响。此外，还评估了放疗相关特征、治疗相关并发症及其对PCF发生的潜在影响。
材料与方法： 回顾性收集2010年至2025年间接受TL患者的病历中的临床和手术变量。分析了PCF发生与若干放疗相关因素之间的关联，包括既往化疗、放疗与手术之间的间隔、放射剂量、照射野、放疗技术（IMRT/VMAT vs. 3D-CRT）、分割方案，以及根据EORTC/RTOG分类的早期放疗相关并发症。
结果： 共纳入194例接受TL的患者。PCF发生率为47.9%。108例（56.3%）患者曾接受既往放疗，其中66例发生PCF（61.1%）。既往放疗与PCF发生显著相关（p=0.005；OR 2.31，95% CI 1.29-4.14）。放射剂量因靶体积不同而异，原发肿瘤的中位剂量为69.3 Gy（58-72.1；IQR 4），淋巴结引流区的中位剂量为59.4 Gy（50-70.2；IQR 9.5）。原发肿瘤的放射剂量与PCF发生无显著关联（p=0.572），而淋巴结引流区的剂量则显示出显著关联（p=0.018）。根据RTOG/EORTC量表，出现大于1级急性放射性毒性的患者发生PCF的风险显著更高（p=0.012；OR 3.02，95% CI 1.26-7.25）。多变量分析确定淋巴结区域的最大剂量（p=0.016）和急性放射性毒性RTOG>1（p=0.034）是PCF的独立预测因素。按解剖亚区分解时，这种关联具体归因于黏膜毒性（p=0.045），而皮肤、腺体和吞咽困难毒性则与PCF无显著关系。
结论： 既往放疗被证实是TL后PCF发生的重要相关因素。此外，照射到周围健康组织而非肿瘤体积本身的放射剂量，以及急性放射性毒性（RTOG>1）的存在，均与PCF风险增加独立相关。尽管这些关联在调整后仍具有统计学显著性，但该研究的回顾性性质以及多变量模型中纳入的患者数量有限，需要谨慎解读。值得注意的是，这种毒性相关风险具体归因于黏膜毒性（G>1），而皮肤、腺体和吞咽困难毒性则与PCF无显著关联。

英文摘要

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.