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确定头颈部癌下颌骨放射性骨坏死风险分层的最佳辐射阈值。

Defining the optimal radiation thresholds for Stratifying jaw osteoradionecrosis risk in head and neck cancer.

作者信息

Moharrami Mohammad, Watson Erin, Huang Shao Hui, Madathil Sreenath, Kim John, McPartlin Andrew, Malik Nauman H, Singhal Sonica, Tsai Chiaojung Jillian, Waldron John, Bratman Scott, Hope Andrew, de Almeida John, Yao Christopher Mkl, Goldstein David, Quinonez Carlos, Glogauer Michael, Hosni Ali

机构信息

Faculty of Dentistry, University of Toronto, Toronto, ON, Canada; Department of Dental Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada.

Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada; Department of Otolaryngology-Head & Neck Surgery, University Health Network/University of Toronto, Toronto, ON, Canada.

出版信息

Radiother Oncol. 2025 Aug;209:110996. doi: 10.1016/j.radonc.2025.110996. Epub 2025 Jun 20.

Abstract

PURPOSE

Osteoradionecrosis (ORN) of the jaw is a serious complication following radiation therapy (RT) for head and neck cancer (HNC). This study aimed to establish optimal thresholds for dose-volume histogram (DVH) parameters to differentiate between low- and high-risk HNC groups for developing ORN while accounting for the competing risk of death.

METHODS

A retrospective cohort of HNC patients treated with curative-intent RT between 2011 and 2018 was analyzed. ORN was defined as a binary outcome, with ClinRad grades ≥ 1 considered positive. Maximally selected rank statistics were employed to determine the optimal DVH cutoff points, with risk group discrimination assessed using Gray's statistics and the cumulative incidence function (CIF). Adjusted cause-specific hazard ratios (csHR) and sub-distribution hazard ratios (sdHR) were calculated using Cox proportional hazards and Fine-Gray models for dichotomized DVH parameters, controlling for established ORN risk factors.

RESULTS

Among 2,466 patients, 183 developed ORN. A threshold for D10cc of 59.2 Gy (95 % CI: 56.1-60.6) was identified as the most discriminative parameter, producing significantly different CIF curves between risk groups. Adjusted regression analyses demonstrated that dichotomized D10cc was significantly associated with ORN, with a csHR of 2.54 (95 % CI: 1.80-3.58) and a sdHR of 2.27 (95 % CI: 1.59-3.25). Additionally, periodontal condition, primary tumor site, and dental insurance coverage were significant predictors in all multivariable models.

CONCLUSIONS

The identification of clinically relevant DVH thresholds improves risk stratification for ORN. Integrating these thresholds into pre- and post-RT treatment planning may enhance evidence-based clinical decision-making and ultimately improve patient outcomes.

摘要

目的

颌骨放射性骨坏死(ORN)是头颈部癌(HNC)放射治疗(RT)后的一种严重并发症。本研究旨在确定剂量体积直方图(DVH)参数的最佳阈值,以区分发生ORN的低风险和高风险HNC组,同时考虑死亡的竞争风险。

方法

分析了2011年至2018年接受根治性放疗的HNC患者的回顾性队列。ORN被定义为二元结局,ClinRad分级≥1视为阳性。采用最大选择秩统计量确定最佳DVH切点,使用Gray统计量和累积发病率函数(CIF)评估风险组的区分度。对于二分的DVH参数,使用Cox比例风险模型和Fine-Gray模型计算调整后的特定病因风险比(csHR)和亚分布风险比(sdHR),并控制已确定的ORN风险因素。

结果

在2466例患者中,183例发生了ORN。D10cc的阈值为59.2 Gy(95%CI:56.1-60.6)被确定为最具区分性的参数,在风险组之间产生了显著不同的CIF曲线。调整后的回归分析表明,二分的D10cc与ORN显著相关,csHR为2.54(95%CI:1.80-3.58),sdHR为2.27(95%CI:1.59-3.25)。此外,牙周状况、原发肿瘤部位和牙科保险覆盖范围在所有多变量模型中都是显著的预测因素。

结论

确定临床相关的DVH阈值可改善ORN的风险分层。将这些阈值纳入放疗前后的治疗计划中,可能会加强基于证据的临床决策,最终改善患者预后。

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