Department of Oncology, Odense University Hospital , Odense , Denmark.
Institute of Clinical Research, University of Southern Denmark , Odense , Denmark.
Acta Oncol. 2019 Oct;58(10):1373-1377. doi: 10.1080/0284186X.2019.1643037. Epub 2019 Jul 31.
The project aimed at determining the incidence of mandibular osteoradionecrosis (ORN) after radiotherapy, possible risk factors, and mandibular dose-volume effects in a large cohort of head and neck cancer patients (HNC). The cohort consisted of 1224 HNC patients treated with 66-68 Gy in 2007-2015 predominantly with IMRT. ORN cases were defined from clinical observations at follow-up and through hospital code diagnostics after oral-maxillofacial surgery and cross-checked with the national Danish Head and Neck Cancer database. In a nested case-control study, patients with ORN cases were matched with two controls (1:2) and pre-RT dental procedures including surgery to the mandible were documented. Multivariable Cox regression analysis was applied using demographic and treatment variables including dental procedures, smoking and tumor characteristics, and combined with dosimetric data. Mean mandibular dose () was pre-selected for the multivariable model. ORN was recorded in 56 cases (4.6%) with a median time to event of 10.9 months (range 1.8-89.7) after RT, 90% occurred within 37.4 months. Median follow-up time was 22 months (0.3-95). Average was significantly higher in the ORN event cohort and significant dose-volume differences were observed for population mean DVH doses between 30 Gy and 60 Gy. In univariable analysis, smoking (HR = 1.69; CI 1.14-2.5), pre-RT surgery/tooth extraction (HR = 2.76; 1.48-5.14), and several dosimetric parameters including (HR = 1.05, 1.02-1.08) were all significantly associated with ORN. and surgery/tooth extraction remained significant predictors of ORN in multivariable analysis, HR = 1.04 (CI 1.01-1.07) and HR = 2.09 (CI 1.1-3.98), respectively, while smoking only retained its significance in an interaction analysis with pre-RT dental procedures. The onset of ORN of the mandible was early (median 10.8 months) and the incidence low (4.6%) after IMRT in HNC cancer patients. Surgery to the mandible and pre-RT tooth extraction, tobacco smoking, and treatment dose were associated with the development of ORN.
该项目旨在确定接受放疗后下颌骨放射性骨坏死（ORN）的发生率、可能的危险因素以及头颈癌（HNC）患者中下颌骨剂量-体积效应。该队列由 1224 名 HNC 患者组成，他们在 2007 年至 2015 年间接受了 66-68Gy 的治疗，主要采用调强放疗（IMRT）。ORN 病例是通过随访时的临床观察以及口腔颌面手术后医院代码诊断确定的，并与丹麦全国头颈部癌症数据库进行了交叉核对。在一项嵌套病例对照研究中，将 ORN 病例与两名对照（1:2）匹配，并记录放射治疗前的牙科手术程序，包括下颌手术。使用多变量 Cox 回归分析方法，结合人口统计学和治疗变量（包括牙科手术、吸烟和肿瘤特征）以及剂量学数据。选择平均下颌剂量（）作为多变量模型的预筛选。在放疗后 10.9 个月（范围 1.8-89.7）时记录到 56 例（4.6%）ORN，中位事件时间为 90%发生在 37.4 个月内。中位随访时间为 22 个月（0.3-95）。在 ORN 事件队列中，平均下颌剂量显著较高，人群平均剂量体积直方图（DVH）剂量在 30Gy 至 60Gy 之间存在显著的剂量-体积差异。单变量分析显示，吸烟（HR=1.69；95%CI：1.14-2.5）、放疗前手术/拔牙（HR=2.76；95%CI：1.48-5.14）以及包括（HR=1.05，1.02-1.08）等几个剂量学参数均与 ORN 显著相关。多变量分析中，吸烟和手术/拔牙仍然是 ORN 的显著预测因子，HR=1.04（95%CI：1.01-1.07）和 HR=2.09（95%CI：1.1-3.98），而吸烟仅在与放疗前牙科手术程序的交互分析中保留其意义。HNC 癌症患者接受 IMRT 后，下颌骨 ORN 的发病时间较早（中位时间 10.8 个月），发生率较低（4.6%）。下颌骨手术和放疗前拔牙、吸烟以及治疗剂量与 ORN 的发生有关。
