Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Int J Radiat Oncol Biol Phys. 2023 Nov 1;117(3):750-762. doi: 10.1016/j.ijrobp.2023.04.034. Epub 2023 May 6.
Despite improvements to treatment, patients with head and neck cancer (HNC) still experience radiation-induced xerostomia due to salivary gland damage. The stem cells of the parotid gland (PG), concentrated in the gland's main ducts (stem cell rich [SCR] region), play a critical role in the PG's response to radiation. Treatment optimization requires a dose metric that properly accounts for the relative contributions of dose to this SCR region and the PG's remainder (non-SCR region) to the risk of xerostomia in normal tissue complication probability (NTCP) models for xerostomia.
Treatment and toxicity data of 1013 prospectively followed patients with HNC treated with definitive radiation therapy (RT) were used. The regeneration-weighted dose, enabling accounting for the hypothesized different effects of dose to the SCR and non-SCR region on the risk of xerostomia, was defined as D PG = D SCR region + r × D non-SCR region, where D is the regeneration-weighted dose, D is the mean dose, and r is the weighting factor. Considering the different volumes of these regions, r > 3.6 in D PG demonstrates an enhanced effect of the SCR region. The most predictive value of r was estimated in 102 patients of a previously published trial testing stem cell sparing RT. For each endpoint, D PG, dose to other organs, and clinical factors were used to develop NTCP models using multivariable logistic regression analysis in 663 patients. The models were validated in 350 patients.
Dose to the contralateral PG was associated with daytime, eating-related, and physician-rated grade ≥2 xerostomia. Consequently, r was estimated and found to be smaller than 3.6 for most PG function-related endpoints. Therefore, the contribution of D SCR region to the risk of xerostomia was larger than predicted by D PG. Other frequently selected predictors were pretreatment xerostomia and D oral cavity. The validation showed good discrimination and calibration.
Tools for clinical implementation of stem cell sparing RT were developed: regeneration-weighted dose to the parotid gland that accounted for regional differences in radiosensitivity within the gland and NTCP models that included this new dose metric and other prognostic factors.
尽管治疗方法有所改善，但头颈部癌症（HNC）患者仍会因唾液腺损伤而出现放射性口干症。腮腺（PG）的干细胞集中在腺体的主要导管（富含干细胞区[SCR]），在 PG 对辐射的反应中起着至关重要的作用。治疗优化需要一种剂量指标，该指标可以正确考虑到剂量对 SCR 区域和 PG 其余部分（非 SCR 区域）对正常组织并发症概率（NTCP）模型中口干症风险的相对贡献。
使用 1013 例接受根治性放射治疗（RT）的前瞻性随访 HNC 患者的治疗和毒性数据。再生加权剂量，使我们能够解释剂量对 SCR 和非 SCR 区域对口干症风险的假设不同影响，定义为 DP G= DSCR 区域+r× D 非 SCR 区域，其中 D 是再生加权剂量， D 是平均剂量， r 是加权因子。考虑到这些区域的不同体积， DP G 中 r > 3.6 表明 SCR 区域的影响增强。在之前发表的一项测试干细胞保护 RT 的试验中，对 102 例患者进行了 r 的最佳预测值估计。对于每个终点， DP G 、其他器官的剂量和临床因素用于使用多变量逻辑回归分析在 663 例患者中开发 NTCP 模型。在 350 例患者中进行了模型验证。
对侧 PG 的剂量与日间、与进食相关的以及医生评估的口干症≥2 级相关。因此， r 的估计值发现对于大多数与 PG 功能相关的终点都小于 3.6。因此， SCR 区域对口干症风险的贡献大于 DP G 预测的贡献。其他经常选择的预测因素是治疗前的口干症和 D 口腔。验证显示出良好的区分度和校准度。
开发了用于临床实施干细胞保护 RT 的工具：考虑到腺体内部放射敏感性的区域差异的腮腺再生加权剂量以及包括这种新剂量指标和其他预后因素的 NTCP 模型。
