Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, Ohio.
Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, Ohio.
Int J Radiat Oncol Biol Phys. 2018 Mar 1;100(3):748-755. doi: 10.1016/j.ijrobp.2017.11.025. Epub 2017 Nov 23.
To test the hypothesis that increasing radiation therapy (RT) dose to the thoracic vertebral bodies (TVBs) contributes to the development of hematologic toxicities (HTs) in patients with lung cancer.
Cases of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) treated with definitive chemoradiation with concurrent platinum-based doublet chemotherapy at our institution from 2007 to 2016 were identified. Mean TVB dose and the volume of TVBs receiving at least 5 to 60 Gy (V-V) were retrospectively recorded. Logistic regression was used to test associations between grade ≥3 HT (HT3+) and dosimetric/clinical parameters. Normal tissue complication probability was evaluated using the Lyman-Kutcher-Burman (LKB) model for HT3+, and receiver operating characteristics analysis was used to determine dosimetric cut-points.
We identified 201 patients, the majority having NSCLC (n=162, 81%) and stage III to IV disease (n=179, 89%). All patients received either cisplatin/etoposide (n=107, 53%) or carboplatin/paclitaxel (n=94, 47%). Median RT dose was 60 Gy (range, 60-70 Gy). The rate of HT3+ was 49% (n=99). Increasing mean TVB dose (per Gy) was associated with higher odds of developing HT3+ (odds ratio 1.041, 95% confidence interval 1.004-1.080, P=.032), as were increasing TVB V to V. These dosimetric correlates to HT3+ persisted on multivariate analysis. Constrained optimization of the LKB model for HT3+ yielded the parameters: n=1, m=1.79, and TD=21.4 Gy. Optimal cut-points identified were V=65%, V=60%, V=50%, and mean dose=23.5 Gy. Patients with values above these cut-points had an approximately 2-fold increased risk of HT3+.
We found that mean TVB dose and low-dose parameters (V-V) were associated with HT3+ in chemoradiation for lung cancer. Per the LKB model, bone marrow behaves like a parallel organ (n=1), implying that mean TVB dose is a useful predictor for toxicity. These data suggest that efforts to spare dose to the TVBs may reduce rates of severe HT.
检验增加胸椎体（TVB）放射治疗（RT）剂量会导致肺癌患者出现血液学毒性（HT）这一假设。
我们在本机构回顾性地识别了 2007 年至 2016 年间接受根治性放化疗并同时接受含铂双联化疗的非小细胞肺癌（NSCLC）和小细胞肺癌（SCLC）病例。记录平均 TVB 剂量和接受至少 5 至 60Gy（V-V）的 TVB 体积。使用逻辑回归测试 HT3+与剂量学/临床参数之间的关联。使用 Lyman-Kutcher-Burman（LKB）模型评估 HT3+的正常组织并发症概率，并使用受试者工作特征分析确定剂量学切点。
我们确定了 201 名患者，其中大多数为 NSCLC（n=162，81%）和 III 至 IV 期疾病（n=179，89%）。所有患者均接受顺铂/依托泊苷（n=107，53%）或卡铂/紫杉醇（n=94，47%）治疗。中位 RT 剂量为 60Gy（范围为 60-70Gy）。HT3+的发生率为 49%（n=99）。TVB 平均剂量每增加 1Gy（per Gy），发生 HT3+的几率就会增加（比值比 1.041，95%置信区间 1.004-1.080，P=.032），TVB V-V 也会增加。这些与 HT3+相关的剂量学指标在多变量分析中仍然存在。对 HT3+的 LKB 模型进行约束优化，得到参数：n=1，m=1.79，TD=21.4Gy。确定的最佳切点为 V=65%，V=60%，V=50%和平均剂量=23.5Gy。值高于这些切点的患者，发生 HT3+的风险约增加两倍。
我们发现，胸椎体平均剂量和低剂量参数（V-V）与肺癌放化疗中的 HT3+相关。根据 LKB 模型，骨髓的行为类似于一个平行器官（n=1），这意味着胸椎体平均剂量是毒性的一个有用预测因子。这些数据表明，减少胸椎体剂量可能会降低严重 HT 的发生率。
