Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 510060, Guangzhou, People's Republic of China.
Department of Oncology, Renmin Hospital, Hubei University of Medicine, 442000, Shiyan, People's Republic of China.
Radiat Oncol. 2023 Jun 9;18(1):100. doi: 10.1186/s13014-023-02269-6.
To explore the hematological toxicity (HT) induced by neoadjuvant chemoradiotherapy (nCRT) compared with neoadjuvant chemotherapy (nCT) and to identify the appropriate vertebral body (VB) dosimetric parameters for predicting HT in patients with locally advanced gastric cancer (GC).
In the phase III study, 302 patients with GC from an ongoing multi-center randomized clinical trial (NCT01815853) were included. Patients from two major centers were grouped into training and external validation cohorts. The nCT group received three cycles of XELOX chemotherapy, while the nCRT received the same dose-reduced chemotherapy plus 45 Gy radiotherapy. The complete blood counts at baseline, during neoadjuvant treatment, and in the preoperative period were compared between the nCT and nCRT groups. The VB was retrospectively contoured and the dose-volume parameters were extracted in the nCRT group. Patients' clinical characteristics, VB dosimetric parameters, and HTs were statistically analyzed. Instances of HT were graded according to the Common Terminology Criteria for Adverse Events v5.0 (CTCAE v5.0). The receiver operating characteristic (ROC) curves were generated to identify the optimal cut-off points for dosimetric variables and verify the prediction efficiency of the dosimetric index in both training and external validation cohorts.
In the training cohort, 27.4% Grade 3 + HTs were noted in the nCRT group and 16.2% in the nCT group (P = 0.042). A similar result was exhibited in the validation cohort, with 35.0% Grade 3 + HTs in the nCRT group and 13.2% in the nCT group (P = 0.025). The multivariate analysis of the training cohort revealed that V was associated with Grade 3 + leukopenia (P = 0.000), Grade 3 + thrombocytopenia (P = 0.001), and Grade 3 + total HTs (P = 0.042). The Spearman correlation analysis identified a significant correlation of V with the white blood cell nadir (P = 0.0001) and platelet nadir (P = 0.0002). The ROC curve identified the optimal cut-off points for V and showed that V < 88.75% could indicate a decreased risk of Grade 3 + leukopenia, thrombocytopenia, and total HTs in the training as well as the external validation cohorts.
Compared with nCT, nCRT could increase the risk of Grade 3 + HT in patients with locally advanced GC. Dose constraints of V < 88.75% in irradiated VB could reduce the incidence of Grade 3 + HT.
本研究旨在探讨新辅助放化疗（nCRT）相较于新辅助化疗（nCT）引起血液学毒性（HT）的差异，并确定合适的椎体剂量学参数，以预测局部晚期胃癌（GC）患者的 HT。
在这项 III 期研究中，我们纳入了来自正在进行的多中心随机临床试验（NCT01815853）的 302 例 GC 患者。两个主要中心的患者被分为训练队列和外部验证队列。nCT 组接受了 3 个周期的 XELOX 化疗，而 nCRT 组则接受了相同剂量减少的化疗联合 45 Gy 放疗。比较了 nCT 和 nCRT 组患者的基线、新辅助治疗期间和术前的全血细胞计数。对 nCRT 组进行了回顾性椎体勾画，并提取了剂量-体积参数。对患者的临床特征、椎体剂量学参数和 HT 进行了统计学分析。HT 根据不良事件通用术语标准 5.0（CTCAE v5.0）进行分级。绘制受试者工作特征（ROC）曲线，以确定剂量学变量的最佳截断点，并验证剂量学指标在训练和外部验证队列中的预测效率。
在训练队列中，nCRT 组有 27.4%的患者出现 3+级 HT，而 nCT 组有 16.2%（P=0.042）。在验证队列中也观察到了类似的结果，nCRT 组有 35.0%的患者出现 3+级 HT，而 nCT 组有 13.2%（P=0.025）。训练队列的多变量分析显示，V 与 3+级白细胞减少症（P=0.000）、3+级血小板减少症（P=0.001）和 3+级总 HT 相关（P=0.042）。Spearman 相关性分析显示，V 与白细胞最低点（P=0.0001）和血小板最低点（P=0.0002）显著相关。ROC 曲线确定了 V 的最佳截断点，并表明 V < 88.75%可降低训练队列和外部验证队列中 3+级白细胞减少症、血小板减少症和总 HT 的发生风险。
与 nCT 相比，nCRT 可增加局部晚期 GC 患者发生 3+级 HT 的风险。照射 VB 中 V < 88.75%的剂量限制可降低 3+级 HT 的发生率。
