Division of Thoracic Tumor Multidisciplinary Treatment, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Department of Oncology, Sichuan Provincial People's Hospital, Chengdu, China.
Thorac Cancer. 2023 Sep;14(27):2735-2744. doi: 10.1111/1759-7714.15057. Epub 2023 Jul 30.
The immune system may influence prognosis, and lymphopenia is a frequent side effect of concurrent chemoradiotherapy (CCRT). Radical irradiation for locally advanced esophageal cancer (LA-EC) exposes significant vascular and heart volumes. In this study, we hypothesized that lymphopenia is linked to cardiac and pericardial doses and affects patient prognosis.
We identified 190 LA-EC patients who received radical CCRT. Multivariate analysis (MVA) was performed to correlate clinical factors and dosimetric parameters with overall survival (OS). We collected lymphocyte-related variables and ratios before and during CCRT. MVA was performed to correlate hematologic toxicity with OS. The relationship between dosimetric parameters and G4 lymphopenia was determined using logistic stepwise regression. Finally, a nomogram of G4 lymphopenia was developed and validated externally.
Median follow-up time for all patients was 27.5 months. On MVA for OS, higher pericardial V (PV ) was linked to worse survival (HR: 1.013, 95% CI: 1.001-1.026, p = 0.039). The median OS stratified by PV > 55.3% and PV ≤ 55.3% was 24.0 months and 54.0 months, respectively (p = 0.004). G4 lymphopenia was shown to be linked with worse OS in the MVA of hematological toxicity with OS (HR: 2.042, 95% CI: 1.335-3.126, p = 0.001). Thirty of the 100 patients in the training set had G4 lymphopenia. Logistic stepwise regression was used to identify variables associated with G4 lymphopenia, and the final model consisted of stage-IVA (p = 0.017), platelet-to-lymphocyte ratio during CCRT (p = 0.008), Heart V50 (p = 0.046), and PV (p = 0.048). Finally, a nomogram predicting G4 lymphocytopenia were constructed and externally validated. The ROC curve showed an AUC for internal validation of 0.775 and external validation of 0.843.
Higher doses of pericardial radiation might affect LA-EC patients' prognosis by inducing G4 lymphopenia during CCRT. Further prospective studies are warranted to confirm these findings, especially in the era of immune-checkpoint inhibitor treatment.
免疫系统可能会影响预后，而淋巴细胞减少症是同步放化疗（CCRT）的常见副作用。局部晚期食管癌（LA-EC）的根治性放疗会暴露大量的血管和心脏体积。在这项研究中，我们假设淋巴细胞减少症与心脏和心包剂量有关，并影响患者的预后。
我们确定了 190 名接受根治性 CCRT 的 LA-EC 患者。采用多变量分析（MVA）将临床因素和剂量学参数与总生存期（OS）相关联。我们在 CCRT 前后收集与淋巴细胞相关的变量和比值。MVA 将血液学毒性与 OS 相关联。使用逻辑逐步回归确定剂量学参数与 G4 淋巴细胞减少症的关系。最后，开发并外部验证 G4 淋巴细胞减少症的列线图。
所有患者的中位随访时间为 27.5 个月。在 OS 的 MVA 中，较高的心包 V（PV）与较差的生存相关（HR：1.013，95%CI：1.001-1.026，p=0.039）。按 PV >55.3%和 PV ≤55.3%分层的中位 OS 分别为 24.0 个月和 54.0 个月（p=0.004）。在 MVA 中，血液学毒性与 OS 的 G4 淋巴细胞减少症与 OS 相关（HR：2.042，95%CI：1.335-3.126，p=0.001）。训练集中的 100 名患者中有 30 名出现 G4 淋巴细胞减少症。使用逻辑逐步回归确定与 G4 淋巴细胞减少症相关的变量，最终模型包括 IVA 期（p=0.017）、CCRT 期间血小板与淋巴细胞比值（p=0.008）、心脏 V50（p=0.046）和心包 V（p=0.048）。最后，构建并外部验证了预测 G4 淋巴细胞减少症的列线图。内部验证的 ROC 曲线 AUC 为 0.775，外部验证的 AUC 为 0.843。
在 CCRT 期间，较高的心包辐射剂量可能通过诱导 G4 淋巴细胞减少症来影响 LA-EC 患者的预后。需要进一步的前瞻性研究来证实这些发现，特别是在免疫检查点抑制剂治疗时代。
