Zhao Qi, Bi Yanping, Xue Jiao, Liu Yandong, Zhu Jiaxing, Qin Songbing
Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Ann Transl Med. 2022 Jul;10(13):744. doi: 10.21037/atm-22-2669.
Immunotherapy has become the standard of treatment for recurrent metastatic esophageal cancer (EC), and the value of efficacy predictive markers represented by programmed death-ligand 1 (PD-L1) is limited. The purpose of this study is to analyze the prognostic value of peripheral blood absolute lymphocyte count (ALC) at baseline in patients with recurrent metastatic EC treated with immunotherapy, and to further investigate the relationship between the minimal ALC value (Min ALC) and radiotherapy (RT) parameters.
The main inclusion criteria were: histologically or imaging confirmed recurrent or metastatic EC; complete routine blood test data. A total of 105 patients were included in a single-center institution, 65 of whom had previously received RT. The optimal cut-off value for baseline lymphopenia was determined by the receiver operating characteristic (ROC) curve. The prognostic value of baseline phase lymphopenia for immunotherapy were determined by cox regression analysis and the associated factors affecting lymphopenia were explored by logistic regression analysis.
The cut-off value for baseline ALC predicting 1-year overall survival (OS) was 625 cells/µL. The OS was significantly lower in the lymphopenia group (ALC ≤625 cells/µL) than in the non-lymphopenia group (ALC >625 cells/µL) (median OS: 6 12 months, P=0.002). Multivariate analysis showed that pre-immunotherapy lymphopenia was an important factor influencing patient prognosis [hazard ratio (HR): 1.771, 95% confidence interval (CI): 1.051-2.985; P=0.032)] (adjusted for clinical factors including sex, age, tumor location, histology, degree of differentiation, distant metastasis, use of RT). Patients with a previous grade 4 (G4) Min ALC during RT were more likely to develop pre-immunotherapy lymphopenia following diagnosis of recurrent metastasis [odds ratio (OR): 10.809, 95% CI: 2.185-53.471; P=0.004]. Planning target volume (PTV) volume greater than 521.2 cm (OR: 19.981, 95% CI: 1.372-290.985; P=0.028) was an independent risk factor affecting the G4 Min ALC during RT.
Lymphopenia is associated with a poorer immunotherapy prognosis in patients with recurrent metastatic EC and those with previous G4 Min ALC after RT. RT-related parameters, especially irradiation volume, can significantly affect lymphocyte counts.
免疫疗法已成为复发性转移性食管癌（EC）的治疗标准，而以程序性死亡配体1（PD-L1）为代表的疗效预测标志物的价值有限。本研究旨在分析接受免疫疗法治疗的复发性转移性EC患者基线外周血绝对淋巴细胞计数（ALC）的预后价值，并进一步探讨最低ALC值（Min ALC）与放疗（RT）参数之间的关系。
主要纳入标准为：组织学或影像学确诊为复发性或转移性EC；有完整的血常规检查数据。一个单中心机构共纳入105例患者，其中65例曾接受过放疗。通过受试者工作特征（ROC）曲线确定基线淋巴细胞减少的最佳截断值。通过cox回归分析确定基线期淋巴细胞减少对免疫疗法的预后价值，并通过逻辑回归分析探索影响淋巴细胞减少的相关因素。
预测1年总生存期（OS）的基线ALC截断值为625个细胞/µL。淋巴细胞减少组（ALC≤625个细胞/µL）的OS显著低于非淋巴细胞减少组（ALC>625个细胞/µL）（中位OS：6对12个月，P=0.002）。多因素分析显示，免疫治疗前淋巴细胞减少是影响患者预后的重要因素[风险比（HR）：1.771，95%置信区间（CI）：1.051 - 2.985；P=0.032]（根据包括性别、年龄、肿瘤位置、组织学、分化程度、远处转移、放疗使用情况等临床因素进行调整）。放疗期间既往最低ALC为4级（G4）的患者在复发性转移诊断后更有可能出现免疫治疗前淋巴细胞减少[比值比（OR）：10.809，95%CI：2.185 - 53.471；P=0.004]。计划靶体积（PTV）体积大于521.2 cm（OR：19.981，95%CI：1.372 - 290.985；P=0.028）是影响放疗期间G4 Min ALC的独立危险因素。
淋巴细胞减少与复发性转移性EC患者以及放疗后既往G4 Min ALC患者较差的免疫治疗预后相关。放疗相关参数，尤其是照射体积，可显著影响淋巴细胞计数。
