Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
Oncologist. 2023 Aug 3;28(8):e645-e652. doi: 10.1093/oncolo/oyad109.
This study aimed to explore the relationship between irradiation of lymphocyte-related organs at risk (LOARs) and lymphopenia during definitive concurrent chemoradiotherapy (dCCRT) for esophageal squamous cell carcinoma (ESCC).
Cases of ESCC patients who received dCCRT from 2 prospective clinical trials were identified. To find its correlation with survival outcomes, grades of absolute lymphocyte counts (ALCs) nadir during radiotherapy were recorded following COX analysis. Associations of lymphocytes at nadir and dosimetric parameters including relative volumes of spleen and bone marrow receiving 0.5, 1, 2, 3, 5, 10, 20, 30, and 50Gy (V0.5, V1, V2, V3, V5, V10, V20, V30, and V50), and effective dose to circulating immune cells (EDIC) were examined by logistic risk regression analysis. The cutoffs of dosimetric parameters were determined by the receiver operating characteristic curve (ROC).
A total of 556 patients were included. The incidences of grades 0, 1, 2, 3, and 4 (G4) lymphopenia during dCCRT were 0.2%, 0.5%, 9.7%, 59.7%, and 29.8%, respectively. Their median overall survival (OS) and progression-free survival (PFS) time were 50.2 and 24.3 months, respectively; the incidence of local recurrence and distant metastasis were 36.6% and 31.8%, respectively. Patients once suffering from G4 nadir during radiotherapy had unfavorable OS (HR, 1.28; P = .044) and a higher incidence of distant metastasis (HR, 1.52; P = .013). Furthermore, patients with EDIC ≤8.3Gy plus spleen V0.5 ≤11.1% and bone marrow V10 ≤33.2% were strongly associated with lower risk of G4 nadir (OR, 0.41; P = .004), better OS (HR, 0.71; P = .011) and lower risk of distant metastasis (HR, 0.56; P = .002).
Smaller relative volumes of spleen V0.5 and bone marrow V10 plus lower EDIC were jointly prone to reduce the incidence of G4 nadir during definitive concurrent chemoradiotherapy. This modified therapeutic strategy could be a significant prognostic factor for survival outcomes in ESCC.
本研究旨在探讨在接受根治性同期放化疗（dCCRT）的食管鳞状细胞癌（ESCC）患者中，淋巴细胞相关危及器官（LOARs）的照射与淋巴细胞减少之间的关系。
本研究纳入了两项前瞻性临床试验中接受 dCCRT 的 ESCC 患者。通过 COX 分析记录放疗期间绝对淋巴细胞计数（ALC）最低值的等级，以寻找与生存结局的相关性。通过逻辑风险回归分析，检查淋巴细胞最低值和剂量学参数（包括接受 0.5、1、2、3、5、10、20、30 和 50Gy 的脾脏和骨髓的相对体积[V0.5、V1、V2、V3、V5、V10、V20、V30 和 V50]和循环免疫细胞的有效剂量[EDIC]）与生存结局的相关性。通过受试者工作特征曲线（ROC）确定剂量学参数的截断值。
共纳入 556 例患者。dCCRT 期间 0、1、2、3 和 4 级（G4）淋巴细胞减少的发生率分别为 0.2%、0.5%、9.7%、59.7%和 29.8%。中位总生存（OS）和无进展生存（PFS）时间分别为 50.2 和 24.3 个月，局部复发和远处转移的发生率分别为 36.6%和 31.8%。放疗期间曾发生 G4 级最低点的患者 OS 不良（HR，1.28；P =.044），远处转移发生率较高（HR，1.52；P =.013）。此外，EDIC≤8.3Gy 加脾 V0.5≤11.1%和骨髓 V10≤33.2%的患者与 G4 级最低点的风险较低（OR，0.41；P =.004）、更好的 OS（HR，0.71；P =.011）和远处转移风险较低（HR，0.56；P =.002）显著相关。
较小的脾脏 V0.5 和骨髓 V10 的相对体积加上较低的 EDIC 联合起来更有可能降低根治性同期放化疗期间 G4 级最低点的发生率。这种改良的治疗策略可能是 ESCC 生存结局的一个重要预后因素。
