Yin Tianwen, Wang Peiliang, Yu Jinming, Teng Feifei
Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Department of Radiation Oncology, Shandong Cancer Hospital & Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People's Republic of China.
Department of Radiation Oncology, Shandong Cancer Hospital & Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People's Republic of China.
Int Immunopharmacol. 2022 May;106:108623. doi: 10.1016/j.intimp.2022.108623. Epub 2022 Feb 21.
Great interest has been focused on radiotherapy (RT) with immunotherapy. We sought to investigate the significance of treatment-related lymphopenia (TRL) in esophageal squamous cell carcinoma (ESCC) patients receiving anti-PD-1 therapy and the factors associated with TRL, especially RT.
167 patients with ESCC that received anti-PD-1 therapy wereidentified, 72 of them received RT. TRL was defined as absolute lymphocyte count (ALC) < 0.50 × 10 cells/L at the start of immunotherapy and/or during immunotherapy. Depending on the presence of TRL, patients were divided into two groups.
At median follow-up of 6.5 months, the ORR of patients without TRL (n = 65; 38.9%) reached 29.4% while patients (n = 102; 61.1%) with TRL was 23.1%, DCR was 81.4% and 75.4% respectively. Patients with TRL showed shorter progression-free survival (PFS) compared with patients without TRL (median PFS: 4.8 vs. 7.0 months, P = 0.009). Multivariate analyses confirmed TRL is an independent prognostic factor for poorer PFS (HR, 1.855; P = 0.008). RT significantly increased the occurrence of TRL (OR = 0.502, P = 0.035). Patients receiving ICIs < 33.5 days after RT showed a poorer PFS compared to that ≥ 33.5 days (median PFS: 4.1 vs 7.3 months, P = 0.008). The explanation is that patients with shorter time interval had a higher incidence of TRL (P = 0.028).
TRL was an independent predictor of poor outcomes in ESCC patients receiving anti-PD-1 therapy. RT was a key factor affecting TRL. A shorter time interval of < 33.5 days between RT and anti-PD-1 therapy can lead to a poor prognosis by increasing the occurrence of TRL.
放疗（RT）联合免疫治疗已引起广泛关注。我们试图研究接受抗PD-1治疗的食管鳞状细胞癌（ESCC）患者中治疗相关淋巴细胞减少（TRL）的意义以及与TRL相关的因素，尤其是放疗。
确定了167例接受抗PD-1治疗的ESCC患者，其中72例接受了放疗。TRL定义为免疫治疗开始时和/或免疫治疗期间绝对淋巴细胞计数（ALC）<0.50×10⁹细胞/L。根据是否存在TRL，将患者分为两组。
在中位随访6.5个月时，无TRL的患者（n = 65；38.9%）的客观缓解率（ORR）达到29.4%，而有TRL的患者（n = 102；61.1%）为23.1%，疾病控制率（DCR）分别为81.4%和75.4%。与无TRL的患者相比，有TRL的患者无进展生存期（PFS）更短（中位PFS：4.8个月对7.0个月，P = 0.009）。多因素分析证实TRL是PFS较差的独立预后因素（风险比[HR]，1.855；P = 0.008）。放疗显著增加了TRL的发生率（比值比[OR] = 0.502，P = 0.035）。放疗后<33.5天接受免疫检查点抑制剂（ICIs）治疗的患者与≥33.5天接受治疗的患者相比，PFS更差（中位PFS：4.1个月对7.3个月，P = 0.008）。原因是时间间隔较短的患者TRL发生率更高（P = 0.028）。
TRL是接受抗PD-1治疗的ESCC患者预后不良的独立预测因素。放疗是影响TRL的关键因素。放疗与抗PD-1治疗之间<33.5天的较短时间间隔会通过增加TRL的发生率导致预后不良。
