淋巴细胞在抗肿瘤免疫中发挥重要作用，然而，在化疗和放疗期间，它们也特别容易减少。本研究的目的是比较质子束放疗（PBT）和调强光子放疗（IMRT）在化疗和放疗期间引起Ⅳ度淋巴细胞减少（G4L）的发生率，并根据治疗和已建立的预后因素确定G4L风险的患者异质性。 自2012年4月至2019年3月，在德克萨斯大学MD安德森癌症中心进行了一项单中心、无盲控、Ⅱ期随机试验（NCT01512589）。患者随机分配给IMRT或PBT进行放疗，可以进行根治性或术前治疗。这个随机试验的二次分析是根据CTCAE第5.0版评估与同步放化疗期间G4L的发生情况。 在105名可供分析的患者中，有44名患者（42%）在同步放化疗开始后中位数28天经历G4L。诱导化疗（p=0.003），基线淋巴细胞绝对计数（p<0.001），放疗模式（p=0.002）和计划治疗体积（PTV）（p=0.033）与G4L显著相关。多变量分类分析将患者分为五个亚组，其中G4L的发生率分别为0%、14%、35%、70%和100%。在基线淋巴细胞绝对计数（ALC）中等风险患者和大的PTV的患者中，PBT相比于IMRT的优势最为显著（p=0.011）。 这是首个证实PBT通过限制剂量散射显著减少G4L发生率的前瞻性证据，尤其是在中等风险患者中。PBT的这种免疫保护效应，尤其是在标准辅助免疫疗法的背景下，需要在当前Ⅲ期随机试验中进一步研究。 版权所有 © 2023. Elsevier Inc.出版

Lymphocytes play an important role in anti-tumor immunity, however, they are also especially vulnerable to depletion during chemoradiotherapy (CRT). The purpose of this study was to compare the incidence of grade 4 lymphopenia (G4L) between proton beam therapy (PBT) and intensity-modulated photon radiotherapy (IMRT) in esophageal cancer patients treated with CRT in a completed randomized trial and to ascertain patient heterogeneity to G4L risk based on treatment and established prognostic factors.Between April 2012 and March 2019, a single-institutional, open-label, nonblinded, phase II randomized trial (NCT01512589) was conducted at The University of Texas MD Anderson Cancer Center. Patients were randomly assigned to IMRT or PBT, either definitively or pre-operatively. This secondary analysis of the randomized trial was G4L during concurrent CRT according to CTCAE version 5.0.Among 105 patients evaluable for analysis, 44 patients (42%) experienced G4L at a median of 28 days after the start date of concurrent CRT. Induction chemotherapy (p=0.003), baseline absolute lymphocyte count (p<0.001), radiotherapy modality (p=0.002), and planning treatment volume (PTV) (p=0.033) were found to be significantly associated with G4L. Multivariate classification analysis partitioned patients into five subgroups for whom the incidence of G4L was observed in 0%, 14%, 35%, 70%, and 100% of patients. The benefit of PBT over IMRT was most pronounced in patients with an intermediate baseline absolute lymphocyte count (ALC) and large PTV (p=0.011).This is the first prospective evidence that limiting dose scatter by PBT significantly reduced the incidence of G4L, especially in the intermediate-risk patients. The implication of this immune sparing effect of PBT, especially in the context of standard adjuvant immunotherapy, needs further examination in the current phase 3 randomized trials.Copyright © 2023. Published by Elsevier Inc.