食管癌放化疗期间严重淋巴细胞减少症：质子束放疗与调强放疗随机 2B 期试验的综合分析。

Severe Lymphopenia During Chemoradiation Therapy for Esophageal Cancer: Comprehensive Analysis of Randomized Phase 2B Trial of Proton Beam Therapy Versus Intensity Modulated Radiation Therapy.

机构信息

Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.

Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.

出版信息

Int J Radiat Oncol Biol Phys. 2024 Feb 1;118(2):368-377. doi: 10.1016/j.ijrobp.2023.08.058. Epub 2023 Aug 29.

DOI:10.1016/j.ijrobp.2023.08.058

PMID:37652304

Abstract

PURPOSE

Lymphocytes play an important role in antitumor immunity; however, they are also especially vulnerable to depletion during chemoradiation therapy (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 radiation therapy (IMRT) in patients with esophageal cancer treated with CRT in a completed randomized trial and to ascertain patient heterogeneity to G4L risk based on treatment and established prognostic factors.

METHODS AND MATERIALS

Between April 2012 and March 2019, a single-institution, open-label, nonblinded, phase 2 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 preoperatively. This secondary analysis of the randomized trial was G4L during concurrent CRT according to Common Terminology Criteria for Adverse Events version 5.0.

RESULTS

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 = .003), baseline absolute lymphocyte count (P < .001), radiation therapy modality (P = .002), and planning treatment volume (P = .033) were found to be significantly associated with G4L. Multivariate classification analysis partitioned patients into 5 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 and large planning treatment volume (P = .011).

CONCLUSIONS

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.

摘要

目的

淋巴细胞在抗肿瘤免疫中发挥着重要作用；然而，它们在放化疗（CRT）期间也特别容易被消耗殆尽。本研究旨在比较质子束治疗（PBT）与强度调制光子放射治疗（IMRT）在 CRT 治疗的食管癌患者中发生 4 级淋巴细胞减少症（G4L）的发生率，并根据治疗和既定的预后因素确定患者对 G4L 风险的异质性。

方法和材料

2012 年 4 月至 2019 年 3 月，德克萨斯大学 MD 安德森癌症中心进行了一项单机构、开放性、非盲、2 期随机试验（NCT01512589）。患者被随机分配至 IMRT 或 PBT，无论是确定性治疗还是术前治疗。这是对随机试验的二次分析，根据不良事件通用术语标准 5.0 评估 CRT 期间的 G4L。

结果

在 105 例可评估的患者中，有 44 例（42%）在 CRT 开始后 28 天中位数时出现 G4L。诱导化疗（P=0.003）、基线绝对淋巴细胞计数（P<0.001）、放疗方式（P=0.002）和计划治疗体积（P=0.033）与 G4L 显著相关。多变量分类分析将患者分为 5 组，每组 G4L 的发生率分别为 0%、14%、35%、70%和 100%。在基线绝对淋巴细胞计数中等和计划治疗体积较大的患者中，PBT 优于 IMRT 的获益最为显著（P=0.011）。