Off-Protocol Radiotherapy in Prospective Systemic Therapy Trials for Metastatic Non–Small Cell Lung Cancer

IF 3.9 3区医学 Q2 ONCOLOGY

Clinical lung cancer Pub Date : 2026-07-01 Epub Date: 2026-05-29 DOI:10.1016/j.cllc.2026.05.009

Kara M. Ruicci, George J. Li, Andrew Warner, Andrew Youssef, Ambica Parmar, Adam Mutsaers, David A. Palma, Alexander V. Louie

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Abstract

Purpose

Radiotherapy is commonly used for patients with metastatic non–small cell lung cancer (NSCLC)—for symptom palliation, or ablation of metastases. Increasing evidence shows that radiotherapy alters the natural history of metastatic NSCLC. Here, we evaluate prospective systemic therapy trials for protocol specifications and documentation of radiation use during and before trial enrollment.

Materials and Methods

Clinicaltrials.gov was queried for completed, phase II-IV systemic therapy trials for metastatic NSCLC. Trial information was summarized using descriptive statistics. Fisher’s exact test and logistic regression were used to assess associations between trial-related factors, radiation allowance, and trial positivity.

Results

A total of 405 trials were screened, and 79 were included. Most trials were phase III (n = 50, 63.3%), randomized (n = 68, 86.1%), and unmasked (n = 56, 70.9%). PD-1/PD-L1, EGFR, and VEGF were the most common drug targets, in 46.9% (n = 37), 34.2% (n = 27), and 15.2% (n = 12) of studies, respectively. Most studies (n = 74, 93.7%) allowed radiation before trial enrollment and required a washout period. During the study period, 8.9% (n = 7) of studies prohibited (“off-protocol”) radiation. A drug washout around radiation delivery was required in 21.5% (n = 17) of studies. No studies permitting off-protocol radiation addressed allowable total dose, fractionation, technique or organ-at-risk constraints. Allowance of off-protocol radiation was not significantly associated with trial positivity (OR 0.23; 95% CI, 0.01-1.49; P = .19). While pre-enrollment radiation was reported in 32.9% (n = 26) of studies, no study reported off-protocol radiation use or adjusted for it during outcome analyses.

Conclusion

Among prospective systemic therapy trials for NSCLC, radiation details are inconsistently reported. Given overlapping toxicities and the common use of radiotherapy in this setting, future trials require clear parameters regarding radiotherapy use before and during trial enrollment.

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转移性非小细胞肺癌前瞻性全身治疗试验中的非方案放疗。

目的：放疗常用于转移性非小细胞肺癌（NSCLC）患者，用于症状缓解或转移灶消融。越来越多的证据表明放疗改变了转移性非小细胞肺癌的自然史。在这里，我们评估前瞻性全身治疗试验的方案规范和在试验入组期间和之前的辐射使用文件。材料和方法：在Clinicaltrials.gov网站上查询转移性NSCLC已完成的II-IV期全身治疗试验。试验信息采用描述性统计进行汇总。使用Fisher精确检验和逻辑回归来评估试验相关因素、辐射容许量和试验阳性之间的关联。结果：共筛选405项试验，纳入79项。大多数试验为III期（n = 50, 63.3%）、随机化（n = 68, 86.1%）和非盲化（n = 56, 70.9%）。PD-1/PD-L1、EGFR和VEGF是最常见的药物靶点，分别占46.9% （n = 37）、34.2% （n = 27）和15.2% （n = 12）的研究。大多数研究（n = 74, 93.7%）允许在试验入组前进行放疗，并要求有一段洗脱期。在研究期间，8.9% （n = 7）的研究禁止（“非协议”）辐射。21.5% （n = 17）的研究需要在放疗前后进行药物洗脱。没有一项允许非方案辐射的研究涉及允许的总剂量、分离、技术或器官风险限制。允许的非方案辐射与试验阳性无显著相关（OR 0.23; 95% CI, 0.01-1.49; P = 0.19）。虽然32.9% （n = 26）的研究报告了入组前的辐射，但没有研究报告了方案外的辐射使用或在结果分析期间进行了调整。结论：在NSCLC的前瞻性全身治疗试验中，放疗细节的报道不一致。考虑到重叠的毒性和在这种情况下放疗的普遍使用，未来的试验需要在试验入组前和入组期间关于放疗使用的明确参数。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical lung cancer 医学-肿瘤学

CiteScore

7.00

自引率

2.80%

发文量

159

审稿时长

24 days

期刊介绍： Clinical Lung Cancer is a peer-reviewed bimonthly journal that publishes original articles describing various aspects of clinical and translational research of lung cancer. Clinical Lung Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of lung cancer. The main emphasis is on recent scientific developments in all areas related to lung cancer. Specific areas of interest include clinical research and mechanistic approaches; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; and integration of various approaches.