Department of Radiation and Cellular Oncology, University of Chicago Medical Center, Chicago, Illinois.
Department of Medicine, Section of Hematology/Oncology, University of Chicago Medical Center, Chicago, Illinois.
Int J Radiat Oncol Biol Phys. 2022 Nov 15;114(4):645-654. doi: 10.1016/j.ijrobp.2022.06.068. Epub 2022 Jun 23.
Thoracic stereotactic body radiation therapy (SBRT) is associated with high rates of local control but carries a risk of pneumonitis. Immunotherapy is a standard treatment for patients with metastatic disease but can also cause pneumonitis. To evaluate the feasibility and safety of thoracic SBRT with systemic immunotherapy, clinical outcomes of patients treated with immune checkpoint blockade (ICB) and SBRT on prospective trials were reviewed.
Three consecutive phase 1 trials of combination SBRT and ICB conducted between 2016 to 2020 for widely metastatic solid tumors were reviewed. The protocols mandated adherence to NRG BR001/BR002 organs at risk constraints, resulting in <100% coverage of some target volumes. ICB was administered either sequentially (within 7 days after completion of SBRT) or concurrently (before or at the start of SBRT), depending on protocol. End points included pneumonitis, dose-volume constraints, local failure, and overall survival. The cumulative incidence estimator and Kaplan-Meier method were used.
In the study, 123 patients met eligibility with 311 metastases irradiated. The most common histologies included non-small cell lung cancer (33%) and colorectal cancer (12%). Median follow-up was 12 months. The overall rate of grade 3+ pneumonitis was 8.1%; 1-year local failure was 3.6%. Established dosimetric parameters were significantly associated with the development of pneumonitis (P < .05). In most patients, the lungs were not challenged with high doses of radiation, defined as receiving ≥75% of the maximum for a given lung dose-volume constraint. Patients who were challenged were not found to have a significantly higher risk of pneumonitis.
In the largest series of thoracic SBRT and immunotherapy, local control was excellent with acceptable toxicity and support the conclusion that established dose-volume constraints for the lung are safe. However, these results highlight the potential value in reporting of organs at risk being challenged with doses approaching protocol specified limits.
胸部立体定向体放射治疗（SBRT）局部控制率高，但有发生放射性肺炎的风险。免疫疗法是转移性疾病患者的标准治疗方法，但也会引起放射性肺炎。为了评估胸部 SBRT 联合全身免疫治疗的可行性和安全性，我们回顾了接受免疫检查点抑制剂（ICB）和 SBRT 治疗的患者在前瞻性试验中的临床结果。
我们回顾了 2016 年至 2020 年期间进行的三项连续的 ICB 联合 SBRT 治疗广泛转移性实体瘤的 I 期临床试验。这些方案要求遵守 NRG BR001/BR002 危及器官限制，导致部分靶区覆盖率低于 100%。ICB 要么在 SBRT 完成后 7 天内序贯给药（sequentially），要么在 SBRT 之前或开始时同时给药（concurrently），具体取决于方案。终点包括放射性肺炎、剂量-体积限制、局部失败和总生存期。使用累积发生率估计器和 Kaplan-Meier 方法。
在这项研究中，123 名符合条件的患者共接受了 311 个转移灶放疗。最常见的组织学类型包括非小细胞肺癌（33%）和结直肠癌（12%）。中位随访时间为 12 个月。总体 3+级放射性肺炎发生率为 8.1%；1 年局部失败率为 3.6%。已建立的剂量学参数与放射性肺炎的发生显著相关（P <.05）。在大多数患者中，肺部未受到高剂量辐射的挑战，定义为接受了给定肺剂量-体积限制的最大剂量的≥75%。未发现接受挑战的患者放射性肺炎风险显著增加。
在最大的胸部 SBRT 和免疫治疗系列中，局部控制效果非常好，毒性可接受，支持这样的结论，即已建立的肺剂量-体积限制是安全的。然而，这些结果强调了在报告接近方案规定限制的剂量挑战危及器官方面的潜在价值。
