Combined Stereotactic Body Radiation Therapy and Immune Checkpoint Inhibition for Liver Metastases: Safety and Outcomes in a Pooled Analysis of 3 Phase 1 Trials

被引：2

作者：

Lynch, Connor ^{[1
]}

Korpics, Mark C. ^{[1
]}

Katipally, Rohan R. ^{[1
]}

Wu, Tianming ^{[1
]}

Bestvina, Christine M. ^{[2
]}

Pitroda, Sean ^{[1
]}

Chmura, Steven J. ^{[1
]}

Juloori, Aditya ^{[1
]}

机构：

[1] Univ Chicago, Med Ctr, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA

[2] Univ Chicago, Med Ctr, Dept Hematol Oncol, Chicago, IL USA

来源：

INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS | 2024年 / 118卷 / 05期

关键词：

PHASE-I; RADIOTHERAPY; IPILIMUMAB; NIVOLUMAB; TOXICITY; PEMBROLIZUMAB; CRITERIA; SBRT;

D O I：

10.1016/j.ijrobp.2024.01.002

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose: Stereotactic body radiation therapy (SBRT) safely and effectively controls liver metastases (LMs), but its safety and ef fi cacy when combined with immune checkpoint inhibitors (ICIs) are not well characterized. This analysis of 3 phase 1 trials of combination SBRT and ICI evaluates whether LM-SBRT increases the risk for hepatotoxicity when combined with ICI and explores ef fi cacy endpoints. Methods and Materials: Data were analyzed from 3 phase 1 trials of combination SBRT and ICI for patients with metastatic solid tumors conducted between 2016 and 2020. ICI was administered per trial protocol with LM-SBRT delivered to 45 Gy in 3 fractions with mean liver dose < 16 Gy and >= 700 cc of normal liver spared 17.1 Gy. Hepatic adverse events (HAEs) were de fi ned as hepatic failure, autoimmune hepatitis, or elevation of aspartate transaminase, alanine transaminase, bilirubin, or alkaline phosphatase using Common Terminology Criteria for Adverse Events version 4.0. Cumulative incidence of HAEs and local failure were modeled with death as a competing risk. Competing risk regression was performed using Fine-Gray modeling. Survival was estimated via the Kaplan-Meier method. Results: Two hundred patients were analyzed, including 81 patients with LM, 57 of whom received LM-SBRT. The 12-month rate of any grade >= 2 HAE was 11% and 10% in LM-SBRT and non-LM-SBRT patients, respectively non-signi fi cant (NS). Radiographic evidence for liver disease and dual-agent ICI was signi fi cantly associated with HAEs on univariable and multivariable analysis, but liver dose metrics were not. Patients with LM had signi fi cantly worse progression-free and overall survival compared with those without, and local failure of treated LM was signi fi cantly higher than for treated extrahepatic metastases (28% vs 4% at 12 months, P < .001). Conclusions: Combination LM-SBRT and ICI did not signi fi cantly increase the risk for HAEs compared with ICI without LM-SBRT, suggesting hepatotoxicity is largely driven by factors other than liver radiation therapy, such as choice of ICI. LM is associated with worse overall survival and local control outcomes.

引用

页码：1519 / 1530

页数：12