Immunotherapy, particularly immune checkpoint inhibitors (ICIs), has revolutionized the treatment of patients with many tumor histologies. Simultaneously, stereotactic body radiotherapy (SBRT) provides excellent local control (LC) and plays an important role in the management of spine metastasis. Promising preclinical work suggests the potential therapeutic benefit of combining SBRT with ICI therapy, but the safety profile of combined therapy is unclear. This study aimed to evaluate the toxicity profile associated with ICI in patients receiving SBRT and, secondarily, whether ICI administration sequence with respect to SBRT affects LC or overall survival (OS) outcomes.
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The authors retrospectively reviewed patients with spine metastasis treated with SBRT at an academic center. Patients who received ICI at any point during their disease course were compared to those with the same primary tumor types who did not receive ICI by using Cox proportional hazards analyses. Primary outcomes were long-term sequelae, including radiation-induced spinal cord myelopathy, esophageal stricture, and bowel obstruction. Secondarily, models were created to evaluate OS and LC in the cohort.
RESULTS
Two hundred forty patients who received SBRT to 299 spine metastases were included in this study. The most common primary tumor types were non–small cell lung cancer (n = 59 [24.6%]) and renal cell carcinoma (n = 55 [22.9%]). One hundred eight patients received at least 1 dose of ICI, with the most common regimen being single-agent anti–PD-1 (n = 80 [74.1%]), followed by combination CTLA-4/PD-1 inhibitors (n = 19 [17.6%]). Three patients experienced long-term radiation-induced sequelae: 2 had esophageal stricture and 1 had bowel obstruction. No patients developed radiation-induced myelopathy. There was no association between receipt of ICI and development of any of these adverse events (p > 0.9). Similarly, ICI was not significantly associated with either LC (p = 0.3) or OS (p = 0.6). In the entire cohort, patients who received ICI prior to beginning SBRT had worse median survival, but ICI sequence with respect to SBRT was not significantly prognostic of either LC (p > 0.3) or OS (p > 0.07); instead, baseline performance status was most predictive of OS (HR 1.38, 95% CI 1.07–1.78, p = 0.012).
CONCLUSIONS
Treatment regimens that combine ICIs before, concurrent with, and after SBRT for spine metastases are safe, with minimal risk for increased rates of long-term toxicity.
CorrespondenceKristin J. Redmond: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD.kjanson3@jhmi.edu.
INCLUDE WHEN CITINGPublished online May 5, 2023; DOI: 10.3171/2023.3.SPINE221086.
DisclosuresDr. Kleinberg reported grants from Novartis and BMS; and nonfinancial support from Incyte outside the submitted work. Dr. Forde reported personal fees from AstraZeneca, BMS, Novartis, Regeneron, Amgen, Daiichi, F Star, GI, Genentech, Janssen, Iteos, Merck, Sanofi, and Surface outside the submitted work. Dr. Brahmer reported personal fees from Merck, Genentech, AstraZeneca, Bristol Myers Squibb, and Regeneron; and grants from Bristol Myers Squibb and AstraZeneca outside the submitted work. Dr. Lipson reported personal fees from Bristol Myers Squibb, Novartis, EMD Serono, Array BioPharma, Macrogenics, Merck, Sanofi/Regeneron, Genentech, Odonate Therapeutics, Eisai, Natera, Instil Bio, Pfizer, Rain Therapeutics, OncoSec, and Immunocore; and grants from Bristol Myers Squibb, Sanofi/Regeneron, and Merck outside the submitted work. Dr. Bydon is a consultant for NuVasive. Dr. Redmond reported travel expenses from Elekta AB and Brainlab; grants from Accuray and Canon; membership on the data and safety monitoring board of Biomimetix; consulting and travel expenses from Icotec outside the submitted work; and is an employee of Johns Hopkins University.
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