Safety and clinical efficacy of immune checkpoint inhibition and stereotactic body radiotherapy in patients with spine metastasis
OBJECTIVE: 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.
METHODS: 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:39 |
|---|---|
| Enthalten in: |
Journal of neurosurgery. Spine - 39(2023), 2 vom: 01. Aug., Seite 278-286 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lee, Emerson [VerfasserIn] |
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| Links: |
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| Themen: |
Adverse events |
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| Anmerkungen: |
Date Completed 03.08.2023 Date Revised 03.08.2023 published: Electronic-Print Citation Status MEDLINE |
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| doi: |
10.3171/2023.3.SPINE221086 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM356513963 |
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| 100 | 1 | |a Lee, Emerson |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Safety and clinical efficacy of immune checkpoint inhibition and stereotactic body radiotherapy in patients with spine metastasis |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 03.08.2023 | ||
| 500 | |a Date Revised 03.08.2023 | ||
| 500 | |a published: Electronic-Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a OBJECTIVE: 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 | ||
| 520 | |a METHODS: 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 | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a immune checkpoint inhibitor | |
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| 650 | 4 | |a oncology | |
| 650 | 4 | |a safety profile | |
| 650 | 4 | |a stereotactic body radiotherapy | |
| 650 | 4 | |a survival | |
| 650 | 4 | |a toxicity | |
| 650 | 7 | |a Immune Checkpoint Inhibitors |2 NLM | |
| 700 | 1 | |a Chen, Xuguang |e verfasserin |4 aut | |
| 700 | 1 | |a LeCompte, Michael C |e verfasserin |4 aut | |
| 700 | 1 | |a Kleinberg, Lawrence R |e verfasserin |4 aut | |
| 700 | 1 | |a Hales, Russell K |e verfasserin |4 aut | |
| 700 | 1 | |a Voong, Khinh Ranh |e verfasserin |4 aut | |
| 700 | 1 | |a Forde, Patrick M |e verfasserin |4 aut | |
| 700 | 1 | |a Brahmer, Julie R |e verfasserin |4 aut | |
| 700 | 1 | |a Markowski, Mark C |e verfasserin |4 aut | |
| 700 | 1 | |a Lipson, Evan J |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Sang Hun |e verfasserin |4 aut | |
| 700 | 1 | |a Bydon, Ali |e verfasserin |4 aut | |
| 700 | 1 | |a Lo, Sheng-Fu Larry |e verfasserin |4 aut | |
| 700 | 1 | |a Lubelski, Daniel |e verfasserin |4 aut | |
| 700 | 1 | |a Redmond, Kristin J |e verfasserin |4 aut | |
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