Rupesh Kotecha1,2, Joseph M Kim3, Jacob A Miller4, Aditya Juloori5, Samuel T Chao5,6,7, Erin S Murphy5,6,7, David M Peereboom6,7,8, Alireza M Mohammadi6,7,9, Gene H Barnett6,7,9, Michael A Vogelbaum6,7,9, Lilyana Angelov6,7, John H Suh5,6,7, Manmeet S Ahluwalia6,7,8. 1. Department of Radiation Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida. 2. Herbert Wertheim College of Medicine, Florida International University, Miami, Florida. 3. School of Medicine, Case Western Reserve University, Cleveland Clinic, Cleveland, Ohio. 4. Department of Radiation Oncology, Stanford University, Palo Alto, California. 5. Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio. 6. Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Taussig Cancer Institute, Cleveland, Ohio. 7. Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio. 8. Department of Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio. 9. Department of Neurological Surgery, Neurological Institute, Cleveland Clinic, Cleveland, Ohio.
Abstract
BACKGROUND: The response of brain metastases (BM) treated with stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICIs; programmed cell death 1 and its ligand) is of significant interest. METHODS: Patients were divided into cohorts based on ICI sequencing around SRS. The primary outcome was best objective response (BOR) that was lesion specific. Secondary outcomes included overall objective response (OOR), response durability, radiation necrosis (RN), and overall survival (OS). RESULTS: One hundred fifty patients underwent SRS to 1003 BM and received ICI. Five hundred sixty-four lesions (56%) treated with concurrent ICI (±5 half-lives) demonstrated superior BOR, OOR, and response durability compared with lesions treated with SRS and delayed ICI. Responses were best in those treated with immediate (±1 half-life) ICI (BOR: -100 vs -57%, P < 0.001; complete response: 50 vs 32%; 12-month durable response: 94 vs 71%, P < 0.001). Lesions pre-exposed to ICI and treated with SRS had poorer BOR (-45%) compared with ICI naive lesions (-63%, P < 0.001); best response was observed in ICI naive lesions receiving SRS and immediate ICI (-100%, P < 0.001). The 12-month cumulative incidence of RN with immediate ICI was 3.2% (95% CI: 1.3-5.0%). First radiographic follow-up and best intracranial response were significantly associated with longer OS; steroids were associated with inferior response rates and poorer OS (median 10 vs 25 mo, P = 0.002). CONCLUSIONS: Sequencing of ICI around SRS is associated with overall response, best response, and response durability, with the most substantial effect in ICI naive BM undergoing immediate combined modality therapy. First intracranial response for patients treated with immediate ICI and SRS may be prognostic for OS, whereas steroids are detrimental.
BACKGROUND: The response of brain metastases (BM) treated with stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICIs; programmed cell death 1 and its ligand) is of significant interest. METHODS: Patients were divided into cohorts based on ICI sequencing around SRS. The primary outcome was best objective response (BOR) that was lesion specific. Secondary outcomes included overall objective response (OOR), response durability, radiation necrosis (RN), and overall survival (OS). RESULTS: One hundred fifty patients underwent SRS to 1003 BM and received ICI. Five hundred sixty-four lesions (56%) treated with concurrent ICI (±5 half-lives) demonstrated superior BOR, OOR, and response durability compared with lesions treated with SRS and delayed ICI. Responses were best in those treated with immediate (±1 half-life) ICI (BOR: -100 vs -57%, P < 0.001; complete response: 50 vs 32%; 12-month durable response: 94 vs 71%, P < 0.001). Lesions pre-exposed to ICI and treated with SRS had poorer BOR (-45%) compared with ICI naive lesions (-63%, P < 0.001); best response was observed in ICI naive lesions receiving SRS and immediate ICI (-100%, P < 0.001). The 12-month cumulative incidence of RN with immediate ICI was 3.2% (95% CI: 1.3-5.0%). First radiographic follow-up and best intracranial response were significantly associated with longer OS; steroids were associated with inferior response rates and poorer OS (median 10 vs 25 mo, P = 0.002). CONCLUSIONS: Sequencing of ICI around SRS is associated with overall response, best response, and response durability, with the most substantial effect in ICI naive BM undergoing immediate combined modality therapy. First intracranial response for patients treated with immediate ICI and SRS may be prognostic for OS, whereas steroids are detrimental.
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Authors: Shearwood McClelland; Tim Lautenschlaeger; Yong Zang; Nasser H Hanna; Kevin Shiue; Aaron P Kamer; Namita Agrawal; Susannah G Ellsworth; Ryan M Rhome; Gordon A Watson Journal: Rep Pract Oncol Radiother Date: 2020-04-23