title: The effect of timing of stereotactic radiosurgery treatment of melanoma brain metastases treated with ipilimumab.
abstract: OBJECTIVE Melanoma represents the third most common cause of CNS metastases. Immunotherapy has evolved as a treatment option for patients with Stage IV melanoma. Stereotactic radiosurgery (SRS) also elicits an immune response within the brain and may interact with immunotherapy. The authors report on a cohort of patients treated for brain metastases with immunotherapy and evaluate the effect of SRS timing on the intracranial response. METHODS All consecutively treated melanoma patients receiving ipilimumab and SRS for treatment of brain metastases at the University of Virginia between 2009 and 2014 were included in this retrospective analysis; data from 46 patients harboring 232 brain metastases were reviewed. The median duration of clinical follow-up was 7.9 months (range 3-42.6 months). The median age of the patients was 63 years (range 24.3-83.6 years). Thirty-two patients received SRS before or during ipilimumab cycles (Group A), whereas 14 patients received SRS after ipilimumab treatment (Group B). Radiographic and clinical responses were assessed at approximately 3-month intervals after SRS. RESULTS The 2 cohorts were comparable in pertinent baseline characteristics with the exception of SRS timing relative to ipilimumab. Local recurrence-free duration (LRFD) was significantly longer in Group A (median 19.6 months, range 1.1-34.7 months) than in Group B patients (median 3 months, range 0.4-20.4 months) (p = 0.002). Post-SRS perilesional edema was more significant in Group A. CONCLUSIONS The effect of SRS and ipilimumab on LRFD seems greater when SRS is performed before or during ipilimumab treatments. The timing of immunotherapy and SRS may affect LRFD and postradiosurgical edema. The interactions between immunotherapy and SRS warrant further investigation so as to optimize the therapeutic benefits and mitigate the risks associated with multimodality, targeted therapy.
authors.affiliation: Department of Neurological Surgery, University of Virginia, Charlottesville, Virginia.|Department of Neurosurgery, Rambam Health Care Center, Haifa, Israel.
authors.forename: Or
authors.initials: O
authors.lastname: Cohen-Inbar
authors.affiliation: Department of Neurological Surgery, University of Virginia, Charlottesville, Virginia.|Department of Anesthesiology, Taichung Veterans General Hospital, Taichung City; and.|National Yang-Ming University, Taipei, Taiwan.
authors.forename: Han-Hsun
authors.initials: HH
authors.lastname: Shih
authors.affiliation: Department of Neurological Surgery, University of Virginia, Charlottesville, Virginia.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Neurological Surgery, University of Virginia, Charlottesville, Virginia.
authors.forename: David
authors.initials: D
authors.lastname: Schlesinger
authors.affiliation: Department of Neurological Surgery, University of Virginia, Charlottesville, Virginia.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Sheehan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000074322:Antineoplastic Agents, Immunological / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000556:secondary / Q000628:therapy*; D005260:Female; D006801:Humans; D000074324:Ipilimumab / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000532:radiotherapy / Q000556:secondary / Q000628:therapy*; D008875:Middle Aged; D016634:Radiosurgery; D012189:Retrospective Studies; D013997:Time Factors; D055815:Young Adult
chemical_list: D000074322:Antineoplastic Agents, Immunological; D000074324:Ipilimumab
keywords: GPA = graded prognostic assessment; KPS = Karnofsky Performance Status; LRFD = local recurrence–free duration; OS = overall survival; RRFD = regional recurrence–free duration; SRS = stereotactic radiosurgery; TIL = tumor infiltrating radiosensitive T-cell; UVA = University of Virginia; brain metastases; ipilimumab; melanoma; oncology; stereotactic radiosurgery