Stereotactic radiosurgery for melanoma brain metastases in patients receiving ipilimumab: Safety profile and efficacy of combined treatment Journal Article


Authors: Kiess, A. P.; Wolchok, J. D.; Barker, C. A.; Postow, M. A.; Tabar, V.; Huse, J. T.; Chan, T. A.; Yamada, Y.; Beal, K.
Article Title: Stereotactic radiosurgery for melanoma brain metastases in patients receiving ipilimumab: Safety profile and efficacy of combined treatment
Abstract: Purpose Ipilimumab (Ipi), a monoclonal antibody against cytotoxic T-lymphocyte antigen-4, has been shown to improve survival in patients with metastatic melanoma. In this single-institution study, we investigated the safety and efficacy of stereotactic radiosurgery (SRS) for patients with melanoma brain metastases (BMs) who also received Ipi. Methods and Materials From 2005 to 2011, 46 patients with melanoma received Ipi and underwent single-fraction SRS for BMs. A total of 113 BMs (91% intact, 9% postoperative) were treated with a median dose of 21 Gy (range, 15-24 Gy). Ipi was given at 3 mg/kg (54%) or 10 mg/kg (46%) for a median of 4 doses (range, 1-21). Adverse events were recorded with the use of the Common Terminology Criteria for Adverse Events 3.0. Kaplan-Meier methods were used to estimate survival, and Cox regression was used to investigate associations. Results Fifteen patients received SRS during Ipi, 19 received SRS before Ipi, and 12 received SRS after Ipi. Overall survival (OS) was significantly associated with the timing of SRS/Ipi (P=.035) and melanoma-specific graded prognostic assessment (P=.013). Patients treated with SRS during or before Ipi had better OS and less regional recurrence than did those treated with SRS after Ipi (1-year OS 65% vs 56% vs 40%, P=.008; 1-year regional recurrence 69% vs 64% vs 92%, P=.003). SRS during Ipi also yielded a trend toward less local recurrence than did SRS before or after Ipi (1-year local recurrence 0% vs 13% vs 11%, P=.21). On magnetic resonance imaging, an increase in BM diameter to >150% was seen in 50% of patients treated during or before Ipi but in only 13% of patients treated after Ipi. Grade 3 to 4 toxicities were seen in 20% of patients. Conclusion Overall, the combination of Ipi and SRS appears to be well tolerated. Concurrent delivery of Ipi and SRS is associated with favorable locoregional control and possibly longer survival. It may also cause a temporary increase in tumor size, possibly because of an enhanced immunomodulatory effect. © 2015 Elsevier Inc.
Keywords: adult; cancer chemotherapy; cancer survival; clinical article; controlled study; aged; cancer surgery; overall survival; fatigue; cancer recurrence; hepatitis; cisplatin; diarrhea; drug efficacy; drug safety; multimodality cancer therapy; temozolomide; nuclear magnetic resonance imaging; follow up; magnetic resonance imaging; interleukin 2; ipilimumab; enzyme inhibition; lung disease; nausea; radiotherapy; dexamethasone; patient monitoring; oncology; vinblastine; monoclonal antibodies; pruritus; rash; drug induced headache; cardiovascular disease; computer assisted emission tomography; brain metastasis; intermethod comparison; cognitive defect; lactate dehydrogenase; seizure; headache; stereotactic radiosurgery; antibodies; patient treatment; locoregional control; neurologic disease; lactate dehydrogenase blood level; dermatology; central nervous system bleeding; concurrency control; enterocolitis; recurrence free survival; central nervous system disease; metastatic melanoma; common terminology criteria; cytotoxic t lymphocyte antigen-4; methods and materials; human; male; female; priority journal; article; kaplan-meier method; prognostic assessment; immunomodulatory effects; cardiopulmonary disease
Journal Title: International Journal of Radiation Oncology, Biology, Physics
Volume: 92
Issue: 2
ISSN: 0360-3016
Publisher: Elsevier Inc.  
Date Published: 2015-06-01
Start Page: 368
End Page: 375
Language: English
DOI: 10.1016/j.ijrobp.2015.01.004
PROVIDER: scopus
PUBMED: 25754629
PMCID: PMC4955924
DOI/URL:
Notes: Export Date: 3 June 2015 -- Source: Scopus
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MSK Authors
  1. Timothy Chan
    317 Chan
  2. Jedd D Wolchok
    905 Wolchok
  3. Viviane S Tabar
    226 Tabar
  4. Yoshiya Yamada
    480 Yamada
  5. Michael Andrew Postow
    365 Postow
  6. Kathryn Beal
    221 Beal
  7. Ana Ponce Kiess
    9 Kiess
  8. Christopher Barker
    219 Barker
  9. Jason T Huse
    143 Huse