Radiosurgery for melanoma brain metastases in the ipilimumab era and the possibility of longer survival Clinical article

Department of Radiation Medicine, Hofstra University North Shore-LIJ School of Medicine, Hofstra University, Manhasset, New York 11030, USA. .
Journal of Neurosurgery (Impact Factor: 3.74). 06/2012; 117(2):227-33. DOI: 10.3171/2012.5.JNS111929
Source: PubMed


A prospectively collected cohort of 77 patients who underwent definitive radiosurgery between 2002 and 2010 for melanoma brain metastases was retrospectively reviewed to assess the impact of ipilimumab use and other clinical variables on survival.
The authors conducted an institutional review board-approved chart review to assess patient age at the time of brain metastasis diagnosis, sex, primary disease location, initial radiosurgery date, number of metastases treated, performance status, systemic therapy and ipilimumab history, whole-brain radiation therapy (WBRT) use, follow-up duration, and survival at the last follow-up. The Diagnosis-Specific Graded Prognostic Assessment (DSGPA) score was calculated for each patient based on performance status and the number of brain metastases treated.
Thirty-five percent of the patients received ipilimumab. The median survival in this group was 21.3 months, as compared with 4.9 months in patients who did not receive ipilimumab. The 2-year survival rate was 47.2% in the ipilimumab group compared with 19.7% in the nonipilimumab group. The DS-GPA score was the most significant predictor of overall survival, and ipilimumab therapy was also independently associated with an improvement in the hazard for death (p = 0.03).
The survival of patients with melanoma brain metastases managed with ipilimumab and definitive radiosurgery can exceed the commonly anticipated 4-6 months. Using ipilimumab in a supportive treatment paradigm of radiosurgery for brain oligometastases was associated with an increased median survival from 4.9 to 21.3 months, with a 2-year survival rate of 19.7% versus 47.2%. This association between ipilimumab and prolonged survival remains significant even after adjustment for performance status without an increased need for salvage WBRT.

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    • "The combination of SRS and ipilimumab has recently been studied in a retrospective cohort of patients with melanoma brain metastases and showed improved survival as compared to SRS alone [8]. However, little has been reported about this treatment combination in patients with HIV. "
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    • "As TMZ crosses the intact BBB, the drug can be used early in patient treatment. Large MW drugs such as ipilimumab (MW 148 kDa) have shown to improve patient survival when combined with SRS [65]. Our study clearly shows that 64 Cu-BSA leaks into tumor parenchyma late in tumor development, suggesting that large MW drugs should preferably be used on larger and well-established brain metastases. "
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    • "Preliminary evidence suggests that this approach of combining radiation with immune checkpoint inhibitors may be translated effectively and safely to the clinic. Retrospective data of patients with intracranial melanoma metastases who received SRS with or without anti-CTLA-4, showed a significant improvement in overall survival (21.3 vs. 4.9 months) vs. SRS alone, with 47% of patients who received anti-CTLA-4 still living at 2 years [82]. "
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