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.

Abstract:The management of patients harboring central nervous system (CNS) hemangiopericytomas (HPCs) is a partially answered challenge. These are rare locally aggressive lesions, with potential for local recurrence, distal neural metastasis (DNM), and extraneural metastasis (ENM). Resection, when feasible, remains the initial treatment option, providing histological diagnosis and immediate relief of tumor-related mass effect. Patients receiving surgery alone or surgery and external beam radiotherapy (EBRT) show improved overall survival (OS) and progression-free survival as compared to those undergoing a biopsy alone (p = 0.01 and p = 0.02, respectively). Yet, in many instances, patient and tumor-related parameters preclude complete resection. EBRT or stereotactic radiosurgery (SRS) shares a significant role in achieving local tumor control, not shown to impact OS in HPC patients. The benefits of SRS/EBRT are clearly limited to improved local tumor volume control and neurologic function, not affecting DNM or ENM development. SRS provides acceptable rates of local tumor volume control coupled with treatment safety and a patient-friendly apparatus and procedure. Single-session SRS is most effective for lesions measuring <2 cm in their largest diameter (10 cm3 volume), with prescription doses of at >15 Gy. Systemic HPC disease is managed with various chemotherapeutic, immunotherapeutic, and anti-angiographic agents, with limited success. We present a short discussion on CNS HPCs, focusing our discussion on available evidence regarding the role of microsurgical resection, EBRT, SRS, chemotherapy, and immunotherapy for upfront, part of adoptive hybrid surgery approach or for recurrent HPCs.