Properly planned single isocenter volumetric modulated arc therapy (VMAT) radiosurgery plans exhibit high quality and efficiency. We report here the largest clinical experience to date, to our knowledge, comparing manual planning with a new automated platform designed to standardize and simplify radiosurgery planning and delivery processes. Methods: We treated 693 patients with single isocenter VMAT radiosurgical plans generated by either our conventional manual (mVMAT) or a recently implemented automated (HyperArc TM ) technique. All plans targeted the gross tumor volume without margin. Radiochromic film was used for patient-specific quality assurance (PSQA). We evaluated local control and toxicity data for a subgroup of 107 patients having 377 metastatic tumors that were treated with HyperArc. Results: The median Radiation Therapy Oncology Group (RTOG) conformity index was 1.14 and was not different between the 2 techniques. The median Paddick gradient index was 5.42 for HyperArc versus 7.09 for mVMAT (P < .001). The median mean brain doses were 4.6% and 5.1% for HyperArc and mVMAT, respectively (P Z .04). The PSQA for both techniques met clinical criteria, but 97% of the HyperArc plans satisfied the gamma tolerance limit recommended by the American Association of Physicists in Medicine Task Group No. 218, compared with 94% of the mVMAT plans (P Z .02). The median treatment-planning times were not significantly different. The median treatment times were 10.5 and 11.4 minutes for HyperArc and mVMAT, respectively (P < .001). The Kaplan-Meier estimate of local control was 90.1% at 1 year.

Purpose Prior studies have mixed conclusions about the efficacy and central nervous system (CNS) toxicity profile of combining radiosurgery with anti-programed cell death 1 (PD-1) immune checkpoint inhibition (ICI) for brain metastases. This study evaluates the safety and efficacy of combined radiosurgery and anti-PD-1 ICI for melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC) brain metastases (BM). Methods and Materials Forty-one patients with 153 radiation naïve melanoma BM and 33 patients with 118 BM of NSCLC and RCC origin from 2014 through 2019 received radiosurgery and either anti PD-1 receptor inhibition or anti PD-L1 inhibition targeting the PD-1 ligand with less than 4 months separating either therapy. Similar to Radiation Therapy Oncology Group 9005, high-grade CNS toxicity was defined as irreversible grade 3 or any grade 4/5 neurologic event. Salvage resection revealing necrosis and viable tumor was considered grade 4 toxicity and local failure. An increase in greatest cross-sectional diameter of 25% on contrasted magnetic resonance imaging was designated as a local failure. Results Median follow-up was 10 months (range, 1-41 months). Local control was estimated to be 90.3% at 1 year. Distant control was 38.8% at 1 year, and neither local nor distant control were significantly influenced by limiting steroids to the day of treatment ( P = .55, .52 respectively). One-year freedom from high-grade toxicity was 90.4% for patients and 94.6% for tumors. Though melanoma accounted for 41 (55%) patients and 153 (56%) tumors, it accounted for all high-grade toxicities ( P = .03). These patients had some combination of high tumor burden, aggressive steroid taper, and treatment with ipilimumab. Conclusions Stereotactic radiosurgery combined with anti-PD-1 ICI appears to result in a high rate of local tumor control and a low rate of high-grade CNS toxicity, comparable to historical series with radiosurgery alone. High-grade toxicity is more likely in melanoma than RCC and NSCLC. Coming prospective studies will shed light on further questions about treatment timing, steroids, and response.

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