Objectives: The anti-CTLA-4 and antiprogrammed cell death-1 (PD-1) therapies have significantly improved survival of patients with metastatic melanoma. However, there is limited data regarding the interaction between immunotherapy (IT) and stereotactic radiosurgery (SRS) in patients with brain metastasis, particularly how combination therapy may affect toxicity and intracranial tumor control. Methods: We retrospectively reviewed 26 patients with metastatic melanoma who received immune check point inhibitors and SRS for brain metastasis from 2011 to 2017. We evaluated lesions receiving SRS concurrently (within 30 days) and sequentially with IT. Overall survival (OS), local control (LC), and regional progression free survival (RPFS) were determined. Results: In total, 26 patients and 90 lesions were treated using pembrolizumab, nivolumab and/or ipilimumab, sequentially, or concurrently with SRS. Median follow-up was 18.9 months (range, 4.9 to 62.3 mo). Median overall survival was 26.1 months. There were 3 local failures, but no significant difference between the 2 groups. Following concurrent SRS and immunotherapy, patients had a significantly longer period of intracranial progression free survival than those treated with nonconcurrent therapy, 19 months versus 3.4 months (P<0.0001). No grade 4-5 toxicities were observed. Conclusions: Patients with melanoma metastatic to brain treated with SRS and immune checkpoint inhibitors had favorable median survival of 26.1 months compared with historical controls. Patients receiving immunotherapy within 30 days of SRS had significantly improved regional intracranial progression free survival compared with patients receiving sequential therapy. Our findings suggest synergy between checkpoint inhibitor immunotherapy and radiosurgery. Further studies are needed to confirm these findings.

Background There is growing evidence supporting the need for a short time delay before starting radiotherapy (RT) treatment post-surgery for most optimal responses. The timing of RT initiation and effects on outcomes have been evaluated in a variety of malignancies, but the relationship remains to be well established for brain metastasis. Methods Retrospective study of 176 patients (aged 18 to 89 years) with brain metastases at a single institution (03/2009 to 08/2018) who received RT following surgical resection. Time interval (≤ 22 days and &gt; 22 days) from surgical resection to initiation of RT and any potential impact on patient outcomes were assessed. Results Patients who underwent RT &gt; 22 days after surgical resection had a decreased risk for all-cause mortality of 47.2% (95% CI 8.60, 69.5%). Additionally, waiting &gt; 40 days for RT after surgical resection more than doubled the risk of tumor progression; adjusted hazard ratio 2.02 (95% CI 1.12, 3.64). Conclusions Findings indicate that a short interval delay (&gt; 22 days) following surgical resection is required before RT initiation for optimal treatment effects in brain metastasis. Our timing of RT post-surgical resection data add definition to current heterogeneity in RT timing, which is especially important for standardized clinical trial design and patient outcomes.

Prognosis in colon cancer is intimately linked to the patient's immune response. Assuming standardised surgical technique and sub specialty pathology, lymph node count is reduced when systemic inflammatory response is activated.

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