Search

New therapies for melanoma have been associated with increasing survival expectations, as opposed to the dismal outcomes of only a decade ago. Using a prospective registry, we aimed to define current survival goals for melanoma patients with brain metastases (BM), based on state-of-the-art multimodality care.We reviewed 171 melanoma patients with BM receiving stereotactic radiosurgery (SRS) who were followed with point-of-care data collection between 2012 and 2020. Clinical, molecular and imaging data were collected, including systemic treatment and radiosurgical parameters.Mean age was 63 ± 15 years, 39% were female and 29% had BRAF-mutated tumors. Median overall survival after radiosurgery was 15.7 months (95% Confidence Interval 11.4-27.7) and 25 months in patients managed since 2015. Thirty-two patients survived [Formula: see text] 5 years from their initial SRS. BRAF mutation-targeted therapies showed a survival advantage in comparison to chemotherapy (p = 0.009), but not to immunotherapy (p = 0.09). In a multivariable analysis, both immunotherapy and the number of metastases at 1Long-term survival in patients with melanoma BM is achievable in the current era of SRS combined with immunotherapies. For those alive [Formula: see text] 5 years after first SRS, 16% had been also off systemic or local brain therapy for over 5 years. Given late recurrences of melanoma, caution is warranted, however prolonged survival off active treatment in a subset of our patients raises the potential for cure.

OBJECTIVE Patients with non–small cell lung cancer (NSCLC) metastatic to the brain are living longer. The risk of new brain metastases when these patients stop systemic therapy is unknown. The authors hypothesized that the risk of new brain metastases remains constant for as long as patients are off systemic therapy. METHODS A prospectively collected registry of patients undergoing radiosurgery for brain metastases was analyzed. Of 606 patients with NSCLC, 63 met the inclusion criteria of discontinuing systemic therapy for at least 90 days and undergoing active surveillance. The risk factors for the development of new tumors were determined using Cox proportional hazards and recurrent events models. RESULTS The median duration to new brain metastases off systemic therapy was 16.0 months. The probability of developing an additional new tumor at 6, 12, and 18 months was 26%, 40%, and 53%, respectively. There were no additional new tumors 22 months after stopping therapy. Patients who discontinued therapy due to intolerance or progression of the disease and those with mutations in RAS or receptor tyrosine kinase (RTK) pathways (e.g., KRAS, EGFR) were more likely to develop new tumors (hazard ratio [HR] 2.25, 95% confidence interval [CI] 1.33–3.81, p = 2.5 × 10−3; HR 2.51, 95% CI 1.45–4.34, p = 9.8 × 10−4, respectively). CONCLUSIONS The rate of new brain metastases from NSCLC in patients off systemic therapy decreases over time and is uncommon 2 years after cessation of cancer therapy. Patients who stop therapy due to toxicity or who have RAS or RTK pathway mutations have a higher rate of new metastases and should be followed more closely.

INTRODUCTION The effects of radiosurgery for primary intracranial tumors on systemic immune response are unknown. Vestibular schwannomas (VS) treated with Gamma Knife (GK) have high control rates and low risk of adverse effects. This study examines if radiosurgery for VS is associated with an immune response detectable by peripheral blood sampling, and if that response can be correlated with tumoral expansion and/or toxicity. METHODS 50 patients treated with GK for VS were enrolled on an IRB-approved, prospective study at initial consultation. Blood samples were drawn preceding GK and 6 months and 1 year follow-up. Neurological and hearing outcomes were assessed. Tumor volume was measured at treatment, 6 months, and 1 year follow-up. Tumoral expansion (TE) was defined by volumetric increase >20%. Immunophenotyping via multicolor flow cytometry panels evaluated lymphoid and myeloid differentiation, phenotypic characterization, activation, tissue homing, and immune exhaustion. RESULTS Median volume at radiosurgery was 0.55cc (range 0.04-11.94) and median margin dose was 12.5Gy (11.5-13) prescribed to the 50% isodose line (50-60). 22 tumors exhibited TE, 20 at six months and 2 at one year. No VS with TE grew at median follow-up of 30.8 months (9.8-52.8). 1 tumor, non-expanding (NE) post-GK, showed progression at 24 months. Presence of cranial neuropathy and hearing decline was similar in both groups. Immunophenotyping showed numerous significant (p< .05) changes in the TE group, not seen in NE, at 6 months and 1 year follow-up compared to baseline. Major changes were observed in cytokine secretion (e.g. IFNg, TNF or IL-17) of CD4+ and CD8+ memory T cells, frequencies of regulatory T cells, increased death of CD8+ effector cells in culture, suggesting chronic activated state. CONCLUSION Vestibular schwannomas that expand after GK are associated with a peripherally measurable change in systemic immune response that is absent from non-expanding tumors. The biologic underpinnings of these findings require further study.

Purpose Patients with non-small cell lung cancer (NSCLC) metastatic to the brain increasingly are living longer due to improvements in systemic therapy and local modalities. The risk of new brain metastases when these patients stop systemic therapy is unknown. Recognizing patterns of new tumor occurrence is necessary to determine the frequency of follow-up and the need for further treatment. Methods We included patients in a prospective registry who had non-small cell lung cancer (NSCLC) brain metastases, discontinued systemic therapy for at least 90 days, and underwent active surveillance. 63 patients with 73 off-periods were studied. The risk factors for the development of new tumors were determined using Cox regression and multi-state Markov modeling. Results The median time to new brain metastases off systemic therapy was 16.0 months. The probability of developing an additional new tumor at 6, 12, and 18 months was 26%, 40%, and 53%, respectively. There were no additional new tumors 22 months after stopping therapy. Patients who discontinued therapy due to intolerance or progression of the disease and those with mutations in RAS or receptor tyrosine kinase pathways (e.g. KRAS, EGFR) were more likely to develop new tumors (HR: 2.21, 95% CI: 1.25–3.91, p=6.3 x 10–3; HR: 2.03, 95% CI: 1.09–3.77, p=0.026, respectively). Conclusion The rate of new brain metastases from NSCLC in patients off systemic therapy decreases over time and is uncommon 2 years after cessation of cancer therapy. Patients who stop therapy due to toxicity or who have RAS or receptor tyrosine kinase pathway mutations have a higher rate of new metastases and should be followed more closely.