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While neurotrophic tropomyosin receptor kinase (NTRK) fusions represent rare oncogenic drivers (<1% of solid cancers), the recent approval of NTRK inhibitors (larotrectinib and entrectinib) led to dramatic responses in patients with NTRK fusion+ tumors. Both drugs have phase I data, demonstrating efficacy in the central nervous system (CNS), including both primary brain tumors and brain metastases. We present a 29-year-old woman who was diagnosed with NTRK3-SPECC1L fusion+ undifferentiated uterine sarcoma and underwent resection, chemotherapy, and radiotherapy. Two years later, lung metastases were discovered. She was started on larotrectinib with complete response. She remained stable on larotrectinib until she presented with altered mental status and seizures. MRI demonstrated leptomeningeal enhancement, but because leptomeningeal progression from sarcoma is exceedingly rare and her symptoms improved dramatically with antiepileptics, these findings were initially attributed to seizures. After 2 unrevealing lumbar punctures and stable systemic imaging, a brain biopsy demonstrated metastatic sarcoma, still showing NTRK positivity. She underwent whole brain radiotherapy and was switched to entrectinib, but had clinical progression 1 month later and transitioned to hospice. This case demonstrates the efficacy of NTRK inhibitors in rare and aggressive cancer but highlights that these patients can develop isolated CNS progression even in the setting of CNS-penetrant drugs. CNS progression can occur if there is incomplete CNS drug penetration, discordance in molecular profiles between CNS and systemic disease, or acquired NTRK inhibitor resistance. In this case, CNS disease maintained the NTRK fusion status, but either inadequate CNS penetration or development of a resistance gene may explain the isolated CNS progression. [ABSTRACT FROM AUTHOR]

Brain metastases (BMs) from hepatocellular carcinoma (HCC) are rare, with a paucity of reported cases. In the present retrospective cohort report, we assessed the proportion of BMs arising from HCC and characterized the related details, including patient demographics, clinical characteristics, treatment modalities, and survival outcomes. We retrospectively identified and reviewed the medical records of 14 patients with BMs from HCC seen at our institution from 2008 to 2018. Among all patients with BMs, the proportion originating from primary liver cancer was 0.39%. In every case (n = 14), the liver cancer was HCC. The median age at the BM diagnosis was 64 years (range, 37–82 years). The median alpha-fetoprotein level at the diagnosis of BM was 540 ng/mL (range, 3–10,000 ng/mL). The median interval from the HCC diagnosis to the development of BMs was 31.1 months (range, 3.17–107 months). Of the 14 patients, 8 (57%) had had metastases to the brain parenchyma and 6 had had skull or dural metastases. For patients with brain parenchymal metastases, the median number of metastases was 1 (range, 1–5). Of the 14 patients, 13 have died, with a median overall survival after the BM diagnosis of 2.83 months (range, 0.430–24.0 months). At the latest follow-up examination, the survival for the 14th patient was 142 months after the BM diagnosis. Resection of BMs with radiosurgery was associated with increased survival compared with radiosurgery alone (10.9 months vs. 2.8 months; P = 0.04). HCC BMs are rare and constitute a small fraction of the total incidence of BMs. The prognostic data we have provided can aid medical providers in caring for patients with HCC BMs. [ABSTRACT FROM AUTHOR]

In the present study, we used a validated socioeconomic status (SES) index and population-based registry to identify and quantify the impact of SES on access to treatment and overall survival for patients diagnosed with synchronous brain metastases. The Surveillance, Epidemiology, and End Results database was used to extract all patients between 2010 and 2016 with brain metastases at initial presentation. SES was stratified into tertiles and quintiles using the validated Yost index. Multivariable logistic regressions were used to evaluate the impact of demographic, tumor, and socioeconomic covariates on receipt of radiotherapy and chemotherapy. Kaplan-Meier curves were used to estimate survival. Between 2010 and 2016, 35,595 patients presented with brain metastases at the time of primary cancer diagnosis. Most patients received radiation and/or chemotherapy as part of the initial course of their treatment; 71.6% (n = 25,484) were irradiated while 54.4% (n = 19,371) received chemotherapy and 44.9% (n = 15,984) received chemoradiation. Patients in the highest Yost tertile and quintile experienced longer overall survival (P < 0.001). Additionally, multivariable logistic regression revealed that the lowest Yost quintile was significantly less likely to receive either radiation (adjusted OR: 0.82; 95% confidence interval: 0.75–0.89; P < 0.001) or chemotherapy (adjusted OR: 0.62; 95% confidence interval: 0.58–0.67; P < 0.001). In a large, population-based analysis of brain metastasis patients, we found significant differences in treatment access and mild survival differences along socioeconomic strata. More specifically, patients in lower SES tiers suffered worse outcomes and received radiation and chemotherapy less frequently than patients in higher tiers, even after accounting for other tumor- and demographic-related information. [ABSTRACT FROM AUTHOR]

Brain metastases from prostate cancer are rare and poorly described. We sought to assess the proportion of brain metastases arising from prostate cancer and to detail clinical characteristics, treatment modalities, and survival outcomes. We retrospectively identified and reviewed the charts of 31 patients with intraparenchymal brain metastases from prostate adenocarcinoma seen at our institution from 2008 to 2018. Among all patients with brain metastases, the proportion originating from prostate adenocarcinoma was 0.86%. The median age at the time of brain metastasis diagnosis was 69 (range, 57–90). The median original Gleason score was 8 (range, 6–10), and the median prostate-specific antigen at the time of brain metastasis was 60 ng/mL (range, 0.34–4600). The median months from initial cancer diagnosis to brain metastasis was 81 (range, 3–195). The median number of brain metastases was 2 (range, 1–5). Patients had concurrent metastases to bone (100%), lung (48%), and liver (35%). Median overall survival was 3 months (range, 0.4–25.0). Treatment of the brain metastases was correlated with an increase in median survival from 1.2 months to 4.6 months with radiosurgery (hazard ratio = 0.11, P = 0.001) and surgical resection plus radiotherapy to 13 months (hazard ratio = 0.05, P < 0.001). All patients died of advanced, systemic disease and not of their intracranial disease. Brain metastasis from prostate cancer constitutes a small fraction of total brain metastases, but is associated with poor prognosis and is seen in the setting of advanced, castrate resistant disease. These data enable treating physicians to appropriately counsel their patients with prostate adenocarcinoma brain metastasis. [ABSTRACT FROM AUTHOR]

Few prognostic markers are available for patients with non-small-cell lung cancer (NSCLC) undergoing neurosurgical resection of symptomatic brain metastases. We investigated whether tumor mutation status (EGFR , KRAS, ALK, ROS1, and BRAF) and treatment history were associated with survival after neurosurgery. We reviewed the electronic health records of 104 patients with NSCLC with genomic profiling who underwent neurosurgical resection for symptomatic brain metastases at an academic institution between January 2000 and January 2018. We used multivariate Cox proportional hazards regression models to evaluate the association between overall survival (OS) after neurosurgery and clinicopathologic factors, including mutation status. Mean age of patients in this study was 61 (±12) years, and 44% were men. The median OS after neurosurgery was 24 months (95% confidence interval, 18–34 months). Our multivariate analysis showed that the presence of an EGFR mutation in the tumor was significantly associated with improved OS (hazard ratio [HR], 0.214; P = 0.029), independent of tyrosine kinase inhibitor use. Presence of KRAS , ALK , ROS1 , and BRAF alterations was not associated with survival (all P > 0.05). Conversely, older age (HR, 1.039; P = 0.029), a history of multiple brain irradiation procedures (HR, 9.197; P < 0.001), and presence of extracranial metastasis (HR, 2.556; P = 0.016) resulted in increased risk of mortality. Patients requiring surgical resection of an epidermal growth factor receptor–mutated NSCLC brain metastasis had an associated improved survival compared with patients without this mutation, independent of tyrosine kinase inhibitor use. Decreased survival was associated with older age, multiple previous brain radiation therapies, and extracranial metastasis. [ABSTRACT FROM AUTHOR]