INTRODUCTION Brain metastases from lung cancer (BMLC) are common and represent an aggressive form of disease. Numerous ongoing clinical trials are investigating targeted molecular therapies against epidermal growth factor receptor (EGFR), which have demonstrated blood-brain-barrier permeability and intracranial activity. However, there is limited real-world efficacy data on second and third-generation EGFR tyrosine kinase inhibitors (TKI), Afatinib and Osimertinib, for the treatment of BMLC. This study provides a real-world assessment to evaluate the impact of these agents on overall survival (OS) at the population-level. METHODS This retrospective cohort study queried data from TriNetX, a multi-institutional de-identified database, aggregating data from 90 U.S. healthcare organizations. Three cohorts were established, consisting of patients with BMLC treated with 1) Osimertinib, 2) Afatinib, or 3) Neither Osimertinib nor Afatinib. Cohorts 1 and 3, as well as cohorts 2 and 3, were propensity matched on demographics and comorbidities. Median overall survival (OS) was compared via Kaplan Meier analyses, using log-rank tests and Cox proportional hazards ratios (HR). RESULTS After matching, we identified 1,990 BMLC patients treated with Osimertinib (cohort 1) and 1,990 treated without Afatinib and Osimertinib (cohort 3). Median OS was 21.2 months and 13.5 months for the two cohorts, respectively (p < 0.0001; HR [95% CI], 0.69 [0.63-0.77]). Furthermore, we identified 685 BMLC patients treated with Afatinib (cohort 2) and 685 treated without Afatinib and Osimertinib (cohort 3) after matching. Median OS was 19.0 months and 11.5 months, respectively (p < 0.0185; HR [95% CI], 0.83 [0.71-0.97]). CONCLUSION Afatinib and Osimertinib demonstrated a significant survival benefit for patients with BMLC, with comparable, if not better, results to other therapeutic options. These findings suggest strong intracranial efficacy of these agents, while indicating a greater generalizability of the results. Further prospective studies are warranted to better understand their potential role in the BMLC treatment paradigm.

INTRODUCTION Mounting evidence demonstrates the therapeutic promise of immunotherapies (ITs) for brain metastases (BM). However, there is concern that stringent eligibility criteria in these clinical studies have selected against patients with comorbid conditions. As a result, it remains unclear if these results are truly applicable to the general population, particularly in individuals with end-stage renal disease (ESRD) on dialysis. Therefore, we sought to determine the impact of concomitant dialysis treatment and IT on overall survival (OS) of patients with BM. METHODS Data were collected from TriNetX (TriNetX, Inc., Cambridge, MA), a global research network that aggregates clinical data from 92 healthcare organizations. Independent variables included ‘secondary malignant neoplasm of brain’, ‘ipilimumab’, ‘pembrolizumab’, ‘ESRD’, ‘dependence on renal dialysis’, and ‘dialysis services and procedures’. Patients with BM receiving IT were dichotomized by dialysis use. Cohorts were propensity matched on age, gender, and race. Kaplan-Meier analyses and log rank tests were conducted to assess overall survival (OS) and survival probability over a five-year period. RESULTS Of the 14,368 confirmed BM patients treated with IT, 95 (0.6%) began dialysis within three months of IT initiation. Propensity matching established 95 patients in each cohort. The dialyzed cohort had a median OS of 277 days with a survival probability of 11.6%, compared to the non-dialyzed group with a median OS of 419 days and survival probability of 40.29% (p=0.109; hazard ratio 1.422, 95% confidence interval, 0.923-2.191, p=0.891). A separate comparison cohort was created to compare ESRD diagnosis with or without dialysis (n=56 and n=106 respectively). The comparison cohorts did not show a difference in median OS and survival probability (p=0.49). CONCLUSION Despite their health complexities, individuals with ESRD, with or without dependence on dialysis, may nonetheless derive a similar survival benefit from ITs. Therefore, we advocate for greater inclusion of patients with advanced comorbidities in clinical trials to assess for real-world safety and efficacy outcomes.

INTRODUCTION: Melanoma brain metastases (BM) are common and are historically associated with poor prognosis. In the early 2010s, the treatment paradigm for malignant metastatic melanoma shifted with the introduction of immunotherapy (IT). Recent studies suggest that IT provides survival benefits for patients with BM from melanoma primary. The goal of this study was to validate these findings in a large population cohort. METHODS: Data were collected from the Surveillance, Epidemiology and End Results (SEER) database, version 8.3.4 (22 March 2017). Three cohorts were created based on the FDA approval date of IT: ipilimumab (2011), nivolumab (2014), and nivolumab plus ipilimumab (2015) for use in metastatic melanomas. Respectively, the cohorts are defined as the pre-IT era cohort (2010), early-IT era cohort (2011-2015) and late-IT era cohort (2016-2018). One-year overall survival (OS), 2-year OS, and median OS were assessed using a Kaplan-Meier analysis and log rank tests. RESULTS: 1,893 patients were included in this analysis (190 in the pre-IT era, 1,021 in the early-IT era, and 682 in the late-IT era) that had histologically confirmed melanoma with secondary BM at diagnosis. Median OS was significantly increased across the pre-, early-, and late-IT era cohorts, respectively, with the largest increase occurring between the early-IT and late-IT eras (1-year OS: 20.6% vs. 17.0% vs. 38.2%, 2-year OS: 10.5% vs. 14.2% vs. 27.1%, and median OS: 5 vs. 6 vs. 8 months, p < 0.001 by log-rank test). CONCLUSION: The introduction of IT for malignant melanomas has significantly improved the survival outcomes of melanoma patients with brain metastasis. Novel treatment paradigms involving IT with other adjuvant therapies need to be explored to further improve intracranial activity in melanoma patients.

INTRODUCTION Glioblastoma (GBM) is the most aggressive primary brain tumor with a universally poor prognosis. Living in disadvantaged neighborhoods is associated with poor health outcomes, including increased cancer incidence. This study was designed to elucidate the relationship between GBM patients’ survival, isocitrate dehydrogenase (IDH) mutation status, and residential areas of deprivation in the state of Pennsylvania. METHODS Patients from Pennsylvania with a pathological diagnosis of GBM WHO Grade IV between January 2007 and December 2018 were retrospectively reviewed in the Penn State Health database. Demographic variables and molecular features were assessed. Area Deprivation Index (ADI) is a validated measure of regional socioeconomic deprivation that indexes neighborhoods by percentile, with low ADI scores representing less deprivation. Patients were assigned to low ( < 50) or high ( ≥ 51) ADI groups. Survival was measured against IDH status and ADI score; log-rank tests were performed. RESULTS 121 GBM WHO Grade IV patients were identified (median age at diagnosis: 63, 39.7% female, 60.3% male, 93.4% of white race). Among those, 64 (52.9%) had low ADI, and 57 (47.1%) had high ADI. Patients with high ADI had similar overall survival (OS) rates and progression free survival (PFS) at 18 months (56% OS, 95% confidence interval [CI]: 48-64%; 37.4% PFS, 95%CI: 30-44%; P=0.27) compared to patients with low ADI (50% OS, 95%CI: 43-57%; 32.4% PFS, 95%CI: 26-39%; P = 0.27). Further classification by IDH status resulted in 17 (14%) IDH mutant (IDHm) and 104 (86%) IDH wildtype (IDHwt) patients. Survival analysis demonstrated no significant difference in OS between IDHwt and IDHm patients, regardless of ADI score. CONCLUSION The aggressive nature of GBM requires early diagnostic approaches to impact survival. Living in socioeconomic disadvantaged areas may diminish survival outcomes; however, our data indicate that GBM may be too aggressive for ADI to have a significant impact on prognosis.

Gastric glomus tumours (GGTs) are rare predominantly benign, mesenchymal neoplasms that commonly arise from the muscularis or submucosa of the gastric antrum and account for <1% of gastrointestinal soft-tissue tumours. Historically, GGT has been difficult to diagnose preoperatively due to the lack of unique clinical, endoscopic and CT features. We present a case of an incidentally identified GGT in an asymptomatic man that was initially considered a neuroendocrine tumour (NET) by preoperative fine-needle aspiration biopsy with focal synaptophysin reactivity. An elective robotic distal gastrectomy and regional lymphadenectomy were performed. Postoperative review by pathology confirmed the diagnosis of GGT. GGTs should be considered by morphology as a differential diagnosis of gastric NET on cytology biopsy, especially if there is focal synaptophysin reactivity. Additional staining for SMA and BRAF, if atypical/malignant, can help with this distinction. Providers should be aware of the biological behaviour and treatment of GGTs.