Pancreatic cancer remains a leading cause of cancer-related death with few available therapies for advanced disease. Recently, patients with germline BRCA mutations have received increased attention due to advances in the management of BRCA mutated ovarian and breast tumors. Germline BRCA mutations significantly increase risk of developing pancreatic cancer and can be found in up to 8% of patients with sporadic pancreatic cancer. In patients with germline BRCA mutations, platinum-based chemotherapies and poly (ADP-ribose) polymerase inhibitors are effective treatment options which may offer survival benefits. This review will focus on the molecular biology, epidemiology, and management of BRCA -mutated pancreatic cancer. Furthermore, we will discuss future directions for this area of research and promising active areas of research.

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This cohort study describes clinical cumulative incidence of brain metastases among patients with de novo metastatic breast cancer using population health administrative databases in Ontario, Canada.

BACKGROUND: Although neuraxial anesthesia may promote improved outcomes for patients undergoing lower limb revascularization surgery, its use is decreasing over time. Our objective was to estimate variation in neuraxial (versus general) anesthesia use for lower limb revascularization at the hospital, anesthesiologist, surgeon, and patient levels, which could inform strategies to increase uptake. METHODS: Following protocol registration, we conducted a historical cross-sectional analysis of population-based linked health administrative data in Ontario, Canada. All adults undergoing lower limb revascularization surgery between 2009 and 2018 were identified. Generalized linear models with binomial response distributions, logit links and random intercepts for hospitals, anesthesiologists, and surgeons were used to estimate the variation in neuraxial anesthesia use at the hospital, anesthesiologist, surgeon, and patient levels using variance partition coefficients and median odds ratios. Patient-and hospital-level predictors of neuraxial anesthesia use were identified. RESULTS: We identified 11,849 patients; 3489 (29.4%) received neuraxial anesthesia. The largest proportion of variation was attributable to the hospital level (50.3%), followed by the patient level (35.7%); anesthesiologists and surgeons had small attributable variation (11.3% and 2.8%, respectively). Mean odds ratio estimates suggested that 2 similar patients would experience a 5.7-fold difference in their odds of receiving a neuraxial anesthetic were they randomly sent to 2 different hospitals. Results were consistent in sensitivity analyses, including limiting analysis to patients with diagnosed peripheral artery disease and separately to those aged >66 years with complete prescription anticoagulant and antiplatelet usage data. CONCLUSIONS: Neuraxial anesthesia use primarily varies at the hospital level. Efforts to promote use of neuraxial anesthesia for lower limb revascularization should likely focus on the hospital context. (Anesth Analg 2022;135:1282-92) KEY POINTS• Question: To what extent do the hospital, anesthesiologist, and surgeon involved in lower limb revascularization surgery explain variation in use of neuraxial anesthesia? • Findings: The hospital providing care explained the greatest degree of variation in neuraxial anesthesia use, with almost 6-fold differences in use across hospitals. • Meaning: Increasing use of neuraxial anesthesia for lower limb revascularization surgery will likely require a focus on hospital-level structures and processes of care.

2027 Background: Brain Metastases (BrM) are a major cause of morbidity and mortality in patients with metastatic breast cancer (MBC). Real-word data regarding time to development of breast cancer BrM and survival outcomes is lacking. Methods: We conducted a retrospective, observational population-based cohort study to assess treatment patterns and outcomes of patients with de-novo MBC who received radiotherapy for intracranial metastatic disease between January 2009 and December 2018. We used population health administrative databases in Ontario held at ICES, an independent, non-profit research institute. Primary endpoints were i) cumulative incidence of radiotherapy for BrM accounting for the competing risk of death, and ii) time from MBC diagnosis to brain radiotherapy. Secondary endpoints included overall survival (OS) and radiation therapy toxicity. Data were censored if patients were alive on the same therapy at last available follow-up with the last cut-off date being March 31, 2019. Kaplan-Meier analyses were performed for the time to event endpoints and compared using the log-rank test. Cumulative incidence of radiotherapy for BrM from the diagnosis of MBC was calculated using the Cumulative Incidence Function (CIF), accounting for the competing risk of death using a competing risk analysis. Multivariable regression models were used to account for confounding variables. Results: 3,916 patients with de-novo MBC were identified, among whom 549 (14%) developed BrM requiring radiotherapy; cumulative incidence of BrM at 7-year follow-up was highest among patients with HER2+/HR- (34.7%) and HER2+/HR+ (28.1%) disease, followed by triple negative MBC (21.9%) and HR+/HER2- (12.1%) subtypes. The median time from diagnosis of MBC to first radiotherapy treatment for BrM was 7.5 months, 15.0 months, 16.8 months and 19.8 months, in TNBC, HER2+/HR-, HR+/HER2- and HER2+/HR+ subtypes, respectively. The median OS from radiotherapy among patients with breast cancer BrM was 5.1 months in the overall cohort. When analyzed by subtype, the median OS was 2.6 months, 4.8 months, 8.7 months, and 9.4 months in TNBC, HR+/HER2, HER2+/HR+ and HER2+/HR- subtypes, respectively. In a multivariable Cox regression model, a triple negative or HR+/HER2- breast cancer subtype, treatment with WBRT, age > 60 and a high-income quintile (4 or 5) were independently prognostic for shorter OS after adjustment for the index year at diagnosis. Patients treated with stereotactic radiosurgery (SRS) had lower 30-day mortality (6.4% vs. 18.9%, p = 0.003) and lower likelihood of hospitalization within 30 days of therapy (9.6% vs. 20.2%, p = 0.015) compared to patients treated with WBRT. Conclusions: Approximately 1 in 7 patients with MBC will require radiotherapy for BrM. Our data support the use of SRS when clinically indicated and provide insights regarding the time to development of BrM by breast cancer subtype.