Lockdowns implemented during the COVID-19 pandemic were utilized to evaluate the associations between “social distancing policies” (SDPs), traffic congestion, mobility, and NO2 air pollution. Spatiotemporal linear mixed models were used on city-day data from 22 US cities to estimate the associations between SDPs, traffic congestion and mobility. Autoregressive integrated moving average models with Fourier terms were then used on historical data to forecast expected 2020 NO2. Time series models were subsequently employed to measure how much reductions in local traffic congestion were associated with lower-than-forecasted 2020 NO2. Finally, the equity of NO2 pollution was assessed with community-level sociodemographics. When cities’ most stringent SDPs were implemented, they observed a 23.47 (95% CI: 18.82–28.12) percent reduction in average daily congestion and a 13.48 (95% CI: 10.36–16.59) percent decrease in average daily mobility compared to unrestricted days. For each standard deviation (8.38%) reduction in local daily congestion, average daily NO2 decreased by 1.37 (95% CI: 1.24–1.51) parts per billion relative to its forecasted value. Citizenship, education, and race were associated with elevated absolute NO2 pollution levels but were not detectibly associated with reductions in 2020 NO2 relative to its forecasted value. This illustrates the immediate behavioral and environmental impacts of local SDPs during the COVID-19 pandemic.

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This clinical trial combined fulvestrant with the anti-androgen enzalutamide in women with metastatic ER+/HER2− breast cancer (BC). Eligible patients were women with ECOG 0–2, ER+/HER2− measurable or evaluable metastatic BC. Prior fulvestrant was allowed. Fulvestrant was administered at 500 mg IM on days 1, 15, 29, and every 4 weeks thereafter. Enzalutamide was given at 160 mg po daily. Fresh tumor biopsies were required at study entry and after 4 weeks of treatment. The primary efficacy endpoint of the trial was the clinical benefit rate at 24 weeks (CBR24). The median age was 61 years (46–87); PS 1 (0–1); median of 4 prior non-hormonal and 3 prior hormonal therapies for metastatic disease. Twelve had prior fulvestrant, and 91% had visceral disease. CBR24 was 25% (7/28 evaluable). Median progression-free survival (PFS) was 8 weeks (95% CI: 2–52). Adverse events were as expected for hormonal therapy. Significant (p < 0.1) univariate relationships existed between PFS and ER%, AR%, and PIK3CA and/or PTEN mutations. Baseline levels of phospho-proteins in the mTOR pathway were more highly expressed in biopsies of patients with shorter PFS. Fulvestrant plus enzalutamide had manageable side effects. The primary endpoint of CBR24 was 25% in heavily pretreated metastatic ER+/HER2− BC. Short PFS was associated with activation of the mTOR pathway, and PIK3CA and/or PTEN mutations were associated with an increased hazard of progression. Thus, a combination of fulvestrant or other SERD plus AKT/PI3K/mTOR inhibitor with or without AR inhibition warrants investigation in second-line endocrine therapy of metastatic ER+ BC.

Introduction Historical reservations regarding radiosurgery (SRS) for small-cell-lung-cancer (SCLC) brain metastases (BrM) include concerns for short-interval/diffuse CNS-progression, poor prognoses, and increased neurological mortality specific to SCLC histology. We compared SRS outcomes for SCLC and non-small-cell-lung-cancer (NSCLC) where SRS is well established. Methods Multicenter first-line SRS outcomes for SCLC and NSCLC from 2000-2022 were retrospectively collected (N=892-SCLC/N=4,785-NSCLC). Data from the prospective JLGK0901 SRS trial were analyzed as a comparison cohort (N=98-SCLC/N=794-NSCLC). OS and CNS-progression were analyzed using Cox-Proportional-Hazard and Fine-Gray models, respectively, with multivariable (MV) adjustment (including age/sex/performance-status/year/extracranial disease/BrM-number/BrM-volume). Mutation-stratified analyses were performed in propensity score-matched (PSM) retrospective cohorts of EGFR/ALK-positive-NSCLC, mutation-negative-NSCLC, and SCLC. Results OS was superior with NSCLC over SCLC in the retrospective dataset (median-OS, 10.5 vs 8.6 months, MV-p&lt;0.001) and JLGK0901. Hazard estimates for first CNS-progression favoring NSCLC were similar in both datasets but reached significance in the retrospective dataset only (MV-HR:0.82 [95%-CI:0.73-0.92], p=0.001). In the PSM cohorts, there were continued OS advantages for NSCLC (median-OS, 23.7 [EGFR/ALK-positive-NSCLC] vs 13.6 [mutation-negative-NSCLC] vs 10.4 months [SCLC], pairwise-p-values&lt;0.001), but no significant differences in CNS-progression. Neurological mortality and number of lesions at CNS-progression were similar for NSCLC and SCLC patients. Leptomeningeal-progression was increased in NSCLC patients in the retrospective dataset only (MV-HR:1.61 [95%-CI:1.14-2.26], p=0.007). Conclusion After SRS, SCLC was associated with shorter OS compared to NSCLC. CNS progression occurred earlier in SCLC overall but was similar in patients matched on baseline characteristics. Neurological mortality, lesions at CNS-progression, and leptomeningeal-progression were comparable. These findings may better inform clinical decision-making for SCLC patients.