BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced melanoma, but racial disparities in melanoma outcomes continue. These inequities are not fully explained by individual factors. OBJECTIVE: To investigate the associations of neighborhood factors with the use of ICIs in metastatic melanoma. METHODS: We conducted a retrospective cohort study of commercially insured US adults with metastatic melanoma diagnosed between January 2011 and December 2020. We examined the associations between the county-level percentage of population from racial and ethnic minority groups and the time from metastatic melanoma diagnosis to initiating ICIs using Cox proportional hazards models adjusting for patient characteristics. RESULTS: We identified 4,052 patients with metastatic melanoma, of which 49% used ICIs. We found that the adoption of ICIs in a county declined with increasing minority quintile (quintile 1: 52.4%, quintile 2: 50.4%, quintile 3: 50.1%, quintile 4: 45.8%, and quintile 5: 44.7%). The delay in ICI initiation also went up as the percentage of minorities in a county increased (log-rank test P = 0.03). Compared with the lowest quintile, the adjusted hazard ratio of ICI initiation of the second, third, fourth, and highest minority quintile was 0.94 (95% CI = 0.81-1.08), 0.88 (95% CI = 0.76-1.02), 0.81 (95% CI = 0.68-0.97), and 0.77 (95% CI = 0.66-0.91), respectively. Secondary analysis revealed that the slower initiation was driven by the counties with the highest percentage of Hispanic population (hazard ratio = 0.74; 95% CI = 0.61-0.89) in both Cox models and sensitivity analyses. High-minority counties correlated with metro areas, higher poverty levels, and a greater number of medical oncologists. CONCLUSIONS: We found that patients with metastatic melanoma living in counties with higher proportion of minorities, particularly of Hispanic origin, are more likely to experience delays in ICI treatment. This study provides important population-level data on neighborhood-level disparity in medication use. More research is needed on the underlying provider- and system-level factors that directly contributed to the lower use of cancer medicines in high-minority areas, which can help inform the development of evidence-based medication use strategies that can improve health outcomes and equity.

Purpose

Prior studies have reported differing results regarding the association between endocrine therapy (ET) in the treatment of breast cancer and dementia risk. However, existing findings may be limited by common sources of bias and confounding. Here we investigate the association of ET utilized in the definitive setting to treat non-metastatic breast cancer with dementia risk accounting for multiple potential sources of bias and confounding.

Patients and methods

We conducted a retrospective study in SEER-Medicare of women aged ≥ 66 years with non-metastatic breast cancer. We examined the risk of all-cause dementia among ET users versus non-ET users using multivariable regression models, accounting for the competing risk of death, and using a start of the follow-up period as 12-months following breast cancer diagnosis for both groups to avoid immortal time bias.

Results

Among 25,777 individuals there were 2,869 incident dementia cases. We found a statistically significantly decreased risk of any dementia among ET users in unadjusted and adjusted models that completely attenuated when accounting for the competing risk of death (hazard ratio, 0.98; 95% confidence interval, 0.90-1.07).

Conclusion

When accounting for common sources of bias and confounding we did not find evidence to support an association between ET in the definitive treatment of non-metastatic breast cancer and dementia risk. These results suggest that ET may not be associated with dementia risk.

Clonal hematopoiesis (CH) mutations are common among individuals without known hematologic disease. CH mutations have been associated with numerous adverse clinical outcomes across many different studies. We systematically reviewed the available literature for clinical outcomes associated with CH mutations in patients without hematologic disease. We searched PubMed, EMBASE, and Scopus for eligible studies. Three investigators independently extracted the data, and each study was verified by a second author. Risk of bias was assessed using the Newcastle-Ottawa Scale. We identified 32 studies with 56 cohorts that examine the association between CH mutations and clinical outcomes. We conducted meta-analyses comparing outcomes among individuals with and without detectable CH mutations. We conducted meta-analyses for cardiovascular diseases (nine studies; HR = 1.61, 95% CI = 1.26-2.07, p = .0002), hematologic malignancies (seven studies; HR = 5.59, 95% CI = 3.31-9.45, p < .0001), therapy-related myeloid neoplasms (four studies; HR = 7.55, 95% CI = 4.3-13.57, p < .001), and death (nine studies; HR = 1.34, 95% CI = 1.2-1.5, p < .0001). The cardiovascular disease analysis was further stratified by variant allele fraction (VAF) and gene, which showed a statistically significant association only with a VAF of ≥ 10% (HR = 1.42, 95% CI = 1.24-1.62, p < .0001), as well as statistically significant associations for each gene examined with the largest magnitude of effect found for CH mutations in JAK2 (HR = 3.5, 95% CI = 1.84-6.68, p < .0001). Analysis of the association of CH mutations with hematologic malignancy demonstrated a numeric stepwise increase in risk with increasing VAF thresholds. This analysis strongly supports the association of CH mutations with a clinically meaningful increased risk of adverse clinical outcomes among individuals without hematologic disease, particularly with increasing VAF thresholds.