Impact of the 2021 CKD-EPI equation on anticancer pharmacotherapy in black and non-black cancer patients.

Cancer and kidney disease disproportionately impact Black patients. The CKD-EPI2021 equation was developed to estimate glomerular filtration rate (eGFR) without using race. We assessed the impact of using CKD-EPI2021 instead of CKD-EPI2009 or Cockcroft-Gault (CG) on dosing and eligibility of anticancer drugs in Black and non-Black patients. Utilizing the National Cancer Institute Theradex database, deindexed eGFR (mL/min) was calculated for 3931 patients (8.6 % Black) using CKD-EPI2021, CKD-EPI2009, and CG. Dosing simulations based on each eGFR were performed for ten anticancer drugs with kidney function-based eligibility or dosing cutoffs. eGFR differences using CKD-EPI2021 versus CKD-EPI2009 varied between Black and non-Black patients (p < 0.001); on average, Black patients had 10.3 mL/min lower eGFR and non-Black patients had 4.2 mL/min higher eGFR using CKD-EPI2021. This corresponded to a difference in relative odds of cisplatin ineligibility using CKD-EPI2021 versus CKD-EPI2009; Black patients had 48 % higher odds of ineligibility and non-Black patients had 27 % lower odds of ineligibility using CKD-EPI2021 (p < 0.001). When using CKD-EPI2021 versus CG, eGFR differences were similar between Black and non-Black patients (p = 0.679) and relative difference in odds of cisplatin ineligibility did not vary. Using CKD-EPI2021 versus CKD-EPI2009 differentially impacts Black versus non-Black cancer patients; Black patients have lower calculated eGFR and are less likely to receive full doses of drug using CKD-EPI2021. From the historical default of CG, adopting CKD-EPI2021 would not disparately impact patients based on race, but would result in Black patients being less likely to receive full doses of drug than if CKD-EPI2009 were used.

Racial disparity in tumor microenvironment and distant recurrence in residual breast cancer after neoadjuvant chemotherapy.

Black, compared to white, women with residual estrogen receptor-positive (ER+) breast cancer after neoadjuvant chemotherapy (NAC) have worse distant recurrence-free survival (DRFS). Such racial disparity may be due to difference in density of portals for systemic cancer cell dissemination, called TMEM doorways, and pro-metastatic tumor microenvironment (TME). Here, we evaluate residual cancer specimens after NAC from 96 Black and 87 white women. TMEM doorways are visualized by triple immunohistochemistry, and cancer stem cells by immunofluorescence for SOX9. The correlation between TMEM doorway score and pro-metastatic TME parameters with DRFS is examined using log-rank and multivariate Cox regression. Black, compared to white, patients are more likely to develop distant recurrence (49% vs 34.5%, p = 0.07), receive mastectomy (69.8% vs 54%, p = 0.04), and have higher grade tumors (p = 0.002). Tumors from Black patients have higher TMEM doorway and macrophages density overall (p = 0.002; p = 0.002, respectively) and in the ER+/HER2- (p = 0.02; p = 0.02, respectively), but not in the triple negative disease. Furthermore, high TMEM doorway score is associated with worse DRFS. TMEM doorway score is an independent prognostic factor in the entire study population (HR, 2.02; 95%CI, 1.18-3.46; p = 0.01), with a strong trend in ER+/HER2- disease (HR, 2.38; 95%CI, 0.96-5.95; p = 0.06). SOX9 expression is not associated with racial disparity in TME or outcome. In conclusion, higher TMEM doorway density in residual breast cancer after NAC is associated with higher distant recurrence risk, and Black patients are associated with higher TMEM doorway density, suggesting that TMEM doorway density may contribute to racial disparities in breast cancer.

Predictive Factors for Cancer Treatment Delay in a Racially Diverse and Socioeconomically Disadvantaged Urban Population.

PURPOSE: Incremental delays in time to treatment initiation (TTI) have been shown to cause a proportional, increased independent risk of disease-specific mortality for breast cancer, colorectal cancer (CRC), head and neck cancer (HNC), non-small-cell lung cancer (NSCLC), and pancreatic cancer. Studies suggest that delays are associated with racial and socioeconomic disparities. We evaluated associations between patient factors and TTI to identify those associated with delay. MATERIALS AND METHODS: This is a retrospective cohort study at an urban community-based academic center of patients diagnosed with or referred for curative-intent treatment of breast cancer, CRC, HNC, NSCLC, and pancreatic cancer from January 2019 to December 2021. Variables of interest included Charlson Comorbidity Index (CCI) score, insurance type, language preference, and inpatient admission 30 days before diagnosis. Factors associated with TTI delay, defined as TTI ≥ 30 days, were assessed using multivariable logistic regression. RESULTS: Among 2,543 patients (69% female), the mean age was 63.4 years and the median TTI was 25 days (IQR, 6-44). Within multivariable models, patients treated as outpatient and not admitted 30 days before diagnosis experienced statistically significant greater delay for CRC (odds ratio [OR], 2.82; 95% CI, 1.71 to 4.66) and NSCLC (OR, 2.11; 95% CI, 1.31 to 3.39). Higher CCI score was associated with delay for HNC (OR, 2.63; 95% CI, 1.04 to 6.66) and NSCLC (OR, 1.75; 95% CI, 1.14 to 2.71). For breast cancer, uninsured and Spanish-speaking patients (OR, 1.79; 95% CI, 1.21 to 2.67) experienced increased TTI. CONCLUSION: Care coordination/compliance (eg, inpatient 30 days before diagnosis), clinical (eg, medical comorbidities), and socioeconomic (eg, uninsured status) predictors for delayed TTI were identified and may inform delay minimizing interventions. Our data support evidence that TTI delays are associated with demographic and socioeconomic disparities. Existing disparities are likely exacerbated by delays that disproportionately affect patients with care coordination/compliance issues, multiple comorbidities, and lower socioeconomic status.

Association Between Socioeconomic and Insurance Status and Delayed Diagnosis of Gastrointestinal Cancers.

INTRODUCTION: Association between socioeconomic status (SES) and stage at diagnosis in gastrointestinal (GI) cancers is poorly described. Relationship between low SES and stage at diagnosis as well as the mediating role of insurance status (IS) was examined. METHODS: The Surveillance, Epidemiology, and End Results database was queried for esophageal, gastric, liver, biliary, pancreatic, colon, and rectal cancers diagnosed in 2012-2016. Relationship between census-tract SES index quintiles and late diagnosis (distant disease at diagnosis) was examined. Uni and multivariable logistic regressions were performed. Mediation analyses were conducted to determine the degree to which IS (private/Medicare versus Medicaid/uninsured) mediates the relationship between SES and late diagnosis of cancer. RESULTS: Analysis included 236,713 adult patients from 18 Surveillance, Epidemiology, and End Results areas. In univariable analysis, lowest SES quintile was significantly associated with late diagnosis for all cancers except gastric and biliary cancers. In multivariable analysis controlling for age, gender, marital status and race, this association remained significant for liver (odds ratio (OR) 1.41 [95% confidence interval (CI) 1.25-1.58]), pancreatic (OR 1.13 [95% CI 1.06-1.21]), and rectal (OR 1.31 [95% CI 1.20-1.42]) cancers. Further controlling for IS showed the largest effect size reduction for rectal cancer (OR 1.18 [95% CI 1.09-1.29]), with IS mediating 36.5% (P < 0.0001) of SES effect. CONCLUSIONS: Low SES is an independent risk factor for late diagnosis in liver, pancreas, and rectal cancers. Insurance is not a critical mediator of difference by SES for most GI cancers, with the exception of rectal cancer. Further research is needed to understand factors beyond IS that can account for SES differences in late diagnosis for GI cancers. Insurance related differences for rectal cancer deserves further attention.

Depressive symptoms mediate the relationship between diabetes and cognitive performance in a community-based sample of older adults.

AIMS: To evaluate whether diabetes and prediabetes are associated with impaired cognitive performance among older adults and examine depressive symptoms as a mediator. METHODS: We used cross-sectional data from the Einstein Aging Study, a systematically recruited, community-based cohort study of diverse older adults (N = 794; Age Mean (SD) = 78.9 (5.3); 64.4% Non-Hispanic White, 28.7% Non-Hispanic Black, 5.7% Hispanic). Diabetes status was established via self-reported diagnosis, prescribed medications, and fasting blood glucose. Depressive symptoms were assessed using the Geriatric Depression Scale. Cognitive tests included Digit Symbol, Trails-B, Free Recall, Category Fluency, Boston Naming, and Block Design. Linear regression and mediation analyses were applied. RESULTS: Compared to those without diabetes, diabetes was associated with worse performance on all cognitive tests (ps < 0.05), except Trails-B (p = 0.53), and increased depressive symptoms (p < 0.01). For diabetes, mediation via increased depressive symptoms was observed for Free Recall (p = 0.044), Category Fluency (p = 0.033), and Boston Naming (p = 0.048). CONCLUSIONS: Diabetes was consistently associated with worse cognitive performance and increased depressive symptoms among this older cohort, while prediabetes was not. Mediation findings suggest depressive symptoms may be a biobehavioral pathway linking diabetes and cognition, though the temporal sequence is unclear. If causal, addressing both diabetes and depressive symptoms among older adults may protect cognitive function.

Racial disparity in distant recurrence-free survival in patients with localized breast cancer: A pooled analysis of National Surgical Adjuvant Breast and Bowel Project trials.

BACKGROUND: Black race is associated with worse outcome in patients with breast cancer. The distant relapse-free survival (DRFS) between Black and White women with localized breast cancer who participated in National Cancer Institute-sponsored clinical trial was evaluated. METHODS: Pooled data were analyzed from 8 National Surgical Adjuvant Breast and Bowel Project (NSABP) trials including 9702 women with localized breast cancer treated with adjuvant chemotherapy (AC, n = 7485) or neoadjuvant chemotherapy (NAC, n = 2217), who self-reported as Black (n = 1070) or White (n = 8632) race. The association between race and DRFS was analyzed using log-rank tests and multivariate Cox regression. RESULTS: After adjustment for covariates including age, tumor size, nodal status, body mass index and taxane use, and treatment (AC vs NAC), Black race was associated with an inferior DRFS in estrogen receptor-positive (ER+; hazard ratio [HR], 1.24; 95% CI, 1.05-1.46; P = .01), but not in ER- disease (HR, 0.97; 95% CI, 0.83-1.14; P = .73), and significant interaction between race and ER status was observed (P = .03). There was no racial disparity in DRFS among patients with pathologic complete response (pCR) (log-rank P = .8). For patients without pCR, Black race was associated with worse DRFS in ER+ (HR, 1.67; 95% CI, 1.14-2.45; P = .01), but not in ER- disease (HR, 0.91; 95% CI, 0.65-1.28; P = .59). CONCLUSIONS: Black race was associated with significantly inferior DRFS in ER+ localized breast cancer treated with AC or NAC, but not in ER- disease. In the NAC group, racial disparity was also observed in patients with residual ER+ breast cancer at surgery, but not in those who had pCR. LAY SUMMARY: Black women with breast cancer have worse outcomes compared with White women. We investigated if this held true in the context of clinical trials that provide controlled treatment setting. Black women with cancer expressing estrogen receptors (ERs) had worse outcome than White women. If breast cancers did not express ERs, there was no racial disparity in outcome. We also observed racial disparity in women who received chemotherapy before their cancer was removed, but only if they had cancer expressing ERs and residual disease on completion of treatment. If the cancer disappeared with presurgical chemotherapy, there was no racial disparity.

The Effect of a Multidisciplinary Spine Clinic on Time to Care in Patients with Chronic Back and/or Leg Pain: A Propensity Score-Matched Analysis.

Chronic back and leg pain are leading causes of disability worldwide. The purpose of this study was to compare the care in a unidisciplinary (USC) versus multidisciplinary (MSC) spine clinic, where patients are evaluated by different specialists during the same office visit. Adult patients presenting with a chief complaint of back and/or leg pain between June 2018 and July 2019 were assessed for eligibility. The main outcome measures included the first treatment recommendations, the time to treatment order, and the time to treatment occurrence. A 1:1 propensity score-matched analysis was performed on 874 patients (437 in each group). For all patients, the most common recommendation was physical therapy (41.4%), followed by injection (14.6%), and surgery (9.7%). Patients seen in the MSC were more likely to be recommended injection (p < 0.001) and less likely to be recommended surgery as first treatment (p = 0.001). They also had significantly shorter times to the injection order (log-rank test, p = 0.004) and the injection occurrence (log-rank test, p < 0.001). In this study, more efficient care for patients with back and/or leg pain was delivered in the MSC setting, which was evidenced by the shorter times to the injection order and occurrence. The impact of the MSC approach on patient satisfaction and health-related quality-of-life outcome measures warrants further investigation.

The 21-gene recurrence score in early non-ductal breast cancer: a National Cancer Database analysis.

The 21-gene recurrence score (RS) is prognostic for recurrence and predictive of chemotherapy benefit in early estrogen receptor-positive (ER +) HER2-negative (HER2-) breast cancer (BCA). We evaluated clinicopathologic characteristics, RS and chemotherapy benefit in invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and carcinomas of mixed histologies (ductal + lobular (DLC), ductal + other (DOC), lobular + other (LOC)). Women diagnosed between 1/1/2010 and 1/1/2014 with ER + HER2- BCA, measuring <5 cm, with 0-3 involved axillary nodes, surgery as first treatment, and available RS, were identified from the NCDB. Associations between categorical variables were examined using chi-square test. Cox proportional hazards model was used to examine overall survival (OS) differences among histology subtypes. IDC was associated with smaller size, high grade, and RS > 26. ILC was associated with larger size, and least likely to be high grade (p < 0.0001). Lobular histology was associated with lower incidence of RS > 26. IDC patients (pts) were more likely to receive chemotherapy than pts with other histologies (p < 0.0001). OS for IDC, ILC and DOC were similar. DLC was associated with improved OS (HR 0.82, p = 0.02). Adjuvant chemotherapy was associated with improved OS in IDC (HR = 0.76, p < 0.0001) but not in ILC (HR = 0.99, p = 0.93), DLC (HR = 1.04, p = 0.86), DOC (HR = 0.87, p = 0.71), or LOC (HR = 2.91, p = 0.10). Lobular and mixed BCA histologies have distinct clinicopathologic features compared with IDC, and are less likely to have high RS. OS is similar for IDC and ILC. Although chemotherapy benefit was seen only in IDC, benefit for ILC with RS > 26 cannot be excluded.