Faculty Bibliography

Individuals with cancer exposed to SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), are more susceptible to COVID-19-related complications [...].

South Asians are among the fastest-growing immigrant population group in the United States (U.S.) with a unique disease risk profile. Due in part to immigration and acculturation factors, South Asians engage differently with behavioural risk factors (e.g. smoking, alcohol intake, physical activity, sedentary behaviour, and diet) for hypertension, which may be modified for the primary prevention of cardiovascular disease. Using data from the Mediators of Atherosclerosis in South Asians Living in America cohort, we conducted a cross-sectional analysis to evaluate the association between behavioural risk factors for cardiovascular disease and diet. We created a behavioural risk factor score based on smoking status, alcohol consumption, physical activity, and TV watching. We also calculated a Dietary Approaches to Stop Hypertension (DASH) dietary score based on inclusion of relevant dietary components. We used both scores to examine the association between engaging with risk factors for hypertension and the DASH diet among a cohort of South Asian adults. We found that participants with 3-4 behavioural risk factors had a DASH diet score that was 3 units lower than those with no behavioural risk factors (aβ: -3.25; 95% CI: -4.28, -2.21) and were 86% less likely to have a DASH diet score in the highest category compared to the lowest DASH diet score category (aOR: 0.14; 95% CI: 0.05, 0.37) in the fully adjusted models. These findings highlight the relationship between behavioural risk factors for hypertension among South Asians in the U.S.

INTRODUCTION/UNASSIGNED:South Asian adults are at high risk for atherosclerotic cardiovascular disease, for which coronary artery calcification is an early predictor. Adherence to the Dietary Approaches to Stop Hypertension diet is a modifiable risk factor that may mitigate the progression of coronary artery calcification and atherosclerotic cardiovascular disease. METHODS/UNASSIGNED:Using data from the Mediators of Atherosclerosis in South Asians Living in America cohort, the authors calculated a Dietary Approaches to Stop Hypertension dietary score (categorized as low, moderate, and high) to examine the associations of Dietary Approaches to Stop Hypertension diet adherence with coronary artery calcification after a 5-year follow up. RESULTS/UNASSIGNED:The authors found that participants in the high Dietary Approaches to Stop Hypertension category were 41% less likely to have coronary artery calcification score >100 (age-adjusted incidence rate ratio=0.59; 95% CI=0.36, 0.95) than those in the low category; this association was attenuated in multivariable models. Differences were observed by sex. Men in the high Dietary Approaches to Stop Hypertension category were 51% less likely to have coronary artery calcification score >100 (adjusted incidence rate ratio=0.49; 95% CI=0.26, 0.95) and experienced 0.46-fold coronary artery calcification change (fold change=0.46; 95% CI=0.18, 0.90) in multivariable models. CONCLUSIONS/UNASSIGNED:The findings indicate a relationship between Dietary Approaches to Stop Hypertension diet and early predictors of atherosclerotic cardiovascular disease risk among South Asians living in the U.S., particularly men.

The objective of this multicenter retrospective study was to examine the incidence, patient characteristics, pathology, and outcomes associated with Epstein-Barr virus (EBV)-related CNS lymphoma (CNSL) in older patients. Among 309 CNSL patients aged ≥60, 11.7% had EBV + tumors of which 72.2% were solid organ transplant (SOT)-related post-transplant lymphoproliferative disorders (PTLD). Younger age, SOT or autoimmune disease, and immunosuppressive treatment correlated highly with EBV-positivity. EBV + tumors were associated with absent C-MYC and BCL6 expression. EBV + PTLD was more likely to be associated with the absence of CD5 expression. EBV + non-PTLD had better median OS (not reached) compared to EBV + PTLD (10.8 months) and EBV-negative patients (43 months). Multivariable Cox regression analysis showed that age, performance status, and PTLD were negative predictors of OS. EBV status and immunosuppressive treatment were not correlated with OS. Our findings merit further investigation of EBV + PCNSL tumors and EBV-directed therapies.

There is a paucity of large-scale data delineating outcomes and prognostication of older patients with primary central nervous system lymphoma (PCNSL). We retrospectively analyzed 539 newly-diagnosed PCNSL patients ages ≥60 years across 20 U.S. academic centers. The median age was 70 years (range 60-88); at least one geriatric syndrome was present in 46%; the median Cumulative Index Ratings Scale-Geriatrics (CIRS-G) score was 6 (range, 0-27); and 36% had impairment in activities of daily living (ADL). The most common induction regimens were high-dose methotrexate (HD-MTX) ± rituximab; methotrexate, temozolomide, rituximab (MTR); and rituximab, methotrexate, procarbazine, vincristine (R-MPV). Overall, 70% of patients achieved remission, with 14% undergoing consolidative autologous stem cell transplant (ASCT) and 24% receiving maintenance. With 58-month median follow-up, median progression-free survival (PFS) and overall survival (OS) were 17 months (95% CI 13-22 months) and 43 months (95% CI 31-56 months), respectively. Three-year PFS and OS were highest with MTR (55% and 74%, respectively). With single-agent methotrexate ± rituximab, 3-year PFS and OS were 30% (p = .0002) and 47% (p = .0072). On multivariate analysis, increasing age at diagnosis and Cooperative Oncology Group (ECOG) performance status (PS) was associated with inferior PFS; age, hypoalbuminemia, higher CIRS-G score, and ECOG PS adversely affected OS. Among patients receiving maintenance, 3-year PFS was 65% versus 45% without maintenance (p = 0.02), with 3-year OS of 84% versus 61%, respectively (p = .0003). Altogether, outcomes in older PCNSL patients appeared optimized with HD-MTX combination induction regimens and maintenance therapy. Furthermore, several prognostic factors, including geriatric measures, were associated with inferior outcomes.

IMPORTANCE:There is a disproportionately greater burden of COVID-19 among Hispanic and non-Hispanic Black individuals, who also experience poorer cancer outcomes. Understanding individual-level and area-level factors contributing to inequities at the intersection of COVID-19 and cancer is critical. OBJECTIVE:To evaluate associations of individual-level and area-level social determinants of health (SDOH) with delayed or discontinued cancer treatment following SARS-CoV-2 infection. DESIGN, SETTING, AND PARTICIPANTS:This retrospective, registry-based cohort study used data from 4768 patients receiving cancer care who had positive test results for SARS-CoV-2 and were enrolled in the American Society for Clinical Oncology COVID-19 Registry. Data were collected from April 1, 2020, to September 26, 2022. EXPOSURES:Race and ethnicity, sex, age, and area-level SDOH based on zip codes of residence at the time of cancer diagnosis. MAIN OUTCOMES AND MEASURES:Delayed (≥14 days) or discontinued cancer treatment (any cancer treatment, surgery, pharmacotherapy, or radiotherapy) and time (in days) to restart pharmacotherapy. RESULTS:A total of 4768 patients (2756 women [57.8%]; 1558 [32.7%] aged ≥70 years at diagnosis) were included in the analysis. There were 630 Hispanic (13.2%), 196 non-Hispanic Asian American or Pacific Islander (4.1%), 568 non-Hispanic Black (11.9%), and 3173 non-Hispanic White individuals (66.5%). Compared with non-Hispanic White individuals, Hispanic and non-Hispanic Black individuals were more likely to experience a delay of at least 14 days or discontinuation of any treatment and drug-based treatment; only estimates for non-Hispanic Black individuals were statistically significant, with correction for multiple comparisons (risk ratios [RRs], 1.35 [95% CI, 1.22-1.49] and 1.37 [95% CI, 1.23-1.52], respectively). Area-level SDOH (eg, geography, proportion of residents without health insurance or with only a high school education, lower median household income) were associated with delayed or discontinued treatment. In multivariable Cox proportinal hazards regression models, estimates suggested that Hispanic (hazard ratio [HR], 0.87 [95% CI, 0.71-1.05]), non-Hispanic Asian American or Pacific Islander (HR, 0.79 [95% CI, 0.46-1.35]), and non-Hispanic Black individuals (HR, 0.81 [95% CI, 0.67-0.97]) experienced longer delays to restarting pharmacotherapy compared with non-Hispanic White individuals. CONCLUSIONS AND RELEVANCE:The findings of this cohort study suggest that race and ethnicity and area-level SDOH were associated with delayed or discontinued cancer treatment and longer delays to the restart of drug-based therapies following SARS-CoV-2 infection. Such treatment delays could exacerbate persistent cancer survival inequities in the United States.

High blood pressure is an important predictor of atherosclerotic cardiovascular disease (ASCVD), particularly among South Asians, who are at higher risk for ASCVD when compared to other population groups. The Dietary Approaches to Stop Hypertension (DASH) dietary pattern is established as the best proven nonpharmacological approach to preventing hypertension in adults. Using data from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort, we calculated a DASH dietary score to examine the association between adherence to the DASH diet and its components, and prevalent and incident hypertension and systolic and diastolic blood pressure, after five years of follow-up. We found that the relative risk ratio (RRR) of incident hypertension was 67% lower among participants in the highest DASH diet score category (aRRR: 0.33; 95% CI: 0.13, 0.82; p_trend = 0.02) compared with those in the lowest DASH diet score category in fully adjusted models. These findings are consistent with previous clinical trials and large prospective cohort studies, adding to evidence that supports the diet-disease relationship established between DASH diet and hypertension. This study is the first to examine DASH diet adherence and hypertension among South Asian adults in the U.S.

PURPOSE/OBJECTIVE:Veliparib (V), an oral poly(ADP-ribose) polymerase (PARP) inhibitor, potentiates effects of alkylating agents and topoisomerase inhibitors in preclinical tumor models. We conducted a phase I trial of V with iv cyclophosphamide (C) and V plus iv doxorubicin (A) and C. METHODS:) Day 3 in 21-day cycles. In Group 3, patients received AC Day 1 plus V Days 1-7, and in Group 4, AC Day 1 plus V Days 1-14 was given in 21-day cycles to evaluate effects on γH2AX foci. RESULTS:Eighty patients were enrolled. MTD was not reached for V and C. MTD for V and AC was V 100 mg every 12 h Days 1-4 with AC (60/600 mg/m2) Day 3 every 21 days. V PK appears to be dose-dependent and has no effect on the PK of C. Overall, neutropenia and anemia were the most common adverse events. Objective response in V and AC treated groups was 22% (11/49). Overall clinical benefit rate was 31% (25/80). PAR decreased in PBMCs. Percentage of γH2AX-positive CTCs increased after treatment with V and AC. CONCLUSION/CONCLUSIONS:V and AC can be safely combined. Activity was observed in patients with metastatic breast cancer.

PURPOSE/OBJECTIVE:Limited epidemiologic data are available on the expression of adipokines leptin (LEP) and adiponectin (ADIPOQ) and adipokine receptors (LEPR, ADIPOR1, ADIPOR2) in the breast tumor microenvironment (TME). The associations of gene expression of these biomarkers with tumor clinicopathology are not well understood. METHODS:NanoString multiplexed assays were used to assess the gene expression levels of LEP, LEPR, ADIPOQ, ADIPOR1, and ADIPOR2 within tumor tissues among 162 Black and 55 White women with newly diagnosed breast cancer. Multivariate mixed effects models were used to estimate associations of gene expression with breast tumor clinicopathology (overall and separately among Blacks). RESULTS:Black race was associated with lower gene expression of LEPR (P = 0.002) and ADIPOR1 (P = 0.01). Lower LEP, LEPR, and ADIPOQ gene expression were associated with higher tumor grade (P = 0.0007, P < 0.0001, and P < 0.0001, respectively) and larger tumor size (P < 0.0001, P = 0.0005, and P < 0.0001, respectively). Lower ADIPOQ expression was associated with ER- status (P = 0.0005), and HER2-enriched (HER2-E; P = 0.0003) and triple-negative (TN; P = 0.002) subtypes. Lower ADIPOR2 expression was associated with Ki67+ status (P = 0.0002), ER- status (P < 0.0001), PR- status (P < 0.0001), and TN subtype (P = 0.0002). Associations of lower adipokine and adipokine receptor gene expression with ER-, HER2-E, and TN subtypes were confirmed using data from The Cancer Genome Atlas (P-values < 0.005). CONCLUSION/CONCLUSIONS:These findings suggest that lower expression of ADIPOQ, ADIPOR2, LEP, and LEPR in the breast TME might be indicators of more aggressive breast cancer phenotypes. Validation of these findings are warranted to elucidate the role of the adipokines and adipokine receptors in long-term breast cancer prognosis.

Data addressing prognostication in patients with HIV related Burkitt lymphoma (HIV-BL) currently treated remain scarce. We present an international analysis of 249 (United States: 140; United Kingdom: 109) patients with HIV-BL treated from 2008 to 2019 aiming to identify prognostic factors and outcomes. With a median follow up of 4.5 years, the 3-year progression-free survival (PFS) and overall survival (OS) were 61% (95% confidence interval [CI] 55% to 67%) and 66% (95%CI 59% to 71%), respectively, with similar results in both countries. Patients with baseline central nervous system (CNS) involvement had shorter 3-year PFS (36%) compared to patients without CNS involvement (69%; P < .001) independent of frontline treatment. The incidence of CNS recurrence at 3 years across all treatments was 11% with a higher incidence observed after dose-adjusted infusional etoposide, doxorubicin, vincristine, prednisone, cyclophosphamide (DA-EPOCH) (subdistribution hazard ratio: 2.52; P = .03 vs other regimens) without difference by CD4 count 100/mm3. In multivariate models, factors independently associated with inferior PFS were Eastern Cooperative Oncology Group (ECOG) performance status 2-4 (hazard ratio [HR] 1.87; P = .007), baseline CNS involvement (HR 1.70; P = .023), lactate dehydrogenase >5 upper limit of normal (HR 2.09; P < .001); and >1 extranodal sites (HR 1.58; P = .043). The same variables were significant in multivariate models for OS. Adjusting for these prognostic factors, treatment with cyclophosphamide, vincristine, doxorubicin, and high-dose methotrexate, ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) was associated with longer PFS (adjusted HR [aHR] 0.45; P = .005) and OS (aHR 0.44; P = .007). Remarkably, HIV features no longer influence prognosis in contemporaneously treated HIV-BL.