Broadening Eligibility Criteria and Diversity among Patients for Cancer Clinical Trials.

BACKGROUND: Certain populations have been historically underrepresented in clinical trials. Broadening eligibility criteria is one approach to inclusive clinical research and achieving enrollment goals. How broadened trial eligibility criteria affect the diversity of eligible participants is unknown. METHODS: Using a nationwide electronic health record-derived deidentified database, we identified a retrospective cohort of patients diagnosed with 22 cancer types between April 1, 2013 and December 31, 2022 who received systemic therapy (N=235,234) for cancer. We evaluated strict versus broadened eligibility criteria using performance status and liver, kidney, and hematologic function around first line of therapy. We performed logistic regression to estimate odds ratios for exclusion by strict criteria and their association with measures of patient diversity, including sex, age, race or ethnicity, and area-level socioeconomic status (SES); estimated the impact of broadening criteria on the number and distribution of eligible patients; and performed Cox regression to estimate hazard ratios for real-world overall survival (rwOS) comparing patients meeting strict versus broadened criteria. RESULTS: When applying common strict cutoffs for eligibility criteria to patients with complete data and weighting each cancer type equally, 48% of patients were eligible for clinical trials. Female (odds ratio, 1.30; 95% confidence interval [CI], 1.25 to 1.35), older (age 75+ vs. 18 to 49 years old: odds ratio, 3.04; 95% CI, 2.85 to 3.24), Latinx (odds ratio, 1.46; 95% CI, 1.39 to 1.54), non-Latinx Black (odds ratio, 1.11; 95% CI, 1.06 to 1.16), and lower-SES patients were more likely to be excluded using strict eligibility criteria. Broadening criteria increased the number of eligible patients by 78%, with the strongest impact for older, female, non-Latinx Black, and lower-SES patients. Patients who met only broadened criteria had worse rwOS versus those with strict criteria (hazard ratio, 1.31; 95% CI, 1.27 to 1.34). CONCLUSIONS: Data-driven evaluation of clinical trial eligibility criteria may optimize the eligibility of certain historically underrepresented groups and promote access to more inclusive trials. (Sponsored by Flatiron Health.).

Lower endoscopy, early-onset, and average-onset colon cancer among Medicaid beneficiaries with and without HIV.

BACKGROUND: Studies suggest a lower colorectal cancer (CRC) risk and lower or similar CRC screening among people with HIV (PWH) compared with the general population. We evaluated the incidence of lower endoscopy and average-onset (diagnosed at ≥50) and early-onset (diagnosed at <50) colon cancer by HIV status among Medicaid beneficiares with comparable sociodemographic factors and access to care. METHODS: We obtained Medicaid Analytic eXtract (MAX) data from 2001 to 2015 for 14 states. We included 41 727 243 and 42 062 552 unique individuals with at least 7 months of continuous eligibility for the endoscopy and colon cancer analysis, respectively. HIV and colon cancer diagnoses and endoscopy procedures were identified from inpatient and other nondrug claims. We used Cox proportional hazards regression models to assess endoscopy and colon cancer incidence, controlling for age, sex, race/ethnicity, calendar year and state of enrollment, and comorbidities conditions. RESULTS: Endoscopy and colon cancer incidence increased with age in both groups. Compared with beneficiaries without HIV, PWH had an increased hazard of endoscopy; this association was strongest among those 18-39 years [hazard ratio: 1.85, 95% confidence interval (95% CI) 1.77-1.92] and attenuated with age. PWH 18-39 years also had increased hazard of early-onset colon cancer (hazard ratio: 1.66, 95% CI:1.05-2.62); this association was attenuated after comorbidity adjustment. Hazard ratios were null among all beneficiaries less than 50 years of age. PWH had a lower hazard of average-onset colon cancer compared with those without HIV (hazard ratio: 0.79, 95% CI: 0.66-0.94). CONCLUSION: PWH had a higher hazard of endoscopy, particularly at younger ages. PWH had a lower hazard of average-onset colon cancer. Early-onset colon cancer was higher among the youngest PWH but not associated with HIV overall.

A national study of alcohol consumption patterns among population-based U.S. cancer survivors compared with cancer-free individuals.

BACKGROUND: This study characterized alcohol consumption behaviors among adult cancer survivors and determined how these behaviors compared with cancer-free individuals using NHANES data (1999-2016). METHODS: Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were estimated using multinomial logistic regression for the association between cancer survivors vs cancer-free individuals and odds of drinking status (former/current/never drinkers), accounting for demographic and socioeconomic factors. Among current drinkers, multivariable logistic regression was used to calculate the aORs for binge drinking and exceeding moderate drinking. RESULTS: A total of 3113 survivors and 39,527 cancer-free individuals were included. Cancer survivors were less likely to be current drinkers (63.4% vs. 72.6% in cancer-free) and were more likely to be former drinkers (24.4% vs. 15.5% in cancer-free). Cancer survivors had significant lower odds of being current vs. never drinkers (aOR, 0.84, 95% CI: 0.71-0.99). By cancer types, cervical cancer survivors were more likely to be binge drinkers (aOR, 2.51, 95% CI: 1.27-4.92), particularly among women aged ≥ 55 years (aOR, 6.90, 95% CI: 1.28-37.3). CONCLUSION: Given the high odds of binge drinking among cervical cancer survivors, public health strategies are needed to reduce alcohol consumption in this group.

Disparities in healthcare utilization and access by length of cancer survivorship among population-based female cancer survivors.

PURPOSE: The current study examined disparities in the associations between medically vulnerable populations and healthcare-related outcomes among population-based female cancer survivors and determined if these associations differed by length of cancer survivorship. METHODS: One thousand eight hundred ninety-seven women with a cancer history from the National Health and Nutrition Examination Survey from 1999 to 2016 contributed data. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated with multivariable logistic regression models to measure the associations between the predictors (race/ethnicity, poverty status, education, comorbidity status, US nativity) and outcomes (perceived health, healthcare utilization and access outcomes), overall and by length of survivorship. RESULTS: There was an average of 14.3 years (SD = 11.7; range = 2-84) since initial cancer diagnosis, with 25.1% being short-term and 74.9% being long-term survivors. Overall, racial/ethnic minority women were more likely to report poor/fair health status (OR, 2.68; 95% CI 1.73-4.15) and utilizing routine care other than a doctor's office/HMO (OR, 1.61; 95% CI 1.12-2.29) in comparison with NHW survivors. Length of survivorship significantly modified the association between race/ethnicity and odds of seeing a mental health provider in the last year (p-interaction = 0.003), with short-term minority survivors being significantly more likely (OR, 2.63; 95% CI 1.29-5.35) and long-term minority survivors being less likely (OR, 0.68; 95% CI 0.37-1.23). CONCLUSIONS: Racial/ethnic disparities exist among female cancer survivors for perceived health status and certain healthcare utilization outcomes, with some differences observed by length of cancer survivorship. IMPLICATIONS FOR CANCER SURVIVORS: This study can begin to inform cancer survivorship care for medically vulnerable women along the cancer continuum.

Evaluation of health perceptions and healthcare utilization among population-based female cancer survivors and cancer-free women.

PURPOSE: Cancer survivors are more likely to report having a poor health status when compared to the general population. Few studies have focused on the impact of cancer on health status and healthcare utilization/access outcomes among women from medically underserved populations. METHODS: 25,741 women with and without a history of cancer from the National Health and Nutrition Examination Survey from 1999 to 2016 contributed data. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression for associations between cancer status and perceived health and healthcare utilization/access outcomes stratified by race/ethnicity, poverty status, education, and comorbidities. RESULTS: 1,897 (7.0%) women had a history of cancer with breast cancer as the most common (n = 671, 35.7%). While most survivors were non-Hispanic white (69.4%), 13.9% were Hispanic, 12.0% were non-Hispanic Black, and 4.6% were additional racial/ethnic groups. Survivors were 1.32 times more likely to be hospitalized within the last year (95% CI 1.11-1.58) and 1.32 times more likely to see a mental health provider within the last year (95% CI 1.05-1.66) compared to cancer-free women. Race/ethnicity was a significant effect modifier in the association between being a survivor and seeing a mental health provider, with Hispanic survivors having the highest odds (aOR 3.44; 95% CI 2.06-5.74; p-interaction < 0.00). CONCLUSION: Our study identifies disparities in healthcare utilization among female cancer survivors, highlighting the importance of evaluating these associations among medically underserved populations. These findings can educate healthcare professionals working with these populations to inform gaps in survivorship care utilization/access.

Racial disparities in mortality outcomes among women diagnosed with breast cancer in Maryland: Impact of cardiovascular disease and clinical characteristics.

BACKGROUND: Although racial disparities in breast cancer (BC) mortality have been well documented in the United States, little is known about the impact of coexisting cardiovascular disease (CVD) and other clinical factors on Black-White survival disparities after the diagnosis of BC. This study examined the associations of race, CVD, and clinical factors at diagnosis with the hazard of BC and CVD-related mortality among patients with BC identified from the Maryland Cancer Registry. METHODS: A total of 36,088 women (25,181 Whites and 10,907 Blacks) diagnosed with incident invasive BC between 2007 and 2017 were included. Subdistribution hazard ratios (sdHRs) for CVD-related and BC mortality were estimated with Fine and Gray regression models, which accounted for the influence of competing events. RESULTS: After a median follow-up of 5.8 years, 8019 deaths occurred; 3896 were BC deaths, and 1167 deaths were CVD-related. Black women had a higher hazard of BC mortality (sdHR, 1.66; 95% confidence interval [CI], 1.55-1.77) and CVD mortality (sdHR, 1.33; 95% CI, 1.17-1.51) in comparison with White women. Associations with CVD mortality were significantly stronger among Black women aged 50 to 59 years (sdHR, 2.86; 95% CI, 1.84-4.44; P for interaction < .001). Among Black women with CVD, the hazard of BC death was 41% higher in comparison with White women. By treatment, a significant association with CVD mortality was observed only among Black women undergoing surgery and radiation (sdHR, 1.61; 95% CI, 1.22-2.13). CONCLUSIONS: Clinicians should consider the impact of younger age, preexisting CVD, and BC treatments among Black patients. Early identification of those at risk for worse survival may improve surveillance and outcomes.

Racialized Economic Segregation and Breast Cancer Mortality among Women in Maryland.

BACKGROUND: Our objective was to determine the association between racialized economic segregation and the hazard of breast cancer mortality in Maryland. METHODS: Among 35,066 women (24,540 White; 10,526 Black) diagnosed with incident invasive breast cancer in Maryland during 2007 to 2017, exposure to racialized economic segregation was measured at the census tract level using Index of Concentration at the Extremes metrics. HRs and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression for the association between racialized economic segregation and the hazard of breast cancer mortality, accounting for clustering at the census tract level. Models were adjusted for age and stratified by race, median age (<60 years, ≥60 years), and clinical characteristics. RESULTS: Overall, the hazard of breast cancer mortality was 1.84 times as high (95% CI, 1.64-2.06) for the least privileged quintile of racialized economic segregation compared with the most privileged quintile. This association differed significantly (P interaction< 0.05) by race and age, with 1.20 (95% CI, 0.90-1.60) times the hazard of breast cancer mortality for Black women versus 1.66 (95% CI, 1.41-1.95) times the hazard for White women, and with greater hazards for younger women (HR, 2.17; 95% CI, 1.83-2.57) than older women (HR, 1.62; 95% CI, 1.40-1.88). CONCLUSIONS: Our results suggest that breast cancer survival disparities exist in Maryland among women residing in the least privileged census tracts with lower income households and higher proportions of Black residents. IMPACT: Our findings provide new insights into the breast cancer mortality disparities observed among women in Maryland.

Trends in breast cancer incidence rates by race/ethnicity: Patterns by stage, socioeconomic position, and geography in the United States, 1999-2017.

BACKGROUND: The incidence rate of breast cancer has been increasing over time across race/ethnicity in the United States. It is unclear whether these trends differ among stage, poverty, and geography subgroups. METHODS: Using data from the North American Association of Central Cancer Registries, this study estimated trends in age-adjusted breast cancer incidence rates among women aged 50 to 84 years from 1999 to 2017 by race/ethnicity (non-Hispanic Black, non-Hispanic White, and Hispanic) and across subgroups (stage, county-level poverty, county urban/rural status, and geographic region [West, Midwest, South, and Northeast]). RESULTS: From 2004 to 2017, breast cancer incidence rates increased across race/ethnicity and subgroups, with the greatest average annual percent increases observed for non-Hispanic Black women, overall (0.9%) and those living in lower poverty areas (0.8%), rural areas (1.2%), and all regions except the West (0.8%-1.0%). Stronger increases among non-Hispanic Black women were observed for local-stage disease and for some subgroups of distant-stage disease. Non-Hispanic Black women had the smallest decrease in regional-stage disease across most subgroups. Similarly, Hispanic women had the strongest increases in some subgroups, including areas with higher poverty (0.6%-1.2%) and in the West (0.8%), for local- and distant-stage disease. CONCLUSIONS: These trends highlight concerns for an increasing burden of breast cancer among subpopulations, with some already experiencing disparate breast cancer mortality rates, and they highlight the need for targeted breast cancer prevention and efforts to reduce mortality disparities in areas with increasing incidence.

Platelet count correlates with stage and predicts survival in melanoma.

Cancer is a chronic inflammatory state which is often associated with increased platelet counts. Cancer cells induce thrombopoiesis and activate platelets, which in turn facilitate cancer invasion and metastasis. In this study, we investigate the correlation between platelet counts with each of stage and overall survival in melanoma. This is a retrospective cohort study of 642 melanoma patients diagnosed or treated at a tertiary medical center between 2000 and 2016. Multivariable analysis adjusted for age, sex, stage, and treatment modality. Using multivariable analysis, patients with thrombocytosis around time of diagnosis were more likely to present with distant metastasis (Prevalence Ratio 3.5, 95% CI 2.35-5.22). In patients with metastatic disease and in all stages combined, thrombocytosis predicted decreased 5-year overall survival in univariate and multivariable analysis, and this was most pronounced during the first year after diagnosis. Finally, we show that mice with thrombocytopenia due to the lack of heat shock protein gp96 in their megakaryocytes are protected from melanoma dissemination to the lungs. These findings are concordant with preclinical studies showing a role for platelets in cancer metastasis and suppression of antitumor immunity, further supporting targeting platelets as an adjuvant to immunotherapy in melanoma.

Correlates of Prenatal and Early-Life Tobacco Smoke Exposure and Frequency of Common Gene Deletions in Childhood Acute Lymphoblastic Leukemia.

Tobacco smoke exposure has been associated with risk of childhood acute lymphoblastic leukemia (ALL). Understanding the relationship between tobacco exposures and specific mutations may yield etiologic insights. We carried out a case-only analysis to explore whether prenatal and early-life tobacco smoke exposure influences the formation of leukemogenic genomic deletions. Somatic copy number of 8 genes frequently deleted in ALL (CDKN2A, ETV6, IKZF1, PAX5, RB1, BTG1, PAR1 region, and EBF1) was assessed in 559 pretreatment tumor samples from the California Childhood Leukemia Study. Parent and child's passive tobacco exposure was assessed using interview-assisted questionnaires as well as DNA methylation in aryl-hydrocarbon receptor repressor (AHRR), a sentinel epigenetic biomarker of exposure to maternal smoking during pregnancy. Multivariable Poisson regressions were used to test the association between the smoking exposures and total number of deletions. Deletion burden varied by subtype, with a lower frequency in high-hyperdiploid and higher frequency in ETV6-RUNX1 fusion ALL. The total number of deletions per case was positively associated with tobacco smoke exposure, in particular for maternal ever-smoking (ratio of means, RM, 1.31; 95% CI, 1.08-1.59), maternal smoking during pregnancy (RM, 1.48; 95% CI, 1.12-1.94), and during breastfeeding (RM, 2.11; 95% CI, 1.48-3.02). The magnitude of association with maternal ever-smoking was stronger in male children compared with females (Pinteraction = 0.04). The total number of deletions was also associated with DNA methylation at the AHRR epigenetic biomarker (RM, 1.32; 95% CI, 1.02-1.69). Our results suggest that prenatal and early-life tobacco smoke exposure increase the frequency of somatic deletions in children who develop ALL. Cancer Res; 77(7); 1674-83. ©2017 AACR.

Tobacco Smoke and Ras Mutations Among Latino and Non-Latino Children with Acute Lymphoblastic Leukemia.

BACKGROUND AND AIMS: Childhood acute lymphoblastic leukemia (ALL) is a biologically heterogeneous disease, and mutations in the KRAS and NRAS oncogenes are present at diagnosis in about one-fifth of cases. Ras mutations were previously associated with environmental exposures in leukemias as well as in many other cancer types. This study examined whether Ras mutation could define a unique etiologic group of childhood ALL associated with tobacco smoke, a well-established mutagen and carcinogen. METHODS: We included 670 children with ALL enrolled in a case-control study in California (1995-2013), including 50.6% Latinos. Parental and child exposure to tobacco smoke was obtained from interviews. Sanger sequencing was used to detect the common KRAS and NRAS hotspot mutations in diagnostic bone marrow DNA. ALL cases were also characterized for common chromosome abnormalities. In case-case analyses, logistic regression analyses were used to estimate odds ratios to describe the association between tobacco smoke exposure and childhood ALL with Ras mutations. RESULTS: KRAS or NRAS mutations were detected in ∼18% of children diagnosed with ALL. Ras mutations were more common among Latino cases compared with non-Latino whites and in high-hyperdiploid ALL. No associations were observed between parental smoking or child's passive exposure to smoke and Ras positive ALL. CONCLUSIONS: The apparent lack of association between tobacco smoke and Ras mutation in childhood ALL suggests that Ras mutations do not specifically define a tobacco-related etiologic pathway. Reasons for racial and ethnic differences in ALL are not well understood and could reflect differences in etiology that warrant further examination.

Traumatic anterior hip dislocation in a 12-year-old child.

Hip dislocation in children can occur congenitally in isolation or in conjunction with other congenital abnormalities. Traumatic hip dislocations in children are relatively uncommon and anterior dislocation of hip joint is even rarer. We report such a case following unusual mode of injury in a 12-year-old child. The patient underwent successful emergent closed reduction of left hip. The clinical course and follow-up assessment of the patient was otherwise uneventful. At 2 years' follow-up there was no evidence of osteoarthritis, coxa magna, heterotrophic calcification, in congruency of the joints or avascular necrosis of the head of femur.