Investigating the Impact of Tumor Biology and Social Determinants on Time to Diagnosis and Stage at Presentation of Wilms Tumor.

Delays in diagnosis and time to diagnosis generally are used interchangeably in cancer disparity research, but these terms may have important differences. Although these terms are related, we hypothesize that time to diagnosis is determined by the aggressiveness of the tumor based on intrinsic factors such as tumor biology, whereas delays in diagnosis are caused by extrinsic factors such as socioeconomic status, leading to presentation at higher stage of disease due to barriers of care. We conducted a retrospective study of 306 patients diagnosed with Wilms tumor at Children's Hospital Colorado between 1971 and 2016 identifying patient barriers as extrinsic markers and using unfavorable histology and loss of heterozygosity as markers of aggressive tumor biology. Multivariable logistic regression was performed. Patients with Medicaid were more likely to present greater than 4 days after initial symptoms compared to those with private insurance, and those with housing concerns were more likely to be diagnosed greater than 9 days from initial symptoms. Tumor biology was noted to be associated with higher stage at diagnosis, but patient barriers were not. These findings suggest the interplay between tumor biology, patient barriers, diagnostic timing, and stage at diagnosis is more complex, multifactorial, and in need of further study.

Medical Record Level-Evaluation of Impact of Demographic and Socioeconomic Factors on Pediatric Neuro-Oncology Outcomes at Children's Hospital Colorado.

Purpose: A medical record-level cohort study to investigate demographic and socioeconomic factors influencing treatment, timing of care, and survival outcomes in pediatric patients diagnosed with central nervous system (CNS) tumors. Methods: Using electronic health records of patients at Children's Hospital Colorado from 1986-2020, we identified 898 patients treated for CNS tumors. The primary outcomes of interest were 5-year survival, timing of diagnosis, and treatment. Multivariable logistic regression and Cox regression were used to identify covariates associated with our outcomes of interest. Results: We found that age, race, tumor type, diagnosis year, and social concerns influenced receipt and timing of treatment. Age, race, patient rural vs. urban residence, and tumor impacted survival outcomes. Time to presentation and treatment were significantly different between White and minority patients. American Indian/Alaska Native and Black patients were less likely to receive chemo compared to White patients (OR 0.28, 0.93 p = 0.037, < 0.001). Patients with 3 + social concerns were more likely to survive after 5 years than children with no or unknown social concerns (OR 1.84, p = 0.011). However, with an adjusted hazards ratio, children with 2 social concerns were less likely to survive to 5 years than children with no or unknown concerns (OR 0.58, p = 0.066). Conclusions: Demographic and socioeconomic factors influence timing of care and survival outcomes in pediatric patients with CNS tumors. Minority status, age, social factors, rural, and urban patients experience differences in care. This emphasizes the importance of considering these factors and addressing disparities to achieve equitable care.

Early death from childhood cancer: First medical record-level analysis reveals insights on diagnostic timing and cause of death.

BACKGROUND: Approximately 7.5% of pediatric cancer deaths occur in the first 30 days post diagnosis, termed early death (ED). Previous database-level analyses identified increased ED in Black/Hispanic patients, infants, late adolescents, those in poverty, and with specific diagnoses. Socioeconomic and clinical risk factors have never been assessed at the medical record level and are poorly understood. METHODS: We completed a retrospective case-control study of oncology patients diagnosed from 1995 to 2016 at Children's Hospital Colorado. The ED group (n = 45) was compared to a non-early death (NED) group surviving >31 days, randomly selected from the same cohort (n = 44). Medical records and death certificates were manually reviewed for sociodemographic and clinical information to identify risk factors for ED. RESULTS: We identified increased ED risk in central nervous system (CNS) tumors and, specifically, high-grade glioma and atypical teratoid/rhabdoid tumor. There was prolonged time from symptom onset to seeking care in the ED group (29.4 vs. 9.8 days) with similar time courses to diagnosis thereafter. Cause of death was most commonly from tumor progression in brain/CNS tumors and infection in hematologic malignancies. CONCLUSIONS: In this first medical record-level analysis of ED, we identified socioeconomic and clinical risk factors. ED was associated with longer time from first symptoms to presentation, suggesting that delayed presentation may be an addressable risk factor. Many individual patient-level risk factors, including socioeconomic measures and barriers to care, were unable to be assessed through record review, highlighting the need for a prospective study to understand and address childhood cancer ED.

Melanoma survival by age group: Population-based disparities for adolescent and young adult patients by stage, tumor thickness, and insurance type.

BACKGROUND: Melanoma survival literature predominantly represents patients >65 years of age. Study of younger patients may reveal potential age-group-specific differences in survival outcome. OBJECTIVE: Identify factors associated with differences in melanoma survival in 2 age groups, adolescents and young adults (AYAs; ages 15-39) and older adults (ages 40-64). METHODS: This population-based registry study included all cases (n = 81,597) of cutaneous melanoma diagnosed at ages 15 to 64 from 2004 to 2015 in California. Age-group-specific multivariable Cox hazard regressions were used. RESULTS: In the adjusted, age-group-specific models, AYA patients with stage IV melanoma had worse survival (hazard ratio: 20.39, 95% CI: 13.30-31.20) than was observed among older adults (hazard ratio: 10.79, 95% CI: 9.33-12.48). Thicker tumors and public insurance were also associated with worse survival for AYAs than observed in models for older adults. AYAs experienced better survival when detected at earlier stages. LIMITATIONS: Registry data do not routinely collect behavioral information or family history of melanoma. CONCLUSIONS: Survival was much worse for AYAs with stage IV melanoma than observed among older adults. To improve AYA survival, early melanoma detection is critical. Greater awareness, suspicion, and screening for AYA melanoma may disrupt delays in diagnosis and reduce the excess burden of mortality from stage IV melanoma in young patients.

Sociodemographic Disparities in Presentation and Survival of Pediatric Bone Cancers.

Osteosarcoma (OST) and Ewing sarcoma (ES) are the most common pediatric bone cancers. Patients with metastatic disease at diagnosis have poorer outcomes compared with localized disease. Using the Surveillance, Epidemiology, and End Results registries, we identified children and adolescents diagnosed with OST or ES between 2004 and 2015. We examined whether demographic and socioeconomic disparities were associated with a higher likelihood of metastatic disease at diagnosis and poor survival outcomes. In OST, Hispanic patients and those living in areas of high language isolation were more likely to have metastatic disease at diagnosis. Regardless of metastatic status, OST patients with public insurance had increased odds of death compared to those with private insurance. Living in counties with lower education levels increased odds of death for adolescents with metastatic disease. In ES, non-White adolescents had higher odds of death compared with white patients. Adolescents with metastatic ES living in higher poverty areas had increased odds of death compared with those living in less impoverished areas. Disparities in both diagnostic and survival outcomes based on race, ethnicity, and socioeconomic factors exist in pediatric bone cancers, potentially due to barriers to care and treatment inequities.

Population-based analysis of radiation-induced gliomas after cranial radiotherapy for childhood cancers.

Background: Cranial radiotherapy (RT) used for pediatric CNS cancers and leukemias carries a risk of secondary CNS malignancies, including radiation-induced gliomas (RIG). Our aim was to characterize the epidemiology of RIG. Methods: This retrospective study used SEER data (1975-2016). Cohort 1 included patients diagnosed with glioma as a second malignancy ≥2 years after receiving treatment for a first malignancy diagnosed at 0-19 years, either a primary CNS tumor (1a, n = 57) or leukemia (1b, n = 20). Cohort 2 included patients who received RT for a pediatric CNS tumor and died of presumed progressive disease >7 years after diagnosis, since previous studies have documented many missed RIGs in this group (n = 296). Controls (n = 10 687) included all other patients ages 0-19 years who received RT for a first CNS tumor or leukemia. Results: For Cohort 1, 0.77% of patients receiving cranial RT developed RIG. 3.39% of patients receiving cranial RT for primary CNS tumors fell in cohort 2. Median latency to RIG diagnosis was 11.1 years and was significantly shorter for cohort 1b than 1a. Median OS for cohort 1 was 9.0 months. Receiving surgery, radiation, or chemotherapy were all associated with a nonstatistically significant improvement in OS (P .1-.2). A total of 1.8% of all brain tumor deaths fell in cohort 1, with 7.9% in cohort 2. Conclusion: A total of 1%-4% of patients undergoing cranial RT for pediatric cancers later developed RIG, which can occur 3-35 years after RT. Given the substantial and likely underestimated impact on overall CNS tumor mortality, RIG is deserving of increased attention in preclinical and clinical studies.

Pre-implementation evaluation for an HPV vaccine provider communication intervention among primary care clinics.

OBJECTIVES: Interventions to improve health care provider communication about HPV vaccination can increase vaccine acceptance. Our objectives were to (1) identify clinics in locations with high HPV-associated cancer and low HPV-vaccination rates that would potentially benefit from dissemination of a proposed HPV Provider Communication intervention and (2) use qualitative interviews and a dissemination and implementation framework to assess readiness for change and fit of the HPV Provider Communication intervention to the context of these clinics. METHODS: Local HPV-associated cancer and HPV vaccination rates were assigned to Practice-Based Research Network clinics using data from the Colorado Central Cancer Registry, the Colorado Immunization Information System, and the American Community Survey. Staff from 38 clinics located in areas with high numbers of adolescents not up-to-date for HPV vaccine and high rates of HPV-associated cancers were recruited for qualitative interviews. Interview questions used the Promoting Action on Research Implementation in Health Services (PARIHS) conceptual framework and addressed the proposed intervention, current vaccination practices and prior quality improvement (QI) experience. RESULTS: Twenty-seven interviews were completed with clinicians, clinic managers, and other staff across 17 clinics (9 pediatric, 5 family medicine, 3 public/school-based health). Most clinics had some prior QI experience and there were few thematic differences between sites with more or less foundation for QI/immunization work. Participants were motivated to improve the health of their patients and valued both guidelines and local experience as important evidence to consider adopting an intervention. Interviewees were more interested in implementing the proposed intervention if it aligned with existing priorities and fit within clinic workflows. Facilitation needs included adequate time and external facilitation support for data tracking and analysis. CONCLUSIONS: Qualitative interviews to understand clinic context and fit of an HPV Provider Communication intervention can inform implementation in settings with the highest potential for clinical impact.

Population-based analysis of CNS tumor diagnoses, treatment, and survival in congenital and infant age groups.

BACKGROUND: Congenital (< 3 months) and infant (3 to 11 months) brain tumors are biologically different from tumors in older children, but their epidemiology has not been studied comprehensively. Insight into epidemiological differences could help tailor treatment recommendations by age and increase overall survival (OS). METHODS: Population-based data from SEER were obtained for 14,493 0-19-year-olds diagnosed with CNS tumors 1990-2015. Congenital and infant age groups were compared to patients aged 1-19 years based on incidence, treatment, and survival using Chi-square and Kaplan-Meier analyses. Hazard ratios were estimated from univariate and multivariable Cox proportional hazards survival analyses. RESULTS: Between the < 3-month, 3-5-month, 6-11 month, and 1-19-year age groups, tumor type distribution differed significantly (p < 0.001). 5-year OS for all tumors was 36.7% (< 3 months), 56.0% (< 3-5 months), 63.8% (6-11 months), and 74.7% (1-19 years) (p < 0.001). Comparing between age groups by tumor type, OS was worst for < 3-month-olds with low-grade glioma, medulloblastoma, and other embryonal tumors; OS was worst for 3-5-month-olds with ependymoma, < 1-year-olds collectively with atypical teratoid-rhabdoid tumor, and 1-19-year-olds with high-grade glioma (HGG) (log rank p < 0.02 for all tumor types). Under 3-month-olds were least likely to receive any treatment for each tumor type and least likely to undergo surgery for all except HGG. Under 1-year-olds were far less likely than 1-19-year-olds to undergo both radiation and chemotherapy for embryonal tumors. CONCLUSIONS: Subtype distribution, treatment patterns, and prognosis of congenital/infant CNS tumors differ from those in older children. Better, more standardized treatment guidelines may improve poorer outcomes seen in these youngest patients.

Ethnicity, socioeconomic status, income inequality, and colorectal cancer outcomes: evidence from the 4C2 collaboration.

PURPOSE: National Cancer Institute (NCI)-Designated Cancer Centers are required to assess and address the needs of their catchments. In rural regions, catchment areas are vast, populations small, and infrastructure for data capture limited, making analyses of cancer patterns challenging. METHODS: The four NCI-Designated Comprehensive Cancer Centers in the southern Rocky Mountain region formed the Four Corners Collaboration (4C2) to address these challenges. Colorectal cancer (CRC) was identified as a disease site where disparities exist. The 4C2 leaders examined how geographic and sociodemographic characteristics were correlated to stage at diagnosis and survival in the region and compared those relationships to a sample from the surveillance, epidemiology, and end results (SEER) program. RESULTS: In 4C2, Hispanics were more likely to live in socioeconomically disadvantaged areas relative to their counterparts in the SEER program. These residency patterns were positively correlated with later stage diagnosis and higher mortality. Living in an area with high-income inequality was positively associated with mortality for Non-Hispanic whites in 4C2. In SEER, Hispanics had a slightly higher likelihood of distant stage disease, and disadvantaged socioeconomic status was associated with poor survival. CONCLUSION: CRC interventions in 4C2 will target socioeconomically disadvantaged areas, especially those with higher income inequality, to improve outcomes among Hispanics and Non-Hispanic whites. The collaboration demonstrates how bringing NCI-Designated Cancer Centers together to identify and address common population catchment issues provides opportunity for pooled analyses of small, but important populations, and thus, capitalize on synergies among researchers to reduce cancer disparities.

Assessment of enrollment characteristics for Children's Oncology Group (COG) upfront therapeutic clinical trials 2004-2015.

BACKGROUND: Improvements in pediatric cancer survival are attributed to cooperative clinical trials. Under-representation of specific demographic groups has been described in adult and pediatric cancer trials and poses a threat to the generalizability of results. An evaluation of data provided by the Children's Oncology Group (COG) of upfront trial enrollment for US patients 0 to 29 years old between 2004 and 2015 was performed. METHODS: US cancer cases were estimated using incidence data and US population estimates from the Surveillance, Epidemiology, and End Results Program and compared to observed COG cases. Percent enrollment and standardized ratios of enrollment were calculated across demographic, disease, and socioeconomic groups. The COG website was utilized to quantify available trials and assess age eligibility. RESULTS: 19.9% of estimated US cancer patients age 0 to 19 years enrolled on COG trials. Younger patients were more represented across diseases and races/ethnicities. Patients with hematologic malignancies were more represented compared to solid and central nervous system (CNS) tumors. CONCLUSION: COG trial enrollment rates are declining when compared to previously published data, potentially from challenges in pediatric drug development, difficulty designing feasible trials for highly curable diagnoses, and issues ensuring trial availability for the heterogeneous group of solid and CNS tumors. Though racial/ethnic groups and county-level socioeconomic factors were proportionally represented, under representation of the adolescent/young adult (AYA) population and younger patients with solid and CNS tumors remains a concern. Targeted efforts should focus on these subgroups and further research should evaluate AYA enrollment rates across all available trials.

Chronic pain, health-related quality of life, and employment in working-age cancer survivors.

PURPOSE: This study estimated the prevalence of cancer-related pain in working-age cancer survivors (age 25-64 years) and evaluated differences in demographic and clinical variables in those with and without pain. We also investigated the impact of cancer-related pain on health-related quality of life (HRQoL) and employment outcomes in this population. METHODS: We used cross-sectional data from the 2016 Behavioral Risk Factor Surveillance System (BRFSS). Analyses were conducted with a sample of 1702 cancer survivors who completed treatment. All analyses were conducted using procedures to account for the complex sampling design of the BRFSS. RESULTS: Nearly 17% (95% CI [13.94-19.58]) of working-age cancer survivors reported experiencing cancer-related pain. Among those who experienced pain, the majority were female, white, non-Hispanic, married/partnered, and non-employed, with breast as the most common cancer disease site. Those with cancer-related pain experienced more physically unhealthy days (adjusted rate ratio [aRR] 1.63, 95% CI [1.16-2.28]), mentally unhealthy days (aRR 1.52, 95% CI [1.02-2.26]), and activity interference (aRR 2.15, 95% CI [1.53-3.02]). Cancer-related pain decreased the odds of being employed, but only in female survivors (adjusted odds ratio 0.34, 95% CI [0.22-0.54]). CONCLUSION: Cancer-related chronic pain is a prevalent, long-term condition that is negatively associated with HRQoL and employment in working-age cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: Clinical interventions targeting chronic pain may improve HRQoL in working-age cancer survivors and employment outcomes, particularly in women.

The potential population-based impact of an HPV vaccination intervention in Colorado.

BACKGROUND: Human papillomavirus (HPV) infection is the most common cause of cervical cancer and can be prevented with vaccination, but HPV vaccination rates remain low. An intervention to improve health care provider communication about vaccination has been shown to increase HPV vaccination rates in an initial trial in Colorado, where about 160 cases of cervical cancer are diagnosed each year. METHODS: Census data were combined with Colorado cancer and immunization registry data to identify clinics in locations that would most benefit from implementation of this intervention to improve HPV vaccination rates. ArcGIS Pro was used to map cervical cancer incidence, immunization rates, population data, and location of clinics participating in practice-based research networks (PBRNs). Results from the provider communication intervention trial and published estimates of the number needed to vaccinate to prevent a case of cervical cancer were used to predict the number of cervical cancer cases prevented based on increased vaccination due to the intervention. RESULTS: Ninety-eight Colorado PBRN clinics were analyzed. For the 10 clinics with the highest predicted number of cervical cancer cases prevented, 5218 additional patients would be vaccinated and 43 cervical cancer cases prevented with implementation of the intervention. If implemented in all 98 clinics, the intervention would lead to 20 490 additional patients vaccinated (range 7-658/clinic) and 171 cases of cervical cancer prevented (range 0.05-5.48/clinic). CONCLUSIONS: Geographic data from cancer and immunization registries can inform the dissemination of evidence-based practices like the provider communication intervention for HPV vaccination to maximize impact on public health.

Measuring the Health of an Invisible Population: Lessons from the Colorado Transgender Health Survey.

BACKGROUND: Transgender people, those whose gender identity does not match their sex assigned at birth, face barriers to receiving health care. These include discrimination, prohibitive cost, and difficulty finding transgender-inclusive providers. As transgender identities are not typically recognized in public health research, the ability to compare the health of the transgender population to the overall population is limited. OBJECTIVE: The Colorado Transgender Health Survey sought to explore current disparities and their effects on the health of transgender people in Colorado. DESIGN AND PARTICIPANTS: The Colorado Transgender Health Survey, based on the Behavioral Risk Factor Surveillance System (BRFSS), was developed by the Colorado Department of Public Health and Environment, transgender advocates, and transgender community members. Outreach was targeted to transgender-inclusive events and organizations. MAIN MEASURES: Responses to the 2014 Colorado Transgender Health Survey were compared side by side to Colorado 2014 BRFSS data. RESULTS: Results from 406 transgender or gender-nonconforming adults who live in Colorado were included in the analysis. Forty percent of respondents report delaying medical care due to cost, inadequate insurance, and/or fear of discrimination. Respondents report significant mental health concerns, with 43% reporting depression, 36% reporting suicidal thoughts, and 10% attempting suicide in the past year. Respondents with a transgender-inclusive provider were more likely to receive wellness exams (76 versus 48%), less likely to delay care due to discrimination (24 versus 42%), less depressed (38 versus 54%), and less likely to attempt suicide (7 versus 15%) than those without. CONCLUSIONS: The transgender community in Colorado faces significant disparities, especially around mental health. However, a transgender-inclusive provider is associated with improved mental and physical health and health behaviors. Further population-level research and provider education on transgender health should to be incorporated into national efforts to eliminate health disparities.