Remote Field Application of Digital Technology for Hearing Assessments in a Cohort of Pediatric Germ Cell Tumor Survivors.

BACKGROUND: Childhood cancer survivors treated with platinum-based chemotherapy are at risk of treatment-induced hearing loss. Accurate evaluation of hearing thresholds has historically been limited to clinical audiometry, which is logistically challenging and expensive to include in epidemiological studies. We evaluated the feasibility of using a remote, tablet-based hearing assessment in a cohort of pediatric germ cell tumor (GCT) survivors treated with platinum-based chemotherapy. METHODS: Survivors from the GCT Outcomes and Late effects Data (GOLD) study were recruited to the pilot study (n=100). Study personnel conducted remote hearing assessments of standard and extended high frequency thresholds using validated tablet-based audiometry (SHOEBOX Inc). T-tests and Wilcoxon rank-sum tests evaluated differences in assessment characteristics between children and adults. Agreement between self-reported and measured hearing loss was calculated using Cohen's kappa. RESULTS: We were able to reach 136/168 (81%) eligible participants, of which 100 (74%) agreed to participate. Successful completion of the remote hearing assessment was high (97%; 20 children [ages 7-17], 77 adults [ages 18-31]). Mean assessment length was 37.6 minutes and mean turnaround time was 8.3 days. We observed hearing loss at standard frequencies in 21% of participants. Agreement between self-reported and measured hearing loss was significant (p-value = 1.41 x 10-7), with 83.5% concordance. CONCLUSIONS: Hearing loss measured using the remote assessment aligns with self-reporting and rates of hearing loss reported in the literature for this population. IMPACT: Remote application of tablet-based audiometry is a feasible and efficacious method for measuring hearing in epidemiologic studies with participants spread across large geographical areas.

PM2.5, vegetation density, and childhood cancer: a case-control registry-based study from Texas 1995-2011.

BACKGROUND: Air pollution is positively associated with some childhood cancers, whereas greenness is inversely associated with some adult cancers. The interplay between air pollution and greenness in childhood cancer etiology is unclear. We estimated the association between early-life air pollution and greenness exposure and childhood cancer in Texas (1995 to 2011). METHODS: We included 6101 cancer cases and 109 762 controls (aged 0 to 16 years). We linked residential birth address to census tract annual average fine particulate matter <2.5 µg/m³ (PM2.5) and Normalized Difference Vegetation Index (NDVI). We estimated odds ratios (ORs) and 95% confidence intervals (CIs) between PM2.5/NDVI interquartile range increases and cancer. We assessed statistical interaction between PM2.5 and NDVI (likelihood ratio tests). RESULTS: Increasing residential early-life PM2.5 exposure was associated with all childhood cancers (OR = 1.10, 95% CI = 1.06 to 1.15), lymphoid leukemias (OR = 1.15, 95% CI = 1.07 to 1.23), Hodgkin lymphomas (OR = 1.27, 95% CI = 1.02 to 1.58), non-Hodgkin lymphomas (OR = 1.24, 95% CI = 1.02 to 1.51), ependymoma (OR = 1.27, 95% CI = 1.01 to 1.60), and others. Increasing NDVI exposure was inversely associated with ependymoma (0- to 4-year-old OR = 0.75, 95% CI = 0.58 to 0.97) and medulloblastoma (OR = 0.75, 95% CI = 0.62 to 0.91) but positively associated with malignant melanoma (OR = 1.75, 95% CI = 1.23 to 2.47) and Langerhans cell histiocytosis (OR = 1.56, 95% CI = 1.07 to 2.28). There was evidence of statistical interaction between NDVI and PM2.5 (P < .04) for all cancers. CONCLUSION: Increasing early-life exposure to PM2.5 increased the risk of childhood cancers. NDVI decreased the risk of 2 cancers yet increased the risk of others. These findings highlight the complexity between PM2.5 and NDVI in cancer etiology.

Racial and ethnic and socioeconomic disparities in childhood cancer incidence trends in the United States, 2000-2019.

BACKGROUND: Population-based surveillance of pediatric cancer incidence trends is critical to determine high-risk populations, drive hypothesis generation, and uncover etiologic heterogeneity. We provide a comprehensive update to the current understanding of pediatric cancer incidence trends by sex, race and ethnicity, and socioeconomic status (SES). METHODS: The Surveillance, Epidemiology, and End Results 22 data (2000-2019) was used to summarize age-adjusted incidence rates for children and adolescents aged 0-19 years at diagnosis. The annual percentage change (APC) and 95% confidence interval (CI) were estimated to evaluate incidence trends by sex, race and ethnicity, and SES overall and for cancer subtypes. Tests of statistical significance were 2-sided. RESULTS: Substantial variation was observed overall and for several histologic types in race and ethnicity- and SES-specific rates. Overall, we observed a statistically significant increase in incidence rates (APC = 0.8%, 95% CI = 0.6% to 1.1%). All race and ethnic groups saw an increase in incidence rates, with the largest occurring among non-Hispanic American Indian and Alaska Native children and adolescents (APC = 1.7%, 95% CI = 0.5% to 2.8%) and the smallest increase occurring among non-Hispanic White children and adolescents (APC = 0.7%, 95% CI = 0.5% to 1.0%). The lowest SES quintiles saw statistically significant increasing trends, while the highest quintile remained relatively stable (quintile 1 [Q1] APC = 1.6%, 95% CI = 0.6% to 2.6%; quintile 5 [Q5] APC = 0.3%, 95% CI = -0.1% to 0.7%). CONCLUSIONS: Childhood cancer incidence is increasing overall and among every race and ethnic group. Variation by race and ethnicity and SES may enable hypothesis generation on drivers of disparities observed.

Growth Hormone Deficiency in Childhood Intracranial Germ Cell Tumor Survivors.

Background and Aims: Intracranial germ cell tumor (iGCT) survivors have multiple risk factors for growth hormone (GH) deficiency, a commonly reported late effect in childhood cancer survivors. The objective of this study is to examine the prevalence of GH deficiency among childhood iGCT survivors. Methods: Participants were previously enrolled in the Germ Cell Tumor Epidemiology Study (GaMETES), a case parent triad study conducted using the Children's Oncology Group registry protocols, including 216 cases with iGCTs. Data on late effects and outcomes are available for 129 iGCT cases who consented for a follow-up study including a self-administered questionnaire and medical record retrieval. GH deficiency was identified via self-report and validated through medical record review. Chi-squared and Fisher's exact tests were used to examine cases with GH deficiency predating iGCT detection. Logistic regression was used to identify predictors of GH deficiency as a late effect. Results: Of 129 iGCT cases who participated in the late effects study, 45% had GH deficiency; 18% had GH deficiency predating the iGCT and 27% developed GH deficiency within a median of 19 months after diagnosis. Younger age at diagnosis, suprasellar location, and higher radiation doses were associated with GH deficiency as a late effect. Conclusions: GH deficiency is highly prevalent as an early clinical sign for iGCT and frequently arises as an early late effect after treatment. Additional investigation is needed to address earlier detection and treatment for this highly prevalent late effect in iGCT survivors.

Global variation in young adult central nervous system tumor incidence by region, age, and sex from 1988 to 2012.

BACKGROUND: Central nervous system (CNS) tumors result in tremendous morbidity and mortality. Incidence of CNS tumors in young adults is less studied. It is unknown how young adult CNS tumor incidence has changed globally in recent decades. METHODS: We used Cancer Incidence in Five Continents (CI5) data (1988-2012) to estimate incidence rates (IR), average annual percent change in incidence (AAPC; 95% confidence intervals [95% CI]), and male-to-female incidence rate ratios (IRR; 95% CI) by six histologies and age at diagnosis (20-29years, 30-39years). Tumors were classified as astrocytic, medulloblastoma, ependymal, oligodendroglial, meninges, and other embryonal. Geographic regions were defined using the United Nations Statistics Division geoscheme. RESULTS: There were 78,240 CNS tumor cases included. 20-29-year-old (yo) rates were lower than 30-39 yo in most regions for astrocytic, oligodendroglial and ependymal tumors. Globally, astrocytic tumor incidence decreased (20-29 yo AAPC: - 0.70; 95% CI: - 1.32, - 0.08) while incidence increased for oligodendroglial (20-29 yo AAPC: 3.03; 95% CI: 1.57-4.51; 30-39 yo AAPC: 2.67; 95% CI: 0.79-4.58), ependymal (20-29 yo AAPC: 1.16; 95% CI: 0.31-2.03; 30-39 yo AAPC: 2.29; 95% CI: 1.14-3.46), medulloblastoma (30-39 yo AAPC: 0.6; 95% CI: 0.04-1.24) and tumors of the meninges (20-29 yo AAPC: 1.55; 95% CI: 0.04-3.07). There was a 20-40% male incidence excess in all histologies except for meninge tumors (30-39 yo IRR: 0.71; 95% CI: 0.61, 0.84). CONCLUSIONS: Incidence of oligodendroglial and ependymal tumors increased globally in 20-39 yo suggesting better diagnoses or changes in risk factors. Males had a higher incidence of CNS tumors for most tumors studied and in most regions.

Racial/ethnic and sex differences in young adult malignant brain tumor incidence by histologic type.

BACKGROUND: Brain tumors are among the top four cancers in young adults. We assessed important windows of tumor development and examined the interplay of race/ethnicity, age, and sex in young adult brain tumor incidence. METHODS: Using SEER 18 data (2000-2017), incidence rates were estimated by Poisson regression in individuals aged 20-39 years at diagnosis. Incidence rate ratios (IRR) and 95% confidence intervals (95% CI) were estimated by race/ethnicity, sex and age for 12 malignant histologies. RESULTS: White incidence for all histologies was higher (White vs. Black IRR: 2.09, 95% CI: 1.94, 2.24; White vs Asian Pacific Islander IRR: 1.88, 95% CI: 1.75, 2.03; White vs Hispanic IRR: 1.70, 95% CI: 1.62, 1.78; White vs American Indian IRR: 1.40, 95% CI: 1.14, 1.73). Minority groups had higher lymphoma incidence (White vs Black IRR: 0.32, 95% CI: 0.25, 0.40, White vs Hispanic HR: 0.55, 95% CI: 0.44, 0.68). Males had higher incidence than females for all histologies (IRR: 1.36, 95% CI: 1.31, 1.41). Male rates were highest for lymphoma (male-to-female [MF] IRR: 2.00, 95% CI: 1.65, 2.42) and glioblastoma (MF IRR: 1.61, 95% CI: 1.48, 1.75). The male excess in incidence was similar by race/ethnicity and increased with age (20-24-year-old IRR: 1.18, 95% CI: 1.07, 1.29; 35-39-year-old IRR: 1.44, 95% CI: 1.35, 1.54). CONCLUSIONS: A White race and male incidence excess was observed among brain tumors. IMPACT: The male excess was similar by race/ethnicity and increased with age suggesting male sex may be an intrinsic risk factor for brain tumor development.

Racial and ethnic disparities in pediatric cancer incidence among children and young adults in the United States by single year of age.

BACKGROUND: Incidence rates of pediatric cancers in the United States are typically reported in 5-year age groups, obscuring variation by single year of age. Additionally, racial and ethnic variation in incidence is typically presented in broad categories rather than by narrow age ranges. METHODS: The Surveillance, Epidemiology, and End Results (SEER) 18 data (2000-2017) were examined to calculate frequencies and age-adjusted incidence rates among individuals aged birth to 39 years. Incidence rate ratios (IRRs) and 95% confidence intervals (95% CIs) were estimated as the measure of association for rate comparisons by race and Hispanic origin overall and by single year of age. RESULTS: Several histologic types showed substantial variation in race/ethnicity-specific and overall rates by single year of age. Overall, Black children and young adults experienced substantially decreased incidence of acute lymphoid leukemia (IRR, 0.52; 95% CI, 0.49-0.55) compared to Whites, and this decreased incidence was strongest at ages 1 through 7 years and 16 through 20 years. Hispanic individuals experienced decreased overall incidence of Hodgkin lymphoma (IRR, 0.50; 95% CI, 0.48-0.52) and astrocytoma (IRR, 0.54; 95% CI, 0.52-0.56) and increased risk of acute lymphoblastic leukemia (IRR, 1.46; 95% CI, 1.42-1.51) compared to non-Hispanic Whites, and the increased risk was strongest at ages 10 through 23 years. Substantial decreased risk across many tumor types was also observed for Asian/Pacific Islanders and American Indian/Alaska Natives. CONCLUSIONS: Examination of incidence rates for pediatric cancers by narrow age groups may provide insights regarding etiological differences in subgroups. Additionally, variation in age-specific incidence rates by race and ethnicity may enable hypothesis generation on drivers of disparities observed.

Estimating the Public Health Impact of Air Pollution for Informing Policy in the Twin Cities: A Minnesota Tracking Collaboration.

OBJECTIVE: The Minnesota Department of Health and the Minnesota Pollution Control Agency used local air pollution and public health data to estimate the impacts of particulate matter and ozone on population health, to identify disparities, and to inform decisions that will improve health. SETTING: While air quality in Minnesota currently meets federal standards, urban communities are concerned about the impact of air pollution on their health. The Twin Cities (Minneapolis-St Paul) metropolitan area includes 7 counties where fine particulate levels and rates of asthma exacerbations are elevated in some communities. DESIGN: We used the Environmental Protection Agency's BenMAP (Environmental Benefits Mapping and Analysis Program) software, along with local PM2.5 (fine particulate) and ozone ambient concentrations, census and population health data, to calculate impacts for 2008 at the zip code level. The impacts were summed across all zip codes for area-wide estimates. American Community Survey data were used to stratify zip codes by poverty and race for assessment of disparities. MAIN OUTCOME MEASURES: Attributable fraction, attributable rate and counts for all-cause mortality, asthma and chronic obstructive pulmonary disease hospitalizations, asthma emergency department (ED) visits, and cardiovascular disease hospitalizations. RESULTS: In the Twin Cities (2008), air pollution was a contributing cause for an estimated 2% to 5% of respiratory and cardiovascular hospitalizations and ED visits and between 6% and 13% of premature deaths. The elderly (aged 65+ years) experienced the highest air pollution-attributable rates of death and respiratory hospitalizations; children experienced the highest asthma ED visit rates. Geographical and demographic differences in air pollution-attributable health impacts across the region reflected the differences in the underlying morbidity and mortality rates. CONCLUSIONS: Method was effective in demonstrating that changes in air quality can have quantifiable health impacts across the Twin Cities. Key messages and implications from this work were shared with the media, community groups, legislators and the public. The results are being used to inform initiatives aimed at reducing sources of air pollution and to address health disparities in urban communities.