Background
For many childhood cancers, survival is lower among non‐Hispanic blacks and Hispanics in comparison with non‐Hispanic whites, and this may be attributed to underlying socioeconomic ...factors. However, prior childhood cancer survival studies have not formally tested for mediation by socioeconomic status (SES). This study applied mediation methods to quantify the role of SES in racial/ethnic differences in childhood cancer survival.
Methods
This study used population‐based cancer survival data from the Surveillance, Epidemiology, and End Results 18 database for black, white, and Hispanic children who had been diagnosed at the ages of 0 to 19 years in 2000‐2011 (n = 31,866). Black‐white and Hispanic‐white mortality hazard ratios and 95% confidence intervals, adjusted for age, sex, and stage at diagnosis, were estimated. The inverse odds weighting method was used to test for mediation by SES, which was measured with a validated census‐tract composite index.
Results
Whites had a significant survival advantage over blacks and Hispanics for several childhood cancers. SES significantly mediated the race/ethnicity–survival association for acute lymphoblastic leukemia, acute myeloid leukemia, neuroblastoma, and non‐Hodgkin lymphoma; SES reduced the original association between race/ethnicity and survival by 44%, 28%, 49%, and 34%, respectively, for blacks versus whites and by 31%, 73%, 48%, and 28%, respectively, for Hispanics versus whites ((log hazard ratio total effect – log hazard ratio direct effect)/log hazard ratio total effect).
Conclusions
SES significantly mediates racial/ethnic childhood cancer survival disparities for several cancers. However, the proportion of the total race/ethnicity–survival association explained by SES varies between black‐white and Hispanic‐white comparisons for some cancers, and this suggests that mediation by other factors differs across groups.
Socioeconomic status mediates the association between race/ethnicity and childhood cancer survival, though to varying degrees across cancers. The proportion of the total effect explained by socioeconomic status varies by race/ethnicity for some cancers.
See also pages 3975‐8.
Background
The male excess in childhood cancer incidence is well‐established; however, the underlying biologic mechanisms remain unknown. Examining the association between male sex and childhood ...cancer by single year of age and tumor type may highlight important periods of risk such as variation in growth and hormonal changes, which will inform etiologic hypotheses.
Methods
Using data from the Surveillance, Epidemiology, and End Results (SEER) 18 registries (2000–2015), incidence rate ratios (IRR) and 95% confidence intervals (95% CI) were estimated as the measure of association between male sex and childhood cancer by single year of age (0–19).
Results
The IRR for male cancer overall was 1.19 (95% CI, 1.18–1.20) and was similar in magnitude at nearly every year of age. Burkitt lymphoma was strongly associated with male sex (IRRs ≥2 at each year of age). Increased incidence was observed among males for acute lymphoblastic leukemia, Hodgkin and non‐Hodgkin lymphomas for nearly all years of age. Medulloblastoma was the only central nervous system tumor with a significant male predominance at nearly every age. Male sex displayed a consistent inverse association with nephroblastoma and thyroid carcinoma over the ages studied.
Conclusions
Male sex was positively associated with most cancers. The higher incidence rates observed in males remained consistent over the childhood and adolescent periods, suggesting that childhood and adolescent hormonal fluctuations may not be the primary driving factor for the sex disparities in childhood cancer. The observed incidence disparities may be due to sex differences in exposures, genetics, or immune responses.
Innovations in the care of adolescent and young adult (AYA) germ cell tumors (GCTs) are needed for one of the most common AYA cancers for which treatment has not significantly changed for several ...decades. Testicular GCTs (TGCTs) are the most common cancers in 15- to 39-year-old men, and ovarian GCTs (OvGCTs) are the leading gynecologic malignancies in women younger than 25 years. Excellent outcomes, even in widely metastatic disease using cisplatin-based chemotherapy, can be achieved since Einhorn and Donohue's landmark 1977 study in TGCT. However, as the severity of accompanying late effects (ototoxicity, neurotoxicity, cardiovascular disease, second malignant neoplasms, nephrotoxicity, and others) has emerged, efforts to deintensity treatment and find alternatives to cisplatin have taken on new urgency. Current innovations include the collaborative design of clinical trials that accrue GCTs across all ages and both sexes, including adolescents (previously on pediatric trials), and OvGCT (previously on gynecologic-only trials). Joint trials accrue larger sample sizes at a faster rate and therefore evaluate new approaches more rapidly. These joint trials also allow for biospecimen collection to further probe GCT etiology and underlying mechanisms of tumor growth, thus providing new therapeutic options. This AYA approach has been fostered by The Malignant Germ Cell International Consortium, which includes over 115 GCT disease experts from pediatric, gynecologic, and genitourinary oncologies in 16 countries. Trials in development incorporate, to our knowledge, for the first time, molecular risk stratification and precision oncology approaches on the basis of specific GCT biology. This collaborative AYA approach pioneering successfully in GCT could serve as a model for impactful research for other AYA cancer types.
AbstractObjectiveOvarian germ cell tumors (OGCT) are the primary ovarian malignancy affecting girls and young women. Globally, incidence rates and trends for OGCTs have not been compared in the ...literature and their etiology is not well described. Comparisons of incidence globally could inform etiologic hypotheses. The aim of this analysis was to evaluate geographic variation in OGCT incidence and to identify trends in incidence rates. MethodsData were extracted from Cancer Incidence in 5 Continents ( CI5) from 1988 to 2012. Rates of OGCT in women and girls were calculated for ages 0–9, 10–19, and 20–39 years and standardized to the 2000–2025 average world population. Data were aggregated within subregions corresponding to the United Nations Statistics Division (UNSD) geoscheme. Incidence rates were compared in subregions and average annual percent change (AAPC) was estimated using Poisson regression. ResultsOverall, the highest incidence rates were observed in 10–19-year-olds. Incidence was generally the highest in Eastern Asia, Central America and North America. While incidence was variable by geographic region, less variation was observed in 0–9-year-olds as compared to adolescents and young adults. Significant increases in incidence were seen in some regions (Eastern Asia, Oceania, Western Europe, Southern Europe, and North America) and in countries with a high or very high human development index for one or more age groups. ConclusionsEvaluating 25 years of OGCT incidence data, the highest incidence rates and largest increases in incidence were seen in Eastern Asia. Future studies should focus on etiologic features that may account for geographic variation and increases in incidence of OGCT.
Abstract 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 epidemiologic studies. We evaluated the feasibility of using a remote, tablet-based hearing assessment in a cohort of pediatric germ cell tumor 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 κ. 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). The mean assessment length was 37.6 minutes, and the 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 × 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 geographic areas.
BACKGROUND
Males with Klinefelter syndrome (KS) (47,XXY) may be more likely to develop germ cell tumors (GCTs), particularly mediastinal GCTs. To date, there are no reports characterizing the ...prevalence of KS among male GCT cases.
METHODS
The authors used array genotyping data from a Children’s Oncology Group epidemiology study to estimate the prevalence of KS in males with GCTs (433 males aged birth‐19 years). Using Fisher’s exact tests, the authors examined differences in age at diagnosis, race/ethnicity, tumor location and histology, and several birth characteristics between cases of KS‐GCT and GCT cases without chromosomal abnormalities. Using publicly available data, the authors estimated the 1‐year risk, risk ratio, and corresponding 95% confidence interval of GCTs among KS cases.
RESULTS
Based on analysis of array genotyping data, 3% of male GCT cases (13 cases) had KS. The additional X chromosome was of maternal origin in 7 of the 13 cases. Of these 13 KS cases, 5 of 9 KS‐GCT cases with parental questionnaire data (56%) reported a diagnosis of KS. No significant differences were observed with regard to patient or birth characteristics between KS‐GCT and non–KS‐GCT cases. KS‐GCT cases were significantly more likely to be diagnosed with mediastinal tumors than non–KS‐GCT cases (P<.01). The authors estimated the risk of developing a GCT among males with KS to be 0.00025, or 1 per 4000 males (risk ratio, 18.8; 95% confidence interval, 11.7‐30.0).
CONCLUSIONS
Compared with males without chromosomal abnormalities, males with KS are more likely to be diagnosed with a mediastinal GCT. The presence of KS should be considered in males with a diagnosis of mediastinal GCT. In the current study, the authors report that approximately one‐third of males with mediastinal germ cell tumors have Klinefelter syndrome, and therefore screening of these individuals for the syndrome may be warranted. Males with Klinefelter syndrome are 19 times as likely as males without Klinefelter syndrome to develop germ cell tumors.
The authors observed 1/3 of males with mediastinal germ cell tumors had Klinefelter syndrome; therefore, screening of these cases for Klinefelter syndrome may be warranted. Klinefelter syndrome males are 19 times as likely as non‐Klinefelter males to develop germ cell tumors.
Survival differences by racial and ethnic group have been reported in children and adolescents with germ cell tumors (GCTs), but whether these differences depend on stage of disease is unclear. Using ...the SEER 18 registries (2000–2015), we examined GCT survival differences by race/ethnicity (non‐Hispanic white NHW, Black, Asian/Pacific Islander API, Hispanic) separately for males and females aged 0–19 years at diagnosis. We used Kaplan–Meier survival curves (Log‐Rank p values) to characterize survival differences. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for the association between race/ethnicity and death. Using an inverse odds weighting mediation analysis, we estimated the association between race/ethnicity and death treating stage of disease as the mediator. There were no significant racial/ethnic survival differences among females. Male survival differed by race/ethnicity (p < 0.0001) with NHW males having the best survival. Compared to NHW, API and Hispanic males had significantly higher risks of death (API HR: 2.18; 95% CI: 1.32–3.56; Hispanic HR: 1.98; 95% CI: 1.42–2.78) (model adjusted for age and year at diagnosis, tumor histology and location, stage). This association was mediated by stage of disease only among Hispanic males with gonadal tumors (indirect HR: 1.18; 95% CI: 1.03–1.35). The increased risk of death after a testicular GCT diagnosis observed among Hispanic males was mediated by stage of disease. For API males and Hispanic males with extragonadal tumors, other unidentified factors including differences in exposures, tumor biology or treatment received may impact the observed racial/ethnic survival disparities.
What's new?
Survival differences by racial and ethnic group have been reported in children and adolescents with germ cell tumors (GCTs), but whether these differences depend on stage of disease is unclear. Using data from 3,300 children and adolescents diagnosed with a GCT, here the authors observed significant racial/ethnic differences in survival among males but not females, with Hispanic and Asian/Pacific Islander males having worse survival than whites. This association was not mediated by stage of disease, except for gonadal tumors in Hispanic males. For Asian/Pacific Islander and Hispanic males with extragonadal tumors, other unidentified factors may be driving the observed disparity.
Pediatric cancer incidence has been steadily increasing over the last several decades with the largest increases reported in infants. Few evaluations have looked at international pediatric cancer ...incidence trends in the youngest children. The aim of this analysis was to evaluate trends in cancer incidence in children under 5 years of age, overall and by type, using data from
(
) from 1988 to 2012 (CI5 volumes VII-XI).
Rates of cancers in children ages 0-4 years were extracted from registries available in
from 1988 to 2012. To overcome small numbers in individual registries, numerators and denominators were aggregated within regions corresponding to the United Nations' geoscheme. Average annual percent change (AAPC) was estimated using Poisson regression. Robust standard errors were used in all models to correct for overdispersion in some regions, and 95% Wald confidence intervals and
values were reported. The top five cancers by increasing AAPC were ranked within each region.
Overall, in children under 5 years, increasing incidence was seen in multiple regions for acute lymphoblastic leukemia, acute myeloid leukemia, ependymal tumors, neuroblastoma, and hepatoblastoma. Hepatoblastoma had the largest AAPC in 11 out of 15 regions and showed an increase in all regions except southern Asia. Astrocytic tumors were the only cancer that decreased over the time period.
We evaluated 25 years of cancer incidence in children ages 0-4 years and observed increases in incidence for hepatoblastoma, leukemia, neuroblastoma, and ependymal tumors. Further etiologic evaluation will be required to explain these increases in incidence.
Genomewide association studies (GWAS) have been widely used in recent years to identify common variants that are associated with multiple types of cancer, including testicular germ cell tumors. These ...studies require no a priori hypotheses and have advantages, including the ability to highlight new pathways relevant to the biology of common diseases. GWAS require collection of germline DNA from individuals with and without the disease of interest. Following DNA extraction and quantification, a variety of array based platforms are available to evaluate common and moderately rare germline variation throughout the genome in an agnostic fashion. Here, we describe DNA extraction methods from samples typically used in the evaluation of germline genetic variation (blood and saliva). We also describe assays used to assess DNA quality and quantity. Finally, we include methods describing array based genotyping using the Illumina platform and validation of relevant variants using the iPLEX Agena Multiplexed Genotyping (formerly Sequenom).
Epidemiologic analyses of sarcoma are limited by the heterogeneity and rarity of the disease. Utilizing population-based surveillance data enabled us to evaluate the contribution of census ...tract-level socioeconomic status (CT-SES) and race/ethnicity on sarcoma incidence rates.
We utilized the Surveillance, Epidemiology, and End Results program to evaluate associations between CT-SES and race/ethnicity on the incidence rates of sarcoma. Incidence rate ratios and 99% confidence intervals were estimated from quasi-Poisson models. All models were stratified by broad age groups (pediatric: <20 years, adult: 20-65 years, older adult: 65+ years) and adjusted for sex, age, and year of diagnosis. Within each age group, we conducted analyses stratified by somatic genome (fusion-positive and fusion-negative sarcomas) and for subtypes with >200 total cases. A
value less than 0.01 was considered statistically significant.
We included 55,415 sarcoma cases in 35 sarcoma subtype-age group combinations. Increasing CT-SES was statistically significantly associated with 11 subtype-age group combinations, primarily in the older age group strata (8 subtypes), whereas malignant peripheral nerve sheath tumors in adults were associated with decreasing CT-SES. Nearly every sarcoma subtype-age group combination displayed racial/ethnic disparities in incidence that were independent of CT-SES.
We found race/ethnicity to be more frequently associated with sarcoma incidence than CT-SES. Our findings suggest that genetic variation associated with ancestry may play a stronger role than area-level SES-related factors in the etiology of sarcoma.
These findings provide direction for future etiologic studies of sarcomas.
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