Pediatric Cancer Incidence Research Articles

Pediatric Patients with Acute Lymphoblastic Leukemia in Honduras: Demographic Characteristics, Clinical Features, and Laboratory Findings

Approximately 90% of confirmed cancer cases annually are reported in low to middleincome countries. In Honduras, the incidence of pediatric cancer has been steadily increasing, accompanied by a higher cancer mortality rate attributed to diagnostic errors, limited access to healthcare, and management challenges. Diagnostic pitfalls, such as failure to recognize signs of malignancy, inadequate assessment of persistent symptoms, and misinterpretation of diagnostic tests, significantly impede effective cancer care. This retrospective case study collected data from 68 pediatric patients diagnosed with Acute Lymphoblastic Leukemia (ALL) at the Honduran Social Security Institute in Tegucigalpa between January 2015 and December 2022. Data retrieval encompassed demographic features, clinical characteristics, and laboratory findings. We used SPSS Statistics version 29.0.2.0 to perform all statistical analysis. The cohort comprised patients of equal gender distribution, with 42.6% (N: 29) belonging to the age group of 1 to 4 years. The hospital diagnosed an average of 8.5 cases each year. Fever was the most prevalent symptom, affecting 80.9% of patients (N: 55). Hemoglobin levels were below 10 mg/dL in 67.6% of patients, with 33.8% exhibiting levels below 7 mg/dL (N: 23) and equal proportion falling within the 7-10 mg/dL range (N: 23). Platelet levels were below 150,000/μL, with 48.5% experiencing severe thrombocytopenia (platelet levels <50,000/μL). Additionally, most patients presented phosphorus levels exceeding 4.5 mg/dl (N: 33, 48.5%), along with elevated LDH levels surpassing 500 U/l (N: 34, P: 50%). The presence of persistent fever should trigger suspicion of cancer, necessitating thorough assessment. Implementing guidelines outlining common symptoms and referral protocols could significantly reduce mortality in Honduran children with ALL.

Incidence of Pediatric Cancers in French Guiana: How Does It Compare to Global Estimates?

French Guiana is a French territory in South America. The exposome of persons living there is quite different from that in mainland France and the ethnic make-up of the population is also quite different. Poverty is also widespread with difficulties in accessing care magnified by the low medical-professional density. In this singular context, we aimed to measure the incidence of pediatric cancers and to compare it with other continents. We used French Guiana's certified cancer registry to study this between 2003 and 2017. Incidences were standardized using the world population with three strata: 0-4 years, 5-9 years, and 10-14 years. There were 164 solid tumors or hematologic malignancies diagnosed in children under the age of 15 (92 in boys and 72 in girls). Over the study period, the standardized incidence rate was 14.1 per 100,000 among children aged under 15 years. There was no significant trend during the study period. The three most common causes of cancer were leukemias-mostly lymphoblastic-CNS tumors, and sarcoma. The standardized incidence of pediatric cancers in French Guiana was similar to those in Western Europe and North America. As others have discovered, we found that males tended to be more likely to develop cancer, notably leukemia, CNS tumors, sarcoma, and retinoblastoma. As elsewhere, the predominant cancer types changed with age. Our initial assumption was that given the singular context of French Guiana, there may have been differences in pediatric cancer incidences. Here we showed that overall, contrary to our assumption and to trends in tropical countries, the incidence of pediatric cancers was in a range between Western Europe and North America with some apparent but non-significant differences in the main types of cancers observed in global statistics. Quality cancer registry data in this tropical region confirm the suspicion that lower incidences in tropical low- and middle-income countries are likely to result from incomplete diagnosis and data collection.

Can non-contrast magnetic resonance imaging replace contrast-enhanced computerized tomography in the local staging of pediatric renal tumors?

BackgroundRenal tumors account for approximately 6–7% of the total incidence of pediatric cancers. Wilms tumor (WT) is the most common renal malignancy observed in the pediatric population under 5 years old. Computed tomography (CT) is used for staging of the renal tumors. Magnetic resonance imaging (MRI) offers enhanced soft tissue resolution and provides more comprehensive insights into tumor extension through the capsule, including tumor infiltration into the renal vein or IVC. MRI is a noninvasive imaging modality that does not involve any radiation hazards, making it safe for children. In addition, MRI can be performed without the administration of contrast agents in patients with impaired renal function. Therefore, MRI plays a vital role in screening, staging, preoperative evaluation, and follow-up. Diffusion-weighted imaging (DWI) is a functional tool that aids in locating the most receptive tumoral region to guide confirmatory biopsies. In this study, we aim to evaluate the potential value of non-contrast MRI in staging pediatric renal tumors compared to contrast-enhanced CT.ResultsThis study included 50 patients presented with renal mass, with ages ranging from 1 to 8 years and a mean age of 4.27 ± 1.27 (mean ± SD). The final diagnosis was Wilm’s tumor at 86%, clear cell sarcoma at 4%, rhabdoid tumor at 4%, rhabdomyosarcoma at 2%, and nephroblastomatosis with no malignant transformation at 4%. CT accurately diagnosed stages 4 and 5 in agreement with pathological findings while upstaging the other cases, with a CT sensitivity of 90.91%, specificity of 82.35%, PPV of 92%, and NPV of 84%. MRI is superior to CT in stages 1 and 3, accurately diagnosing stages 2, 4, and 5, with a sensitivity of 93.30%, specificity of 95.65%, PPV of 95%, and NPV of 97%.ConclusionsNon-contrast MRI could be considered the optimal radiation-free imaging modality in staging pediatric renal tumors mainly Wilm’s tumor as it offers high sensitivity and specificity of capsular and vascular infiltration, compared to contrast-enhanced CT especially in cases with impaired renal functions.

Pediatric cancer incidence among individuals with overgrowth syndromes and overgrowth features: A population-based assessment in seven million children.

Overgrowth syndromes (e.g., Beckwith-Wiedemann) are associated with an increased risk of pediatric cancer, although there are few population-based estimates of risk. There are also limited studies describing associations between other overgrowth features (e.g., hepatosplenomegaly) and pediatric cancer. Therefore, cancer risk among children with these conditions was evaluated with data from a large, diverse population-based registry linkage study. This study includes all live births in Texas during the years 1999-2017. Children with overgrowth features and syndromes were identified from the Texas Birth Defects Registry; children with cancer were identified by linkage to the Texas Cancer Registry. Cox regression models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the association between each overgrowth syndrome/feature and cancer, which were adjusted for infant sex and maternal age. In the total birth cohort (n=6,997,422), 21,207 children were identified as having an overgrowth syndrome or feature. Children with Beckwith-Wiedemann syndrome were 42 times more likely to develop pediatric cancer (95% CI, 24.20-71.83), with hepatoblastoma being the most common, followed by Wilms tumor. The presence of any isolated overgrowth feature was associated with increased cancer risk (HR, 4.70; 95% CI, 3.83-5.77); associations were strongest for hepatosplenomegaly (HR, 23.04; 95% CI, 13.37-39.69) and macroglossia (HR, 11.18; 95% CI, 6.35-19.70). This population-based assessment confirmed prior findings that children with either overgrowth syndromes or features were significantly more likely to develop cancer. Overall, this study supports recommendations for cancer surveillance in children with these conditions and may also inform future research into cancer etiology.

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

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). 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. 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%). 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.

Counts, incidence rates, and trends of pediatric cancer in the United States, 2003-2019.

Cancer is a leading cause of death by disease among children and adolescents in the United States. This study updates cancer incidence rates and trends using the most recent and comprehensive US cancer registry data available. We used data from US Cancer Statistics to evaluate counts, age-adjusted incidence rates, and trends among children and adolescents younger than 20 years of age diagnosed with malignant tumors between 2003 and 2019. We calculated the average annual percent change (APC) and APC using joinpoint regression. Rates and trends were stratified by demographic and geographic characteristics and by cancer type. With 248 749 cases reported between 2003 and 2019, the overall cancer incidence rate was 178.3 per 1million; incidence rates were highest for leukemia (46.6), central nervous system neoplasms (30.8), and lymphoma (27.3). Rates were highest for males, children 0 to 4 years of age, Non-Hispanic White children and adolescents, those in the Northeast census region, the top 25% of counties by economic status, and metropolitan counties with a population of 1 million people or more. Although the overall incidence rate of pediatric cancer increased 0.5% per year on average between 2003 and 2019, the rate increased between 2003 and 2016 (APC = 1.1%), and then decreased between 2016 and 2019 (APC = -2.1%). Between 2003 and 2019, rates of leukemia, lymphoma, hepatic tumors, bone tumors, and thyroid carcinomas increased, while melanoma rates decreased. Rates of central nervous system neoplasms increased until 2017, and then decreased. Rates of other cancer types remained stable. Incidence of pediatric cancer increased overall, although increases were limited to certain cancer types. These findings may guide future public health and research priorities.

Incidence, Mortality and Survival of Pediatric Cancer in Uruguay 2011-2015

Introduction: Childhood cancer is a small proportion of all cancers but is still a major public health problem. Objective: To describe the 5-year incidence and mortality rates and net survival of childhood cancer in Uruguay. Method: Data on all malignant tumors diagnosed in children aged 0-14 were included for the period 2011-2015, obtained from the National Pediatric Registry of Cancer and from the Ministry of Health Mortality Registry, classified according to the International Classification of Childhood Cancer (ICCC-3). Information on the total population was obtained from national census records. Follow up was made until December 2020. Results: The standardized incidence rate was 128/million children per year. The distribution of the disease was similar to developed countries. The overall mortality rate was 28.2/million, with a net overall survival of 79.6% for the total population. Conclusion: Childhood cancer incidence in Uruguay is similar to developed countries. Progress in diagnosis and care have improved survival immensely, but efforts must continue to keep this trend and ameliorate the outcomes.

Pediatric Cancer in the Northeast United States—Reply

Our article (1) set out to analyze data relating to childhood cancer following Dr. Siegel's Centers for Disease Control and Prevention (CDC) descriptive study in 2018 (2) in which a headline result was that “rates were highest in New Hampshire.” Messmer raises several questions, which seem to distill to: (i) was our conclusion appropriate, that New Hampshire's (NH) incidence of childhood cancer was not statistically significantly higher than the rest of the Northeast; (ii) did we draw conclusions beyond the scope of the analyses; and (iii) how should resources be directed in the goal of preventing childhood cancer?(i) When all races are analyzed together, NH has the highest incidence of all states, but as we reported, it is not a statistical outlier. However, incidence varied across race/ethnicity groups by more than 38% and was highest in White children (Table 1; ref. 1), making race/ethnicity a potentially important confounder. To avoid the criticism that differences in incidence were simply due to differences in population composition, stratification by race/ethnicity was needed. Both overall and stratified measures are potentially useful, depending on the goal. If we want to discuss the burden of childhood cancer, then overall incidence should be the focus. If we want to make unbiased comparisons as a first step in the journey toward causal inferences, stratifying by major confounders is the methodologically correct approach. We note that NH's age-standardized rates do not rank highest in any race/ethnicity stratum, and this is not dependent on the use of Bonferroni (Table 1; ref. 1). Did the high incidence in NH bias our regional comparisons? NH accounted for only 2.5% of cases in the Northeast, and 2.4% of the population, so this seems unlikely. The Tiwari method of modification that we used means that the comparison we reported is between NH and the rest of the Northeast, and not between NH and the Northeast including NH.(ii) Messmer is incorrect in her assertion that we drew conclusions that de-emphasized any single possible cause of the observed patterns because we drew no conclusions about etiology. Our conclusions are limited to the findings relating to our a priori hypotheses that assessed NH's comparison with the Northeast, and the Northeast's comparison with other regions. We presented a balanced discussion of many possible causes but drew no conclusions about them.(iii) Our study was a first step toward identifying the extent of the problem, and we believe our neighbors in the Northeast should be as deeply concerned about childhood cancer as we are in NH. A different kind of study is needed to explore the reasons for these patterns, but etiologic research requires large numbers of participants with detailed individual-level data which are not readily available and this would be difficult to conduct in a single state with a relatively small number of cancers. The NCI is leading the National Childhood Cancer Data Initiative to pool data from many sources and states for research, recognizing that, “due to their rare nature, it has been challenging to collect substantial and vital information on a large scale to study and understand the needs for this unique population of cancer patients.” (3) NH is eligible to participate.NH and neighboring states each have special local concerns about high pediatric cancer incidence, pollution, and other factors. Arguments over whether NH ranks #1 are distracting; clearly the state's very high incidence should be investigated, but our findings open the door to a larger effort, if those involved in government throughout the Northeast act together on their collective responsibility. A Northeastern coalition could pool resources toward the conduct of research that includes local areas of concern in multiple states, because large-scale, rigorously designed and analyzed studies of childhood cancer etiology have the greatest chance of determining causes.The findings and conclusions in this report are those of the authors and do not necessarily represent the official positions of the New Hampshire Department of Environmental Services, the New Hampshire Department of Health and Human Services, or the CDC.See the original Letter to the Editor, p. 149J.R. Rees reports other support from the New Hampshire Department of Health and Human Services during the conduct of the study. M.O. Celaya reports other support from the New Hampshire Department of Health & Human Services during the conduct of the study. No disclosures were reported by the other authors.

Pediatric cancer incidence in China.

Pediatric cancer incidence in China.

Selected Articles from This Issue

Evaluations of cancer etiology and safety and effectiveness of cancer treatments are predicated on large numbers of patients with sufficient baseline and follow-up data. To assess feasibility of FDA's Sentinel System's electronic healthcare data for surveillance of malignancy onset and examination of product safety, this study by Haug and colleagues examined patterns of enrollment surrounding new-onset cancers. The study found that the FDA Sentinel System's electronic healthcare data may be useful for characterizing relatively short latency cancer risk, examining cancer drug utilization and safety post diagnosis, and conducting surveillance for acute adverse events among patients with cancers. As a national distributed system with electronic health data, the Sentinel system provides opportunity for rapid pharmacoepidemiologic assessments relevant in oncology.This study sought to clarify and extend a 2018 descriptive study by the Centers for Disease Control and Prevention that reported high pediatric cancer incidence in New Hampshire. Statistically comparing national, regional and state data, this new study by Rees and colleagues confirms that the Northeast has the highest pediatric cancer incidence in the country, and that no single state within the Northeast is a statistical outlier. These findings emphasize the need for partnerships between northeastern states’ health departments and epidemiologists, to understand the causes of the region's high burden of pediatric cancer, and to identify possible solutions.Prior studies suggest there are persistent racial/ethnic disparities in overall and breast cancer mortality among women with metastatic disease, yet to what extent comorbidity burden contributes to these disparities is unclear. In this retrospective cohort study of 995 women newly diagnosed with metastatic breast cancer in a large diverse, integrated healthcare system, Wallner and colleagues found that medical comorbidities such as diabetes, and hypertension were common. They also found comorbidities were associated with an increased risk of both overall and breast cancer mortality and may influence disparities in these outcomes among women with metastatic breast cancer. Optimizing the management of comorbidities may therefore help to reduce these disparities and improve mortality outcomes in women with metastatic breast cancer.Lung cancer is the leading cause of cancer-related death. Smith-Byrne and colleagues used two complementary approaches to triangulate the role of circulating isovalerylcarnitine (IVC) in lung cancer aetiology - one based on genetic measurements of IVC in large genome-wide associations studies and one based on direct measurements of IVC in pre-diagnostic samples from population cohorts. The authors observed a protective effect for IVC that was independent of tobacco exposure (ORlog10 = 0.43, 95% CI: 0.29–0.63). Circulating IVC is modifiable through diet and warrants further investigation for a potential role in lung cancer prevention.

Survival estimates of childhood malignancies treated at the Mexican telethon pediatric oncology hospital.

Pediatric cancer incidence in Mexico is ~160/million/year with leukemias making 49.8% of the cases. While survival rates have been reported in various Mexican studies, no data is available from the Telethon Pediatric Oncology Hospital-HITO, a nonprofit private institution specialized exclusively in comprehensive pediatric oncology care in the country that closely follows high-income countries' advanced standards of cancer care. To determine overall survival (OS) and relapse-free survival (RFS) in patients treated at HITO between December 2013 and February 2018. Secondary analysis of data extracted from medical records. It included 286 children aged 0-17 years diagnosed with various cancers grouped into three categories based on location: (1) Acute lymphoblastic leukemia (ALL), (2) tumors within the central nervous system (TWCNS), and (3) tumors outside the CNS (TOCNS). OS and RFS rates for patients who completed 1 (n=230) and 3 (n=132) years of follow-up after admission were computed by sex, age, and cancer location, and separately for a subsample (1-year=191, 3-years=110) who fulfilled the HITO criteria (no prior treatment, underwent surgery/chemotherapy when indicated, and initiated therapy). TOCNS accounted for 45.1%, but ALL was the most frequent single diagnosis with 28%. Three-year OS for patients with ALL, TWCNS, and TOCNS who fulfilled the HITO criteria were 91.9%, 86.7%, and 79.3%, respectively; for 3-year RFS these were 89.2%, 60%, and 72.4%. Boys showed slightly higher OS and RFS, but no major differences or trends were seen by age group. This study sets a relevant reference in terms of survival and relapse for children with cancer in Mexico treated at a private oncology center that uses a comprehensive and integrated therapeutic model.

Pediatric Cancer By Race, Ethnicity and Region in the United States.

In a 2018 descriptive study, cancer incidence in children (age 0-19) in diagnosis years 2003 to 2014 was reported as being highest in New Hampshire and in the Northeast region. Using the Cancer in North America (CiNA) analytic file, we tested the hypotheses that incidence rates in the Northeast were higher than those in other regions of the United States either overall or by race/ethnicity group, and that rates in New Hampshire were higher than the Northeast region as a whole. In 2003 to 2014, pediatric cancer incidence was significantly higher in the Northeast than other regions of the United States overall and among non-Hispanic Whites and Blacks, but not among Hispanics and other racial minorities. However, there was no significant variability in incidence in the states within the Northeast overall or by race/ethnicity subgroup. Overall, statistically significantly higher incidence was seen in the Northeast for lymphomas [RR, 1.15; 99% confidence interval (CI), 1.10-1.19], central nervous system neoplasms (RR, 1.12; 99% CI, 1.07-1.16), and neuroblastoma (RR, 1.13; 99% CI, 1.05-1.21). Pediatric cancer incidence is statistically significantly higher in the Northeast than in the rest of the United States, but within the Northeast, states have comparable incidence. Differences in cancer subtypes by ethnicity merit further investigation. Our analyses clarify and extend previous reports by statistically confirming the hypothesis that the Northeast has the highest pediatric cancer rates in the country, by providing similar comparisons stratified by race/ethnicity, and by assessing variability within the Northeast.

Abstract 5223: Pediatric cancer incidence among racial/ethnic groups living in rural/urban areas of the United States

Abstract Background: The impact of urban/rural residence on pediatric cancer incidence has not been well studied. Additionally, the impact of race/ethnicity on pediatric cancer incidence by urban/rural status has not been evaluated, which could inform our understanding of the roles of shared genetic and environmental causes of these malignancies. Methods: Using SEER18, we calculated pediatric cancer incidences for individuals diagnosed 2000-2018 by residence (urban/rural). Next we calculated incidence rate ratios (IRR) to evaluate the role of race/ethnicity on incidence stratified by urban vs. rural status. Results: See Table. Overall, most incidences were similar by residence, i.e., lower or equal in rural versus urban areas, except the rural group having significantly lower incidences of leukemias and germ cell tumors (GCTs). Additionally, the incidence of most pediatric cancers was consistently higher among NHW in both urban and rural areas. Yet, incidence of some cancers differed by urban/rural residence within race/ethnicity: retinoblastoma (NHB, Hispanic, and API); soft tissue sarcomas (NHB and AI/AN); hepatic tumors (AI/AN); and GCTs (API). Conclusions: In general, Hispanic, NHB, and AI/AN populations have similar incidence of pediatric cancers in urban or rural areas. These groups have some shared bio-geographical ancestry, suggesting a possible effect of genetics on risk. Further, differences in incidence by urban/rural residence within race/ethnicity suggest a possible role of environment for some cancers. Interestingly, for GCTs, NHB had a lower IRR in urban and rural areas, but Hispanic populations had a significantly higher IRR. This finding, consistent with a recent study in adults, suggest that African ancestry may confer a protective effect on risk of GCTs. Further, the GCT effect sizes were more protective in the rural group for each race/ethnicity group, suggesting the possible role of environmental factors and interactions of environment with ancestry. Pediatric cancer incidence by race/ethnicity group and urban/rural residence Citation Format: Priya B. Shetty, Philip J. Lupo, Michael E. Scheurer. Pediatric cancer incidence among racial/ethnic groups living in rural/urban areas of the United States [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5223.

Abstract 3652: Maternal body mass index, diabetes, and gestational weight gain and risk for pediatric cancer in offspring: A systematic review and meta-analysis

Abstract Introduction: Pediatric cancer incidence has steadily increased concurrent with the rise in adult obesity, however, associations between maternal obesity and associated comorbidities and pediatric cancer risk remain understudied. Methods: A comprehensive and systematic literature search in PubMed and EMBASE databases from their inception to March 15th, 2021. Eligible studies reported risk estimates, sample sizes, and provided sufficient description of outcome and exposure ascertainment. Studies were excluded if not complete, published, peer-reviewed studies, or if provided incompatible exposure data. Data quality was assessed according to Newcastle-Ottawa Scale (NOS) guidelines and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Random-effects models were used to estimate pooled effects. Results: Thirty-four studies were included, covering 3,404,747 subjects and 14,706 pediatric cancer cases for pre-pregnancy BMI; 14,748,772 subjects and 44,628 pediatric cancer patients for maternal diabetes; and 2,124,647 participants and 15,915 pediatric cancer cases for gestational weight gain. Pre-pregnancy BMI was significantly associated with leukemia risk in offspring (OR per 5-unit BMI increase =1.07 [95% CI = 1.04-1.11] I2 = 0.0%). Any maternal diabetes was positively associated with acute lymphoblastic leukemia risk (OR=1.46 [95% CI = 1.28-1.67] I2 = 0.0%), even after restricting to birthweight-adjusted analyses (OR [95% CI] = 1.74 [1.29-2.34] I2 = 0.0%), and inversely associated with risk of central nervous system tumors (OR=0.73 [95% CI = 0.55-0.97] I2 = 0.0%). Pre-gestational diabetes (OR=1.57 [95% CI = 1.11-2.24] I2 = 26.8%) and gestational diabetes (OR=1.40 [95% CI = 1.12-1.75] I2 = 0.0%) were also significantly associated with acute lymphoblastic leukemia risk. No significant associations were observed for gestational weight gain and pediatric cancer risk. Conclusions: Maternal obesity and diabetes may be etiologically linked to pediatric cancer, particularly leukemia and central nervous system tumors. Our findings support appropriate weight management and glycemic control as important components of maternal care and offspring health. Further validation studies are warranted. Citation Format: Andrew R. Marley, Allison Domingues, Taumoha Ghosh, Lucie M. Turcotte, Logan G. Spector. Maternal body mass index, diabetes, and gestational weight gain and risk for pediatric cancer in offspring: A systematic review and meta-analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3652.

Investigation of Relationships Between the Geospatial Distribution of Cancer Incidence and Estimated Pesticide Use in the U.S. West.

The objective of the study was to evaluate the potential geospatial relationship between agricultural pesticide use and two cancer metrics (pediatric cancer incidence and total cancer incidence) across each of the 11 contiguous states in the Western United States at state and county resolution. The pesticide usage data were collected from the U.S. Geological Survey Pesticide National Synthesis Project database, while cancer data for each state were compiled from the National Cancer Institute State Cancer Profiles. At the state spatial scale, this study identified a significant positive association between the total mass of fumigants and pediatric cancer incidence, and also between the mass of one fumigant in particular, metam, and total cancer incidence (P‐value < 0.05). At the county scale, the relationship of all cancer incidence to pesticide usage was evaluated using a multilevel model including pesticide mass and pesticide mass tertiles. Low pediatric cancer rates in many counties precluded this type of evaluation in association with pesticide usage. At the county scale, the multilevel model using fumigant mass, fumigant mass tertiles, county, and state predicted the total cancer incidence (R‐squared = 0.95, NSE = 0.91, and Sum of square of residuals [SSR] = 8.22). Moreover, this study identified significant associations between total fumigant mass, high and medium tertiles of fumigant mass, total pesticide mass, and high tertiles of pesticide mass relative to total cancer incidence across counties. Fumigant application rate was shown to be important relative to the incidence of total cancer and pediatric cancer, at both state and county scales.

Assessment of Pediatric Cancer and Its Relationship to Environmental Contaminants: An Ecological Study in Idaho.

The primary aim of this study was to determine the degree to which a multivariable principal component model based on several potentially carcinogenic metals and pesticides could explain the county‐level pediatric cancer rates across Idaho. We contend that human exposure to environmental contaminants is one of the reasons for increased pediatric cancer incidence in the United States. Although several studies have been conducted to determine the relationship between environmental contaminants and carcinogenesis among children, research gaps exist in developing a meaningful association between them. For this study, pediatric cancer data was provided by the Cancer Data Registry of Idaho, concentrations of metals and metalloids in groundwater were collected from the Idaho Department of Water Resources, and pesticide use data were collected from the United States Geological Survey. Most environmental variables were significantly intercorrelated at an adjusted P‐value <0.01 (97 out of 153 comparisons). Hence, a principal component analysis was employed to summarize those variables to a smaller number of components. An environmental burden index (EBI) was constructed using these principal components, which categorized the environmental burden profiles of counties into low, medium, and high. EBI was significantly associated with pediatric cancer incidence (P‐value <0.05). The rate ratio of high EBI profile to low EBI profile for pediatric cancer incidence was estimated as 1.196, with lower and upper confidence intervals of 1.061 and 1.348, respectively. A model was also developed in the study using EBI to estimate the county‐level pediatric cancer incidence in Idaho (Nash‐Sutcliffe Efficiency = 0.97).

Pediatric neurological cancer incidence and trends in the United States, 2000-2018.

To characterize the epidemiological trends and sociodemographic variation of pediatric and adolescent neurological cancers by histological subtypes over time in the USA. A total of 16,511 patients aged 0-19years diagnosed with neurological cancers between 2000 and 2018, including 13,024 with central nervous system (CNS) neoplasms and 3,487 with neuroblastomas, were identified from 18 registries of the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Incidence trends over time and incidence rate ratios by race/ethnicity, sex, and age were calculated for histological subtype. Age-standardized incidence rates (ASIR) by year of diagnosis and average annual percent changes (AAPC) were calculated to measure incidence rates. ASIR by race/ethnicity, sex, and age were calculated to examine the incidence variation by these factors. Overall, age-standardized annual incidence per 100,000 person-years increased from 2.20 in 2000 to 3.21 in 2018 with an AAPC of 1.4% (95% confidence interval or CI: 0.5% to 2.4%); however, that of Hispanic decreased from 2.93 in 2000 to 2.59 in 2018 with an AAPC of -0.8% (95% CI: -1.2% to -0.3%). Non-Hispanic Black children and adolescents had a statistically significantly lower incidence than non-Hispanic White peers both for CNS neoplasms (incidence rate ratio or IRR: 0.67; 95% CI: 0.63 to 0.71) and neuroblastomas (IRR: 0.75; 95% CI: 0.68 to 0.83). Females generally had a lower incidence than males, especially among those with intracranial and intraspinal embryonal tumors (IRR: 0.69; 95% CI: 0.64 to 0.75). The highest incidence rate of neuroblastoma was among newborns aged less than 1year, and the highest incidence rate of CNS neoplasms was among children aged 1-4years. The incidence of neurological cancers has increased among children and adolescents from 2000 to 2018, with wide variation across demographic groups.

Puberty and sex in pediatric thyroid cancer: could expression of estrogen and progesterone receptors affect prognosis?

ObjectiveA sharp increase in pediatric thyroid cancer incidence is observed during adolescence, driven mainly by girls. Differences in disease presentation across sexual maturity stages raise the question of whether sex steroids have a role in the heterogeneity. The aims of this study were to analyze the influence of puberty and sex on clinical presentation and prognosis and to evaluate the correlation between the expression of sex hormone receptors.Design and methodsClinical records and immunohistochemical of specimens from 79 patients were analyzed. Puberty was analyzed by two criteria: end of puberty and beginning, in which the age of 10 was the cutoff.ResultsPostpubertal were more frequently classified as having low-risk disease and a lower frequency of persistent disease, especially when the completion of puberty was used as the criteria. Male sex was associated with a higher risk of persistent disease at the end of the observation period. Estrogen receptor α positivity was low in the entire sample, while progesterone receptor positivity was positive in 30% of the cases. Female hormone receptor expression was not associated with sex, American Thyroid Association risk score, persistent structural disease, or pubertal status.ConclusionOur study showed that the completion of puberty correlated best with the clinical behaviour of pediatric thyroid cancer. It was also shown that postpubertal patients have a less aggressive initial presentation and better outcomes. However, this observation could not be explained by the expression of estrogen and progesterone receptors in the primary tumors.

Geospatial Distribution of Age-Adjusted Incidence of the Three Major Types of Pediatric Cancers and Waterborne Agrichemicals in Nebraska.

This study was conducted to examine, at the county level, the relationship between pediatric cancer incidence rate and atrazine and nitrate mean concentrations in surface and groundwater. A negative binomial regression analysis was performed to investigate the association between central nervous system (CNS) tumors, leukemia, lymphoma, and atrazine and nitrate mean concentrations in groundwater. The age‐adjusted brain and other CNS cancer incidence was higher than the national average in 63% of the Nebraska counties. After controlling for the counties socio‐economic status and nitrate concentrations in groundwater, counties with groundwater atrazine concentrations above 0.0002 µg/L had a higher incidence rate for pediatric cancers (brain and other CNS, leukemia, and lymphoma) compared to counties with groundwater atrazine concentrations in the reference group (0.0000–0.0002 µg/L). Additionally, compared to counties with groundwater nitrate concentrations between 0 and 2 mg/L (reference group), counties with groundwater nitrate concentrations between 2.1 and 5 mg/L (group 2) had a higher incidence rate for pediatric brain and other CNS cancers (IRR = 8.39; 95% CI: 8.24–8.54), leukemia (IRR = 7.35; 95% CI: 7.22–7.48), and lymphoma (IRR = 5.59; CI: 5.48–5.69) after adjusting for atrazine groundwater concentration and the county socio‐economic status. While these findings do not indicate a causal relationship, because other contaminants or cancer risk factors have not been accounted for, they suggest that atrazine and nitrate may pose a risk relative to the genesis of pediatric brain and CNS cancers, leukemia, and lymphoma.

Surveillance, Epidemiology, and End Results Database update for pediatric thyroid carcinomas incidence and survival trends 2000–2016

ObjectiveReview the trends in pediatric thyroid carcinomas using the Surveillance, Epidemiology, and End Results (SEER) Database. MethodsInstitutional review board approval was obtained from Mercy-Bon Secours. The National Cancer Institute's SEER database was used for all cases of pediatric thyroid cancer between the years 2000 and 2016 for patients aged 0–19. Patients were grouped by carcinoma histological subtype, disease specific survival based on treatment modality, and demographic data. Treatment methods were compared using Fifteen-Year Disease Specific Survival Curves. Results1175 pediatric patients were identified. The average age-adjusted rate of malignancy was 0.3 per 100,000 patients. Incidence of pediatric thyroid cancer was approximately 1:3.6, male to female. The papillary follicular variant histological subtype was the most common (n = 689, 58.6%), followed by papillary (n = 223, 18.9%), follicular (n = 153, 13.1%), and medullary (n = 110, 9.4%). Overall incidence of thyroid carcinomas increased with age, highest in patients aged 15–19 (69.8%). Incidence of medullary thyroid carcinomas was highest in patients aged 0–9. Patients aged 10–19 treated with surgery alone had the highest disease specific survival fifteen-years past initial diagnoses and treatment in all histologic subtypes (p < 0.05). Patients with metastatic medullary thyroid carcinoma at initial diagnosis who underwent surgery alone showed significantly poorer fifteen-year disease specific survival when compared to other histologic subtypes (p < 0.05). ConclusionThere was improved prognosis in pediatric thyroid carcinomas if diagnosed and treated early. All four major histological subtypes exhibit an increase in overall survival rates, (excluding medullary carcinomas).