The incidence of chemotherapy-induced transient hyperglycemia in the present study cohort is comparable to that reported in previous pediatric ALL patients. This finding is interesting in view of the elevated prevalence of obesity and the underlying dietary behaviors in this Hispanic study cohort.
Despite oncology practice settings that might be expected to achieve otherwise, CCOP sites did not enroll a larger proportion of AYAs in clinical trials than traditional COG institutions. Our findings suggest that the CCOP (now the NCI Community Oncology Research Program) can be leveraged for developing targeted interventions for overcoming AYA enrollment barriers.
In our cohort of ALL patients, BMI was elevated at diagnosis (mean standardized BMI z-score = 0.22, standard deviation = 1.4) then increased and remained elevated for the entire duration of chemotherapy. Children who were 2-9 years of age at diagnosis began therapy with a substantially lower BMI and remained lower over the course of chemotherapy than patients aged 10-18 years at diagnosis. It will be important for future investigations to explore the biological and behavioral factors that may underlie such differential patterns of BMI change over time.
Acute lymphoblastic leukemia (ALL), the most common malignancy in children, constitutes 25% of all pediatric cancer. Childhood cancer patients who are obese at diagnosis represent a particular challenge for the oncologist. Obesity may complicate chemotherapy dose determination, and has been associated with decreased overall and event-free survival in a number of adult cancer patients, and more recently in pediatric patients. The purpose of the present study was to examine whether obesity at diagnosis was associated with decreased overall and event-free survival in a cohort of 322 predominantly Hispanic pediatric patients with B-precursor ALL. Obesity was classified as an age-standardized and sex-standardized body mass index z-score at or above the 95th percentile. Hazard ratios (HRs) for overall and event-free survival were assessed using Cox proportional hazards regression modeling. Obesity at diagnosis was not associated with decreased overall survival (HR = 1.40, 95% confidence interval = 0.69-2.87) or event-free survival (HR = 1.08, 95% confidence interval = 0.65-1.82) in the overall cohort or in either of the 2 age-at-diagnosis (2 to 9 y; 10 to 18 y) subgroups. Our finding of no obesity-related prognostic effect in the overall cohort and in the under 2 to 9-year age-at-diagnosis cohort was consistent with the previous large-scale study of ALL patients; the absence of a prognostic effect in the 10 to 18-year age-at-diagnosis cohort, however, conflicted with previous findings.
PurposeOsteosarcoma is the most common bone tumor in children, adolescents, and young adults. In contrast to other childhood malignancies, no biomarkers have been consistently identified as predictors of outcome. This study was conducted to assess the microRNAs(miRs) expression signatures in pre-treatment osteosarcoma specimens and correlate with outcome to identify biomarkers for disease relapse.ResultsA 42-miRs signature whose expression levels were associated with overall and relapse-free survival waas identified. There were 8 common miRs between the two sets of survival-associated miRs. Bioinformatic analyses of these survival-associated miRs suggested that they might regulate genes involved in ubiquitin proteasome system, TGFb, IGF, PTEN/AKT/mTOR, MAPK, PDGFR/RAF/MEK/ERK, and ErbB/HER pathways.MethodsThe cohort consisted of 27 patients of 70% Mexican-American ethnicity. High-throughput RT-qPCR approach was used to generate quantitative expression of 754 miRs in the human genome. We examined tumor recurrence status, survival time and their association with miR expression levels by Cox proportional hazard regression analysis. TargetScan was used to predict miR/genes interactions, and functional analyses using KEGG, BioCarta, Gene Ontology were applied to these potential targets to predict deregulated pathways.ConclusionsOur findings suggested that these miRs might be potentially useful as prognostic biomarkers and therapeutic targets in pediatric osteosarcoma.
The 15% response rate to Rebeccamycin analogue observed in patients with rhabdomyosarcoma, while of interest, is associated with significant myelosuppression. With a global response rate of 3% observed in children with relapsed CNS and non-CNS solid tumors, further development of Rebeccamycin analogue in pediatric solid tumors is not recommended.
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