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Background: Childhood melanocytic tumors represent a diagnostic and therapeutic challenge, and additional research is needed to better define the natural history of these tumors. Methods: The authors developed a comprehensive, prospective registry called Molecular Analysis of Childhood Melanocytic Tumors for children and adolescents with an atypical Spitz tumor/Spitz melanoma (AST/SM), conventional or adult‐type melanoma (CM), melanoma arising in a giant congenital nevus (MCM), or atypical melanocytic proliferation of other types (OT) to better define the clinical behavior of these lesions by incorporating an integrated clinicopathologic and molecular analysis using centralized pathology review and various platforms, including fluorescence in situ hybridization; array comparative genomic hybridization; and whole genome, exome, and capture targeted panels. Results: From May 2016 to November 2019, 70 children were enrolled with a median age at diagnosis of 9.1 years. Thirty‐seven had AST/SM, 17 had CM, 4 had MCM, and 12 had OT. Patients with AST/SM were younger (median age, 7 years), and their tumor most commonly arose in the extremities and trunk. The most common gene rearrangements included MAP3K8 and ALK. None of the 33 patients who underwent a TERT promoter mutation analysis had a mutation, and all patients were alive. Among the CM patients, the median age was 13 years; 11 had a BRAFV600E mutation, and 7 had a TERT promoter mutation. Three patients died of their disease. All 4 patients with MCM harbored an NRASQ61 mutation and died of their disease. The OT group was heterogenous, and all patients survived. Conclusions: The incorporation of an integrated clinicopathologic and genomic analysis identifies distinct subgroups of pediatric melanocytic lesions that have different clinical behaviors. The integration of this combined diagnostic modality can help to individualize diagnoses and treatments for these patients. This is a prospective registry of pediatric melanocytic lesions that integrates clinicopathologic and genomic features to better predict the clinical behavior of these lesions. [ABSTRACT FROM AUTHOR]

Background: Children with acute lymphoblastic leukemia (ALL) have an increased risk of obesity and short stature. To the authors' knowledge, data regarding patients treated on contemporary protocols without cranial irradiation are limited.Methods: Changes in z scores for body mass index (BMI), height, and weight from the time of diagnosis to 5 years off therapy were evaluated using multivariable analysis in 372 children with ALL who were aged 2 to 18 years at the time of diagnosis and were enrolled on the St. Jude Children's Research Hospital Total XV protocol from 2000 through 2007.Results: The percentage of overweight/obese patients increased from 25.5% at the time of diagnosis to approximately 50% during the off-therapy period. Median BMI z scores increased significantly during glucocorticoid therapy (induction: ∆0.56; 95% confidence interval [95% CI], 0.29-0.64 [P<.001]; and reinduction II: ∆0.22; 95% CI, 0.13-0.49 [P=.001]) and during the first year after therapy (∆0.18; 95% CI, 0.08-0.46 [P=.006]). Among patients who were of healthy weight/underweight at the time of diagnosis, those aged 2 to <10 years at diagnosis had a significantly higher risk of becoming overweight/obese during or after therapy compared with those aged ≥10 years (P=.001). Height z scores declined during treatment and improved after therapy. Being aged 2 to <10 years at the time of diagnosis, being of low-risk status, having a white blood cell count < 50×109 /L at the time of diagnosis, and having negative central nervous system disease were associated with significantly better improvements in z scores for height during the off-therapy period compared with being aged ≥10 years, being of standard-risk/high-risk status, having a white blood cell count  ≥ 50×109 /L, and having positive central nervous system disease, respectively.Conclusions: The results of the current study demonstrate that obesity is prevalent, and height growth, especially in patients with identified risk factors, appears compromised. Multidisciplinary intervention should begin during induction therapy and continue during the off-therapy period. [ABSTRACT FROM AUTHOR]

Background: Children with acute lymphoblastic leukemia (ALL) can develop reduced bone mineral density (BMD). However, data from patients who received treatment on a frontline regimen without cranial irradiation are limited, and no genome-wide analysis has been reported.Methods: Lumbar BMD was evaluated by quantitative computed tomography at diagnosis, after 120 weeks of continuation therapy, and after 2 years off therapy in pediatric patients with ALL (ages 2-18 years at diagnosis) who were treated on the St. Jude Total XV Protocol. Clinical, pharmacokinetic, and genetic risk factors associated with decreased BMD Z-scores were evaluated.Results: The median BMD Z-score in 363 patients was 0.06 at diagnosis, declined to -1.08 at week 120, but partly recovered to -0.72 after 2 years off therapy; BMD in patients with low BMD Z-scores at diagnosis remained low after therapy. Older age (≥10 years vs 2-9.9 years at diagnosis; P < .001), a higher BMD Z-score at diagnosis (P = .001), and a greater area under the plasma drug concentration-time curve for dexamethasone in weeks 7 and 8 of continuation therapy (P = .001) were associated with a greater decrease in BMD Z-score from diagnosis to week 120. Single-nucleotide polymorphisms in 2 genes important in osteogenesis and bone mineralization (COL11A1 [reference single-nucleotide polymorphism rs2622849]; P = 2.39 × 10-7 ] and NELL1 [rs11025915]; P = 4.07 × 10-6 ]) were associated with a decreased BMD Z-score. NELL1 (P = .003) also was associated with a greater dexamethasone area under the plasma drug concentration-time curve.Conclusions: BMD Z-scores decreased during therapy, especially in patients who had clinical, pharmacokinetic, and genetic risk factors. Early recognition of BMD changes and strategies to optimize bone health are essential. Cancer 2018;124:1025-35. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Sedentary behaviors are associated with poor health outcomes in the general population, but their clinical impact on adult survivors of childhood acute lymphoblastic leukemia (ALL) has not been characterized to date. In the current study, we described the prevalence of sedentary behaviors in survivors of ALL and examined associations between time spent sedentary and body composition and onset of cardiovascular disease (CVD) risk factors.Methods: Participants' self-reported screen time (eg, television, computer) and activity as measured by accelerometer were used to determine activity time (sedentary, light activity, and moderate or vigorous physical activity). The percentage of time spent in each activity was compared between 331 survivors of ALL and 330 controls. Associations between time sedentary and body composition were evaluated in survivors using linear regression models. Cox proportional hazard models were used to examine the association between time sedentary at baseline and CVD risk factor onset during follow-up.Results: Survivors spent approximately 65% of their time sedentary, 32% in light activity, and 2% in moderate or vigorous physical activity compared with 67% (P = .04), 30% (P<.01), and 3% (P<.01), respectively, in controls. Among survivors, percentage lean body mass decreased by 1.0% ± 0.4% (P = .01) per 10% increase in time sedentary. Survivors who were sedentary ≥60% per day were found to be at an increased risk of high total cholesterol (hazard ratio, 2.52; 95% confidence interval, 1.12-5.64) and any CVD risk factor (hazard ratio, 1.96; 95% confidence interval, 1.16-3.30).Conclusions: Sedentary behavior is associated with low lean mass and CVD risk factor development and should be limited in survivors of childhood ALL. Cancer 2018;124:1036-43. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Indications for and delivery of adjuvant therapies for pediatric nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) have been derived largely from adult studies; therefore, significant concern remains regarding radiation exposure to normal tissue. The authors report long-term treatment outcomes and toxicities for pediatric and young adult patients with high-grade NRSTS who were treated on a prospective trial using limited-margin radiotherapy.Methods: Sixty-two patients (ages 3-22 years) with predominantly high-grade NRSTS requiring radiation were treated on a phase 2 institutional study of conformal external-beam radiotherapy and/or brachytherapy using a 1.5-cm to 2-cm anatomically constrained margin. The estimated cumulative incidence of local failure, Gray's method estimated cumulative incidence of local failure, Kaplan-Meier method estimated survival, competing-risk regression model determined predictors of disease outcome, and toxicity was reported according to CTCAE v2.0.Results: At a median follow-up of 5.1 years (range, 0.2-10.9 years), 9 patients had experienced local failure. The 5-year overall cumulative incidence of local failure was 14.8% (95% confidence interval [CI], 7.2%-25%), and all but 1 local failure occurred outside the highest-dose irradiation volume. The 5-year Kaplan-Meier estimates for event-free and overall survival were 49.3% (95% CI, 36.3%-61.1%) and 67.9% (95% CI, 54.2%-78.3%), respectively. Multivariable analysis indicated that younger age was the only independent predictor of local recurrence (P = .004). The 5-year cumulative incidence of grade 3 or 4 late toxicity was 15% (95% CI, 7.2%-25.3%).Conclusions: The delivery of limited-margin radiotherapy using conformal external-beam radiotherapy or brachytherapy provides a high rate of local tumor control without an increase in marginal failures and with acceptable treatment-related morbidity. Cancer 2017;123:4419-29. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND Childhood cancer survivors (CCSs) are at risk for obesity. The purpose of this project was to determine which clinical measures of body composition are most accurate among CCSs in comparison with dual-energy x-ray absorptiometry (DXA). METHODS The agreement between the body mass index (BMI), skinfold percent body fat, and waist-to-height ratio (WHtR) and DXA was evaluated among 1361 CCSs (mean age, 32.4 ± 7.7 years) 10 or more years after the diagnosis. The sensitivity and specificity of BMI, skinfold, and WHtR obesity classifications were calculated with respect to DXA. Log-binomial regression, stratified by sex, was used to evaluate treatment-related factors for misclassification as nonobese by BMI, skinfolds, and WHtR. RESULTS The mean body fat values were 23.3% ± 7.7% (males) and 32.3% ± 8.1% (females) for skinfolds and 26.9% ± 7.4% (males) and 38.4% ± 7.7% (females) for DXA. Pearson correlations between skinfolds and DXA were high ( R = 0.83 for males, R = 0.84 for females). Skinfolds incorrectly classified 34.5% of obese males and 27.3% of obese females. BMI measures were the least sensitive with false-negative rates of 46.4% (males) and 53.1% (females). Males exposed to abdominal/pelvic radiation were at increased risk for misclassification as nonobese by BMI (relative risk, 1.57; 95% confidence interval, 1.25-1.95). The percentages classified as obese were highest with DXA (males, 63.1%; females, 84.8%) and lowest with BMI (males, 35.7%; females, 39.7%). Although skinfolds and WHtR underestimated the percentage classified as obese in comparison with DXA, the differences were not as large. CONCLUSIONS Findings suggest that skinfolds and WHtR are better than BMI for obesity classification in CCSs. Clinicians should be aware of the high risk of misclassifying obese CCSs as nonobese. Cancer 2015;121:2036-2043. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: It is unclear whether routine pelvic imaging is needed in patients with Wilms tumor. Thus, the primary objective of the current study was to examine the role of routine pelvic computed tomography (CT) in a cohort of pediatric patients with Wilms tumor. METHODS: With institutional review board approval, the authors retrospectively identified 110 patients who had Wilms tumor diagnosed between January 1999 and December 2009 with surveillance imaging that continued through March 2011. The authors estimated overall survival (OS), event-free survival (EFS), and dosimetry from dose length product (DLP) conversion to the effective dose (ED) for every CT in a subgroup of 80 patients who had CT studies obtained using contemporary scanners (2002-2011). Metal-oxide-semiconductor field-effect transistor (MOSFET) dosimeters were placed within organs of anthropomorphic phantoms to directly calculate the truncal ED. EDDLP was correlated with EDMOSFET to calculate potential pelvic dose savings. RESULTS: Eighty patients underwent 605 CT examinations that contained DLP information, including 352 CT scans of the chest, abdomen, and pelvis; 123 CT scans of the chest and abdomen; 102 CT scans of the chest only; 18 CT scans of the abdomen and pelvis; 9 CT scans of the abdomen only; and 1 CT that was limited to the pelvis. The respective 5-year OS and EFS estimates were 92.8% ± 3% and 2.6% ± 4.3%. Sixteen of 110 patients (15%) developed a relapse a median of 11.3 months (range, 5.0 months to 7.3 years) after diagnosis, and 4 patients died of disease recurrence. Three patients developed pelvic relapses, all 3 of which were symptomatic. The estimated ED savings from sex-neutral CT surveillance performed at a 120-kilovolt peak without pelvic imaging was calculated as 30.5% for the average patient aged 1 year, 30.4% for the average patient aged 5 years, 39.4% for the average patient aged 10 years, and 44.9% for the average patient aged 15 years. CONCLUSIONS: Omitting pelvic CT from the routine, off-therapy follow-up of patients with Wilms tumor saved an average 30% to 45% of the ED without compromising disease detection. Cancer 2013. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Although reductions in bone mineral density are well documented among children during treatment for cancer and among childhood cancer survivors, little is known about the long-term risk of fracture. The objective of this study was to ascertain the prevalence of and risk factors for fractures among individuals participating in the Childhood Cancer Survivor Study (CCSS).Methods: Analyses included 7414 ≥ 5-year survivors of childhood cancer diagnosed between 1970 and 1986 who completed the 2007 CCSS follow-up questionnaire and a comparison group of 2374 siblings. Generalized linear models stratified by sex were used to compare the prevalence of reported fractures between survivors and siblings.Results: The median ages at follow-up among survivors and siblings were 36.2 years (range, 21.2-58.8 years) and 38.1 years (range, 18.4-62.6 years), respectively, with a median 22.7 years of follow-up after cancer diagnosis for survivors. Approximately 35% of survivors and 39% of siblings reported ≥ 1 fracture during their lifetime. The prevalence of fractures was lower among survivors than among siblings, both in males (prevalence ratio, 0.87; 95% confidence interval, 0.81-0.94; P < .001) and females (prevalence ratio, 0.94; 95% confidence interval, 0.86-1.04; P = .22). In multivariable analyses, increasing age at follow-up, white race, methotrexate treatment, and balance difficulties were associated with increased prevalence of fractures among female survivors (P = .015). Among males, only smoking history and white race were associated with an increased prevalence of fracture (P < .001).Conclusions: Findings from this study indicated that the prevalence of fractures among adult survivors did not increase compared with that of siblings. Additional studies of bone health among aging female cancer survivors may be warranted. [ABSTRACT FROM AUTHOR]

BACKGROUND: The objective of this study was to prospectively evaluate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as an early imaging indicator of tumor histologic response to preoperative chemotherapy and as a possible prognostic factor for event-free survival (EFS) and overall survival in pediatric patients with newly diagnosed, nonmetastatic osteosarcoma who were treated on a single, multi-institutional phase 2 trial. METHODS: Three serial DCE-MRI examinations at week 0 (before treatment), week 9, and week 12 (tumor resection) were performed in 69 patients with nonmetastatic osteosarcoma to monitor the response to preoperative chemotherapy. Four DCE-MRI kinetic parameters (the influx volume transfer constant [ K trans], the efflux rate constant [ k ep], the relative extravascular extracellular space [ v e], and the relative vascular plasma space [ v p]) and the corresponding differences (Δ K trans, Δ k ep, Δ v e, and Δ v p) of averaged kinetic parameters between the outer and inner halves of tumors were calculated to assess their associations with tumor histologic response, EFS, and overall survival. RESULTS: The parameters K trans, v e, v p, and k ep decreased significantly from week 0 to week 9 and week 12. The parameters K trans, v p, and Δ k ep at week 9 were significantly different between responders and nonresponders ( P = .046, P = .021, and P = .008, respectively). These 3 parameters were indicative of histologic response. The parameter Δ v e at week 0 was a significant prognostic factor for both EFS ( P = .02) and overall survival ( P = .03). CONCLUSIONS: DCE-MRI was identified as a prognostic factor for EFS and overall survival before treatment on this trial and was indicative of a histologic response to neoadjuvant therapy. Further studies are needed to verify these findings with other treatment regimens and establish the potential role of DCE-MRI in the development of risk-adapted therapy for osteosarcoma. Cancer 2012. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

The article examines the factors that predicted outcome in pediatric Hodgkin lymphoma (HL) patients who progressed or relapsed after initial treatment with a combined-modality therapy regimen consisting of both chemotherapy and radiation therapy. It was found out that an inadequate response to initial salvage therapy was a significant variable in the analysis of overall survival. It was concluded that there is a very poor prognosis for pediatric patients with relapsed HL who have an inadequate response after initial primary salvage chemotherapy.

The article presents a study on dental abnormalities in childhood cancer survivors. The study centers on the survey containing oral-dental health information that was answered by cancer survivors who were diagnosed between 1970 and 1986, and 2951 siblings from the Childhood Cancer Survivor Study. It suggests that survivors commonly report dental problems such as teeth loss, and severe gingivitis. The study also concludes that radiation and chemotherapy increased the risk of dental abnormalities.