Bone mineral density surveillance for childhood, adolescent, and young adult cancer survivors: evidence-based recommendations from the International Late Effects of Childhood Cancer Guideline Harmonization Group.

2021

2021 Jul 30

2213-8595

<p>Childhood, adolescent, and young adult cancer survivors are at increased risk of reduced bone mineral density. Clinical practice surveillance guidelines are important for timely diagnosis and treatment of these survivors, which could improve bone mineral density parameters and prevent fragility fractures. Discordances across current late effects guidelines necessitated international harmonisation of recommendations for bone mineral density surveillance. The International Late Effects of Childhood Cancer Guideline Harmonization Group therefore established a panel of 36 experts from ten countries, representing a range of relevant medical specialties. The evidence of risk factors for very low and low bone mineral density and fractures, surveillance modality, timing of bone mineral density surveillance, and treatment of very low and low bone mineral density were evaluated and critically appraised, and harmonised recommendations for childhood, adolescent, and young adult cancer survivors were formulated. We graded the recommendations based on the quality of evidence and balance between potential benefits and harms. Bone mineral density surveillance is recommended for survivors treated with cranial or craniospinal radiotherapy and is reasonable for survivors treated with total body irradiation. Due to insufficient evidence, no recommendation can be formulated for or against bone mineral density surveillance for survivors treated with corticosteroids. This surveillance decision should be made by the survivor and health-care provider together, after careful consideration of the potential harms and benefits and additional risk factors. We recommend to carry out bone mineral density surveillance using dual-energy x-ray absorptiometry at entry into long-term follow-up, and if normal (Z-score &gt; -1), repeat when the survivor is aged 25 years. Between these measurements and thereafter, surveillance should be done as clinically indicated. These recommendations facilitate evidence-based care for childhood, adolescent, and young adult cancer survivors internationally.</p>

10.1016/S2213-8587(21)00173-X

Lancet Diabetes Endocrinol

34339631

Sarcopenia and preserved bone mineral density in paediatric survivors of high-risk neuroblastoma with growth failure.

2021

2021 Jun 29

2190-6009

<p><strong>BACKGROUND: </strong>Survival from paediatric high-risk neuroblastoma (HR-NBL) has increased, but cis-retinoic acid (cis-RA), the cornerstone of HR-NBL therapy, can cause osteoporosis and premature physeal closure and is a potential threat to skeletal structure in HR-NBL survivors. Sarcopenia is associated with increased morbidity in survivors of paediatric malignancies. Low muscle mass may be associated with poor prognosis in HR-NBL patients but has not been studied in these survivors. The study objective was to assess bone density, body composition and muscle strength in HR-NBL survivors compared with controls.</p>

<p><strong>METHODS: </strong>This prospective cross-sectional study assessed areal bone mineral density (aBMD) of the whole body, lumbar spine, total hip, femoral neck, distal 1/3 and ultradistal radius and body composition (muscle and fat mass) using dual-energy X-ray absorptiometry (DXA) and lower leg muscle strength using a dynamometer. Measures expressed as sex-specific standard deviation scores (Z-scores) included aBMD (adjusted for height Z-score), bone mineral apparent density (BMAD), leg lean mass (adjusted for leg length), whole-body fat mass index (FMI) and ankle dorsiflexion peak torque adjusted for leg length (strength-Z). Muscle-specific force was assessed as strength relative to leg lean mass. Outcomes were compared between HR-NBL survivors and controls using Student's t-test or Mann-Whitney U test. Linear regression models examined correlations between DXA and dynamometer outcomes.</p>

<p><strong>RESULTS: </strong>We enrolled 20 survivors of HR-NBL treated with cis-RA [13 male; mean age: 12.4&nbsp;±&nbsp;1.6&nbsp;years; median (range) age at therapy initiation: 2.6 (0.3-9.1) years] and 20 age-, sex- and race-matched controls. Height-Z was significantly lower in HR-NBL survivors compared with controls (-1.73&nbsp;±&nbsp;1.38 vs. 0.34&nbsp;±&nbsp;1.12, P&nbsp;&lt;&nbsp;0.001). Areal BMD-Z, BMAD-Z, FMI-Z, visceral adipose tissue and subcutaneous adipose tissue were not significantly different in HR-NBL survivors compared with controls. Compared with controls, HR-NBL survivors had lower leg lean mass-Z (-1.46&nbsp;±&nbsp;1.35 vs. -&nbsp;0.17&nbsp;±&nbsp;0.84, P&nbsp;&lt;&nbsp;0.001) and strength-Z (-1.13&nbsp;±&nbsp;0.86 vs. -&nbsp;0.15&nbsp;±&nbsp;0.71, P&nbsp;&lt;&nbsp;0.001). Muscle-specific force was lower in HR-NBL survivors compared with controls (P&nbsp;&lt;&nbsp;0.05).</p>

<p><strong>CONCLUSIONS: </strong>Bone mineral density and adiposity are not severely impacted in HR-NBL survivors with growth failure, but significant sarcopenia persists years after treatment. Future studies are needed to determine if sarcopenia improves with muscle-specific interventions in this population of cancer survivors.</p>

10.1002/jcsm.12734

J Cachexia Sarcopenia Muscle

34184837

Endocrine Health in Childhood Cancer Survivors.

2020

1171-1186

2020 Dec

1557-8240

<p>Endocrine late effects, including reproductive disorders and secondary thyroid cancer, have been reported in up to 50 %childhood cancer survivors (CCS) more than&nbsp;5&nbsp;years after treatment. Most endocrine disorders are amenable to treatment; awareness of symptoms is therefore of great importance. Recognition of these symptoms may be delayed however because many are nonspecific. Timely treatment of endocrine disorders improves quality of life in CCS and prevents possible consequences, such as short stature, bone and cardiovascular disorders, and depression. At-risk CCS must therefore be regularly and systematically monitored. This article provides a summary of the most commonly reported endocrine late effects in CCS.</p>

10.1016/j.pcl.2020.08.002

Pediatr Clin North Am

33131540

Leg length and sitting height reference data and charts for children in the United States.

2020

106131

2020 Oct

2352-3409

<p>Population-specific reference data are required to interpret growth measurements in children. Sitting height and leg length (standing height minus sitting height) measurements are indicators of proportionality and can be used to evaluate children with disordered growth. NHANES III recorded sitting height and standing height measurements in a strategic random sample of the United States population from 1988 to 1994, and we have previously published reference charts for sitting height to standing height ratio in this population. In this study, we have developed separate sitting height and leg length reference charts for Non-Hispanic Black, Non-Hispanic White, and Mexican-American children in the United States. In addition, we provide mean (SD) and LMS data to support the use of these reference charts in clinical care.</p>

10.1016/j.dib.2020.106131

Data Brief

32904356

Genetic syndromes associated with endocrine tumors in children.

2020

150919

2020 Jun

1532-9453

<p>Endocrine tumors comprise a variety of benign and malignant neoplasms that arise from the endocrine glands and neuroendocrine tissues. Functioning tumors are associated with typical clinical syndromes related to specific hormone(s) secreted, whereas nonfunctioning tumors present incidentally or secondary to symptoms related to mass effect. Endocrine tumors represent a minority of all neoplasms observed in the pediatric population and are generally associated with underlying hereditary syndromes. While most are clinically benign or low-grade cancers, a small percentage of endocrine tumors are high-grade malignancies requiring multimodal therapies. As with any rare childhood disease, treatment is best provided at tertiary care centers with multidisciplinary expertise in the management of such tumors.</p>

10.1016/j.sempedsurg.2020.150919

Semin. Pediatr. Surg.

32571504

Sitting Height to Standing Height Ratio Reference Charts for Children in the United States.

2020

2020 Jun 21

1097-6833

<p><strong>OBJECTIVE: </strong>To create reference charts for Sitting height to standing height ratio (SitHt/Ht) for children in the United States, and to describe the trajectory of SitHt/Ht during puberty.</p>

<p><strong>STUDY DESIGN: </strong>This was a cross-sectional study using data from the 1988-1994 National Health and Nutrition Examination Survey III, a strategic random sample of the United States population. Comparison between Non-Hispanic White (NHW), Non-Hispanic Black (NHB) and Mexican American groups was performed by analysis of variance (ANOVA) to determine if a single population reference chart could be used. ANOVA was used to compare SitHt/Ht in pre-, early and late puberty.</p>

<p><strong>RESULTS: </strong>NHANES III recorded sitting height and standing height measurements in 9,569 children aged 2 to 18 years of NHW (n=2,715), NHB (n=3,336), and Mexican American (n=3,518) ancestry. NHB children had lower SitHt/Ht than NHW and Mexican American children throughout childhood (p &lt; 0.001). In both sexes, SitHt/Ht decreased from prepuberty to early puberty and increased in late puberty. Sex-specific percentile charts of SitHt/Ht vs age were generated for NHB and for NHW and Mexican American youth combined.</p>

<p><strong>CONCLUSIONS: </strong>SitHt/Ht assessment can detect disproportionate short stature in children with skeletal dysplasia, but age-, sex- and population-specific reference charts are required to interpret this measurement. NHB children in the United States have significantly lower SitHt/Ht than other children, which adds complexity to interpretation. We recommend the use of standardized ancestry-specific reference charts in screening for skeletal dysplasias and have developed such charts in this study.</p>

10.1016/j.jpeds.2020.06.051

J. Pediatr.

32579888

Management of pediatric differentiated thyroid cancer: An overview for the pediatric oncologist.

2020

e28141

2020 Apr 10

1545-5017

<p>Differentiated thyroid cancer (DTC) is the most common childhood thyroid malignancy. The standard of care for pediatric DTC is total thyroidectomy followed by radioactive iodine (RAI) treatment when indicated. Molecular changes and potential therapeutic targets have been recently described in pediatric thyroid cancer. Pediatric oncologists are increasingly involved in the evaluation of thyroid nodules in childhood cancer survivors and in the management of advanced thyroid cancer. In 2015, the American Thyroid Association published management guidelines for children with DTC. We provide an overview of the current standard of care and highlight available targeted therapies for progressive or RAI refractory DTC.</p>

10.1002/pbc.28141

Pediatr Blood Cancer

32275118

Abnormal body composition is a predictor of adverse outcomes after autologous haematopoietic cell transplantation.

2020

2020 Mar 25

2190-6009

<p><strong>BACKGROUND: </strong>The number of patients undergoing autologous haematopoietic cell transplant (HCT) is growing, but little is known about the factors that predict adverse outcomes. Low muscle mass and obesity are associated with disability and premature mortality in individuals with non-malignant diseases and may predict outcomes after autologous HCT.</p>

<p><strong>METHODS: </strong>This was a retrospective cohort study of 320 patients who underwent autologous HCT for Hodgkin or non-Hodgkin lymphoma between 2009 and 2014. Sarcopenia {skeletal muscle index male: &lt;43 cm/m [body mass index (BMI) &lt; 25 kg/m ] or &lt; 53 cm/m [BMI ≥ 25 kg/m ] and female: &lt;41 cm/m [regardless of BMI]) and obesity [total abdominal adiposity ≥450.0 cm (male), ≥396.4 cm (female)] were assessed from single-slice abdominal pre-HCT computed tomography images. Length of hospital stay, first unplanned intensive care unit admission, and 30-day unplanned readmission were evaluated based on body composition using multivariable regression analysis, and mortality was evaluated with Kaplan-Meier analysis and Gray's test.</p>

<p><strong>RESULTS: </strong>Median age at HCT was 53.3 years (range, 18.5 to 78.1 years); 26.3% were sarcopenic and an additional 7.8% were sarcopenic obese pre-HCT. Sarcopenic obesity was associated with increased risk of prolonged hospitalization [odds ratio (OR) = 3.6, 95% confidence interval (CI) 1.3-9.8], intensive care unit admission (OR = 4.7, 95% CI 1.5-16.1), and unplanned readmission after HCT (OR = 13.6, 95% CI 2.5-62.8). Patients who were sarcopenic obese also had the highest mortality risk at 1 year [hazard ratio (HR): 3.9, 95% CI 1.1-11.0] and 5 years (HR: 2.5, 95% CI 1.1-5.5), compared with patients with normal body composition. Sarcopenia alone, but not obesity alone, was associated with an increased risk of these outcomes, albeit with a lower magnitude of risk than in patients who were sarcopenic obese.</p>

<p><strong>CONCLUSIONS: </strong>Sarcopenic obesity was an important predictor of outcomes in patients undergoing autologous HCT. These findings could inform targeted prevention strategies in patients at highest risk of complications after HCT.</p>

10.1002/jcsm.12570

J Cachexia Sarcopenia Muscle

32212263

Bilateral papillary thyroid cancer in children: Risk factors and frequency of postoperative diagnosis.

2020

2020 Feb 27

1531-5037

<p><strong>BACKGROUND: </strong>The recommendation for children with papillary thyroid cancer (PTC) is total thyroidectomy (TT) based on the incidence of bilateral disease. Evaluating this assumption, we reviewed the characteristics of bilateral PTC in a large cohort of children.</p>

<p><strong>METHODS: </strong>A retrospective chart review for patients surgically treated for PTC from 2009 to 2018 analyzing preoperative risk factors, ultrasound findings, and pathology results was performed. Bilateral disease was defined as pathologic PTC in the contralateral lobe, including microscopic disease.</p>

<p><strong>RESULTS: </strong>Of the 172 patients included, 38.4% had bilateral disease with 23% diagnosed postoperatively. Multifocal disease on ultrasound was associated with bilateral disease (OR 2.9, 95% CI 1.5-5.9, p = 0.002). Nodule dimension &gt;2 cm was associated with increased risk for postoperative bilateral disease (OR 3.5, 95% CI 1.6-7.4, p = 0.001). Patients with bilateral disease were more likely to have extrathyroidal extension, lymphovascular invasion, positive central lymph nodes, and extranodal extension (p &lt; 0.001 for all). Diffuse-sclerosing variant PTC was also associated with bilateral disease.</p>

<p><strong>CONCLUSION: </strong>Thirty-eight percent of children were diagnosed with PTC demonstrate bilateral disease. Nearly one in four have occult bilateral disease. The features that predicted bilateral disease were multifocality, widely invasive PTC on ultrasound, and the presence of lymphadenopathy. Thus, TT is the appropriate surgical approach for pediatric patients with PTC.</p>

<p><strong>TYPE OF STUDY: </strong>Clinical Research, Retrospective Review.</p>

<p><strong>LEVEL OF EVIDENCE: </strong>Level IV.</p>

10.1016/j.jpedsurg.2020.02.040

J. Pediatr. Surg.

32171533

miRNA expression can classify pediatric thyroid lesions and increases the diagnostic yield of mutation testing.

2020

e28276

2020 Mar 20

1545-5017

<p><strong>BACKGROUND: </strong>Genetic alterations in multiple cell signaling pathways are involved in the molecular pathogenesis of thyroid cancer. Oncogene mutation testing and gene-expression profiling are routinely used for the preoperative risk management of adult thyroid nodules. In this study, we evaluated the potential value of miRNA biomarkers for the classification of pediatric thyroid lesions.</p>

<p><strong>PROCEDURE: </strong>Double-blind case-control study with 113 resected pediatric lesions: 66 malignant and 47 benign. Quantitative and qualitative molecular data generated with a 10-miRNA expression panel (ThyraMIR) and a next-generation sequencing oncogene panel (ThyGeNEXT) were compared with clinicopathological parameters.</p>

<p><strong>RESULTS: </strong>miRNAs were differentially expressed in benign versus malignant tumors with distinct expression patterns in different histopathology categories. The 10-miRNA classifier identified 39 (59%) malignant lesions with 100% specificity. A positive classifier score was associated with lymph node metastasis, extrathyroidal extension and intrathyroidal spread. Genetic alterations associated with increased risk for malignancy were detected in 35 (53%) malignant cases, 20 positive for point mutations in BRAF, HRAS, KRAS, NRAS, PIK3CA, or TERT and 15 positive for gene rearrangements involving ALK, NTRK3, PPARG, or RET. The 10-miRNA classifier correctly identified 11 mutation-negative malignant cases. The performance of the combined molecular test was 70% sensitivity and 96% specificity with an area under the curve of 0.924.</p>

<p><strong>CONCLUSIONS: </strong>These data suggest that the regulatory miRNA pathways underlying thyroid tumorigenesis are similar in adults and children. miRNA expression can identify malignant lesions with high specificity, augment the diagnostic yield of mutation testing, and improve the molecular classification of pediatric thyroid nodules.</p>

10.1002/pbc.28276

Pediatr Blood Cancer

32196952