Vitamin D levels differ by cancer diagnosis and decline over time in survivors of childhood cancer.

BACKGROUND: The aim of this study was to evaluate serum 25-hydroxyvitamin D (25OHD) concentrations in survivors of childhood cancer and compare levels by underlying diagnosis and as a function of time. PROCEDURE: A retrospective review of 201 pediatric cancer survivors enrolled in a hospital-based cancer survivor registry. Demographic characteristics and 25OHD levels were extracted from the registry. Vitamin D status was determined during routine clinical care and was categorized as normal, insufficient, or deficient. RESULTS: 25OHD levels differed significantly across diagnoses (P = 0.017), with the lowest levels found in patients treated for osteosarcoma, retinoblastoma, hepatoblastoma, and myeloid leukemias. Age was inversely correlated with 25OHD levels (P = 0.03). Average 25OHD level at study entry was 29.8 ng/ml (range: 5-79.7), with 14.4% vitamin D deficient, 39.3% insufficient, and 46.3% normal. 25OHD concentrations decreased 11.4% over time (P < 0.00001). CONCLUSION: Fewer than half of childhood cancer survivors have normal 25OHD concentrations, which further declined over time. Patients with solid tumors were the most affected, despite their lack of routine exposure to glucocorticoids. Future investigations should focus on why vitamin D level varies by diagnosis and how best to replete in this population.

High Prevalence of Gene Fusions and Copy Number Alterations in Pediatric Radiation Therapy-Induced Papillary and Follicular Thyroid Carcinomas.

Background: Childhood cancer survivors and bone marrow transplant recipients treated with radiation therapy (RT) are at increased risk for subsequent thyroid cancer. However, the genetic landscape of pediatric thyroid cancer, both primary and RT-induced, remains poorly defined, as pediatric papillary thyroid carcinoma (PTC) has been understudied compared with adults and data on pediatric follicular thyroid carcinoma (FTC) are virtually nonexistent. The objective of this study was to characterize and compare the molecular profiles of pediatric RT-induced PTC and FTC cases with primary pediatric thyroid cancers. Methods: A total of 41 differentiated thyroid carcinomas (11 RT cases and 30 primary cases) from 37 patients seen at Phoenix Children's Hospital between January 1, 2010 and December 31, 2019 were evaluated by targeted next-generation sequencing and/or BRAF immunohistochemistry. Results: Eighty-six percent (6/7) of RT-PTC harbored a gene fusion (GF) compared with 56% (14/25) of primary PTC; 14% (1/7) of RT-PTC had a single-nucleotide variant (SNV; specifically, a point mutation in the DICER1 gene) compared with 44% (11/25) of primary PTC (all of the latter had the BRAFV600E mutation). An exceedingly rare ROS1 fusion was identified in a child with RT-PTC. With respect to FTC, copy number alterations (CNAs) were seen in 75% (3/4) of RT cases compared with 40% (2/5) of primary cases. None of the RT-FTC had SNVs compared with 100% (5/5) of primary FTC. Conclusions: In children, the molecular profile of subsequent RT-induced thyroid cancers appears to differ from primary (sporadic and syndromic) cases, with a high prevalence of GFs in RT-PTC (similar to PTC occurring after the Chernobyl nuclear reactor accident) and CNAs in RT-FTC. A better understanding of the molecular mechanisms underlying these cancers may lead to more accurate diagnosis, prognosis, and treatment, as some of the genomic alterations are potentially targetable.