Feasibility, reproducibility, and accuracy of echocardiographic right ventricular systolic function assessments in childhood cancer survivors at risk for heart failure.

PURPOSE: We sought to assess the feasibility, reproducibility, and accuracy of conventional and newer echocardiographic measures of right ventricular (RV) systolic function in adolescent and young adult childhood cancer survivors treated with anthracyclines. METHODS: Echocardiography and cardiac magnetic resonance imaging (CMR) were acquired ≤60 days apart in prospectively recruited survivors and RV functional measures were quantitated by blinded observers. Repeat quantitation was performed in a subset to evaluate reproducibility. For each echocardiographic measure, Spearman correlations with CMR measures were calculated, and values in participants with CMR RV ejection fraction (RVEF) ≥48% and RVEF <48% were compared using two sample Wilcoxon rank-sum tests. RESULTS: Among 58 participants, mean age was 18.2 years (range 13.1-25.2) and five participants had CMR RVEF <48%. Intra- and inter-observer coefficients of variation were 8.2%-10.1% and 10.5%-12.0% for adjusted automated strain measures, and 5.2%-8.7% and 2.7% for 3D RVEF, respectively. No echocardiographic measures were significantly correlated with CMR RVEF; only tricuspid annular plane systolic excursion was correlated with CMR RV stroke volume (r = .392, p = .003). Participants with RV dysfunction had worse automated global longitudinal strain (-20.3% vs. -23.9%, p = .007) and free wall longitudinal strain (-23.7% vs. -26.7%, p = .09). CONCLUSIONS: Echocardiographic strain and 3D RV function measurements were feasible and reproducible in at-risk childhood cancer survivors. Although not associated with CMR RVEF in this population with predominantly normal RV function, automated strain measurements were more abnormal in participants with RV dysfunction, suggesting potential clinical utility of these measures.

Molecular and phenotypic diversity of CBL-mutated juvenile myelomonocytic leukemia.

Mutations in the gene CBL were first identified in adults with various myeloid malignancies. Some patients with juvenile myelomonocytic leukemia (JMML) were also noted to harbor mutations in CBL, but were found to have generally less aggressive disease courses compared to other forms of Ras pathway-mutant JMML. Importantly, and in contrast to most reports in adults, the majority of CBL mutations in JMML patients are germline with acquired uniparental disomy occurring in affected marrow cells. Here, we systematically studied a large cohort of 33 JMML patients with CBL mutations and found this disease to be highly diverse in presentation and overall outcome. Moreover, we discovered somatically-acquired CBL mutations in 15% of pediatric patients who presented with more aggressive disease. Neither clinical features nor methylation profiling were able to distinguish somatic CBL patients from germline CBL patients, highlighting the need for germline testing. Overall, we demonstrate that disease courses are quite heterogeneous even among germline CBL patients. Prospective clinical trials are warranted to find ideal treatment strategies for this diverse cohort of patients.

Screening for Chemotherapy-induced Peripheral Neuropathy and Utilization of Physical Therapy in Pediatric Patients Receiving Treatment for Hematologic Malignancies.

Physical therapy (PT) has been shown to be a helpful intervention in the treatment of chemotherapy-induced peripheral neuropathy (CIPN). Our aim was to screen for CIPN in patients with hematologic malignancies receiving vincristine chemotherapy and obtain a baseline assessment on the percentage of patients utilizing PT in the treatment of CIPN. A retrospective review of surveys administered to parents and patients regarding the severity of peripheral neuropathy symptoms from October 2016 through March 2018 was conducted. Of 116 patients, a total of 102 patients (67 male and 35 female; 4 to 10 y of age, N=63; 11 to 15 y of age, N=19; 16 to 20 y of age, N=20) were eligible for the study, with 67.6% (N=69) reporting symptoms of CIPN. Of these patients, 16.7% scored 4 or greater on the surveys, suggesting clinically severe CIPN. Common parental concerns included decreased strength, difficulty walking up stairs, tripping, and foot drops. Approximately 55.1% of the 69 patients who reported CIPN symptoms were referred to outpatient PT, while 44.9% were not referred. A simple survey consisting of 4 questions that only took several minutes to administer was capable of identifying CIPN in 67.6% of patients receiving vincristine chemotherapy.

The Application of Next-generation Sequencing Tumor Molecular Profiling in the Diagnosis and Management of a Case of Acute Myelogenous Leukemia With MLL-PTD in a Pediatric Heart Transplant Recipient.

A 6-year-old girl with a history of heart transplantation was diagnosed with myelodysplastic syndrome, which progressed to acute myelogenous leukemia. Comprehensive genomic profiling of her tumor discovered an MLL-PTD (partial tandem duplication) and she received chemotherapy and a hematopoietic stem cell transplant (HSCT). She subsequently relapsed and tumor molecular profiling was repeated, revealing 2 new potentially targetable mutations (FLT3 and IDH2). A novel treatment regimen targeting these mutations with sorafenib and azacitidine without using cytotoxic chemotherapy produced remission and she subsequently pursued a second HSCT. She remains disease-free 17 months after HSCT. This case report demonstrates how repeated tumor molecular profiling provided novel actionable information for the diagnosis and management at 2 timepoints.

Safety, pharmacokinetics, and pharmacodynamics of panobinostat in children, adolescents, and young adults with relapsed acute myeloid leukemia.

BACKGROUND: Novel therapies are urgently needed for pediatric patients with relapsed acute myeloid leukemia (AML). METHODS: To determine whether the histone deacetylase inhibitor panobinostat could be safely given in combination with intensive chemotherapy, a phase 1 trial was performed in which 17 pediatric patients with relapsed or refractory AML received panobinostat (10, 15, or 20 mg/m2 ) before and in combination with fludarabine and cytarabine. RESULTS: All dose levels were tolerated, with no dose-limiting toxicities observed at any dose level. Pharmacokinetic studies demonstrated that exposure to panobinostat was proportional to the dose given, with no associations between pharmacokinetic parameters and age, weight, or body surface area. Among the 9 patients who had sufficient (>2%) circulating blasts on which histone acetylation studies could be performed, 7 demonstrated at least 1.5-fold increases in acetylation. Although no patients had a decrease in circulating blasts after single-agent panobinostat, 8 of the 17 patients (47%), including 5 of the 6 patients treated at dose level 3, achieved complete remission. Among the 8 complete responders, 6 (75%) attained negative minimal residual disease status. CONCLUSIONS: Panobinostat can be safely administered with chemotherapy and results in increased blast histone acetylation. This suggests that it should be further studied in AML.

Acute Pancreatitis Associated With Cytarabine During the Treatment of Pediatric Acute Myeloid Leukemia.

Pancreatitis is a common complication of many pediatric oncology drugs - most commonly asparaginase, followed by pentamidine, mercaptopurine, corticosteroids, and trimethoprim-sulfamethoxazole. Cytarabine-associated pancreatitis is not often mentioned in the pediatric oncology literature. We report the case of a 10-year-old female with acute myeloid leukemia who developed cytarabine-associated pancreatitis.

Leiomyosarcoma in Birt-Hogg-Dubé Syndrome.

Birt-Hogg-Dubé syndrome (BHDS) is an autosomal dominant genodermatosis characterized by benign cutaneous tumors (fibrofolliculomas, trichodiscomas, and acrochordons), basal lung cysts, pneumothoraces, and a 20% to 30% lifetime risk for renal cancer. There are isolated cases of other cancers in BHDS reported in the literature, including oncocytoma, rhabdomyoma, melanoma, thyroid cancer, meningioma, colon cancer, and breast cancer, but only the increased renal cancer risk has been substantiated. This is the case of a 9-year-old girl who presented with a leiomyosarcoma whose tumor genetic analysis showed FLCN c.365_372del, p.Arg122Leufs*8. She was diagnosed with BHDS when the same mutation was confirmed in her germline lymphocytes. This is the second known reported case of leiomyosarcoma in BHDS.

Treatment of Recurrent Refractory Pediatric Pre-B Acute Lymphoblastic Leukemia Using Inotuzumab Ozogamicin Monotherapy Resulting in CD22 Antigen Expression Loss as a Mechanism of Therapy Resistance.

BACKGROUND: Inotuzumab ozogamicin is a novel antibody-drug conjugate that targets CD22, a common antigen on pre-B acute lymphoblastic leukemia cells. OBSERVATIONS: A 7-year-old boy with pre-B acute lymphoblastic leukemia in his second relapse was given 2 cycles of inotuzumab ozogamicin. He responded morphologically with a negative bone marrow evaluation. However, he relapsed in cycle 3 of therapy with a loss of CD22 expression on his lymphoblast population. CONCLUSION: To our knowledge, this is the first published case of CD22 expression loss as a mechanism of therapy resistance for inotuzumab ozogamicin.

Identification of NTRK fusions in pediatric mesenchymal tumors.

BACKGROUND: NTRK fusions are known oncogenic drivers and have recently been effectively targeted by investigational agents in adults. We sought to assess the frequency of NTRK fusions in a large series of pediatric and adolescent patients with advanced cancers. PROCEDURE: Genomic profiles from 2,031 advanced cancers from patients less than 21 years old who were assayed with comprehensive genomic profiling were reviewed to identify NTRK fusions. RESULTS: Total of nine cases (0.44%) harbored NTRK fusions, including novel partners. Four of these cases were in children less than 2 years old for which infantile fibrosarcoma was considered as a diagnosis, and two harbored the canonical ETV6-NTRK3. The remaining cases carried other diagnoses, at least one that carried the diagnosis of inflammatory myofibroblastic tumor. CONCLUSIONS: NTRK fusions occur in a subset of young patients with mesenchymal or sarcoma-like tumors at a low frequency, and are eminently druggable targets via either investigational agents or approved drugs.

Melanotic Neuroectodermal Tumor of Infancy in the Epididymis: A Brief Report and Review of the Role of Chemotherapy in Management.

Melanotic neuroectodermal tumor of infancy is a rare benign tumor of neural crest origin. The tumor generally presents in the jawbones; however, it occasionally occurs in extracranial sites. Although 95% of these tumors present within the first year of life and 15% in extracranial locations, we report an unusual case of a 15-month-old male with melanotic neuroectodermal tumor of infancy of the epididymis. The patient underwent orchiectomy without adjuvant chemotherapy or radiation. Twenty months later, there was no sign of recurrence. In addition, we discuss the role of chemotherapy and radiation and the potential importance of molecular genetics in establishing guidelines for management.

Treatment of Metastatic, Refractory Alveolar Soft Part Sarcoma: Case Reports and Literature Review of Treatment Options in the Era of Targeted Therapy.

BACKGROUND: Alveolar soft part sarcoma is a rare soft tissue sarcoma that is characterized by a pattern of slow growth with metastases to the lung, bone, and brain that is not responsive to conventional cytotoxic chemotherapy. OBSERVATIONS: We describe 2 patients, with a combined 19 years of treatment experience including multiple different chemotherapeutic and targeted therapy regimens, surgery, and radiotherapy. We also present a review of the literature regarding treatment options to highlight recent findings. CONCLUSIONS: Alveolar soft part sarcoma is an indolent, but persistently progressive disease. Novel therapeutic agents hold promise in its management.

Dose-Related Effect of Chemotherapy on Bone Mineral Density Among Pediatric Acute Lymphoblastic Leukemia Survivors.

OBJECTIVES: Reduced bone mineral density (BMD) can negatively affect lifelong skeletal health by -increasing the risk for developing osteopenia and osteoporosis. This study evaluated the relationship between BMD and cumulative doses of intravenous (IV) methotrexate (MTX) and glucocorticoids in pediatric acute lymphoblastic leukemia (ALL) survivors. The association between BMD and vitamin D concentrations measured at the time of entry into the long-term follow-up program was also assessed. METHODS: This retrospective study included pediatric ALL survivors who had received a dual-energy X-ray absorptiometry (DXA) scan after the end of therapy (EOT) or within the 6 months prior to the EOT. Low/-intermediate and high cumulative IV MTX doses were defined as doses less than 20,000 mg/m2 and -greater than or equal to 20,000 mg/m2, respectively. Descriptive statistics, Student t test, and linear -regression were used to analyze the data. RESULTS: A total of 62 patients, with 34 patients in the low/intermediate and 28 patients in the high -cumulative IV MTX dose groups, were analyzed. The median time from EOT to DXA scan was 2.3 years. The mean DXA lumbar spine z score was significantly lower in the high cumulative IV MTX dose group -compared with the low/intermediate dose group (-0.86 vs -0.14; p = 0.008). Cumulative glucocorticoid doses and vitamin D concentrations were not associated with BMD. CONCLUSIONS: Pediatric patients who had received cumulative IV MTX doses of greater than or equal to 20,000 mg/m2 during their ALL treatment had lower BMD than those who had received lower cumulative doses.

Parent and patient knowledge and attitudes about cancer predisposition syndrome genetic testing in pediatric oncology: Understanding sociodemographic and parent-child differences.

BACKGROUND: Cancer predisposition syndromes (CPS) impact about 10% of patients with pediatric cancer. Genetic testing (CPS-GT) has multiple benefits, but few studies have described parent and child knowledge and attitudes regarding CPS-GT decision-making. This study examined parent and patient CPS-GT decision-making knowledge and attitudes. PROCEDURE: English- or Spanish-speaking parents of children with pediatric cancer and patients with pediatric cancer ages 15-18 within 12 months of diagnosis or relapse were eligible to participate. Seventy-five parents and 19 parent-patient dyads (N = 94 parents, 77.7% female, 43.6% Latino/a/Hispanic; 19 patients, 31.6% female) completed surveys measuring CPS-GT-related beliefs. Independent samples t-tests compared parent responses across sociodemographic characteristics and parent-patient responses within dyads. RESULTS: Spanish-speaking parents were significantly more likely than English-speaking parents to believe that CPS-GT not being helpful (p < .001) and possibly causing personal distress (p = .002) were important considerations for deciding whether to obtain CPS-GT. Parents with less than four-year university education, income less than $75,000, or Medicaid (vs. private insurance) were significantly more likely to endorse that CPS-GT not being helpful was an important consideration for deciding whether to obtain CPS-GT (p < .001). Parents felt more strongly than patients that they understood what CPS-GT was (p = .01) and that parents should decide whether patients under 18 should receive CPS-GT (p = .002). CONCLUSIONS: Spanish-speaking parents and parents with lower socioeconomic statuses were more strongly influenced by the potential disadvantages of CPS-GT in CPS-GT decision-making. Parents felt more strongly than patients that parents should make CPS-GT decisions. Future studies should investigate mechanisms behind these differences and how to best support CPS-GT knowledge and decision-making.

Genome-Wide Association Study of Pregnancy in Childhood Cancer Survivors: A Report from the Childhood Cancer Survivor Study.

BACKGROUND: Gonadotoxic treatment-related infertility has a significant impact on quality of life in childhood cancer survivors. Genome-wide association analyses to delineate the risk of infertility in childhood cancer survivors have not been previously reported. METHODS: Leveraging genotype data from a large survivor cohort, the Childhood Cancer Survivor Study (CCSS), we investigated the role of SNPs on future pregnancy or siring a pregnancy in survivors without pelvic, testicular, or brain radiation who had ever been married. We calculated sex-stratified hazard ratios, using Cox proportional hazards modeling, adjusting for birth cohort (before 1965 vs. 1965 or later) and doses of relevant chemotherapies; replication was attempted in the independent St. Jude Lifetime Cohort study (SJLIFE). RESULTS: In the CCSS cohort, nine SNPs were found to be suggestive (P < 10-7) or statistically significantly (P < 5 × 10-8) associated with pregnancy, however, none of the SNPs were replicated in SJLIFE. Cohorts differed based on the overall pregnancy rate, frequency of sterilizing procedures, and birth cohort. CONCLUSIONS: We were not able to replicate our findings of SNPs associated with pregnancy in childhood cancer survivors. IMPACT: Future attempts at replication should be considered in cohorts treated in a comparable era. In addition, understanding the role of genetics in fertility in childhood cancer survivors may be better approached using more advanced sequencing techniques.

Southern California Pediatric and Adolescent Cancer Survivorship (SC-PACS): Establishing a Multi-Institutional Childhood, Adolescent, and Young Adult Cancer Survivorship Consortium in Southern California.

Introduction Given their risk for late effects and early mortality, childhood/adolescent cancer survivors (CACSs) should receive longitudinal monitoring and care. The Southern California Pediatric and Adolescent Cancer Survivorship (SC-PACS) consortium was established in February 2017 to combine resources and expertise across seven participating survivorship programs. Its over-arching objective is to address the unique needs of its demographically diverse CACS population through collaborative survivorship research and care initiatives. The first SC-PACS study was an assessment of survivorship needs and evaluation of current services as reported by CACSs and their parents/primary care givers (PPCGs) receiving survivorship care at consortium sites. Methods As an initial investigation, a cross-sectional survey for CACSs and their parents/primary care givers was conducted. The goal was to enroll 10 CACSs and 10 PPCGs from each of the seven institutions (total of 140 participants). The eligibility criteria for CACSs were age ≥13 years at the time of enrollment, >2 years from the end of treatment, sufficient cognitive function to complete the survey, and English or Spanish language proficiency. For CACSs <13 years old, their PPCGs completed the survey. This was a convenience sample using frequencies and proportions to describe participant characteristics and survey responses, which were entered into a Research Electronic Data Capture (REDCap) database. Results Across the consortium, of the recruitment target of 140 participants (CACSs, n=70; PPCGs, n=70), 127 (90.7%) participants were enrolled. Of the 127 participants enrolled, 65 (51.2%) were CACSs and 62 (48.8%) were PPCGs. The majority of participants were female (51.2%), were Hispanic (62.2%), spoke English as the primary language at home (57.5%), and were diagnosed between one to four years of age (45.7%). Information considered most important by both CACSs and PPCGs was related to cancer diagnosis (90.8%) and future risks as a result of cancer treatment received (98.0%). Overall, 78% of CACSs and PPCGs found the survivorship information (treatment summary) useful, and 83% felt that they received the right amount of information about their cancer. Conclusion Our aim was to obtain baseline data that would characterize our CACS population, inform consortium priorities, and establish a collaborative research platform. The ultimate goal of the consortium is to develop a comprehensive survivorship care approach that addresses the most important needs of cancer survivors in our catchment area and promotes best practice interventions. Future plans are to expand the needs assessment survey to obtain a wider representation of the survivor population at SC-PACS institutions, helping create strategies to improve cancer-specific education, delivery of treatment summary, and access to community resources for this demographically and socioeconomically diverse population.

High-Dose Methotrexate in Pediatric Acute Lymphoblastic Leukemia: Predictors of Delayed Clearance and the Effect of Increased Hydration Rate on Methotrexate Clearance.

Objectives High-dose methotrexate (HDMTX) is an important chemotherapeutic agent in the treatment of many cancers. Identification of the predictors of poor clearance during HDMTX infusions could advance the introduction of improved supportive care to prevent toxicities and reduce hospital length of stay. The purpose of this study was to identify relationships between patient physical characteristics and HDMTX clearance in the treatment of pediatric acute lymphoblastic leukemia (ALL). At our hospital, patients who have delayed methotrexate (MTX) clearance during a cycle of HDMTX receive an increased rate of hydration with subsequent cycles. This increase in hydration rate was examined for its potential to mitigate predictors of poor clearance and to prevent nephrotoxicity. Methods This study retrospectively examined the treatment records of 87 pediatric patients diagnosed with ALL who were treated on or according to Children's Oncology Group (COG) protocols AALL0232, AALL0434, AALL1131, and AALL1231. Each patient received four cycles of HDMTX (5 g/m2 over 24 hours) at two-week intervals. Patients received either 125 ml/m2/hour (standard) or 200 ml/m2/hour (delayed clearance protocol) hydration before, with, and after each infusion. MTX levels taken at 24-, 42-, and 48-hour time points were used as an indirect measure of drug clearance. Two-tailed inference for ordinary least squares regression and both heteroskedastic and paired two-tailed t-tests were performed to identify physical characteristics associated with delayed MTX clearance and the effects of hydration rate on MTX clearance, respectively. Results Patient age and body surface area (BSA) were found to have statistically significant (p<0.05) positive associations with the serum MTX levels at 24, 42, and 48 hours in cycle 1. Age and BSA were significant only at the 24-hour time point in cycles 2 and 4. Weight alone was not associated with delayed MTX clearance. For patients who had delayed MTX clearance once and thus received the delayed clearance protocol in subsequent cycles, increasing the hydration rate from 125 to 200 ml/m2/hour was associated with a statistically significant decrease in average MTX levels as well as serum creatinine levels at the 24-, 42-, and 48-hour time points. Once patients with delayed clearance received the 200 ml/m2/hour rate of hydration, the history of prior poor clearance lost its predictive value for serum MTX levels and delayed clearance. Conclusions These results suggest that patient age and BSA are significant predictors of MTX clearance if all patients receive the same rate of hydration. Age and BSA affect the distribution phase of MTX kinetics, with downstream effects in the elimination phase. Increased hydration mitigates the effects of these physical characteristics on the elimination phase kinetics by improving renal elimination of MTX, causing a loss of significance of age and BSA as predictors of MTX levels in subsequent cycles at the 42- and 48-hour time points, but with less effect at 24 hours. Thus, hyperhydration regimens prior to cycle 1 of HDMTX could be considered for patients presenting with risk factors of advanced age or high BSA to avoid delayed clearance.

Yoga as a Complementary and Alternative Therapy in Children with Hematologic and Oncologic Disease.

A diagnosis of a hematologic or oncologic disease in a child can be stressful for the patient and the family. Yoga as an intervention has been reported to decrease stress in adults diagnosed with chronic disorders but few studies have been reported with children and their families. A convenience sample of patients diagnosed with cancer or a blood disorder (ages 7-17 years) and their caregivers was selected to participate in a single bedside yoga class. Participants were surveyed pre and post yoga with the Spielberger State Trait Anxiety Scale. Children were also surveyed pre and post yoga with the Wong-Baker Faces Pain Scale. Children had a significant decrease in pain post yoga but no change in anxiety. Adolescents and parents had a significant decrease in anxiety post yoga intervention.

Real-world data from a molecular tumor board demonstrates improved outcomes with a precision N-of-One strategy.

Next-generation sequencing (NGS) can identify novel cancer targets. However, interpreting the molecular findings and accessing drugs/clinical trials is challenging. Furthermore, many tumors show resistance to monotherapies. To implement a precision strategy, we initiated a multidisciplinary (basic/translational/clinical investigators, bioinformaticians, geneticists, and physicians from multiple specialties) molecular tumor board (MTB), which included a project manager to facilitate obtaining clinical-grade biomarkers (blood/tissue NGS, specific immunohistochemistry/RNA expression including for immune-biomarkers, per physician discretion) and medication-acquisition specialists/clinical trial coordinators/navigators to assist with medication access. The MTB comprehensively reviewed patient characteristics to develop N-of-One treatments implemented by the treating physician's direction under the auspices of a master protocol. Overall, 265/429 therapy-evaluable patients (62%) were matched to ≥1 recommended drug. Eighty-six patients (20%) matched to all drugs recommended by MTB, including combinatorial approaches, while 38% received physician's choice regimen, generally with unmatched approach/low degree of matching. Our results show that patients who receive MTB-recommended regimens (versus physician choice) have significantly longer progression-free (PFS) and overall survival (OS), and are better matched to therapy. High (≥50%) versus low (<50%) Matching Score therapy (roughly reflecting therapy matched to ≥50% versus <50% of alterations) independently correlates with longer PFS (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.50-0.80; P < 0.001) and OS (HR, 0.67; 95% CI, 0.50-0.90; P = 0.007) and higher stable disease ≥6 months/partial/complete remission rate (52.1% versus 30.4% P < 0.001) (all multivariate). In conclusion, patients who receive MTB-based therapy are better matched to their genomic alterations, and the degree of matching is an independent predictor of improved oncologic outcomes including survival.

Clinical Impact of Next-generation Sequencing in Pediatric Neuro-Oncology Patients: A Single-institutional Experience.

The implementation of next-generation sequencing (NGS) in pediatric neuro-oncology may impact diagnosis, prognosis, therapeutic strategies, clinical trial enrollment, and germline risk. We retrospectively analyzed 58 neuro-oncology patients (31 boys, 27 girls, average age 7.4 years) who underwent NGS tumor profiling using a single commercially available platform on paraffin-embedded tissue obtained at diagnosis (20 low-grade gliomas, 12 high-grade gliomas, 11 embryonal tumors, four ependymal tumors, three meningeal tumors, and eight other CNS tumors) from May 2014 to December 2016. NGS results were analyzed for actionable mutations, variants of unknown significance and clinical impact. Seventy-four percent of patients (43 of 57) had actionable mutations; 26% had only variants of uncertain significance (VUS). NGS findings impacted treatment decisions in 55% of patients; 24% were given a targeted treatment based on NGS findings. Seven of eight patients with low-grade tumors treated with targeted therapy (everolimus, trametinib, or vemurafenib) experienced partial response or stable disease. All high-grade tumors had progressive disease on targeted therapy. Forty percent of patients had a revision or refinement of their diagnosis, and nine percent of patients were diagnosed with a previously unconfirmed cancer predisposition syndrome. Turnaround time between sample shipment and report generation averaged 13.4 ± 6.4 days. One sample failed due to insufficient DNA quantity. Our experience highlights the feasibility and clinical utility of NGS in the management of pediatric neuro-oncology patients. Future prospective clinical trials using NGS are needed to establish efficacy.

Effect of Vitamin D Supplementation on Delayed Hyperphosphatemia in Pediatric Acute Lymphoblastic Leukemia Patients During Induction Chemotherapy.

OBJECTIVES: Vitamin D plays a role in maintaining bone health and calcium metabolism, but recent studies cast doubt on vitamin D supplementation's benefits in survivors of acute lymphoblastic leukemia (ALL). Vitamin D supplementation could increase serum phosphate through increased intestinal absorption of phosphate and suppression of parathyroid hormone, which would lead to decreased renal phosphate excretion. Because of the potential for renal injury during induction chemotherapy for ALL, Vitamin D supplementation's potential for increasing hyperphosphatemia could outweigh its suggested but unproven benefits. METHODS: To measure the interaction between vitamin D supplementation and phosphate during chemotherapy induction, a retrospective study was done. Demographic data; clinical information about the diagnosis; laboratory data regarding calcium, phosphate, and vitamin D concentrations; and medication histories were reviewed. RESULTS: A retrospective study of 41 children with ALL showed no statistically significant difference in the final phosphate concentrations that were obtained (4.41 mg/dL vs. 4.53 mg/dL, p = 0.635) with regard to their vitamin D supplementation status. Longitudinal effects with vitamin D and phosphate showed a trend toward increasing phosphate concentrations in patients who received supplemental vitamin D (0.035 vs. 0.010 mg/dL per day; p = 0.102). CONCLUSIONS: Vitamin D potentially poses a risk of hyperphosphatemia in children undergoing induction chemotherapy for ALL.