Clinical characteristics and outcome of central nervous system tumors harboring NTRK gene fusions.

Purpose: TRK fusions are detected in less than 2% of central nervous system tumors. There are limited data on the clinical course of affected patients.

Experimental Design: We conducted an international retrospective cohort study of patients with TRK fusion-driven CNS tumors.

"Oncocytoid Renal Cell Carcinomas After Neuroblastoma" Represent TSC -mutated Eosinophilic Solid and Cystic Renal Cell Carcinomas : Association With Prior Childhood Malignancy and Multifocality With Therapeutic Implications.

The concept of oncocytoid renal cell carcinoma in patients who have survived neuroblastoma as a distinct biologic entity has been controversial since its original description in 1999. This is in part because similar oncocytoid renal cell carcinomas have been described in association with other pediatric cancers, and also because other renal cell carcinoma subtypes (such as MiT family translocation renal cell carcinoma) have been described in children who have survived neuroblastoma. We identified an index case of a child who survived medulloblastoma and developed multifocal bilateral oncocytoid renal cell carcinomas with morphology and immunophenotype compatible with eosinophilic solid and cystic renal cell carcinoma (ESC RCC) and demonstrated that both neoplasms harbored distinctive mutations in the TSC1/TSC2 genes.

Relevance of Molecular Groups in Children with Newly Diagnosed Atypical Teratoid Rhabdoid Tumor: Results from Prospective St. Jude Multi-institutional Trials.

Purpose: Report relevance of molecular groups to clinicopathologic features, germline alterations (GLA), and survival of children with atypical teratoid rhabdoid tumor (ATRT) treated in two multi-institutional clinical trials.

Materials And Methods: Seventy-four participants with newly diagnosed ATRT were treated in two trials: infants (SJYC07: age < 3 years; = 52) and children (SJMB03: age 3-21 years; = 22), using surgery, conventional chemotherapy (infants), or dose-dense chemotherapy with autologous stem cell rescue (children), and age- and risk-adapted radiotherapy [focal (infants) and craniospinal (CSI; children)]. Molecular groups ATRT-MYC (MYC), ATRT-SHH (SHH), and ATRT-TYR (TYR) were determined from tumor DNA methylation profiles.

Atypical teratoid/rhabdoid tumors (ATRTs) with SMARCA4 mutation are molecularly distinct from SMARCB1-deficient cases.

Atypical teratoid/rhabdoid tumors (ATRTs) are very aggressive childhood malignancies of the central nervous system. The underlying genetic cause are inactivating bi-allelic mutations in SMARCB1 or (rarely) in SMARCA4. ATRT-SMARCA4 have been associated with a higher frequency of germline mutations, younger age, and an inferior prognosis in comparison to SMARCB1 mutated cases.

Effects of proactive and rescue enteral tube feedings on weight change in children undergoing treatment for high-grade CNS tumors.

Background: Children with high-grade CNS cancers frequently experience malnutrition during treatment. We assessed the effects of proactive enteral tube (ET) placement/enteral tube feedings (ETF) on weight in infants/children with high-grade CNS tumors treated with aggressive chemotherapy.

Methods: We conducted a retrospective study of patients age 0 to 19 years treated for new high-grade CNS tumors between 2002 and 2017 at a tertiary pediatric hospital system.

Medical Cannabis Certification in a Large Pediatric Oncology Center.

In Minnesota, medical cannabis was approved for use in 2014. From July 2015 to February 2019, our center certified 103 pediatric and young adult patients for the use of medical cannabis under the qualifying conditions of cancer and treatment-related symptoms. Here, we provide a review of the literature on medical cannabis use in pediatric and young adult cancer patients.

Molecular grouping and outcomes of young children with newly diagnosed ependymoma treated on the multi-institutional SJYC07 trial.

Background: This report documents the clinical characteristics, molecular grouping, and outcome of young children with ependymoma treated prospectively on a clinical trial.

Methods: Fifty-four children (aged ≤3 y) with newly diagnosed ependymoma were treated on the St Jude Young Children 07 (SJYC07) trial with maximal safe surgical resection, 4 cycles of systemic chemotherapy, consolidation therapy using focal conformal radiation therapy (RT) (5-mm clinical target volume), and 6 months of oral maintenance chemotherapy. Molecular groups were determined by tumor DNA methylation using Infinium Methylation EPIC BeadChip and profiled on the German Cancer Research Center/Molecular Neuropathology 2.

Conformal Radiation Therapy for Pediatric Ependymoma, Chemotherapy for Incompletely Resected Ependymoma, and Observation for Completely Resected, Supratentorial Ependymoma.

Purpose: The Children's Oncology Group trial ACNS0121 estimated event-free survival (EFS) and overall survival for children with intracranial ependymoma treated with surgery, radiation therapy, and-selectively-with chemotherapy. Treatment was administered according to tumor location, histologic grade, and extent of resection. The impacts of histologic grade, focal copy number gain on chromosome 1q, and DNA methylation profiles were studied for those undergoing surgery and immediate postoperative conformal radiation therapy (CRT).

Physical Therapist Coaching to Improve Physical Activity in Children With Brain Tumors: A Pilot Study.

Purpose: Children with brain tumors (BTs) experience fatigue and decreased quality of life (QOL). Physical activity (PA) is recommended during and after cancer treatment. We explored whether a fitness tracker intervention combined with tailored coaching by a physical therapist (PT) increased PA and QOL and decreased fatigue in children with BTs.

Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort.

Background: Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines.

Methods: In this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED).

Multiple pilomatrixomas in a survivor of WNT-activated medulloblastoma leading to the discovery of a germline APC mutation and the diagnosis of familial adenomatous polyposis.

Because children diagnosed with WNT-activated medulloblastoma have a 10-year overall survival rate of 95%, active long-term follow-up is critically important in reducing mortality from other causes. Here, we describe an 11-year-old adopted female who developed multiple pilomatrixomas 3 years after diagnosis of WNT-activated medulloblastoma, an unusual finding that prompted deeper clinical investigation. A heterozygous germline APC gene mutation was discovered, consistent with familial adenomatous polyposis.

Divergent clonal selection dominates medulloblastoma at recurrence.

The development of targeted anti-cancer therapies through the study of cancer genomes is intended to increase survival rates and decrease treatment-related toxicity. We treated a transposon-driven, functional genomic mouse model of medulloblastoma with 'humanized' in vivo therapy (microneurosurgical tumour resection followed by multi-fractionated, image-guided radiotherapy). Genetic events in recurrent murine medulloblastoma exhibit a very poor overlap with those in matched murine diagnostic samples (<5%).

Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations.

Diffuse intrinsic pontine glioma (DIPG) is a fatal brain cancer that arises in the brainstem of children, with no effective treatment and near 100% fatality. The failure of most therapies can be attributed to the delicate location of these tumors and to the selection of therapies on the basis of assumptions that DIPGs are molecularly similar to adult disease. Recent studies have unraveled the unique genetic makeup of this brain cancer, with nearly 80% found to harbor a p.

A phase II trial of a multi-agent oral antiangiogenic (metronomic) regimen in children with recurrent or progressive cancer.

Background: Preclinical models show that an antiangiogenic regimen at low-dose daily (metronomic) dosing may be effective against chemotherapy-resistant tumors. We undertook a prospective, open-label, single-arm, multi-institutional phase II study to evaluate the efficacy of a "5-drug" oral regimen in children with recurrent or progressive cancer.

Procedure: Patients ≤21 years old with recurrent or progressive tumors were eligible.

Morphoproteomic confirmation of constitutively activated mTOR, ERK, and NF-kappaB pathways in Ewing family of tumors.

In 3 patients with the Ewing family of tumors (EFT), morphoproteomic analyses of the tumors revealed constitutive activation of the mTOR, ERK, and NF-kappaB pathways, as evidenced by: (a) expression of phosphorylated (p)-mTOR, p-p70S6K, p-ERK 1/2, and p-NF-kappaB proteins using phosphospecific immunohistochemical probes directed against the activation sites; (b) nuclear translocation of p-p70S6K, p-ERK 1/2, and p-NF-kappaB p65; and (c) correlative expression of Ki-67 and Skp2 proteins consistent with cell cycling consequent to signal transduction by these pathways of convergence. This study examines the cytogenetic and molecular correlates and provides insight into therapeutic strategies relevant to this morphoproteomic profile. Based on a literature review, these observations appear to be the first morphoproteomic study of such pathways of convergence in tumors from EFT patients.

Sleep in children with neoplasms of the central nervous system: case review of 14 children.

Objective: Sleep is a complex neurologic process that is generated by and primarily benefits the brain. Sleep can be disrupted by a wide range of brain injuries, many of which may occur in children with neoplasms of the central nervous system (CNS). The specific sleep problems that have been associated with brain injuries include sleepiness, apnea, insomnia, and loss of circadian rhythmicity.