Slipped capital femoral epiphyses: A major on-target adverse event associated with FGFR tyrosine kinase inhibitors in pediatric patients.

Fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitors (TKIs) are increasingly being used off label in pediatrics. Long-term safety data are limited, and serious toxicities unique to pediatrics may emerge. In a retrospective analysis of patients less than 18 years of age with recurrent/refractory FGFR altered gliomas treated with FGFR TKIs at MSKCC (n = 7), we observed slipped capital femoral epiphyses in three of seven patients along with increased linear growth velocity.

Treatment of Pediatric Low-Grade Gliomas.

Purpose Of Review: Pediatric low-grade gliomas and glioneuronal tumors (pLGG) account for approximately 30% of pediatric CNS neoplasms, encompassing a heterogeneous group of tumors of primarily glial or mixed neuronal-glial histology. This article reviews the treatment of pLGG with emphasis on an individualized approach incorporating multidisciplinary input from surgery, radiation oncology, neuroradiology, neuropathology, and pediatric oncology to carefully weigh the risks and benefits of specific interventions against tumor-related morbidity. Complete surgical resection can be curative for cerebellar and hemispheric lesions, while use of radiotherapy is restricted to older patients or those refractory to medical therapy.

Progress in precision therapy in pediatric oncology.

Purpose Of Review: The fields of precision medicine and cancer genomics in pediatric oncology are rapidly evolving. Novel diagnostic tools are critical in refining cancer diagnoses, stratifying patient risk, and informing treatment decisions. This review is timely and relevant as it discusses advantages and drawbacks of common molecular profiling techniques and highlights novel platforms, which may address select limitations.

Lack of complete response pretransplant is not associated with inferior overall survival for stage 4a metastatic retinoblastoma.

Background: Stage 4a metastatic retinoblastoma (RB) is curable with intensive multimodality therapy including myeloablative chemotherapy with autologous stem cell transplant (HDC-ASCT) and involved field radiation therapy (IFRT). To our knowledge, no data exist on the impact of (a) pre-ASCT disease status, and (b) IFRT to sites of metastatic disease post ASCT on survival.

Procedure: We retrospectively reviewed patients with stage 4a metastatic RB who underwent induction chemotherapy followed by HDC-ASCT, with or without IFRT, to residual tumor sites at Memorial Sloan Kettering Cancer Center (MSKCC) (n = 24).

Integrated Drug Mining Reveals Actionable Strategies Inhibiting Plexiform Neurofibromas.

Neurofibromatosis Type 1 (NF1) is one of the most common genetic tumor predisposition syndromes, affecting up to 1 in 2500 individuals. Up to half of patients with NF1 develop benign nerve sheath tumors called plexiform neurofibromas (PNs), characterized by biallelic NF1 loss. PNs can grow to immense sizes, cause extensive morbidity, and harbor a 15% lifetime risk of malignant transformation.

Upfront molecular targeted therapy for the treatment of BRAF-mutant pediatric high-grade glioma.

Background: The prognosis for patients with pediatric high-grade glioma (pHGG) is poor despite aggressive multimodal therapy. Objective responses to targeted therapy with BRAF inhibitors have been reported in some patients with recurrent BRAF-mutant pHGG but are rarely sustained.

Methods: We performed a retrospective, multi-institutional review of patients with BRAF-mutant pHGG treated with off-label BRAF +/- MEK inhibitors as part of their initial therapy.

Prospective pan-cancer germline testing using MSK-IMPACT informs clinical translation in 751 patients with pediatric solid tumors.

The spectrum of germline predisposition in pediatric cancer continues to be realized. Here we report 751 solid tumor patients who underwent prospective matched tumor-normal DNA sequencing and downstream clinical use (clinicaltrials.gov NCT01775072).

Genetic syndromes predisposing to pediatric brain tumors.

The application of high-throughput sequencing approaches including paired tumor/normal sampling with therapeutic intent has demonstrated that 8%-19% of pediatric CNS tumor patients harbor a germline alteration in a classical tumor predisposition gene (, ). In addition, large-scale germline sequencing studies in unselected cohorts of pediatric neuro-oncology patients have demonstrated novel candidate tumor predisposition genes ( alterations in sonic hedgehog medulloblastoma). Therefore, the possibility of an underlying tumor predisposition syndrome (TPS) should be considered in all pediatric patients diagnosed with a CNS tumor which carries critical implications including accurate prognostication, selection of optimal therapy, screening, risk reduction, and family planning.

Stem-like cells drive NF1-associated MPNST functional heterogeneity and tumor progression.

NF1-associated malignant peripheral nerve sheath tumors (MPNSTs) are the major cause of mortality in neurofibromatosis. MPNSTs arise from benign peripheral nerve plexiform neurofibromas that originate in the embryonic neural crest cell lineage. Using reporter transgenes that label early neural crest lineage cells in multiple NF1 MPNST mouse models, we discover and characterize a rare MPNST cell population with stem-cell-like properties, including quiescence, that is essential for tumor initiation and relapse.

Oncolytic HSV-1 G207 Immunovirotherapy for Pediatric High-Grade Gliomas.

Background: Outcomes in children and adolescents with recurrent or progressive high-grade glioma are poor, with a historical median overall survival of 5.6 months. Pediatric high-grade gliomas are largely immunologically silent or "cold," with few tumor-infiltrating lymphocytes.

A Potential Role For Apparent Diffusion Coefficient in the Diagnosis of Trilateral Retinoblastoma.

We attempted to investigate the potential role for apparent diffusion coefficient (ADC) to diagnose trilateral retinoblastoma (TRb) by retrospectively reviewing brain magnetic resonance images of retinoblastoma patients. Observations: The median ADC measured 620.95 for TRb (n=6) and 1238.

Spontaneous Regression in a Patient With Infantile Fibrosarcoma.

Infantile fibrosarcoma usually presents as a rapidly growing mass on the extremities or trunk. We describe spontaneous regression in a 5-month-old female infant with biopsy proven, molecularly confirmed, right leg infantile fibrosarcoma currently at 26 months of age with no signs of local recurrence. Previously reported cases of spontaneous regression are reviewed, suggesting a benign clinical course in some cases.

Ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication of assisted reproduction technology. The syndrome is characterized by cystic enlargement of the ovaries and a fluid shift from the intravascular to the third space due to increased capillary permeability and ovarian neoangiogenesis. Its occurrence is dependent on the administration of human chorionic gonadotrophin (hCG).

Luteinizing hormone and its dilemma in ovulation induction.

Concept of a 'therapeutic window' of luteinizing hormone (LH) for successful conception in assisted reproductive technology and ovulation induction has been reviewed in this literature. The separate but complementary roles of follicle stimulating hormone and LH in stimulating folliculogenesis and ovulation are well established. Levels under which low LH concentrations may be equally or suboptimally needed for oocyte quality and subsequent embryonic development competence has been reviewed along with the data related to the high levels of LH promoting follicular atresia.