Outcomes after first relapse of childhood intracranial ependymoma.

Background: Ependymoma is the third most common malignant CNS tumor in children. Despite multimodal therapy, prognosis of relapsed ependymoma remains poor. Approaches to therapy for relapsed ependymoma are varied.

Trametinib for the treatment of recurrent/progressive pediatric low-grade glioma.

Purpose: Pediatric low-grade gliomas (pLGGs) are the most common CNS tumor of childhood and comprise a heterogenous group of tumors. Children with progressive pLGG often require numerous treatment modalities including surgery, chemotherapy, rarely radiation therapy and, more recently, molecularly targeted therapy. We describe our institutional experience using the MEK inhibitor, trametinib, for recurrent/progressive pLGGs.

Immune checkpoint inhibition for pediatric patients with recurrent/refractory CNS tumors: a single institution experience.

Introduction: Immune checkpoint inhibition through PD-1 and CTLA-4 blockade has shown efficacy in some adult malignancies and generated interest in pediatrics, including central nervous system (CNS) tumors. We describe our experience with immune checkpoint inhibition in recurrent/refractory pediatric CNS tumors.

Methods: We performed a retrospective chart review of pediatric patients with recurrent or refractory CNS tumors treated with ipilimumab, nivolumab and/or pembrolizumab at Dana-Farber/Boston Children's Hospital between 2018 and 2019.

B355252, A Novel Small Molecule, Confers Neuroprotection Against Cobalt Chloride Toxicity In Mouse Hippocampal Cells Through Altering Mitochondrial Dynamics And Limiting Autophagy Induction.

Cerebral hypoxia as often occurs in cases of stroke, hemorrhage, or other traumatic brain injuries, is one of the leading causes of death worldwide and a main driver of disabilities in the elderly. Using a chemical mimetic of hypoxia, cobalt chloride (CoCl), we tested the ability of a novel small molecule, 4-chloro-N-(naphthalen-1-ylmethyl)-5-(3-(piperazin-1-yl)phenoxy)thiophene-2-sulfonamide (B355252), to alleviate CoCl-induced damage in mouse hippocampal HT22 cells. A dose-dependent decrease in cell viability was observed during CoCl treatment along with increases in mitochondrial membrane potential and generation of reactive oxygen species (ROS).

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.

A prospective, blinded analysis of A-PROTEIN (recoverin or CAR protein) levels in pediatric patients with central nervous system tumors.

Background: Abnormal expression of A-PROTEIN has been identified in a number of tumors including carcinoma of the lung, breast, colon, prostate, and cervix. Brain tumors have been reported to express high plasma levels of A-PROTEIN, suggesting that it may be of significant diagnostic and prognostic value.

Procedure: This prospective study evaluated the sensitivity and specificity of A-PROTEIN levels in pediatric brain tumor patients.

Intensive multimodality treatment for children with newly diagnosed CNS atypical teratoid rhabdoid tumor.

Purpose: Atypical teratoid rhabdoid tumor (ATRT) of the CNS is a highly malignant neoplasm primarily affecting young children, with a historic median survival ranging from 6 to 11 months. Based on a previous pilot series, a prospective multi-institutional trial was conducted for patients with newly diagnosed CNS ATRT.

Patients And Methods: Treatment was divided into five phases: preirradiation, chemoradiation, consolidation, maintenance, and continuation therapy.

Phase II study of thalidomide and radiation in children with newly diagnosed brain stem gliomas and glioblastoma multiforme.

A phase II study was conducted to assess the efficacy of administering daily thalidomide concomitantly with radiation and continuing for up to 1 year following radiation in children with brain stem gliomas (BSG) or glioblastoma multiforme (GBM). Secondary objectives were to obtain preliminary evidence of biologic activity of thalidomide and to evaluate toxicities from chronic administration of thalidomide in this population. Thirteen patients (2-14 years old) with newly diagnosed BSG (12 patients) or GBM (one patient) were enrolled between July 1999 and June 2000.

Transverse myelitis after therapy for primitive neuroectodermal tumors.

Traditional therapy for malignant primitive neuroectodermal tumors in children includes surgery, multi-agent chemotherapy, and radiation. Given the poor prognosis with conventional therapy alone, newer treatment approaches have incorporated high-dose chemotherapy followed by autologous stem cell rescue. Treatment with chemotherapy and radiation is not without unanticipated and unwanted side effects.

A feasibility trial of antiangiogenic (metronomic) chemotherapy in pediatric patients with recurrent or progressive cancer.

Standard chemotherapeutic drugs, when modified by the frequency and dose of administration, can target angiogenesis. This approach is referred to as antiangiogenic chemotherapy, low-dose chemotherapy, or metronomic chemotherapy. This study evaluated the feasibility of 6 months of metronomic chemotherapy, its toxicity and tolerability, surrogate markers of activity, and preliminary evidence of activity in children with recurrent or progressive cancer.

Continuous remission of newly diagnosed and relapsed central nervous system atypical teratoid/rhabdoid tumor.

Atypical teratoid/rhabdoid tumors (AT/RT) are highly malignant lesions of childhood that carry a very poor prognosis. AT/RT can occur in the central nervous system (CNS AT/RT) and disease in this location carries an even worse prognosis with a median survival of 7 months. In spite of multiple treatment regimens consisting of maximal surgical resection (including second look surgery), radiation therapy (focal and craniospinal), and multi-agent intravenous, oral and intrathecal chemotherapy, with or without high-dose therapy and stem cell rescue, only seven long-term survivors of CNS AT/RT have been reported, all in patients with newly diagnosed disease.