A5030335484- Glioma Diagnosis and Treatment
- Neuroblastoma Research and Treatments
- Childhood Cancer Survivors' Quality of Life
- Pituitary Gland Disorders and Treatments
- Meningioma and schwannoma management
- Family Support in Illness
- Neurofibromatosis and Schwannoma Cases
- Adrenal and Paraganglionic Tumors
- Epilepsy research and treatment
- Cancer Genomics and Diagnostics
- Chromatin Remodeling and Cancer
- Protein Degradation and Inhibitors
- Acute Lymphoblastic Leukemia research
- DNA Repair Mechanisms
- Vascular Malformations Diagnosis and Treatment
- Pharmacological Effects and Toxicity Studies
- Ocular Oncology and Treatments
- Pediatric Pain Management Techniques
- Family and Disability Support Research
- Melanoma and MAPK Pathways
- Myasthenia Gravis and Thymoma
- Cancer-related cognitive impairment studies
- PARP inhibition in cancer therapy
- Management of metastatic bone disease
- Brain Metastases and Treatment
NGM Biopharmaceuticals (United States)
2023-2025
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
2015-2024
Harvard University
2009-2024
Boston Children's Hospital
2013-2024
University of Leeds
2024
University of Oxford
2021-2023
John Radcliffe Hospital
2023
Wellcome Centre for Integrative Neuroimaging
2021
Dana-Farber Cancer Institute
2012-2020
Indiana University School of Medicine
2019
Atypical teratoid rhabdoid tumor (ATRT) of the CNS is a highly malignant neoplasm primarily affecting young children, with historic median survival ranging from 6 to 11 months. Based on previous pilot series, prospective multi-institutional trial was conducted for patients newly diagnosed ATRT.Treatment divided into five phases: preirradiation, chemoradiation, consolidation, maintenance, and continuation therapy. Intrathecal chemotherapy administered, alternating intralumbar intraventricular...
Background Children with pediatric low‐grade gliomas (PLGG) are known to have excellent 10‐year survival rates; however the outcomes of adult survivors PLGG unknown. We identified patients diagnosed between 1973 and 2008 through Surveillance Epidemiology End Results (SEER) database examine PLGG. Procedure Four thousand forty either WHO grade I or II were outcome data retrieved. Two analyses performed assess risk death from tumor. Competing risks analysis was conducted cumulative incidence...
Abstract BRAF genomic alterations are the most common oncogenic drivers in pediatric low-grade glioma (pLGG). Arm 1 ( n = 77) of ongoing phase 2 FIREFLY-1 (PNOC026) trial investigated efficacy oral, selective, central nervous system–penetrant, type II RAF inhibitor tovorafenib (420 mg m − once weekly; 600 maximum) patients with -altered, relapsed/refractory pLGG. 60) is an extension cohort, which provided treatment access for -altered pLGG after arm closure. Based on independent review,...
Predictive biomarkers of response are essential to effectively guide targeted cancer treatment. Ataxia telangiectasia and Rad3-related kinase inhibitors (ATRi) have been shown be synthetic lethal with loss function (LOF) ataxia telangiectasia-mutated (ATM) kinase, preclinical studies identified ATRi-sensitizing alterations in other DNA damage (DDR) genes. Here we report the results from module 1 an ongoing phase trial ATRi camonsertib (RP-3500) 120 patients advanced solid tumors harboring...
Abstract Background Pediatric low-grade glioma (pLGG) is essentially a single pathway disease, with most tumors driven by genomic alterations affecting the mitogen-activated protein kinase/ERK (MAPK) pathway, predominantly KIAA1549::BRAF fusions and BRAF V600E mutations. This makes pLGG an ideal candidate for MAPK pathway-targeted treatments. The type I inhibitor, dabrafenib, in combination MEK trametinib, has been approved United States Food Drug Administration systemic treatment of...
BACKGROUND The determinants of outcomes for adult survivors pediatric low‐grade glioma (PLGG) are largely unknown. METHODS This study collected population‐based follow‐up information all PLGG patients diagnosed in Ontario, Canada from 1985 to 2012 (n = 1202) and determined factors affecting survival. impact upfront radiation treatment on overall survival (OS) was a cohort Ontario an independent reference the Surveillance, Epidemiology, End Results database. RESULTS At median 12.73 years...
Abstract 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 “5‐drug” oral in children with recurrent or progressive cancer. Procedure Patients ≤21 years old tumors were eligible. Treatment consisted continuous celecoxib, thalidomide, and fenofibrate, alternating 21‐day...
Abstract Background Diagnosis of diffuse intrinsic pontine glioma (DIPG) has relied on imaging studies, since the appearance is pathognomonic, and surgical risk was felt to be high unlikely affect therapy. The DIPG Biology Treatment Study (DIPG-BATS) reported here incorporated a biopsy at presentation stratified subjects receive FDA-approved agents chosen basis specific biologic targets. Methods Subjects were eligible for trial if clinical features newly diagnosed tumor consistent with DIPG....
Ependymoma is the third most common brain tumor in children, but there a paucity of large studies with more than 10 years follow-up examining long-term survival and recurrence patterns this disease. We conducted retrospective chart review 103 pediatric patients WHO Grades II/III intracranial ependymoma, who were treated at Dana-Farber/Boston Children's Cancer Blood Disorders Center Chicago's Ann & Robert H. Lurie Hospital between 1985 2008, an additional 360 ependymoma identified from...
Craniopharyngiomas are neoplasms of the sellar/parasellar region that classified into adamantinomatous craniopharyngioma (ACP) and papillary (PCP) subtypes. Surgical resection craniopharyngiomas is challenging, recurrence common, frequently leading to profound morbidity. BRAF V600E mutations render PCP susceptible BRAF/MEK inhibitors, but effective targeted therapies needed for ACP. We explored feasibility targeting programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1)...
Clinical genomics platforms are needed to identify targetable alterations, but implementation of these technologies and best practices in routine clinical pediatric oncology practice not yet well established.Profile is an institution-wide prospective research initiative that uses targeted sequencing alterations tumors. OncoPanel, a multiplexed exome-sequencing platform includes 300 cancer-causing genes, was used assess single nucleotide variants rearrangements/indels. Alterations were...
Gene-mediated cytotoxic immunotherapy (GMCI) is a tumor-specific immune stimulatory strategy implemented through local delivery of aglatimagene besadenovec (AdV-tk) followed by anti-herpetic prodrug. GMCI induces T-cell dependent tumor immunity and synergizes with radiotherapy. Clinical trials in adult malignant gliomas demonstrated safety potential efficacy. This the first trial pediatric brain tumors. phase I dose escalation study was conducted to evaluate patients 3 years age or older...
Activation of the mammalian target rapamycin (mTOR) pathway is observed in neurofibromatosis type 1 (NF1) associated low-grade gliomas (LGGs), but agents that inhibit this pathway, including mTOR inhibitors, have not been studied population. We evaluate efficacy orally administered inhibitor everolimus for radiographically progressive NF1-associated pediatric LGGs.Children with radiologic-progressive, LGG and prior treatment a carboplatin-containing chemotherapy were prospectively enrolled...
There is no proven medical therapy for plexiform neurofibromas (PNs). We undertook a phase II trial of pegylated interferon (PI) to evaluate response and time progression (TTP). PI was administered as subcutaneous injection patients with neurofibromatosis type 1‒related PN, stratified by the presence symptoms (asymptomatic: stratum 1, symptomatic: 2) or documented imaging (stratum 3). Patients in strata 1 2 received up one year if stable, years those clinical (≥20% decrease volume). on 3...
Seizures are common during and after treatment for a primary brain tumor. Our objective was to describe the incidence risk factors seizures in long-term survivors of pediatric tumors.In retrospective, longitudinal study, we reviewed all consecutive patients 12-month period who were at least 2 years post initial diagnosis Data collection included age diagnosis, length follow-up, extent resection, tumor histology, modalities. For had experienced any time, timing frequency seizures, seizure...