A5031795097- Glioma Diagnosis and Treatment
- Neuroblastoma Research and Treatments
- Brain Metastases and Treatment
- Meningioma and schwannoma management
- Chromatin Remodeling and Cancer
- Ocular Oncology and Treatments
- Vascular Malformations Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Sarcoma Diagnosis and Treatment
- Childhood Cancer Survivors' Quality of Life
- CAR-T cell therapy research
- Histone Deacetylase Inhibitors Research
- Radiation Therapy and Dosimetry
- Renal cell carcinoma treatment
- Protein Degradation and Inhibitors
- Neurofibromatosis and Schwannoma Cases
- Radiopharmaceutical Chemistry and Applications
- Melanoma and MAPK Pathways
- Radiomics and Machine Learning in Medical Imaging
- Cancer Cells and Metastasis
- Cancer Genomics and Diagnostics
- Cerebrospinal fluid and hydrocephalus
- Hedgehog Signaling Pathway Studies
- Acute Lymphoblastic Leukemia research
- Immune Cell Function and Interaction
The University of Texas MD Anderson Cancer Center
2016-2025
University Surgical Associates
2022
European School of Oncology
2022
Scripps MD Anderson Cancer Center
2014-2020
Office of Patient Care Services
2017
Johns Hopkins Hospital
2013
National Institute of Mental Health and Neurosciences
2013
Columbia University
2013
Orlando Health
2013
Fred Hutch Cancer Center
2012
Abstract Background ONC201, a dopamine receptor D2 (DRD2) antagonist and caseinolytic protease P (ClpP) agonist, has induced durable tumor regressions in adults with recurrent H3 K27M-mutant glioma. We report results from the first phase I pediatric clinical trial of ONC201. Methods This open-label, multi-center (NCT03416530) ONC201 for diffuse midline glioma (DMG) or intrinsic pontine (DIPG) employed dose-escalation dose-expansion design. The primary endpoint was recommended II dose (RP2D)....
Abstract Background Atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system (CNS) is a rare embryonal neoplasm early childhood with dismal outcome and no current uniformly accepted treatment. Given its highly aggressive nature predilection for dissemination at diagnosis, intensive multimodal therapy required. Materials Methods Nineteen children newly diagnosed CNS AT/RT were treated on head start (HS) III protocol. Treatment consisted surgical resection, 5 cycles induction...
Abstract Background Choroid plexus carcinoma (CPC) is a rare aggressive intracranial neoplasm with predilection for young children and historically poor outcome. Currently, no defined optimal therapeutic strategy exists. The Head Start (HS) regimens have included irradiation‐avoiding strategies in malignant brain tumors using high dose chemotherapy to improve survival minimize neurocognitive sequelae. Procedure Three sequential HS studies been conducted from 1991 2009. treatment has...
Recurrent pediatric medulloblastoma and ependymoma have a grim prognosis. We report first-in-human, phase I study of intraventricular infusions ex vivo expanded autologous natural killer (NK) cells in these tumors, with correlative studies.Twelve patients were enrolled, 9 received protocol therapy up to 3 weekly, escalating doses from × 106 108 NK cells/m2/infusion, for cycles. Cerebrospinal fluid (CSF) was obtained cellular profile, persistence, phenotypic analysis cells. Radiomic...
Diffuse midline gliomas (DMG), including brainstem diffuse intrinsic pontine glioma (DIPG), are incurable pediatric high-grade (pHGG). Mutations in the H3 histone tail (H3.1/3.3-K27M) a feature of DIPG, rendering them therapeutically sensitive to small-molecule inhibition chromatin modifiers. Pharmacological lysine-specific demethylase 1 (LSD1) is clinically relevant but has not been carefully investigated pHGG or DIPG.Patient-derived DIPG cell lines, orthotopic mouse models, and datasets...
Central nervous system (CNS) cancers account for approximately one quarter of all pediatric tumors and are the leading cause cancer-related death in children. More than 4,000 brain CNS diagnosed each year children teens, incidence rate has remained stagnant recent years. The most common malignant gliomas, embryonal consisting predominately medulloblastomas, germ cell tumors. inaugural version NCCN Guidelines Pediatric Nervous System Cancers focuses on diagnosis management patients with...
Abstract Background This study evaluated the safety and pharmacokinetics (PK) of oral ONC201 administered twice-weekly on consecutive days (D1D2) in pediatric patients with newly diagnosed DIPG and/or recurrent/refractory H3 K27M glioma. Methods phase 1 dose-escalation expansion included K27M-mutant glioma following ≥1 line therapy (NCT03416530). was D1D2 at 3 dose levels (DLs; −1, 1, 2). The actual within DLs dependent weight. Safety assessed all DLs; PK analysis conducted DL2. Patients...
ABSTRACT Background Diffuse intrinsic pontine glioma (DIPG) carries a poor prognosis with median survival of less than 12 months. Key molecular features include histone H3 mutation (K27M) and AKT pathway dysregulation. There is currently no curative treatment. Methods This Phase I study vorinostat temsirolimus in newly diagnosed (Stratum 1) progressive 2) DIPG (NCT02420613). The primary aims are to determine the safety, maximum tolerated dose (MTD), toxicities. A modified 3 + design was used...
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pediatric Central Nervous System Cancers provide multidisciplinary diagnostic workup, staging, and treatment recommendations diffuse high-grade gliomas medulloblastomas children adolescents. This article summarizes the studies panel discussion that serve as rationale comprehensive care included Cancers.
Brainstem toxicity after radiation therapy (RT) is a devastating complication and particular concern with proton (PBT). We investigated the incidence clinical correlates of brainstem injury in pediatric brain tumors treated PBT.All patients <21 years PBT at our institution from 2007-2019, Dmean >30 Gy and/or Dmax >50.4 were included. Symptomatic (SBI) was defined as any new or progressive cranial neuropathy, ataxia, motor weakness corresponding radiographic abnormality within brainstem.A...
Despite advances in treatment options, the clinical outcomes of pediatric patients with advanced solid tumors have hardly improved decades, and alternative options are urgently needed. Innovative therapies, such as chimeric antigen receptor (CAR) T cells oncolytic viruses (OVs), currently being evaluated both adults children refractory tumors. Because remarkably diverse biologically different from their adult counterparts, more research is required to develop effective regimens for these...
Diffuse intrinsic pontine gliomas (DIPG) are inoperable and highly resistant tumors to chemotherapy irradiation. DIPG has the worst prognosis among all pediatric brain overwhelming majority of patients die within 6-18 months after diagnosis.We retrospectively reviewed charts six treated with chemoradiotherapy (daily carboplatin oral etoposide in five temozolomide one patient) followed by maintenance consisting irinotecan, temozolomide, bevacizumab at our institution between January 2007...
Background Ikaros, the product of IKZF1, is a regulator lymphoid development and polymorphisms in gene have been associated with acute lymphoblastic leukemia (ALL). Additionally, IKZF1 deletions mutations identify high-risk biological subsets childhood ALL [Georgopoulos et al. Cell 1995;83(2):289–299; Mullighan N Engl J Md 2009;360(5):470–480]. Procedures To discover underlying pathways modulated by Ikaros we performed expression ontology analysis deleted primary B-ALL pediatric patient...
We hypothesize that chemotherapy can be safely administered directly into the fourth ventricle to treat recurrent malignant brain tumors in children. For first time humans, methotrexate was infused children with recurrent, tumors. A catheter surgically placed and attached a ventricular access device. Cerebrospinal fluid (CSF) flow confirmed by CINE MRI postoperatively. Each cycle consisted of 4 consecutive daily infusions (2 milligrams). Disease response monitored serial scans CSF cytologic...
Diffuse midline glioma, H3-K27M mutant (DMG-K27M) is a newly described, molecularly distinct infiltrative glioma that almost exclusively arises in CNS structures, including the brain stem, especially pons, as well thalamus and spinal cord with rare examples seen cerebellum, third ventricle, hypothalamus. To our knowledge, only 1 case of confirmed DMG-K27M arising pineal region has been previously reported. We present second occurrence tissue-confirmed region, which, to first reported child...
Medulloblastoma in adults is rare and treatment decisions are largely driven from pediatric literature. We sought to characterize recurrent medulloblastoma adults.From a single-institution dataset of 200 adult patients diagnosed with during 1978-2017, those recurrence were analyzed for clinical features, treatment, outcome.Of the patients, 82 (41%) median age 29 years (18-59) had after follow-up time 8.4 (95% CI = 7.1, 10.3). Of these, 30 (37%) standard-risk, 31 (38%) high-risk, 21 (26%)...
Abstract Background Adult medulloblastoma (MB) is rare, and management guidelines are largely based on pediatric clinical trials retrospective series. Limited data exist with respect to characteristics, prognostic factors, outcomes first-line treatments. Methods Two hundred adults MB seen at a single institution from January 1978 April 2017 were identified followed for median of 8.4 y (7.1, 10.3). Results Patient’s age diagnosis was 29 (18, 63). One eleven (55.5%) standard-risk, 59 (29.5%)...