A5080536692- Glioma Diagnosis and Treatment
- Cancer Immunotherapy and Biomarkers
- Melanoma and MAPK Pathways
- Immunotherapy and Immune Responses
- Protein Degradation and Inhibitors
- Brain Metastases and Treatment
- CAR-T cell therapy research
- Click Chemistry and Applications
- Cancer Genomics and Diagnostics
- Nanoplatforms for cancer theranostics
- PARP inhibition in cancer therapy
- Cutaneous Melanoma Detection and Management
- Nonmelanoma Skin Cancer Studies
- Meningioma and schwannoma management
- Radiopharmaceutical Chemistry and Applications
- Ferroptosis and cancer prognosis
- Chronic Lymphocytic Leukemia Research
- Radiomics and Machine Learning in Medical Imaging
- Cutaneous lymphoproliferative disorders research
- Polyomavirus and related diseases
- Cancer Mechanisms and Therapy
- Quinazolinone synthesis and applications
- Cancer Research and Treatments
- Cancer Treatment and Pharmacology
- Antenna Design and Analysis
Washington University in St. Louis
2016-2025
Neurological Surgery
2022
American Academy of Dermatology
2022
Alvin J. Siteman Cancer Center
2020-2021
Jewish Hospital
2016-2018
Washington School of Psychiatry
2018
Barnes-Jewish Hospital
2016-2018
Abstract Background Nearly all patients with newly diagnosed glioblastoma experience recurrence following standard-of-care radiotherapy (RT) + temozolomide (TMZ). The purpose of the phase III randomized CheckMate 548 study was to evaluate RT TMZ combined immune checkpoint inhibitor nivolumab (NIVO) or placebo (PBO) in methylated MGMT promoter (NCT02667587). Methods Patients (N = 716) were 1:1 NIVO [(240 mg every 2 weeks × 8, then 480 4 weeks) (60 Gy over 6 (75 mg/m2 once daily during RT,...
We present the case of a patient with left frontal glioblastoma primitive neuroectodermal tumor features and hypermutated genotype in setting POLE germline alteration. During standard-of-care chemoradiation, developed cervical spine metastasis was subsequently treated pembrolizumab. Shortly thereafter, an additional metastatic spinal lesion. Using whole-exome DNA sequencing clonal analysis, we report changes subclonal architecture throughout treatment. Furthermore, persistently high...
Glioblastoma is the most lethal primary brain cancer. Clinical outcomes for glioblastoma remain poor, and new treatments are needed.To investigate whether adding autologous tumor lysate-loaded dendritic cell vaccine (DCVax-L) to standard of care (SOC) extends survival among patients with glioblastoma.This phase 3, prospective, externally controlled nonrandomized trial compared overall (OS) in newly diagnosed (nGBM) recurrent (rGBM) treated DCVax-L plus SOC vs contemporaneous matched external...
LBA9503 Background: mRNA-4157 is a novel mRNA-based personalized cancer vaccine which encodes up to 34 patient-specific tumor neoantigens. The open-label randomized Phase 2 mRNA-4157-P201/Keynote-942 trial met its primary endpoint of recurrence free survival (RFS) in patients with resected high-risk stage IIIB/C/D and IV melanoma. study has shown statistically significant clinically meaningful improvement RFS the combination therapy compared pembrolizumab monotherapy, reduction risk or death...
Abstract Background: Targeting of mutation-derived epitopes (neoantigens) by T cells has been demonstrated to drive anti-tumor immune responses. mRNA-4157 is a novel mRNA-based personalized cancer vaccine, which encodes up 34 patient-specific tumor neoantigens. It was hypothesized could synergize with adjuvant pembrolizumab improve recurrence free survival (RFS) in patients resected stages IIIB/IIIC/IIID and IV melanoma. Methods: Eligible completely resected, high-risk cutaneous melanoma...
Patients with progressive or recurrent meningiomas have limited systemic therapy options. Focal adhesion kinase (FAK) inhibition has a synthetic lethal relationship
Autophagy is a resistance mechanism to BRAF/MEK inhibition in BRAFV600-mutant melanoma. Here we used hydroxychloroquine (HCQ) inhibit autophagy combination with dabrafenib 150 mg twice daily and trametinib 2 every day (D+T).
LBA9512 Background: mRNA-4157 is a novel, mRNA-based individualized neoantigen therapy designed to increase endogenous antitumor T-cell responses by targeting unique patient (pt) tumor mutations. In the primary analysis of Ph 2 mRNA-4157-P201 (KEYNOTE-942) trial (median planned follow-up, 23 mo), pts with completely resected high-risk stage IIIB–IV cutaneous melanoma receiving + pembrolizumab (pembro; combo) had prolonged recurrence-free survival (RFS) and distant metastasis-free (DMFS) vs...
Immune checkpoint inhibitors (ICPis) are a novel class of immunotherapeutic agents that have revolutionized the treatment cancer; however, these drugs can also cause unique spectrum autoimmune toxicity. Autoimmune hemolytic anemia (AIHA) is rare, but often severe, complication ICPis. We identified 14 patients from nine institutions across United States who developed ICPi-AIHA. The median interval ICPi initiation to development AIHA was 55 days (interquartile range [IQR], 22-110 days)....
BRAF V600E mutations have been successfully treated with targeted therapy in melanoma, non–small cell lung cancer, and thyroid cancer. Interestingly, these also identified a subset of pediatric adult brain tumors, several cases reportedly responding to therapy. However, reports limited single-agent inhibitor recurrent disease. Herein, we report dramatic clinical radiographic responses combination dabrafenib (BRAF inhibitor) trametinib (MEK 2 adults high-grade gliomas (HGGs), 1 patient the...
The blood-brain barrier (BBB) is a major limiting factor for drug delivery in brain tumors. Laser interstitial thermal therapy (LITT) disrupts the peritumoral BBB. In this study, we examine survival patients with recurrent glioblastoma (GBM) treated LITT followed by low-dose doxorubicin, potent anti-neoplastic poor BBB permeability.Forty-one GBM were enrolled; thirty evaluable. Participants underwent 6 weekly doxorubicin treatments starting within one week (Early Arm) or at 6-8 weeks (Late...
Gliomas are the most common primary brain tumor in adults. Current treatments involve surgery, radiation, and temozolomide (TMZ) chemotherapy; however, prognosis remains poor new approaches required. Circadian medicine aims to maximize treatment efficacy and/or minimize toxicity by timed delivery of medications accordance with daily rhythms patient. We published a retrospective study showing greater anti-tumor for morning, relative evening, administration TMZ patients glioblastoma. conducted...
Abstract ARID genes encode subunits of SWI/SNF chromatin remodeling complexes and are frequently mutated in human cancers. We investigated the correlation between mutations, molecular features, clinical outcomes melanoma patients. Cutaneous samples (n = 1577) were analyzed by next-generation sequencing. Samples stratified pathogenic/likely pathogenic mutation ( ARID1A/2/1B/5B ). PD-L1 expression was assessed using IHC (SP142; positive (+): ≥ 1%). Tumor burden (TMB)-high defined as 10...
Despite the improved understanding of molecular and genetic heterogeneity glioblastoma, there is still an unmet need for better therapeutics, as treatment approaches have remained unchanged in recent years. Research into role immune microenvironment has generated enthusiasm testing immunotherapy (specifically, checkpoint inhibitors). However, to date, trials glioblastoma not demonstrated a survival advantage. Combination aimed at optimally inducing response inhibitors with radiotherapy are...
Craniopharyngiomas are rare tumors that arise in the suprasellar region of brain and known for their aggressive nature despite WHO grade I. This is due to complex neuroanatomy sellar/suprasellar proximity optic nerve apparatus, hypothalamic-pituitary tract, other critical neuroanatomical structures. Definitive treatment based on a multidisciplinary approach often involves combination surgical, radiation, medical therapy. However, there high morbidity associated with surgery RT this region....
Abstract BACKGROUND Novel therapies are needed in newly diagnosed glioblastoma as nearly all patients experience recurrence following standard-of-care radiotherapy (RT) + temozolomide (TMZ), including with tumors methylated MGMT promoter, a positive prognostic factor and predictor of benefit TMZ. Here, we report the final analysis progression-free survival (PFS), overall (OS), safety from an international randomized, single-blind phase-3 study nivolumab (NIVO)+RT+TMZ methylated/indeterminate...