A5024146796- Pancreatic and Hepatic Oncology Research
- Cancer Genomics and Diagnostics
- PARP inhibition in cancer therapy
- Neutropenia and Cancer Infections
- Gastric Cancer Management and Outcomes
- Cancer Diagnosis and Treatment
- Colorectal Cancer Treatments and Studies
- Neuroendocrine Tumor Research Advances
- Cancer Research and Treatments
- Head and Neck Cancer Studies
- Metastasis and carcinoma case studies
- Cancer Treatment and Pharmacology
- Lung Cancer Treatments and Mutations
- Cancer Immunotherapy and Biomarkers
- Genetic factors in colorectal cancer
- Renal cell carcinoma treatment
- Tumors and Oncological Cases
- CAR-T cell therapy research
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Colorectal and Anal Carcinomas
- Hepatocellular Carcinoma Treatment and Prognosis
- Gastrointestinal Tumor Research and Treatment
- Esophageal Cancer Research and Treatment
- Pancreatitis Pathology and Treatment
- Extracellular vesicles in disease
The University of Texas MD Anderson Cancer Center
2020-2025
Baylor College of Medicine
2017-2022
Georgetown Lombardi Comprehensive Cancer Center
2015-2020
Dan L Duncan Comprehensive Cancer Center
2017-2019
Georgetown University
2012-2018
Georgetown University Medical Center
2012-2018
MedStar Georgetown University Hospital
2013-2017
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
2016
Caris Life Sciences (United States)
2016
Vassar College
2003
Pembrolizumab significantly improves clinical outcomes in advanced/metastatic microsatellite instability high (MSI-H)/deficient mismatch repair (dMMR) solid tumors but is not well studied the neoadjuvant space.
Abstract The relevance of KRAS mutation alleles to clinical outcome remains inconclusive in pancreatic adenocarcinoma (PDAC). We conducted a retrospective study 803 patients with PDAC (42% metastatic disease) at MD Anderson Cancer Center. Overall survival (OS) analysis demonstrated that status and subtypes were prognostic ( p < 0.001). Relative wildtype tumors (median OS 38 months), G12R had similar 34 while Q61 G12D mutated shorter 20 months [HR: 1.9, 95% CI 1.2–3.0, = 0.006] 22 1.7,...
The EXTEND trial tested the hypothesis that adding comprehensive metastasis-directed therapy (MDT) to chemotherapy would improve progression-free survival (PFS) over alone among patients with oligometastatic pancreatic ductal adenocarcinoma (PDAC).
603 Background: Standard treatment of oligometastatic pancreatic ductal adenocarcinoma (PDAC) consists multi-agent chemotherapy, although outcomes remain poor. We tested the hypothesis that addition comprehensive metastasis-directed therapy (MDT) to standard-of-care systemic would improve progression-free survival (PFS) compared with alone. Methods: The External Beam Radiation Eliminate Nominal Metastatic Disease (EXTEND) trial is a multicenter phase II basket randomizing patients ≤ 5 solid...
Abstract Purpose: Prognostic uncertainty is a major challenge for cancer of unknown primary (CUP). Current models limit meaningful patient-provider dialogue. We aimed to establish nomogram predicting overall survival (OS) in CUP based on robust clinicopathologic prognostic factors. Experimental Design: evaluated 521 patients with at MD Anderson Cancer Center (MDACC; Houston, TX; 2012–2016). Baseline variables were analyzed using Cox regression and developed significant predictors. Predictive...
Objective: To characterize associations between carbohydrate antigen 19–9 (CA19–9) dynamics during neoadjuvant therapy (NT) and survival for patients with pancreatic ductal adenocarcinoma (PDAC). Background: Although normalization of CA19–9 NT is associated improved outcomes following PDAC resection, we hypothesize that can improve prognostication. Methods: Characteristics undergoing (July 2011–October 2018) ≥3 results (bilirubin<2mg/dL) were collected grouped by dynamics. Nonproducers...
Background Cancer of unknown primary (CUP) is an aggressive rare malignancy with limited treatment options. Data regarding clinical activity immune checkpoint inhibitors in CUP lacking. Therefore, we evaluated the efficacy pembrolizumab, a programmed cell death-1 inhibitor, patients CUP. Methods The study was designed as phase 2 basket trial for independent tumor cohorts including Adult who had progressed on previous systemic therapy, performance status 0/1 and measurable disease per...
// Brandon G. Smaglo 1 , Anteneh Tesfaye 2 Thorvardur R. Halfdanarson 3 Joshua E. Meyer 4 Jue Wang 5 Zoran Gatalica 6 Sandeep Reddy David Arguello and Patrick M. Boland 7 The Ruesch Center for the Cure of GI Cancers, Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, USA Departments Hematology/Oncology, Department Medicine, Mayo Clinic, Rochester, MN, Radiation Oncology, Fox Chase Philadelphia, PA, Division University Arizona Phoenix, AZ, Pathology, Caris Life Sciences, Roswell...
Up to 17% of patients with pancreatic ductal adenocarcinoma (PDAC) harbor pathogenic (germline or somatic) mutations in a homologous recombination, DNA damage response and repair (HR-DDR) gene, such as
TPS633 Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with few effective therapeutic options. Over 90% of patients PDAC harbor activating mutations in KRAS, known oncogenic driver tumor growth, cancer cell survival and metastasis thus making for an attractive target. However, targeting the most common KRAS pancreatic (KRAS G12D G12V ) remains pharmacological challenge. Exosomes are extracellular nano-vesicles that efficiently internalized by target...
Abstract Real-world evidence regarding the value of integrating genomic profiling (GP) in managing cancer unknown primary (CUP) is limited. We assessed this clinical utility using a prospective trial 158 patients with CUP (October 2016-September 2019) who underwent GP next-generation sequencing designed to identify alterations (GAs). Only 61 (38.6%) had sufficient tissue for successful profiling. GAs were seen 55 (90.2%) which US Food and Drug Administration–approved genomically matched...
743 Background: Despite recent advances, there are limited effective therapeutic options for pancreatic ductal adenocarcinoma (PDAC). Conventional chemotherapy can be difficult to tolerate and offers modest survival benefits. Lixumistat is a small molecule biguanide that inhibits the first rate-limiting step of oxidative phosphorylation pathway, which critical PDAC tumor cells. A first-in-human dose escalation trial in solid tumors demonstrated favorable safety profile recommended phase 2...
Abstract Oncogenic KRAS drives initiation and maintenance of pancreatic ductal adenocarcinoma (PDAC). Here, we show that engineered exosomes with Kras G12D specific siRNA (iExoKras ) reveal impressive biodistribution in pancreas negligible toxicity preclinical studies mice Rhesus macaques. Clinical testing iExoKras the iEXPLORE Pancreatic Cancer) Phase I study employed a classical 3+3 dose escalation design (Phase Ia), followed by an accelerated titration Ib) ( NCT03608631 ). Patients...
Abstract Despite its pivotal role in pancreatic ductal adenocarcinoma (PDAC), oncogenic Kras has eluded pharmacological targeting design, albeit with more recent and promising development. Given the preponderance of KrasG12D mutation PDAC, we engineered exosomes from allogenic bone marrow derived mesenchymal cells incorporation KrasG12DsiRNA payload. We report on a comprehensive preclinical toxicology biodistribution analysis clinical grade iExosomes mice rhesus macaques, which informed...
To determine the antitumor efficacy and tolerability of combination temozolomide (TMZ) veliparib (ABT-888) in patients with advanced, sorafenib-refractory hepatocellular carcinoma (HCC). This single-arm phase II trial enrolled pathologically confirmed, HCC. All received 40 mg ABT-888 PO daily on days 1–7 150 mg/m2 TMZ 1–5 a 28-day cycle. The primary endpoint was objective response rate (ORR) at 2 months. Secondary endpoints included overall survival (OS), progression-free (PFS), toxicity...
Objective: We aimed to determine if advances in neoadjuvant therapy affected recurrence patterns and survival outcomes after pancreatectomy for pancreatic ductal adenocarcinoma (PDAC). Background: Data are limited on how modern multimodality affects PDAC post-recurrence survival. Methods: Patients who received followed by curative-intent during 1998-2018 were identified. Treatments, sites timing, compared between patients completed 1998-2004, 2005-2011, 2012-2018. Results: The study included...
4138 Background: Due to its low tumor immunogenicity and immunosuppressive microenvironment, pancreatic ductal adenocarcinoma (PDAC) remains an immunotherapeutic challenge. LOAd703, oncolytic adenovirus with transgenes encoding TMZ-CD40L 4-1BBL, has been shown lyse cells selectively, induce anti-tumor cytotoxic T-cell responses, reduce myeloid-derived suppressor cell (MDSC) infiltration, regression in preclinical studies. Methods: In this phase I/II trial, patients unresectable or metastatic...
Resection techniques for esophageal carcinoma continue to evolve, from endoscopic mucosal resection or submucosal dissection early stage disease standard and robot-assisted minimally invasive esophagectomy as part of multimodal therapy locally advanced disease. Though currently limited assessing conduit perfusion sentinel lymph nodes, embedded technology in the robotic surgical platform will likely play an expanded role during future. The use targeted therapies, checkpoint inhibitors,...
Abstract Introduction The safety, target engagement, and benefit of iExosomes, short interfering RNA targeting KrasG12D encapsulated within exosomes intravenously administered, were explored in patients with advanced pancreatic cancer harboring a mutation. Methods initial phase I protocol was conventional 3+3 design three escalating dose levels (levels 1-3) defined as exosomal protein containing equal amounts siRNA. Lack toxicity at the highest level subsequently guided amendment to an...