4 results on '"Oberstein, Paul E."'
Search Results
2. Impact of comprehensive family history and genetic analysis in the multidisciplinary pancreatic tumor clinic setting.
- Author
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Everett, Jessica N., Dettwyler, Shenin A., Jing, Xiaohong, Stender, Cody, Schmitter, Madeleine, Baptiste, Ariele, Chun, Jennifer, Kawaler, Emily A., Khanna, Lauren G., Gross, Seth A., Gonda, Tamas A., Beri, Nina, Oberstein, Paul E., and Simeone, Diane M.
- Subjects
PANCREATIC tumors ,GENETIC testing ,INTERDISCIPLINARY research ,FAMILY history (Medicine) ,CONTINUUM of care ,PANCREATIC duct ,HEREDITARY cancer syndromes - Abstract
Background: Genetic testing is recommended for all pancreatic ductal adenocarcinoma (PDAC) patients. Prior research demonstrates that multidisciplinary pancreatic cancer clinics (MDPCs) improve treatment‐ and survival‐related outcomes for PDAC patients. However, limited information exists regarding the utility of integrated genetics in the MDPC setting. We hypothesized that incorporating genetics in an MDPC serving both PDAC patients and high‐risk individuals (HRI) could: (1) improve compliance with guideline‐based genetic testing for PDAC patients, and (2) optimize HRI identification and PDAC surveillance participation to improve early detection and survival. Methods: Demographics, genetic testing results, and pedigrees were reviewed for PDAC patients and HRI at one institution over 45 months. Genetic testing analyzed 16 PDAC‐associated genes at minimum. Results: Overall, 969 MDPC subjects were evaluated during the study period; another 56 PDAC patients were seen outside the MDPC. Among 425 MDPC PDAC patients, 333 (78.4%) completed genetic testing; 29 (8.7%) carried a PDAC‐related pathogenic germline variant (PGV). Additionally, 32 (9.6%) met familial pancreatic cancer (FPC) criteria. These PDAC patients had 191 relatives eligible for surveillance or genetic testing. Only 2/56 (3.6%) non‐MDPC PDAC patients completed genetic testing (p < 0.01). Among 544 HRI, 253 (46.5%) had a known PGV or a designation of FPC, and were eligible for surveillance at baseline; of the remainder, 15/291 (5.2%) were eligible following genetic testing and PGV identification. Conclusion: Integrating genetics into the multidisciplinary setting significantly improved genetic testing compliance by reducing logistical barriers for PDAC patients, and clarified cancer risks for their relatives while conserving clinical resources. Overall, we identified 206 individuals newly eligible for surveillance or genetic testing (191 relatives of MDPC PDAC patients, and 15 HRI from this cohort), enabling continuity of care for PDAC patients and at‐risk relatives in one clinic. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
3. Tumor infiltrating T cell states and checkpoint inhibitor expression in hepatic and pancreatic malignancies.
- Author
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Shanshan Wan, Ende Zhao, Weissinger, Daniel, Krantz, Benjamin A., Werba, Gregor, Freeman, Daniel, Khanna, Lauren G., Siolas, Despina, Oberstein, Paul E., Chattopadhyay, Pratip K., Simeone, Diane M., and Welling, Theodore H.
- Subjects
T cells ,IPILIMUMAB ,PANCREATIC tumors ,PANCREATIC duct ,CANCER chemotherapy ,IMMUNOLOGIC memory ,IMMUNE checkpoint proteins - Abstract
Hepato-pancreatico-biliary (HPB) malignancies are difficult-to-treat and continue to to have a high mortality and significant therapeutic resistance to standard therapies. Immune oncology (IO) therapies have demonstrated efficacy in several solid malignancies when combined with chemotherapy, whereas response rates in pancreatic ductal adenocarcinoma (PDA) are poor. While promising in hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), there remains an unmet need to fully leverage IO therapies to treat HPB tumors. We therefore defined T cell subsets in the tumor microenvironment of HPB patients utilizing a novel, multiparameter flow cytometry and bioinformatics analysis. Our findings quantify the T cell phenotypic states in relation to checkpoint receptor expression. We demonstrate the presence of CD103
+ tissue resident memory T cells (TRM), CCR7+ central memory T cells, and CD57+ terminally differentiated effector cells across all HPB cancers, while the anti-tumor function was dampened by expression of multiple co-inhibitory checkpoint receptors. Terminally exhausted T cells lacking co-stimulatory receptors were more prevalent in PDA, whereas partially exhausted T cells expressing both co-inhibitory and co-stimulatory receptors were most prevalent in HCC, especially in early stage. HCC patients had significantly higher TRM with a phenotype that could confer restored activation in response to immune checkpoint therapies. Further, we found a lack of robust alteration in T cell activation state or checkpoint expression in response to chemotherapy in PDA patients. These results support that HCC patients might benefit most from combined checkpoint therapies, whereas efforts other than cytotoxic chemotherapy will likely be necessary to increase overall T cell activation in CCA and PDA for future clinical development. [ABSTRACT FROM AUTHOR]- Published
- 2023
- Full Text
- View/download PDF
4. Safety and Efficacy of Everolimus in Adult Patients with Neuroendocrine Tumors.
- Author
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Oberstein, Paul E. and Saif, M. Wasif
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ANTINEOPLASTIC agents , *CLINICAL trials , *NEUROENDOCRINE tumors , *HEALTH outcome assessment , *PANCREATIC tumors , *PATIENT monitoring , *SAFETY , *RAPAMYCIN , *TREATMENT effectiveness - Abstract
Neuroendocrine tumors (NETs) consist of a diverse family of tumors which are derived from the neuroendocrine system. Most NETs are well or moderately differentiated tumors with a relatively indolent growth pattern. However, these tumors can cause significant clinical disease due to release of functional products that mediate the carcinoid syndrome and other diverse sequela. They also can grow progressively and cause symptoms from local invasion or distant metastasis. NETs are optimally treated with surgery and somatosatin analogs (SSA's) to control symptoms but are relatively insensitive to systemic chemotherapy. As a result, patients with advanced unresectable NETs have a poor prognosis. In 2011, two targeted therapies, sunitinib and everolimus were approved in the subset of progressive pancreatic NETs (pNETs). Everolimus is an oral inhibitor of the growth stimulatory mTOR pathway. In Phase 2 trials in NETs and pNETs, everolimus was well tolerated and associated with some response and widespread disease stabilization. In follow-up, randomized Phase 3 trials, everolimus was compared to placebo. In the RADIANT-2 trial, everolimus and a somatostatin analog were used in patients with functional NETs and treatment was associated with an improvement in progression-free survival (PFS). In the RADIANT-3 trial, patients with pNET were randomized to receive everolimus or placebo along with best supportive care. Everolimus was again associated with improvement in PFS compared to placebo and it has been approved by the FDA for patients with progressive pNET. Everolimus is associated with frequent low grade toxicity but is also notable for increased rates of infection as well as non-infectious pneumonitis. mTOR inhibition with everolimus represents a significant advance in the treatment of advanced neuroendocrine tumors. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
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