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2. Corrigendum: Tumor infiltrating T cell states and checkpoint inhibitor expression in hepatic and pancreatic malignancies

Author

Wan, Shanshan, primary, Zhao, Ende, additional, Freeman, Daniel, additional, Weissinger, Daniel, additional, Krantz, Benjamin A., additional, Werba, Gregor, additional, Khanna, Lauren G., additional, Siolas, Despina, additional, Oberstein, Paul E., additional, Chattopadhyay, Pratip K., additional, Simeone, Diane M., additional, and Welling, Theodore H., additional

Published
2023
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3. Tumor infiltrating T cell states and checkpoint inhibitor expression in hepatic and pancreatic malignancies

Author

Wan, Shanshan, primary, Zhao, Ende, additional, Weissinger, Daniel, additional, Krantz, Benjamin A., additional, Werba, Gregor, additional, Freeman, Daniel, additional, Khanna, Lauren G., additional, Siolas, Despina, additional, Oberstein, Paul E., additional, Chattopadhyay, Pratip K., additional, Simeone, Diane M., additional, and Welling, Theodore H., additional

Published
2023
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5. Abstract PR010: Single-cell sequencing elucidates the effects of chemotherapy on cancer cell heterogeneity and the tumor microenvironment of human pancreatic adenocarcinoma

Author

Weissinger, Daniel, primary, Kawaler, Emily A., additional, Werba, Gregor, additional, Zhao, Ende, additional, Kalfakakou, Despoina, additional, Dhara, Surajit, additional, Oh, Grace, additional, Jing, Xiaohong, additional, Beri, Nina, additional, Khanna, Lauren, additional, Gonda, Tamas, additional, Oberstein, Paul E., additional, Hajdu, Cristina, additional, Loomis, Cynthia, additional, Heguy, Adriana, additional, Sherman, Mara H., additional, Lund, Amanda W., additional, Welling, Theodore H., additional, Dolgalev, Igor, additional, Tsirigos, Aristotelis, additional, and Simeone, Diane M., additional

Published
2022
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6. Abstract PR005: Primary results of PanCAN-SR1, a phase 1b study evaluating Gemcitabine, nab-Paclitaxel, Canakinumab, and Spartalizumab to target IL-1β and PD-1 in metastatic pancreatic cancer with correlative tissue and blood biomarker analysis

Author

Oberstein, Paul E., primary, Rahma, Osama, additional, Beri, Nina, additional, Stoll-D'Astice, Amy, additional, Kawaler, Emily A., additional, Dolgalev, Igor, additional, Werba, Gregor, additional, Cardo-Ruffino, Victoire, additional, Böllenrücher, Naïma, additional, Costa, Andressa Dias, additional, Nazeer, Saloney, additional, Squires, Matthew, additional, Nowak, Jonathan, additional, Bar-Sagi, Dafna, additional, Wolpin, Brian, additional, Simeone, Diane M, additional, and Dougan, Stephanie K, additional

Published
2022
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7. Impact of comprehensive family history and genetic analysis in the multidisciplinary pancreatic tumor clinic setting

Author

Everett, Jessica N., primary, Dettwyler, Shenin A., additional, Jing, Xiaohong, additional, Stender, Cody, additional, Schmitter, Madeleine, additional, Baptiste, Ariele, additional, Chun, Jennifer, additional, Kawaler, Emily A., additional, Khanna, Lauren G., additional, Gross, Seth A., additional, Gonda, Tamas A., additional, Beri, Nina, additional, Oberstein, Paul E., additional, and Simeone, Diane M., additional

Published
2022
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9. Multiplexed single-cell analysis reveals prognostic and nonprognostic T cell types in human colorectal cancer

Author

Masuda, Kazuya, primary, Kornberg, Adam, additional, Miller, Jonathan, additional, Lin, Sijie, additional, Suek, Nathan, additional, Botella, Theo, additional, Secener, Kerim A., additional, Bacarella, Alyssa M., additional, Cheng, Liang, additional, Ingham, Matthew, additional, Rosario, Vilma, additional, Al-Mazrou, Ahmed M., additional, Lee-Kong, Steven A., additional, Kiran, Ravi P., additional, Stoeckius, Marlon, additional, Smibert, Peter, additional, Del Portillo, Armando, additional, Oberstein, Paul E., additional, Sims, Peter A., additional, Yan, Kelley S., additional, and Han, Arnold, additional

Published
2022
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10. Impact of comprehensive family history and genetic analysis in the multidisciplinary pancreatic tumor clinic setting.

Author

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
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11. Tumor infiltrating T cell states and checkpoint inhibitor expression in hepatic and pancreatic malignancies.

Author

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
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13. Abstract LB-003: OncoMatch: Unbiased, quantitative assessment of cancer model fidelity for drug sensitivity and mechanism of action elucidation

Author

Alvarez, Mariano J., primary, Pengrong, Yan, additional, Alpaugh, Mary L., additional, Bowden, Michaela, additional, Sicinska, Ewa T., additional, Zhou, Chensheng W., additional, Karan, Charles, additional, Realubit, Ronald B., additional, Mundi, Prabhjot S., additional, Grunn, Adina, additional, Dirk, Jager, additional, Chabot, John A., additional, Fojo, Antonio T., additional, Oberstein, Paul E., additional, Hibshoosh, Hanina, additional, Milsom, Jeffrey W., additional, Kulke, Matthew H., additional, Loda, Massimo, additional, Chiosis, Gabriela, additional, Reidy-Lagunes, Diane L., additional, and Califano, Andrea, additional

Published
2020
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15. Harmonic Motion Imaging of Pancreatic Tumor Stiffness Indicates Disease State and Treatment Response

Author

Payen, Thomas, primary, Oberstein, Paul E., additional, Saharkhiz, Niloufar, additional, Palermo, Carmine F., additional, Sastra, Stephen A., additional, Han, Yang, additional, Nabavizadeh, Alireza, additional, Sagalovskiy, Irina R., additional, Orelli, Barbara, additional, Rosario, Vilma, additional, Desrouilleres, Deborah, additional, Remotti, Helen, additional, Kluger, Michael D., additional, Schrope, Beth A., additional, Chabot, John A., additional, Iuga, Alina C., additional, Konofagou, Elisa E., additional, and Olive, Kenneth P., additional

Published
2020
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16. Noninvasive Young's modulus visualization of fibrosis progression and delineation of pancreatic ductal adenocarcinoma (PDAC) tumors using Harmonic Motion Elastography (HME) in vivo

Author

Nabavizadeh, Alireza, primary, Payen, Thomas, additional, Iuga, Alina C., additional, Sagalovskiy, Irina R., additional, Desrouilleres, Deborah, additional, Saharkhiz, Niloufar, additional, Palermo, Carmine F., additional, Sastra, Stephen A., additional, Oberstein, Paul E., additional, Rosario, Vilma, additional, Kluger, Michael D., additional, Schrope, Beth A., additional, Chabot, John A., additional, Olive, Kenneth P., additional, and Konofagou, Elisa E., additional

Published
2020
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17. Olaparib in combination with irinotecan, cisplatin, and mitomycin C in patients with advanced pancreatic cancer

Author

Yarchoan, Mark, primary, Myzak, Melinda C., additional, Johnson, Burles A., additional, De Jesus-Acosta, Ana, additional, Le, Dung T., additional, Jaffee, Elizabeth M., additional, Azad, Nilofer S., additional, Donehower, Ross C., additional, Zheng, Lei, additional, Oberstein, Paul E., additional, Fine, Robert L., additional, Laheru, Daniel A., additional, and Goggins, Michael, additional

Published
2017
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19. Stromal Elements Act to Restrain, Rather Than Support, Pancreatic Ductal Adenocarcinoma

Author

Rhim, Andrew D., primary, Oberstein, Paul E., additional, Thomas, Dafydd H., additional, Mirek, Emily T., additional, Palermo, Carmine F., additional, Sastra, Stephen A., additional, Dekleva, Erin N., additional, Saunders, Tyler, additional, Becerra, Claudia P., additional, Tattersall, Ian W., additional, Westphalen, C. Benedikt, additional, Kitajewski, Jan, additional, Fernandez-Barrena, Maite G., additional, Fernandez-Zapico, Martin E., additional, Iacobuzio-Donahue, Christine, additional, Olive, Kenneth P., additional, and Stanger, Ben Z., additional

Published
2014
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25. First-line treatment for advanced pancreatic cancer. Highlights from the "2011 ASCO Gastrointestinal Cancers Symposium". San Francisco, CA, USA. January 20-22, 2011.

Author

Oberstein PE and Saif MW

Subjects
Benzenesulfonates administration & dosage, Capecitabine, Clinical Trials as Topic, Deoxycytidine administration & dosage, Deoxycytidine analogs & derivatives, Erlotinib Hydrochloride, Fluorouracil administration & dosage, Fluorouracil analogs & derivatives, Humans, Lapatinib, Medicine, Chinese Traditional, Niacinamide analogs & derivatives, Pancreatic Neoplasms pathology, Pancreatic Neoplasms therapy, Phenylurea Compounds, Pyridines administration & dosage, Quinazolines administration & dosage, Sorafenib, Treatment Outcome, Gemcitabine, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Pancreatic Neoplasms drug therapy
Abstract

Pancreatic adenocarcinoma remains a treatment-refractory cancer. Although pancreatic adenocarcinoma is only the 10th most common cause of new cancer in the United States, it is the fourth most common cause of cancer-related death. Most cases are not suitable for resection and a majority is metastatic at presentation. Gemcitabine, with or without erlotinib, has been the standard chemotherapy in this setting but the benefit is only modest. Because gemcitabine has been considered a standard treatment for advanced pancreatic cancer for the past decade, several randomized trials have tested the combination of gemcitabine plus a second agent, including platinum based agents, topoisomerase inhibitors, taxanes, bevacizumab and cetuximab, as biologically "targeted" agents. At large this approach has not been successful and novel strategies are clearly needed. In this article, the authors summarizes the data from the 2011 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, including: Abstract #175 (review of survival data in a large cohort); Abstract #286 (rapid change in prescriber patterns after the suggestion of benefit of a new regimen, FOLFIRINOX); Abstracts #238, #277, #304, and #315 (phase II trials looking at combinations that utilized EGFR blockade); Abstracts #221, #266, and #284 (phase I/II trials including VEGF blockade, anticoagulation, and traditional Chinese medicines).

Published
2011

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