Rachna Shroff

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Journals/Publications

• Ahmad, S. A., Bogdanov, V., Kharofa, J., Moreland, K., Olowokure, O. O., Patel, S. H., Patra, K., Riall, T. S., Rojan, A., Shroff, R. T., Sohal, D., Sussman, J. J., Wilson, G. C., & Zavros, Y. (2023).

  An adaptive approach to neoadjuvant therapy to maximize resection rates for pancreatic adenocarcinoma: A phase II trial.

  . Journal of Clinical Oncology, 41(4_suppl), TPS771-TPS771. doi:10.1200/jco.2023.41.4_suppl.tps771
• Alexander, B. M., Baldo, L., Goodman, K. A., Highsmith, Q. B., Kunz, P. L., Mehnert, J. M., Mills, J. M., Moran, S. E., Shroff, R. T., Vose, J. M., & Yessaian, J. L. (2023).

  Where Are All the Women in Industry Advisory Boards?

  . Journal of Clinical Oncology, 41(9), 1659-1663. doi:10.1200/jco.21.02219
• Arrivé, L., Assis, D. N., Bergquist, A., Bowlus, C. L., Deneau, M., Forman, L., Ilyas, S., Lundsford, K. E., Martinez, M., Sapisochin, G., Shroff, R., & Tabibian, J. H. (2023).

  Reply: insurance should cover vancomycin for primary sclerosing cholangitis

  . Hepatology. doi:10.1097/hep.0000000000000305
• Bowlus, C. L., Arrivé, L., Bergquist, A., Deneau, M., Forman, L., Ilyas, S. I., Lunsford, K. E., Martinez, M., Sapisochin, G., Shroff, R., Tabibian, J. H., & Assis, D. N. (2023). Reply: Insurance should cover vancomycin for primary sclerosing cholangitis. Hepatology (Baltimore, Md.), 77(6), E176-E177.
• Florou, V., Elliott, A., Bailey, M. H., Stone, D., Affolter, K., Soares, H. P., Nevala-Plagemann, C., Scaife, C., Walker, P., Korn, W. M., Lou, E., Shroff, R. T., Hosein, P. J., & Garrido-Laguna, I. (2023). Comparative Genomic Analysis of Pancreatic Acinar Cell Carcinoma (PACC) and Pancreatic Ductal Adenocarcinoma (PDAC) Unveils New Actionable Genomic Aberrations in PACC. Clinical cancer research : an official journal of the American Association for Cancer Research, 29(17), 3408-3417.
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  Pure pancreatic acinar cell carcinomas (PACC) are rare malignancies with no established treatment. PACC demonstrates significant genetic intertumoral heterogeneity with multiple pathways involved, suggesting using targeted cancer therapeutics to treat this disease. We aggregated one of the largest datasets of pure PACC to examine the genomic variability and explore patient-specific therapeutic targets.
• Forman, L. M., Sapisochin, G., Assis, D. N., Arrivé, L., Bergquist, A., Bowlus, C. L., Deneau, M., Ilyas, S. I., Lunsford, K. E., Martinez, M., Shroff, R., & Tabibian, J. H. (2023). Reply: Living donor liver transplantation for people with PSC. Hepatology (Baltimore, Md.), 77(5), E97-E98.
• Hatia, R. I., Eluri, M., Hawk, E. T., Shalaby, A., Karatas, E., Shalaby, A., Abdelhakeem, A., Abdel-Wahab, R., Chang, P., Rashid, A., Jalal, P. K., Amos, C. I., Han, Y., Armaghany, T., Shroff, R. T., Li, D., Javle, M., & Hassan, M. M. (2023). Independent of Primary Sclerosing Cholangitis and Cirrhosis, Early Adulthood Obesity Is Associated with Cholangiocarcinoma. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 32(10), 1338-1347.
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  It is estimated that 6% to 20% of all cholangiocarcinoma (CCA) diagnoses are explained by primary sclerosing cholangitis (PSC), but the underlying risk factors in the absence of PSC are unclear. We examined associations of different risk factors with intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) in the United States.
• Ogobuiro, I., Baca, Y., Ribeiro, J. R., Walker, P., Wilson, G. C., Gulhati, P., Marshall, J. L., Shroff, R. T., Spetzler, D., Oberley, M. J., Abbott, D. E., Kim, H. J., Kooby, D. A., Maithel, S. K., Ahmad, S. A., Merchant, N. B., Xiu, J., Hosein, P. J., & Datta, J. (2023). Multi-omic characterization reveals a distinct molecular landscape in young-onset pancreatic cancer. medRxiv : the preprint server for health sciences.
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  Using a real-world database with matched genomic-transcriptomic molecular data, we sought to characterize the distinct molecular correlates underlying clinical differences between young-onset pancreatic cancer (YOPC;
• Ogobuiro, I., Baca, Y., Ribeiro, J. R., Walker, P., Wilson, G. C., Gulhati, P., Marshall, J. L., Shroff, R. T., Spetzler, D., Oberley, M. J., Abbott, D. E., Kim, H. J., Kooby, D. A., Maithel, S. K., Ahmad, S. A., Merchant, N. B., Xiu, J., Hosein, P. J., & Datta, J. (2023). Multiomic Characterization Reveals a Distinct Molecular Landscape in Young-Onset Pancreatic Cancer. JCO precision oncology, 7, e2300152.
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  Using a real-world database with matched genomic-transcriptomic molecular data, we sought to characterize the distinct molecular correlates underlying clinical differences between patients with young-onset pancreatic cancer (YOPC; younger than 50 years) and patients with average-onset pancreatic cancer (AOPC; 70 years and older).
• Pappas, L., Baiev, I., Reyes, S., Bocobo, A. G., Jain, A., Spencer, K., Le, T. M., Rahma, O. E., Maurer, J., Stanton, J., Zhang, K., De Armas, A. D., Deleon, T. T., Roth, M., Peters, M. L., Zhu, A. X., Boyhen, K., VanCott, C., Patel, T., , Roberts, L. R., et al. (2023). The Cholangiocarcinoma in the Young (CITY) Study: Tumor Biology, Treatment Patterns, and Survival Outcomes in Adolescent Young Adults With Cholangiocarcinoma. JCO precision oncology, 7, e2200594.
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  Increased awareness of the distinct tumor biology for adolescents and young adults (AYAs) with cancer has led to improvement in outcomes for this population. However, in cholangiocarcinoma (CCA), a paucity of data exist on the AYA population. To our knowledge, we present the largest study to date on AYA disease biology, treatment patterns, and survival outcomes in CCA.
• Snyder, R. A., Burtness, B., Cho, M., Del Rivero, J., Doroshow, D. B., Hitchcock, K. E., Kalyan, A., Kim, C. A., Lukovic, J., Parikh, A. R., Sanford, N. N., Singh, B., Shen, C., Shroff, R. T., Vijayvergia, N., Goodman, K. A., & Kunz, P. L. (2023). The room where it happens: addressing diversity, equity, and inclusion in National Clinical Trials Network clinical trial leadership. Journal of the National Cancer Institute, 115(10), 1132-1138.
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  Many multicenter randomized clinical trials in oncology are conducted through the National Clinical Trials Network (NCTN), an organization consisting of 5 cooperative groups. These groups are made up of multidisciplinary investigators who work collaboratively to conduct trials that test novel therapies and establish best practice for cancer care. Unfortunately, disparities in clinical trial leadership are evident. To examine the current state of diversity, equity, and inclusion across the NCTN, an independent NCTN Task Force for Diversity in Gastrointestinal Oncology was established in 2021, the efforts of which serve as the platform for this commentary. The task force sought to assess existing data on demographics and policies across NCTN groups. Differences in infrastructure and policies were identified across groups as well as a general lack of data regarding the composition of group membership and leadership. In the context of growing momentum around diversity, equity, and inclusion in cancer research, the National Cancer Institute established the Equity and Inclusion Program, which is working to establish benchmark data regarding diversity of representation within the NCTN groups. Pending these data, additional efforts are recommended to address diversity within the NCTN, including standardizing membership, leadership, and publication processes; ensuring diversity of representation across scientific and steering committees; and providing mentorship and training opportunities for women and individuals from underrepresented groups. Intentional and focused efforts are necessary to ensure diversity in clinical trial leadership and to encourage design of trials that are inclusive and representative of the broad population of patients with cancer in the United States.
• Spencer, K., Pappas, L., Baiev, I., Maurer, J., Bocobo, A. G., Zhang, K., Jain, A., De Armas, A. D., Reyes, S., Le, T. M., Rahma, O. E., Stanton, J., DeLeon, T. T., Roth, M., Peters, M. L., Zhu, A. X., Lennerz, J. K., Iafrate, A. J., Boyhen, K., , VanCott, C., et al. (2023). Molecular profiling and treatment pattern differences between intrahepatic and extrahepatic cholangiocarcinoma. Journal of the National Cancer Institute, 115(7), 870-880.
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  Treatment patterns for intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) differ, but limited studies exist comparing them. This study examines differences in molecular profiling rates and treatment patterns in these populations, focusing on use of adjuvant, liver-directed, targeted, and investigational therapies.
• Young, S., Hannallah, J., Goldberg, D., Khreiss, M., Shroff, R., Arshad, J., Scott, A., & Woodhead, G. (2023). Liver-Directed Therapy Combined with Systemic Therapy: Current Status and Future Directions. Seminars in interventional radiology, 40(6), 515-523.
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  In the past several decades, major advances in both systemic and locoregional therapies have been made for many cancer patients. This has led to modern cancer treatment algorithms frequently calling for active interventions by multiple subspecialists at the same time. One of the areas where this can be clearly seen is the concomitant use of locoregional and systemic therapies in patients with primary or secondary cancers of the liver. These combined algorithms have gained favor over the last decade and are largely focused on the allure of the combined ability to control systemic disease while at the same time addressing refractory/resistant clonal populations. While the general concept has gained favor and is likely to only increase in popularity with the continued establishment of viable immunotherapy treatments, for many patients questions remain. Lingering concerns over the increase in toxicity when combining treatment methods, patient selection, and sequencing remain for multiple cancer patient populations. While further work remains, some of these questions have been addressed in the literature. This article reviews the available data on three commonly treated primary and secondary cancers of the liver, namely, hepatocellular carcinoma, cholangiocarcinoma, and metastatic colorectal cancer. Furthermore, strengths and weaknesses are reviewed and future directions are discussed.
• Abbott, D., Ahmad, S., Baca, Y., Datta, J., Gulhati, P., Hosein, P. J., Kim, H. J., Kooby, D. A., Korn, W. M., Maithel, S. K., Marshall, J., Merchant, N. B., Oberley, M. J., Ogobuiro, I., Parikh, A. A., Shroff, R. T., Snyder, R. A., Spetzler, D., Walker, P., & Wilson, G. (2022).

  Multiomic characterization to reveal a distinct molecular landscape in young-onset pancreatic cancer.

  . Journal of Clinical Oncology, 40(4_suppl), 594-594. doi:10.1200/jco.2022.40.4_suppl.594
• Armstrong, S. A., Banovac, F., Brown, D., Ganguli, S., Goff, L. W., He, A. R., Iyer, R. V., Jiang, Y., Johnson, M., Kim, R. D., Kim, K., Kulke, M. H., Parikh, N., Petroziello, M., Shroff, R. T., Toskich, B., & Woodhead, G. (2022).

  An open-label, multicenter, randomized phase II study of atezolizumab and bevacizumab with Y90 TARE in patients with unresectable hepatocellular carcinoma (HCC).

  . Journal of Clinical Oncology, 40(16_suppl), TPS4177-TPS4177. doi:10.1200/jco.2022.40.16_suppl.tps4177
• Bhosale, P., Danner De Armas, A., Javle, M., Lee, S., Makawita, S., Pant, S., Raghav, K., Reddy, K., Shalaby, A., Shroff, R. T., Wolff, R. A., & Xiao, L. (2022).

  Phase II Study of Ramucirumab in Advanced Biliary Tract Cancer Previously Treated By Gemcitabine-Based Chemotherapy

  . Clinical Cancer Research, 28(11), 2229-2236. doi:10.1158/1078-0432.ccr-21-3548
• Bowlus, C. L., Arrivé, L., Bergquist, A., Deneau, M., Forman, L., Ilyas, S. I., Lunsford, K. E., Martinez, M., Sapisochin, G., Shroff, R., Tabibian, J. H., & Assis, D. N. (2022). AASLD practice guidance on primary sclerosing cholangitis and cholangiocarcinoma. Hepatology (Baltimore, Md.).
• Call, S. G., Chagani, S., Dustin, D. J., Gouda, M. A., Holley, V. R., Huang, H. J., Janku, F., Javle, M., Kwong, L. N., Lanman, R. B., Lapin, M., Madwani, K., Meric-Bernstam, F., Pant, S., Raina, A., Raymond, V. M., & Shroff, R. T. (2022).

  Monitoring of Dynamic Changes and Clonal Evolution in Circulating Tumor DNA From Patients With IDH-Mutated Cholangiocarcinoma Treated With Isocitrate Dehydrogenase Inhibitors

  . JCO Precision Oncology. doi:10.1200/po.21.00197
• Carapeto, F., Bozorgui, B., Shroff, R. T., Chagani, S., Solis Soto, L., Foo, W. C., Wistuba, I., Meric-Bernstam, F., Shalaby, A., Javle, M., Korkut, A., & Kwong, L. N. (2022). The immunogenomic landscape of resected intrahepatic cholangiocarcinoma. Hepatology (Baltimore, Md.), 75(2), 297-308.
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  Cholangiocarcinoma (CCA) is a deadly and highly therapy-refractory cancer of the bile ducts, with early results from immune checkpoint blockade trials showing limited responses. Whereas recent molecular assessments have made bulk characterizations of immune profiles and their genomic correlates, spatial assessments may reveal actionable insights.
• Cazeau, N., Palazzo, M., Savani, M., & Shroff, R. T. (2022). COVID-19 Vaccines and Immunosuppressed Patients With Cancer: Critical Considerations. Clinical journal of oncology nursing, 26(4), 367-373.
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   Patients with cancer are highly vulnerable to COVID-19 because of immunosuppression from diseases and treatments. Emerging data characterize the impact of COVID-19 vaccines related to cancer malignancies and treatments.
• Doki, Y., Ajani, J. A., Kato, K., Xu, J., Wyrwicz, L., Motoyama, S., Ogata, T., Kawakami, H., Hsu, C. H., Adenis, A., El Hajbi, F., Di Bartolomeo, M., Braghiroli, M. I., Holtved, E., Ostoich, S. A., Kim, H. R., Ueno, M., Mansoor, W., Yang, W. C., , Liu, T., et al. (2022). Nivolumab Combination Therapy in Advanced Esophageal Squamous-Cell Carcinoma. The New England journal of medicine, 386(5), 449-462.
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  First-line chemotherapy for advanced esophageal squamous-cell carcinoma results in poor outcomes. The monoclonal antibody nivolumab has shown an overall survival benefit over chemotherapy in previously treated patients with advanced esophageal squamous-cell carcinoma.
• Halder, R., Amaraneni, A., & Shroff, R. T. (2022). Cholangiocarcinoma: a review of the literature and future directions in therapy. Hepatobiliary surgery and nutrition, 11(4), 555-566.
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  Cholangiocarcinomas (CCA) are a group of rare cancers with an incidence of about 1.26 per 100,000 people. The disease reflects one of three different subtypes: intrahepatic, perihilar or hilar and distal cholangiocarcinoma. The preferred modality of definitive therapy is surgical resection with or without adjuvant therapy, however the majority of patients with this disease do not present at an early stage. Some efforts to improve survival rates have come in the form of offering neoadjuvant therapy prior to surgical resection or liver transplantation. Some new protocols are in the process of development for neoadjuvant therapy. Despite advancements in locally advanced or borderline resectable lesions, most patient present at an advanced stage. The mainstay of treatment for advanced stage disease is chemotherapy regardless of location. The mainstay of treatment in fit patients is the combination of gemcitabine and cisplatin. The addition of nab-paclitaxel to this backbone is currently being evaluated in phase III trial. In addition, the role of targeted therapy is currently being studied extensively through multiple different mutational pathways including isocitrate dehydrogenase-1 (IDH1), fibroblast growth factor receptor (FGFR), epidermal growth factor receptor (EGFR) and ERBB2 (HER2/neu). CCA remains a significant challenge in medicine, however recent studies have shown that there is significant interest in advancing therapy in the form of neoadjuvant, adjuvant and palliative intent treatment.
• Koshiol, J., Yu, B., Kabadi, S. M., Baria, K., & Shroff, R. T. (2022). Epidemiologic patterns of biliary tract cancer in the United States: 2001-2015. BMC cancer, 22(1), 1178.
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  Biliary tract cancer (BTC) includes intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma, gallbladder cancer, and ampulla of Vater cancer (AVC). Although BTC is rare in the US, incidence is increasing and elevated in certain populations. This study examined BTC epidemiology in the US by age, sex, race/ethnicity, geographic region, and anatomic site.
• Lapin, M., Huang, H. J., Chagani, S., Javle, M., Shroff, R. T., Pant, S., Gouda, M. A., Raina, A., Madwani, K., Holley, V. R., Call, S. G., Dustin, D. J., Lanman, R. B., Meric-Bernstam, F., Raymond, V. M., Kwong, L. N., & Janku, F. (2022). Monitoring of Dynamic Changes and Clonal Evolution in Circulating Tumor DNA From Patients With -Mutated Cholangiocarcinoma Treated With Isocitrate Dehydrogenase Inhibitors. JCO precision oncology, 6, e2100197.
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  mutations occur in about 30% of patients with cholangiocarcinoma. Analysis of mutations in circulating tumor DNA (ctDNA) can be performed by droplet digital polymerase chain reaction (ddPCR). The analysis of ctDNA is a feasible approach to detect mutations.
• Lee, S., Shroff, R. T., Makawita, S., Xiao, L., Danner De Armas, A., Bhosale, P., Reddy, K., Shalaby, A., Raghav, K., Pant, S., Wolff, R. A., & Javle, M. (2022). Phase II Study of Ramucirumab in Advanced Biliary Tract Cancer Previously Treated By Gemcitabine-Based Chemotherapy. Clinical cancer research : an official journal of the American Association for Cancer Research, 28(11), 2229-2236.
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  VEGF receptor-2 (VEGFR-2)-mediated angiogenesis contributes to pathogenesis of biliary tract cancers (BTC). We investigated ramucirumab, a mAb targeting VEGFR-2 for treatment of advanced, chemorefractory BTC.
• Mai, A. S., Lee, A. R., Tay, R. Y., Shapiro, L., Thakkar, A., Halmos, B., Grinshpun, A., Herishanu, Y., Benjamini, O., Tadmor, T., Shroff, R. T., LaFleur, B. J., Bhattacharya, D., Peng, S., Tey, J., Lee, S. C., Chai, L. Y., Soon, Y. Y., Sundar, R., & Lee, M. X. (2022). Booster doses of COVID-19 vaccines for patients with haematological and solid cancer: a systematic review and individual patient data meta-analysis. European journal of cancer (Oxford, England : 1990), 172, 65-75.
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  Patients with cancer have an increased risk of severe disease and mortality from COVID-19, as the disease and antineoplastic therapy cause reduced vaccine immunogenicity. Booster doses have been proposed to enhance protection, and efficacy data are emerging from several studies.
• McNamara, M. G., Bridgewater, J., Goyal, L., Jacobs, T., Wagner, A. D., Goldstein, D., Shroff, R., Moehler, M., Lowery, M., Bekaii-Saab, T., Kelley, R. K., Furuse, J., Rimassa, L., Morizane, C., Lamarca, A., Hubner, R., Knox, J., & Valle, J. (2022). What is the gender representation in authorship in later phase systemic clinical trials in biliary tract cancer (BTC)? - a retrospective review of the published literature. BMJ open, 12(10), e064954.
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  Female physicians in medicine are increasing, but disparities in female authorship exist. The aim of this study was to characterise factors associated with female first (FF) and female senior (SF) authorship in later phase systemic oncological clinical trials in biliary tract cancer (BTC) and identify any changes over time.
• Mody, K., Jain, P., El-Refai, S. M., Azad, N. S., Zabransky, D. J., Baretti, M., Shroff, R. T., Kelley, R. K., El-Khouiery, A. B., Hockenberry, A. J., Lau, D., Lesinski, G. B., & Yarchoan, M. (2022). Clinical, Genomic, and Transcriptomic Data Profiling of Biliary Tract Cancer Reveals Subtype-Specific Immune Signatures. JCO precision oncology, 6, e2100510.
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  Biliary tract cancers (BTCs) are aggressive cancers that carry a poor prognosis. An enhanced understanding of the immune landscape of anatomically and molecularly defined subsets of BTC may improve patient selection for immunotherapy and inform immune-based combination treatment strategies.
• Munugala, N., Maithel, S. K., & Shroff, R. T. (2022). Novel biomarkers and the future of targeted therapies in cholangiocarcinoma: a narrative review. Hepatobiliary surgery and nutrition, 11(2), 253-266.
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  Cholangiocarcinoma is a highly aggressive and heterogenous group of biliary malignancies arising from any site in the biliary tree, comprising 15% of all primary liver cancers. The nature of the disease and nonspecific presentation leads to late diagnosis and ultimately poor outcomes for patients. Combination gemcitabine and cisplatin has been the standard of care for cholangiocarcinoma (CCA) since 2010, with a median overall survival of 11.7 months. The five-year survival for CCA remains 5-10%, revealing a clear need for improved treatment options.
• Savani, M., & Shroff, R. T. (2022). Decision-Making Regarding Perioperative Therapy in Individuals with Localized Pancreatic Adenocarcinoma. Hematology/oncology clinics of North America, 36(5), 961-978.
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  Pancreatic cancer is a fatal malignancy that is projected to emerge as the second leading cause of cancer-related death in the United States. Despite the critical advances in surgical strategies, radiographic techniques, and systemic therapy, the treatment modality has remained largely unchanged over the past two decades eliciting a dire need for clinical trials in improving quality of life and prolonging survival in this patient population. Emergence of innovative strategies including novel combination chemotherapy, immunotherapy, vaccines, small compound drugs, among others is avenues under investigation to improve perioperative outcomes in localized pancreatic cancer.
• Scott, A. J., Sharman, R., & Shroff, R. T. (2022).

  Precision Medicine in Biliary Tract Cancer

  . Journal of Clinical Oncology, 40(24), 2716-2734. doi:10.1200/jco.21.02576
• Scott, A. J., Sharman, R., & Shroff, R. T. (2022). Precision Medicine in Biliary Tract Cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 40(24), 2716-2734.
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  Precision medicine has become a dominant theme in the treatment of biliary tract cancers (BTCs). Although prognosis remains poor, technologies for improved molecular characterization along with the US Food and Drug Administration approval of several targeted therapies have changed the therapeutic landscape of advanced BTC. The hallmark of BTC oncogenesis is chronic inflammation of the liver and biliary tract regardless of the anatomical subtype. Subtypes of BTC correspond to distinct molecular characteristics, making BTC a molecularly heterogenous collection of tumors. Collectively, up to 40% of BTCs harbor a potentially targetable molecular abnormality, and the National Comprehensive Cancer Network guidelines recommend molecular profiling for all patients with advanced BTC. Use of circulating tumor DNA, immunohistochemistry, and next-generation sequencing continues to expand the utility for biomarker-driven management and molecular monitoring of BTC. Improving outcomes using biomarker-agnostic treatment for nontargetable tumors also remains a priority, and combinational treatment strategies such as immune checkpoint inhibition plus chemotherapy hold promise for this subgroup of patients.
• Shroff, R. T., Goodman, K. A., Mehnert, J. M., Vose, J. M., Moran, S. E., Yessaian, J. L., Baldo, L., Alexander, B. M., Highsmith, Q. B., Mills, J. M., & Kunz, P. L. (2022). Where Are All the Women in Industry Advisory Boards?. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, JCO2102219.
• Tewari, K. S., Monk, B. J., Vergote, I., Miller, A., de Melo, A. C., Kim, H. S., Kim, Y. M., Lisyanskaya, A., Samouëlian, V., Lorusso, D., Damian, F., Chang, C. L., Gotovkin, E. A., Takahashi, S., Ramone, D., Pikiel, J., Maćkowiak-Matejczyk, B., Guerra Alía, E. M., Colombo, N., , Makarova, Y., et al. (2022). Survival with Cemiplimab in Recurrent Cervical Cancer. The New England journal of medicine, 386(6), 544-555.
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  Patients with recurrent cervical cancer have a poor prognosis. Cemiplimab, the fully human programmed cell death 1 (PD-1)-blocking antibody approved to treat lung and skin cancers, has been shown to have preliminary clinical activity in this population.
• Vrba, L., Futscher, B. W., Oshiro, M., Watts, G. S., Menashi, E., Hu, C., Hammad, H., Pennington, D. R., Golconda, U., Gavini, H., Roe, D. J., Shroff, R. T., & Nelson, M. A. (2022). Liquid biopsy, using a novel DNA methylation signature, distinguishes pancreatic adenocarcinoma from benign pancreatic disease. Clinical epigenetics, 14(1), 28.
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  We tested the ability of a novel DNA methylation biomarker set to distinguish metastatic pancreatic cancer cases from benign pancreatic cyst patients and to monitor tumor dynamics using quantitative DNA methylation analysis of cell-free DNA (cfDNA) from blood samples. The biomarkers were able to distinguish malignant cases from benign disease with high sensitivity and specificity (AUC = 0.999). Furthermore, the biomarkers detected a consistent decline in tumor-derived cfDNA in samples from patients undergoing chemotherapy. The study indicates that our liquid biopsy assay could be useful for management of pancreatic cancer patients.
• Abou-Alfa, G. K., Adeva, J., Aguado-Fraile, E., Borad, M. J., Bridgewater, J. A., Catenacci, D. V., Chamberlain, C. X., Choe, S., Cleary, J. M., El-Khoueiry, A. B., Gliser, C., Goyal, L., Harris, W. P., Javle, M. M., Kelley, R. K., Liu, H., Lowery, M. A., Lubner, S. J., Macarulla, T., , Murphy, A. G., et al. (2021).

  Final Overall Survival Efficacy Results of Ivosidenib for Patients With Advanced Cholangiocarcinoma With IDH1 Mutation: The Phase 3 Randomized Clinical ClarIDHy Trial

  . JAMA Oncology, 7(11), 1669. doi:10.1001/jamaoncol.2021.3836
• Bekaii-Saab, T. S., Bridgewater, J. A., Furuse, J., Goldstein, D., Goyal, L., Hubner, R., Kelley, R. K., Knox, J. J., Lamarca, A., Lowery, M. A., McNamara, M. G., Moehler, M. H., Morizane, C., Rimassa, L., Shroff, R. T., & Valle, J. W. (2021).

  Gender representation in authorship in later-phase systemic clinical trials in biliary tract cancer (BTC).

  . Journal of Clinical Oncology, 39(3_suppl), 348-348. doi:10.1200/jco.2021.39.3_suppl.348
• Bozorgui, B., Carapeto, F., Chagani, S., Foo, W. C., Javle, M., Korkut, A., Kwong, L. N., Meric‐Bernstam, F., Shalaby, A., Shroff, R. T., Solis Soto, L., & Wistuba, I. (2021).

  The immunogenomic landscape of resected intrahepatic cholangiocarcinoma

  . Hepatology, 75(2), 297-308. doi:10.1002/hep.32150
• Kam, A. E., Masood, A., & Shroff, R. T. (2021). Current and emerging therapies for advanced biliary tract cancers. The lancet. Gastroenterology & hepatology, 6(11), 956-969.
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  Biliary tract cancers (cholangiocarcinomas and gallbladder cancers) are increasing in incidence and have a poor prognosis. Most patients present with advanced disease, for which the treatment is palliative chemotherapy. Over the past few years, the genomic landscape of biliary tract cancers has been examined and several targeted therapies have been developed. Molecular targets with clinically meaningful activity include fibroblast growth factor receptor (FGFR), isocitrate dehydrogenase (IDH), RAS-RAF-MEK (MAP2K1)-ERK (MAPK3), HER2 (also known as ERBB2), DNA mismatch repair, and NTRK. Pemigatinib, a FGFR1-3 inhibitor, showed encouraging response rates and survival data as second-line treatment and received US Food and Drug Administration (FDA) approval in April, 2020, for previously treated advanced or metastatic cholangiocarcinoma with FGFR2 gene fusion or rearrangements. Ivosidenib, an IDH1 inhibitor, showed improved progression-free survival versus placebo in second-line treatment in the phase 3 ClarIDHy trial. Early phase trials of dabrafenib plus trametinib (BRAF and MEK inhibition) and zanidatamab (a bispecific HER2-antibody) have yielded encouraging response rates. Immunotherapy has mainly produced responses in tumours with deficient mismatch repair or high microsatellite instability (also known as dMMR or MSI-H) or higher PD-L1 score, or both. However, early phase trials of immunotherapy plus chemotherapy in unselected patient populations appear promising. NTRK inhibitors have also shown promise in early phase trials of NTRK-fusion positive solid tumours, including cholangiocarcinoma. In this Review, we discuss current and emerging therapies for advanced biliary tract cancers, with a focus on molecularly targeted therapy.
• Rogers, J. E., Mizrahi, J. D., Nogueras Gonzalez, G. M., Surana, R., Shroff, R. T., Wolff, R., Varadhachary, G. R., Javle, M. M., Overman, M., Raghav, K., & Pant, S. (2021). Outcomes of patients with metastatic pancreatic cancer who progress on first restaging imaging. Journal of gastrointestinal oncology, 12(5), 2268-2274.
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  Objective responses to first-line systemic chemotherapy in metastatic pancreatic cancer patients are seen in less than one third of cases. Unfortunately, a significant amount will have disease progression (PD) on their first restaging imaging. With patients' short life expectancy, it is crucial for clinicians to be prudent when deciding whom and when to treat. Our study aimed to evaluate outcomes of patients that progressed on their first restaging imaging on 1 line therapy.
• Shroff, R. (2019). A Phase II Study of Gemcitabine, Cisplatin, and Nab-paclitaxel in Advanced Biliary Tract Cancer. Manuscript in revision at JAMA Oncology.
• Shroff, R. (2019). Phase I study of Ivosidenib in IDH1-mutant cholangiocarcinoma. Manuscript in preparation.
• Shroff, R. T., & Sardar, M. (2021). Biliary cancer: gateway to comprehensive molecular profiling.. Clinical advances in hematology & oncology : H&O, 19(1), 27-34.
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  Cholangiocarcinoma is a rare malignancy with a poor prognosis. The majority of tumors present at an advanced stage, and relapse often occurs after surgery conducted with curative intent. In both of these cases, standard treatment is a combination of cisplatin and gemcitabine. The use of folinic acid, 5-fluorouracil, and oxaliplatin (FOLFOX) in second-line treatment improves survival, but outcomes remain dismal. Studies have shown that cholangiocarcinoma possesses a wide spectrum of genetic aberrations. Clinical trials evaluating targeted therapies in patients with FGFR2 fusions, IDH1 mutations, and BRAF mutations have yielded very promising results, and the agents were generally well tolerated. Several FGFR2 fusion-targeted agents have achieved response rates between 20.7% and 35.5%, with disease stability rates ranging between 76% and 82%. Agents targeting FGFR2 fusions also have produced median progression-free survival (PFS) ranging from 5.7 to 6.9 months and median overall survival (OS) ranging from 12.5 to 21.1 months. Ivosidenib in patients with an IDH1/2 mutation has produced a response rate of 2% and a disease stability rate of 51%, with median PFS of 2.7 months and median OS of 10.8 months. In patients with a BRAF mutation, a combination of dabrafenib and trametinib led to an overall response rate of 51% and disease stability in another 40% of patients. Median PFS and OS were 9 and 14 months, respectively. Patients should be encouraged to participate in clinical trials.
• Shroff, R. T., Chalasani, P., Wei, R., Pennington, D., Quirk, G., Schoenle, M. V., Peyton, K. L., Uhrlaub, J. L., Ripperger, T. J., Jergović, M., Dalgai, S., Wolf, A., Whitmer, R., Hammad, H., Carrier, A., Scott, A. J., Nikolich-Žugich, J., Worobey, M., Sprissler, R., , Dake, M., et al. (2021). Immune Responses to COVID-19 mRNA Vaccines in Patients with Solid Tumors on Active, Immunosuppressive Cancer Therapy. medRxiv : the preprint server for health sciences.
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  Vaccines against SARS-CoV-2 have shown high efficacy, but immunocompromised participants were excluded from controlled clinical trials. We compared immune responses to the Pfizer/BioNTech mRNA vaccine in solid tumor patients (n=53) on active cytotoxic anti-cancer therapy to a control cohort (n=50) as an observational study. Using live SARS-CoV-2 assays, neutralizing antibodies were detected in 67% and 80% of cancer patients after the first and second immunizations, respectively, with a 3-fold increase in median titers after the booster. Similar trends were observed in serum antibodies against the receptor-binding domain (RBD) and S2 regions of Spike protein, and in IFN+ Spike-specific T cells. Yet the magnitude of each of these responses was diminished relative to the control cohort. We therefore quantified RBD- and Spike S1-specific memory B cell subsets as predictors of anamnestic responses to additional immunizations. After the second vaccination, Spike-specific plasma cell-biased memory B cells were observed in most cancer patients at levels similar to those of the control cohort after the first immunization. We initiated an interventional phase 1 trial of a third booster shot (NCT04936997); primary outcomes were immune responses with a secondary outcome of safety. After a third immunization, the 20 participants demonstrated an increase in antibody responses, with a median 3-fold increase in virus-neutralizing titers. Yet no improvement was observed in T cell responses at 1 week after the booster immunization. There were mild adverse events, primarily injection site myalgia, with no serious adverse events after a month of follow-up. These results suggest that a third vaccination improves humoral immunity against COVID-19 in cancer patients on active chemotherapy with no severe adverse events.
• Shroff, R. T., Chalasani, P., Wei, R., Pennington, D., Quirk, G., Schoenle, M. V., Peyton, K. L., Uhrlaub, J. L., Ripperger, T. J., Jergović, M., Dalgai, S., Wolf, A., Whitmer, R., Hammad, H., Carrier, A., Scott, A. J., Nikolich-Žugich, J., Worobey, M., Sprissler, R., , Dake, M., et al. (2021). Immune responses to two and three doses of the BNT162b2 mRNA vaccine in adults with solid tumors. Nature medicine, 27(11), 2002-2011.
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  Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have shown high efficacy, but immunocompromised participants were excluded from controlled clinical trials. In this study, we compared immune responses to the BNT162b2 mRNA Coronavirus Disease 2019 vaccine in patients with solid tumors (n = 53) who were on active cytotoxic anti-cancer therapy to a control cohort of participants without cancer (n = 50). Neutralizing antibodies were detected in 67% of patients with cancer after the first immunization, followed by a threefold increase in median titers after the second dose. Similar patterns were observed for spike protein-specific serum antibodies and T cells, but the magnitude of each of these responses was diminished relative to the control cohort. In most patients with cancer, we detected spike receptor-binding domain and other S1-specific memory B cell subsets as potential predictors of anamnestic responses to additional immunizations. We therefore initiated a phase 1 trial for 20 cancer cohort participants of a third vaccine dose of BNT162b2 ( NCT04936997 ); primary outcomes were immune responses, with a secondary outcome of safety. At 1 week after a third immunization, 16 participants demonstrated a median threefold increase in neutralizing antibody responses, but no improvement was observed in T cell responses. Adverse events were mild. These results suggest that a third dose of BNT162b2 is safe, improves humoral immunity against SARS-CoV-2 and could be immunologically beneficial for patients with cancer on active chemotherapy.
• Shroff, R. T., Halder, R., & Amaraneni, A. (2021). Cholangiocarcinoma: a review of the literature and future directions in therapy. Hepatobiliary surgery and nutrition. doi:10.21037/hbsn-20-396
• Sipra, Q. U., & Shroff, R. (2021). The impact of molecular profiling on cholangiocarcinoma clinical trials and experimental drugs. Expert opinion on investigational drugs, 30(4), 281-284.
• Valle, J. W., Shroff, R. T., Rimassa, L., Morizane, C., Moehler, M., Mcnamara, M. G., Lowery, M. A., Lamarca, A., Knox, J. J., Kelley, R. K., Hubner, R. A., Goyal, L., Goldstein, D., Furuse, J., Bridgewater, J., & Bekaii-saab, T. (2021). Gender representation in authorship in later-phase systemic clinical trials in biliary tract cancer (BTC).. Journal of Clinical Oncology, 39, 348-348. doi:10.1200/jco.2021.39.3_suppl.348
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  348Background: The proportion of females in medicine is increasing (approx. 50% in medical school/workforce), but disparities in female authorship in oncology research publications exist; female co...
• Xu, X., Turk, A. A., Tupper, R., Shroff, R. T., Shimizu, T., Peters, M. L., Pauff, J. M., Papadopoulos, K. P., Kizilbash, S. H., Janku, F., Jaeckle, K. A., Ikeda, M., Hill, E. G., Harding, J. J., Hanley, M. P., Goyal, L., Furin, C. E., Cleary, J. M., Borad, M. J., & Azad, N. S. (2021). A phase I study of LY3410738, a first-in-class covalent inhibitor of mutant IDH1 in cholangiocarcinoma and other advanced solid tumors.. Journal of Clinical Oncology, 39. doi:10.1200/jco.2021.39.3_suppl.tps350
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  TPS350Background: Mutations in isocitrate dehydrogenase 1 (mIDH1) are found in approximately 20-30% of patients with intrahepatic cholangiocarcinoma (CCA), and less commonly in glioma, chondrosarco...
• Zalcberg, J., Verdaguer, H., Valle, J. W., Springfeld, C., Sjoquist, K. M., Shroff, R. T., Ross, P., Park, J. O., Palmer, D. H., Mcnamara, M. G., Knox, J. J., Gramont, A. D., Goyal, L., Cosgrove, D. O., & Braconi, C. (2021). Phase III study of NUC-1031 + cisplatin vs gemcitabine + cisplatin for first-line treatment of patients with advanced biliary tract cancer (NuTide:121).. Journal of Clinical Oncology, 39. doi:10.1200/jco.2021.39.3_suppl.tps351
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  TPS351Background: Biliary tract cancer (BTC) carries a poor prognosis and no first-line treatments are approved. The accepted global standard of care is gemcitabine + cisplatin (GemCis). NUC-1031 i...
• Zhu, A. X., Macarulla, T., Javle, M. M., Kelley, R. K., Lubner, S. J., Adeva, J., Cleary, J. M., Catenacci, D. V., Borad, M. J., Bridgewater, J. A., Harris, W. P., Murphy, A. G., Oh, D. Y., Whisenant, J. R., Lowery, M. A., Goyal, L., Shroff, R. T., El-Khoueiry, A. B., Chamberlain, C. X., , Aguado-Fraile, E., et al. (2021). Final Overall Survival Efficacy Results of Ivosidenib for Patients With Advanced Cholangiocarcinoma With IDH1 Mutation: The Phase 3 Randomized Clinical ClarIDHy Trial. JAMA oncology, 7(11), 1669-1677.
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  Isocitrate dehydrogenase 1 (IDH1) variations occur in up to approximately 20% of patients with intrahepatic cholangiocarcinoma. In the ClarIDHy trial, progression-free survival as determined by central review was significantly improved with ivosidenib vs placebo.
• Abou-Alfa, G. K., Beg, M. S., Brower, S. T., Gade, T. P., Goff, L., Gordan, J. D., Gupta, S., Guy, J., Harris, W. P., Iyer, R., Jaiyesimi, I., Jhawer, M., Karippot, A., Kaseb, A. O., Kelley, R. K., Kennedy, E. B., Knox, J. J., Kortmansky, J., Leaf, A., , Remak, W. M., et al. (2020).

  Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline

  . Journal of Clinical Oncology, 38(36), 4317-4345. doi:10.1200/jco.20.02672
• Abou-Alfa, G. K., Macarulla, T., Javle, M. M., Kelley, R. K., Lubner, S. J., Adeva, J., Cleary, J. M., Catenacci, D. V., Borad, M. J., Bridgewater, J., Harris, W. P., Murphy, A. G., Oh, D. Y., Whisenant, J., Lowery, M. A., Goyal, L., Shroff, R. T., El-Khoueiry, A. B., Fan, B., , Wu, B., et al. (2020). Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. The Lancet. Oncology, 21(6), 796-807.
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  Isocitrate dehydrogenase 1 (IDH1) mutations occur in approximately 13% of patients with intrahepatic cholangiocarcinoma, a relatively uncommon cancer with a poor clinical outcome. The aim of this international phase 3 study was to assess the efficacy and safety of ivosidenib (AG-120)-a small-molecule targeted inhibitor of mutated IDH1-in patients with previously treated IDH1-mutant cholangiocarcinoma.
• Algaze, S., Allen, R., El-Khoueiry, A. B., Golan, T., Halpern, N., & Shroff, R. T. (2020).

  Moving Beyond Chemotherapy for Pancreaticobiliary Tumors: Targeted and Immunotherapy Strategies

  . American Society of Clinical Oncology Educational Book, e333-e343. doi:10.1200/edbk_280901
• Bocobo, A. G., Borad, M. J., Boyhen, K., DeLeon, T., Goff, L. W., Goyal, L., Horick, N., Javle, M. M., Kelley, R. K., Lanka, A., Le, T. M., Mody, K., Pappas, L., Peters, M. L., Rahma, O. E., Reyes, S., Roth, M. T., Shroff, R. T., VanCott, C., & Zhu, A. X. (2020).

  Comparison of the clinical features, treatment patterns, and tumor mutations of patients with intrahepatic (ICC) and extrahepatic (ECC) cholangiocarcinoma.

  . Journal of Clinical Oncology, 38(4_suppl), 580-580. doi:10.1200/jco.2020.38.4_suppl.580
• Borad, M. J., Bridgewater, J. A., Morizane, C., Shroff, R. T., Oh, D., Moehler, M. H., Furuse, J., Benhadji, K. A., He, H., & Valle, J. W. (2020). A phase III study of futibatinib (TAS-120) versus gemcitabine-cisplatin (gem-cis) chemotherapy as first-line (1L) treatment for patients (pts) with advanced (adv) cholangiocarcinoma (CCA) harboring fibroblast growth factor receptor 2 (FGFR2) gene rearrangements (FOENIX-CCA3).. Journal of Clinical Oncology, 38(4_suppl), TPS600-TPS600. doi:10.1200/jco.2020.38.4_suppl.tps600
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  TPS600Background: Pts with adv CCA have poor survival outcomes, and chemotherapy offers limited survival benefit (5-year survival rates, 5–10%; median overall survival [OS], 8–12 months). FGFR2 gen...
• Borbath, I., Cho, T., Cohn, A., Goyal, L., Howland, M., Javle, M., K Abou-Alfa, G., Lamarca, A., Li, A., Macarulla, T., Makawita, S., Oh, D., Pande, A., Roychowdhury, S., Sadeghi, S., & T Shroff, R. (2020).

  Infigratinib in patients with advanced cholangiocarcinoma with FGFR2 gene fusions/translocations: the PROOF 301 trial

  . Future Oncology, 16(30), 2375-2384. doi:10.2217/fon-2020-0299
• Fogelman, D. R., Futreal, A., Ghelman, Y., Goldstein, J. B., Javle, M. M., McAllister, F., Overman, M. J., Shroff, R. T., Varadhachary, G. R., Wang, X., Wolff, R. A., & Zhao, L. (2020).

  Germline DNA Sequencing Reveals Novel Mutations Predictive of Overall Survival in a Cohort of Patients with Pancreatic Cancer

  . Clinical Cancer Research, 26(6), 1385-1394. doi:10.1158/1078-0432.ccr-19-0224
• Futscher, B. W., Shroff, R. T., Gavini, H., Wertheim, B. C., Vrba, L., Shroff, R. T., Scott, A. J., Roe, D. J., Pennington, D., Oshiro, M. M., Nelson, M. A., Munugala, N., Latura, L., Hammad, H., Gavini, H., Futscher, B. W., Elquza, E., Dalgai, S., & Babiker, H. M. (2020). Detection of pancreatic cancer using a novel blood-based DNA methylation signature.. Journal of Clinical Oncology, 38(15_suppl), e15546-e15546. doi:10.1200/jco.2020.38.15_suppl.e15546
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  e15546Background: Pancreatic cancer (PC) is a high mortality malignancy typically found when curative surgery is not an option. Liquid biopsies are a minimally invasive option that may allow earlie...
• Goldstein, J. B., Zhao, L., Wang, X., Ghelman, Y., Overman, M. J., Javle, M. M., Shroff, R. T., Varadhachary, G. R., Wolff, R. A., Mcallister, F., Futreal, A., & Fogelman, D. R. (2020). Germline DNA Sequencing Reveals Novel Mutations Predictive of Overall Survival in a Cohort of Patients with Pancreatic Cancer.. Clinical cancer research : an official journal of the American Association for Cancer Research, 26(6), 1385-1394. doi:10.1158/1078-0432.ccr-19-0224
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  Family history of BRCA-related tumors may correlate with response to chemotherapy and overall survival (OS) in pancreatic cancer. The frequency of germline mutations has been reported in patients predominantly under the age of 60 or with strong family history. We examine the incidence of deleterious germline mutations and compare the chemotherapy responses and OS in an unselected group of patients with metastatic pancreatic cancer..Patients with metastatic pancreatic cancer, who were seen at a single cancer center between 2010 and 2016, were included. Germline DNA was sequenced using a 263-gene panel to identify novel mutations (N = 133 MD Anderson cohort, N = 127 TCGA cohort). Chemotherapy response and OS were determined by review of medical records..Deleterious germline mutations were identified in 26 of 133 patients (19.5%). Patients with DNA damage repair (DDR) gene mutations (ATM, BRCA1/2, CDKN2A, CHEK2, ERCC4, PALB2, n = 15) had an improved OS as compared with patients without (16.8 vs. 9.1 months, P = 0.03). Conversely, patients with other deleterious mutations had a trend toward worse OS. However, survival in the latter group was longer (P = NS) in those mutants initially treated with gemcitabine/nab-paclitaxel. A family history of multiple breast, ovarian, and pancreatic cancers was associated with DDR gene mutations and better survival..We have identified novel germline mutations that are prognostic for survival in patients with pancreatic cancer. We observe improved survival in patients with DDR gene mutations and worsened survival in patients with deleterious mutations in non-DDR genes.
• Gordan, J. D., Kennedy, E. B., Abou-Alfa, G. K., Beg, M. S., Brower, S. T., Gade, T. P., Goff, L., Gupta, S., Guy, J., Harris, W. P., Iyer, R., Jaiyesimi, I., Jhawer, M., Karippot, A., Kaseb, A. O., Kelley, R. K., Knox, J. J., Kortmansky, J., Leaf, A., , Remak, W. M., et al. (2020). Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 38(36), 4317-4345.
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  To develop an evidence-based clinical practice guideline to assist in clinical decision making for patients with advanced hepatocellular carcinoma (HCC).
• Halder, R., & Shroff, R. T. (2020).

  What is the role of PARP inhibitors in pancreatic cancer?

  . Expert Review of Anticancer Therapy, 20(11), 913-918. doi:10.1080/14737140.2020.1816174
• Halder, R., & Shroff, R. T. (2020). What is the role of PARP inhibitors in pancreatic cancer?. Expert review of anticancer therapy, 20(11), 913-918.
• Holokai, L., Chakrabarti, J., Lundy, J., Croagh, D., Adhikary, P., Richards, S. S., Woodson, C., Steele, N., Kuester, R., Scott, A., Khreiss, M., Frankel, T., Merchant, J., Jenkins, B. J., Wang, J., Shroff, R. T., Ahmad, S. A., & Zavros, Y. (2020). Murine- and Human-Derived Autologous Organoid/Immune Cell Co-Cultures as Pre-Clinical Models of Pancreatic Ductal Adenocarcinoma. Cancers, 12(12).
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  : Pancreatic ductal adenocarcinoma (PDAC) has the lowest five-year survival rate of all cancers in the United States. Programmed death 1 receptor (PD-1)-programmed death ligand 1 (PD-L1) immune checkpoint inhibition has been unsuccessful in clinical trials. Myeloid-derived suppressor cells (MDSCs) are known to block anti-tumor CD8+ T cell immune responses in various cancers including pancreas. This has led us to our objective that was to develop a clinically relevant in vitro organoid model to specifically target mechanisms that deplete MDSCs as a therapeutic strategy for PDAC. : Murine and human pancreatic ductal adenocarcinoma (PDAC) autologous organoid/immune cell co-cultures were used to test whether PDAC can be effectively treated with combinatorial therapy involving PD-1 inhibition and MDSC depletion. : Murine in vivo orthotopic and in vitro organoid/immune cell co-culture models demonstrated that polymorphonuclear (PMN)-MDSCs promoted tumor growth and suppressed cytotoxic T lymphocyte (CTL) proliferation, leading to diminished efficacy of checkpoint inhibition. Mouse- and human-derived organoid/immune cell co-cultures revealed that PD-L1-expressing organoids were unresponsive to nivolumab in vitro in the presence of PMN-MDSCs. Depletion of arginase 1-expressing PMN-MDSCs within these co-cultures rendered the organoids susceptible to anti-PD-1/PD-L1-induced cancer cell death. : Here we use mouse- and human-derived autologous pancreatic cancer organoid/immune cell co-cultures to demonstrate that elevated infiltration of polymorphonuclear (PMN)-MDSCs within the PDAC tumor microenvironment inhibit T cell effector function, regardless of PD-1/PD-L1 inhibition. We present a pre-clinical model that may predict the efficacy of targeted therapies to improve the outcome of patients with this aggressive and otherwise unpredictable malignancy.
• Martinez, F. J., & Shroff, R. T. (2020). Biliary tract cancers: systemic therapy for advanced disease. Chinese clinical oncology, 9(1), 5.
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  Biliary tract carcinomas (BTC) present with minimal symptoms and thus they are often diagnosed in advanced stages that require systemic therapy. Unfortunately, if not resected, BTC's prognosis is generally poor, in part due to limited therapeutic options. Herein we will highlight the various systemic therapies that have proven efficacy in these diseases in both 1st and 2nd line. As it stands now, the combination of Gemcitabine and Cisplatin is the gold standard. Gemcitabine plus Cisplatin (Gem-Cis)-nab-paclitaxel showed improved survival in a phase II trial compared with historical controls. SWOG 1815 is a phase III trial currently underway comparing Gem-Cis-nab-paclitaxel to Gem-Cis and if positive, this has the potential to establish a new standard of care. New data from the ABC-06 study has shown a survival benefit using FOLFOX in the 2nd line setting. Molecularly targeted agents in BTC have demonstrated potential beyond Gem-Cis and while currently limited to second- and later-line therapies, ongoing trials are testing their efficacy even in newly diagnosed patients. With both incremental improvements in existing therapies and the development of entirely novel agents, the future of systemic therapy for BTC is promising.
• Mizrahi, J. D., & Shroff, R. T. (2020). New Treatment Options for Advanced Biliary Tract Cancer. Current treatment options in oncology, 21(8), 63.
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  The standard of care first-line therapy for patients with advanced biliary tract cancers eligible for treatment continues to be the combination of gemcitabine and cisplatin. Based on the promising results of a phase II study, an ongoing multi-institutional phase III study is assessing the benefit of adding nab-paclitaxel to the chemotherapy doublet, and appropriate patients should be considered for enrollment at participating centers. We would recommend early comprehensive genomic profiling of patients' tumors to identify potentially targetable aberrations with available therapies. Results with therapeutic implications include tumors with microsatellite instability/deficient mismatch repair, alterations in FGFR, IDH1/2, and HER-2, and potentially other molecular vulnerabilities. Patients in whom a targetable genomic abnormality is found should be matched with appropriate agent. If a targetable fusion or mutation is not detected, patients eligible for second-line therapy should be considered for either clinical trial enrollment or a second-line cytotoxic chemotherapy regimen such as modified FOLFOX. Strategies incorporating immunotherapy into the treatment of patients with microsatellite stable advanced biliary tract cancers have yielded largely disappointing results thus far, and routine use of checkpoint inhibitors outside of a clinical trial is not recommended.
• Mizrahi, J. D., Gunchick, V., Mody, K., Xiao, L., Surapaneni, P., Shroff, R. T., & Sahai, V. (2020). Multi-institutional retrospective analysis of FOLFIRI in patients with advanced biliary tract cancers. World journal of gastrointestinal oncology, 12(1), 83-91.
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  Gemcitabine plus platinum is the standard of care first-line treatment for advanced biliary tract cancers (BTC). There is no established second-line therapy, and retrospective reviews report median progression-free survival (PFS) less than 3 mo on second-line therapy. 5-Fluorouracil plus irinotecan (FOLFIRI) is a commonly used regimen in patients with BTC who have progressed on gemcitabine plus platinum, though there is a paucity of data regarding its efficacy in this population.
• Mizrahi, J. D., Rogers, J. E., Hess, K. R., Wolff, R. A., Varadhachary, G. R., Javle, M. M., Shroff, R. T., Ho, L., Fogelman, D. R., Raghav, K. P., Overman, M. J., & Pant, S. (2020). Modified FOLFIRINOX in pancreatic cancer patients Age 75 or older. Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.].
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  Although FOLFIRINOX (5-Fluorouracil + leucovorin + irinotecan + oxaliplatin) is now the standard of care for patients (pts) with metastatic pancreatic cancer (PC) based on the 2011 study by Conroy et al. which demonstrated improved median overall survival (mOS), pts > 75 yrs old were excluded from this study. The purpose of this study was to assess the safety and efficacy of modified FOLFIRINOX (mFOLFIRINOX) in this population.
• Mizrahi, J. D., Surana, R., Valle, J. W., & Shroff, R. T. (2020). Pancreatic cancer. Lancet (London, England), 395(10242), 2008-2020.
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  Pancreatic cancer is a highly fatal disease with a 5-year survival rate of approximately 10% in the USA, and it is becoming an increasingly common cause of cancer mortality. Risk factors for developing pancreatic cancer include family history, obesity, type 2 diabetes, and tobacco use. Patients typically present with advanced disease due to lack of or vague symptoms when the cancer is still localised. High quality computed tomography with intravenous contrast using a dual phase pancreatic protocol is typically the best method to detect a pancreatic tumour and to determine surgical resectability. Endoscopic ultrasound is an increasingly used complementary staging modality which also allows for diagnostic confirmation when combined with fine needle aspiration. Patients with pancreatic cancer are often divided into one of four categories based on extent of disease: resectable, borderline resectable, locally advanced, and metastatic; patient condition is also an important consideration. Surgical resection represents the only chance for cure, and advancements in adjuvant chemotherapy have improved long-term outcomes in these patients. Systemic chemotherapy combinations including FOLFIRINOX (5-fluorouracil, folinic acid [leucovorin], irinotecan, and oxaliplatin) and gemcitabine plus nab-paclitaxel remain the mainstay of treatment for patients with advanced disease. Data on the benefit of PARP inhibition as maintenance therapy in patients with germline BRCA1 or BRACA2 mutations might prove to be a harbinger of advancement in targeted therapy. Additional research efforts are focusing on modulating the pancreatic tumour microenvironment to enhance the efficacy of the immunotherapeutic strategies.
• Pappas, L., Reyes, S., Lanka, A., Shroff, R. T., Le, T. M., Rahma, O. E., Bocobo, A. G., Borad, M. J., Deleon, T., Mody, K., Roth, M. T., Goff, L. W., Boyhen, K., Vancott, C., Horick, N., Zhu, A. X., Javle, M. M., Kelley, R. K., Goyal, L., & Peters, M. L. (2020). Comparison of the clinical features, treatment patterns, and tumor mutations of patients with intrahepatic (ICC) and extrahepatic (ECC) cholangiocarcinoma.. Journal of Clinical Oncology, 38(4_suppl), 580-580. doi:10.1200/jco.2020.38.4_suppl.580
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  580Background: Though studies indicate that the genomic profiles of ICC and ECC are distinct, the clinical features that differentiate them still remain to be well characterized. The purpose of thi...
• Rogers, J. E., Mizrahi, J. D., Shroff, R. T., Nelson, D. A., Tu, J., Javle, M. M., Wolff, R. A., & Pant, S. (2020). Dose-modified gemcitabine plus nab-paclitaxel front-line in advanced pancreatic ductal adenocarcinoma with baseline hyperbilirubinemia. Journal of gastrointestinal oncology, 11(1), 55-60.
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  Von Hoff demonstrated survival improvement with gemcitabine (GEM) + nab-paclitaxel (NabP) for metastatic pancreatic ductal adenocarcinoma (PDAC) compared to GEM alone. GEM + NabP resulted in a median overall survival (OS) and progression-free survival (PFS) of 8.5 and 5.5 months, respectively. Patients with baseline hyperbilirubinemia were excluded. Primary objective was OS. Secondary objectives included time on treatment (TOT), disease control rate, dosing practices, delays/admissions, and adverse effects.
• Rogers, J. E., Mizrahi, J. D., Xiao, L., Mohindroo, C., Shroff, R. T., Wolff, R., Varadhachary, G. R., Javle, M. M., Overman, M., Fogelman, D. R., Raghav, K. P., Pant, S., & McAllister, F. (2020). Modified gemcitabine plus nab-paclitaxel regimen in advanced pancreatic ductal adenocarcinoma. Cancer medicine, 9(15), 5406-5415.
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  Gemcitabine (GEM) plus nab-paclitaxel (NabP) (GEM 1000 mg/m IV over 30 minutes + NabP 125 mg/m IV given days 1, 8, and 15 every 28 days) is one of the two standard of care combination therapies for metastatic pancreatic ductal adenocarcinoma (PDAC). Our cancer center has utilized GEM-NabP given every two-weeks due to tolerability and patient convenience. Here, we review the safety and efficacy of this modified regimen.
• Scott, A. J., & Shroff, R. T. (2020).

  Moving the Needle Forward With Locoregional Treatment in Unresectable Cholangiocarcinoma—The Jury Is Still Out

  . JAMA Oncology, 6(1), 29. doi:10.1001/jamaoncol.2019.3691
• Segar, J., & Shroff, R. T. (2020). Charging forward in locally advanced pancreatic cancer. The lancet. Gastroenterology & hepatology, 5(3), 234-236.
• Shroff, R. (2020). managing-cca-in-the-setting-of-covid-19/2751-managing-cholangiocarcinoma-in-the-setting-of-covid-19-unique-challenges-and-opportunities. CCA News Special Issue.
• Shroff, R. T., Halpern, N., Golan, T., El-khoueiry, A. B., Allen, R., & Algaze, S. (2020). Moving Beyond Chemotherapy for Pancreaticobiliary Tumors: Targeted and Immunotherapy Strategies. American Society of Clinical Oncology Educational Book, e333-e343. doi:10.1200/edbk_280901
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  Pancreaticobiliary cancers are a group of malignancies affecting the pancreas and biliary tract and are often associated with poor prognosis. Existing treatment strategies for these malignancies ar...
• Shroff, R. T., Munugala, N., & Maithel, S. K. (2020). Novel biomarkers and the future of targeted therapies in cholangiocarcinoma. Hepatobiliary surgery and nutrition. doi:10.21037/hbsn-20-475
• Shroff, R. T., Raymond, V. M., Raina, A., Pant, S., Meric-bernstam, F., Madwani, K., Lapin, M., Lanman, R. B., Kwong, L. N., Javle, M., Janku, F., Huang, H., Holley, V. R., & Call, S. G. (2020). Abstract 734: Monitoring of dynamic changes and clonal evolution in circulating tumor DNA from patients with IDH-mutated cholangiocarcinoma treated with IDH inhibitors. Clinical Trials. doi:10.1158/1538-7445.am2020-734
• Shroff, R. T., Sadeghi, S., Roychowdhury, S., Pande, A., Oh, D., Macarulla, T., Li, A., Lamarca, A., Javle, M., Howland, M., Goyal, L., Cohn, A. L., Cho, T., Borbath, I., & Abou-alfa, G. K. (2020). 1014TiP PROOF: A multicenter, open-label, randomized, phase III trial of infigratinib vs gemcitabine + cisplatin in patients with advanced cholangiocarcinoma with FGFR2 gene rearrangements. Annals of Oncology, 31. doi:10.1016/j.annonc.2020.08.1130
• Shroff, R. T., Sadeghi, S., Roychowdhury, S., Pande, A., Oh, D., Macarulla, T., Li, A., Lamarca, A., Javle, M., Howland, M., Goyal, L., Cohn, A. L., Cho, T., Borbath, I., & Abou-alfa, G. K. (2020). P-144 Infigratinib versus gemcitabine plus cisplatin as first-line therapy in patients with advanced cholangiocarcinoma with FGFR2 gene fusions/translocations: phase 3 PROOF trial. Annals of Oncology, 31. doi:10.1016/j.annonc.2020.04.226
• Shroff, R. T., Shroff, R. T., & Scott, A. J. (2020). Moving the Needle Forward With Locoregional Treatment in Unresectable Cholangiocarcinoma-The Jury Is Still Out.. JAMA oncology, 6(1), 29-31. doi:10.1001/jamaoncol.2019.3691
• Shroff, R. T., Zavros, Y., Wang, J., Shroff, R. T., Scott, A., Lundy, J., Jenkins, B. J., Dua-awereh, M., Croagh, D., Chakrabarti, J., Ahmad, S. A., & Adhikary, P. (2020). Mo1050 CABOZANTINIB TREATMENT OF PANCREATIC DUCTAL ADENOCARCINOMA PROMOTES A STROMAL ENVIRONMENT THAT IS CONDUCIVE TO IMMUNOTHERAPY. Gastroenterology, 158(6), S-769. doi:10.1016/s0016-5085(20)32597-x
• Shroff, R. T., Zavros, Y., Wang, J., Shroff, R. T., Scott, A., Lundy, J., Jenkins, B. J., Falcon, K. V., Dua-awereh, M., Croagh, D., Chakrabarti, J., & Ahmad, S. A. (2020). Mo1051 CD44 VARIANT ISOFORM 9 AND ITS ROLE IN PANCREATIC DUCTAL ADENOCARCINOMA STEM CELL SURVIVAL POST STANDARD-OF-CARE CHEMOTHERAPY. Gastroenterology, 158(6), S-769-S-770. doi:10.1016/s0016-5085(20)32598-1
• Singh, A., Shroff, R. T., & Mcbride, A. (2020). Retrospective analysis of institutional outcomes with FOLFIRINOX versus nab-paclitaxel plus gemcitabine in metastatic pancreatic cancer.. Journal of Clinical Oncology, 38(4_suppl), 776-776. doi:10.1200/jco.2020.38.4_suppl.776
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  776Background: With an estimated six percent five-year survival, metastatic pancreatic adenocarcinoma is one of the most lethal cancers in the United States. Previously, treatments with FOLFIRINOX ...
• T shroff, R., Shroff, R. T., Sadeghi, S., Roychowdhury, S., Pande, A., Oh, D., Makawita, S., Macarulla, T., Li, A., Lamarca, A., K abou-alfa, G., Javle, M., Howland, M., Goyal, L., Cohn, A., Cho, T., Borbath, I., & Abou-alfa, G. K. (2020). Infigratinib in patients with advanced cholangiocarcinoma with FGFR2 gene fusions/translocations: the PROOF 301 trial.. Future oncology (London, England), 16(30), 2375-2384. doi:10.2217/fon-2020-0299
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  Cholangiocarcinoma is an aggressive malignancy with poor overall survival. Approximately 15% of intrahepatic cholangiocarcinomas contain FGFR alterations. Infigratinib is an oral FGFR 1-3 kinase inhibitor. Favorable results from a Phase II trial of infigratinib in advanced/metastatic FGFR-altered cholangiocarcinomas has led to its further investigation in the front-line setting. In this article we describe the design, objectives and rationale for PROOF 301, a Phase III multicenter, open label, randomized trial of infigratinib in comparison to standard of care gemcitabine and cisplatin in advanced/metastatic cholangiocarcinoma with FGFR2 translocations. The results of this study have the potential to define a new role for a chemotherapy-free, targeted therapy option in the front-line setting for these patients. Clinical Trial Registration: NCT03773302 (ClincalTrials.gov).
• Yao, J. C., Wolff, R. A., Wistuba, I. I., Varadhachary, G. R., Vainstein-haras, A., Townson, S. M., Sorani, E., Solis, L. M., Shroff, R. T., Parra, E. R., Pant, S., Pandurengan, R. K., Overman, M. J., Lustig, T. M., Ledesma, D. A., Kashtan, O., Jiang, M., Javle, M., Gozlan, Y., , Gite, S., et al. (2020). Abstract CT204: High cytotoxic T-cell or polymorphonuclear cell infiltrates in the tumor microenvironment correlate with responses to BL8040 plus pembrolizumab combination therapy in metastatic pancreatic tumors: Scientific correlates of a phase II clinical trial. Cancer Research, 80. doi:10.1158/1538-7445.am2020-ct204
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  Background: We recently conducted a clinical trial assessing Pembrolizumab (P) and BL-8040 (BL) in patients with pancreatic cancer. We prospectively collected serial biopsies to help understand the impact of this treatment on the tumor microenvironment (TME). Methods: Twenty patients were enrolled and were treated with BL8040 (1.25mg/kg) monotherapy for 2 weeks followed by dual therapy with BL8040 (d1, 4, 8, 11) plus Pembrolizumab (200 mg IV, d1) every 3 weeks. Biopsies were collected at baseline (T0) and during therapy. Some patients had biopsies after BL monotherapy (Tm) and some after combined therapy (Tc) due to a protocol change mid-study. Malignant cells expressing PD-L1 were assessed using immunohistochemistry (IHC) and TME was studied using 3 multiplex immunofluorescence panels including one each for T-cells subpopulations, macrophages and myeloid-derived suppressor cells (MDSCs). Median densities of the different phenotypes were analyzed in tumor and stromal compartments and correlated with serial biopsies. Results: Of 20 patients enrolled and 15 were evaluable for response of whom 2 had stability and 1 had a partial response. 17 patients had at least one viable biopsy; 4 had biopsies at T0 and Tm, 3 had biopsies at T0, Tm, and Tc, and 2 had biopsies at T0 and Tc. In general, we noted that cytotoxic T cells increased from baseline when measured at Tm or Tc. In contrast, MDSC counts and overall T cells decreased at Tm or Tc from baseline. Additionally, we saw an increase in CD 68+ and PD-L1 expressing macrophages (P=0.059 and P=0.046, respectively). Patients who had clinical benefit (PR/SD) had greater numbers of cytotoxic T-cells (CD3+CD8+, median, 226.08 cells/mm2) and regulatory T cells (CD3+FOXP3+, median, 48.20 cells/mm2) at baseline than PD patients (median, 26.15 cells/mm2, P=0.03; 13.31 cells/mm2, P=0.016, respectively). Conversely, at T0, the lowest numbers of tumor cytotoxic T-cells activated CD3+CD8+GB+ (median, 0.34 cells/mm2) and highest numbers of PMN-cells (CD66b+CD11b+, median, 16.66 cells/mm2) were observed in patients with PD when compared with PR or SD (median, 4.54 cells/mm2, P=0.097; 3.38 cells/mm2, P=0.023, respectively), suggesting that highest densities of PMN-cells may contribute to downregulation of T-cells in those cases. Conclusions: Higher cytotoxic T-cells or PMN-cell counts at T0 may predict changes in the TME and radiologic response to treatment with BL8040+Pembrolizumab therapy in metastatic pancreatic cancer. PMN-cells may play a role promoting immune suppression of T-cells, increase the risk of metastasis and interfering with the treatment. Trial Registration: NCT02907099, Ethics Approval: This study was approved by the M.D. Anderson Institutional Review Board, approval number 2016-0410. Citation Format: Carmelia M. Noia Barreto, Debora A. Ledesma, Swati Gite, Luisa M. Solis, Mei Jiang, Renganayaki K. Pandurengan, Robert Wolff, Milind Javle, Shubham Pant, Gauri Varadhachary, Rachna Shroff, Abi Vainstein-Haras, Ella Sorani, Tzipora M. Lustig, Osnat Kashtan, Yosi Gozlan, Steven M. Townson, Jeanne M. Fahey, James Yao, Ignacio I. Wistuba, Michael Overman, David Fogelman, Edwin R. Parra. High cytotoxic T-cell or polymorphonuclear cell infiltrates in the tumor microenvironment correlate with responses to BL8040 plus pembrolizumab combination therapy in metastatic pancreatic tumors: Scientific correlates of a phase II clinical trial [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT204.
• Zettl, M., Tolcher, A. W., Shroff, R. T., Piha-paul, S. A., Patnaik, A., Olwill, S., Noonan, A. M., Matrana, M., Mar, L., Ku, G. Y., Krishnamurthy, A., Jolicoeur, P., Hurvitz, S. A., Hahn, N. M., El-khoueiry, A. B., Bruns, I., Bendell, J. C., & Aviano, K. (2020). 525O A phase I dose escalation study of PRS-343, a HER2/4-1BB bispecific molecule, in patients with HER2-positive malignancies. Annals of Oncology, 31. doi:10.1016/j.annonc.2020.08.639
• Zettl, M., Yusuf, R., Tolcher, A. W., Shroff, R. T., Pohlmann, P. R., Piha-paul, S. A., Patnaik, A., Olwill, S. A., Mei, J., Matis, L., Ku, G. Y., Krishnamurthy, A., Hurvitz, S. A., Hahn, N., Duerr, M., Bruns, I., Bendell, J. C., & Aviano, K. (2020). O82 A phase 1 dose escalation study of PRS-343, a HER2/4–1BB bispecific molecule, in patients with HER2-positive malignancies. Journal for ImmunoTherapy of Cancer, 8(Suppl 1), A1.2-A2. doi:10.1136/lba2019.2
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  Background Anticalin® proteins are recombinantly engineered human proteins based on lipocalins. PRS-343 is a first-in-class bispecific antibody-Anticalin fusion protein targeting the oncogenic tumor antigen HER2 and the costimulatory immune receptor 4-1BB on T and other immune cells. Here, we report the results of a phase 1 single-agent dose escalation trial in patients with HER2+ solid tumors. Methods PRS-343 has been evaluated in sequential dose cohorts from 0.0005 to 8 mg/kg i.v. Doses were administered Q3W and the 8 mg/kg dose was also given Q2W. An accelerated titration design was utilized for the initial dose escalation followed by a modified 3+3 design and the option to back-fill cohorts. Dose-limiting toxicities (DLTs) were reported during the first cycle of each schedule. The primary study objectives include the safety profile and RP2D of PRS-343. Secondary objectives include ORR and DCR, PD biomarker response and PK profile. PD response was assessed in tumor biopsies (CD8+ T cell IHC) pre- and post- PRS-343 treatment. Results 51 patients (median age 61.2 years, 61% female, 82% caucasian, 57% with more than three lines of prior therapy) with a variety of solid tumor indications [gastric/GEJ (n=19); BC (n=12); gynecological cancer (n=6); CRC (n=5); BTC (n=4); UC (n=2); melanoma, pancreatic and salivary duct (n=1 each)] have been treated with PRS-343. Based on pharmacokinetic analyses and observed kinetics of the CD8+ T cell expansion post-treatment, the low end of the active dose range is considered 2.5 mg/kg. 19 patients treated at active dose levels before the data cut-off on 09-06-2019 were evaluable for response [DCR 58% (11% confirmed PR) as per RECIST 1.1]. At the active doses, we observed significant and pronounced post-treatment expansion of CD8+ T cells particularly in the tumor nests, consistent with the MoA of PRS-343, while there was no increase in the doses below 2.5 mg/kg. The post-treatment expansion of CD8+ T cells was more pronounced in patients with a confirmed PR or prolonged SD. PRS-343 was very well tolerated, with no SAEs reported. The most frequent TRAEs were fatigue (9%), chills (6%) and diarrhea (5%) of mild to moderate severity. None qualified as a DLT. Conclusions PRS-343 is the first molecule of its kind to demonstrate encouraging evidence of safety and clinical benefit with a correlative PD effect in a heavily pre-treated population. These initial data suggest that PRS-343, the first 4-1BB bispecific to enter clinical development, merits further investigation in clinical trials. Trial Registration NCT03330561
• Abou-Alfa, G. K., Borad, M. J., Bullock, A. J., Chung, V., Hecht, J. R., Muhsin, M., Oh, D., Shroff, R. T., Sigal, D., & Wu, W. (2019).

  Halo 110-101: Early safety results of pegvorhyaluronidase alfa (PEGPH20; PVHA) + cisplatin (C) + gemcitabine (G) ± atezolizumab (ATZ) in patients (pts) with locally advanced or metastatic cholangiocarcinoma (CCA) and gallbladder cancer (GBC).

  . Journal of Clinical Oncology, 37(4_suppl), 408-408. doi:10.1200/jco.2019.37.4_suppl.408
• Ahn, D. H., Bekaii-Saab, T. S., Borad, M. J., Iwasaki, M., Javle, M. M., Kaseb, A. O., Masci, P., Raghav, K. P., Ramanathan, R. K., Shroff, R. T., Varadhachary, G. R., Wolff, R. A., & Xiao, L. (2019).

  Gemcitabine, Cisplatin, and nab-Paclitaxel for the Treatment of Advanced Biliary Tract Cancers: A Phase 2 Clinical Trial

  . JAMA Oncology, 5(6), 824. doi:10.1001/jamaoncol.2019.0270
• Bachini, M., Bekaii-Saab, T., Crane, C., Edeline, J., El-Khoueiry, A., Feng, M., Katz, M. H., Kennedy, E. B., Maithel, S. K., Primrose, J., Shroff, R. T., Soares, H. P., & Valle, J. (2019).

  Adjuvant Therapy for Resected Biliary Tract Cancer: ASCO Clinical Practice Guideline

  . Journal of Clinical Oncology, 37(12), 1015-1027. doi:10.1200/jco.18.02178
• Fogelman, D. R., Ho, L., Javle, M. M., Mizrahi, J. D., Nogueras-Gonzalez, G. M., Overman, M. J., Pant, S., Raghav, K. P., Rogers, J. E., Shroff, R. T., Varadhachary, G. R., & Wolff, R. A. (2019).

  Abstract B35: Outcomes of patients with metastatic pancreatic cancer who progress on first restaging imaging

  . Cancer Research, 79(24_Supplement), B35-B35. doi:10.1158/1538-7445.panca19-b35
• Goldstein, J. B., Zhao, L., Wang, X., Ghelman, Y., Overman, M. J., Javle, M., Shroff, R. T., Varadhachary, G. R., Wolf, R. A., McAllister, F., Futreal, P. A., & Fogelman, D. R. (2019). Germline DNA Sequencing Reveals Novel Mutations Predictive of Overall Survival in a Cohort of Pancreatic Cancer Patients. Clinical cancer research : an official journal of the American Association for Cancer Research.
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  Background and Aims Family history of BRCA-related tumors may correlate with response to chemotherapy and overall survival (OS) in pancreatic cancer. The frequency of germline mutations has been reported in patients predominantly under the age of 60 or with strong family history. We examine the incidence of deleterious germline mutations and compare the chemotherapy responses and OS in an unselected group of metastatic pancreatic cancer patients. Methods Metastatic pancreatic cancer patients, who were seen at a single cancer center between 2010 and 2016, were included. Germline DNA was sequenced using a 263-gene panel to identify novel mutations (N = 133 MD Anderson cohort, N = 127 TCGA cohort). Chemotherapy response and OS were determined by review of medical records. Results Deleterious germline mutations were identified in 26 of 133 patients (19.5%). Patients with DNA damage repair (DDR) gene mutations (ATM, BRCA1/2, CDKN2A, CHEK2, ERCC4, PALB2, n = 15) had an improved OS as compared to patients without (16.8 versus 9.1 months, P = 0.03). Conversely, patients with other deleterious mutations had a trend towards worse OS. Although, survival in the later group was longer (P= NS) in those mutants initially treated with gemcitabine/nab-paclitaxel. A family history of multiple breast, ovarian, and pancreatic cancers was associated with DDR gene mutations and better survival. Conclusion We have identified novel germline mutations that are prognostic for survival in pancreatic cancer patients. We observe improved survival in patients with DDR gene mutations and worsened survival in patients with deleterious mutations in non-DDR genes.
• Gulhati, P., Katz, M. H., Wang, X., Javle, M., Lee, J. E., Tzeng, C. D., Lee, J. H., Weston, B., Bhosale, P., Koay, E. J., Maitra, A., Wang, H., Wolff, R. A., Varadhachary, G. R., Tamm, E. P., Shroff, R. T., Prakash, L. R., & Fogelman, D. R. (2019). First-Line Gemcitabine and Nab-Paclitaxel Chemotherapy for Localized Pancreatic Ductal Adenocarcinoma.. Annals of surgical oncology, 26(2), 619-627. doi:10.1245/s10434-018-6807-9
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  Preoperative chemotherapy provides early treatment of micro-metastases and guaranteed delivery of all components of multimodality therapy for localized pancreatic ductal adenocarcinoma (PDAC). For locally advanced (LA) PDAC, induction chemotherapy is the standard of care. This study evaluated the use of gemcitabine and nab-paclitaxel (Gem/nab-P) as first-line therapy for localized PDAC..Clinicopathologic features, treatment, and outcomes were evaluated for 99 patients with localized PDAC. The patients were staged using previously published criteria as follows: potentially resectable (PR), borderline type A (BR-A) (anatomy amenable to vascular resection), BR-B (biology suspicious for metastatic disease including high CA19-9), BR-C (comorbidities requiring medical optimization), and LA..The 99 patients (PR/BR/LA: 45/14/40) were treated with Gem/nab-P. Clinical staging showed that 20 patients had PR or BR-A disease, whereas 39 patients had BR-B or BR-C disease. The BR-B+C cases included one or more of the following: age of 80 years or older (13%), Eastern Cooperative Oncology Group performance status (ECOG PS) of 2 or more (13%), moderate to severe comorbidities (55%), CA19-9 of 1000 or higher (28%), and suspicion for metastases (21%). The majority of the patients received biweekly Gem/nab-P dosing, which was well tolerated. Pancreatectomy was performed for 12 (60%) of 20 patients with PR+BR-A, 2 (5%) of 39 patients with BR-B+C, and 1 (3%) of 40 patients with LA disease. During a median follow-up period of 26 months, the median overall survival (OS) period was 18 months (95% confidence interval [CI], 15.6-20.5 months) for all the patients, 17 months (95% CI, 14.6-19.5 months) for the unresected patients, and not reached for the resected patients (p = 0.028 for resected vs unresected patients)..A significant number of patients with radiographically resectable PDAC albeit aggressive biology (BR-B), medically inoperable conditions (BR-C), or both received biweekly first-line Gem/nab-P. The resection rates were lower for the BR-B/BR-C patients than for the PR/BR-A patients (hazard ratio [HR], 0.43; 95% CI, 0.19-1.00; p = 0.05).
• Gunchick, V., Mizrahi, J., Mody, K., Sahai, V., Shroff, R. T., Surapaneni, P. K., & Xiao, L. (2019).

  FOLFIRI in advanced biliary tract cancers.

  . Journal of Clinical Oncology, 37(4_suppl), 451-451. doi:10.1200/jco.2019.37.4_suppl.451
• Gunchick, V., Mody, K., Xiao, L., Surapaneni, P. K., Shroff, R. T., Sahai, V., & Mizrahi, J. D. (2019). FOLFIRI in advanced biliary tract cancers.. Journal of Clinical Oncology, 37(4_suppl), 451-451. doi:10.1200/jco.2019.37.4_suppl.451
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  451Background: Gemcitabine plus platinum (GP) is the standard of care first-line treatment for advanced biliary tract cancers (BTC). There is no established second-line therapy, and retrospective reviews report progression-free survival (PFS) for second-line treatment to be < 3 months. 5-Fluorouracil plus irinotecan (FOLFIRI) is a commonly used regimen in patients (pts) with BTC who have progressed on GP, though there is a paucity of data regarding its efficacy in this population. Methods: We retrospectively evaluated pts with advanced BTC who were treated with FOLFIRI at MD Anderson, University of Michigan and Mayo Clinic in Jacksonville. Data were obtained on pt demographics, type of BTC, PFS, and overall survival (OS). Results: Ninety-eight pts were included of which 74 (76%) had metastatic disease at the time of treatment with FOLFIRI. The median age was 59 (range, 22 to 86) years. The number of pts with extrahepatic cholangiocarcinoma (CCA)/gall bladder (GB)/intrahepatic CCA were 10, 17, and 71. FOLF...
• Hess, K. R., Wolff, R. A., Varadhachary, G. R., Shroff, R. T., Ho, L., Fogelman, D. R., Overman, M. J., Pant, S., Rogers, J. E., Raghav, K. P., & Mizrahi, J. D. (2019). FOLFIRINOX in pancreatic cancer patients age 75 years or older.. Journal of Clinical Oncology, 37(4_suppl), 362-362. doi:10.1200/jco.2019.37.4_suppl.362
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  362Background: Although FOLFIRINOX (5-Fluorouracil + leucovorin + irinotecan + oxaliplatin) is now the standard of care for patients (pts) with metastatic pancreatic cancer (PC) based on the 2011 s...
• Javle, M. M., Murugesan, K., Shroff, R. T., Borad, M. J., Abdel-wahab, R., Schrock, A. B., Chung, J., Goyal, L., Frampton, G. M., Kelley, R. K., Miller, V. A., Ross, J. S., Bekaii-saab, T. S., Ali, S. M., & Albacker, L. A. (2019). Profiling of 3,634 cholangiocarcinomas (CCA) to identify genomic alterations (GA), tumor mutational burden (TMB), and genomic loss of heterozygosity (gLOH).. Journal of Clinical Oncology, 37(15_suppl), 4087-4087. doi:10.1200/jco.2019.37.15_suppl.4087
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  4087Background: The management of CCA has evolved as targeted and immune checkpoint inhibitor (ICPI) therapies have emerged. We used comprehensive genomic profiling (CGP) to characterize the genomi...
• Koay, E. J., Katz, M. H., Wang, H., Wang, X., Prakash, L., Javle, M., Shroff, R., Fogelman, D., Avila, S., Zaid, M., Elganainy, D., Lee, Y., Crane, C. H., Krishnan, S., Das, P., Fleming, J. B., Lee, J. E., Tamm, E. P., Bhosale, P., , Lee, J. H., et al. (2019). Computed Tomography-Based Biomarker Outcomes in a Prospective Trial of Preoperative FOLFIRINOX and Chemoradiation for Borderline Resectable Pancreatic Cancer. JCO precision oncology, 3.
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  Effective preoperative regimens and biomarkers for pancreatic ductal adenocarcinoma (PDAC) are lacking. We prospectively evaluated fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX)-based treatment and imaging-based biomarkers for borderline resectable PDAC.
• Lowery, M. A., Burris, H. A., Janku, F., Shroff, R. T., Cleary, J. M., Azad, N. S., Goyal, L., Maher, E. A., Gore, L., Hollebecque, A., Beeram, M., Trent, J. C., Jiang, L., Fan, B., Aguado-Fraile, E., Choe, S., Wu, B., Gliser, C., Agresta, S. V., , Pandya, S. S., et al. (2019). Safety and activity of ivosidenib in patients with IDH1-mutant advanced cholangiocarcinoma: a phase 1 study. The lancet. Gastroenterology & hepatology, 4(9), 711-720.
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  Isocitrate dehydrogenase-1 (IDH1) is mutated in up to 25% of cholangiocarcinomas, especially intrahepatic cholangiocarcinoma. Ivosidenib is an oral, targeted inhibitor of mutant IDH1 (mIDH1) approved in the USA for the treatment of mIDH1 acute myeloid leukaemia in newly diagnosed patients ineligible for intensive chemotherapy and patients with relapsed or refractory disease. Ivosidenib is under clinical evaluation in a phase 1 study that aims to assess its safety and tolerability in patients with mIDH1 solid tumours. Here we report data for the mIDH1-cholangiocarcinoma cohort.
• Oh, D., Muhsin, M., Bullock, A. J., Abou-alfa, G. K., Shroff, R. T., Sigal, D., Chung, V., Hecht, J. R., Wu, W., & Borad, M. J. (2019). Halo 110-101: Early safety results of pegvorhyaluronidase alfa (PEGPH20; PVHA) + cisplatin (C) + gemcitabine (G) ± atezolizumab (ATZ) in patients (pts) with locally advanced or metastatic cholangiocarcinoma (CCA) and gallbladder cancer (GBC).. Journal of Clinical Oncology, 37(4_suppl), 408-408. doi:10.1200/jco.2019.37.4_suppl.408
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  408Background: Standard of care for CCA/GBC is C-G therapy. MAbs (ATZ, pembrolizumab) targeting PD-L1 show promise in treating CCA/GBC. Hyaluronan (HA), which may impede drug and immune cell access...
• Recio-Boiles, A., Veeravelli, S., Vondrak, J., Babiker, H. M., Scott, A. J., Shroff, R. T., Patel, H., Elquza, E., & McBride, A. (2019). Evaluation of the safety and effectiveness of direct oral anticoagulants and low molecular weight heparin in gastrointestinal cancer-associated venous thromboembolism. World journal of gastrointestinal oncology, 11(10), 866-876.
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  Gastrointestinal cancer (GICA) is associated with a higher incidence of venous thromboembolism (VTE) compared to other solid tumors, moreover, recurrent VTE and major bleeding (MB) complications during anticoagulation treatment have an associated increase rate. GICA-VTE remains a challenging clinical scenario with MB concerns for utilization of direct oral anticoagulants (DOAC), especially with active cancer therapies.
• Scott, A. J., & Shroff, R. T. (2019). Moving the Needle Forward With Locoregional Treatment in Unresectable Cholangiocarcinoma-The Jury Is Still Out. JAMA oncology.
• Shroff, R. (2019). Computed Tomography-Based biomarker outcomes in a prospective trial of preoperative FOLFIRINOX and chemoradiation for borderline resectable pancreatic cancer. JCO Precision Oncology. doi:10.1200/PO.19.00001
• Shroff, R. (2019). Outcomes of patients with metastatic pancreatic cancer who progress on first restaging imaging. AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical, 79(Issue 24 Supplement), Abstract B35. doi:10.1158/1538-7445.PANCA19-B35
• Shroff, R. (2019). Safey and activity of ivosidenib in patients with IDH1-mutant advanced cholangiocarcinoma: a phase 1 study. The Lancet Gastroenterology & Hepatology. doi:https://doi.org/10.1016/S2468-1253(19)30189-X
• Shroff, R. T., Javle, M. M., Xiao, L., Kaseb, A. O., Varadhachary, G. R., Wolff, R. A., Raghav, K. P., Iwasaki, M., Masci, P., Ramanathan, R. K., Ahn, D. H., Bekaii-Saab, T. S., & Borad, M. J. (2019). Gemcitabine, Cisplatin, and nab-Paclitaxel for the Treatment of Advanced Biliary Tract Cancers: A Phase 2 Clinical Trial. JAMA oncology, 5(6), 824-830.
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  Administration of gemcitabine-cisplatin, the current standard therapy for advanced biliary tract cancers, results in median progression-free survival and overall survival of 8.0 and 11.7 months, respectively. New treatments offering improved survival outcomes are therefore needed.
• Shroff, R. T., Javle, M. M., Xiao, L., Kaseb, A. O., Varadhachary, G. R., Wolff, R. A., Raghav, K., Iwasaki, M., Masci, P., Ramanathan, R. K., Ahn, D. H., Bekaii-Saab, T. S., & Borad, M. J. (2019). Gemcitabine, Cisplatin, and nab-Paclitaxel for the Treatment of Advanced Biliary Tract Cancers: A Phase 2 Clinical Trial. JAMA ONCOLOGY, 5(6), 824-830.
• Shroff, R. T., Kennedy, E. B., Bachini, M., Bekaii-Saab, T., Crane, C., Edeline, J., El-Khoueiry, A., Feng, M., Katz, M. H., Primrose, J., Soares, H. P., Valle, J., & Maithel, S. K. (2019). Adjuvant Therapy for Resected Biliary Tract Cancer: ASCO Clinical Practice Guideline. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 37(12), 1015-1027.
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  To develop an evidence-based clinical practice guideline to assist in clinical decision making for patients with resected biliary tract cancer.
• Shroff, R. T., Kennedy, E. B., Bachini, M., Bekaii-Saab, T., Crane, C., Edeline, J., El-Khoueiry, A., Feng, M., Katz, M., Primrose, J., Soares, H. P., Valle, J., & Maithel, S. K. (2019). Adjuvant Therapy for Resected Biliary Tract Cancer: ASCO Clinical Practice Guideline. JOURNAL OF CLINICAL ONCOLOGY, 37(12), 1015-+.
• Abdel-Wahab, R., Abdel-Wahab, R., Abdel-Wahab, R., Varadhachary, G. R., Varadhachary, G. R., Varadhachary, G. R., Bhosale, P. R., Bhosale, P. R., Bhosale, P. R., Wang, X., Wang, X., Wang, X., Fogelman, D. R., Fogelman, D. R., Fogelman, D. R., Shroff, R. T., Shroff, R. T., Shroff, R. T., Overman, M. J., , Overman, M. J., et al. (2018). Randomized, phase I/II study of gemcitabine plus IGF-1R antagonist (MK-0646) versus gemcitabine plus erlotinib with and without MK-0646 for advanced pancreatic adenocarcinoma. JOURNAL OF HEMATOLOGY & ONCOLOGY, 11.
• Abdel-Wahab, R., Ali, S. M., Borad, M. J., Shroff, R. T., Kwong, L., & Vauthey, J. (2018). Variations in DNA repair genomic alterations and tumor mutation burden in biliary tract cancer (BTC) subtypes.. JOURNAL OF CLINICAL ONCOLOGY, 36(4).
• Abdel-Wahab, R., Varadhachary, G. R., Bhosale, P. R., Wang, X., Fogelman, D. R., Shroff, R. T., Overman, M. J., Wolff, R. A., & Javle, M. (2018). Randomized, phase I/II study of gemcitabine plus IGF-1R antagonist (MK-0646) versus gemcitabine plus erlotinib with and without MK-0646 for advanced pancreatic adenocarcinoma. Journal of hematology & oncology, 11(1), 71.
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  Binding of insulin-like growth factor-I (IGF-1) to its receptor (IGF-1R) initiates downstream signals that activate PI3K/Akt/mTOR and MEK/Erk pathways, which stimulate cancer cell proliferation and induce drug resistance. Cross talk between IGF-1R and epidermal growth factor receptor (EGFR) mediates resistance to anti-EGFR agents. We studied safety, tolerability, and outcomes of MK-0646, IGF-1 monoclonal antibody, in combination with gemcitabine (G) ± erlotinib (E) in metastatic pancreatic cancer.
• Abdel-wahab, R., Liu, S., Ross, J. S., Schrock, A. B., Ali, S. M., Cao, J., Zhuang, L., Lin, J., Shroff, R. T., Javle, M. M., Wang, K., & Zhao, H. (2018). Genomic diversity between Asian and United States intrahepatic cholangiocarcinoma patients.. Journal of Clinical Oncology, 36(15_suppl), e16137-e16137. doi:10.1200/jco.2018.36.15_suppl.e16137
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  e16137Background: Genetic heterogeneity in intrahepatic cholangiocarcinoma (IHCCA) has been hypothesized based on differing disease etiologies between Eastern and Western population. Our study aim ...
• Abou-Alfa, G. K., Valle, J. W., Kelley, R. K., Goyal, L., Shroff, R. T., Javle, M. M., Borad, M. J., Cleary, J. M., El-Khoueiry, A. B., Bendell, J. C., Macarulla, T. M., Vogel, A., Korth, C., Jiang, L., Gliser, C., Bin, W. u., Agresta, S. V., Pandya, S. S., & Zhu, A. X. (2018). ClarIDHy: A phase 3 multicenter randomized double-blind study of AG-120 versus placebo in patients with non-resectable or metastatic cholangiocarcinoma with an IDH1 mutation.. JOURNAL OF CLINICAL ONCOLOGY, 36(4).
• Borad, M. J., Shroff, R. T., Abou-Alfa, G. K., Hecht, J. R., Bullock, A. J., Ritch, P. S., Chondros, D., Muhsin, M., & Oh, D. (2018). HALO 110-101: A phase Ib, randomized, open-label study of PEGPH20 (pegvorhyaluronidase alfa) in combination with cisplatin (CIS) plus gemcitabine (GEM) (PEGCISGEM) or atezolizumab and CIS plus GEM (PEGCISGEMATEZO) in hyaluronan-high subjects with locally advanced or metastatic cholangiocarcinoma and gallbladder cancer.. JOURNAL OF CLINICAL ONCOLOGY, 36(4).
• Elganainy, D., Holliday, E. B., Taniguchi, C. M., Smith, G. L., Shroff, R., Javle, M., Raghav, K., Kaseb, A., Aloia, T. A., Vauthey, J. N., Tzeng, C. D., Herman, J. M., Koong, A. C., Krishnan, S. X., Minsky, B. D., Crane, C. H., Das, P., & Koay, E. J. (2018). Dose escalation of radiotherapy in unresectable extrahepatic cholangiocarcinoma. CANCER MEDICINE, 7(10), 4880-4892.
• Elganainy, D., Holliday, E. B., Taniguchi, C. M., Smith, G. L., Shroff, R., Javle, M., Raghav, K., Kaseb, A., Aloia, T. A., Vauthey, J. N., Tzeng, C. D., Herman, J. M., Koong, A. C., Krishnan, S. X., Minsky, B. D., Crane, C. H., Das, P., & Koay, E. J. (2018). Dose escalation of radiotherapy in unresectable extrahepatic cholangiocarcinoma. Cancer medicine, 7(10), 4880-4892.
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  To evaluate the effect of escalated dose radiation therapy (EDR, defined as doses >50.4 Gy in 28 fractions [59.5 Gy BED]) on overall survival (OS), freedom from local progression (FFLP), and freedom from distant progression (FFDP) of patients with unresectable extrahepatic cholangiocarcinoma (EHCC).
• Fogelman, D. R., Townson, S. M., Varadhachary, G. R., Javle, M. M., Shroff, R. T., Wolff, R. A., Overman, M. J., Ho, L., Haras, A. V., Lustig, T. M., Sorani, E., Lane, M. E., Kaufman, D. R., & Yao, J. C. (2018). A pilot study to assess the efficacy, safety, and pharmacodynamic effects of pembrolizumab and BL-8040 in patients with metastatic pancreatic cancer.. JOURNAL OF CLINICAL ONCOLOGY, 36(4).
• Golan, T., Varadhachary, G. R., Sela, T., Fogelman, D. R., Halperin, N., & Shroff, R. T. (2018). Phase II study of olaparib for BRCAness phenotype in pancreatic cancer.. JOURNAL OF CLINICAL ONCOLOGY, 36(4).
• Goyal, L., Mody, K., Parikh, A., Reyes, S., Maurer, J. R., Corcoran, R. B., Cusnir, M., Nagy, B., Javle, M., Zhu, A. X., Tan, B. R., Shroff, R. T., Morse, M. A., Lanman, R. B., Kiedrowski, L. A., Kelley, R. K., Fanta, P. T., & Catenacci, D. V. (2018). Abstract A183: Blood-based genomic profiling of cell-free tumor DNA (ctDNA) in patients with biliary tract cancer. Molecular Cancer Therapeutics, 17. doi:10.1158/1535-7163.targ-17-a183
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  Background: Targeted therapies are increasingly under evaluation in clinical trials for the treatment of biliary tract cancer (BTC), and cell-free tumor DNA assays are an emerging technology for the detection of actionable alterations. Methods: ctDNA analysis was performed in patients with BTC using the CLIA-certified Guardant360 liquid biopsy assay as part of routine clinical care. The assay screens up to 73 genes for single-nucleotide variants (SNVs), 23 for insertions or deletions (INDELs), 18 for copy number variations (CNVs), and 6 for fusions. Results: 855 samples were analyzed from 751 unique BTC patients. Median age was 64 years (range, 29-89), 53% were female, and 631 (84%) had at least one alteration in their first sample. In the 751 patients, the most common genes altered were TP53 (39%), KRAS (15%), PIK3CA (13%), ARID1A (13%), EGFR (11%), FGFR2 (11%), ERBB2 (11%), NF1 (10%), IDH1 (10%), APC (9%), BRAF (9%), MYC (8%), MET (7%), CCNE1 (7%), and FGFR1 (7%). Alterations in DNA damage response genes were also seen, including BRCA2 (6%), BRCA1 (5%), ATM (4%), and MLH1 (1%). The median number of alterations per sample was 3 (range, 0-40). In a clinically annotated dataset from the Massachusetts General Hospital Cancer Center, 112 samples were obtained from 61 unique patients. Among these, 52 (85%) had intrahepatic cholangiocarcinoma (ICC), 3 (5%) had extrahepatic cholangiocarcinoma, and 6 (10%) had gallbladder cancer. 20/61 (33%) patients were treated with targeted therapy. Among 20 patients with both ctDNA and tumor sequencing results, the targetable mutation was found in both ctDNA and tumor tissue in 7/20 (35%), solely in ctDNA in 1/20 (5%), and solely in tissue in 12/20 (60%) patients. The patient with the alteration detected solely in ctDNA had insufficient tissue for analysis; she was found to have an FGFR2 F276C mutation and benefited for 8.5 months from an FGFR inhibitor on a clinical trial. Of the 12 patients whose targetable mutation was not detected in plasma, 10 (83%) had an FGFR2 fusion, 1 had an INDEL in FGFR2 (Leu262_Ala266delinsAsp), and 1 had an FGFR3 splice site mutation. 15/20 (75%) patients treated with targeted therapy were followed with serial ctDNA analysis, and a potential resistance mechanism was identified in 5/15 (33%). All 5 patients had FGFR2-fusion positive ICC and developed mutations in the FGFR2 kinase domain as a potential resistance mechanism to FGFR inhibition, including the FGFR2 V564F gatekeeper mutation in 4/5 patients. Conclusions: In patients with BTC, ctDNA-based genomic profiling can detect alterations in IDH, FGFR, PIK3CA, ERBB2, BRAF, and MET. The technology is still evolving for the detection of FGFR2 fusions, which is hindered in capture-based methods in plasma by the large number of unique breakpoints and fusion partners. ctDNA analysis may also provide a noninvasive mechanism to study resistance to targeted therapy and clonal dynamics in BTC. Citation Format: Lipika Goyal, Robin Kate Kelley, Lesli Kiedrowski, Daniel Catenacci, Kabir Mody, Rachna Shroff, Aparna Parikh, Stephanie Reyes, Jordan R. Maurer, Ryan B. Corcoran, Paul Fanta, Mike Cusnir, Becky Nagy, Richard Lanman, Michael Morse, Benjamin Tan, Milind Javle, Andrew Zhu. Blood-based genomic profiling of cell-free tumor DNA (ctDNA) in patients with biliary tract cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A183.
• Gulhati, P., Prakash, L., Katz, M. H., Wang, X., Javle, M., Shroff, R., Fogelman, D., Lee, J. E., Tzeng, C. D., Lee, J. H., Weston, B., Tamm, E., Bhosale, P., Koay, E. J., Maitra, A., Wang, H., Wolff, R. A., & Varadhachary, G. R. (2018). First-Line Gemcitabine and Nab-Paclitaxel Chemotherapy for Localized Pancreatic Ductal Adenocarcinoma. Annals of surgical oncology.
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  Preoperative chemotherapy provides early treatment of micro-metastases and guaranteed delivery of all components of multimodality therapy for localized pancreatic ductal adenocarcinoma (PDAC). For locally advanced (LA) PDAC, induction chemotherapy is the standard of care. This study evaluated the use of gemcitabine and nab-paclitaxel (Gem/nab-P) as first-line therapy for localized PDAC.
• Gulhati, P., Prakash, L., Katz, M., Wang, X., Javle, M. M., & Shroff, R. T. (2018). First line gemcitabine and nab-paclitaxel chemotherapy for localized pancreatic ductal adenocarcinoma.. JOURNAL OF CLINICAL ONCOLOGY, 36(4).
• Gulhati, P., Raghav, K., Shroff, R., Varadhachary, G., Javle, M., Qiao, W., Wang, H., Morris, J., Wolff, R., & Overman, M. J. (2018). Phase II Study of Panitumumab in RAS Wild-Type Metastatic Adenocarcinoma of Small Bowel or Ampulla of Vater. ONCOLOGIST, 23(3), 277-+.
• Gulhati, P., Raghav, K., Shroff, R., Varadhachary, G., Javle, M., Qiao, W., Wang, H., Morris, J., Wolff, R., & Overman, M. J. (2018). Phase II Study of Panitumumab in RAS Wild-Type Metastatic Adenocarcinoma of Small Bowel or Ampulla of Vater. The oncologist, 23(3), 277-e26.
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  Panitumumab has no clinical activity in metastatic RAS wild-type small bowel adenocarcinoma (SBA) and ampullary adenocarcinoma (AAC), possibly due to the foregut and midgut derivation of small bowel and ampulla.These results, along with findings from genomic characterization of SBA, suggest that SBA represents a unique intestinal malignancy and treatments should not be habitually extrapolated from colorectal cancer.Further studies evaluating the benefit of targeted therapies exclusively in SBA and AAC are warranted.
• Jadhav, P., Rogers, J. E., & Shroff, R. (2018). A Case Report-Stevens-Johnson Syndrome as an Adverse Effect of Capecitabine. Journal of gastrointestinal cancer, 49(3), 349-350.
• Jain, A., Borad, M. J., Kelley, R. K., Wang, Y., Abdel-Wahab, R., Meric-Bernstam, F., Baggerly, K. A., Kaseb, A. O., Al-Shamsi, H. O., Ahn, D. H., DeLeon, T., Bocobo, A. G., Bekaii-Saab, T., Shroff, R. T., & Javle, M. (2018). Cholangiocarcinoma With Genetic Aberrations: A Unique Clinical Phenotype. JCO precision oncology, 2, 1-12.
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  genetic aberrations (GAs) occur in an estimated 10% to 16% of intrahepatic cholangiocarcinomas (CCAs). The natural history of CCA with GAs, the prognostic role of coexisting GAs, and the outcome with FGFR-targeted inhibitors are unknown.
• Jain, A., Borad, M. J., Kelley, R. K., Wang, Y., Abdel-wahab, R., Meric-bernstam, F., Baggerly, K. A., Kaseb, A. O., Al-shamsi, H. O., Ahn, D. H., Deleon, T., Bocobo, A. G., Bekaii-saab, T., Shroff, R. T., & Javle, M. (2018). Cholangiocarcinoma With FGFR Genetic Aberrations: A Unique Clinical Phenotype. JCO Precision Oncology, 2(2), 1-12. doi:10.1200/po.17.00080
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  PurposeFGFR genetic aberrations (GAs) occur in an estimated 10% to 16% of intrahepatic cholangiocarcinomas (CCAs). The natural history of CCA with FGFR GAs, the prognostic role of coexisting GAs, and the outcome with FGFR-targeted inhibitors are unknown.Patients and MethodsPatients with CCA with FGFR GAs were identified using next-generation sequencing or fluorescence in situ hybridization from four tertiary cancer centers and compared with FGFR wild-type counterparts. Data reviewed included demographic, treatment, overall survival (OS), and GA data. Fisher’s exact test, Kaplan-Meier plots, and log-rank tests were used for statistical analysis.ResultsThree hundred seventy-seven patients with CCA were identified, and 95 had FGFR GAs. FGFR2 GA was most common (n = 74, with 63 fusions) and seen in intrahepatic CCA. In patients with CCA, FGFR GAs occurred more frequently in younger patients (≤ 40 years; 20%) compared with older patients (> 40 years; 6.7%; P < .001), presented at an earlier stage (TNM stage I/...
• Javle, M. M., Xiao, L., Varadhachary, G. R., Wolff, R. A., Shroff, R. T., Raghav, K. P., & Mizrahi, J. D. (2018). A phase II study of ramucirumab for advanced, pre-treated biliary cancers.. Journal of Clinical Oncology, 36(15_suppl), 4081-4081. doi:10.1200/jco.2018.36.15_suppl.4081
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  4081Background: Biliary cancers (BC) have no clear second-line therapy in advanced disease after progression on standard of care gemcitabine and cisplatin. Angiogenesis has been shown to be a poten...
• Javle, M., Lowery, M., Shroff, R. T., Weiss, K. H., Springfeld, C., Borad, M. J., Ramanathan, R. K., Goyal, L., Sadeghi, S., Macarulla, T., El-Khoueiry, A., Kelley, R. K., Borbath, I., Choo, S. P., Oh, D. Y., Philip, P. A., Chen, L. T., Reungwetwattana, T., Van Cutsem, E., , Yeh, K. H., et al. (2018). Phase II Study of BGJ398 in Patients With FGFR-Altered Advanced Cholangiocarcinoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 36(3), 276-282.
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  Purpose No standard treatment exists for patients with cholangiocarcinoma for whom first-line gemcitabine-based therapy fails. Fibroblast growth factor receptor 2 ( FGFR2) fusions/translocations are present in 13% to 17% of intrahepatic cholangiocarcinomas. BGJ398, an orally bioavailable, selective pan-FGFR kinase inhibitor, has shown preliminary clinical activity against tumors with FGFR alterations. Methods A multicenter, open-label, phase II study ( ClinicalTrials.gov identifier: NCT02150967) evaluated BGJ398 antitumor activity in patients age ≥ 18 years with advanced or metastatic cholangiocarcinoma containing FGFR2 fusions or other FGFR alterations whose disease had progressed while receiving prior therapy. Patients received BGJ398 125 mg once daily for 21 days, then 7 days off (28-day cycles). The primary end point was investigator-assessed overall response rate. Results Sixty-one patients (35 women; median age, 57 years) with FGFR2 fusion (n = 48), mutation (n = 8), or amplification (n = 3) participated. At the prespecified data cutoff (June 30, 2016), 50 patients had discontinued treatment. All responsive tumors contained FGFR2 fusions. The overall response rate was 14.8% (18.8% FGFR2 fusions only), disease control rate was 75.4% (83.3% FGFR2 fusions only), and estimated median progression-free survival was 5.8 months (95% CI, 4.3 to 7.6 months). Adverse events included hyperphosphatemia (72.1% all grade), fatigue (36.1%), stomatitis (29.5%), and alopecia (26.2%). Grade 3 or 4 treatment-related adverse events occurred in 25 patients (41%) and included hyperphosphatemia (16.4%), stomatitis (6.6%), and palmar-plantar erythrodysesthesia (4.9%). Conclusion BGJ398 is a first-in-class FGFR kinase inhibitor with manageable toxicities that shows meaningful clinical activity against chemotherapy-refractory cholangiocarcinoma containing FGFR2 fusions. This promising antitumor activity supports continued development of BGJ398 in this highly selected patient population.
• Javle, M., Lowery, M., Shroff, R. T., Weiss, K. H., Springfeld, C., Borad, M. J., Ramanathan, R. K., Goyal, L., Sadeghi, S., Macarulla, T., El-Khoueiry, A., Kelley, R. K., Borbath, I., Choo, S. P., Oh, D., Philip, P. A., Chen, L., Reungwetwattana, T., Van, C. E., , Yeh, K., et al. (2018). Phase II Study of BGJ398 in Patients With FGFR-Altered Advanced Cholangiocarcinoma. JOURNAL OF CLINICAL ONCOLOGY, 36(3), 276-+.
• Koay, E. J., Lee, Y., Cristini, V., Lowengrub, J. S., Kang, Y., Lucas, F. A., Hobbs, B. P., Ye, R., Elganainy, D., Almahariq, M., Amer, A. M., Chatterjee, D., Yan, H., Park, P. C., Rios Perez, M. V., Li, D., Garg, N., Reiss, K. A., Yu, S., , Chauhan, A., et al. (2018). A Visually Apparent and Quantifiable CT Imaging Feature Identifies Biophysical Subtypes of Pancreatic Ductal Adenocarcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research, 24(23), 5883-5894.
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  Pancreatic ductal adenocarcinoma (PDAC) is a heterogeneous disease with variable presentations and natural histories of disease. We hypothesized that different morphologic characteristics of PDAC tumors on diagnostic computed tomography (CT) scans would reflect their underlying biology.
• Koay, E. J., Lee, Y., Cristini, V., Lowengrub, J. S., Kang, Y., Lucas, F., Hobbs, B. P., Ye, R., Elganainy, D., Almahariq, M., Amer, A. M., Chatterjee, D., Yan, H., Park, P. C., Perez, M. R., Li, D., Garg, N., Reiss, K. A., Yu, S., , Chauhan, A., et al. (2018). A Visually Apparent and Quantifiable CT Imaging Feature Identifies Biophysical Subtypes of Pancreatic Ductal Adenocarcinoma. CLINICAL CANCER RESEARCH, 24(23), 5883-5894.
• Lee, J., Kukreja, K., Glover, M. T., DaVee, T., Lanke, G., Deep, A., Nogueras-Gonzalez, G. M., Lum, P., Raju, G. S., Weston, B. R., Wolff, R., Varadhachary, G. R., Shroff, R., & Ross, W. A. (2018). COMPARISON OF THE PERFORMANCE OF COVERED METAL STENTS AND UNCOVERED METAL STENTS IN THE MANAGEMENT OF MALIGNANT BILIARY STRICTURES (MBO) IN 1012 PATIENTS. GASTROINTESTINAL ENDOSCOPY, 87(6), AB580-AB580.
• Lunsford, K. E., Javle, M., Heyne, K., Shroff, R. T., Abdel-Wahab, R., Gupta, N., Mobley, C. M., Saharia, A., Victor, D. W., Nguyen, D. T., Graviss, E. A., Kaseb, A. O., McFadden, R. S., Aloia, T. A., Conrad, C., Li, X. C., Monsour, H. P., Gaber, A. O., Vauthey, J. N., , Ghobrial, R. M., et al. (2018). Liver transplantation for locally advanced intrahepatic cholangiocarcinoma treated with neoadjuvant therapy: a prospective case-series. The lancet. Gastroenterology & hepatology, 3(5), 337-348.
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  At present, intrahepatic cholangiocarcinoma is a contraindication for liver transplantation. However, previous studies in this field did not preselect patients on the basis of chemosensitivity or disease trajectory after neoadjuvant therapy. Experience with hilar cholangiocarcinoma has indicated that neoadjuvant therapy followed by liver transplantation in patients without disease progression results in a long-term survival benefit. We aimed to establish the potential efficacy of liver transplantation in patients with biologically responsive intrahepatic cholangiocarcinoma who have had sustained tumour stability or regression with neoadjuvant therapy.
• Lunsford, K. E., Lunsford, K. E., Lunsford, K. E., Lunsford, K. E., Javle, M., Javle, M., Javle, M., Javle, M., Heyne, K., Heyne, K., Heyne, K., Heyne, K., Shroff, R. T., Shroff, R. T., Shroff, R. T., Shroff, R. T., Abdel-Wahab, R., Abdel-Wahab, R., Abdel-Wahab, R., , Abdel-Wahab, R., et al. (2018). Liver transplantation for locally advanced intrahepatic cholangiocarcinoma treated with neoadjuvant therapy: a prospective case-series. LANCET GASTROENTEROLOGY & HEPATOLOGY, 3(5), 337-348.
• Marcus, R., Lillemoe, H. A., Abdel-Wahab, R., Shroff, R. T., Javle, M. M., & Aloia, T. A. (2018). The impact of tumor genomic profile on the effectiveness of adjuvant chemotherapy in resectable intrahepatic cholangiocarcinoma.. JOURNAL OF CLINICAL ONCOLOGY, 36(4).
• Overman, M. J., Adam, L., Wang, J., Eng, C., Vilar, E., Dasari, A., Karunasena, E., Pisanic, R., Kopetz, S., Wolff, R. A., Shroff, R. T., Raghav, K. P., Pisanic, T. R., Morris, J. S., Kee, B. K., Fogelman, D. R., & Azad, N. S. (2018). Phase II study of nab-paclitaxel in refractory small bowel adenocarcinoma and CpG island methylator phenotype (CIMP)-high colorectal cancer.. Annals of oncology : official journal of the European Society for Medical Oncology, 29(1), 139-144. doi:10.1093/annonc/mdx688
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  Hypermethylation of promoter CpG islands [CpG island methylator phenotype (CIMP)] represents a unique pathway for the development of colorectal cancer (CRC), characterized by lack of chromosomal instability and a low rate of adenomatous polyposis coli (APC) mutations, which have both been correlated with taxane resistance. Similarly, small bowel adenocarcinoma (SBA), a rare tumor, also has a low rate of APC mutations. This phase II study evaluated taxane sensitivity in SBA and CIMP-high CRC..The primary objective was Response Evaluation Criteria in Solid Tumors version 1.1 response rate. Eligibility included Eastern Cooperative Oncology Group performance status 0/1, refractory disease, and SBA or CIMP-high metastatic CRC. Nab-paclitaxel was initially administered at a dose of 260 mg/m2 every 3 weeks but was reduced to 220 mg/m2 owing to toxicity..A total of 21 patients with CIMP-high CRC and 13 with SBA were enrolled from November 2012 to October 2014. The efficacy-assessable population (patients who received at least three doses of the treatment) comprised 15 CIMP-high CRC patients and 10 SBA patients. Common grade 3 or 4 toxicities were fatigue (12%), neutropenia (9%), febrile neutropenia (9%), dehydration (6%), and thrombocytopenia (6%). No responses were seen in the CIMP-high CRC cohort and two partial responses were seen in the SBA cohort. Median progression-free survival was significantly greater in the SBA cohort than in the CIMP-high CRC cohort (3.2 months compared with 2.1 months, P = 0.03). Neither APC mutation status nor CHFR methylation status correlated with efficacy in the CIMP-high CRC cohort. In vivo testing of paclitaxel in an SBA patient-derived xenograft validated the activity of taxanes in this disease type..Although preclinical studies suggested taxane sensitivity was associated with chromosomal stability and wild-type APC, we found that nab-paclitaxel was inactive in CIMP-high metastatic CRC. Nab-paclitaxel may represent a novel therapeutic option for SBA.
• Shroff, R. T., Hendifar, A., McWilliams, R. R., Geva, R., Epelbaum, R., Rolfe, L., Goble, S., Lin, K. K., Biankin, A. V., Giordano, H., Vonderheide, R. H., & Domchek, S. M. (2018). Rucaparib Monotherapy in Patients With Pancreatic Cancer and a Known Deleterious Mutation. JCO precision oncology, 2018.
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  Pancreatic cancer has a poor prognosis and limited treatment options. Approximately 9% of pancreatic cancers harbor a germline or somatic or () mutation. Because poly (ADP-ribose) polymerase inhibitors have significant activity in -mutant ovarian and breast cancers, RUCAPANC investigated the efficacy and safety of rucaparib in -mutant pancreatic cancer.
• Shroff, R. T., Javle, M. M., Xiao, L., Kaseb, A. O., Varadhachary, G. R., & Wolff, R. A. (2018). A phase II trial of gemcitabine (G), cisplatin (C), and nab-paclitaxel (N) in advanced biliary tract cancers (aBTCs): Updated survival analysis.. JOURNAL OF CLINICAL ONCOLOGY, 36(4).
• Shroff, R. T., Yarchoan, M., O'Connor, A., Gallagher, D., Zahurak, M. L., Rosner, G., Ohaji, C., Sartorius-Mergenthaler, S., Parkinson, R., Subbiah, V., Zinner, R., & Azad, N. S. (2018). The oral VEGF receptor tyrosine kinase inhibitor pazopanib in combination with the MEK inhibitor trametinib in advanced cholangiocarcinoma (vol 116, pg 1402, 2017). BRITISH JOURNAL OF CANCER, 118(2), 1-2.
• Shroff, R. T., Yarchoan, M., O'Connor, A., Gallagher, D., Zahurak, M. L., Rosner, G., Ohaji, C., Sartorius-Mergenthaler, S., Parkinson, R., Subbiah, V., Zinner, R., & Azad, N. S. (2018). The oral VEGF receptor tyrosine kinase inhibitor pazopanib in combination with the MEK inhibitor trametinib in advanced cholangiocarcinoma. British journal of cancer, 118(2), e2.
• Solis, L. M., Foo, W. C., Parra, E. R., Mino, B., Abdel-Wahab, R., Wistuba, I., Kwong, L., Javle, M., & Shroff, R. (2018). Tumor-Associated Inflammatory Cells And Immune-Checkpoints markers Correlates With Clinicopathological Characteristics In Intrahepatic Cholangiocarcinoma (ICC). MODERN PATHOLOGY, 31, 649-650.
• Solis, L. M., Wang, X., Abdel-wahab, R., Chen, H., Foo, W. C., Javle, M. M., Wistuba, I. I., Shroff, R. T., Pestana, R. C., & Kwong, L. N. (2018). Immunoprofiling in intrahepatic cholangiocarcinoma (IHCC).. Journal of Clinical Oncology, 36(15_suppl), 12049-12049. doi:10.1200/jco.2018.36.15_suppl.12049
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  12049Background: Molecular profiling has become important in directing therapy for IHCC, while not much has been described about the immune environment of this disease. Understanding the immune mil...
• , C. G., & , C. G. (2017). Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma. Cancer cell, 32(2), 185-203.e13.
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  We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFβR2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations. Protein profiling identified a favorable prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores. Associations of non-coding RNAs with tumor-specific mRNA subtypes were also identified. Our integrated multi-platform analysis reveals a complex molecular landscape of PDAC and provides a roadmap for precision medicine.
• Ahn, D. H., Bekaii-Saab, T. S., Borad, M. J., Iwasaki, M., Javle, M. M., Kaseb, A. O., Masci, P., Raghav, K. P., Ramanathan, R. K., Shroff, R. T., Varadhachary, G. R., Wolff, R. A., & Xiao, L. (2017).

  A phase II trial of gemcitabine (G), cisplatin (C), and nab-paclitaxel (N) in advanced biliary tract cancers (aBTCs).

  . Journal of Clinical Oncology, 35(15_suppl), 4018-4018. doi:10.1200/jco.2017.35.15_suppl.4018
• Cloyd, J. M., Chun, Y. S., Denbo, J., Javle, M., Shroff, R., Vauthey, J. N., Aloia, T., Cuddy, A., Rodriguez-Bigas, M. A., & You, Y. N. (2017). LONG-TERM SURVIVAL AMONG MISMATCH REPAIR DEFICIENT CHOLANGIOCARCINOMAS ASSOCIATED WITH LYNCH SYNDROME. GASTROENTEROLOGY, 152(5), S1254-S1254.
• Cloyd, J. M., Chun, Y. S., Javle, M., Vauthey, J. N., Cuddy, A., Rodriguez-bigas, M. A., You, Y. N., Shroff, R. T., Denbo, J. W., & Aloia, T. A. (2017). Long-Term Survival Among Mismatch Repair Deficient Cholangiocarcinomas Associated with Lynch Syndrome. Gastroenterology, 152(5), S1254. doi:10.1016/s0016-5085(17)34175-6
• Cloyd, J. M., Katz, M. H., Prakash, L., Varadhachary, G. R., Wolff, R. A., Shroff, R. T., Javle, M., Fogelman, D., Overman, M., Crane, C. H., Koay, E. J., Das, P., Krishnan, S., Minsky, B. D., Lee, J. H., Bhutani, M. S., Weston, B., Ross, W., Bhosale, P., , Tamm, E. P., et al. (2017). Preoperative Therapy and Pancreatoduodenectomy for Pancreatic Ductal Adenocarcinoma: a 25-Year Single-Institution Experience. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract, 21(1), 164-174.
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  The purpose of this study was to evaluate a single-institution experience with delivery of preoperative therapy to patients with pancreatic ductal adenocarcinoma (PDAC) prior to pancreatoduodenectomy (PD).
• Cloyd, J. M., Katz, M., Prakash, L., Varadhachary, G. R., Wolff, R. A., Shroff, R. T., Javle, M., Fogelman, D., Overman, M., Crane, C. H., Koay, E. J., Das, P., Krishnan, S., Minsky, B. D., Lee, J. H., Bhutani, M. S., Weston, B., Ross, W., Bhosale, P., , Tamm, E. P., et al. (2017). Preoperative Therapy and Pancreatoduodenectomy for Pancreatic Ductal Adenocarcinoma: a 25-Year Single-Institution Experience. JOURNAL OF GASTROINTESTINAL SURGERY, 21(1), 164-174.
• Cloyd, J. M., Wang, H., Egger, M. E., Tzeng, C. D., Prakash, L. R., Maitra, A., Varadhachary, G. R., Shroff, R., Javle, M., Fogelman, D., Wolff, R. A., Overman, M. J., Koay, E. J., Das, P., Herman, J. M., Kim, M. P., Vauthey, J. N., Aloia, T. A., Fleming, J. B., , Lee, J. E., et al. (2017). Association of Clinical Factors With a Major Pathologic Response Following Preoperative Therapy for Pancreatic Ductal Adenocarcinoma. JAMA surgery, 152(11), 1048-1056.
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  We previously demonstrated that a major pathologic response to preoperative therapy, defined histopathologically by the presence of less than 5% viable cancer cells in the surgical specimen, is an important prognostic factor for patients with pancreatic ductal adenocarcinoma. However, to our knowledge, the patients most likely to experience a significant response to therapy are undefined.
• Cloyd, J. M., Wang, H., Egger, M. E., Tzeng, C. D., Prakash, L. R., Maitra, A., Varadhachary, G. R., Shroff, R., Javle, M., Fogelman, D., Wolff, R. A., Overman, M. J., Koay, E. J., Das, P., Herman, J. M., Kim, M. P., Vauthey, J., Aloia, T. A., Fleming, J. B., , Lee, J. E., et al. (2017). Association of Clinical Factors With a Major Pathologic Response Following Preoperative Therapy for Pancreatic Ductal Adenocarcinoma. JAMA SURGERY, 152(11), 1048-1056.
• Cloyd, J. M., Wang, H., Overman, M., Zhao, J., Denbo, J., Prakash, L., Kim, M. P., Shroff, R., Javle, M., Varadhachary, G. R., Fogelman, D., Wolff, R. A., Koay, E. J., Das, P., Maitra, A., Aloia, T. A., Vauthey, J. N., Fleming, J. B., Lee, J. E., & Katz, M. H. (2017). Influence of Preoperative Therapy on Short- and Long-Term Outcomes of Patients with Adenocarcinoma of the Ampulla of Vater. Annals of surgical oncology, 24(7), 2031-2039.
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  Although preoperative therapy is increasingly administered to patients with pancreatic adenocarcinoma, the role of preoperative therapy for patients with adenocarcinoma of the ampulla of Vater is undefined.
• Cloyd, J. M., Wang, H., Overman, M., Zhao, J., Denbo, J., Prakash, L., Kim, M. P., Shroff, R., Javle, M., Varadhachary, G. R., Fogelman, D., Wolff, R. A., Koay, E. J., Das, P., Maitra, A., Aloia, T. A., Vauthey, J., Fleming, J. B., Lee, J. E., & Katz, M. (2017). Influence of Preoperative Therapy on Short- and Long-Term Outcomes of Patients with Adenocarcinoma of the Ampulla of Vater. ANNALS OF SURGICAL ONCOLOGY, 24(7), 2031-2039.
• Farshidfar, F., Zheng, S., Gingras, M. C., Newton, Y., Shih, J., Robertson, A. G., Hinoue, T., Hoadley, K. A., Gibb, E. A., Roszik, J., Covington, K. R., Wu, C. C., Shinbrot, E., Stransky, N., Hegde, A., Yang, J. D., Reznik, E., Sadeghi, S., Pedamallu, C. S., , Ojesina, A. I., et al. (2017). Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles. Cell reports, 18(11), 2780-2794.
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  Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance.
• Farshidfar, F., Zheng, S., Gingras, M., Newton, Y., Shih, J., Robertson, A. G., Hinoue, T., Hoadley, K. A., Gibb, E. A., Roszik, J., Covington, K. R., Wu, C., Shinbrot, E., Stransky, N., Hegde, A., Yang, J. D., Reznik, E., Sadeghi, S., Pedamallu, C. S., , Ojesina, A. I., et al. (2017). Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles.. Cell reports, 19(13), 2878-2880. doi:10.1016/j.celrep.2017.06.008
• Fogelman, D. R., Xiao, L., Vadhan, S., Javle, S., Maitra, A., Wang, X. S., Wolff, R. A., Vence, L. M., Varadhachary, G. R., Shroff, R. T., Overman, M. J., Morris, J. S., Hassan, M. M., & Cleeland, C. S. (2017). A predictive model of inflammatory markers and patient-reported symptoms for cachexia in newly diagnosed pancreatic cancer patients.. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 25(6), 1809-1817. doi:10.1007/s00520-016-3553-z
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  Cachexia is a frequent manifestation of pancreatic cancer, can limit a patient's ability to take chemotherapy, and is associated with shortened survival. We developed a model to predict the early onset of cachexia in advanced pancreatic cancer patients..Patients with newly diagnosed, untreated metastatic or locally advanced pancreatic cancer were included. Serum cytokines were drawn prior to therapy. Patient symptoms were recorded using the M.D. Anderson Symptom Inventory (MDASI). Our primary endpoint was either 10% weight loss or death within 60 days of the start of therapy..Twenty-seven of 89 patients met the primary endpoint (either having lost 10% of body weight or having died within 60 days of the start of treatment). In a univariate analysis, smoking, history symptoms of pain and difficulty swallowing, high levels of MK, CXCL-16, IL-6, TNF-a, and low IL-1b all correlated with this endpoint. We used recursive partition to fit a regression tree model, selecting four of 26 variables (CXCL-16, IL-1b, pain, swallowing difficulty) as important in predicting cachexia. From these, a model of two cytokines (CXCL-16 > 5.135 ng/ml and IL-1b < 0.08 ng/ml) demonstrated a better sensitivity and specificity for this outcome (0.70 and 0.86, respectively) than any individual cytokine or tumor marker..Cachexia is frequent in pancreatic cancer; one in three patients met our endpoint of 10% weight loss or death within 60 days. Inflammatory cytokines are better than conventional tumor markers at predicting this outcome. Recursive partitioning analysis suggests that a model of CXCL-16 and IL-1B may offer a better ability than individual cytokines to predict this outcome.
• Golan, T., Raitses-Gurevich, M., Kelley, R. K., Bocobo, A. G., Borgida, A., Shroff, R. T., Holter, S., Gallinger, S., Ahn, D. H., Aderka, D., Apurva, J., Bekaii-Saab, T., Friedman, E., & Javle, M. (2017). Overall Survival and Clinical Characteristics of BRCA-Associated Cholangiocarcinoma: A Multicenter Retrospective Study. ONCOLOGIST, 22(7), 804-810.
• Golan, T., Raitses-Gurevich, M., Kelley, R. K., Bocobo, A. G., Borgida, A., Shroff, R. T., Holter, S., Gallinger, S., Ahn, D. H., Aderka, D., Apurva, J., Bekaii-Saab, T., Friedman, E., & Javle, M. (2017). Overall Survival and Clinical Characteristics of BRCA-Associated Cholangiocarcinoma: A Multicenter Retrospective Study. The oncologist, 22(7), 804-810.
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  Biliary tract malignancies, in particular cholangiocarcinomas (CCA), are rare tumors that carry a poor prognosis. mutation carriers have an increased risk of developing CCA with a reported relative risk of ∼5 according to the Breast Cancer Linkage Consortium. In addition to this risk, there are potential therapeutic implications in those harboring somatic and/or germline (GL) mutations. Therefore, it is important to define the clinical characteristics of GL/somatic variants in CCA patients.
• Goldstein, J. B., Zhao, L. i., Javle, M. M., Overman, M. J., Shroff, R. T., Varadhachary, G. R., Wolff, R. A., Futreal, P. A., & Fogelman, D. R. (2017). Characterization of germ line genomic alterations in familial pancreas cancer.. JOURNAL OF CLINICAL ONCOLOGY, 35.
• Goyal, L., Reyes, S., Jain, A., Shroff, R. T., Le, T. M., & Rahma, O. E. (2017). Clinical features and tumor mutational profile of younger versus older patients with cholangiocarcinoma (CCA).. JOURNAL OF CLINICAL ONCOLOGY, 35(4).
• Gulhati, P., Raghav, K., Shroff, R. T., Varadhachary, G. R., Javle, M. M., Qiao, W., Wang, H., Morris, J., Wolff, R. A., & Overman, M. J. (2017). Phase II study of panitumumab in KRAS wild -type metastatic adenocarcinoma of the small bowel or ampulla of vater.. JOURNAL OF CLINICAL ONCOLOGY, 35.
• Gulhati, P., Raghav, K., Shroff, R. T., Varadhachary, G. R., Kopetz, S., Javle, M., Qiao, W., Wang, H., Morris, J., Wolff, R. A., & Overman, M. J. (2017). Bevacizumab Combined With Capecitabine and Oxaliplatin in Patients With Advanced Adenocarcinoma of the Small Bowel or Ampulla of Vater: A Single-Center, Open-Label, Phase 2 Study. CANCER, 123(6), 1011-1017.
• Gulhati, P., Raghav, K., Shroff, R. T., Varadhachary, G. R., Kopetz, S., Javle, M., Qiao, W., Wang, H., Morris, J., Wolff, R. A., & Overman, M. J. (2017). Bevacizumab combined with capecitabine and oxaliplatin in patients with advanced adenocarcinoma of the small bowel or ampulla of vater: A single-center, open-label, phase 2 study. Cancer, 123(6), 1011-1017.
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  Capecitabine with oxaliplatin (CAPOX) has previously demonstrated clinical activity in patients with small bowel adenocarcinoma (SBA) and ampullary adenocarcinoma (AAC). Herein, the authors conducted a phase 2 trial to evaluate the benefit of adding bevacizumab to CAPOX.
• Jain, A., Shroff, R. T., Zuo, M., Weatherly, J., Meric-Bernstam, F., Isaacs, R., Ali, S. M., Bekaii-Saab, T. S., & Javle, M. M. (2017). Tumor mutational burden (TMB) and co-existing actionable mutations in biliary tract cancers (BTC).. JOURNAL OF CLINICAL ONCOLOGY, 35.
• Janku, F., De, G., Javle, M. M., Penas-Prado, M., Shroff, R. T., Luthra, R., Banks, K., Lanman, R. B., Conley, A. P., Broaddus, R., Davies, M. A., Kopetz, S., Yung, W., Heymach, J., Fu, S., Shaw, K. R., & Meric-Bernstam, F. (2017). Simultaneous molecular alterations in solid tumors with IDH1 or IDH2 mutations.. JOURNAL OF CLINICAL ONCOLOGY, 35.
• Janku, F., Huang, H. J., Shroff, R. T., Javle, M., Conley, A. P., Raina, A., Holley, V. R., Naing, A., Karp, D. D., Fogelman, D., Kaseb, A. O., Luthra, R., Karlin-Neumann, G. A., & Meric-Bernstam, F. (2017). Detection and monitoring of IDH mutations in unamplified plasma cell-free DNA in patients with advanced cancers treated with IDH inhibitors. CANCER RESEARCH, 77.
• Javle, M. M., Catenacci, D., Jain, A., Young, L., Wang, K., Chung, J., Hezel, A. F., Schrock, A. B., Goyal, L., Gay, L. M., Ahn, D. H., Kelley, R. K., Ganesan, S., Stephens, P., Miller, V. A., Ali, S. M., Bekaii-Saab, T. S., Shroff, R. T., & Ross, J. S. (2017). Precision medicine for gallbladder cancer using somatic copy number amplifications (SCNA) and DNA repair pathway gene alterations.. JOURNAL OF CLINICAL ONCOLOGY, 35.
• Katz, M. H., Varadhachary, G. R., Bauer, T. W., Acquavella, N., Merchant, N. B., Le, T. M., Javle, M. M., Shroff, R. T., Overman, M. J., Fogelman, D. R., Petroni, G. R., Slingluff, C. L., & Rahma, O. E. (2017). Preliminary safety data from a randomized multicenter phase Ib/II study of neoadjuvant chemoradiation therapy (CRT) alone or in combination with pembrolizumab in patients with resectable or borderline resectable pancreatic cancer.. Journal of Clinical Oncology, 35(15_suppl), 4125-4125. doi:10.1200/jco.2017.35.15_suppl.4125
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  4125Background: Pancreatic cancer (PC) is a challenging target for immunotherapy.Tumor-infiltrating lymphocytes (TILs) do not reach the PC cells in significant numbers due to the presence of stroma...
• Lowery, M. A., Abou-Alfa, G. K., Burris, H. A., Janku, F., Shroff, R. T., Cleary, J. M., Azad, N. S., Goyal, L., Maher, E. A., Gore, L., Hollebecque, A., Beeram, M., Trent, J. C., Jiang, L., Ishii, Y., Auer, J., Gliser, C., Agresta, S. V., Pandya, S. S., & Zhu, A. X. (2017). Phase I study of AG-120, an IDH1 mutant enzyme inhibitor: Results from the cholangiocarcinoma dose escalation and expansion cohorts.. JOURNAL OF CLINICAL ONCOLOGY, 35.
• Lowery, M. A., Abou-Alfa, G. K., Valle, J. W., Kelley, R. K., Goya, L., Shroff, R. T., Javle, M. M., Borad, M. J., Cleary, J. M., El-Khoueiry, A. B., Bendell, J. C., Macarulla, T., Vogel, A., Korth, C., Jiang, L., Gliser, C., Wu, B., Agresta, S. V., Pandya, S. S., & Zhu, A. X. (2017). ClarIDHy: A phase 3, multicenter, randomized, double-blind study of AG-120 vs placebo in patients with an advanced cholangiocarcinoma with an IDH1 mutation.. JOURNAL OF CLINICAL ONCOLOGY, 35.
• Rogers, J. E., Bolonesi, R. M., Rashid, A., Elsayes, K. M., Elbanan, M. G., Law, L., Kaseb, A., & Shroff, R. T. (2017). Systemic therapy for unresectable, mixed hepatocellular-cholangiocarcinoma: treatment of a rare malignancy. Journal of gastrointestinal oncology, 8(2), 347-351.
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  Combined hepatocellular-cholangiocarcinoma (HCC-CC) has a reported incidence of less than 5% of primary hepatic malignancies. The treatment approach to this malignancy is undefined. Our objective of this case series is to provide some insight into chemotherapy and/or targeted therapy in this setting.
• Shalaby, A., Javle, M. M., Shroff, R. T., Abousamra, A., Abdel-Wahab, R., & Rallapalli, V. (2017). Early obesity and risk of cholangiocarcinoma in the United States.. JOURNAL OF CLINICAL ONCOLOGY, 35(4).
• Shroff, R. T., Borad, M. J., Xiao, L., Kaseb, A. O., Varadhachary, G. R., Wolff, R. A., Raghav, K., Iwasaki, M., Masci, P., Ramanathan, R. K., Ahn, D. H., Bekaii-Saab, T. S., & Javle, M. M. (2017). A phase II trial of gemcitabine (G), cisplatin (C), and nab-paclitaxel (N) in advanced biliary tract cancers (aBTCs).. JOURNAL OF CLINICAL ONCOLOGY, 35.
• Shroff, R. T., Yarchoan, M., O'Connor, A., Gallagher, D., Zahurak, M. L., Rosner, G., Ohaji, C., Sartorius-Mergenthaler, S., Parkinson, R., Subbiah, V., Zinner, R., & Azad, N. S. (2017). The oral VEGF receptor tyrosine kinase inhibitor pazopanib in combination with the MEK inhibitor trametinib in advanced cholangiocarcinoma. British journal of cancer, 116(11), 1402-1407.
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  Cholangiocarcinoma is an aggressive malignancy with limited therapeutic options. MEK inhibition and antiangiogenic therapies have individually shown modest activity in advanced cholangiocarcinoma, whereas dual inhibition of these pathways has not been previously evaluated. We evaluated the safety and efficacy of combination therapy with the oral VEGF receptor tyrosine kinase inhibitor pazopanib plus the MEK inhibitor trametinib in patients with advanced cholangiocarcinoma.
• Shroff, R. T., Yarchoan, M., O'Connor, A., Gallagher, D., Zahurak, M. L., Rosner, G., Ohaji, C., Sartorius-Mergenthaler, S., Subbiah, V., Zinner, R., & Azad, N. S. (2017). The oral VEGF receptor tyrosine kinase inhibitor pazopanib in combination with the MEK inhibitor trametinib in advanced cholangiocarcinoma. BRITISH JOURNAL OF CANCER, 116(11), 1402-1407.
• Yamashita, S., Koay, E. J., Passot, G., Shroff, R., Raghav, K. P., Conrad, C., Chun, Y. S., Aloia, T. A., Tao, R., Kaseb, A., Javle, M., Crane, C. H., & Vauthey, J. (2017). Local therapy reduces the risk of liver failure and improves survival in patients with intrahepatic cholangiocarcinoma: A comprehensive analysis of 362 consecutive patients. CANCER, 123(8), 1354-1362.
• Yamashita, S., Koay, E. J., Passot, G., Shroff, R., Raghav, K. P., Conrad, C., Chun, Y. S., Aloia, T. A., Tao, R., Kaseb, A., Javle, M., Crane, C. H., & Vauthey, J. N. (2017). Local therapy reduces the risk of liver failure and improves survival in patients with intrahepatic cholangiocarcinoma: A comprehensive analysis of 362 consecutive patients. Cancer, 123(8), 1354-1362.
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  Treatment methods for intrahepatic cholangiocarcinoma (ICC) have improved, but their impact on outcome remains unclear. We evaluated the outcomes of patients definitively treated with resection, radiation, and chemotherapy for ICC, stratified by era.
• Ahn, D. H., Ahn, C. W., Bekaii-Saab, T., Chen, J. L., Jain, A., Javle, M., Mikhail, S., Noonan, A. M., Shroff, R. T., & Wu, C. (2016).

  Next-generation sequencing survey of biliary tract cancer reveals the association between tumor somatic variants and chemotherapy resistance: Genes, Biliary Cancer, and Therapy Resistance

  . Cancer, 122(23), 3657-3666. doi:10.1002/cncr.30247
• Ahn, D. H., Ahn, C., Jain, A., Mikhail, S., Wu, C. S., Goldberg, R. M., Ciombor, K. K., Noonan, A. M., Sadavartia, P., Shroff, R. T., Javle, M. M., Chen, J. L., & Bekaii-Saab, T. S. (2016). Next Generation Sequencing (NGS) to reveal mutations in IDH1 and its effect on patient (pt) outcomes in advanced biliary tract cancer (aBTC) who received gemcitabine and cisplatin (GC).. JOURNAL OF CLINICAL ONCOLOGY, 34(4).
• Ahn, D. H., Javle, M. M., Ahn, C., Jain, A., Mikhail, S., Shroff, R. T., Ciombor, K. K., Noonan, A. M., Wu, C. S., Chen, J. L., & Bekaii-Saab, T. S. (2016). Next-generation sequencing (NGS) survey of biliary tract cancer (BTC) to reveal the association between tumor somatic variants and chemotherapy resistance.. JOURNAL OF CLINICAL ONCOLOGY, 34(15).
• Ahn, D. H., Javle, M., Ahn, C. W., Jain, A., Mikhail, S., Noonan, A. M., Ciombor, K., Wu, C., Shroff, R. T., Chen, J. L., & Bekaii-Saab, T. (2016). Next-generation sequencing survey of biliary tract cancer reveals the association between tumor somatic variants and chemotherapy resistance. Cancer, 122(23), 3657-3666.
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  Biliary tract cancers (BTCs) are uncommon and are associated with a dismal prognosis. Combinations of gemcitabine and platinum chemotherapy (gemcitabine and platinum-based therapy [GP]) form the standard approach for treating advanced BTC. To characterize the spectrum of mutations and to identify potential biomarkers for a GP response in BTC, this study evaluated the genomic landscape and assessed whether mutations affecting DNA repair were associated with GP resistance.
• Ahn, D. H., Javle, M., Ahn, C. W., Jain, A., Mikhail, S., Noonan, A. M., Wu, C., Shroff, R. T., Chen, J. L., & Bekaii-Saab, T. (2016). Next-Generation Sequencing Survey of Biliary Tract Cancer Reveals the Association Between Tumor Somatic Variants and Chemotherapy Resistance. CANCER, 122(23), 3657-3666.
• Al-Shamsi, H. O., Anand, D., Shroff, R. T., Jain, A., Zuo, M., Conrad, C., Vauthey, J. N., & Javle, M. M. (2016). BRCA-associated protein 1 mutant cholangiocarcinoma: an aggressive disease subtype. Journal of gastrointestinal oncology, 7(4), 556-61.
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  BRCA-associated protein 1, an enzyme encoded by the BAP1 gene, is commonly mutated in uveal melanoma, mesothelioma, and renal cancers. Tumors with BAP1 mutation follow an aggressive course. BAP1 mutations have also been observed in cholangiocarcinoma (CCA). The clinical phenotype of BAP1 mutant CCA may yield useful prognostic and therapeutic information but has not been defined.
• Cloyd, J. M., Crane, C. H., Koay, E. J., Das, P., Krishnan, S., Prakash, L., Snyder, R. A., Varadhachary, G. R., Wolff, R. A., Javle, M., Shroff, R. T., Fogelman, D., Overman, M., Wang, H., Maitra, A., Lee, J. E., Fleming, J. B., & Katz, M. (2016). Impact of hypofractionated and standard fractionated chemoradiation before pancreatoduodenectomy for pancreatic ductal adenocarcinoma. CANCER, 122(17), 2671-2679.
• Cloyd, J. M., Crane, C. H., Koay, E. J., Das, P., Krishnan, S., Prakash, L., Snyder, R. A., Varadhachary, G. R., Wolff, R. A., Javle, M., Shroff, R. T., Fogelman, D., Overman, M., Wang, H., Maitra, A., Lee, J. E., Fleming, J. B., & Katz, M. H. (2016). Impact of hypofractionated and standard fractionated chemoradiation before pancreatoduodenectomy for pancreatic ductal adenocarcinoma. Cancer, 122(17), 2671-9.
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  Previous studies have suggested that preoperative chemoradiation (CRT) is associated with an improved margin-negative resection rate among patients who undergo pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC). However, the optimal preoperative regimen has not been established.
• Cloyd, J. M., Katz, M. H., Fleming, J. B., Wolff, R. A., Varadhachary, G. R., Javle, M., Shroff, R. T., Fogelman, D., Overman, M., Crane, C., Koay, E. H., Minsky, B. D., Das, P., Evans, D. B., & Lee, J. E. (2016). Evolution of Outcomes of Patients With Pancreatic Ductal Adenocarcinoma Undergoing Pancreatoduodenectomy Following Preoperative Therapy. GASTROENTEROLOGY, 150(4), S1180-S1180.
• Crane, C. H., Tao, R., Bhosale, P., Javle, M. M., Shroff, R. T., Aloia, T. A., Kaseb, A. O., Koay, E. J., Bishop, A. J., Swanick, C. W., Hong, T. S., Das, P., & Krishnan, S. (2016). Effect of ablative radiotherapy on survival in patients with inoperable intrahepatic cholangiocarcinoma: A dose response analysis. JOURNAL OF CLINICAL ONCOLOGY, 34(4).
• Denbo, J. W., Bruno, M. L., Cloyd, J. M., Prakash, L., Lee, J. E., Kim, M., Crane, C. H., Koay, E. J., Krishnan, S., Das, P., Minsky, B. D., Varadhachary, G., Shroff, R., Wolff, R., Javle, M., Overman, M. J., Fogelman, D., Aloia, T. A., Vauthey, J. N., , Fleming, J. B., et al. (2016). Preoperative Chemoradiation for Pancreatic Adenocarcinoma Does Not Increase 90-Day Postoperative Morbidity or Mortality. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract, 20(12), 1975-1985.
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  The impact of preoperative chemoradiation on postoperative morbidity and mortality of patients with pancreatic adenocarcinoma remains controversial.
• Denbo, J. W., Bruno, M. L., Cloyd, J. M., Prakash, L., Lee, J. E., Kim, M., Crane, C. H., Koay, E. J., Krishnan, S., Das, P., Minsky, B. D., Varadhachary, G., Shroff, R., Wolff, R., Javle, M., Overman, M. J., Fogelman, D., Aloia, T. A., Vauthey, J., , Fleming, J. B., et al. (2016). Preoperative Chemoradiation for Pancreatic Adenocarcinoma Does Not Increase 90-Day Postoperative Morbidity or Mortality. JOURNAL OF GASTROINTESTINAL SURGERY, 20(12), 1975-1985.
• Domchek, S. M., Hendifar, A. E., McWilliams, R. R., Geva, R., Epelbaum, R., Biankin, A., Vonderheide, R. H., Wolff, R. A., Alberts, S. R., Giordano, H., Goble, S., Lin, K. K., & Shroff, R. T. (2016). RUCAPANC: An open-label, phase 2 trial of the PARP inhibitor rucaparib in patients (pts) with pancreatic cancer (PC) and a known deleterious germline or somatic BRCA mutation. JOURNAL OF CLINICAL ONCOLOGY, 34(15).
• Golan, T., Raitses-Gurevich, M., Kelley, R. K., Bocobo, A. G., Borgida, A., Shroff, R. T., Holter, S., Gallinger, S., Lowery, M. A., Abou-Alfa, G. K., Ahn, D. H., Jain, A., Bekaii-Saab, T. S., Friedman, E., & Javle, M. M. (2016). Overall survival and clinical characteristics of BRCA germline/somatic cholangiocarcinoma (CCA).. JOURNAL OF CLINICAL ONCOLOGY, 34(4).
• Gulhati, P., Raghav, K., Shroff, R. T., Varadhachary, G. R., Kopetz, S., Javle, M. M., Qiao, W., Wang, H., Morris, J., Wolff, R. A., & Overman, M. J. (2016). Phase II study of bevacizumab combined with capecitabine and oxaliplatin in patients with advanced adenocarcinoma of the small bowel or ampulla of vater.. JOURNAL OF CLINICAL ONCOLOGY, 34(4).
• Jain, A., Shroff, R. T., Kelley, R. K., Kaseb, A. O., Wang, Y., Abdel-Wahab, R., Ahn, D. H., Bocobo, A. G., Meric-Bernstam, F., Isaacs, R., Bekaii-Saab, T. S., & Javle, M. M. (2016). FGFR pathway genetic aberrations in cholangiocarcinoma: Demographics and experience with targeted therapy.. JOURNAL OF CLINICAL ONCOLOGY, 34(15).
• Javle, M. M., Shroff, R. T., Zhu, A., Sadeghi, S., Choo, S., Borad, M. J., Lowery, M. A., El-Khoueiry, A., Macarulla, T., Philip, A. P., Oh, D., Van, C. E., Yeh, K., Isaacs, R., McGarry, C., Sen, S., & Bekaii-Saab, T. S. (2016). A phase 2 study of BGJ398 in patients (pts) with advanced or metastatic FGFR-altered cholangiocarcinoma (CCA) who failed or are intolerant to platinum-based chemotherapy.. JOURNAL OF CLINICAL ONCOLOGY, 34(4).
• Javle, M., Bekaii-Saab, T., Jain, A., Wang, Y., Kelley, R. K., Wang, K., Kang, H. C., Catenacci, D., Ali, S., Krishnan, S., Ahn, D., Bocobo, A. G., Zuo, M., Kaseb, A., Miller, V., Stephens, P. J., Meric-Bernstam, F., Shroff, R., & Ross, J. (2016). Biliary Cancer: Utility of Next-Generation Sequencing for Clinical Management. CANCER, 122(24), 3838-3847.
• Javle, M., Bekaii-Saab, T., Jain, A., Wang, Y., Kelley, R. K., Wang, K., Kang, H. C., Catenacci, D., Ali, S., Krishnan, S., Ahn, D., Bocobo, A. G., Zuo, M., Kaseb, A., Miller, V., Stephens, P. J., Meric-Bernstam, F., Shroff, R., & Ross, J. (2016). Biliary cancer: Utility of next-generation sequencing for clinical management. Cancer, 122(24), 3838-3847.
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  Biliary tract cancers (BTCs) typically present at an advanced stage, and systemic chemotherapy is often of limited benefit.
• Overman, M. J., Morris, V., Moinova, H., Manyam, G., Ensor, J., Lee, M. S., Eng, C., Kee, B., Fogelman, D., Shroff, R. T., LaFramboise, T., Mazard, T., Feng, T., Hamilton, S., Broom, B., Lutterbaugh, J., Issa, J. P., Markowitz, S. D., & Kopetz, S. (2016). Phase I/II study of azacitidine and capecitabine/oxaliplatin (CAPOX) in refractory CIMP-high metastatic colorectal cancer: evaluation of circulating methylated vimentin. Oncotarget, 7(41), 67495-67506.
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  Hypermethylation of promoter CpG islands (CIMP) has been strongly implicated in chemotherapy resistance and is implicated in the pathogenesis of a subset of colorectal cancers (CRCs) termed CIMP-high.
• Overman, M. J., Morris, V., Moinova, H., Manyam, G., Ensor, J., Lee, M. S., Eng, C., Kee, B., Fogelman, D., Shroff, R. T., LaFramboise, T., Mazard, T., Feng, T., Hamilton, S., Broom, B., Lutterbaugh, J., Issa, J., Markowitz, S. D., & Kopetz, S. (2016). Phase I/II study of azacitidine and capecitabine/oxaliplatin (CAPOX) in refractory CIMP-high metastatic colorectal cancer: evaluation of circulating methylated vimentin. ONCOTARGET, 7(41), 67495-67506.
• Tao, R., Krishnan, S., Bhosale, P. R., Javle, M. M., Aloia, T. A., Shroff, R. T., Kaseb, A. O., Bishop, A. J., Swanick, C. W., Koay, E. J., Thames, H. D., Hong, T. S., Das, P., & Crane, C. H. (2016). Ablative Radiotherapy Doses Lead to a Substantial Prolongation of Survival in Patients With Inoperable Intrahepatic Cholangiocarcinoma: A Retrospective Dose Response Analysis. JOURNAL OF CLINICAL ONCOLOGY, 34(3), 219-U68.
• Tao, R., Krishnan, S., Bhosale, P. R., Javle, M. M., Aloia, T. A., Shroff, R. T., Kaseb, A. O., Bishop, A. J., Swanick, C. W., Koay, E. J., Thames, H. D., Hong, T. S., Das, P., & Crane, C. H. (2016). Ablative Radiotherapy Doses Lead to a Substantial Prolongation of Survival in Patients With Inoperable Intrahepatic Cholangiocarcinoma: A Retrospective Dose Response Analysis. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 34(3), 219-26.
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  Standard therapies for localized inoperable intrahepatic cholangiocarcinoma (IHCC) are ineffective. Advances in radiotherapy (RT) techniques and image guidance have enabled ablative doses to be delivered to large liver tumors. This study evaluated the effects of RT dose escalation in the treatment of IHCC.
• Al-Shamsi, H. O., Barrera, C. D., Surapaneni, R., Kang, H., Shroff, R. T., Janku, F., Krishnan, S., Zuo, M., Wolff, R. A., Kaseb, A. O., Thomas, M. B., Siegel, A. B., & Javle, M. M. (2015). HER2/neu-directed therapy for biliary tract cancer. JOURNAL OF CLINICAL ONCOLOGY, 33(15).
• Anand, D., Churi, C., Rashid, A., Shroff, R. T., Zuo, M., Conrad, C., Vauthey, J., & Javle, M. M. (2015). BAP1 mutation-associated cholangiocarcinoma: An aggressive disease. JOURNAL OF CLINICAL ONCOLOGY, 33(3).
• Crane, C. H., Chanda, A. S., Koay, E. J., Varadhachary, G. R., Das, P., Javle, M. M., Suh, Y., Wolff, R. A., Fleming, J. B., Katz, M., Fogelman, D. R., Shroff, R. T., Lee, J. E., & Krishnan, S. (2015). Effect of dose-escalation of IMRT for unresectable pancreatic cancer 1 cm away from the luminal mucosa on long-term survival.. JOURNAL OF CLINICAL ONCOLOGY, 33(3).
• Domchek, S. M., McWilliams, R., Hendifar, A., Shroff, R. T., Leichman, L., Epelbaum, R., Geva, R., Kim, G., Alberts, S. R., Wolff, R. A., Allen, A., Giordano, H., Raponi, M., Isaacson, J., Rolfe, L., Biankin, A., & Vonderheide, R. H. (2015). A phase 2, open-label study of the PARP inhibitor rucaparib in patients with pancreatic cancer and a known deleterious BRCA mutation. CANCER RESEARCH, 75.
• Fogelman, D., Sugar, E. A., Oliver, G., Shah, N., Klein, A., Alewine, C., Wang, H., Javle, M., Shroff, R., Wolff, R. A., Abbruzzese, J. L., Laheru, D., & Diaz Jr., L. A. (2015). Family history as a marker of platinum sensitivity in pancreatic adenocarcinoma. CANCER CHEMOTHERAPY AND PHARMACOLOGY, 76(3), 489-498.
• Fogelman, D., Sugar, E. A., Oliver, G., Shah, N., Klein, A., Alewine, C., Wang, H., Javle, M., Shroff, R., Wolff, R. A., Abbruzzese, J. L., Laheru, D., & Diaz, L. A. (2015). Family history as a marker of platinum sensitivity in pancreatic adenocarcinoma. Cancer chemotherapy and pharmacology, 76(3), 489-498.
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  Metastatic pancreatic adenocarcinoma is considered a uniformly fatal disease with a median survival of 1 year with modern chemotherapy. While a subset of patients achieve prolonged survival, few of the factors that define this group of patients are known.
• Goldstein, J. B., Nogueras-Gonzalez, G. M., Javle, M. M., Katz, M., Varadhachary, G. R., Fogelman, D. R., Overman, M. J., Wolff, R. A., & Shroff, R. T. (2015). A retrospective single institution review of 90 pancreatic adenosquamous cancer (PASC) patients (pts). JOURNAL OF CLINICAL ONCOLOGY, 33(15).
• He, W., Zhao, H., Chan, W., Lopez, D., Shroff, R. T., & Giordano, S. H. (2015). Underuse of surgical resection among elderly patients with early-stage pancreatic cancer. SURGERY, 158(5), 1226-1234.
• He, W., Zhao, H., Chan, W., Lopez, D., Shroff, R. T., & Giordano, S. H. (2015). Underuse of surgical resection among elderly patients with early-stage pancreatic cancer. Surgery, 158(5), 1226-34.
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  Although surgery improves the health care quality and outcomes of patients with early-stage pancreatic cancer, these patients' operative resection rate has been historically low. We sought to identify factors that are associated with operative resection in this patient population.
• Javle, M., Churi, C., Kang, H. C., Shroff, R., Janku, F., Surapaneni, R., Zuo, M., Barrera, C., Alshamsi, H., Krishnan, S., Mishra, L., Wolff, R. A., Kaseb, A. O., Thomas, M. B., & Siegel, A. B. (2015). HER2/neu-directed therapy for biliary tract cancer. Journal of hematology & oncology, 8, 58.
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  Biliary cancers are highly aggressive tumors that are often diagnosed an advanced disease stage and have a poor outcome with systemic therapy. Recent efforts towards molecular characterization have identified a subset of biliary patients that have HER2/neu amplification or mutation. HER2/neu amplification is associated with response to HER2/neu-directed therapy in breast and gastric cancers. However, the efficacy of HER2/neu-targeted therapy in biliary cancers is unknown.
• Javle, M., Javle, M., Javle, M., Churi, C., Churi, C., Churi, C., Kang, H. C., Kang, H. C., Kang, H. C., Shroff, R., Shroff, R., Shroff, R., Janku, F., Janku, F., Janku, F., Surapaneni, R., Surapaneni, R., Surapaneni, R., Zuo, M., , Zuo, M., et al. (2015). HER2/neu-directed therapy for biliary tract cancer. JOURNAL OF HEMATOLOGY & ONCOLOGY, 8.
• Overman, M. J., Kee, B. K., Fogelman, D. R., Eng, C., Sanchez, E. V., Shroff, R. T., Dasari, A., Wolff, R. A., Morris, J., & Kopetz, S. (2015). A phase II study of nab-paclitaxel in refractory CIMP-high metastatic colorectal cancer.. JOURNAL OF CLINICAL ONCOLOGY, 33(15).
• Reilley, M. J., Shroff, R., & Varadhachary, G. R. (2015). Adjuvant/Perioperative Therapy in Pancreatic and Periampullary Cancer. INDIAN JOURNAL OF SURGERY, 77(5), 403-408.
• Reilley, M. J., Shroff, R., & Varadhachary, G. R. (2015). Adjuvant/Perioperative Therapy in Pancreatic and Periampullary Cancer. The Indian journal of surgery, 77(5), 403-8.
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  The delivery of postoperative combined modality adjuvant therapy for completely resected pancreatic adenocarcinoma was initially shown to be beneficial based on a prospective, randomized trial published 30 years ago. Since then, oncologists have debated whether chemotherapy alone, chemoradiation, or both are optimal adjuvant therapies following pancreatectomy for pancreatic ductal adenocarcinomas (PDAC). No global consensus has emerged, and there is no one superior modality despite randomized trials in part, to poor trial design, poor patient selection, and poor therapy options itself. We need to have a disciplined approach to the selection of patients for pancreatectomy, pathologic assessment of surgical resection margins, and postoperative (pre-treatment) imaging. In the era of the multidetector CT optimized for pancreatic imaging, tumors of "borderline resectability" have emerged as a distinct subset of PDAC. The attempt to standardize the definition of borderline resectable is a work in progress and modified with time. This distinction (between resectable and borderline resectable) is essential to minimize potentially confounding results of clinical trials. Additionally, preoperative therapy is not only preferred but mandatory in a large population of borderline resectable patients. Ultimately, as we develop more effective systemic therapies for PDAC, proceeding with surgery after a period of induction therapy will be even more compelling especially if there is a clear positive impact on overall survival.
• Rogers, J. E., Nguyen, V., Nogueras-Gonzalez, G. M., Crane, C. H., Das, P., Krishnan, S., Law, L., Javle, M. M., Kaseb, A. O., & Shroff, R. T. (2015). Characterization of unresectable cholangiocarcinoma patients treated with or without chemoradiation. JOURNAL OF CLINICAL ONCOLOGY, 33(3).
• Roland, C. L., Katz, M. H., Tzeng, C. W., Lin, H., Varadhachary, G. R., Shroff, R., Javle, M., Fogelman, D., Wolff, R. A., Vauthey, J. N., Crane, C. H., Lee, J. E., & Fleming, J. B. (2015). The Addition of Postoperative Chemotherapy is Associated with Improved Survival in Patients with Pancreatic Cancer Treated with Preoperative Therapy. Annals of surgical oncology, 22 Suppl 3, S1221-8.
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  Preoperative/neoadjuvant therapy (NT) is increasingly utilized for the treatment of pancreatic ductal adenocarcinoma (PDAC). However, little data exist regarding information on the use of additional postoperative therapy following NT. The lymph node ratio (LNR) is a prognostic marker of oncologic outcomes after NT and resection. In this study, we evaluated the effectiveness of postoperative therapy following NT, stratified by LNR.
• Roland, C. L., Katz, M., Tzeng, C. D., Lin, H., Varadhachary, G. R., Shroff, R., Javle, M., Fogelman, D., Wolff, R. A., Vauthey, J. N., Crane, C. H., Lee, J. E., & Fleming, J. B. (2015). The Addition of Postoperative Chemotherapy is Associated with Improved Survival in Patients with Pancreatic Cancer Treated with Preoperative Therapy. ANNALS OF SURGICAL ONCOLOGY, 22, S1221-S1228.
• Ross, J. S., Wang, K., Javle, M. M., Catenacci, D., Shroff, R. T., Ali, S. M., Elvin, J. A., Chmielecki, J., Yelensky, R., Lipson, D., Miller, V. A., Stephens, P. J., & Meric-Bernstam, F. (2015). Comprehensive genomic profiling of biliary tract cancers to reveal tumor-specific differences and frequency of clinically relevant genomic alterations. JOURNAL OF CLINICAL ONCOLOGY, 33(15).
• Shroff, R. T., Knox, J., & Dixon, E. (2015). Consensus Conference on Gallbladder Cancer. HPB, 17(8), 664-665.
• Shroff, R. T., Knox, J., & Dixon, E. (2015). Consensus conference on gallbladder cancer. HPB : the official journal of the International Hepato Pancreato Biliary Association, 17(8), 664-5.
• Shroff, R. T., O'Connor, A., Gallagher, D., Zahurak, M., Rosner, G. L., Ohaji, C., Sartorius-Mergenthaler, S., Zinner, R., & Azad, N. S. (2015). Pazopanib (P) and trametinib (T) in advanced cholangiocarcinoma (CC): A phase Ib study.. JOURNAL OF CLINICAL ONCOLOGY, 33(15).
• Tao, R., Krishnan, S., Bhosale, P., Javle, M., Kaseb, A., Jensen, G., Bishop, A. J., Swanick, C. W., Koay, E. J., Thames, H. D., Hong, T. S., Das, P., Crane, C. H., & Shroff, R. T. (2015). Ablative Radiation Therapy Doses Lead to a Substantial Prolongation of Survival in Patients With Inoperable Intrahepatic Cholangiocarcinoma. International Journal of Radiation Oncology Biology Physics, 93(3), S113. doi:10.1016/j.ijrobp.2015.07.269
• Varadhachary, G. R., Fleming, J. B., Crane, C. H., Fogelman, D. R., Shroff, R. T., Lee, J. E., Lee, J. H., Tamm, E. P., Bhosale, P., Das, P., Krishnan, S., Javle, M. M., Weston, B., Wang, H., Wolff, R. A., & Katz, M. (2015). Phase II study of preoperation mFOLFIRINOX and chemoradiation for high-risk resectable and borderline resectable pancreatic adenocarcinoma.. JOURNAL OF CLINICAL ONCOLOGY, 33(3).
• Churi, C. R., Shroff, R., Wang, Y., Rashid, A., Kang, H. C., Weatherly, J., Zuo, M., Zinner, R., Hong, D., Meric-Bernstam, F., Janku, F., Crane, C. H., Mishra, L., Vauthey, J. N., Wolff, R. A., Mills, G., & Javle, M. (2014). Mutation profiling in cholangiocarcinoma: prognostic and therapeutic implications. PloS one, 9(12), e115383.
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  Cholangiocarcinoma (CCA) is clinically heterogeneous; intra and extrahepatic CCA have diverse clinical presentations. Next generation sequencing (NGS) technology may identify the genetic differences between these entities and identify molecular subgroups for targeted therapeutics.
• Churi, C. R., Shroff, R., Wang, Y., Rashid, A., Kang, H. C., Weatherly, J., Zuo, M., Zinner, R., Hong, D., Meric-Bernstam, F., Janku, F., Crane, C. H., Mishra, L., Vauthey, J., Wolff, R. A., Mills, G., & Javle, M. (2014). Mutation Profiling in Cholangiocarcinoma: Prognostic and Therapeutic Implications. PLOS ONE, 9(12).
• Domchek, S. M., McWilliams, R. R., Hendifar, A. E., Shroff, R. T., Lelchman, L. P., Epelbaum, R., Geva, R., Kim, G. P., Alberts, S. R., Wolff, R. A., Allen, A. R., Giordano, H., Raponi, M., Isaacson, J. D., Rolfe, L., Biankin, A., & Vonderheide, R. H. (2014). A phase 2, open-label study of rucaparib in patients with pancreatic cancer and a known deleterious BRCA mutation.. JOURNAL OF CLINICAL ONCOLOGY, 32(15).
• Fogelman, D. R., Holmes, H., Mohammed, K., Katz, M. H., Prado, C. M., Lieffers, J., Garg, N., Varadhachary, G. R., Shroff, R., Overman, M. J., Garrett, C., Wolff, R. A., & Javle, M. (2014). Does IGFR1 inhibition result in increased muscle mass loss in patients undergoing treatment for pancreatic cancer?. Journal of cachexia, sarcopenia and muscle, 5(4), 307-13.
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  IGF-1 plays a role in the growth of multiple tumor types, including pancreatic cancer. IGF-1 also serves as a growth factor for muscle. The impact of therapeutic targeting of IGF-1 on muscle mass is unknown.
• Fogelman, D. R., Holmes, H., Mohammed, K., Katz, M., Prado, C. M., Lieffers, J., Garg, N., Varadhachary, G. R., Shroff, R., Overman, M. J., Garrett, C., Wolff, R. A., & Javle, M. (2014). Does IGFR1 inhibition result in increased muscle mass loss in patients undergoing treatment for pancreatic cancer?. JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE, 5(4), 307-313.
• Javle, M., Rashid, A., Churi, C., Kar, S., Zuo, M., Eterovic, A. K., Nogueras-Gonzalez, G. M., Janku, F., Shroff, R. T., Aloia, T. A., Vauthey, J. N., Curley, S., Mills, G., & Roa, I. (2014). Molecular characterization of gallbladder cancer using somatic mutation profiling. Human pathology, 45(4), 701-8.
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  Gallbladder cancer is relatively uncommon, with a high incidence in certain geographic locations, including Latin America, East and South Asia, and Eastern Europe. Molecular characterization of this disease has been limited, and targeted therapy options for advanced disease remain an open area of investigation. In the present study, surgical pathology obtained from resected gallbladder cancer cases (n = 72) was examined for the presence of targetable, somatic mutations. All cases were formalin fixed and paraffin embedded (FFPE). Two approaches were used: (a) mass spectroscopy-based profiling for 159 point ("hot spot") mutations in 33 genes commonly involved in solid tumors and (b) next-generation sequencing (NGS) platform that examined the complete coding sequence of in 182 cancer-related genes. Fifty-seven cases were analyzed for hot spot mutations; and 15, for NGS. Fourteen hot spot mutations were identified in 9 cases. Of these, KRAS mutation was significantly associated with poor survival on multivariate analysis. Other targetable mutations included PIK3CA (n = 2) and ALK (n = 1). On NGS, 26 mutations were noted in 15 cases. TP53 and PI3 kinase pathway (STK11, RICTOR, TSC2) mutations were common. One case had FGF10 amplification, whereas another had FGF3-TACC gene fusion, not previously described in gallbladder cancer. In conclusion, somatic mutation profiling using archival FFPE samples from gallbladder cancer is feasible. NGS, in particular, may be a useful platform for identifying novel mutations for targeted therapy.
• Javle, M., Rashid, A., Churi, C., Kar, S., Zuo, M., Eterovic, A. K., Nogueras-Gonzalez, G. M., Janku, F., Shroff, R. T., Aloia, T. A., Vauthey, J., Curley, S., Mills, G., & Roa, I. (2014). Molecular characterization of gallbladder cancer using somatic mutation profiling. HUMAN PATHOLOGY, 45(4), 701-708.
• Morris, V. K., Overman, M. J., Kee, B. K., Fogelman, D. R., Eng, C., Dasari, A., Shroff, R. T., Deaton, L., Manuel, S., Garrett, C. R., Sanchez, E. V., Dennis, C. S., Shureiqi, I., Mills, G. B., Shaw, K. R., Hamilton, S. R., Wolff, R. A., Meric-Bernstam, F., Maru, D. M., & Kopetz, S. (2014). Efficiency of biomarker screening for enriched metastatic colorectal cancer trials: The ATTACC program experience.. JOURNAL OF CLINICAL ONCOLOGY, 32(15).
• Morris, V. K., Overman, M. J., Kee, B. K., Fogelman, D. R., Eng, C., Dasari, A., Shroff, R. T., Deaton, L., Manuel, S., Garrett, C. R., Sanchez, E. V., Pini, T. M., Shureiqi, I., Mills, G. B., Hamilton, S. R., Wolff, R. A., Meric-Bernstam, F., Abbruzzese, J. L., Maru, D. M., & Kopetz, S. (2014). Efficiency of biomarker screening for enriched metastatic colorectal cancer trials: The ATTACC program experience. JOURNAL OF CLINICAL ONCOLOGY, 32(3).
• Overman, M. J., Eng, C., Kee, B. K., Fogelman, D. R., Shroff, R. T., Fark, C., Moinova, H., Lutterbaugh, J., Issa, J. J., Markowitz, S. D., & Kopetz, S. (2014). A phase I/II study of azacitidine and capecitabine/oxaliplatin (CAPOX) in refractory CIMP-high metastatic colorectal cancer.. JOURNAL OF CLINICAL ONCOLOGY, 32(3).
• Rogers, J. E., Law, L., Nguyen, D. V., Qiao, W., Javle, M. M., Kaseb, A. O., & Shroff, R. T. (2014). Second-line systemic treatment for advanced cholangiocarcinoma. JOURNAL OF CLINICAL ONCOLOGY, 32(3).
• Rogers, J. E., Law, L., Nguyen, V. D., Qiao, W., Javle, M. M., Kaseb, A., & Shroff, R. T. (2014). Second-line systemic treatment for advanced cholangiocarcinoma. Journal of gastrointestinal oncology, 5(6), 408-13.
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  Gemcitabine plus platinum (GEM-P) combination chemotherapy is standard treatment for first-line advanced cholangiocarcinoma (aCC). GEM-P first-line therapy reports a progression-free survival (PFS) of 8 months and overall survival (OS) of 11.7 months. Treatment in the second-line setting is less clear. Five-year survival for aCC remains dismal at 5-10%. The purpose of this study was to describe the outcomes with second-line systemic treatment at our institution.
• Shroff, R. T., Churi, C., Rashid, A., Mishra, L., Zuo, M., Kaseb, A. O., Janku, F., Aloia, T. A., Vauthey, J., Curley, S. A., & Javle, M. M. (2014). Next-generation sequencing yields promising targets in advanced cholangiocarcinoma (CCA). JOURNAL OF CLINICAL ONCOLOGY, 32(3).
• Stephens, P., Wang, K., Palma, N. A., Chmielecki, J., Shroff, R. T., Churl, C., Frampton, G. M., Ali, S. M., Javle, M. M., & Ross, J. S. (2014). Comprehensive genomic profiling of gallbladder adenocarcinoma and frequent genomic-derived targets of therapy.. JOURNAL OF CLINICAL ONCOLOGY, 32(15).
• Churi, C. R., Rashid, A., Shroff, R., Mishra, L., Zuo, M., Kaseb, A., Janku, F., Aloia, T. A., Vauthey, J., Curley, S., Ali, S., Palmer, G., & Javie, M. (2013). Next generation sequencing yields promising targets in advanced cholangiocarcinoma (CCA).. MOLECULAR CANCER THERAPEUTICS, 12(11).
• Gupta, V., Gupta, V., Garza, M., Garza, M., Hasegawa, D. K., Hasegawa, D. K., Anderes, K. L., Anderes, K. L., Wolff, R. A., Wolff, R. A., Varadhachary, G. R., Varadhachary, G. R., Shroff, R. T., Shroff, R. T., Neal, C. L., Neal, C. L., Melnikova, V. O., Melnikova, V. O., Davis, D. W., , Davis, D. W., et al. (2013). Abstract 1449: ApoStream™, a new dielectrophoretic device for antibody-independent isolation and recovery of circulating tumor cells from blood of patients with metastatic pancreatic adenocarcinoma.. Cancer Research, 73, 1449-1449. doi:10.1158/1538-7445.am2013-1449
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  Pancreatic adenocarcinoma (PAC) remains the fourth most common cause of cancer-related mortality with a 5-year survival rate of less than 5%. The available diagnostic tools and biomarkers for PAC fail at early detection and suffer from low specificity and sensitivity. Advances in the isolation, recovery, and characterization of circulating tumor cells (CTCs) offer hope for the development of noninvasive techniques for disease detection, monitoring, and biomarker discovery. While CTC enumeration provides prognostic information in patients with various cancer types, the biological characterization of CTCs may offer insight into the molecular determinants of disease progression. Epithelial cell adhesion molecule (EpCAM) and cytokeratin (CK) dependent CTC technologies fare poorly in the metastatic PAC setting, due to altered phenotypes acquired during epithelial mesenchymal transition (EMT). The links between EMT, plectin-1, mesothelin and metastatic progression of PAC are emerging and underscore the need for biomarker information in real time. Here we used ApoStream™, a novel, antibody-independent device which uses dielectrophoretic (DEP) technology in a continuous flow system to isolate CTCs from the blood of patients with metastatic PAC and expand their phenotypic characterization in order to elucidate the population heterogeneity and characterize pancreatic specific markers (CA19-9, KRAS, plectin-1 and mesothelin). This prospective study will evaluate thirty patients. Paired blood samples from 11 metastatic PAC patients were analyzed by CellSearch® and ApoStream™. Collected cells were immunostained using antibodies against CK, CD45, DAPI, CA19-9, plectin-1 and mesothelin. CTC enumeration was performed using laser scanning cytometry (LSC). A multiplexed immunofluorescent assay and LSC analysis were applied to identify cell phenotypes based on combinations of CK, CD45, plectin-1 and mesothelin marker expression. Results:The detection of CK+/CD45−/DAPI+ cells was comparable between CellSearch® and ApoStream™ with counts ranging from 1-10 CTCs/7.5 mL blood in 50% of patients. In addition, ApoStream™, recovered CK−/CD45−/DAPI+ cells in 100% of patients with counts in the range of 12-166 cells/7.5 mL of blood. CA19-9+ cells were identified in both CK+/CD45−/DAPI+ and CK−/CD45−/DAPI+ subpopulations isolated by ApoStream™. KRAS, plectin-1 and mesothelin analysis is pending. Conclusions: ApoStream™ recovers putative CTCs with multiple phenotypes in patients with metastatic PAC. Preliminary data is encouraging and if confirmed in a larger sample size of PAC patients, ApoStream™ could prove to be a sensitive method for isolating and detecting biomarkers in CTCs of PAC patients. Acknowledgments: Supported in part by the Lockton Fund. Citation Format: Gauri Varadhachary, James Abbruzzese, Rachna Shroff, Vladislava Melnikova, Vishal Gupta, Chris Neal, Miguel Garza, David K. Hasegawa, Kenna L. Anderes, Darren Davis, Robert A. Wolff. ApoStream™, a new dielectrophoretic device for antibody-independent isolation and recovery of circulating tumor cells from blood of patients with metastatic pancreatic adenocarcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1449. doi:10.1158/1538-7445.AM2013-1449
• Raj, S. V., Zhou, X., Varadhachary, G. R., Milind, J., Fogelman, D., Shroff, R., Ramos, C., Nguyen, M., Wang, X., Wolff, R. A., Abbruzzese, J. L., & Overman, M. J. (2013). Randomized Controlled Trial Of Dalteparin For Primary Thromboprophylaxis For Venous Thromboembolism (VTE) In Patients With Advanced Pancreatic Cancer (APC): Risk Factors Predictive Of VTE. BLOOD, 122(21).
• Shroff, S., Overman, M. J., Rashid, A., Shroff, R. T., Wang, H., Chatterjee, D., Katz, M. H., Lee, J. E., Wolff, R. A., Abbruzzese, J. L., Fleming, J. B., & Wang, H. (2013). The expression of PTEN is associated with improved prognosis in patients with ampullary adenocarcinoma after pancreaticoduodenectomy. Archives of pathology & laboratory medicine, 137(11), 1619-26.
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  Phosphatase and tensin homolog (PTEN) is one of the most frequently inactivated tumor suppressor genes in sporadic cancers. Somatic mutations of PTEN occur in many tumors including those of the gastrointestinal and hepatobiliary tracts. Loss of PTEN expression is associated with poor prognosis in patients with metastatic colonic adenocarcinoma, gastroesophageal junction adenocarcinoma, gastric adenocarcinoma, and pancreatic ductal adenocarcinoma.
• Shroff, S., Shroff, S., Shroff, S., Overman, M. J., Overman, M. J., Overman, M. J., Rashid, A., Rashid, A., Rashid, A., Shroff, R. T., Shroff, R. T., Shroff, R. T., Wang, H., Wang, H., Wang, H., Chatterjee, D., Chatterjee, D., Chatterjee, D., Katz, M. H., , Katz, M. H., et al. (2013). The Expression of PTEN Is Associated With Improved Prognosis in Patients With Ampullary Adenocarcinoma After Pancreaticoduodenectomy. ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE, 137(11), 1619-1626.
• Fogelman, D. R., Wang, X. S., Li, D., Javle, M. M., Katz, M. H., Overman, M. J., Varadhachary, G. R., Shroff, R. T., Wolff, R. A., Abbruzzese, J. L., & Hassan, M. M. (2012). Can we identify patients with cancer at high risk for cachexia? A prospective study in pancreatic cancer (PC).. Journal of Clinical Oncology, 30(4_suppl), 219-219. doi:10.1200/jco.2012.30.4_suppl.219
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  219 Background: Identifying PC patients at high risk for cachexia may allow for early intervention to prevent it. Symptoms such as pain, nausea and anorexia may predict weight loss. Inflammatory cytokines are also associated with cachexia. We evaluated the ability of each to predict weight loss in newly diagnosed PC patients. Methods: Using the M. D. Anderson Symptom Inventory (MDASI), we assessed baseline symptoms in untreated advanced or metastatic PC patients. The survey assesses severity of symptoms on a 0-10 scale. Baseline serum levels of IL-1a, IL-1b, IGF-1, CXCL-12, CXCL-16, CRP, IL-6, IL-8, VEGF, CEA, and CA 19-9 were measured via ELISA. Using STATA (version 12), we generated multivariable logistic regression models with a backward selection procedure. This allowed us to evaluate all potential univariate correlates with 5% and 10% weight loss at P
• Javle, M. M., Shroff, R. T., Varadhachary, G. R., Wolff, R. A., Fogelman, D. R., Bhosale, P., Wang, X., Kar, S. P., Overman, M. J., Sathyanarayanan, S., Ayers, M., Mauro, D. J., & Abbruzzese, J. L. (2012). Tumor IGF-1 expression as a predictive biomarker for IGF1R-directed therapy in advanced pancreatic cancer (APC). JOURNAL OF CLINICAL ONCOLOGY, 30(15).
• Javle, M., Bhosale, P., Wang, X., Sathyanarayanan, S., Ayers, M., Wolff, R. A., Varadhachary, G. R., Shroff, R. T., Overman, M. J., Mauro, D. J., Fogelman, D. R., & Abbruzzese, J. L. (2012). O-0004 Updated Analysis of Phase II Study of the Anti-IGF-1R Antibody MK-0646 with Gemcitabine +/- Erlotinib for Advanced Pancreatic Cancer (APC). Annals of Oncology, 23, iv6. doi:10.1016/s0923-7534(19)66469-0
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  ABSTRACT Introduction IGF-1R activation results in the phosphorylation of IRS-1 and downstream effector proteins of the PI3-Kinase/ Akt, mTOR and S6 kinase pathways that are important in cellular proliferation, survival, and drug resistance in pancreatic cancer. The monoclonal antibody MK-0646 (dalotozumab) blocks the ligand-receptor interaction, internalizes the receptor, and causes its degradation. Receptor cross-talk between IGF-1R and EGFR and enhanced IGF-1R-induced activation of the PI3-kinase/Akt pathways mediate resistance to anti-EGFR agents. Prior phase I established the MTD of MK-0646 as 10 mg/kg with G and 5 mg/kg with G + E. Methods Patients with stage IV, previously untreated APC, ECOG performance status (PS) 0-1, adequate hematologic and organ function were enrolled. Uncontrolled hyperglycemia or cardio-respiratory conditions were exclusions. Phase II study uses adaptive randomized design with Arm A (G + MK-0646), Arm B (G + E + MK-0646) and Arm C (G + E). G was administered as 1000 mg/m2 over 100 min, weekly x 3, MK-0646 over 60 min, weekly x 4 and E 100 mg daily. Cycles repeated q 4 weeks. Study endpoints: Overall survival (OS), progression-free survival (PFS), response rate and toxicity. Results 72 pts were enrolled (68 evaluable; A = 24, B = 28, C = 16 pts). Median PFS of arms A, B and C were 5.5 months (95% CI: 3.9 – NA), 3.0 months (95% CI: 1.8 – 5.6) and 2.0 months (95% CI: 1.8 – NA), respectively (log-rank test; p-value = 0.17). Median OS of A was 11.3 months (95% CI: 8.9 – NA), B- 8.9 months (95% CI: 5.3 – NA) and C- 5.7 months (95% CI: 2.0 – NA) (log-rank test; p-value = 0.44). 35 archival core biopsies were analyzed, 21 had adequate tissue for analysis. Biomarker analysis with available blood and tissue samples is ongoing and preliminary data will be presented at ASCO 2012. Conclusion The combination of G + M may be a promising combination for APC. Biomarker analysis may help identify those patients who would benefit from anti-IGF-1R therapy.
• Shroff, R. T., Morris, J., Nogueras-Gonzalez, G. M., Anderson, J. M., Hollingsworth, M. A., Abbruzzese, J. L., & Wang, H. M. (2012). Analysis of fibrosis and stromal components in metastatic pancreatic cancer (PC) autopsy specimens. CANCER RESEARCH, 72.
• Shroff, R. T., Nogueras-gonzalez, G. M., Anderson, J. M., Hollingsworth, M. A., Abbruzzese, J. L., Wang, H. M., & Morris, J. S. (2012). Abstract 1493: Analysis of fibrosis and stromal components in metastatic pancreatic cancer (PC) autopsy specimens. Cancer Research, 72, 1493-1493. doi:10.1158/1538-7445.am2012-1493
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  Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Background: PC remains a deadly malignancy with a paucity of effective therapeutic options. Recent data generated in a genetically engineered mouse model of PC suggests that the notorious chemoresistance of this disease is due to dense fibrosis and stromal proliferation that precludes effective drug delivery to the cancer cells. However clinical experience in patients with metastatic disease suggests that metastatic sites may respond differently from the pancreatic primary (PP). Such variability could be related to differences in the tumor-stroma relationship between the PP and metastatic sites. We used paired specimens from the University of Nebraska Medical Center's rapid autopsy program (RAP) to assess histologic markers of fibrosis and stromal proliferation between the PP and metastatic sites to better characterize these differences. Methods: The RAP has been previously described (Stratford et al. PLoS Med 2010). We identified 12 matched specimens that included PP tissue in addition to metastatic lesions from liver, lung, abdominal cavity, or other sites. Slides were stained with hematoxylin and eosin (to assess for % fibrosis) and vimentin, CD10, and CD68 (stromal markers) and scored based on pathologic review (HMW). Percent fibrosis was a composite measure based on stromal components, including collagen, fibroblasts, and inflammatory cells. Mixed linear model methods with repeated measures were used to determine whether there was a difference in % fibrosis and CD68 between patients’ tumors. Generalized estimating equations were used to determine whether there was a difference in vimentin and CD10 between patients’ tumors. Bonferroni adjusted p-value=0.0125 (α=0.05 / 4 tests) was used as significant alpha level for the tests. Statistical analysis was performed using SAS version 9.2 and STATA/SE version 11.2 software. Results: Percent fibrosis was statistically different between PP tissue and all metastatic sites (p=0.002) with metastatic lesions demonstrating less fibrosis than the respective paired PP. There were no statistically significant differences in CD10, CD68 or vimentin staining between the PP and metastatic sites; however liver metastases did trend towards significantly more stromal cellular proliferation, based on CD10, vimentin, and CD68 staining, when compared to other metastatic sites. Conclusions: There was less stromal deposition and fibrosis in metastatic sites versus the PP's that were examined. This difference could play a role in the chemosensitivity of the primary tumor compared to metastatic sites of disease. Furthermore, the liver appears to have more striking stromal cellular proliferation compared to other metastatic sites, which could also affect drug penetration and outcome. These differences in the tumor-stroma relationship should be further validated and interventions evaluated to improve drug delivery to the PP and metastatic sites in PC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1493. doi:1538-7445.AM2012-1493
• Shroff, R. T., Varadhachary, G. R., Crane, C. H., Lee, J. E., Lee, J. H., Ho, L., Tamm, E. P., Evans, D. B., Abbruzzese, J. L., & Wolff, R. A. (2012). Updated survival analysis of preoperative gemcitabine (gem) plus bevacizumab (bev)-based chemoradiation for resectable pancreatic adenocarcinoma. JOURNAL OF CLINICAL ONCOLOGY, 30(15).
• Shroff, R., Javle, M., Varadhachary, G., Wolff, R., Fogelman, D., Bhosale, P., Wang, X., Overman, M., Sathyanarayanan, S., Ayers, M., Mauro, D., & Abbruzzese, J. (2012). UPDATED ANALYSIS OF PHASE II STUDY OF THE ANTI-IGF-1R ANTIBODY MK-0646 WITH GEMCITABINE +/- ERLOTINIB FOR ADVANCED PANCREATIC CANCER (APC). ANNALS OF ONCOLOGY, 23, 6-6.
• Javle, M. M., Varadhachary, G. R., Fogelman, D. R., Shroff, R. T., Overman, M. J., Ukegbu, L., Bekele, B. N., Kar, S. P., Wolff, R. A., & Abbruzzese, J. L. (2011). Randomized phase II study of gemcitabine (G) plus anti-IGF-1R antibody MK-0646, G plus erlotinib (E) plus MK-0646 and G plus E for advanced pancreatic cancer.. JOURNAL OF CLINICAL ONCOLOGY, 29(15).
• Dong, X., Javle, M., Hess, K. R., Shroff, R., Abbruzzese, J. L., & Li, D. (2010). Insulin-Like Growth Factor Axis Gene Polymorphisms and Clinical Outcomes in Pancreatic Cancer. GASTROENTEROLOGY, 139(2), 464-473.
• Dong, X., Javle, M., Hess, K. R., Shroff, R., Abbruzzese, J. L., & Li, D. (2010). Insulin-like growth factor axis gene polymorphisms and clinical outcomes in pancreatic cancer. Gastroenterology, 139(2), 464-73, 473.e1-3.
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  Insulin-like growth factor (IGF)-axis mediated signaling pathways play an important role in pancreatic cancer development and progression. We examined whether IGF-axis gene variants are associated with clinical outcomes in pancreatic cancer.
• Javle, M. M., Shroff, R. T., Xiong, H., Varadhachary, G. A., Fogelman, D., Reddy, S. A., Davis, D., Zhang, Y., Wolff, R. A., & Abbruzzese, J. L. (2010). Inhibition of the mammalian target of rapamycin (mTOR) in advanced pancreatic cancer: results of two phase II studies. BMC CANCER, 10.
• Javle, M. M., Shroff, R. T., Xiong, H., Varadhachary, G. A., Fogelman, D., Reddy, S. A., Davis, D., Zhang, Y., Wolff, R. A., & Abbruzzese, J. L. (2010). Inhibition of the mammalian target of rapamycin (mTOR) in advanced pancreatic cancer: results of two phase II studies. BMC cancer, 10, 368.
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  The phosphoinositide 3-kinase (PI3K)/Akt pathway is constitutively activated in pancreatic cancer and the mammalian target of rapamycin (mTOR) kinase is an important mediator for its signaling. Our recent in vitro studies suggest that prolonged exposure of pancreatic cancer cells to mTOR inhibitors can promote insulin receptor substrate-PI3K interactions and paradoxically increase Akt phosphorylation and cyclin D1 expression in pancreatic cancer cells (negative feedback loop). The addition of erlotinib to rapamycin can down-regulate rapamycin-stimulated Akt and results in synergistic antitumor activity with erlotinib in preclinical tumor models.
• Shroff, R. T., Varadhachary, G. R., Bhosale, P., Ukegbu, L., Overman, M. J., Wolff, R. A., Abbruzzese, J. L., & Javle, M. M. (2010). Phase I study of MK-0646, the humanized monoclonal antibody against IGF-1R in combination with gemcitabine or gemcitabine plus erlotinib (E) for advanced, previously untreated pancreatic cancer. CANCER RESEARCH, 70.
• Javie, M., Varadhachary, G., Bhosale, P., Shroff, R., Tjkegbu, L., Overman, M., Wolff, R., & Abbruzzese, J. (2009). Phase I study of MK-0646, a humanized monoclonal antibody against IGF-1R in combination with gemcitabine or gemcitabine plus erlotinib (E) for advanced previously untreated pancreatic cancer. MOLECULAR CANCER THERAPEUTICS, 8(12).
• Shroff, R. T., & Wolff, R. A. (2009). Consensus and Controversy in the Adjuvant Treatment of Pancreatic Cancer. ONCOLOGY-NEW YORK, 23(12), 7-13.
• Shroff, R. T., Javle, M. M., Dong, X., Kumar, V. S., Krishnan, S., Wolff, R. A., Abbruzzese, J. L., & Li, D. (2009). The prognostic value of polymorphisms in the insulin-like growth factor receptor (IGFR) pathway in patients with locally advanced pancreatic cancer (LAPC). JOURNAL OF CLINICAL ONCOLOGY, 27(15).
• Mani, M. A., Shroff, R. T., Jacobs, C., Wolff, R. A., Ajani, J. A., Yao, J. C., & Phan, A. T. (2008). A phase II study of irinotecan and cisplatin for metastatic or unresectable high grade neuroendocrine carcinoma. JOURNAL OF CLINICAL ONCOLOGY, 26(15).

Proceedings Publications

• Shroff, R. (2020, March/Spring). Co-organizer. In Society for Immunotherapy of Cancer (SITC).
• Shroff, R. T. (2019).

  AB023. S4-3. Down-staging locally advanced disease

  . In Journal.
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  : Cholangiocarcinoma is often diagnosed at an advanced stage and carries with it a poor prognosis. Surgical resection is the only curative therapy available for this disease and can be offered upfront in rare instances. The majority of patients with intrahepatic cholangiocarcinoma typically have large tumors or multifocal disease which preclude immediate resection. New approaches to locally advanced cholangiocarcinoma include neoadjuvant chemotherapy or targeted therapies that allow for down-staging disease. Combination chemotherapy with gemcitabine and cisplatin remains the standard of care for treating advanced cholangiocarcinoma. Chemo-intensification with triplet combinations such as gemcitabine, cisplatin and nab-paclitaxel have also shown promise in the palliative setting with a phase II study of 60 patients demonstrating an overall survival of over 19 months. Interestingly, in this study, 12 patients (20%) were converted from unresectable disease and underwent successful surgical resection. Two of these patients also demonstrated a pathologic complete response, suggesting a utility to this triplet chemotherapy regimen in the neoadjuvant setting. To this end, an ongoing multicenter study is investigating gemcitabine, cisplatin, and nab-paclitaxel in high-risk or borderline resectable cholangiocarcinoma to better understand its potential for down-staging disease and for offering these patients potentially curative therapy. Furthermore, as we identify the actionable mutations in patients with cholangiocarcinoma through next generation sequencing, consideration should be given to the role of targeted approaches based on individual molecular profiles in the neoadjuvant setting. As we better identify personalized approaches to down-staging locally advanced disease, the hope would be to increase the surgical resection and cure rate for this otherwise deadly malignancy.

Presentations

• Shroff, R. (2023, April / Spring). Discussant: Clinical Trials Plenary Session / Title: CTPL02 - Hope for Rare Cancers: Novel Targeted and Immunotherapy. American Association for Cancer Research. Orlando, FL: AACR.
• Shroff, R. (2023, April / Spring). Presenter/Discussant,  “Chemotherapy: Hold on or Let if Go?”
  
  . 10th Annual Cholangiocarcinoma Foundation Conference. Salt Lake, Utah: CCF.
• Shroff, R. (2023, August / Summer).

  Presenter  “Augmenting Standard Treatment Options in Pancreatic Cancer”

  . Great Debates & Updates in Gastrointestinal Malignancies. Virtual: GDU.
• Shroff, R. (2023, August / Summer). Co-Chair/Presenter  “Current Systemic Therapies and Therapeutics Challenges in the Management of Advanced Cholangiocarcinoma”. FASEB Scientific Research Conference: Advances in Management of CCA. Palm Spring, CA: FASEB.
• Shroff, R. (2023, August / Summer). Moderator. 5th Annual Cholangiocarcinoma. Phoenix, AZ: Amplity Health.
• Shroff, R. (2023, December / Winter). Chairing/Moderator. Cholangiocarcinoma Regional Symposium. Tucson, AZ: UACC and CCF.
• Shroff, R. (2023, February / Winter).

  Chairing/Presenter, “Novel Immunotherapy Approaches in Hepatobiliary Malignancies”

  . Practical Recommendations in Immuno & Molecular Oncology. Honolulu, HI.
• Shroff, R. (2023, January / Winter). Chairing Session,  ASCO Gastrointestinal Cancers Symposium, San Francisco, CA. ASCO Gastrointestinal Cancers Symposium. San Francisco, CA: ASCO.
• Shroff, R. (2023, June / Summer).

  Keynote Speaker, The 2023 Liver & Bile Duct Cancer Symposium: Advances in Genomic Profiling & Multidisciplinary Approach.

  . 2023 Liver & Bile Duct Cancer Symposium:Advances in Genomic Profiling & Multidisciplinary Approach.. Orlando, FL: AdventHealth Cancer Institute.
• Shroff, R. (2023, June / Summer).

  Presenter, Special Presentation “Division of Hematology/Oncology: Avison for Growth”

  . University of Arizona, Department of Medicine. Tucson, AZ: UA DOM.
• Shroff, R. (2023, June / Summer). Chairing/Presenter “FGFR Inhibition: Crossing the Heme/Solid Tumor Divide” 
  
  . ASCO Annual Meeting. Chicago, IL: ASCO.
• Shroff, R. (2023, June / Summer). Keynote Speaker/Presenter  “Biliary Cancers: Team Science is closing the GAP”
  
  . Liver & Bile Duct Symposium: Advances in Genomic Profiling & Multidisciplinary Approach. Orlando, FL: AdventHealth Cancer Institute.
• Shroff, R. (2023, March / Spring). Moderator. Center for Advanced Molecular and Immunological Therapies (CAMI) Spring Event Series Cancer Symposium. Tucson, AZ: COM, UACC.
• Shroff, R. (2023, May / Spring). Presenter ” Biliary Cancers: Team Science is Closing the GAP”. Department of Medicine Grand Rounds. UACC: UA DOM.
• Shroff, R. (2023, November / Fall). Presenter   “FGFR and IDH Targeting in Cholangiocarcinoma”
  
  . Mayo Clinic Hepato-Pancreatico-Biliary Cancer Symposium. Las Vegas, Nevada: Mayo.
• Shroff, R. (2023, October / Fall).

  “Topaz-1: Updates and Analyses” 

  . 2023 Bermuda GI Summit. Fairmont Hamilton Princess, Bermuda: DAVA Oncology.
• Shroff, R. (2023, October / Fall). Co-Chair. 5th Annual LEAD Enriching Experiences for Women in Hematology & Oncology. Scottsdale, AZ: LEAD.
• Shroff, R. (2023, October / Fall). Moderator/Discussant “Hepatobiliary Cancer”  
  
  . 20th Annual Meeting of the International Society of Gastrointestinal Oncology (ISGIO). Tempe, AZ: ISGO.
• Shroff, R. (2023, September / Fall).

  Presenter “New systemic therapy options for iCCA”
  

  . International Liver Cancer Association (ILCA). Amsterdam, Netherlands: 17th Annual ILCA.
• Sohal, D., Kharofa, J., Olowokure, O. O., Rojan, A., Patel, S. H., Wilson, G. C., Sussman, J. J., Moreland, K., Patra, K., Bogdanov, V., Riall, T. S., Zavros, Y., Shroff, R., & Ahmed, S. A. (2023). An adaptive approach to neoadjuvant therapy to maximize resection rates for pancreatic adenocarcinoma: A phase II trial. 2023 ASCO Gastrointestinal Cancers Symposium.
• Shroff, R. (2022, Fall/September). Changing Lanscape of Front-Line Treatment for Biliary Tract Cancers. 19th Annual Meeting of the International Society of Gastrointestinal Oncology. Nashville, TN: ISGIO.
• Shroff, R. (2022, February/Winter). Changing the Landscape in Pacreatic/Biliary Cancers. PRIMO 2022. Waikoloa, Hawaii: PRIMO.
• Shroff, R. (2022, February/Winter). The Hottest Targeted Therapies on the Horizon for Cholangiocarcinoma . Cholangiocarcinoma Foundation Annual Conference. Salt Lake City, Utah: CCF.
• Shroff, R. (2022, February/Winter). The Targeted and Immunotherapy Revolution in Upper GI Malignancies. PRIMO 2022. Waikoloa, Hawaii: PRIMO.
• Shroff, R. (2022, October/Fall). Early detection and screening for BTC. 4th Annual Cholangiocarcinoma Summit. Aurora, CO.
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  Developing an Integrated and Multidisciplinary Approach to the Management of Biliary Tract Cancer
• Shroff, R. (2022, October/Fall). Targeted therapies and immunotherapy. 3rd Annual Cholangiocarcinoma Symposium. Chicago, IL: UChicago Medicine.
• Shroff, R. (2021, April/Spring). On the Horizon for BTC's. ASCO Advantage. virtual conference: ASCO.
• Shroff, R. (2021, August/Summer). Research Opportunities. COM-Tucson. HSIB: Banner/COM-T New Faculty Connection /virtual.
• Shroff, R. (2021, February/Winter). Hot Topics in Pancreatic and Biliary Cancer. Practical Recommendations in Immuno & Molecular Oncology (PRIMO). virtual conference: PRIMO.
• Shroff, R. (2021, March/Winter). Straight talk: Role of neoadjuvant chemotherapy in resectable biliary tract cancer. Advances in Gastrointestinal (GI) Cancers: A Virtual International Conference. virtual conference: Binaytara Foundation.
• Shroff, R. (2021, March/Winter). The new era of therapy in biliary cancers. Houston Methodist Cancer Center Grand Rounds. Virtual: Houston Methodist Hospital.
• Shroff, R. (2021, November/Winter). GI Lighting update. The Arizona Clinical Oncology Society (TACOS) Fall Conference. Scottsdale, AZ: TACOS.
• Shroff, R. (2021, November/Winter). Keynote Speaker. 8th Biennial HPB Oncology Symposium: Systemic Therapy for Advanced ICCA: Beyond Gemcitabine and platinum Keynote. Virtual: Wake Forest School of Medicine.
• Shroff, R. (2021, October/Fall). Systemic Therapy. Master Class for Community Oncologist and Oncology Fellows. virtual conference: The Lynx Group.
• Shroff, R. (2021, September/Fall). Presentation to MD/PhD students on career development. COM-Tucson. AHSL, 4th floor, room 4150A: University of Arizona.
• Shroff, R. (2020, December/Fall). Cholangiocarcinoma. Hepatology Weekly Conference. Virtual conference: University of Arizona/Department of Medicine.
• Shroff, R. (2020, December/Winter). Updates in the Management of HCC and Cholangiocarcinoma. GI Division Guest Lecture. Virtual conference: University of Arizona: Department of Medicine.
• Shroff, R. (2020, February/Winter). Changing the Landscape of Therapy: Molecular Subtype. Society of Interventional Oncology (SIO). New Orleans, LA: SIO.
• Shroff, R. (2020, February/Winter). Lower GI: Colorectal Cancer: Therapeutic Options & Future Directions. Practical Recommendations in Immuno & Molecular Oncology (PRIMO). Honolulu, Hawaii: PRIMO.
• Shroff, R. (2020, February/Winter). Upper GI Malignancies: Role of Immunotherapy. Practical Recommendations in Immuno & Molecular Oncology (PRIMO). Honolulu, Hawaii: PRIMO.
• Shroff, R. (2020, July/Summer). Co-Chair / presenter "Global Clinical Update". Cholangiocarcinoma Foundation (CCF). Virtual conference: CCF.
• Shroff, R. (2020, June/Summer). The Promise of Targeted Therapy in Cholangiocarcinoma. ASCO. virtual conference: ASCO.
• Shroff, R. (2020, March/Spring). Mutations Matter-Incorporating Personalized Therapy in the Peri-operative Setting. American Hepato-Pancreato-Biliary Association (AHPBA). Miami Beach, FL: AHPBA.
• Shroff, R. (2020, October/Fall). Incorporation of Emerging Treatment Options into Clinical Practice Paradigms: Gastrointestinal Cancer. Leadership, Empowerment and Development (LEAD). Virtual conference: LEAD.
• Shroff, R. (2020, September/Summer). Novel and Targeted Therapies in Biliary Cancer. Great Debates & Updates. Virtual conference: GDU.
• Shroff, R. (2020, September/Summer). Optimal First-Line Therapy for HCC is VEGF-Targeted Therapy. Great Debates & Updates. Virtual conference: GDU.
• Shroff, R. (2019, August/Summer). Sequencing in Metastatic Disease. International Congress of Gastrointestinal Tumors. Sao Paulo, Brazil: V International Gastrointestinla Symposium.
• Shroff, R. (2019, January/Winter). Novel Therapies for Cholangiocarcinoma: One Size Fits All. Gastrointestinal Cancers Symposium. San Francisco, CA.
• Shroff, R. (2019, July/Summer). Hepatobiliary/Pancreatic/Gastrointestional Cancer. ASCO Direct Highlights : 2019 Official Annual Meeting Review. New York, NY: Accociation of Community Cancer Centers.
• Shroff, R. (2019, June/Summer). The Evolving Role of PARP. Pancreatic Cancer Expert Input Forum. Chicago, IL: MERCK.
• Shroff, R. (2019, March/Spring). Down-staging Locally Advanced Disease. 3rd Asia Pacific Cholangiocarcinoma Conference. Taipei, Taiwan: APC.
• Shroff, R. (2019, March/Spring). Where is Progress in Systemic Therapy?. Regional Summit Series : Gastrointestinal Malignancies. Pasadena, CA: DAVA Oncology.
• Shroff, R. (2019, November/Winter). Highlight Research and Community Efforts at UACC. 7th Annual Arizona Cancer Summit. University of Arizona: U of A.
• Shroff, R. (2019, October/Fall). Moderator. Spotlight on Stomach Cancer Symposium. Tucson.
• Shroff, R. (2019, October/Fall). Systemic Therapies for Cholangiocarcinoma: One Size Fits All?. The International Society of Gastrointestinal Oncology (ISGIO). Arlington, Virginia: ISGIO.
• Shroff, R. (2019, October/Fall). When Biomarkers Define Indication - MSI, MMR, and Mutations. Leadership Empowerment and Development (LEAD) : Enriching Experiences for Women in Hematology and Oncology. Santa Monica, CA: LEAD.
• Shroff, R. (2019, September/Fall). Single-agent and Combination PARP Inhibitors for Pancreatic Cancer. Eepert Forum on Gastrointestinal Malignancies. Dallas, TX: DAVA Oncology.
• Shroff, R. (2018, December/Winter). ASCO Voices Session. ASCO. Chicago, IL: ASCO.
• Shroff, R. (2018, January/Winter). Engaging Patients in Cholangiocarcinoma. 2018 Chlangiocarcinoma Foundation Annual Conference. Salt Lake City, UT.
• Shroff, R. (2018, July/Summer). GI Noncolorectal Abstracts. Best of ASCO - Delhi 2018. New Delhi, India: Delhi 2018.
• Shroff, R. (2018, March/Spring). Management of Advanced Biliary Cancers,. PNUH-ICRN Summit Conference. Pusan, South Korea: Pusan University National Hospital.
• Shroff, R. (2018, March/Spring). Management of Advanced Biliary Cancers. International Hepatobiliary Summit. Shanghai, China.
• Shroff, R. (2018, October/Fall). FOR Adjuvant Therapy in Biliary Cancers. Mayo Clinic Pancreatic and Hepato-biliary Cancer Symposium. Phoenix, AZ.
• Shroff, R. (2018, October/Fall). Gallbladder Cancer: New Horizons in Therapy. Japanese Society of Clinical Oncology Annual Meeting. Yokohama, Japan: JSCO.

Poster Presentations

• Shroff, R. (2018, June/Summer). Noncolorectal Poster Discussion Session. ASCO Annual Meeting. Chicago, IL: ASCO.

Other Teaching Materials

• Shroff, R. (2019. Co-organizer: Workshop: Strategic Planning Retreat. University of Arizona Cancer Center.

Others

• Shroff, R. (2023, August).

  76^th Indian Society of Southern Arizona (ISSA), Tucson, Arizona

  . Volunteer Activity.
• Shroff, R. (2022, August/Summer). Novel and Targeted Therapies in Cholangiocarcinoma. Great Debate & Updates - Gastrointestinal Malignancies.
• Shroff, R. (2022, November/Fall).

  The Biliary Tract Cancer Algorithm 
  ·       STEP 1—Understanding the Cancer 
  o   Review of biliary tract cancers 
  o   Understanding the pathogenesis of biliary tract cancers 
  ·       STEP 2—Identifying the Patient 
  o   Discuss the signs and symptoms of patients with potential biliary tract cancers 
  o   Review the appropriate steps of diagnosis 
  ·       STEP 3—Gastroenterologist, Hepatologist, and Primary Care Provider Role in the BTC Algorithm 
  o   Conceptualizing the steps of diagnosis 
  o   Building communication pathways with other specialties to ensure seamless transitions of care 
  o   Understanding the immunotherapy-based treatment approaches for front-line BTC 

  . Medscape Live Program in Hepatobiliary Carcinomas.
  More info

  Target Audience: This activity is intended for gastroenterologists, oncologists, primary care physicians, and other clinicians involved in the care of patients at risk of or diagnosed with hepatobiliary cancersLearning Objectives – Upon completion of this activity, will have:  Increased knowledge regarding the Epidemiological patterns of hepatobiliary carcinomas Identification and management of patients who are at risk of developing hepatobiliary carcinoma Immunotherapy-based treatment approaches for patients with hepatobiliary carcinomas in the front-line setting Role of the multispecialty team in the management of patients with hepatobiliary carcinomas Greater confidence in their ability to effectively communicating among specialties regarding the care of patients with hepatobiliary carcinoma 
• Shroff, R. (2019, January). Cholangiocarcinoma Foundation Annual Conference. Chairing.
  More info

  EPIC Session I/ Industry Forum Precision Medicine in CCA - Shroff, chairingEPIC Session II/ Industry Forum II