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The Call of “The Wild”-Type GIST: It's Time for Domestication

Maha Alkhuziem, Adam M. Burgoyne, Paul T. Fanta, Chih-Min Tang, and Jason K. Sicklick

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A Novel PRKAR1B-BRAF Fusion in Gastrointestinal Stromal Tumor Guides Adjuvant Treatment Decision-Making During Pregnancy

Lindsey M. Charo, Adam M. Burgoyne, Paul T. Fanta, Hitendra Patel, Juliann Chmielecki, Jason K. Sicklick, and Michael T. McHale

Gastrointestinal stromal tumors (GISTs) are rare in pregnancy, with only 11 reported cases. Adjuvant imatinib therapy, which targets the most common driver mutations in GIST (KIT and PDGFRA), is recommended for patients with high-risk GIST, but it has known teratogenicity in the first trimester. A 34-year-old G3P2 woman underwent exploratory laparotomy at 16 weeks' gestation for a presumed adnexal mass. Surgical findings included normal adnexa and a 14-cm solid small bowel mass. The mass was resected en bloc with a segment of jejunum followed by a primary anastomosis. Histopathology and genomic analyses demonstrated a GIST with high-risk features but lack of KIT/PDGFRA mutations and identified the presence of a previously unreported, pathogenic PRKAR1B-BRAF gene fusion. Given her tumor profile, adjuvant therapy with imatinib was not recommended. GIST is rare in pregnancy, but can masquerade as an adnexal mass in women of childbearing age. Because neoadjuvant/adjuvant imatinib has risks of teratogenicity, tumor molecular profiling is critical as we identified a previously unreported gene fusion of PRKAR1B with BRAF that is predicted to be imatinib-resistant. In this case, testing provided the rationale for not offering adjuvant imatinib to avoid unnecessary toxicity to the patient and fetus.

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NCCN Guidelines Insights: Hepatobiliary Cancers, Version 1.2017

Al B. Benson III, Michael I. D'Angelica, Daniel E. Abbott, Thomas A. Abrams, Steven R. Alberts, Daniel A. Anaya, Chandrakanth Are, Daniel B. Brown, Daniel T. Chang, Anne M. Covey, William Hawkins, Renuka Iyer, Rojymon Jacob, Andrea Karachristos, R. Kate Kelley, Robin Kim, Manisha Palta, James O. Park, Vaibhav Sahai, Tracey Schefter, Carl Schmidt, Jason K. Sicklick, Gagandeep Singh, Davendra Sohal, Stacey Stein, G. Gary Tian, Jean-Nicolas Vauthey, Alan P. Venook, Andrew X. Zhu, Karin G. Hoffmann, and Susan Darlow

The NCCN Guidelines for Hepatobiliary Cancers provide treatment recommendations for cancers of the liver, gallbladder, and bile ducts. The NCCN Hepatobiliary Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding locoregional therapy for treatment of patients with hepatocellular carcinoma.

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NCCN Guidelines® Insights: Gastrointestinal Stromal Tumors, Version 2.2022

Featured Updates to the NCCN Guidelines

Margaret von Mehren, John M. Kane III, Richard F. Riedel, Jason K. Sicklick, Seth M. Pollack, Mark Agulnik, Marilyn M. Bui, Janai Carr-Ascher, Edwin Choy, Mary Connelly, Sarah Dry, Kristen N. Ganjoo, Ricardo J. Gonzalez, Ashley Holder, Jade Homsi, Vicki Keedy, Ciara M. Kelly, Edward Kim, David Liebner, Martin McCarter, Sean V. McGarry, Nathan W. Mesko, Christian Meyer, Alberto S. Pappo, Amanda M. Parkes, Ivy A. Petersen, Matthew Poppe, Scott Schuetze, Jacob Shabason, Matthew B. Spraker, Melissa Zimel, Mary Anne Bergman, Hema Sundar, and Lisa E. Hang

Gastrointestinal stromal tumors (GIST) are the most common type of soft tissue sarcoma that occur throughout the gastrointestinal tract. Most of these tumors are caused by oncogenic activating mutations in the KIT or PDGFRA genes. The NCCN Guidelines for GIST provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with these tumors. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including revised systemic therapy options for unresectable, progressive, or metastatic GIST based on mutational status, and updated recommendations for the management of GIST that develop resistance to specific tyrosine kinase inhibitors.

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Soft Tissue Sarcoma, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology

Margaret von Mehren, John M. Kane, Mark Agulnik, Marilyn M. Bui, Janai Carr-Ascher, Edwin Choy, Mary Connelly, Sarah Dry, Kristen N. Ganjoo, Ricardo J. Gonzalez, Ashley Holder, Jade Homsi, Vicki Keedy, Ciara M. Kelly, Edward Kim, David Liebner, Martin McCarter, Sean V. McGarry, Nathan W. Mesko, Christian Meyer, Alberto S. Pappo, Amanda M. Parkes, Ivy A. Petersen, Seth M. Pollack, Matthew Poppe, Richard F. Riedel, Scott Schuetze, Jacob Shabason, Jason K. Sicklick, Matthew B. Spraker, Melissa Zimel, Lisa E. Hang, Hema Sundar, and Mary Anne Bergman

Soft tissue sarcomas (STS) are rare malignancies of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Soft Tissue Sarcoma provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as retroperitoneal/intra-abdominal STS, desmoid tumors, and rhabdomyosarcoma. This portion of the NCCN Guidelines discusses general principles for the diagnosis and treatment of retroperitoneal/intra-abdominal STS, outlines treatment recommendations, and reviews the evidence to support the guidelines recommendations.

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NCCN Guidelines Insights: Soft Tissue Sarcoma, Version 1.2021

Featured Updates to the NCCN Guidelines

Margaret von Mehren, John M. Kane III, Marilyn M. Bui, Edwin Choy, Mary Connelly, Sarah Dry, Kristen N. Ganjoo, Suzanne George, Ricardo J. Gonzalez, Martin J. Heslin, Jade Homsi, Vicki Keedy, Ciara M. Kelly, Edward Kim, David Liebner, Martin McCarter, Sean V. McGarry, Christian Meyer, Alberto S. Pappo, Amanda M. Parkes, I. Benjamin Paz, Ivy A. Petersen, Matthew Poppe, Richard F. Riedel, Brian Rubin, Scott Schuetze, Jacob Shabason, Jason K. Sicklick, Matthew B. Spraker, Melissa Zimel, Mary Anne Bergman, and Giby V. George

The NCCN Guidelines for Soft Tissue Sarcoma provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with soft tissue sarcomas. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including the development of a separate and distinct guideline for gastrointestinal stromal tumors (GISTs); reconception of the management of desmoid tumors; inclusion of further recommendations for the diagnosis and management of extremity/body wall, head/neck sarcomas, and retroperitoneal sarcomas; modification and addition of systemic therapy regimens for sarcoma subtypes; and revision of the principles of radiation therapy for soft tissue sarcomas.

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NCCN Guidelines Insights: Hepatobiliary Cancers, Version 2.2019

Featured Updates to the NCCN Guidelines

Al B. Benson III, Michael I. D’Angelica, Daniel E. Abbott, Thomas A. Abrams, Steven R. Alberts, Daniel A. Anaya, Robert Anders, Chandrakanth Are, Daniel Brown, Daniel T. Chang, Jordan Cloyd, Anne M. Covey, William Hawkins, Renuka Iyer, Rojymon Jacob, Andreas Karachristos, R. Kate Kelley, Robin Kim, Manisha Palta, James O. Park, Vaibhav Sahai, Tracey Schefter, Jason K. Sicklick, Gagandeep Singh, Davendra Sohal, Stacey Stein, G. Gary Tian, Jean-Nicolas Vauthey, Alan P. Venook, Lydia J. Hammond, and Susan D. Darlow

The NCCN Guidelines for Hepatobiliary Cancers provide treatment recommendations for cancers of the liver, gallbladder, and bile ducts. The NCCN Hepatobiliary Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel’s discussion and updated recommendations regarding systemic therapy for first-line and subsequent-line treatment of patients with hepatocellular carcinoma.