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Clinical Sequencing Contributes to a BRCA-Associated Cancer Rediagnosis That Guides an Effective Therapeutic Course

Jocelyn S. Chapman, Saurabh Asthana, Lindsay Cade, Matthew T. Chang, Zhen Wang, Charles J. Zaloudek, Stefanie Ueda, Eric A. Collisson, and Barry S. Taylor

Cancer is currently classified and treated using an approach based on tissue of origin. Ambiguous or incorrect diagnoses, however, are common and often go unnoticed. Clinical cancer sequencing can provide diagnostic precision, therapeutic direction, and hereditary cancer risk assessment. This report presents a patient with an initial diagnosis of metastatic pancreatic adenocarcinoma (PDA), a disease with a dismal prognosis. Tumor sequencing revealed genomic abnormalities inconsistent with PDA, instead suggesting serous ovarian cancer. This molecular rediagnosis was further refined by the identification of a BRCA2 truncating mutation in the tumor, subsequently confirmed to be a germline event. These findings prompted the initiation of platinum-based chemotherapy, which produced a life-altering response, and referral to genetic counseling for her offspring. These results suggest that clinical tumor sequencing can simultaneously clarify diagnoses, guide therapy, and inform familial risk, even in patients with end-stage metastatic disease, making the case for the development of specific strategies to deploy sequencing coupled with big data in oncology to improve clinical cancer management.

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Vulvar Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology

Wui-Jin Koh, Benjamin E. Greer, Nadeem R. Abu-Rustum, Susana M. Campos, Kathleen R. Cho, Hye Sook Chon, Christina Chu, David Cohn, Marta Ann Crispens, Don S. Dizon, Oliver Dorigo, Patricia J. Eifel, Christine M. Fisher, Peter Frederick, David K. Gaffney, Ernest Han, Susan Higgins, Warner K. Huh, John R. Lurain III, Andrea Mariani, David Mutch, Christa Nagel, Larissa Nekhlyudov, Amanda Nickles Fader, Steven W. Remmenga, R. Kevin Reynolds, Todd Tillmanns, Stefanie Ueda, Fidel A. Valea, Emily Wyse, Catheryn M. Yashar, Nicole McMillian, and Jillian Scavone

Vulvar cancer is a rare gynecologic malignancy. Ninety percent of vulvar cancers are predominantly squamous cell carcinomas (SCCs), which can arise through human papilloma virus (HPV)–dependent and HPV-independent pathways. The NCCN Vulvar Cancer panel is an interdisciplinary group of representatives from NCCN Member Institutions consisting of specialists in gynecological oncology, medical oncology, radiation oncology, and pathology. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Vulvar Cancer provide an evidence- and consensus-based approach for the management of patients with vulvar SCC. This manuscript discusses the recommendations outlined in the NCCN Guidelines for diagnosis, staging, treatment, and follow-up.

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NCCN Guidelines® Insights: Uterine Neoplasms, Version 3.2021

Featured Updates to the NCCN Guidelines

Nadeem R. Abu-Rustum, Catheryn M. Yashar, Kristin Bradley, Susana M. Campos, Junzo Chino, Hye Sook Chon, Christina Chu, David Cohn, Marta Ann Crispens, Shari Damast, Elisabeth Diver, Christine M. Fisher, Peter Frederick, David K. Gaffney, Suzanne George, Robert Giuntoli II, Ernest Han, Brooke Howitt, Warner K. Huh, Jayanthi Lea, Andrea Mariani, David Mutch, Larissa Nekhlyudov, Mirna Podoll, Steven W. Remmenga, R. Kevin Reynolds, Ritu Salani, Rachel Sisodia, Pamela Soliman, Edward Tanner, Stefanie Ueda, Renata Urban, Stephanie L. Wethington, Emily Wyse, Kristine Zanotti, Nicole R. McMillian, and Angela D. Motter

The NCCN Guidelines for Uterine Neoplasms provide recommendations for diagnostic workup, clinical staging, and treatment options for patients with endometrial cancer or uterine sarcoma. These NCCN Guidelines Insights focus on the recent addition of molecular profiling information to aid in accurate diagnosis, classification, and treatment of uterine sarcomas.

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NCCN Guidelines Insights: Cervical Cancer, Version 1.2020

Featured Updates to the NCCN Guidelines

Nadeem R. Abu-Rustum, Catheryn M. Yashar, Sarah Bean, Kristin Bradley, Susana M. Campos, Hye Sook Chon, Christina Chu, David Cohn, Marta Ann Crispens, Shari Damast, Christine M. Fisher, Peter Frederick, David K. Gaffney, Robert Giuntoli II, Ernest Han, Warner K. Huh, John R. Lurain III, Andrea Mariani, David Mutch, Christa Nagel, Larissa Nekhlyudov, Amanda Nickles Fader, Steven W. Remmenga, R. Kevin Reynolds, Rachel Sisodia, Todd Tillmanns, Stefanie Ueda, Renata Urban, Emily Wyse, Nicole R. McMillian, and Angela D. Motter

The NCCN Guidelines for Cervical Cancer provide recommendations for diagnostic workup, staging, and treatment of patients with the disease. These NCCN Guidelines Insights focus on recent updates to the guidelines, including changes to first- and second-line systemic therapy recommendations for patients with recurrent or metastatic disease, and emerging evidence on a new histopathologic classification system for HPV-related endocervical adenocarcinoma.

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Gestational Trophoblastic Neoplasia, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology

Nadeem R. Abu-Rustum, Catheryn M. Yashar, Sarah Bean, Kristin Bradley, Susana M. Campos, Hye Sook Chon, Christina Chu, David Cohn, Marta Ann Crispens, Shari Damast, Oliver Dorigo, Patricia J. Eifel, Christine M. Fisher, Peter Frederick, David K. Gaffney, Ernest Han, Warner K. Huh, John R. Lurain III, Andrea Mariani, David Mutch, Christa Nagel, Larissa Nekhlyudov, Amanda Nickles Fader, Steven W. Remmenga, R. Kevin Reynolds, Rachel Sisodia, Todd Tillmanns, Stefanie Ueda, Emily Wyse, Nicole R. McMillian, and Jillian Scavone

Gestational trophoblastic neoplasia (GTN), a subset of gestational trophoblastic disease (GTD), occurs when tumors develop in the cells that would normally form the placenta during pregnancy. The NCCN Guidelines for Gestational Trophoblastic Neoplasia provides treatment recommendations for various types of GTD including hydatidiform mole, persistent post-molar GTN, low-risk GTN, high-risk GTN, and intermediate trophoblastic tumor.

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Cervical Cancer, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology

Wui-Jin Koh, Nadeem R. Abu-Rustum, Sarah Bean, Kristin Bradley, Susana M. Campos, Kathleen R. Cho, Hye Sook Chon, Christina Chu, Rachel Clark, David Cohn, Marta Ann Crispens, Shari Damast, Oliver Dorigo, Patricia J. Eifel, Christine M. Fisher, Peter Frederick, David K. Gaffney, Ernest Han, Warner K. Huh, John R. Lurain III, Andrea Mariani, David Mutch, Christa Nagel, Larissa Nekhlyudov, Amanda Nickles Fader, Steven W. Remmenga, R. Kevin Reynolds, Todd Tillmanns, Stefanie Ueda, Emily Wyse, Catheryn M. Yashar, Nicole R. McMillian, and Jillian L. Scavone

Cervical cancer is a malignant epithelial tumor that forms in the uterine cervix. Most cases of cervical cancer are preventable through human papilloma virus (HPV) vaccination, routine screening, and treatment of precancerous lesions. However, due to inadequate screening protocols in many regions of the world, cervical cancer remains the fourth-most common cancer in women globally. The complete NCCN Guidelines for Cervical Cancer provide recommendations for the diagnosis, evaluation, and treatment of cervical cancer. This manuscript discusses guiding principles for the workup, staging, and treatment of early stage and locally advanced cervical cancer, as well as evidence for these recommendations. For recommendations regarding treatment of recurrent or metastatic disease, please see the full guidelines on NCCN.org.

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Uterine Neoplasms, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology

Wui-Jin Koh, Nadeem R. Abu-Rustum, Sarah Bean, Kristin Bradley, Susana M. Campos, Kathleen R. Cho, Hye Sook Chon, Christina Chu, David Cohn, Marta Ann Crispens, Shari Damast, Oliver Dorigo, Patricia J. Eifel, Christine M. Fisher, Peter Frederick, David K. Gaffney, Suzanne George, Ernest Han, Susan Higgins, Warner K. Huh, John R. Lurain III, Andrea Mariani, David Mutch, Christa Nagel, Larissa Nekhlyudov, Amanda Nickles Fader, Steven W. Remmenga, R. Kevin Reynolds, Todd Tillmanns, Stefanie Ueda, Emily Wyse, Catheryn M. Yashar, Nicole R. McMillian, and Jillian L. Scavone

Endometrial carcinoma is a malignant epithelial tumor that forms in the inner lining, or endometrium, of the uterus. Endometrial carcinoma is the most common gynecologic malignancy. Approximately two-thirds of endometrial carcinoma cases are diagnosed with disease confined to the uterus. The complete NCCN Guidelines for Uterine Neoplasms provide recommendations for the diagnosis, evaluation, and treatment of endometrial cancer and uterine sarcoma. This manuscript discusses guiding principles for the diagnosis, staging, and treatment of early-stage endometrial carcinoma as well as evidence for these recommendations.

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NCCN Guidelines® Insights: Cervical Cancer, Version 1.2024

Featured Updates to the NCCN Guidelines

Nadeem R. Abu-Rustum, Catheryn M. Yashar, Rebecca Arend, Emma Barber, Kristin Bradley, Rebecca Brooks, Susana M. Campos, Junzo Chino, Hye Sook Chon, Marta Ann Crispens, Shari Damast, Christine M. Fisher, Peter Frederick, David K. Gaffney, Stephanie Gaillard, Robert Giuntoli II, Scott Glaser, Jordan Holmes, Brooke E. Howitt, Jayanthi Lea, Gina Mantia-Smaldone, Andrea Mariani, David Mutch, Christa Nagel, Larissa Nekhlyudov, Mirna Podoll, Kerry Rodabaugh, Ritu Salani, John Schorge, Jean Siedel, Rachel Sisodia, Pamela Soliman, Stefanie Ueda, Renata Urban, Emily Wyse, Nicole R. McMillian, Shaili Aggarwal, and Sara Espinosa

The NCCN Guidelines for Cervical Cancer provide recommendations for all aspects of management for cervical cancer, including the diagnostic workup, staging, pathology, and treatment. The guidelines also include details on histopathologic classification of cervical cancer regarding diagnostic features, molecular profiles, and clinical outcomes. The treatment landscape of advanced cervical cancer is evolving constantly. These NCCN Guidelines Insights provide a summary of recent updates regarding the systemic therapy recommendations for recurrent or metastatic disease.

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Vulvar Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology

Nadeem R. Abu-Rustum, Catheryn M. Yashar, Rebecca Arend, Emma Barber, Kristin Bradley, Rebecca Brooks, Susana M. Campos, Junzo Chino, Hye Sook Chon, Marta Ann Crispens, Shari Damast, Christine M. Fisher, Peter Frederick, David K. Gaffney, Stephanie Gaillard, Robert Giuntoli II, Scott Glaser, Jordan Holmes, Brooke E. Howitt, Kari Kendra, Jayanthi Lea, Nita Lee, Gina Mantia-Smaldone, Andrea Mariani, David Mutch, Christa Nagel, Larissa Nekhlyudov, Mirna Podoll, Kerry Rodabaugh, Ritu Salani, John Schorge, Jean Siedel, Rachel Sisodia, Pamela Soliman, Stefanie Ueda, Renata Urban, Stephanie L. Wethington, Emily Wyse, Kristine Zanotti, Nicole McMillian, and Sara Espinosa

Vulvar cancer is annually diagnosed in an estimated 6,470 individuals and the vast majority are histologically squamous cell carcinomas. Vulvar cancer accounts for 5% to 8% of gynecologic malignancies. Known risk factors for vulvar cancer include increasing age, infection with human papillomavirus, cigarette smoking, inflammatory conditions affecting the vulva, and immunodeficiency. Most vulvar neoplasias are diagnosed at early stages. Rarer histologies exist and include melanoma, extramammary Paget’s disease, Bartholin gland adenocarcinoma, verrucous carcinoma, basal cell carcinoma, and sarcoma. This manuscript discusses recommendations outlined in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for treatments, surveillance, systemic therapy options, and gynecologic survivorship.

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Uterine Neoplasms, Version 1.2023, NCCN Clinical Practice Guidelines in Oncology

Nadeem Abu-Rustum, Catheryn Yashar, Rebecca Arend, Emma Barber, Kristin Bradley, Rebecca Brooks, Susana M. Campos, Junzo Chino, Hye Sook Chon, Christina Chu, Marta Ann Crispens, Shari Damast, Christine M. Fisher, Peter Frederick, David K. Gaffney, Robert Giuntoli II, Ernest Han, Jordan Holmes, Brooke E. Howitt, Jayanthi Lea, Andrea Mariani, David Mutch, Christa Nagel, Larissa Nekhlyudov, Mirna Podoll, Ritu Salani, John Schorge, Jean Siedel, Rachel Sisodia, Pamela Soliman, Stefanie Ueda, Renata Urban, Stephanie L. Wethington, Emily Wyse, Kristine Zanotti, Nicole R. McMillian, and Shaili Aggarwal

Adenocarcinoma of the endometrium (also known as endometrial cancer, or more broadly as uterine cancer or carcinoma of the uterine corpus) is the most common malignancy of the female genital tract in the United States. It is estimated that 65,950 new uterine cancer cases will have occurred in 2022, with 12,550 deaths resulting from the disease. Endometrial carcinoma includes pure endometrioid cancer and carcinomas with high-risk endometrial histology (including uterine serous carcinoma, clear cell carcinoma, carcinosarcoma [also known as malignant mixed Müllerian tumor], and undifferentiated/dedifferentiated carcinoma). Stromal or mesenchymal sarcomas are uncommon subtypes accounting for approximately 3% of all uterine cancers. This selection from the NCCN Guidelines for Uterine Neoplasms focuses on the diagnosis, staging, and management of pure endometrioid carcinoma. The complete version of the NCCN Guidelines for Uterine Neoplasms is available online at NCCN.org.