Next-generation sequencing (NGS) has risen to the forefront of tumor analysis and has enabled unprecedented advances in the molecular profiling of solid tumors. Through massively parallel sequencing, previously unrecognized genomic alterations have been unveiled in many malignancies, including gynecologic cancers, thus expanding the potential repertoire for the use of targeted therapies. NGS has expanded the understanding of the genomic foundation of gynecologic malignancies and has allowed identification of germline and somatic mutations associated with cancer development, enabled tumor reclassification, and helped determine mechanisms of treatment resistance. NGS has also facilitated rationale therapeutic strategies based on actionable molecular aberrations. However, issues remain regarding cost and clinical utility. This review covers NGS analysis of and its impact thus far on gynecologic cancers, specifically ovarian, endometrial, cervical, and vulvar cancers.
Next-Generation Sequencing: Role in Gynecologic Cancers
Tarra Evans and Ursula Matulonis
Chemotherapy Hypersensitivity Reactions in Ovarian Cancer
Matthieu Picard, Ursula A. Matulonis, and Mariana Castells
Ovarian cancer is the fifth leading cause of cancer death among women in the United States. Chemotherapy using a taxane and platinum combination is key in improving survival in patients with newly diagnosed advanced ovarian cancer and is also used to treat recurrent platinum-sensitive disease. However, hypersensitivity reactions (HSRs) to chemotherapeutic agents are increasingly common and can greatly limit their use. Moreover, because of the frequent lack of equally effective alternative agents, chances of survival can be compromised. Therefore, physicians caring for these patients must be familiar with the management of HSRs to chemotherapy, and major advancements have recently been made in this field. Most HSRs implicate mast cell and basophil activation either through an IgE-mediated (ie, platinum agents) or nonspecific (ie, taxanes) mechanism. Therefore, these reactions have the potential to lead to anaphylaxis, at which time they should be treated with intramuscular epinephrine. Serum tryptase, which is released alongside histamine after mast cell activation, may be measured after an acute HSR to document mast cell involvement. After an HSR, the decision to re-treat with the same agent or a closely related one will vary depending on the causative drug, the type of HSR, and its severity. Drug desensitization has emerged as a safe and effective way of reintroducing a chemotherapeutic agent or monoclonal antibody responsible for an HSR in a patient who is expected to benefit from its continued use and for whom alternatives are considered less effective and/or more toxic. Currently, candidates for desensitization are preferably evaluated in academic settings with expertise in those procedures, because their use is still limited. Efforts are now needed to increase awareness about desensitization procedures so that more patients may benefit. This challenge will require the close collaboration of patients, nurses, oncologists, and allergists.
Cancer- and Chemotherapy-Induced Anemia
George M. Rodgers III, Pamela Sue Becker, Morey Blinder, David Cella, Asher Chanan-Khan, Charles Cleeland, Peter F. Coccia, Benjamin Djulbegovic, Jeffrey A. Gilreath, Eric H. Kraut, Ursula A. Matulonis, Michael M. Millenson, Denise Reinke, Joseph Rosenthal, Rowena N. Schwartz, Gerald Soff, Richard S. Stein, Gordana Vlahovic, and Alva B. Weir III
Anemia is prevalent in 30% to 90% of patients with cancer. Anemia can be corrected through either treating the underlying cause or providing supportive care through transfusion with packed red blood cells or administration of erythropoiesis-stimulating agents (ESAs), with or without iron supplementation. Recent studies showing detrimental health effects of ESAs sparked a series of FDA label revisions and a sea change in the perception of these once commonly used agents. In light of this, the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cancer- and Chemotherapy-Induced Anemia underwent substantial revisions this year. The purpose of these NCCN Guidelines is twofold: 1) to operationalize the evaluation and treatment of anemia in adult cancer patients, with an emphasis on those who are receiving concomitant chemotherapy, and 2) to enable patients and clinicians to individualize anemia treatment options based on patient condition.
NCCN Biosimilars White Paper: Regulatory, Scientific, and Patient Safety Perspectives
Andrew D. Zelenetz, Islah Ahmed, Edward Louis Braud, James D. Cross, Nancy Davenport-Ennis, Barry D. Dickinson, Steven E. Goldberg, Scott Gottlieb, Philip E. Johnson, Gary H. Lyman, Richard Markus, Ursula A. Matulonis, Denise Reinke, Edward C. Li, Jessica DeMartino, Jonathan K. Larsen, and James M. Hoffman
Biologics are essential to oncology care. As patents for older biologics begin to expire, the United States is developing an abbreviated regulatory process for the approval of similar biologics (biosimilars), which raises important considerations for the safe and appropriate incorporation of biosimilars into clinical practice for patients with cancer. The potential for biosimilars to reduce the cost of biologics, which are often high-cost components of oncology care, was the impetus behind the Biologics Price Competition and Innovation Act of 2009, a part of the 2010 Affordable Care Act. In March 2011, NCCN assembled a work group consisting of thought leaders from NCCN Member Institutions and other organizations, to provide guidance regarding the challenges health care providers and other key stakeholders face in incorporating biosimilars in health care practice. The work group identified challenges surrounding biosimilars, including health care provider knowledge, substitution practices, pharmacovigilance, naming and product tracking, coverage and reimbursement, use in off-label settings, and data requirements for approval.
Ovarian Cancer, Version 2.2013
Robert J. Morgan Jr, Ronald D. Alvarez, Deborah K. Armstrong, Robert A. Burger, Lee-may Chen, Larry Copeland, Marta Ann Crispens, David M. Gershenson, Heidi J. Gray, Ardeshir Hakam, Laura J. Havrilesky, Carolyn Johnston, Shashikant Lele, Lainie Martin, Ursula A. Matulonis, David M. O’Malley, Richard T. Penson, Matthew A. Powell, Steven W. Remmenga, Paul Sabbatini, Joseph T. Santoso, Julian C. Schink, Nelson Teng, Theresa L. Werner, Mary A. Dwyer, and Miranda Hughes
These NCCN Guidelines Insights focus on the major updates to the 2013 NCCN Guidelines for Ovarian Cancer. Four updates were selected based on recent important updates in the guidelines and on debate among panel members about recent clinical trials. The topics include 1) intraperitoneal chemotherapy, 2) CA-125 monitoring for ovarian cancer recurrence, 3) surveillance recommendations for less common ovarian histopathologies, and 4) recent changes in therapy for recurrent epithelial ovarian cancer. These NCCN Guidelines Insights also discuss why some recommendations were not made.
Ovarian Cancer, Version 3.2012
Robert J. Morgan, Ronald D. Alvarez, Deborah K. Armstrong, Robert A. Burger, Mariana Castells, Lee-may Chen, Larry Copeland, Marta Ann Crispens, David Gershenson, Heidi Gray, Ardeshir Hakam, Laura J. Havrilesky, Carolyn Johnston, Shashikant Lele, Lainie Martin, Ursula A. Matulonis, David M. O’Malley, Richard T. Penson, Steven W. Remmenga, Paul Sabbatini, Joseph T. Santoso, Russell J. Schilder, Julian Schink, Nelson Teng, Theresa L. Werner, Miranda Hughes, and Mary A. Dwyer
These NCCN Guidelines Insights focus on the major updates for the 2012 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Ovarian Cancer by describing how and why the new recommendations were made. The 6 update topics were selected based on recent important updates in the guidelines and on debate among panel members about recent clinical trials, and include: 1) screening, 2) diagnostic tests for assessing pelvic masses, 3) primary treatment using neoadjuvant chemotherapy, 4) primary adjuvant treatment using bevacizumab in combination with chemotherapy, 5) therapy for recurrent disease, and 6) management of drug/hypersensitivity reactions. These NCCN Guidelines Insights also discuss why some recommendations were not made (eg, panel members did not feel the new data warranted changing the guideline). See “Updates” in the NCCN Guidelines for Ovarian Cancer for a complete list of all the recent revisions.
Epithelial Ovarian Cancer
Robert J. Morgan Jr., Ronald D. Alvarez, Deborah K. Armstrong, Barry Boston, Robert A. Burger, Lee-may Chen, Larry Copeland, Marta Ann Crispens, David Gershenson, Heidi J. Gray, Perry W. Grigsby, Ardeshir Hakam, Laura J. Havrilesky, Carolyn Johnston, Shashikant Lele, Ursula A. Matulonis, David M. O'Malley, Richard T. Penson, Steven W. Remmenga, Paul Sabbatini, Russell J. Schilder, Julian C. Schink, Nelson Teng, and Theresa L. Werner
Ovarian Cancer, Version 1.2016, NCCN Clinical Practice Guidelines in Oncology
Robert J. Morgan Jr, Deborah K. Armstrong, Ronald D. Alvarez, Jamie N. Bakkum-Gamez, Kian Behbakht, Lee-may Chen, Larry Copeland, Marta Ann Crispens, Maria DeRosa, Oliver Dorigo, David M. Gershenson, Heidi J. Gray, Ardeshir Hakam, Laura J. Havrilesky, Carolyn Johnston, Shashikant Lele, Lainie Martin, Ursula A. Matulonis, David M. O'Malley, Richard T. Penson, Sanja Percac-Lima, Mario Pineda, Steven C. Plaxe, Matthew A. Powell, Elena Ratner, Steven W. Remmenga, Peter G. Rose, Paul Sabbatini, Joseph T. Santoso, Theresa L. Werner, Jennifer Burns, and Miranda Hughes
This selection from the NCCN Guidelines for Ovarian Cancer focuses on the less common ovarian histopathologies (LCOHs), because new algorithms were added for LCOHs and current algorithms were revised for the 2016 update. The new LCOHs algorithms include clear cell carcinomas, mucinous carcinomas, and grade 1 (low-grade) serous carcinomas/endometrioid epithelial carcinomas. The LCOHs also include carcinosarcomas (malignant mixed Müllerian tumors of the ovary), borderline epithelial tumors (also known as low malignant potential tumors), malignant sex cord-stromal tumors, and malignant germ cell tumors.