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Edward E. Partridge, Nadeem Abu-Rustum, Anna Giuliano, Stewart Massad, Joan McClure, Mary Dwyer and Miranda Hughes

These NCCN Guidelines Insights focus on recent recommendations for cervical cancer screening and management of abnormal screening tests. When the NCCN Panel convened to update the NCCN Guidelines for Cervical Cancer Screening, they decided to adopt and endorse guidelines from other organizations to avoid duplication of effort. Therefore, in July 2013, after review and validation of consensus guidelines from the American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology, the NCCN Guidelines for Cervical Cancer Screening were discontinued.

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Mary B. Daly, Robert Pilarski, Jennifer E. Axilbund, Saundra S. Buys, Beth Crawford, Susan Friedman, Judy E. Garber, Carolyn Horton, Virginia Kaklamani, Catherine Klein, Wendy Kohlmann, Allison Kurian, Jennifer Litton, Lisa Madlensky, P. Kelly Marcom, Sofia D. Merajver, Kenneth Offit, Tuya Pal, Boris Pasche, Gwen Reiser, Kristen Mahoney Shannon, Elizabeth Swisher, Nicoleta C. Voian, Jeffrey N. Weitzel, Alison Whelan, Georgia L. Wiesner, Mary A. Dwyer and Rashmi Kumar

During the past few years, several genetic aberrations that may contribute to increased risks for development of breast and/or ovarian cancers have been identified. The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast and Ovarian focus specifically on the assessment of genetic mutations in BRCA1/BRCA2, TP53, and PTEN, and recommend approaches to genetic testing/counseling and management strategies in individuals with these mutations. This portion of the NCCN Guidelines includes recommendations regarding diagnostic criteria and management of patients with Cowden Syndrome/PTEN hamartoma tumor syndrome.

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Brittany Bauman, Rosemarie Mick, Eileen Martinez, Theresa M. Lawless, Lindsey Zinck, Paige Sinclair, Mary Fuhrer, Mark O’Hara, Charles J. Schneider, Peter O’Dwyer, John Plastaras, Ursina Teitelbaum and Kim A. Reiss

Background: Chemotherapy-induced oral thermal hyperalgesia (OTH) is a common and debilitating side effect of platinum-based anticancer agents. This study evaluated the efficacy of oral cryotherapy in preventing OTH during oxaliplatin chemotherapy infusion. Methods: Patients with gastrointestinal cancer treated with biweekly oxaliplatin (85 mg/m2 over 120 minutes) at Abramson Cancer Center at the University of Pennsylvania were randomized to receive oral cryotherapy (ice chips) during oxaliplatin infusion or standard-of-care treatment. All patients completed baseline questionnaires regarding oral and peripheral symptoms and on-treatment questionnaires on day 1 of each subsequent chemotherapy cycle. Those in the treatment arm were asked to document how long they kept the ice chips in their mouths (0, <30, 30, 60, 90, or 120 minutes) and to report their discomfort associated with oral cryotherapy. Evaluable patients were those who had completed at least 2 cycles of oxaliplatin therapy. Results: Of 62 randomized patients with a variety of gastrointestinal malignancies, 50 (25 per treatment arm) were evaluable for efficacy. The rate of patients with oral symptoms after the first treatment cycle was significantly lower in the intervention arm (n=8; 32%) than in the control arm (n=18; 72%), meeting the primary study objective (P=.01). The magnitude of difference in symptom scores before versus after the first treatment cycle was significantly less in the intervention versus control arm (P=.001). No difference in oral symptoms over time was seen between the intervention and control groups (P=.20), although a high attrition rate was noted. Duration of ice chip exposure was associated with improved oral symptoms over time (P=.02). Conclusions: Oral cryotherapy is a tolerable and cost-effective method of diminishing OTH in patients receiving oxaliplatin chemotherapy, and seems to be most effective in the early stages of treatment.

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Peter E. Clark, Neeraj Agarwal, Matthew C. Biagioli, Mario A. Eisenberger, Richard E. Greenberg, Harry W. Herr, Brant A. Inman, Deborah A. Kuban, Timothy M. Kuzel, Subodh M. Lele, Jeff Michalski, Lance C. Pagliaro, Sumanta K. Pal, Anthony Patterson, Elizabeth R. Plimack, Kamal S. Pohar, Michael P. Porter, Jerome P. Richie, Wade J. Sexton, William U. Shipley, Eric J. Small, Philippe E. Spiess, Donald L. Trump, Geoffrey Wile, Timothy G. Wilson, Mary Dwyer and Maria Ho

Bladder cancer is the fourth most common cancer in the United States. Urothelial carcinoma that originates from the urinary bladder is the most common subtype. These NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) provide recommendations on the diagnosis and management of non–muscle-invasive and muscle-invasive urothelial carcinoma of the bladder. This version of the guidelines provides extensive reorganization and updates on the principles of chemotherapy management.

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Dawn Provenzale, Samir Gupta, Dennis J. Ahnen, Travis Bray, Jamie A. Cannon, Gregory Cooper, Donald S. David, Dayna S. Early, Deborah Erwin, James M. Ford, Francis M. Giardiello, William Grady, Amy L. Halverson, Stanley R. Hamilton, Heather Hampel, Mohammad K. Ismail, Jason B. Klapman, David W. Larson, Audrey J. Lazenby, Patrick M. Lynch, Robert J. Mayer, Reid M. Ness, Scott E. Regenbogen, Niloy Jewel Samadder, Moshe Shike, Gideon Steinbach, David Weinberg, Mary Dwyer and Susan Darlow

This is a focused update highlighting the most current NCCN Guidelines for diagnosis and management of Lynch syndrome. Lynch syndrome is the most common cause of hereditary colorectal cancer, usually resulting from a germline mutation in 1 of 4 DNA mismatch repair genes (MLH1, MSH2, MSH6, or PMS2), or deletions in the EPCAM promoter. Patients with Lynch syndrome are at an increased lifetime risk, compared with the general population, for colorectal cancer, endometrial cancer, and other cancers, including of the stomach and ovary. As of 2016, the panel recommends screening all patients with colorectal cancer for Lynch syndrome and provides recommendations for surveillance for early detection and prevention of Lynch syndrome-associated cancers.

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Robert A. Swarm, Amy Pickar Abernethy, Doralina L. Anghelescu, Costantino Benedetti, Sorin Buga, Charles Cleeland, Oscar A. deLeon-Casasola, June G. Eilers, Betty Ferrell, Mark Green, Nora A. Janjan, Mihir M. Kamdar, Michael H. Levy, Maureen Lynch, Rachel M. McDowell, Natalie Moryl, Suzanne A. Nesbit, Judith A. Paice, Michael W. Rabow, Karen L. Syrjala, Susan G. Urba, Sharon M. Weinstein, Mary Dwyer and Rashmi Kumar

Pain is a common symptom associated with cancer and its treatment. Pain management is an important aspect of oncologic care, and unrelieved pain significantly comprises overall quality of life. These NCCN Guidelines list the principles of management and acknowledge the range of complex decisions faced in the management oncologic pain. In addition to pain assessment techniques, these guidelines provide principles of use, dosing, management of adverse effects, and safe handling procedures of pharmacologic therapies and discuss a multidisciplinary approach for the management of cancer pain.

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Robert J. Motzer, Eric Jonasch, Neeraj Agarwal, Sam Bhayani, William P. Bro, Sam S. Chang, Toni K. Choueiri, Brian A. Costello, Ithaar H. Derweesh, Mayer Fishman, Thomas H. Gallagher, John L. Gore, Steven L. Hancock, Michael R. Harrison, Won Kim, Christos Kyriakopoulos, Chad LaGrange, Elaine T. Lam, Clayton Lau, M. Dror Michaelson, Thomas Olencki, Phillip M. Pierorazio, Elizabeth R. Plimack, Bruce G. Redman, Brian Shuch, Brad Somer, Guru Sonpavde, Jeffrey Sosman, Mary Dwyer and Rashmi Kumar

The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for the clinical management of patients with clear cell and non–clear cell renal carcinoma. These guidelines are developed by a multidisciplinary panel of leading experts from NCCN Member Institutions consisting of medical oncologists, hematologists and hematologic oncologists, radiation oncologists, urologists, and pathologists. The NCCN Guidelines are in continuous evolution and are updated annually or sometimes more often, if new high-quality clinical data become available in the interim.

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William G. Wierda, John C. Byrd, Jeremy S. Abramson, Seema Bhat, Greg Bociek, Danielle Brander, Jennifer Brown, Asher Chanan-Khan, Steve E. Coutre, Randall S. Davis, Christopher D. Fletcher, Brian Hill, Brad S. Kahl, Manali Kamdar, Lawrence D. Kaplan, Nadia Khan, Thomas J. Kipps, Jeffrey Lancet, Shuo Ma, Sami Malek, Claudio Mosse, Mazyar Shadman, Tanya Siddiqi, Deborah Stephens, Nina Wagner, Andrew D. Zelenetz, Mary A. Dwyer and Hema Sundar

Hairy cell leukemia (HCL) is a rare type of indolent B-cell leukemia, characterized by symptoms of fatigue and weakness, organomegaly, pancytopenia, and recurrent opportunistic infections. Classic HCL should be considered a distinct clinical entity separate from HCLvariant (HCLv), which is associated with a more aggressive disease course and may not respond to standard HCL therapies. Somatic hypermutation in the IGHV gene is present in most patients with HCL. The BRAF V600E mutation has been reported in most patients with classic HCL but not in those with other B-cell leukemias or lymphomas. Therefore, it is necessary to distinguish HCLv from classic HCL. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of classic HCL.

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Randall W. Burt, Jamie A. Cannon, Donald S. David, Dayna S. Early, James M. Ford, Francis M. Giardiello, Amy L. Halverson, Stanley R. Hamilton, Heather Hampel, Mohammad K. Ismail, Kory Jasperson, Jason B. Klapman, Audrey J. Lazenby, Patrick M. Lynch, Robert J. Mayer, Reid M. Ness, Dawn Provenzale, M. Sambasiva Rao, Moshe Shike, Gideon Steinbach, Jonathan P. Terdiman, David Weinberg, Mary Dwyer and Deborah Freedman-Cass

Mortality from colorectal cancer can be reduced by early diagnosis and by cancer prevention through polypectomy. These NCCN Guidelines for Colorectal Cancer Screening describe various colorectal screening modalities and recommended screening schedules for patients at average or increased risk of developing colorectal cancer. In addition, the guidelines provide recommendations for the management of patients with high-risk colorectal cancer syndromes, including Lynch syndrome. Screening approaches for Lynch syndrome are also described.

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Jeffrey Crawford, James Armitage, Lodovico Balducci, Pamela Sue Becker, Douglas W. Blayney, Spero R. Cataland, Mark L. Heaney, Susan Hudock, Dwight D. Kloth, David J. Kuter, Gary H. Lyman, Brandon McMahon, Hope S. Rugo, Ayman A. Saad, Lee S. Schwartzberg, Sepideh Shayani, David P. Steensma, Mahsa Talbott, Saroj Vadhan-Raj, Peter Westervelt, Michael Westmoreland, Mary Dwyer and Maria Ho

Febrile neutropenia, a common side effect of myelosuppressive chemotherapy in patients with cancer, can result in prolonged hospitalization and broad-spectrum antibiotic use, often prompting treatment delays or dose reductions of drug regimens. Prophylactic use of myeloid growth factors (mainly the colony-stimulating factors filgrastim and pegfilgrastim) in patients of heightened risk can reduce the severity and duration of febrile neutropenia. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Myeloid Growth Factors provide recommendations on the use of these agents mainly in the oncology setting based on clinical evidence and expert consensus. This version includes revisions surrounding the issue of timing of pegfilgrastim administration. It also includes new sections on tbo-filgrastim, a recently approved agent that is biologically similar to filgrastim, and the role of myeloid growth factors in the hematopoietic cell transplant setting