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Andrew D. Zelenetz, Leo I. Gordon, William G. Wierda, Jeremy S. Abramson, Ranjana H. Advani, C. Babis Andreadis, Nancy Bartlett, John C. Byrd, Luis E. Fayad, Richard I. Fisher, Martha J. Glenn, Thomas M. Habermann, Nancy Lee Harris, Francisco Hernandez-Ilizaliturri, Richard T. Hoppe, Steven M. Horwitz, Mark S. Kaminski, Christopher R. Kelsey, Youn H. Kim, Susan Krivacic, Ann S. LaCasce, Matthew Lunning, Auayporn Nademanee, Pierluigi Porcu, Oliver Press, Rachel Rabinovitch, Nishitha Reddy, Erin Reid, Kenneth Roberts, Ayman A. Saad, Lubomir Sokol, Lode J. Swinnen, Julie M. Vose, Joachim Yahalom, Nadeem Zafar, Mary Dwyer and Hema Sundar

Diffuse large B-cell lymphomas (DLBCL) are now considered a heterogeneous group of distinct molecular subtypes (germinal center B-cell DLBCL, activated B-cell DLBCL, and primary mediastinal large B-cell lymphoma (PMBL) with varied natural history and response to therapy. In addition, a subset of patients with DLBCL have concurrent MYC and/or BCL2 gene rearrangements (double-hit lymphomas; DHL) and others have a dual expression of both MYC and BCL2 proteins (double-expressing DLBCL; DEL). The standard of care for the treatment of patients with PMBL, DHL, or DEL has not been established. Adequate immunophenotyping and molecular testing (in selected circumstances) are necessary for the accurate diagnosis of different subtypes of DLBCL. The NCCN Guidelines included in this issue, part of the NCCN Guidelines for non-Hodgkin's lymphomas, address the diagnosis and management of DLBCL and its subtypes.

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James L. Mohler, Philip W. Kantoff, Andrew J. Armstrong, Robert R. Bahnson, Michael Cohen, Anthony Victor D’Amico, James A. Eastham, Charles A. Enke, Thomas A. Farrington, Celestia S. Higano, Eric Mark Horwitz, Christopher J. Kane, Mark H. Kawachi, Michael Kuettel, Timothy M. Kuzel, Richard J. Lee, Arnold W. Malcolm, David Miller, Elizabeth R. Plimack, Julio M. Pow-Sang, David Raben, Sylvia Richey, Mack Roach III, Eric Rohren, Stan Rosenfeld, Edward Schaeffer, Eric J. Small, Guru Sonpavde, Sandy Srinivas, Cy Stein, Seth A. Strope, Jonathan Tward, Dorothy A. Shead and Maria Ho

Prostate cancer has surpassed lung cancer as the most common cancer in men in the United States. The NCCN Guidelines for Prostate Cancer provide multidisciplinary recommendations on the clinical management of patients with prostate cancer based on clinical evidence and expert consensus. NCCN Panel guidance on treatment decisions for patients with localized disease is represented in this version. Significant updates for early disease include distinction between active surveillance and observation, a new section on principles of imaging, and revisions to radiation recommendations. The full version of these guidelines, including treatment of patients with advanced disease, can be found online at the NCCN website.

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Stanley J. Miller, Murad Alam, James Andersen, Daniel Berg, Christopher K. Bichakjian, Glen Bowen, Richard T. Cheney, L. Frank Glass, Roy C. Grekin, Dennis E. Hallahan, Anne Kessinger, Nancy Y. Lee, Nanette Liegeois, Daniel D. Lydiatt, Jeff Michalski, William H. Morrison, Kishwer S. Nehal, Kelly C. Nelson, Paul Nghiem, Thomas Olencki, Allan R. Oseroff, Clifford S. Perlis, E. William Rosenberg, Ashok R. Shaha, Marshall M. Urist and Linda C. Wang

Merkel Cell Carcinoma Clinical Practice Guidelines in Oncology NCCN Categories of Evidence and Consensus Category 1: The recommendation is based on high-level evidence (e.g., randomized controlled trials) and there is uniform NCCN consensus. Category 2A: The recommendation is based on lower-level evidence and there is uniform NCCN consensus. Category 2B: The recommendation is based on lower-level evidence and there is nonuniform NCCN consensus (but no major disagreement). Category 3: The recommendation is based on any level of evidence but reflects major disagreement. All recommendations are category 2A unless otherwise noted. Clinical trials: The NCCN believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. Overview Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous tumor that combines the local recurrence rates of infiltrative non-melanoma skin cancer along with the regional and distant metastatic rates of thick melanoma.1–16 Several large reviews document the development of local recurrence in 25% to 30% of all cases of MCC, regional disease in 52% to 59%, and distant metastatic disease in 34% to 36%.1,16,17 MCC has a mortality rate that exceeds that of melanoma;18 overall 5-year survival rates range from 30% to 64%.3,19 A history of extensive sun exposure is a risk factor for MCC. Older white men (≥ 65 years) are at higher risk for MCC, which tends to occur on the areas of the skin that are exposed to sun.20 The NCCN Non-Melanoma Skin Cancer Panel has developed guidelines outlining treatment of...
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R. Michael Tuttle, Douglas W. Ball, David Byrd, Raza A. Dilawari, Gerard M. Doherty, Quan-Yang Duh, Hormoz Ehya, William B. Farrar, Robert I. Haddad, Fouad Kandeel, Richard T. Kloos, Peter Kopp, Dominick M. Lamonica, Thom R. Loree, William M. Lydiatt, Judith C. McCaffrey, John A. Olson Jr., Lee Parks, John A. Ridge, Jatin P. Shah, Steven I. Sherman, Cord Sturgeon, Steven G. Waguespack, Thomas N. Wang and Lori J. Wirth

OverviewEpidemiologyThyroid nodules are approximately 4 times more common in women than in men. Palpable nodules increase in frequency throughout life, reaching a prevalence of approximately 5% in the United States population aged 50 years and older.1–3 Nodules are even more prevalent when the thyroid gland is examined at autopsy or surgery, or when using ultrasonography, and 50% of these have nodules, which are almost always benign.2,4 New nodules develop at a rate of approximately 0.1% per year beginning in early life, but at a much higher rate (∼2% per year) after exposure to head and neck irradiation.5,6By contrast, thyroid carcinoma is uncommon. For the United States population, the lifetime risk of being diagnosed with thyroid carcinoma is less than 1% (0.83% for women and 0.33% for men).7 Approximately 37,200 new cases of thyroid carcinoma were diagnosed in the United States in 2009.8As with thyroid nodules, thyroid carcinoma occurs 2 to 3 times more often in women than in men. With the incidence increasing by 6.2% per year, thyroid carcinoma is currently the sixth most common malignancy diagnosed in women.8 Among persons age 15 to 24 years, thyroid carcinoma accounts for 7.5% to 10% of all diagnosed malignancies.9–11 The disease is also diagnosed more often in white North Americans than in African Americans. Although thyroid carcinoma can occur at any age, the peak incidence from 2004 to 2006 was near age 45 to 49 years in women and 65 to 69 years in men.7Thyroid carcinoma has...
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R. Michael Tuttle, Douglas W. Ball, David Byrd, Gilbert H. Daniels, Raza A. Dilawari, Gerard M. Doherty, Quan-Yang Duh, Hormoz Ehya, William B. Farrar, Robert I. Haddad, Fouad Kandeel, Richard T. Kloos, Peter Kopp, Dominick M. Lamonica, Thom R. Loree, William M. Lydiatt, Judith McCaffrey, John A. Olson Jr., Lee Parks, John A. Ridge, Jatin P. Shah, Steven I. Sherman, Cord Sturgeon, Steven G. Waguespack, Thomas N. Wang and Lori J. Wirth

Overview There are 3 main histologic types of thyroid carcinoma: differentiated (including papillary, follicular, and Hürthle), medullary, and anaplastic (aggressive undifferentiated tumor). Of 53,856 patients treated for thyroid carcinoma between 1985 and 1995, 80% had papillary, 11% had follicular, 3% had Hürthle cell, 4% had medullary, and 2% had anaplastic thyroid carcinoma.1 These NCCN guidelines focus on medullary thyroid carcinoma (MTC). Another NCCN guideline addresses papillary, follicular, Hürthle cell, and anaplastic thyroid carcinomas (see NCCN Clinical Practice Guidelines in Oncology: Thyroid Carcinoma [to view the most recent version of these guidelines, visit the NCCN Web site at www.NCCN.org]). MTC derives from the neuroendocrine parafollicular calcitonin-producing (C) cells of the thyroid.2–4 Sporadic MTC accounts for approximately 80% of all cases of the disease. The remaining cases consist of inherited tumor syndromes, such as multiple endocrine neoplasia type 2A (MEN 2A), which is the most common type; MEN 2B; or familial MTC.5,6 Sporadic disease typically presents in the fifth or sixth decade. Familial forms of the disease tend to present at earlier ages.2 Because the C cells are predominantly located in the upper portion of each thyroid lobe, patients with sporadic disease typically present with upper pole thyroid nodules. Metastatic cervical adenopathy appears in approximately 50% of patients at initial presentation. Symptoms of upper aerodigestive tract compression or invasion are reported by up to 15% of patients with sporadic disease.7 Symptoms from distant metastases in the lungs or bones occur in 5% to 10% of patients. The ability of the tumor to...
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Stanley J. Miller, Murad Alam, James Andersen, Daniel Berg, Christopher K. Bichakjian, Glen Bowen, Richard T. Cheney, L. Frank Glass, Roy C. Grekin, Anne Kessinger, Nancy Y. Lee, Nanette Liegeois, Daniel D. Lydiatt, Jeff Michalski, William H. Morrison, Kishwer S. Nehal, Kelly C. Nelson, Paul Nghiem, Thomas Olencki, Clifford S. Perlis, E. William Rosenberg, Ashok R. Shaha, Marshall M. Urist, Linda C. Wang and John A. Zic

Overview Basal and squamous cell skin cancers, collectively known as non-melanoma skin cancers (NMSC), are the most common skin cancers.1,2 More than 1 million cases of NMSC are estimated to be diagnosed each year in the United States and their incidence is rising rapidly.3,4 Basal cell carcinomas are approximately 4 to 5 times more common than squamous cell carcinomas. Although rarely metastatic, basal and squamous cell cancers can produce substantial local destruction along with disfigurement, and may involve extensive areas of soft tissue, cartilage, and bone. The estimated annual cost of treating these 2 diseases in the United States Medicare population exceeds $400 million.5 However, NMSCs generally have a good prognosis. The most significant environmental carcinogen for NMSC is sunlight.6 Thus, individuals in Hawaii are at much greater risk than those in the northern parts of the United States. Fair-skinned individuals who have received too much sun exposure are at the greatest risk for these cancers. Most of these tumors develop on sun-exposed skin sites. The most common sites are on the head and neck area. According to a report from the Childhood Cancer Survivor Study, long-term survivors of childhood and adolescent cancers who have undergone prior radiation therapy are also at risk for developing NMSC.7 Actinic keratoses are sun-induced precancerous lesions.8,9 Bowen's disease is characterized by squamous cell carcinoma in situ lesions that occur predominantly in older persons.10 Both types of lesions, if untreated, can progress to invasive squamous cell carcinoma with the potential for metastasis. Skin cancer preventive...
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Erin Reid, Gita Suneja, Richard F. Ambinder, Kevin Ard, Robert Baiocchi, Stefan K. Barta, Evie Carchman, Adam Cohen, Neel Gupta, Kimberly L. Johung, Ann Klopp, Ann S. LaCasce, Chi Lin, Oxana V. Makarova-Rusher, Amitkumar Mehta, Manoj P. Menon, David Morgan, Nitya Nathwani, Ariela Noy, Frank Palella, Lee Ratner, Stacey Rizza, Michelle A. Rudek, Jeff Taylor, Benjamin Tomlinson, Chia-Ching J. Wang, Mary A. Dwyer and Deborah A. Freedman-Cass

People living with HIV (PLWH) are diagnosed with cancer at an increased rate over the general population and generally have a higher mortality due to delayed diagnoses, advanced cancer stage, comorbidities, immunosuppression, and cancer treatment disparities. Lack of guidelines and provider education has led to substandard cancer care being offered to PLWH. To fill that gap, the NCCN Guidelines for Cancer in PLWH were developed; they provide treatment recommendations for PLWH who develop non–small cell lung cancer, anal cancer, Hodgkin lymphoma, and cervical cancer. In addition, the NCCN Guidelines outline advice regarding HIV management during cancer therapy; drug–drug interactions between antiretroviral treatments and cancer therapies; and workup, radiation therapy, surgical management, and supportive care in PLWH who have cancer.

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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.

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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.

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James L. Mohler, Philip W. Kantoff, Andrew J. Armstrong, Robert R. Bahnson, Michael Cohen, Anthony Victor D’Amico, James A. Eastham, Charles A. Enke, Thomas A. Farrington, Celestia S. Higano, Eric Mark Horwitz, Mark H. Kawachi, Michael Kuettel, Richard J. Lee, Gary R. MacVicar, Arnold W. Malcolm, David Miller, Elizabeth R. Plimack, Julio M. Pow-Sang, Sylvia Richey, Mack Roach III, Eric Rohren, Stan Rosenfeld, Eric J. Small, Sandy Srinivas, Cy Stein, Seth A. Strope, Jonathan Tward, Patrick C. Walsh, Dorothy A. Shead and Maria Ho

The NCCN Guidelines for Prostate Cancer provide multidisciplinary recommendations on the clinical management of patients with prostate cancer. This report highlights notable recent updates. Radium-223 dichloride is a first-in-class radiopharmaceutical that recently received approval for the treatment of patients with symptomatic bone metastases and no known visceral disease. It received a category 1 recommendation as both a first-line and second-line option. The NCCN Prostate Cancer Panel also revised recommendations on the choice of intermittent or continuous androgen deprivation therapy based on recent phase III clinical data comparing the 2 strategies in the nonmetastatic and metastatic settings.