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Amit Mahipal, Minsig Choi and Richard Kim

Gastric cancer is a leading cause of cancer death and is associated with poor prognosis. The treatment of advanced gastric cancer is changing with the development of novel agents. Until recently, no standard treatment was available for patients with advanced gastric cancer in the second-line setting. Single-agent chemotherapy with docetaxel or irinotecan has been shown to improve survival and quality of life in patients whose disease has progressed while on prior chemotherapy. Combination chemotherapy is associated with a modest benefit at the expense of increased toxicity. Recently, ramucirumab, a monoclonal antibody targeting vascular endothelial growth factor (VEGF) receptor-2, has been approved for the treatment of refractory advanced gastric cancer as a single agent or in combination with paclitaxel. Apatinib, a small molecule tyrosine kinase inhibitor targeting VEGF, has demonstrated activity in Asian populations whose disease has progressed on 2 lines of therapy. However, much work is still needed, including the development of biomarkers that could predict response to therapy.

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Noman Ashraf, Nishi Kothari and Richard Kim

In an era of personalized medicine, an increased effort is being made to identify patients likely to benefit from targeted therapy. By limiting treatment to selected patients, both unnecessary cost and toxicity may be avoided. Restricting the use of anti-epidermal growth factor receptor (anti-EGFR)-targeted agents in metastatic colorectal cancer to only patients with KRAS exon 2 wild-type tumors has become well-established in clinical practice. However, lack of KRAS exon 2 mutations does not necessarily predict response, and a significant proportion of patients with KRAS wild-type tumors do not benefit from therapy with cetuximab or panitumumab. Further characterization is needed of the subset of patients with KRAS exon 2 wild-type tumors who are likely to benefit from anti-EGFR therapy. Recent data suggest that patients with KRAS mutations at loci other than exon 2, and those with other RAS mutations, might not benefit from EGFR-directed therapy. This article briefly reviews established work on KRAS exon 2 mutations, but focuses primarily on emerging data on non-exon 2 KRAS mutations and additional RAS and BRAF mutations and how this information may impact clinical decision-making.

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Robert J. Motzer, Eric Jonasch, Neeraj Agarwal, Clair Beard, Sam Bhayani, Graeme B. Bolger, Sam S. Chang, Toni K. Choueiri, Ithaar H. Derweesh, Shilpa Gupta, Steven L. Hancock, Jenny J. Kim, Timothy M. Kuzel, Elaine T. Lam, Clayton Lau, Ellis G. Levine, Daniel W. Lin, Kim A. Margolin, M. Dror Michaelson, Thomas Olencki, Roberto Pili, Elizabeth R. Plimack, Edward N. Rampersaud, Bruce G. Redman, Charles J. Ryan, Joel Sheinfeld, Kanishka Sircar, Brad Somer, Jue Wang, Richard B. Wilder, Mary A. Dwyer and Rashmi Kumar

These NCCN Guidelines Insights highlight treatment recommendations and updates specific to the management of patients with advanced non-clear cell carcinoma included in the 2014 version of the NCCN Clinical Practice Guidelines in Oncology for Kidney Cancer.

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Robert J. Motzer, Neeraj Agarwal, Clair Beard, Sam Bhayani, Graeme B. Bolger, Michael A. Carducci, Sam S. Chang, Toni K. Choueiri, Steven L. Hancock, Gary R. Hudes, Eric Jonasch, David Josephson, Timothy M. Kuzel, Ellis G. Levine, Daniel W. Lin, Kim A. Margolin, M. Dror Michaelson, Thomas Olencki, Roberto Pili, Thomas W. Ratliff, Bruce G. Redman, Cary N. Robertson, Charles J. Ryan, Joel Sheinfeld, Philippe E. Spiess, Jue Wang and Richard B. Wilder

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Robert J. Motzer, Neeraj Agarwal, Clair Beard, Sam Bhayani, Graeme B. Bolger, Mark K. Buyyounouski, Michael A. Carducci, Sam S. Chang, Toni K. Choueiri, Shilpa Gupta, Steven L. Hancock, Gary R. Hudes, Eric Jonasch, Timothy M. Kuzel, Clayton Lau, Ellis G. Levine, Daniel W. Lin, Kim A. Margolin, M. Dror Michaelson, Thomas Olencki, Roberto Pili, Thomas W. Ratliff, Bruce G. Redman, Cary N. Robertson, Charles J. Ryan, Joel Sheinfeld, Jue Wang and Richard B. Wilder

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Andrew D. Zelenetz, Leo I. Gordon, William G. Wierda, Jeremy S. Abramson, Ranjana H. Advani, C. Babis Andreadis, Nancy Bartlett, Naresh Bellam, John C. Byrd, Myron S. Czuczman, Luis E. Fayad, Richard I. Fisher, Martha J. Glenn, Nancy Lee Harris, Richard T. Hoppe, Steven M. Horwitz, Christopher R. Kelsey, Youn H. Kim, Susan Krivacic, Ann S. LaCasce, Auayporn Nademanee, Pierluigi Porcu, Oliver Press, Rachel Rabinovitch, Nishitha Reddy, Erin Reid, Lubomir Sokol, Lode J. Swinnen, Christina Tsien, Julie M. Vose, Joachim Yahalom, Nadeem Zafar, Mary Dwyer and Hema Sundar

Non-Hodgkin’s lymphomas (NHLs) are a heterogeneous group of lymphoproliferative disorders originating in B lymphocytes, T lymphocytes, or natural killer cells. Follicular lymphoma (FL) is the most common subtype of indolent NHL, accounting for approximately 22% of all newly diagnosed cases of NHL. The incorporation of rituximab to chemotherapy regimens has become a widely accepted standard of care for first-line therapy for patients with FL. Maintenance and consolidation therapy with rituximab and radioimmunotherapy have also been associated with improved progression-free survival in patients experiencing response to first-line therapy. Despite therapeutic advances that have improved outcomes, FL is generally considered a chronic disease characterized by multiple recurrences with current therapies. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with FL.

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

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are different manifestations of the same disease, which are managed in the same way. The advent of novel monoclonal antibodies (ofatumumab and obinutuzumab) led to the development of effective chemoimmunotherapy regimens. The recently approved small molecule kinase inhibitors (ibrutinib and idelalisib) are effective treatment options for CLL in elderly patients with decreased tolerance for aggressive regimens and in patients with poor prognostic features who do not benefit from conventional chemoimmunotherapy regimens. This portion of the NCCN Guidelines for Non-Hodgkin’s Lymphomas describes the recent specific to the incorporation of recently approved targeted therapies for the management of patients with newly diagnosed and relapsed or refractory CLL/SLL.

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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, Myron S. Czuczman, Luis E. Fayad, Richard I. Fisher, Martha J. Glenn, Nancy Lee Harris, Richard T. Hoppe, Steven M. Horwitz, Christopher R. Kelsey, Youn H. Kim, Susan Krivacic, Ann S. LaCasce, Auayporn Nademanee, Pierluigi Porcu, Oliver Press, Rachel Rabinovitch, Nishitha Reddy, Erin Reid, Ayman A. Saad, Lubomir Sokol, Lode J. Swinnen, Christina Tsien, Julie M. Vose, Joachim Yahalom, Nadeem Zafar, Mary Dwyer and Hema Sundar

Non-Hodgkin’s lymphomas (NHL) are a heterogeneous group of lymphoproliferative disorders originating in B lymphocytes, T lymphocytes, or natural killer cells. Mantle cell lymphoma (MCL) accounts for approximately 6% of all newly diagnosed NHL cases. Radiation therapy with or without systemic therapy is a reasonable approach for the few patients who present with early-stage disease. Rituximab-based chemoimmunotherapy followed by high-dose therapy and autologous stem cell rescue (HDT/ASCR) is recommended for patients presenting with advanced-stage disease. Induction therapy followed by rituximab maintenance may provide extended disease control for those who are not candidates for HDT/ASCR. Ibrutinib, a Bruton tyrosine kinase inhibitor, was recently approved for the treatment of relapsed or refractory disease. This manuscript discusses the recommendations outlined in the NCCN Guidelines for NHL regarding the diagnosis and management of patients with MCL.

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Margaret von Mehren, R. Lor Randall, Robert S. Benjamin, Sarah Boles, Marilyn M. Bui, Kristen N. Ganjoo, Suzanne George, Ricardo J. Gonzalez, Martin J. Heslin, John M. Kane III, Vicki Keedy, Edward Kim, Henry Koon, Joel Mayerson, Martin McCarter, Sean V. McGarry, Christian Meyer, Zachary S. Morris, Richard J. O'Donnell, Alberto S. Pappo, I. Benjamin Paz, Ivy A. Petersen, John D. Pfeifer, Richard F. Riedel, Bernice Ruo, Scott Schuetze, William D. Tap, Jeffrey D. Wayne, Mary Anne Bergman and Jillian L. Scavone

Soft tissue sarcomas (STS) are rare solid tumors 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 Guidelines for STS provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as intra-abdominal/retroperitoneal STS, gastrointestinal stromal tumors, desmoid tumors, and rhabdomyosarcoma. This portion of the NCCN Guidelines discusses general principles for the diagnosis, staging, and treatment of STS of the extremities, superficial trunk, or head and neck; outlines treatment recommendations by disease stage; and reviews the evidence to support the guidelines recommendations.