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Soft Tissue Sarcoma, Version 2.2012

Featured Updates to the NCCN Guidelines

Margaret von Mehren, Robert S. Benjamin, Marilyn M. Bui, Ephraim S. Casper, Ernest U. Conrad III, Thomas F. DeLaney, Kristen N. Ganjoo, Suzanne George, Ricardo Gonzalez, Martin J. Heslin, John M. Kane III, Joel Mayerson, Sean V. McGarry, Christian Meyer, Richard J. O'Donnell, Benjamin Paz, John D. Pfeifer, Raphael E. Pollock, R. Lor Randall, Richard F. Riedel, Scott Schuetze, Karen D. Schupak, Herbert S. Schwartz, Sridhar Shankar, Brian A. Van Tine, Jeffrey Wayne, Hema Sundar and Nicole R. McMillian

The major changes to the 2012 and 2011 NCCN Guidelines for Soft Tissue Sarcoma pertain to the management of patients with gastrointestinal stromal tumors (GISTs) and desmoid tumors (aggressive fibromatosis). Postoperative imatinib following complete resection for primary GIST with no preoperative imatinib is now included as a category 1 recommendation for patients with intermediate or high risk of recurrence. The panel also reaffirmed the recommendation for preoperative use of imatinib in patients with GISTs that are resectable with negative margins but associated with significant surgical morbidity. Observation was included as an option for patients with resectable desmoid tumors that are small and asymptomatic, not causing morbidity, pain, or functional limitation. Sorafenib is included as an option for systemic therapy for patients with desmoid tumors.

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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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Peter F. Coccia, Alberto S. Pappo, Jessica Altman, Smita Bhatia, Scott C. Borinstein, Joseph Flynn, A. Lindsay Frazier, Suzanne George, Robert Goldsby, Robert Hayashi, Mary S. Huang, Rebecca H. Johnson, Lynda Kwon Beaupin, Michael P. Link, Kevin C. Oeffinger, Kathleen M. Orr, Damon Reed, Holly L. Spraker, Deborah A. Thomas, Margaret von Mehren, Daniel S. Wechsler, Kimberly F. Whelan, Brad Zebrack, Dorothy A. Shead and Hema Sundar

The NCCN Guidelines Insights on Adolescent and Young Adult (AYA) Oncology discuss the fertility and endocrine issues that are relevant to the management of AYA patients with cancer. Fertility preservation should be an essential part in the treatment of AYA patients with cancer. The NCCN Guidelines recommend discussion of fertility preservation and contraception before the start of treatment. Oophoropexy and embryo cryopreservation are the 2 established options for fertility preservation in women. Semen cryopreservation before the start of treatment is the most reliable and well-established method of preserving fertility in men. AYA women with cancer also have unique contraception needs, depending on the type of cancer, its treatment, and treatment-related complications. Management of cancer during pregnancy poses significant diagnostic and therapeutic challenges for both the patient and the physician. AYA women diagnosed with cancer during pregnancy require individualized treatment from a multidisciplinary team involving medical, surgical, radiation, and gynecologic oncologists; obstetricians; and perinatologists.

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Richard T. Hoppe, Ranjana H. Advani, Weiyun Z. Ai, Richard F. Ambinder, Patricia Aoun, Celeste M. Bello, Cecil M. Benitez, Karl Bernat, Philip J. Bierman, Kristie A. Blum, Robert Chen, Bouthaina Dabaja, Andres Forero, Leo I. Gordon, Francisco J. Hernandez-Ilizaliturri, Ephraim P. Hochberg, Jiayi Huang, Patrick B. Johnston, Mark S. Kaminski, Vaishalee P. Kenkre, Nadia Khan, David G. Maloney, Peter M. Mauch, Monika Metzger, Joseph O. Moore, David Morgan, Craig H. Moskowitz, Carolyn Mulroney, Matthew Poppe, Rachel Rabinovitch, Stuart Seropian, Mitchell Smith, Jane N. Winter, Joachim Yahalom, Jennifer Burns, Ndiya Ogba and Hema Sundar

This portion of the NCCN Guidelines for Hodgkin lymphoma (HL) focuses on the management of classical HL. Current management of classical HL involves initial treatment with chemotherapy or combined modality therapy followed by restaging with PET/CT to assess treatment response using the Deauville criteria (5-point scale). The introduction of less toxic and more effective regimens has significantly advanced HL cure rates. However, long-term follow-up after completion of treatment is essential to determine potential long-term effects.

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William G. Wierda, John C. Byrd, Jeremy S. Abramson, Syed F. Bilgrami, Greg Bociek, Danielle Brander, Jennifer Brown, Asher A. Chanan-Khan, Julio C. Chavez, Steve E. Coutre, Randall S. Davis, Christopher D. Fletcher, Brian Hill, Brad S. Kahl, Manali Kamdar, Lawrence D. Kaplan, Nadia Khan, Thomas J. Kipps, Shuo Ma, Sami Malek, Anthony Mato, Claudio Mosse, Vishala T. Neppalli, Mazyar Shadman, Tanya Siddiqi, Deborah Stephens, Nina Wagner, Mary A. Dwyer and Hema Sundar

Chronic lymphocytic leukemia (CLL) is generally characterized by an indolent disease course. Histologic transformation (also known as Richter's transformation) to more aggressive lymphomas, such as diffuse large B-cell lymphoma or Hodgkin lymphoma, occurs in approximately 2% to 10% of patients and is associated with a poor prognosis. These NCCN Guidelines Insights discuss the recommendations for the diagnosis and management of patients with histologic transformation.

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Aaron T. Gerds, Jason Gotlib, Prithviraj Bose, Michael W. Deininger, Andrew Dunbar, Amro Elshoury, Tracy I. George, Ivana Gojo, Krishna Gundabolu, Elizabeth Hexner, Gabriela Hobbs, Tania Jain, Catriona Jamieson, Andrew T. Kuykendall, Brandon McMahon, Sanjay R. Mohan, Vivian Oehler, Stephen Oh, Animesh Pardanani, Nikolai Podoltsev, Erik Ranheim, Lindsay Rein, Rachel Salit, David S. Snyder, Brady L. Stein, Moshe Talpaz, Swapna Thota, Pankit Vachhani, Martha Wadleigh, Katherine Walsh, Dawn C. Ward, Mary Anne Bergman and Hema Sundar

Eosinophilic disorders and related syndromes represent a heterogeneous group of neoplastic and nonneoplastic conditions, characterized by more eosinophils in the peripheral blood, and may involve eosinophil-induced organ damage. In the WHO classification of myeloid and lymphoid neoplasms, eosinophilic disorders characterized by dysregulated tyrosine kinase (TK) fusion genes are recognized as a new category termed, myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB or FGFR1 or with PCM1-JAK2. In addition to these aforementioned TK fusion genes, rearrangements involving FLT3 and ABL1 genes have also been described. These new NCCN Guidelines include recommendations for the diagnosis, staging, and treatment of any one of the myeloid/lymphoid neoplasms with eosinophilia (MLN-Eo) and a TK fusion gene included in the 2017 WHO Classification, as well as MLN-Eo and a FLT3 or ABL1 rearrangement.

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Michael W. Deininger, Neil P. Shah, Jessica K. Altman, Ellin Berman, Ravi Bhatia, Bhavana Bhatnagar, Daniel J. DeAngelo, Jason Gotlib, Gabriela Hobbs, Lori Maness, Monica Mead, Leland Metheny, Sanjay Mohan, Joseph O. Moore, Kiran Naqvi, Vivian Oehler, Arnel M. Pallera, Mrinal Patnaik, Keith Pratz, Iskra Pusic, Michal G. Rose, B. Douglas Smith, David S. Snyder, Kendra L. Sweet, Moshe Talpaz, James Thompson, David T. Yang, Kristina M. Gregory and Hema Sundar

Chronic myeloid leukemia (CML) is defined by the presence of Philadelphia chromosome (Ph) which results from a reciprocal translocation between chromosomes 9 and 22 [t(9;22] that gives rise to a BCR-ABL1 fusion gene. CML occurs in 3 different phases (chronic, accelerated, and blast phase) and is usually diagnosed in the chronic phase. Tyrosine kinase inhibitor therapy is a highly effective first-line treatment option for all patients with newly diagnosed chronic phase CML. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with chronic phase CML.

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NCCN Guidelines Insights: T-Cell Lymphomas, Version 1.2021

Featured Updates to the NCCN Guidelines

Steven M. Horwitz, Stephen Ansell, Weiyun Z. Ai, Jeffrey Barnes, Stefan K. Barta, Mark W. Clemens, Ahmet Dogan, Aaron M. Goodman, Gaurav Goyal, Joan Guitart, Ahmad Halwani, Bradley M. Haverkos, Richard T. Hoppe, Eric Jacobsen, Deepa Jagadeesh, Allison Jones, Youn H. Kim, Neha Mehta-Shah, Elise A. Olsen, Barbara Pro, Saurabh A. Rajguru, Sima Rozati, Jonathan Said, Aaron Shaver, Andrei Shustov, Lubomir Sokol, Pallawi Torka, Carlos Torres-Cabala, Ryan Wilcox, Basem M. William, Jasmine Zain, Mary A. Dwyer and Hema Sundar

Hepatosplenic T-cell lymphoma (HSTCL) is a rare subtype of T-cell lymphoma associated with an aggressive clinical course and a worse prognosis. HSTCL develops in the setting of chronic immune suppression or immune dysregulation in up to 20% of cases and is most often characterized by spleen, liver, and bone marrow involvement. Diagnosis and management of HSTCL pose significant challenges given the rarity of the disease along with the absence of lymphadenopathy and poor outcome with conventional chemotherapy regimens. These Guidelines Insights focus on the diagnosis and treatment of HSTCL as outlined in the NCCN Guidelines for T-Cell Lymphomas.

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William G. Wierda, Andrew D. Zelenetz, Leo I. Gordon, Jeremy S. Abramson, Ranjana H. Advani, C. Babis Andreadis, Nancy Bartlett, John C. Byrd, Paolo Caimi, 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, Michael G. Martin, Auayporn Nademanee, Pierluigi Porcu, Oliver Press, Rachel Rabinovitch, Nishitha Reddy, Erin Reid, Kenneth Roberts, Ayman A. Saad, Erin D. Snyder, Lubomir Sokol, Lode J. Swinnen, Julie M. Vose, Joachim Yahalom, Mary A. Dwyer and Hema Sundar

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are different manifestations of the same disease and managed in much the same way. The advent of novel CD20 monoclonal antibodies led to the development of effective chemoimmunotherapy regimens. More recently, small molecule inhibitors targeting kinases involved in a number of critical signaling pathways and a small molecule inhibitor of the BCL-2 family of proteins have demonstrated activity for the treatment of patients with CLL/SLL. These NCCN Guidelines Insights highlight important updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for CLL/SLL for the treatment of patients with newly diagnosed or relapsed/refractory CLL/SLL.

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Steven M. Horwitz, 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, Mark S. Kaminski, Christopher R. Kelsey, Youn H. Kim, Susan Krivacic, Ann S. LaCasce, Matthew Lunning, Auayporn Nademanee, 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, Hema Sundar and Pierluigi Porcu

Peripheral T-cell lymphomas (PTCLs) represent a relatively uncommon heterogeneous group of non-Hodgkin's lymphomas (NHLs) with an aggressive clinical course and poor prognosis. Anthracycline-based multiagent chemotherapy with or without radiation therapy followed by first-line consolidation with high-dose therapy followed by autologous stem cell rescue (HDT/ASCR) is the standard approach to most of the patients with newly diagnosed PTCL. Relapsed or refractory disease is managed with second-line systemic therapy followed by HDT/ASCR or allogeneic stem cell transplant, based on the patient's eligibility for transplant. In recent years, several newer agents have shown significant activity in patients with relapsed or refractory disease across all 4 subtypes of PTCL. These NCCN Guideline Insights highlight the important updates to the NCCN Guidelines for NHL, specific to the management of patients with relapsed or refractory PTCL.