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Margaret von Mehren

Medical management of soft tissue sarcomas (STS) has been restricted by the limited availability of active drugs. A plethora of new oncologic agents are now available, many of which have specific therapeutic targets. Gemcitabine and docetaxel is a combination of drugs that have limited single-agent activity. Yondelis, a novel chemotherapeutic that binds DNA and functions partially by inhibiting transcription, is being tested alone and in combination with doxorubicin. Inhibitors of mTOR, a serine/threonine kinase that regulates cell cycle activation and cell growth, are also being tested. Growth factor receptor inhibitors are being evaluated in a variety of sarcomas that have been found to express the targets. In addition, a variety of agents are being assessed in gastrointestinal stromal tumors (GIST). Single agents and agents combined with imatinib are being tested in imatinib-refractory and in metastatic GIST. The increased use of targeted agents underscores the need for understanding sarcoma biology.

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Sujana Movva, Margaret von Mehren, Eric A. Ross and Elizabeth Handorf

Background: Conflicting data exist on the benefit of chemotherapy in the management of high-risk soft tissue sarcoma (STS). Use of chemotherapy may be dependent on patient, tumor, and facility characteristics. This study sought to identify these factors and compare survival between treatment groups. Patients and Methods: Patients with stage III STS were identified from the National Cancer Data Base (NCDB) from 1998 to 2012. Multiple logistic regression analysis was used to determine factors that influenced the probability of receiving chemotherapy. In a subset of patients, we determined the relationship between chemotherapy use and overall survival, using Kaplan-Meier curves and Cox regression analysis with propensity score adjustment. We also examined the effect of chemotherapy by histologic subgroup using interaction models. Results: A total of 16,370 patients were included (N=5,377 for survival analysis). Patients who were younger than 40 years; male; privately insured; earned a higher income; had no comorbidities; had synovial sarcoma, angiosarcoma or “other” histology; and whose tumors were high-grade, greater than 10 cm, or from the lower extremity were significantly more likely to receive chemotherapy. Median unadjusted overall survival (OS) in the nonchemotherapy and chemotherapy groups was 51.3 and 82.7 months, respectively (P<.001). On adjusted analysis, the survival benefit remained significant (hazard ratio [HR], 0.85; P=.004). The benefit was particularly strong in the undifferentiated pleomorphic sarcoma (UPS) group on adjustment, with a median OS of 49.1 and 77.8 months for nonchemotherapy versus chemotherapy, respectively (HR, 0.77; P=.02). Conclusions: In addition to expected tumor and patient factors, histology, location of primary tumor, and socioeconomic status are associated with receipt/nonreceipt of chemotherapy in stage III STS. Chemotherapy use was associated with improved OS in the overall population, and specifically in the UPS subgroup.

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Caitlin R. Meeker, Yu-Ning Wong, Brian L. Egleston, Michael J. Hall, Elizabeth R. Plimack, Lainie P. Martin, Margaret von Mehren, Bianca R. Lewis and Daniel M. Geynisman

Background: Although financial distress is commonly recognized in patients with cancer, it may be more prevalent in younger adults. This study sought to evaluate disparities in overall and financial distress in patients with cancer as a function of age. Methods: This was a single-center cross-sectional study of patients with solid malignancies requiring cancer therapy. The patient questionnaire included demographics, financial concerns, and measures of overall and financial distress. Data analyses compared patients in 3 age groups: young (<50 years), middle-aged (50–64 years), and elderly (≥65 years). Results: The cohort included 119 patients (median age, 62 years; 52% female; 84% white; 100% insured; 36% income ≥$75,000). Significant financial concerns included paying rent/mortgage (P=.003) and buying food (P=.032). Impact of Event Scale (IES) results revealed significant distress in 73% young, 64% middle-aged, and 44% elderly patients. The mean Distress Thermometer (DT) score was 6.1 (standard deviation [SD], 2.9) for young patients, 5.4 (SD, 2.6) for middle-aged, and 4.4 (SD, 3.3) for elderly patients. Young patients were more likely than elderly patients to have a higher IES distress score (P=.016) and DT score (P=.048). The mean InCharge score was lowest (indicating greatest financial distress) in the young group and progressed with age: 5.0 (SD, 1.9), 5.7 (SD, 2.7), and 7.4 (SD, 1.9), respectively (P<.001). Multivariable analyses revealed that the relationship between financial distress and overall distress was strongest in the middle-age group; as the DT increased by 1 point, the InCharge scores decreased by 0.52 (P<.001). Conclusions: Overall and financial distress are more common in young and middle-aged patients with cancer. There are several factors, including employment, insurance, access to paid sick leave, children, and education, that affect younger and middle-aged adults and are less of a potential stressor for elderly individuals.

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George D. Demetri, Margaret von Mehren, Cristina R. Antonescu, Ronald P. DeMatteo, Kristen N. Ganjoo, Robert G. Maki, Peter W.T. Pisters, Chandrajit P. Raut, Richard F. Riedel, Scott Schuetze, Hema M. Sundar, Jonathan C. Trent and Jeffrey D. Wayne

The standard of care for managing patients with gastrointestinal stromal tumors (GISTs) rapidly changed after the introduction of effective molecularly targeted therapies involving tyrosine kinase inhibitors (TKIs), such as imatinib mesylate and sunitinib malate. A better understanding of the molecular characteristics of GISTs have improved the diagnostic accuracy and led to the discovery of novel immunomarkers and new mechanisms of resistance to TKI therapy, which in turn have resulted in the development of novel treatment strategies. To address these issues, the NCCN organized a task force consisting of a multidisciplinary panel of experts in the fields of medical oncology, surgical oncology, molecular diagnostics, and pathology to discuss the recent advances, identify areas of future research, and recommend an optimal approach to care for patients with GIST at all stages of disease. The task force met for the first time in October 2003 and again in December 2006 and October 2009. This supplement describes the recent developments in the field of GIST as discussed at the October 2009 meeting.

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

Cancer is the leading cause of death among the adolescent and young adult (AYA) population, excluding homicide, suicide, or unintentional injury. AYA patients should be managed by a multidisciplinary team of health care professionals who are well-versed in the specific developmental issues relevant to this patient population. The recommendations for age-appropriate care outlined in these NCCN Guidelines include psychosocial assessment, a discussion of infertility risks associated with treatment and options for fertility preservation, genetic and familial risk assessment for all patients after diagnosis, screening and monitoring of late effects in AYA cancer survivors after successful completion of therapy, and palliative care and end-of-life considerations for patients for whom curative therapy fails.

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J. Sybil Biermann, Douglas R. Adkins, Mark Agulnik, Robert S. Benjamin, Brian Brigman, James E. Butrynski, David Cheong, Warren Chow, William T. Curry, Deborah A. Frassica, Frank J. Frassica, Kenneth R. Hande, Francis J. Hornicek, Robin L. Jones, Joel Mayerson, Sean V. McGarry, Brian McGrath, Carol D. Morris, Richard J. O'Donnell, R. Lor Randall, Victor M. Santana, Robert L. Satcher, Herrick J. Siegel, Margaret von Mehren, Mary Anne Bergman and Hema Sundar

Primary bone cancers are extremely rare neoplasms, accounting for fewer than 0.2% of all cancers. The evaluation and treatment of patients with bone cancers requires a multidisciplinary team of physicians, including musculoskeletal, medical, and radiation oncologists, and surgeons and radiologists with demonstrated expertise in the management of these tumors. Long-term surveillance and follow-up are necessary for the management of treatment late effects related to surgery, radiation therapy, and chemotherapy. These guidelines discuss the management of chordoma, giant cell tumor of the bone, and osteosarcoma.

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George D. Demetri, Scott Antonia, Robert S. Benjamin, Marilyn M. Bui, Ephraim S. Casper, Ernest U. Conrad III, Thomas F. DeLaney, Kristen N. Ganjoo, Martin J. Heslin, Raymond J. Hutchinson, John M. Kane III, G. Douglas Letson, Sean V. McGarry, Richard J. O'Donnell, I. Benjamin Paz, John D. Pfeifer, Raphael E. Pollock, R. Lor Randall, Richard F. Riedel, Karen D. Schupak, Herbert S. Schwartz, Katherine Thornton, Margaret von Mehren and Jeffrey Wayne

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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.

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Margaret von Mehren, R. Lor Randall, Robert S. Benjamin, Sarah Boles, Marilyn M. Bui, Ephraim S. Casper, Ernest U. Conrad III, Thomas F. DeLaney, Kristen N. Ganjoo, Suzanne George, Ricardo J. Gonzalez, Martin J. Heslin, John M. Kane III, Joel Mayerson, Sean V. McGarry, Christian Meyer, Richard J. O’Donnell, Alberto S. Pappo, I. Benjamin Paz, John D. Pfeifer, Richard F. Riedel, Scott Schuetze, Karen D. Schupak, Herbert S. Schwartz, Brian A. Van Tine, Jeffrey D. Wayne, Mary Anne Bergman and Hema Sundar

These NCCN Guidelines Insights highlight the important updates to the NCCN Guidelines for Soft Tissue Sarcoma (STS) specific to the role of radiation therapy in the management of patients with retroperitoneal/intra-abdominal STS. The guidelines have also included recommendations for genetic testing and counseling for patients with a clinical and/or family history of genetic cancer syndromes associated with a predisposition for the development of STS.

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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.