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Lainie Martin and Russell J. Schilder

Although significant improvements in standard therapy for ovarian carcinoma have been made over the past decade, current treatment is limited by the development of resistance to cytotoxic chemotherapy, and most women ultimately die of the disease. New knowledge of the biology of ovarian cancer has led to the identification of potential molecular targets that are differentially expressed in normal cells versus cancer cells, and advances in pharmacology have led to the development of novel agents that work differently from traditional cytotoxic chemotherapy by exploiting these targets. Many of these agents are being evaluated in clinical trials. This article discusses molecular targets that are important in ovarian carcinoma, including angiogenesis, tyrosine kinases, mitogen-activated protein kinases, and phosphatidylinositol-like kinases such as mammalian target of rapamycin, and the proteosome. This article reviews novel non-cytotoxic agents that target these pathways and are currently being evaluated in ovarian carcinoma treatment.

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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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Wui-Jin Koh, Benjamin E. Greer, Nadeem R. Abu-Rustum, Sachin M. Apte, Susana M. Campos, John Chan, Kathleen R. Cho, David Cohn, Marta Ann Crispens, Nefertiti DuPont, Patricia J. Eifel, Amanda Nickles Fader, Christine M. Fisher, David K. Gaffney, Suzanne George, Ernest Han, Warner K. Huh, John R. Lurain III, Lainie Martin, David Mutch, Steven W. Remmenga, R. Kevin Reynolds, William Small Jr, Nelson Teng, Todd Tillmanns, Fidel A. Valea, Nicole McMillian and Miranda Hughes

Adenocarcinoma of the endometrium (also known as endometrial cancer or more broadly as uterine cancer or carcinoma of the uterine corpus) is the most common malignancy of the female genital tract in the United States. An estimated 49,560 new uterine cancer cases will occur in 2013, with 8190 deaths resulting from the disease. Uterine sarcomas (stromal/mesenchymal tumors) are uncommon malignancies, accounting for approximately 3% of all uterine cancers. The NCCN Guidelines for Uterine Neoplasms describe malignant epithelial carcinomas and uterine sarcomas; each of these major categories contains specific histologic groups that require different management. This excerpt of these guidelines focuses on early-stage disease.

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Wui-Jin Koh, Benjamin E. Greer, Nadeem R. Abu-Rustum, Sachin M. Apte, Susana M. Campos, John Chan, Kathleen R. Cho, David Cohn, Marta Ann Crispens, Nefertiti DuPont, Patricia J. Eifel, David K. Gaffney, Robert L. Giuntoli II, Ernest Han, Warner K. Huh, John R. Lurain III, Lainie Martin, Mark A. Morgan, David Mutch, Steven W. Remmenga, R. Kevin Reynolds, William Small Jr, Nelson Teng, Todd Tillmanns, Fidel A. Valea, Nicole R. McMillian and Miranda Hughes

These NCCN Clinical Practice Guidelines in Oncology for Cervical Cancer focus on early-stage disease, because it occurs more frequently in the United States. After careful clinical evaluation and staging, the primary treatment of early-stage cervical cancer is either surgery or radiotherapy. These guidelines include fertility-sparing and non-fertility-sparing treatment for those with early-stage disease, which is disease confined to the uterus. A new fertility-sparing algorithm was added for select patients with stage IA and IB1 disease..

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Daniel G. Coit, Robert Andtbacka, Christopher K. Bichakjian, Raza A. Dilawari, Dominick DiMaio, Valerie Guild, Allan C. Halpern, F. Stephen Hodi, Mohammed Kashani-Sabet, Julie R. Lange, Anne Lind, Lainie Martin, Mary C. Martini, Scott K. Pruitt, Merrick I. Ross, Stephen F. Sener, Susan M. Swetter, Kenneth K. Tanabe, John A. Thompson, Vijay Trisal, Marshall M. Urist, Jeffrey Weber and Michael K. Wong

Melanoma Clinical Practice Guidelines in OncologyNCCN Categories of Evidence and ConsensusCategory 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.In 2008, an estimated 62,480 new cases of melanoma will have been diagnosed and approximately 8420 patients will have died of the disease in the United States.1 However, these projections for new cases may represent a substantial underestimation, because many superficial and in situ melanomas treated in the outpatient setting are not reported. The incidence of melanoma continues to increase dramatically. Melanoma is increasing in men more rapidly than any other malignancy and more rapidly in women than any other malignancy except lung cancer. For someone born in the United States in 2005, the lifetime risk for developing melanoma may be as high as 1 in 55.2 Melanoma ranks second to adult leukemia in terms of loss of years of potential life, per death. The median age at diagnosis is 59 years.Risk factors for melanoma include...
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Benjamin E. Greer, Wui-Jin Koh, Nadeem R. Abu-Rustum, Sachin M. Apte, Susana M. Campos, John Chan, Kathleen R. Cho, Larry Copeland, Marta Ann Crispens, Nefertiti DuPont, Patricia J. Eifel, David K. Gaffney, Warner K. Huh, Daniel S. Kapp, John R. Lurain III, Lainie Martin, Mark A. Morgan, Robert J. Morgan Jr., David Mutch, Steven W. Remmenga, R. Kevin Reynolds, William Small Jr., Nelson Teng and Fidel A. Valea

OverviewAn estimated 12,200 new cases of cervical cancer will be diagnosed in the United States in 2010, and 4200 people will die of the disease.1 Cervical cancer rates are decreasing among women in the United States, although incidence remains high among Hispanic/Latino, black, and Asian women.2–5 However, cervical cancer is a major world health problem for women. The global yearly incidence of cervical cancer for 2002 was 493,200; the annual death rate was 273,500. It is the third most common cancer in women worldwide,6,7 with 78% of cases occurring in developing countries, where cervical cancer is the second most frequent cause of cancer death in women.Persistent human papillomavirus (HPV) infection is regarded as the most important factor contributing to the development of cervical cancer. A relationship seems to exist between the incidence of cervical cancer and the prevalence of HPV in the population. The prevalence of chronic HPV in countries with a high incidence of cervical cancer is 10% to 20%, whereas its prevalence in low-incidence countries is 5% to 10%.6 Immunization against HPV prevents infection with certain types of HPV and, thus, is expected to prevent specific HPV cancer in women (see NCCN Clinical Practice Guidelines in Oncology [NCCN Guidelines] for Cervical Cancer Screening, in this issue; to view the most recent version of these guidelines, visit the NCCN Web site at www.NCCN.org).8–12 Other epidemiologic risk factors associated with cervical cancer are a history of smoking, parity, contraceptive use, early age at onset of coitus, larger number...
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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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Robert J. Morgan, Ronald D. Alvarez, Deborah K. Armstrong, Robert A. Burger, Mariana Castells, Lee-may Chen, Larry Copeland, Marta Ann Crispens, David Gershenson, Heidi Gray, Ardeshir Hakam, Laura J. Havrilesky, Carolyn Johnston, Shashikant Lele, Lainie Martin, Ursula A. Matulonis, David M. O’Malley, Richard T. Penson, Steven W. Remmenga, Paul Sabbatini, Joseph T. Santoso, Russell J. Schilder, Julian Schink, Nelson Teng, Theresa L. Werner, Miranda Hughes and Mary A. Dwyer

These NCCN Guidelines Insights focus on the major updates for the 2012 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Ovarian Cancer by describing how and why the new recommendations were made. The 6 update topics were selected based on recent important updates in the guidelines and on debate among panel members about recent clinical trials, and include: 1) screening, 2) diagnostic tests for assessing pelvic masses, 3) primary treatment using neoadjuvant chemotherapy, 4) primary adjuvant treatment using bevacizumab in combination with chemotherapy, 5) therapy for recurrent disease, and 6) management of drug/hypersensitivity reactions. These NCCN Guidelines Insights also discuss why some recommendations were not made (eg, panel members did not feel the new data warranted changing the guideline). See “Updates” in the NCCN Guidelines for Ovarian Cancer for a complete list of all the recent revisions.

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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.