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Novel Non-Cytotoxic Therapy in Ovarian Cancer: Current Status and Future Prospects

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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Distress and Financial Distress in Adults With Cancer: An Age-Based Analysis

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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Ovarian Cancer, Version 1.2016, NCCN Clinical Practice Guidelines in Oncology

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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Cervical Cancer

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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Uterine Neoplasms, Version 1.2014

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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Ovarian Cancer, Version 2.2013

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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Ovarian Cancer, Version 3.2012

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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Melanoma

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

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Cervical Cancer

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

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NCCN Guidelines® Insights: Ovarian Cancer, Version 3.2022

Featured Updates to the NCCN Guidelines

Deborah K. Armstrong, Ronald D. Alvarez, Floor J. Backes, Jamie N. Bakkum-Gamez, Lisa Barroilhet, Kian Behbakht, Andrew Berchuck, Lee-may Chen, Viola C. Chitiyo, Mihaela Cristea, Maria DeRosa, Eric L. Eisenhauer, David M. Gershenson, Heidi J. Gray, Rachel Grisham, Ardeshir Hakam, Angela Jain, Amer Karam, Gottfried E. Konecny, Charles A. Leath III, Gary Leiserowitz, Joyce Liu, Lainie Martin, Daniela Matei, Michael McHale, Karen McLean, David S. Miller, Sanja Percac-Lima, Steven W. Remmenga, John Schorge, Daphne Stewart, Premal H. Thaker, Roberto Vargas, Andrea Wahner Hendrickson, Theresa L. Werner, Emese Zsiros, Mary A. Dwyer, and Lisa Hang

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States, with less than half of patients living >5 years following diagnosis. The NCCN Guidelines for Ovarian Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with ovarian, fallopian tube, and primary peritoneal cancers. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including revised guidance on alternative chemotherapy regimens for patients with advanced age and/or comorbidities, a new algorithm for recurrent low-grade serous carcinoma based on developing research and novel therapeutic agents, and updated language regarding tumor molecular analysis applications in ovarian cancer.