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New Persistent Opioid and Benzodiazepine Use After Curative-Intent Treatment in Patients With Breast Cancer

Mandy R. Sakamoto, Megan Eguchi, Christine M. Azelby, Jennifer R. Diamond, Christine M. Fisher, Virginia F. Borges, Cathy J. Bradley, and Peter Kabos

Background: Opioid and benzodiazepine use and abuse is a national healthcare crisis to which patients with cancer are particularly vulnerable. Long-term use and risk factors for opioid and benzodiazepine use in patients with breast cancer is poorly characterized. Methods: We conducted a retrospective population-based study of patients with breast cancer diagnosed between 2008 and 2015 undergoing curative-intent treatment identified through the SEER-Medicare linked database. Primary outcomes were new persistent opioid use and new persistent benzodiazepine use. Factors associated with new opioid and benzodiazepine use were investigated by univariate and multivariable logistic regression. Results: Among opioid-naïve patients, new opioid use was observed in 22,418 (67.4%). Of this group, 611 (2.7%) developed persistent opioid use at 3 months and 157 (0.7%) at 6 months after treatment. Risk factors for persistent use at 3 and 6 months included stage III disease (odds ratio [OR], 2.16; 95% CI, 1.49–3.12, and OR, 3.48; 95% CI, 1.58–7.67), surgery plus chemotherapy (OR, 1.44; 95% CI, 1.10–1.88, and OR, 2.28; 95% CI, 1.40–3.71), surgery plus chemoradiation therapy (OR, 1.47; 95% CI, 1.10–1.96, and OR, 2.34; 95% CI, 1.38–3.96), and initial tramadol use (OR, 2.66; 95% CI, 2.05–3.46, and OR, 3.12; 95% CI, 1.93–5.04). Among benzodiazepine-naïve patients, new benzodiazepine use was observed in 955 (10.3%), and 111 (11.6%) developed new persistent use at 3 months. Tamoxifen use was statistically significantly associated with new persistent benzodiazepine use at 3 months. Conclusions: A large percentage of patients receiving curative-intent treatment of breast cancer were prescribed new opioids; however, only a small number developed new persistent opioid use. In contrast, a smaller proportion of patients received a new benzodiazepine prescription; however, new persistent use after completion of treatment was more likely and particularly related to concurrent treatment with tamoxifen.

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The 21-Gene Recurrence Score Assay for Node-Positive, Early-Stage Breast Cancer and Impact of RxPONDER Trial on Chemotherapy Decision-Making: Have Clinicians Already Decided?

Jagar Jasem, Christine M. Fisher, Arya Amini, Elena Shagisultanova, Rachel Rabinovitch, Virginia F. Borges, Anthony Elias, and Peter Kabos

Background: The 21-gene recurrence score (RS) assay is retrospectively validated for assessing prognosis and benefit from chemotherapy in hormone receptor–positive, early-stage breast cancer (EBC) with low RS. We hypothesized that oncologists have already incorporated the RS assay for decision-making in higher-risk, node-positive disease, despite the lack of prospective data and contrary to NCCN Guideline recommendations. This study provides the first analysis of trends and differences in RS use and therapeutic implications in a population-based data set of patients with node-positive EBC. It also assesses the impact of the RxPONDER trial on clinicians' chemotherapy recommendations. Methods: Node-positive EBC cases diagnosed during 2010 through 2012 and included in the National Cancer Data Base were used. Multivariate logistic regression was used to estimate test use and impact on chemotherapy recommendations. Results: The RS assay was ordered for 16.5% of the 80,405 identified patients. Of all variables, the RS assay had the strongest association with chemotherapy recommendation, with adjusted odds ratios (AORs) of 19 for scores >30. Odds of chemotherapy recommendation were significantly lower for the group who received the test (AOR, 0.21; 95% CI, 0.20–0.22). When divided based on the cutoff point of 25 adopted by the RxPONDER trial, those with an RS of 18 to 25 had significantly lower odds of chemotherapy recommendation compared with those with an RS of 26 to 30 (AOR, 0.32; 95% CI, 0.26–0.40). Test use was lower for blacks, community centers, uninsured/governmentally insured patients, higher tumor grade, larger tumor size, and more nodes involved. Chemotherapy recommendation was higher for patients of younger age, with private insurance, and with higher tumor grade, size, and number of nodes involved. Black patients had significantly higher RS (AOR, 1.37; 95% CI, 1.25–1.79). Conclusions: The RS assay influences clinicians' chemotherapy recommendation in node-positive EBC. Clinicians are using the inclusion criteria of the RxPONDER trial before its final release. Black patients have higher RS, likely representing worse biology. Significant differences exist in test use and clinical implications based on race, insurance, and facility.

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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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Uterine Sarcoma, Version 1.2016

Wui-Jin Koh, Benjamin E. Greer, Nadeem R. Abu-Rustum, Sachin M. Apte, Susana M. Campos, Kathleen R. Cho, Christina Chu, David Cohn, Marta Ann Crispens, Don S. Dizon, Oliver Dorigo, Patricia J. Eifel, Christine M. Fisher, Peter Frederick, David K. Gaffney, Suzanne George, Ernest Han, Susan Higgins, Warner K. Huh, John R. Lurain III, Andrea Mariani, David Mutch, Amanda Nickles Fader, Steven W. Remmenga, R. Kevin Reynolds, Todd Tillmanns, Fidel A. Valea, Catheryn M. Yashar, Nicole R. McMillian, and Jillian L. Scavone

The NCCN Guidelines for Uterine Neoplasms provide interdisciplinary recommendations for treating endometrial carcinoma and uterine sarcomas. These NCCN Guidelines Insights summarize the NCCN Uterine Neoplasms Panel's 2016 discussions and major guideline updates for treating uterine sarcomas. During this most recent update, the panel updated the mesenchymal tumor classification to correspond with recent updates to the WHO tumor classification system. Additionally, the panel revised its systemic therapy recommendations to reflect new data and collective clinical experience. These NCCN Guidelines Insights elaborate on the rationale behind these recent changes.

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Cervical Cancer, Version 2.2015

Wui-Jin Koh, Benjamin E. Greer, Nadeem R. Abu-Rustum, Sachin M. Apte, Susana M. Campos, Kathleen R. Cho, Christina Chu, David Cohn, Marta Ann Crispens, Oliver Dorigo, Patricia J. Eifel, Christine M. Fisher, Peter Frederick, David K. Gaffney, Ernest Han, Warner K. Huh, John R. Lurain III, David Mutch, Amanda Nickles Fader, Steven W. Remmenga, R. Kevin Reynolds, Nelson Teng, Todd Tillmanns, Fidel A. Valea, Catheryn M. Yashar, Nicole R. McMillian, and Jillian L. Scavone

The NCCN Guidelines for Cervical Cancer provide interdisciplinary recommendations for treating cervical cancer. These NCCN Guidelines Insights summarize the NCCN Cervical Cancer Panel’s discussion and major guideline updates from 2014 and 2015. The recommended systemic therapy options for recurrent and metastatic cervical cancer were amended upon panel review of new survival data and the FDA’s approval of bevacizumab for treating late-stage cervical cancer. This article outlines relevant data and provides insight into panel decisions regarding various combination regimens. Additionally, a new section was added to provide additional guidance on key principles of evaluation and surgical staging in cervical cancer. This article highlights 2 areas of active investigation and debate from this new section: sentinel lymph node mapping and fertility-sparing treatment approaches.

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Vulvar Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology

Wui-Jin Koh, Benjamin E. Greer, Nadeem R. Abu-Rustum, Susana M. Campos, Kathleen R. Cho, Hye Sook Chon, Christina Chu, David Cohn, Marta Ann Crispens, Don S. Dizon, Oliver Dorigo, Patricia J. Eifel, Christine M. Fisher, Peter Frederick, David K. Gaffney, Ernest Han, Susan Higgins, Warner K. Huh, John R. Lurain III, Andrea Mariani, David Mutch, Christa Nagel, Larissa Nekhlyudov, Amanda Nickles Fader, Steven W. Remmenga, R. Kevin Reynolds, Todd Tillmanns, Stefanie Ueda, Fidel A. Valea, Emily Wyse, Catheryn M. Yashar, Nicole McMillian, and Jillian Scavone

Vulvar cancer is a rare gynecologic malignancy. Ninety percent of vulvar cancers are predominantly squamous cell carcinomas (SCCs), which can arise through human papilloma virus (HPV)–dependent and HPV-independent pathways. The NCCN Vulvar Cancer panel is an interdisciplinary group of representatives from NCCN Member Institutions consisting of specialists in gynecological oncology, medical oncology, radiation oncology, and pathology. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Vulvar Cancer provide an evidence- and consensus-based approach for the management of patients with vulvar SCC. This manuscript discusses the recommendations outlined in the NCCN Guidelines for diagnosis, staging, treatment, and follow-up.

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NCCN Guidelines® Insights: Uterine Neoplasms, Version 3.2021

Featured Updates to the NCCN Guidelines

Nadeem R. Abu-Rustum, Catheryn M. Yashar, Kristin Bradley, Susana M. Campos, Junzo Chino, Hye Sook Chon, Christina Chu, David Cohn, Marta Ann Crispens, Shari Damast, Elisabeth Diver, Christine M. Fisher, Peter Frederick, David K. Gaffney, Suzanne George, Robert Giuntoli II, Ernest Han, Brooke Howitt, Warner K. Huh, Jayanthi Lea, Andrea Mariani, David Mutch, Larissa Nekhlyudov, Mirna Podoll, Steven W. Remmenga, R. Kevin Reynolds, Ritu Salani, Rachel Sisodia, Pamela Soliman, Edward Tanner, Stefanie Ueda, Renata Urban, Stephanie L. Wethington, Emily Wyse, Kristine Zanotti, Nicole R. McMillian, and Angela D. Motter

The NCCN Guidelines for Uterine Neoplasms provide recommendations for diagnostic workup, clinical staging, and treatment options for patients with endometrial cancer or uterine sarcoma. These NCCN Guidelines Insights focus on the recent addition of molecular profiling information to aid in accurate diagnosis, classification, and treatment of uterine sarcomas.

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NCCN Guidelines Insights: Cervical Cancer, Version 1.2020

Featured Updates to the NCCN Guidelines

Nadeem R. Abu-Rustum, Catheryn M. Yashar, Sarah Bean, Kristin Bradley, Susana M. Campos, Hye Sook Chon, Christina Chu, David Cohn, Marta Ann Crispens, Shari Damast, Christine M. Fisher, Peter Frederick, David K. Gaffney, Robert Giuntoli II, Ernest Han, Warner K. Huh, John R. Lurain III, Andrea Mariani, David Mutch, Christa Nagel, Larissa Nekhlyudov, Amanda Nickles Fader, Steven W. Remmenga, R. Kevin Reynolds, Rachel Sisodia, Todd Tillmanns, Stefanie Ueda, Renata Urban, Emily Wyse, Nicole R. McMillian, and Angela D. Motter

The NCCN Guidelines for Cervical Cancer provide recommendations for diagnostic workup, staging, and treatment of patients with the disease. These NCCN Guidelines Insights focus on recent updates to the guidelines, including changes to first- and second-line systemic therapy recommendations for patients with recurrent or metastatic disease, and emerging evidence on a new histopathologic classification system for HPV-related endocervical adenocarcinoma.

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Gestational Trophoblastic Neoplasia, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology

Nadeem R. Abu-Rustum, Catheryn M. Yashar, Sarah Bean, Kristin Bradley, Susana M. Campos, Hye Sook Chon, Christina Chu, David Cohn, Marta Ann Crispens, Shari Damast, Oliver Dorigo, Patricia J. Eifel, Christine M. Fisher, Peter Frederick, David K. Gaffney, Ernest Han, Warner K. Huh, John R. Lurain III, Andrea Mariani, David Mutch, Christa Nagel, Larissa Nekhlyudov, Amanda Nickles Fader, Steven W. Remmenga, R. Kevin Reynolds, Rachel Sisodia, Todd Tillmanns, Stefanie Ueda, Emily Wyse, Nicole R. McMillian, and Jillian Scavone

Gestational trophoblastic neoplasia (GTN), a subset of gestational trophoblastic disease (GTD), occurs when tumors develop in the cells that would normally form the placenta during pregnancy. The NCCN Guidelines for Gestational Trophoblastic Neoplasia provides treatment recommendations for various types of GTD including hydatidiform mole, persistent post-molar GTN, low-risk GTN, high-risk GTN, and intermediate trophoblastic tumor.

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Cervical Cancer, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology

Wui-Jin Koh, Nadeem R. Abu-Rustum, Sarah Bean, Kristin Bradley, Susana M. Campos, Kathleen R. Cho, Hye Sook Chon, Christina Chu, Rachel Clark, David Cohn, Marta Ann Crispens, Shari Damast, Oliver Dorigo, Patricia J. Eifel, Christine M. Fisher, Peter Frederick, David K. Gaffney, Ernest Han, Warner K. Huh, John R. Lurain III, Andrea Mariani, David Mutch, Christa Nagel, Larissa Nekhlyudov, Amanda Nickles Fader, Steven W. Remmenga, R. Kevin Reynolds, Todd Tillmanns, Stefanie Ueda, Emily Wyse, Catheryn M. Yashar, Nicole R. McMillian, and Jillian L. Scavone

Cervical cancer is a malignant epithelial tumor that forms in the uterine cervix. Most cases of cervical cancer are preventable through human papilloma virus (HPV) vaccination, routine screening, and treatment of precancerous lesions. However, due to inadequate screening protocols in many regions of the world, cervical cancer remains the fourth-most common cancer in women globally. The complete NCCN Guidelines for Cervical Cancer provide recommendations for the diagnosis, evaluation, and treatment of cervical cancer. This manuscript discusses guiding principles for the workup, staging, and treatment of early stage and locally advanced cervical cancer, as well as evidence for these recommendations. For recommendations regarding treatment of recurrent or metastatic disease, please see the full guidelines on NCCN.org.