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NCCN Guidelines Update: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Presented by: Deborah M. Stephens

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is characterized by the accumulation of abnormal lymphocytes in the blood, bone marrow, and lymphoid tissues, leading to a weakened immune system and an increased risk of infections for patients. The NCCN Guidelines for CLL/SLL underscore the need for a comprehensive evaluation of multiple factors to determine the most appropriate treatment approach for each patient. For frontline therapy, the selection process should consider the patient’s IGHV status, del(17p)/TP53 mutation status, age, and comorbidities. In choosing subsequent therapy, prior therapy, comorbidities, and resistance mutations should be considered. With no clear evidence of a functional cure, it is important to enroll patients in clinical trials when available.

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Debate: What Is Optimal First-Line Therapy for Chronic Lymphocytic Leukemia?

Presented by: Mazyar Shadman and Deborah M. Stephens

In the era of newer, highly effective targeted therapies for chronic lymphocytic leukemia (CLL), experts debated whether there is still a role for chemoimmunotherapy in the first-line setting for the treatment of this disease. In general, targeted therapies are preferred as first-line treatment for all patients, with the exception of low-risk patients [younger, fit patients with mutated IGHV who are candidates for fludarabine/cyclophosphamide/rituximab (FCR)]. About 37% of low-risk patients experience long-term durable remissions and remain stable after treatment with FCR for many years. Advantages of FCR over small molecule inhibitors include cost, fixed duration treatment, and long-term survival benefit. Disadvantages are an etimated 5% risk of developing myelodysplastic syndrome or acute myeloid leukemia. Advantages of small molecule inhibitors are improvements in progression-free and overall survival and quality of life when compared with chemoimmunotherapy. Disadvantages of small molecule inhibitors are high cost and the need for continuous treatment. However, studies are underway to develop fixed duration regimens with combinations of small molecule inhibitors that aim to deepen remissions.

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CGE23-074: Mutational Landscape in Concurrent and Sequential Cases of Lymphoid Malignancy and CMML

Margaret Kelsey Baron, Ania Shestakova, Tony D Pomicter, Justin Williams, Srinivas K Tantravahi, Ami B Patel, and Deborah M Stephens

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Systemic Therapy for Advanced Appendiceal Adenocarcinoma: An Analysis From the NCCN Oncology Outcomes Database for Colorectal Cancer

Mohamedtaki A. Tejani, Anna ter Veer, Dana Milne, Rebecca Ottesen, Tanios Bekaii-Saab, Al B. Benson III, Deborah Schrag, Stephen Shibata, John Skibber, Martin Weiser, Neal Wilkinson, and Steven J. Cohen

Appendiceal malignancies are rare and represent 1% of intestinal tumors in the United States. The role and efficacy of modern systemic therapy in advanced appendiceal adenocarcinoma has not been established. This study analyzed patients with recurrent or metastatic appendiceal adenocarcinoma in the database for Colorectal Cancer (CRC; 2005-2012). This database tracks longitudinal care for patients treated at 8 specialty centers across the Unites States. Study objectives were to describe and evaluate the efficacy of systemic therapy and investigate relationships with clinicopathologic features. Cox regression analysis was performed to identify predictors of progression-free survival (PFS) and overall survival (OS). Of 248 patients with advanced appendiceal carcinoma, 112 (45%) received systemic therapy for measurable disease and are the focus of this report. The most common chemotherapy regimens included FOLFOX with or without bevacizumab (n=39 and n=37, respectively), FOLFIRI (n=15), and single-agent fluoro-pyrimidine (n=10). Among 99 patients evaluable for best response, 39 experienced a response (response rate [RR], 39%) and 36 (36%) had stable disease. The median PFS was 1.2 years (95% CI, 1.0-1.8) and median OS was 2.1 years (95% CI, 1.6-2.3). Patients with non-mucinous histology or high-grade tumors and those who underwent nondebulking surgery had worse PFS and OS. Treatment of advanced appendiceal adenocarcinoma at NCCN Member Institutions commonly incorporates agents used for CRC. RR, PFS, and OS are comparable to those achieved in the treatment of metastatic CRC. Poor prognostic factors include nonmucinous histology or high-grade tumors and history of nondebulking surgery.

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Concordance with NCCN Colorectal Cancer Guidelines and ASCO/NCCN Quality Measures: An NCCN Institutional Analysis

Dorothy Romanus, Martin R. Weiser, John M. Skibber, Anna Ter Veer, Joyce C. Niland, John L. Wilson, Ashwani Rajput, Yu-Ning Wong, Al B. Benson III, Stephen Shibata, and Deborah Schrag

Background

The National Comprehensive Cancer Network (NCCN) Outcomes Database was created to assess concordance to evidence- and consensus-based guidelines and to measure adherence to quality measures on an ongoing basis. The Colorectal Cancer Database began in 2005 as a collaboration among 8 NCCN centers.

Methods

Newly diagnosed colon and rectal cancer patients presenting to 1 of 8 NCCN centers between September 1, 2005, and May 21, 2008, were eligible for analysis of concordance with NCCN treatment guidelines for colorectal cancer and with a set of quality metrics jointly developed by ASCO and NCCN in 2007. Adherence rates were determined for each metric. Center-specific rates were benchmarked against mean concordance rates for all participating centers.

Results

A total of 3443 patients were evaluable. Mean concordance rates with NCCN colorectal cancer guidelines and ASCO/NCCN quality measures were generally high (≥ 90%). However, relatively low mean concordance rates were noted for adjuvant chemotherapy treatment recommendations within 9 months of diagnosis of stage II to III rectal cancer (81%), and neoadjuvant chemoradiation in clinical T4 rectal primaries (83%). These low rates of concordance seemed to be consistent across centers.

Conclusions

Adherence to guidelines and quality measures is generally high at institutions participating in the NCCN colorectal cancer database. Lack of documentation, patient refusal, delayed treatment initiation, and lack of consensus about whether treatment was essential were the primary reasons for nonconcordance. Measurement of concordance and the reasons for nonconcordance enable participating centers to understand and improve their care delivery systems.

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Treating Second Breast Events After Breast-Conserving Surgery for Ductal Carcinoma in Situ

Michael J. Hassett, Wei Jiang, Melissa E. Hughes, Stephen Edge, Sara H. Javid, Joyce C. Niland, Richard Theriault, Yu-Ning Wong, Deborah Schrag, and Rinaa S. Punglia

Background: Because of screening mammography, the number of ductal carcinoma in situ (DCIS) survivors has increased dramatically. DCIS survivors may face excess risk of second breast events (SBEs). However, little is known about SBE treatment or its relationship to initial DCIS care. Methods: Among a prospective cohort of women who underwent breast-conserving surgery (BCS) for DCIS from 1997 to 2008 at institutions participating in the NCCN Outcomes Database, we identified SBEs, described patterns of care for SBEs, and examined the association between DCIS treatment choice and SBE care. Using multivariable regression, we identified features associated with use of mastectomy, radiation therapy (RT), or antiestrogen therapy (AET) for SBEs. Results: Of 2,939 women who underwent BCS for DCIS, 83% received RT and 40% received AET. During the median follow-up of 4.2 years, 200 women (6.8%) developed an SBE (55% ipsilateral, 45% invasive). SBEs occurred in 6% of women who underwent RT for their initial DCIS versus 11% who did not. Local treatment for these events included BCS (10%), BCS/RT (30%), mastectomy (53%), or none (6%); only 28% of patients received AET. Independent predictors of RT or mastectomy for SBEs included younger age, shorter time to SBE diagnosis, and RT or AET for the initial DCIS. Conclusions: A sizable proportion of patients with SBEs were treated with mastectomy, most especially those who previously received RT for their initial DCIS and those who developed an ipsilateral SBE. Despite the occurrence of an SBE, relatively few patients received AET. Future studies should investigate optimal treatment approaches for SBEs, including the benefit of mastectomy versus lumpectomy for an ipsilateral SBE and the benefit of AET for a hormone-receptor–positive SBE contingent on AET use for the initial DCIS diagnosis.

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YIA23-004: Non-Melanoma Skin Cancer (NMSC) in Patients With Chronic Lymphocytic Leukemia (CLL): Biology and Prevention

Deborah M. Stephens, Kenneth Boucher, David A. Wada, Aaron Atkinson, Jack Abbott, Marianne Bowling, Justin Williams, Anthony D. Pomicter, Renee Vadeboncouer, Clayton Savage, Brynn Parsegov, Lindsey Gilstrap, Christa Shorter, Harsh Shah, Boyu Hu, and Lindsey Fitzgerald

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Survivorship: Sexual Dysfunction (Male), Version 1.2013

Crystal S. Denlinger, Robert W. Carlson, Madhuri Are, K. Scott Baker, Elizabeth Davis, Stephen B. Edge, Debra L. Friedman, Mindy Goldman, Lee Jones, Allison King, Elizabeth Kvale, Terry S. Langbaum, Jennifer A. Ligibel, Mary S. McCabe, Kevin T. McVary, Michelle Melisko, Jose G. Montoya, Kathi Mooney, Mary Ann Morgan, Tracey O’Connor, Electra D. Paskett, Muhammad Raza, Karen L. Syrjala, Susan G. Urba, Mark T. Wakabayashi, Phyllis Zee, Nicole McMillian, and Deborah Freedman-Cass

Various anticancer treatments, especially those directed toward the pelvis, can damage blood vessels and reduce circulation of blood to the penis and/or damage the autonomic nervous system, resulting in higher rates of erectile dysfunction in survivors than in the general population. In addition, hormonal therapy can contribute to sexual problems, as can depression and anxiety, which are common in cancer survivors. This section of the NCCN Guidelines for Survivorship provides screening, evaluation, and treatment recommendations for male sexual problems, namely erectile dysfunction.

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Survivorship: Sexual Dysfunction (Female), Version 1.2013

Crystal S. Denlinger, Robert W. Carlson, Madhuri Are, K. Scott Baker, Elizabeth Davis, Stephen B. Edge, Debra L. Friedman, Mindy Goldman, Lee Jones, Allison King, Elizabeth Kvale, Terry S. Langbaum, Jennifer A. Ligibel, Mary S. McCabe, Kevin T. McVary, Michelle Melisko, Jose G. Montoya, Kathi Mooney, Mary Ann Morgan, Tracey O’Connor, Electra D. Paskett, Muhammad Raza, Karen L. Syrjala, Susan G. Urba, Mark T. Wakabayashi, Phyllis Zee, Nicole McMillian, and Deborah Freedman-Cass

Cancer treatment, especially hormonal therapy and therapy directed toward the pelvis, can contribute to sexual problems, as can depression and anxiety, which are common in cancer survivors. Thus, sexual dysfunction is common in survivors and can cause increased distress and have a significant negative impact on quality of life. This section of the NCCN Guidelines for Survivorship provides screening, evaluation, and treatment recommendations for female sexual problems, including those related to sexual desire, arousal, orgasm, and pain.

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Neuroendocrine Tumors

Matthew H. Kulke, Al B. Benson III, Emily Bergsland, Jordan D. Berlin, Lawrence S. Blaszkowsky, Michael A. Choti, Orlo H. Clark, Gerard M. Doherty, James Eason, Lyska Emerson, Paul F. Engstrom, Whitney S. Goldner, Martin J. Heslin, Fouad Kandeel, Pamela L. Kunz, Boris W. Kuvshinoff II, Jeffrey F. Moley, Venu G. Pillarisetty, Leonard Saltz, David E. Schteingart, Manisha H. Shah, Stephen Shibata, Jonathan R. Strosberg, Jean-Nicolas Vauthey, Rebekah White, James C. Yao, Deborah A. Freedman-Cass, and Mary A. Dwyer

Neuroendocrine tumors comprise a broad family of tumors, the most common of which are carcinoid and pancreatic neuroendocrine tumors. The NCCN Neuroendocrine Tumors Guidelines discuss the diagnosis and management of both sporadic and hereditary neuroendocrine tumors. Most of the recommendations pertain to well-differentiated, low- to intermediate-grade tumors. This updated version of the NCCN Guidelines includes a new section on pathology for diagnosis and reporting and revised recommendations for the surgical management of neuroendocrine tumors of the pancreas.