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Sequencing of Treatment in Advanced Unresectable Colorectal Cancer

Jean L. Grem

This article reviews the various systemic therapy options for patients with metastatic colorectal cancer (CRC) that is judged to be noncurable. The choice of initial therapy depends on patient preferences, treatment goals, performance status, and presence of comorbid conditions. Whether surgical resection of the primary tumor should be considered in patients who present with metastatic CRC is a matter of controversy. The components of the initial systemic regimen influence the options for second- and third-line options when disease progression occurs during therapy. The standard of practice is often to continue chemotherapy until progression, unacceptable side effects, or death. In patients with incurable CRC, the balance between efficacy, toxicity, and repeated hospital or clinic visits must be discussed with the patient. Although continuous treatment may be appropriate for some patients, intermittent treatment strategies or maintenance with the least toxic agents may be preferable for others. If disease progression occurs during a chemotherapy break or while the patient is on maintenance therapy, previously used agents may be reintroduced provided that preexisting toxicities have resolved.

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Rectal Cancer

Al B. Benson III, Tanios Bekaii-Saab, Emily Chan, Yi-Jen Chen, Michael A. Choti, Harry S. Cooper, Paul F. Engstrom, Peter C. Enzinger, Marwan G. Fakih, Charles S. Fuchs, Jean L. Grem, Steven Hunt, Lucille A. Leong, Edward Lin, Michael G. Martin, Kilian Salerno May, Mary F. Mulcahy, Kate Murphy, Eric Rohren, David P. Ryan, Leonard Saltz, Sunil Sharma, David Shibata, John M. Skibber, William Small Jr, Constantinos T. Sofocleous, Alan P. Venook, Christopher G. Willett, Deborah A. Freedman-Cass, and Kristina M. Gregory

These NCCN Clinical Practice Guidelines in Oncology provide recommendations for the management of rectal cancer, beginning with the clinical presentation of the patient to the primary care physician or gastroenterologist through diagnosis, pathologic staging, neoadjuvant treatment, surgical management, adjuvant treatment, surveillance, management of recurrent and metastatic disease, and survivorship. This discussion focuses on localized disease. The NCCN Rectal Cancer Panel believes that a multidisciplinary approach, including representation from gastroenterology, medical oncology, surgical oncology, radiation oncology, and radiology, is necessary for treating patients with rectal cancer.

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Colon Cancer

Paul F. Engstrom, Juan Pablo Arnoletti, Al B. Benson III, Yi-Jen Chen, Michael A. Choti, Harry S. Cooper, Anne Covey, Raza A. Dilawari, Dayna S. Early, Peter C. Enzinger, Marwan G. Fakih, James Fleshman Jr., Charles Fuchs, Jean L. Grem, Krystyna Kiel, James A. Knol, Lucille A. Leong, Edward Lin, Mary F. Mulcahy, Sujata Rao, David P. Ryan, Leonard Saltz, David Shibata, John M. Skibber, Constantinos Sofocleous, James Thomas, Alan P. Venook, and Christopher Willett

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Rectal Cancer

Paul F. Engstrom, Juan Pablo Arnoletti, Al B. Benson III, Yi-Jen Chen, Michael A. Choti, Harry S. Cooper, Anne Covey, Raza A. Dilawari, Dayna S. Early, Peter C. Enzinger, Marwan G. Fakih, James Fleshman Jr., Charles Fuchs, Jean L. Grem, Krystyna Kiel, James A. Knol, Lucille A. Leong, Edward Lin, Mary F. Mulcahy, Sujata Rao, David P. Ryan, Leonard Saltz, David Shibata, John M. Skibber, Constantinos Sofocleous, James Thomas, Alan P. Venook, and Christopher Willett

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Colon Cancer

Al B. Benson III, J. Pablo Arnoletti, Tanios Bekaii-Saab, Emily Chan, Yi-Jen Chen, Michael A. Choti, Harry S. Cooper, Raza A. Dilawari, Paul F. Engstrom, Peter C. Enzinger, James W. Fleshman Jr., Charles S. Fuchs, Jean L. Grem, James A. Knol, Lucille A. Leong, Edward Lin, Kilian Salerno May, Mary F. Mulcahy, Kate Murphy, Eric Rohren, David P. Ryan, Leonard Saltz, Sunil Sharma, David Shibata, John M. Skibber, William Small Jr., Constantinos T. Sofocleous, Alan P. Venook, and Christopher Willett

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Anal Carcinoma

Paul F. Engstrom, Juan Pablo Arnoletti, Al B. Benson III, Jordan D. Berlin, J. Michael Berry, Yi-Jen Chen, Michael A. Choti, Harry S. Cooper, Raza A. Dilawari, Dayna S. Early, Peter C. Enzinger, Marwan G. Fakih, James Fleshman Jr., Charles Fuchs, Jean L. Grem, James A. Knol, Lucille A. Leong, Edward Lin, Mary F. Mulcahy, Eric Rohren, David P. Ryan, Leonard Saltz, David Shibata, John M. Skibber, William Small Jr., Constantinos Sofocleous, James Thomas, Alan P. Venook, and Christopher Willett

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Colon Cancer, Version 3.2014

Al B. Benson III, Alan P. Venook, Tanios Bekaii-Saab, Emily Chan, Yi-Jen Chen, Harry S. Cooper, Paul F. Engstrom, Peter C. Enzinger, Moon J. Fenton, Charles S. Fuchs, Jean L. Grem, Steven Hunt, Ahmed Kamel, Lucille A. Leong, Edward Lin, Wells Messersmith, Mary F. Mulcahy, James D. Murphy, Steven Nurkin, Eric Rohren, David P. Ryan, Leonard Saltz, Sunil Sharma, David Shibata, John M. Skibber, Constantinos T. Sofocleous, Elena M. Stoffel, Eden Stotsky-Himelfarb, Christopher G. Willett, Kristina M. Gregory, and Deborah A. Freedman-Cass

The NCCN Guidelines for Colon Cancer address diagnosis, pathologic staging, surgical management, perioperative treatment, posttreatment surveillance, management of recurrent and metastatic disease,and survivorship. This portion of the guidelines focuses on the use of systemic therapy in metastatic disease. The management of metastatic colorectal cancer involves a continuum of care in which patients are exposed sequentially to a variety of active agents, either in combinations or as single agents. Choice of therapy is based on the goals of treatment, the type and timing of prior therapy, the different efficacy and toxicity profiles of the drugs, the mutational status of the tumor, and patient preference.

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Localized Colon Cancer, Version 3.2013

Al B. Benson III, Tanios Bekaii-Saab, Emily Chan, Yi-Jen Chen, Michael A. Choti, Harry S. Cooper, Paul F. Engstrom, Peter C. Enzinger, Marwan G. Fakih, Moon J. Fenton, Charles S. Fuchs, Jean L. Grem, Steven Hunt, Ahmed Kamel, Lucille A. Leong, Edward Lin, Kilian Salerno May, Mary F. Mulcahy, Kate Murphy, Eric Rohren, David P. Ryan, Leonard Saltz, Sunil Sharma, David Shibata, John M. Skibber, William Small Jr, Constantinos T. Sofocleous, Alan P. Venook, Christopher G. Willett, Kristina M. Gregory, and Deborah A. Freedman-Cass

The NCCN Clinical Practice Guidelines in Oncology for Colon Cancer begin with the clinical presentation of the patient to the primary care physician or gastroenterologist and address diagnosis, pathologic staging, surgical management, perioperative treatment, patient surveillance, management of recurrent and metastatic disease, and survivorship. The NCCN Colon Cancer Panel meets annually to review comments from reviewers within their institutions and to reevaluate and update their recommendations. In addition, the panel has interim conferences as new data necessitate. These NCCN Guidelines Insights summarize the NCCN Colon Cancer Panel’s discussions regarding the treatment of localized disease for the 2013 update of the guidelines.

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Rectal Cancer, Version 2.2015

Al B. Benson III, Alan P. Venook, Tanios Bekaii-Saab, Emily Chan, Yi-Jen Chen, Harry S. Cooper, Paul F. Engstrom, Peter C. Enzinger, Moon J. Fenton, Charles S. Fuchs, Jean L. Grem, Axel Grothey, Howard S. Hochster, Steven Hunt, Ahmed Kamel, Natalie Kirilcuk, Lucille A. Leong, Edward Lin, Wells A. Messersmith, Mary F. Mulcahy, James D. Murphy, Steven Nurkin, Eric Rohren, David P. Ryan, Leonard Saltz, Sunil Sharma, David Shibata, John M. Skibber, Constantinos T. Sofocleous, Elena M. Stoffel, Eden Stotsky-Himelfarb, Christopher G. Willett, Kristina M. Gregory, and Deborah Freedman-Cass

The NCCN Guidelines for Rectal Cancer begin with the clinical presentation of the patient to the primary care physician or gastroenterologist and address diagnosis, pathologic staging, surgical management, perioperative treatment, posttreatment surveillance, management of recurrent and metastatic disease, and survivorship. The NCCN Rectal Cancer Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize major discussion points from the 2015 NCCN Rectal Cancer Panel meeting. Major discussion topics this year were perioperative therapy options and surveillance for patients with stage I through III disease.

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

Al B. Benson III, Alan P. Venook, Lynette Cederquist, Emily Chan, Yi-Jen Chen, Harry S. Cooper, Dustin Deming, Paul F. Engstrom, Peter C. Enzinger, Alessandro Fichera, Jean L. Grem, Axel Grothey, Howard S. Hochster, Sarah Hoffe, Steven Hunt, Ahmed Kamel, Natalie Kirilcuk, Smitha Krishnamurthi, Wells A. Messersmith, Mary F. Mulcahy, James D. Murphy, Steven Nurkin, Leonard Saltz, Sunil Sharma, David Shibata, John M. Skibber, Constantinos T. Sofocleous, Elena M. Stoffel, Eden Stotsky-Himelfarb, Christopher G. Willett, Christina S. Wu, Kristina M. Gregory, and Deborah Freedman-Cass

This portion of the NCCN Guidelines for Colon Cancer focuses on the use of systemic therapy in metastatic disease. Considerations for treatment selection among 32 different monotherapies and combination regimens in up to 7 lines of therapy have included treatment history, extent of disease, goals of treatment, the efficacy and toxicity profiles of the regimens, KRAS/NRAS mutational status, and patient comorbidities and preferences. Location of the primary tumor, the BRAF mutation status, and tumor microsatellite stability should also be considered in treatment decisions.