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Michelle B. Riba, Kristine A. Donovan, Barbara Andersen, IIana Braun, William S. Breitbart, Benjamin W. Brewer, Luke O. Buchmann, Matthew M. Clark, Molly Collins, Cheyenne Corbett, Stewart Fleishman, Sofia Garcia, Donna B. Greenberg, Rev. George F. Handzo, Laura Hoofring, Chao-Hui Huang, Robin Lally, Sara Martin, Lisa McGuffey, William Mitchell, Laura J. Morrison, Megan Pailler, Oxana Palesh, Francine Parnes, Janice P. Pazar, Laurel Ralston, Jaroslava Salman, Moreen M. Shannon-Dudley, Alan D. Valentine, Nicole R. McMillian, and Susan D. Darlow

Distress is defined in the NCCN Guidelines for Distress Management as a multifactorial, unpleasant experience of a psychologic (ie, cognitive, behavioral, emotional), social, spiritual, and/or physical nature that may interfere with the ability to cope effectively with cancer, its physical symptoms, and its treatment. Early evaluation and screening for distress leads to early and timely management of psychologic distress, which in turn improves medical management. The panel for the Distress Management Guidelines recently added a new principles section including guidance on implementation of standards of psychosocial care for patients with cancer.

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Jennifer M. Weiss, Samir Gupta, Carol A. Burke, Lisen Axell, Lee-May Chen, Daniel C. Chung, Katherine M. Clayback, Susan Dallas, Seth Felder, Olumide Gbolahan, Francis M. Giardiello, William Grady, Michael J. Hall, Heather Hampel, Rachel Hodan, Gregory Idos, Priyanka Kanth, Bryson Katona, Laura Lamps, Xavier Llor, Patrick M. Lynch, Arnold J. Markowitz, Sara Pirzadeh-Miller, Niloy Jewel Samadder, David Shibata, Benjamin J. Swanson, Brittany M. Szymaniak, Georgia L. Wiesner, Andrew Wolf, Matthew B. Yurgelun, Mae Zakhour, Susan D. Darlow, Mary A. Dwyer, and Mallory Campbell

Identifying individuals with hereditary syndromes allows for timely cancer surveillance, opportunities for risk reduction, and syndrome-specific management. Establishing criteria for hereditary cancer risk assessment allows for the identification of individuals who are carriers of pathogenic genetic variants. The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal provides recommendations for the assessment and management of patients at risk for or diagnosed with high-risk colorectal cancer syndromes. The NCCN Genetic/Familial High-Risk Assessment: Colorectal panel meets annually to evaluate and update their recommendations based on their clinical expertise and new scientific data. These NCCN Guidelines Insights focus on familial adenomatous polyposis (FAP)/attenuated familial adenomatous polyposis (AFAP) syndrome and considerations for management of duodenal neoplasia.

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Robert I Haddad, Lindsay Bischoff, Douglas Ball, Victor Bernet, Erik Blomain, Naifa Lamki Busaidy, Michael Campbell, Paxton Dickson, Quan-Yang Duh, Hormoz Ehya, Whitney S. Goldner, Theresa Guo, Megan Haymart, Shelby Holt, Jason P. Hunt, Andrei Iagaru, Fouad Kandeel, Dominick M. Lamonica, Susan Mandel, Stephanie Markovina, Bryan McIver, Christopher D. Raeburn, Rod Rezaee, John A. Ridge, Mara Y. Roth, Randall P. Scheri, Jatin P. Shah, Jennifer A. Sipos, Rebecca Sippel, Cord Sturgeon, Thomas N. Wang, Lori J. Wirth, Richard J. Wong, Michael Yeh, Carly J. Cassara, and Susan Darlow

Differentiated thyroid carcinomas is associated with an excellent prognosis. The treatment of choice for differentiated thyroid carcinoma is surgery, followed by radioactive iodine ablation (iodine-131) in select patients and thyroxine therapy in most patients. Surgery is also the main treatment for medullary thyroid carcinoma, and kinase inhibitors may be appropriate for select patients with recurrent or persistent disease that is not resectable. Anaplastic thyroid carcinoma is almost uniformly lethal, and iodine-131 imaging and radioactive iodine cannot be used. When systemic therapy is indicated, targeted therapy options are preferred. This article describes NCCN recommendations regarding management of medullary thyroid carcinoma and anaplastic thyroid carcinoma, and surgical management of differentiated thyroid carcinoma (papillary, follicular, Hürthle cell carcinoma).

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Jimmy J. Caudell, Maura L. Gillison, Ellie Maghami, Sharon Spencer, David G. Pfister, Douglas Adkins, Andrew C. Birkeland, David M. Brizel, Paul M. Busse, Anthony J. Cmelak, A. Dimitrios Colevas, David W. Eisele, Thomas Galloway, Jessica L. Geiger, Robert I. Haddad, Wesley L. Hicks Jr, Ying J. Hitchcock, Antonio Jimeno, Debra Leizman, Loren K. Mell, Bharat B. Mittal, Harlan A. Pinto, James W. Rocco, Cristina P. Rodriguez, Panayiotis S. Savvides, David Schwartz, Jatin P. Shah, David Sher, Maie St. John, Randal S. Weber, Gregory Weinstein, Frank Worden, Justine Yang Bruce, Sue S. Yom, Weining Zhen, Jennifer L. Burns, and Susan D. Darlow

The NCCN Guidelines for Head and Neck Cancers address tumors arising in the oral cavity (including mucosal lip), pharynx, larynx, and paranasal sinuses. Occult primary cancer, salivary gland cancer, and mucosal melanoma (MM) are also addressed. The specific site of disease, stage, and pathologic findings guide treatment (eg, the appropriate surgical procedure, radiation targets, dose and fractionation of radiation, indications for systemic therapy). The NCCN Head and Neck Cancers 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 the panel’s most recent recommendations regarding management of HPV-positive oropharynx cancer and ongoing research in this area.

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A. Dimitrios Colevas, Sue S. Yom, David G. Pfister, Sharon Spencer, David Adelstein, Douglas Adkins, David M. Brizel, Barbara Burtness, Paul M. Busse, Jimmy J. Caudell, Anthony J. Cmelak, David W. Eisele, Moon Fenton, Robert L. Foote, Jill Gilbert, Maura L. Gillison, Robert I. Haddad, Wesley L. Hicks Jr, Ying J. Hitchcock, Antonio Jimeno, Debra Leizman, Ellie Maghami, Loren K. Mell, Bharat B. Mittal, Harlan A. Pinto, John A. Ridge, James Rocco, Cristina P. Rodriguez, Jatin P. Shah, Randal S. Weber, Matthew Witek, Frank Worden, Weining Zhen, Jennifer L. Burns, and Susan D. Darlow

The NCCN Guidelines for Head and Neck (H&N) Cancers provide treatment recommendations for cancers of the lip, oral cavity, pharynx, larynx, ethmoid and maxillary sinuses, and salivary glands. Recommendations are also provided for occult primary of the H&N, and separate algorithms have been developed by the panel for very advanced H&N cancers. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding evaluation and treatment of nasopharyngeal carcinoma.

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Al B. Benson, Michael I. D’Angelica, Daniel E. Abbott, Daniel A. Anaya, Robert Anders, Chandrakanth Are, Melinda Bachini, Mitesh Borad, Daniel Brown, Adam Burgoyne, Prabhleen Chahal, Daniel T. Chang, Jordan Cloyd, Anne M. Covey, Evan S. Glazer, Lipika Goyal, William G. Hawkins, Renuka Iyer, Rojymon Jacob, R. Kate Kelley, Robin Kim, Matthew Levine, Manisha Palta, James O. Park, Steven Raman, Sanjay Reddy, Vaibhav Sahai, Tracey Schefter, Gagandeep Singh, Stacey Stein, Jean-Nicolas Vauthey, Alan P. Venook, Adam Yopp, Nicole R. McMillian, Cindy Hochstetler, and Susan D. Darlow

The NCCN Guidelines for Hepatobiliary Cancers focus on the screening, diagnosis, staging, treatment, and management of hepatocellular carcinoma (HCC), gallbladder cancer, and cancer of the bile ducts (intrahepatic and extrahepatic cholangiocarcinoma). Due to the multiple modalities that can be used to treat the disease and the complications that can arise from comorbid liver dysfunction, a multidisciplinary evaluation is essential for determining an optimal treatment strategy. A multidisciplinary team should include hepatologists, diagnostic radiologists, interventional radiologists, surgeons, medical oncologists, and pathologists with hepatobiliary cancer expertise. In addition to surgery, transplant, and intra-arterial therapies, there have been great advances in the systemic treatment of HCC. Until recently, sorafenib was the only systemic therapy option for patients with advanced HCC. In 2020, the combination of atezolizumab and bevacizumab became the first regimen to show superior survival to sorafenib, gaining it FDA approval as a new frontline standard regimen for unresectable or metastatic HCC. This article discusses the NCCN Guidelines recommendations for HCC.

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Louis Burt Nabors, Jana Portnow, Manmeet Ahluwalia, Joachim Baehring, Henry Brem, Steven Brem, Nicholas Butowski, Jian L. Campian, Stephen W. Clark, Andrew J. Fabiano, Peter Forsyth, Jona Hattangadi-Gluth, Matthias Holdhoff, Craig Horbinski, Larry Junck, Thomas Kaley, Priya Kumthekar, Jay S. Loeffler, Maciej M. Mrugala, Seema Nagpal, Manjari Pandey, Ian Parney, Katherine Peters, Vinay K. Puduvalli, Ian Robins, Jason Rockhill, Chad Rusthoven, Nicole Shonka, Dennis C. Shrieve, Lode J. Swinnen, Stephanie Weiss, Patrick Yung Wen, Nicole E. Willmarth, Mary Anne Bergman, and Susan D. Darlow

The NCCN Guidelines for Central Nervous System (CNS) Cancers focus on management of adult CNS cancers ranging from noninvasive and surgically curable pilocytic astrocytomas to metastatic brain disease. The involvement of an interdisciplinary team, including neurosurgeons, radiation therapists, oncologists, neurologists, and neuroradiologists, is a key factor in the appropriate management of CNS cancers. Integrated histopathologic and molecular characterization of brain tumors such as gliomas should be standard practice. This article describes NCCN Guidelines recommendations for WHO grade I, II, III, and IV gliomas. Treatment of brain metastases, the most common intracranial tumors in adults, is also described.

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David Adelstein, Maura L. Gillison, David G. Pfister, Sharon Spencer, Douglas Adkins, David M. Brizel, Barbara Burtness, Paul M. Busse, Jimmy J. Caudell, Anthony J. Cmelak, A. Dimitrios Colevas, David W. Eisele, Moon Fenton, Robert L. Foote, Jill Gilbert, Robert I. Haddad, Wesley L. Hicks Jr, Ying J. Hitchcock, Antonio Jimeno, Debra Leizman, William M. Lydiatt, Ellie Maghami, Loren K. Mell, Bharat B. Mittal, Harlan A. Pinto, John A. Ridge, James Rocco, Cristina P. Rodriguez, Jatin P. Shah, Randal S. Weber, Matthew Witek, Frank Worden, Sue S. Yom, Weining Zhen, Jennifer L. Burns, and Susan D. Darlow

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers provide treatment recommendations for cancers of the lip, oral cavity, pharynx, larynx, ethmoid and maxillary sinuses, and salivary glands. Recommendations are also provided for occult primary of the head and neck (H&N), and separate algorithms have been developed by the panel for very advanced H&N cancers. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding the increase in human papillomavirus–associated oropharyngeal cancer and the availability of immunotherapy agents for treatment of patients with recurrent or metastatic H&N cancer.

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David G. Pfister, Sharon Spencer, David Adelstein, Douglas Adkins, Yoshimi Anzai, David M. Brizel, Justine Y. Bruce, Paul M. Busse, Jimmy J. Caudell, Anthony J. Cmelak, A. Dimitrios Colevas, David W. Eisele, Moon Fenton, Robert L. Foote, Thomas Galloway, Maura L. Gillison, Robert I. Haddad, Wesley L. Hicks Jr., Ying J. Hitchcock, Antonio Jimeno, Debra Leizman, Ellie Maghami, Loren K. Mell, Bharat B. Mittal, Harlan A. Pinto, John A. Ridge, James W. Rocco, Cristina P. Rodriguez, Jatin P. Shah, Randal S. Weber, Gregory Weinstein, Matthew Witek, Frank Worden, Sue S. Yom, Weining Zhen, Jennifer L. Burns, and Susan D. Darlow

Treatment is complex for patients with head and neck (H&N) cancers with specific site of disease, stage, and pathologic findings guiding treatment decision-making. Treatment planning for H&N cancers involves a multidisciplinary team of experts. This article describes supportive care recommendations in the NCCN Guidelines for Head and Neck Cancers, as well as the rationale supporting a new section on imaging recommendations for patients with H&N cancers. This article also describes updates to treatment recommendations for patients with very advanced H&N cancers and salivary gland tumors, specifically systemic therapy recommendations.

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Craig Horbinski, Louis Burt Nabors, Jana Portnow, Joachim Baehring, Ankush Bhatia, Orin Bloch, Steven Brem, Nicholas Butowski, Donald M. Cannon, Samuel Chao, Milan G. Chheda, Andrew J. Fabiano, Peter Forsyth, Pierre Gigilio, Jona Hattangadi-Gluth, Matthias Holdhoff, Larry Junck, Thomas Kaley, Ryan Merrell, Maciej M. Mrugala, Seema Nagpal, Lucien A. Nedzi, Kathryn Nevel, Phioanh L. Nghiemphu, Ian Parney, Toral R. Patel, Katherine Peters, Vinay K. Puduvalli, Jason Rockhill, Chad Rusthoven, Nicole Shonka, Lode J. Swinnen, Stephanie Weiss, Patrick Yung Wen, Nicole E. Willmarth, Mary Anne Bergman, and Susan Darlow

The NCCN Guidelines for Central Nervous System (CNS) Cancers focus on management of the following adult CNS cancers: glioma (WHO grade 1, WHO grade 2–3 oligodendroglioma [1p19q codeleted, IDH-mutant], WHO grade 2–4 IDH-mutant astrocytoma, WHO grade 4 glioblastoma), intracranial and spinal ependymomas, medulloblastoma, limited and extensive brain metastases, leptomeningeal metastases, non–AIDS-related primary CNS lymphomas, metastatic spine tumors, meningiomas, and primary spinal cord tumors. The information contained in the algorithms and principles of management sections in the NCCN Guidelines for CNS Cancers are designed to help clinicians navigate through the complex management of patients with CNS tumors. Several important principles guide surgical management and treatment with radiotherapy and systemic therapy for adults with brain tumors. The NCCN CNS Cancers 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 the panel’s most recent recommendations regarding molecular profiling of gliomas.