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  • Author: M. Dror Michaelson x
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Philip J. Saylor and M. Dror Michaelson

Systemic treatment options for advanced renal cell carcinoma (RCC) have expanded considerably with the development of targeted therapies. Clear cell RCC commonly features mutation or inactivation of the von Hippel-Lindau gene and resultant overexpression of vascular endothelial growth factor (VEGF). The first drug to validate VEGF as a target in the treatment of clear cell RCC was the monoclonal antibody bevacizumab. Since then, anti-VEGF receptor therapy with multitargeted kinase inhibitors also has shown substantial efficacy. Sunitinib is now a standard first-line therapy for advanced disease and sorafenib is among the second-line treatment options. Other kinase inhibitors are in development. Mammalian target of rapamycin (mTOR) is a second validated therapeutic target as the mTOR inhibitor temsirolimus has been shown to prolong survival in first-line treatment of poor prognosis RCC of all histologies. Everolimus is an oral mTOR inhibitor and has been shown to prolong progression-free survival when used in second-line treatment. Non-clear cell and sarcomatoid RCC are both underrepresented in completed trials but are the subject of active research. Ongoing and planned studies will also evaluate the use of combinations of targeted agents, a strategy that is not advisable outside of clinical trials. Finally, postnephrectomy adjuvant treatment with targeted agents is not yet standard but is under investigation in phase III trials.

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Gary R. Hudes, Michael A. Carducci, Toni K. Choueiri, Peg Esper, Eric Jonasch, Rashmi Kumar, Kim A. Margolin, M. Dror Michaelson, Robert J. Motzer, Roberto Pili, Susan Roethke and Sandy Srinivas

The outcome of patients with metastatic renal cell carcinoma has been substantially improved with administration of the currently available molecularly targeted therapies. However, proper selection of therapy and management of toxicities remain challenging. NCCN convened a multidisciplinary task force panel to address the clinical issues associated with these therapies in attempt to help practicing oncologists optimize patient outcomes. This report summarizes the background data presented at the task force meeting and the ensuing discussion.

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Ayal A. Aizer, Jonathan J. Paly, Anthony L. Zietman, Paul L. Nguyen, Clair J. Beard, Sandhya K. Rao, Irving D. Kaplan, Andrzej Niemierko, Michelle S. Hirsch, Chin-Lee Wu, Aria F. Olumi, M. Dror Michaelson, Anthony V. D’Amico and Jason A. Efstathiou

NCCN Guidelines recommend active surveillance as the primary management option for patients with very-low-risk prostate cancer and an expected survival of less than 20 years, reflecting the favorable prognosis of these men and the lack of perceived benefit of immediate, definitive treatment. The authors hypothesized that care at a multidisciplinary clinic, where multiple physicians have an opportunity to simultaneously review and discuss each case, is associated with increased rates of active surveillance in men with very-low-risk prostate cancer, including those with limited life expectancy. Of 630 patients with low-risk prostate cancer managed at 1 of 3 tertiary care centers in Boston, Massachusetts in 2009, 274 (43.5%) had very-low-risk classification. Patients were either seen by 1 or more individual practitioners in sequential settings or at a multidisciplinary clinic, in which concurrent consultation with 2 or more of the following specialties was obtained: urology, radiation oncology, and medical oncology. Patients seen at a multidisciplinary prostate cancer clinic were more likely to select active surveillance than those seen by individual practitioners (64% vs 30%; P<.001), an association that remained significant on multivariable logistic regression (odds ratio [OR], 4.16; P<.001). When the analysis was limited to patients with an expected survival of less than 20 years, this association remained highly significant (72% vs 34%, P<.001; OR, 5.19; P<.001, respectively). Multidisciplinary care is strongly associated with selection of active surveillance, adherence to NCCN Guidelines and minimization of overtreatment in patients with very-low-risk prostate cancer.

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Robert J. Motzer, Eric Jonasch, Neeraj Agarwal, Sam Bhayani, William P. Bro, Sam S. Chang, Toni K. Choueiri, Brian A. Costello, Ithaar H. Derweesh, Mayer Fishman, Thomas H. Gallagher, John L. Gore, Steven L. Hancock, Michael R. Harrison, Won Kim, Christos Kyriakopoulos, Chad LaGrange, Elaine T. Lam, Clayton Lau, M. Dror Michaelson, Thomas Olencki, Phillip M. Pierorazio, Elizabeth R. Plimack, Bruce G. Redman, Brian Shuch, Brad Somer, Guru Sonpavde, Jeffrey Sosman, Mary Dwyer and Rashmi Kumar

The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for the clinical management of patients with clear cell and non–clear cell renal carcinoma. These guidelines are developed by a multidisciplinary panel of leading experts from NCCN Member Institutions consisting of medical oncologists, hematologists and hematologic oncologists, radiation oncologists, urologists, and pathologists. The NCCN Guidelines are in continuous evolution and are updated annually or sometimes more often, if new high-quality clinical data become available in the interim.

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Robert J. Motzer, Neeraj Agarwal, Clair Beard, Sam Bhayani, Graeme B. Bolger, Mark K. Buyyounouski, Michael A. Carducci, Sam S. Chang, Toni K. Choueiri, Shilpa Gupta, Steven L. Hancock, Gary R. Hudes, Eric Jonasch, Timothy M. Kuzel, Clayton Lau, Ellis G. Levine, Daniel W. Lin, Kim A. Margolin, M. Dror Michaelson, Thomas Olencki, Roberto Pili, Thomas W. Ratliff, Bruce G. Redman, Cary N. Robertson, Charles J. Ryan, Joel Sheinfeld, Jue Wang and Richard B. Wilder

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Robert J. Motzer, Neeraj Agarwal, Clair Beard, Sam Bhayani, Graeme B. Bolger, Michael A. Carducci, Sam S. Chang, Toni K. Choueiri, Steven L. Hancock, Gary R. Hudes, Eric Jonasch, David Josephson, Timothy M. Kuzel, Ellis G. Levine, Daniel W. Lin, Kim A. Margolin, M. Dror Michaelson, Thomas Olencki, Roberto Pili, Thomas W. Ratliff, Bruce G. Redman, Cary N. Robertson, Charles J. Ryan, Joel Sheinfeld, Philippe E. Spiess, Jue Wang and Richard B. Wilder

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Robert J. Motzer, Neeraj Agarwal, Clair Beard, Graeme B. Bolger, Barry Boston, Michael A. Carducci, Toni K. Choueiri, Robert A. Figlin, Mayer Fishman, Steven L. Hancock, Gary R. Hudes, Eric Jonasch, Anne Kessinger, Timothy M. Kuzel, Paul H. Lange, Ellis G. Levine, Kim A. Margolin, M. Dror Michaelson, Thomas Olencki, Roberto Pili, Bruce G. Redman, Cary N. Robertson, Lawrence H. Schwartz, Joel Sheinfeld and Jue Wang

Kidney Cancer Clinical Practice Guidelines in Oncology NCCN Categories of Evidence and Consensus Category 1: The recommendation is based on high-level evidence (e.g., randomized controlled trials) and there isuniform NCCN consensus. Category 2A: The recommendation is based on lower-level evidence and there is uniform NCCN consensus. Category 2B: The recommendation is based on lower-level evidence and there is nonuniform NCCN consensus (but no major disagreement). Category 3: The recommendation is based on any level of evidence but reflects major disagreement. All recommendations are category 2A unless otherwise noted. Clinical trials: The NCCN believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. Overview In 2008, an estimated 54,390 Americans were diagnosed with kidney cancer and 13,010 died of the disease in the United States.1 Renal cell carcinoma (RCC) comprises approximately 2% of all malignancies, with a median age at diagnosis of 65 years. The rate of RCC has increased 2% per year for the past 65 years. The reason for this increase is unknown. Approximately 90% of renal tumors are RCC, and 85% of these are clear cell tumors.2 Other, less-common cell types include papillary, chromophobe, and Bellini (collecting) duct tumors. Collecting duct carcinoma comprises fewer than 1% of all cases. Medullary renal carcinoma is a variant of collecting duct renal carcinoma and was initially described as occurring in patients who are sickle cell–trait positive. Smoking and obesity are among the risk factors for RCC development. Several hereditary types...
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Robert J. Motzer, Neeraj Agarwal, Clair Beard, Graeme B. Bolger, Barry Boston, Michael A. Carducci, Toni K. Choueiri, Robert A. Figlin, Mayer Fishman, Steven L. Hancock, Gary R. Hudes, Eric Jonasch, Anne Kessinger, Timothy M. Kuzel, Paul H. Lange, Ellis G. Levine, Kim A. Margolin, M. Dror Michaelson, Thomas Olencki, Roberto Pili, Bruce G. Redman, Cary N. Robertson, Lawrence H. Schwartz, Joel Sheinfeld and Jue Wang

Testicular Cancer Clinical Practice Guidelines in OncologyNCCN Categories of Evidence and ConsensusCategory 1: The recommendation is based on high-level evidence (e.g., randomized controlled trials) and there is uniform NCCN consensus.Category 2A: The recommendation is based on lower-level evidence and there is uniform NCCN consensus.Category 2B: The recommendation is based on lower-level evidence and there is nonuniform NCCN consensus (but no major disagreement).Category 3: The recommendation is based on any level of evidence but reflects major disagreement.All recommendations are category 2A unless otherwise noted.Clinical trials: The NCCN believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.OverviewAn estimated 8090 new cases of testicular cancer will be diagnosed in the United States in 2008.1 Germ cell tumors (GCTs) comprise 95% of malignant tumors arising in the testes. These tumors also occur occasionally in extragonadal primary sites, but they are still managed the same as testicular GCTs. Although GCTs are relatively uncommon tumors that comprise only 2% of all human malignancies, they constitute the most common solid tumor in men between the ages of 15 and 34 years. In addition, the worldwide incidence of these tumors has more than doubled in the past 40 years.Several risk factors for GCT development have been identified, including prior history, positive family history, cryptorchidism, testicular dysgenesis, and Klinefelter's syndrome. GCTs are classified as seminoma or nonseminoma. Nonseminomatous tumors often include multiple cell types, including embryonal cell...
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Robert J. Motzer, Eric Jonasch, Neeraj Agarwal, Clair Beard, Sam Bhayani, Graeme B. Bolger, Sam S. Chang, Toni K. Choueiri, Ithaar H. Derweesh, Shilpa Gupta, Steven L. Hancock, Jenny J. Kim, Timothy M. Kuzel, Elaine T. Lam, Clayton Lau, Ellis G. Levine, Daniel W. Lin, Kim A. Margolin, M. Dror Michaelson, Thomas Olencki, Roberto Pili, Elizabeth R. Plimack, Edward N. Rampersaud, Bruce G. Redman, Charles J. Ryan, Joel Sheinfeld, Kanishka Sircar, Brad Somer, Jue Wang, Richard B. Wilder, Mary A. Dwyer and Rashmi Kumar

These NCCN Guidelines Insights highlight treatment recommendations and updates specific to the management of patients with advanced non-clear cell carcinoma included in the 2014 version of the NCCN Clinical Practice Guidelines in Oncology for Kidney Cancer.

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Robert J. Motzer, Eric Jonasch, Neeraj Agarwal, Clair Beard, Sam Bhayani, Graeme B. Bolger, Sam S. Chang, Toni K. Choueiri, Brian A. Costello, Ithaar H. Derweesh, Shilpa Gupta, Steven L. Hancock, Jenny J. Kim, Timothy M. Kuzel, Elaine T. Lam, Clayton Lau, Ellis G. Levine, Daniel W. Lin, M. Dror Michaelson, Thomas Olencki, Roberto Pili, Elizabeth R. Plimack, Edward N. Rampersaud, Bruce G. Redman, Charles J. Ryan, Joel Sheinfeld, Brian Shuch, Kanishka Sircar, Brad Somer, Richard B. Wilder, Mary Dwyer and Rashmi Kumar

The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for the clinical management of patients with clear cell and non-clear cell renal carcinoma. These NCCN Guidelines Insights highlight the recent updates/changes in these guidelines, and updates include axitinib as first-line treatment option for patients with clear cell renal carcinoma, new data to support pazopanib as subsequent therapy for patients with clear cell carcinoma after first-line treatment with another tyrosine kinase inhibitor, and guidelines for follow-up of patients with renal cell carcinoma.