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Michael D. Green and James A. Hayman

The management of Merkel cell carcinoma (MCC) requires multidisciplinary care for optimal patient outcomes. Radiotherapy (RT) is most commonly used as adjuvant therapy to improve locoregional control in patients with MCC who undergo surgery. Additionally, it can sometimes be used as definitive monotherapy for patients who decline or are not candidates for surgery and as palliative treatment in those with metastatic MCC. This article discusses the indications, treatment considerations, and recommended dose prescriptions for RT in the management of early- and advanced-stage disease. Considerable hope exists that immunotherapy advances will synergize with RT to further enhance clinical outcomes.

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Robert E. Glasgow, David H. Ilson, James A. Hayman, Hans Gerdes, Mary F. Mulcahy and Jaffer A. Ajani

The clinical spectrum of esophageal cancer has changed dramatically over the past couple of decades. Most notably, a profound rise in esophageal adenocarcinoma and decrease in the incidence of squamous carcinomas have occurred. An understanding of the factors that influence survival for patients with localized esophageal cancer has evolved concomitantly with these changes in epidemiology. Significant advancement in endoscopic and radiographic staging allows for more selective use of treatment modalities. The treatment of localized esophageal cancer mandates a multidisciplinary approach, with treatment tailored to disease extent, location, histology, and an accurate assessment of pretreatment staging. Despite these improvements in the staging and use of multimodality therapy, only modest improvements in patient survival have been observed. This article summarizes these modern approaches to localized cancer of the esophagus.

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David B. Shultz, John C. Grecula, James Hayman, Maximilian Diehn and Billy W. Loo Jr

Small cell lung cancer is an aggressive malignancy that is highly responsive to radiation therapy (RT), which has an important role in all stages of disease. For locally advanced, limited-stage disease, the standard of care is chemotherapy with concurrent radiation, which should be started early. The optimal radiation dose and field design remain to be determined. Randomized trials are currently being conducted to determine if dose intensification will improve outcomes, whereas consensus on elective nodal irradiation is evolving. Current studies are evaluating the potential benefit of consolidative thoracic RT in the management of patients with extensive-stage disease that has responded favorably to chemotherapy. Finally, prophylactic cranial irradiation improves survival in both limited- and extensive-stage disease that has responded to initial therapy.

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Jennifer L. Schwartz, Sandra L. Wong, Scott A. McLean, James A. Hayman, Christopher D. Lao, Jeffrey H. Kozlow, Kelly M. Malloy, Carol R. Bradford, Marcus L. Frohm, Douglas R. Fullen, Lori Lowe and Christopher K. Bichakjian

Merkel cell carcinoma (MCC) is a rare malignancy of the skin, and prospective randomized clinical studies on management and treatment are very limited. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for MCC provide up-to-date, best evidence-based, and consensus-driven management pathways with the purpose of providing best care and outcomes. Multidisciplinary management with consensus treatment recommendations to individualize patient care within the framework of these guidelines is optimal. The University of Michigan multidisciplinary MCC program uses NCCN Guidelines in the management and treatment of its patients. This article discusses 4 patient presentations to highlight the implementation of the NCCN Guidelines for MCC at the University of Michigan.

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Jaffer A. Ajani, James S. Barthel, David J. Bentrem, Thomas A. D'Amico, Prajnan Das, Crystal S. Denlinger, Charles S. Fuchs, Hans Gerdes, Robert E. Glasgow, James A. Hayman, Wayne L. Hofstetter, David H. Ilson, Rajesh N. Keswani, Lawrence R. Kleinberg, W. Michael Korn, A. Craig Lockhart, Mary F. Mulcahy, Mark B. Orringer, Raymond U. Osarogiagbon, James A. Posey, Aaron R. Sasson, Walter J. Scott, Stephen Shibata, Vivian E. M. Strong, Thomas K. Varghese Jr., Graham Warren, Mary Kay Washington, Christopher Willett and Cameron D. Wright

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Jaffer A. Ajani, James S. Barthel, Tanios Bekaii-Saab, David J. Bentrem, Thomas A. D'Amico, Prajnan Das, Crystal Denlinger, Charles S. Fuchs, Hans Gerdes, James A. Hayman, Lisa Hazard, Wayne L. Hofstetter, David H. Ilson, Rajesh N. Keswani, Lawrence R. Kleinberg, Michael Korn, Kenneth Meredith, Mary F. Mulcahy, Mark B. Orringer, Raymond U. Osarogiagbon, James A. Posey, Aaron R. Sasson, Walter J. Scott, Stephen Shibata, Vivian E. M. Strong, Mary Kay Washington, Christopher Willett, Douglas E. Wood, Cameron D. Wright and Gary Yang

OverviewCancers originating in the esophagus, gastroesophageal junctions, and stomach constitute a major health problem worldwide. In the United States, 37,600 new diagnoses of and 25,150 deaths from upper gastrointestinal cancers were estimated in 2009.1 A dramatic shift in the location of upper gastrointestinal tumors has occurred in the United States,2 and changes in histology and location of them were observed in some parts of Europe.3,4 In countries in the Western Hemisphere, the most common sites of gastric cancer are the proximal lesser curvature, cardia, and gastroesophageal junction.2 These changing trends may also begin to occur in South America and Asia.EpidemiologyGastric cancer is rampant in many countries around the world. In Japan, it remains the most common type of cancer among men; in China, more new cases are diagnosed each year than in any other country. The incidence of gastric cancer, however, has been declining globally since World War II and it is one of the least common cancers in North America. By some estimates, it is the fourth most common cancer worldwide.5 In 2009, 21,130 new diagnoses of gastric cancer were estimated in the United States and 10,620 deaths expected.1 In developed countries, the incidence of gastric cancer originating from the cardia follows the distribution of esophageal cancer.6–8 Noncardia gastric adenocarcinoma has marked geographic variation, with countries such as Japan, Korea, China, Taiwan, Costa Rica, Peru, Brazil, Chile, and the former Soviet Union showing a high incidence.9 In contrast to the incidence trends in the West, nonproximal...
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Jaffer A. Ajani, Thomas A. D’Amico, Khaldoun Almhanna, David J. Bentrem, Stephen Besh, Joseph Chao, Prajnan Das, Crystal Denlinger, Paul Fanta, Charles S. Fuchs, Hans Gerdes, Robert E. Glasgow, James A. Hayman, Steven Hochwald, Wayne L. Hofstetter, David H. Ilson, Dawn Jaroszewski, Kory Jasperson, Rajesh N. Keswani, Lawrence R. Kleinberg, W. Michael Korn, Stephen Leong, A. Craig Lockhart, Mary F. Mulcahy, Mark B. Orringer, James A. Posey, George A. Poultsides, Aaron R. Sasson, Walter J. Scott, Vivian E. Strong, Thomas K. Varghese Jr, Mary Kay Washington, Christopher G. Willett, Cameron D. Wright, Debra Zelman, Nicole McMillian and Hema Sundar

Esophageal cancer is the sixth most common cause of cancer deaths worldwide. Adenocarcinoma is more common in North America and Western European countries, originating mostly in the lower third of the esophagus, which often involves the esophagogastric junction (EGJ). Recent randomized trials have shown that the addition of preoperative chemoradiation or perioperative chemotherapy to surgery significantly improves survival in patients with resectable cancer. Targeted therapies with trastuzumab and ramucirumab have produced encouraging results in the treatment of advanced or metastatic EGJ adenocarcinomas. Multidisciplinary team management is essential for patients with esophageal and EGJ cancers. This portion of the NCCN Guidelines for Esophageal and EGJ Cancers discusses management of locally advanced adenocarcinoma of the esophagus and EGJ.

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Jaffer A. Ajani, David J. Bentrem, Stephen Besh, Thomas A. D’Amico, Prajnan Das, Crystal Denlinger, Marwan G. Fakih, Charles S. Fuchs, Hans Gerdes, Robert E. Glasgow, James A. Hayman, Wayne L. Hofstetter, David H. Ilson, Rajesh N. Keswani, Lawrence R. Kleinberg, W. Michael Korn, A. Craig Lockhart, Kenneth Meredith, Mary F. Mulcahy, Mark B. Orringer, James A. Posey, Aaron R. Sasson, Walter J. Scott, Vivian E. Strong, Thomas K. Varghese Jr, Graham Warren, Mary Kay Washington, Christopher Willett, Cameron D. Wright, Nicole R. McMillian and Hema Sundar

The NCCN Clinical Practice Guidelines in Oncology for Gastric Cancer provide evidence- and consensus-based recommendations for a multidisciplinary approach for the management of patients with gastric cancer. For patients with resectable locoregional cancer, the guidelines recommend gastrectomy with a D1+ or a modified D2 lymph node dissection (performed by experienced surgeons in high-volume centers). Postoperative chemoradiation is the preferred option after complete gastric resection for patients with T3-T4 tumors and node-positive T1-T2 tumors. Postoperative chemotherapy is included as an option after a modified D2 lymph node dissection for this group of patients. Trastuzumab with chemotherapy is recommended as first-line therapy for patients with HER2-positive advanced or metastatic cancer, confirmed by immunohistochemistry and, if needed, by fluorescence in situ hybridization for IHC 2+.

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Jaffer A. Ajani, Thomas A. D'Amico, Khaldoun Almhanna, David J. Bentrem, Joseph Chao, Prajnan Das, Crystal S. Denlinger, Paul Fanta, Farhood Farjah, Charles S. Fuchs, Hans Gerdes, Michael Gibson, Robert E. Glasgow, James A. Hayman, Steven Hochwald, Wayne L. Hofstetter, David H. Ilson, Dawn Jaroszewski, Kimberly L. Johung, Rajesh N. Keswani, Lawrence R. Kleinberg, W. Michael Korn, Stephen Leong, Catherine Linn, A. Craig Lockhart, Quan P. Ly, Mary F. Mulcahy, Mark B. Orringer, Kyle A. Perry, George A. Poultsides, Walter J. Scott, Vivian E. Strong, Mary Kay Washington, Benny Weksler, Christopher G. Willett, Cameron D. Wright, Debra Zelman, Nicole McMillian and Hema Sundar

Gastric cancer is the fifth most frequently diagnosed cancer and the third leading cause of death from cancer in the world. Several advances have been made in the staging procedures, imaging techniques, and treatment approaches. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Gastric Cancer provide an evidence- and consensus-based treatment approach for the management of patients with gastric cancer. This manuscript discusses the recommendations outlined in the NCCN Guidelines for staging, assessment of HER2 overexpression, systemic therapy for locally advanced or metastatic disease, and best supportive care for the prevention and management of symptoms due to advanced disease.

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Gregory P. Kalemkerian, Wallace Akerley, Paul Bogner, Hossein Borghaei, Laura QM Chow, Robert J. Downey, Leena Gandhi, Apar Kishor P. Ganti, Ramaswamy Govindan, John C. Grecula, James Hayman, Rebecca Suk Heist, Leora Horn, Thierry Jahan, Marianna Koczywas, Billy W. Loo Jr, Robert E. Merritt, Cesar A. Moran, Harvey B. Niell, Janis O’Malley, Jyoti D. Patel, Neal Ready, Charles M. Rudin, Charles C. Williams Jr, Kristina Gregory and Miranda Hughes

Neuroendocrine tumors account for approximately 20% of lung cancers; most (≈15%) are small cell lung cancer (SCLC). These NCCN Clinical Practice Guidelines in Oncology for SCLC focus on extensive-stage SCLC because it occurs more frequently than limited-stage disease. SCLC is highly sensitive to initial therapy; however, most patients eventually die of recurrent disease. In patients with extensive-stage disease, chemotherapy alone can palliate symptoms and prolong survival in most patients; however, long-term survival is rare. Most cases of SCLC are attributable to cigarette smoking; therefore, smoking cessation should be strongly promoted.