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Modern Approaches to Localized Cancer of the Esophagus

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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Gastroesophageal Adenocarcinomas With Defective Mismatch Repair: Current Knowledge and Clinical Management

Matthew R. Strickland, Eric M. Lander, Michael K. Gibson, David H. Ilson, Jaffer A. Ajani, and Samuel J. Klempner

Esophageal, gastroesophageal junction, and gastric adenocarcinomas, referred to collectively as gastroesophageal adenocarcinomas (GEAs), are a major cause of global cancer-related mortality. Our increasing molecular understanding has led to the addition of biomarker-directed approaches to defined subgroups and has improved survival in selected patients, such as those with HER2 and Claudin18.2 overexpression. Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer, including GEA, but biomarkers beyond PD-L1 expression are lacking. Mismatch repair deficiency and/or high microsatellite instability (dMMR/MSI-H) is observed in 8% to 22% of nonmetastatic GEA, and 3% to 5% of patients with metastatic disease. dMMR/MSI-H tumors are associated with more favorable prognosis and significant benefit from ICIs, although some heterogeneity exists. The activity of ICIs in advanced dMMR/MSI-H cancer is seen across lines of therapy and should be recommended in the frontline setting. In patients with nonmetastatic dMMR/MSI-H cancer, increasing evidence suggests that perioperative and adjuvant chemotherapy may not provide benefit to the dMMR/MSI-H subgroup. The activity of perioperative chemotherapy-free immune checkpoint regimens in patients with nonmetastatic dMMR/MSI-H cancer is highly promising and underscores the need to identify this unique subgroup. We recommend MMR/MSI testing for all patients with GEA at diagnosis, and review the key rationale and clinical management implications for patient with dMMR/MSI-H tumors across disease stages.

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NCCN Task Force: Clinical Utility of PET in a Variety of Tumor Types

Donald A. Podoloff, Douglas W. Ball, Edgar Ben-Josef, Al B. Benson III, Steven J. Cohen, R. Edward Coleman, Dominique Delbeke, Maria Ho, David H. Ilson, Gregory P. Kalemkerian, Richard J. Lee, Jay S. Loeffler, Homer A. Macapinlac, Robert J. Morgan Jr., Barry Alan Siegel, Seema Singhal, Douglas S. Tyler, and Richard J. Wong

Use of PET is widespread and increasing in the United States, mainly for oncologic applications. In November 2006, the National Comprehensive Cancer Network (NCCN) gathered a panel of experts to review the literature and develop clinical recommendations for using PET scans in lymphoma and non–small cell lung, breast, and colorectal cancers. However, because its use is not restricted to these diseases, and evidence is accumulating for its application in other types of cancers, NCCN convened a second meeting in December 2008 to expand on the initial report. A multidisciplinary panel met to discuss the current data on PET application for various tumor types, including genitourinary, gynecologic, pancreatic, hepatobiliary, thyroid, brain, small cell lung, gastric, and esophageal cancers, and sarcoma and myeloma. This report summarizes the proceedings of this meeting, including discussions of the background of PET, the role of PET in oncology, principles of PET use, emerging applications, and possible future developments.

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Gastric Cancer

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

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Gastric Cancer, Version 2.2013

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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Gastric Cancer, Version 3.2016, NCCN Clinical Practice Guidelines in Oncology

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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Esophageal and Esophagogastric Junction Cancers, Version 1.2015

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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Esophageal and Esophagogastric Junction Cancers

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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Esophageal and Esophagogastric Junction Cancers, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology

Jaffer A. Ajani, Thomas A. D’Amico, David J. Bentrem, David Cooke, Carlos Corvera, Prajnan Das, Peter C. Enzinger, Thomas Enzler, Farhood Farjah, Hans Gerdes, Michael Gibson, Patrick Grierson, Wayne L. Hofstetter, David H. Ilson, Shadia Jalal, Rajesh N. Keswani, Sunnie Kim, Lawrence R. Kleinberg, Samuel Klempner, Jill Lacy, Frank Licciardi, Quan P. Ly, Kristina A. Matkowskyj, Michael McNamara, Aaron Miller, Sarbajit Mukherjee, Mary F. Mulcahy, Darryl Outlaw, Kyle A. Perry, Jose Pimiento, George A. Poultsides, Scott Reznik, Robert E. Roses, Vivian E. Strong, Stacey Su, Hanlin L. Wang, Georgia Wiesner, Christopher G. Willett, Danny Yakoub, Harry Yoon, Nicole R. McMillian, and Lenora A. Pluchino

Cancers originating in the esophagus or esophagogastric junction constitute a major global health problem. Esophageal cancers are histologically classified as squamous cell carcinoma (SCC) or adenocarcinoma, which differ in their etiology, pathology, tumor location, therapeutics, and prognosis. In contrast to esophageal adenocarcinoma, which usually affects the lower esophagus, esophageal SCC is more likely to localize at or higher than the tracheal bifurcation. Systemic therapy can provide palliation, improved survival, and enhanced quality of life in patients with locally advanced or metastatic disease. The implementation of biomarker testing, especially analysis of HER2 status, microsatellite instability status, and the expression of programmed death-ligand 1, has had a significant impact on clinical practice and patient care. Targeted therapies including trastuzumab, nivolumab, ipilimumab, and pembrolizumab have produced encouraging results in clinical trials for the treatment of patients with locally advanced or metastatic disease. Palliative management, which may include systemic therapy, chemoradiation, and/or best supportive care, is recommended for all patients with unresectable or metastatic cancer. Multidisciplinary team management is essential for all patients with locally advanced esophageal or esophagogastric junction cancers. This selection from the NCCN Guidelines for Esophageal and Esophagogastric Junction Cancers focuses on the management of recurrent or metastatic disease.

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Gastric Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology

Jaffer A. Ajani, Thomas A. D’Amico, David J. Bentrem, Joseph Chao, David Cooke, Carlos Corvera, Prajnan Das, Peter C. Enzinger, Thomas Enzler, Paul Fanta, Farhood Farjah, Hans Gerdes, Michael K. Gibson, Steven Hochwald, Wayne L. Hofstetter, David H. Ilson, Rajesh N. Keswani, Sunnie Kim, Lawrence R. Kleinberg, Samuel J. Klempner, Jill Lacy, Quan P. Ly, Kristina A. Matkowskyj, Michael McNamara, Mary F. Mulcahy, Darryl Outlaw, Haeseong Park, Kyle A. Perry, Jose Pimiento, George A. Poultsides, Scott Reznik, Robert E. Roses, Vivian E. Strong, Stacey Su, Hanlin L. Wang, Georgia Wiesner, Christopher G. Willett, Danny Yakoub, Harry Yoon, Nicole McMillian, and Lenora A. Pluchino

Gastric cancer is the third leading cause of cancer-related deaths worldwide. Over 95% of gastric cancers are adenocarcinomas, which are typically classified based on anatomic location and histologic type. Gastric cancer generally carries a poor prognosis because it is often diagnosed at an advanced stage. Systemic therapy can provide palliation, improved survival, and enhanced quality of life in patients with locally advanced or metastatic disease. The implementation of biomarker testing, especially analysis of HER2 status, microsatellite instability (MSI) status, and the expression of programmed death-ligand 1 (PD-L1), has had a significant impact on clinical practice and patient care. Targeted therapies including trastuzumab, nivolumab, and pembrolizumab have produced encouraging results in clinical trials for the treatment of patients with locally advanced or metastatic disease. Palliative management, which may include systemic therapy, chemoradiation, and/or best supportive care, is recommended for all patients with unresectable or metastatic cancer. Multidisciplinary team management is essential for all patients with localized gastric cancer. This selection from the NCCN Guidelines for Gastric Cancer focuses on the management of unresectable locally advanced, recurrent, or metastatic disease.