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After Local Therapy for Esophageal Cancer, Should We Continue to Survey Patients and, If So, Why and How?

Jaffer A. Ajani

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Gastroesophageal Cancers: Progress and Problems

Jaffer A. Ajani

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Crescendos and Decrescendos: Gastric and Esophageal Cancers

Jaffer A. Ajani

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Combined Modality Therapy of Localized Gastric and Esophageal Cancers

Prajnan Das, Norio Fukami, and Jaffer A. Ajani

Gastric and esophageal cancers continue to be a significant health problem. The incidence of proximal gastric and distal esophageal cancers has been increasing, especially in white men. Gastric and esophageal cancers have high rates of locoregional and distant failure, resulting in poor overall survival. Therefore, patients with gastric and esophageal cancer may benefit from combined modality therapy. Adjuvant chemoradiation has been shown to improve survival in gastric and gastroesophageal cancers in a phase III trial. In esophageal cancer, most randomized trials have not shown a survival benefit for preoperative chemotherapy or chemoradiation, although these approaches are widely used. This article reviews the role of staging, surgery, and adjuvant and preoperative therapies in the management of localized gastric and esophageal cancers.

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Localized Gastroesophageal Cancers: Can We Shift the Current Treatment Paradigms?

Jane E. Rogers, Allison Trail, and Jaffer A. Ajani

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Anal Carcinoma Therapy: Can We Improve on 5-Fluorouracil/Mitomycin/Radiotherapy?

Yixing Jiang, Heath Mackley, Hua Cheng, and Jaffer A. Ajani

Use of definitive chemoradiation as primary therapy for locoregional squamous cell carcinoma of the anal canal has been the standard approach in the United States since the 1980s. Over the past several years, phase III studies have shown that combination mitomycin C (MMC) and 5-fluorouracil (5-FU) concurrent with radiotherapy had better outcomes than radiotherapy alone or 5-FU with radiotherapy. Two recent phase III studies using diverse treatment strategies showed that cisplatin and 5-FU were not superior to 5-FU and MMC; in one of the trials, use of cisplatin-based chemoradiation resulted in a higher rate of colostomy compared with mitomycin-based chemoradiation. MMC and 5-FU concurrent with radiotherapy remains standard care. Further improvement is likely depending on an increased understanding of the molecular biology of anal carcinoma and the addition of relevant biologic agents to chemoradiation to overcome chemoradiation resistance.

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Impact of the 7th Edition AJCC Staging Classification on the NCCN Clinical Practice Guidelines in Oncology for Gastric and Esophageal Cancers

Vivian E. Strong, Thomas A. D’Amico, Lawrence Kleinberg, and Jaffer Ajani

The 7th edition of the AJCC Cancer Staging Manual has attempted to harmonize gastric and esophageal cancers, including management of gastroesophageal junction (GEJ)-type tumors. The treatment of complex tumor types is best guided by a staging classification that reliably groups patients according to prognosis and therapy. This article reviews and discusses these changes with the goal of elucidating key features of the staging system and outlining how these changes relate to the NCCN Clinical Practice Guidelines in Oncology with regard to the care and treatment of patients. The 7th edition of the AJCC Cancer Staging Manual has certainly improved harmonization of gastric and distal esophageal/GEJ-type adenocarcinomas, although issues persist, particularly regarding the optimal neoadjuvant treatment for the management of GEJ carcinomas.

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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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Surveillance for Esophageal Cancer: Does it Make Sense?

Mariela A. Blum Murphy, Takashi Taketa, Kazuki Sudo, Jeffrey H. Lee, and Jaffer A. Ajani

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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.