Esophageal Cancer

Esophageal cancer generally has a poor prognosis; while preoperative chemotherapy is recommended, tumors often do not respond to treatment.

Recent developments in the epidemiology, staging, and treatment of esophageal and gastroesophageal junction cancers have led to significant changes in the way these malignancies are managed. Although a relationship between gastroesophageal reflux disease and esophageal cancer has been demonstrated, antireflux surgery has been shown to have no preventive effect with regard to the development of esophageal adenocarcinoma. The newly modified staging system of the World Esophageal Cancer Consortium has helped define the optimal number of lymph nodes to dissect during an esophagectomy. Incorporating modern techniques, such as esophageal ultrasound, fine needle aspiration, and positron emission tomography, can improve the prognostic value of staging. Use of higher-volume centers and higher-volume surgeons for the performance of procedures in upper gastrointestinal cancers is associated with better outcomes. Neoadjuvant chemoradiation using a wide variety of chemotherapy regimens appears to have become the new standard of care for stage II and III esophageal cancer.

Esophageal adenocarcinoma (EAC) affects approximately 11,000 persons per year in the United States, is increasing in incidence, and is associated with an exceptionally high mortality rate.[1-4] In this issue of ONCOLOGY, Krasna reviews the role of multimodality therapy in the treatment of EAC. Poor outcome in patients with EAC is reflective of both deficiencies in early detection and the inadequacy of available therapies across stages.

Dr. Krasna has written an overview of multimodality therapy in esophageal cancer, with a particular focus on aspects related to staging and surgical care. The optimal management of locally advanced esophageal cancer remains a subject of controversy and active debate. However, there is now a clear consensus that surgery alone is inadequate therapy for patients with T3 or node-positive disease.

Esophagitis is a known adverse effect of bisphosphonate use and reflux esophagitis is an established risk factor for esophageal cancer through the Barrett pathway.

Although still relatively uncommon in Western countries, esophageal cancer is fatal in the vast majority of cases. In the United States, an estimated 16,470 new cases will be diagnosed in the year 2009, and 14,530 deaths will result from the disease. This high percentage of deaths rivals that of pancreatic cancer and is more than four times that of rectal cancer.

Gastric cancer is more common than esophageal cancer in Western countries but is less fatal. More than 21,130 new cases of gastric cancer will be diagnosed in the United States in the year 2009, with 10,620 deaths expected. Worldwide, gastric cancer represents approximately 930,000 new cases and accounts for more than 700,000 deaths. The incidence and mortality of gastric cancer have been declining in most developed countries, including the United States; the age-adjusted risk (world estimate) fell 5% from 1985 to 1990.

Turmeric, or curcumin (diferuloylmethane), may be a favorable agent for the prevention and treatment of esophageal cancer, according to researchers at the Cork Cancer Research Center and Mercy University Hospital in Cork, Ireland. The authors noted that turmeric was able to induce cell death by a mechanism that is not reliant on apoptosis induction.

BARRX Medical, Inc, a global technology leader in treating Barrett's esophagus, announced the publication of two related European trials that report a 100% eradication rate for early esophageal cancer and precancerous dysplasia using endoscopic resection followed by ablation therapy with the HALO ablation system. Barrett's esophagus is a complication of gastroesophageal reflux disease (GERD) and is a known risk factor for esophageal cancer, the fastest growing cancer in the Western world.

The use of neoadjuvant chemotherapy in resectable esophageal cancer was bolstered by the results of two trials presented at the 2008 Gastrointestinal Cancers Symposium.

Extracts of black raspberries might protect Barrett's esophagus patients against esophageal cancer and also might shift premalignant oral lesions from progression to squamous cell carcinoma (SCC) back toward normal differentiation

Data published in the New England Journal of Medicine show that oral capecitabine (Xeloda) and oxaliplatin (Eloxatin) in combination with epirubicin (Ellence) is a comparable alternative to infused fluorouracil (5-FU) and cisplatin with epirubicin in patients with previously untreated, advanced esophagogastric cancer.

Barrett's esophagus represents replacement of normal distal esophageal squamous epithelium with specialized columnar epithelium containing goblet cells. Typically arising in the setting of chronic gastroesophageal reflux disease, the presence of Barrett's esophagus carries a 50- to 100-fold increased risk of developing esophageal cancer. Risk factors include male sex, smoking history, obesity, Caucasian ethnicity, age > 50 and > 5-year history of reflux symptoms. Aggressive medical or surgical antireflux therapy may ameliorate symptoms, but have not yet been proven to affect the risk of developing esophageal adenocarcinoma in randomized trials. Although dysplasia is an imperfect biomarker for the development of subsequent malignancy, random sampling of esophageal tissue for dysplasia remains the clinical standard. There have been no studies to establish that endoscopic screening/surveillance programs decrease the rates of death from cancer. Fit patients with Barrett's esophagus and high-grade dysplasia should undergo esophagectomy to prevent the risk of developing esophageal adenocarcinoma. For non–operative candidates, endoscopic ablative approaches may represent a reasonable therapeutic alternative.

Barrett's esophagus represents replacement of normal distal esophageal squamous epithelium with specialized columnar epithelium containing goblet cells. Typically arising in the setting of chronic gastroesophageal reflux disease, the presence of Barrett's esophagus carries a 50- to 100-fold increased risk of developing esophageal cancer. Risk factors include male sex, smoking history, obesity, Caucasian ethnicity, age > 50 and > 5-year history of reflux symptoms. Aggressive medical or surgical antireflux therapy may ameliorate symptoms, but have not yet been proven to affect the risk of developing esophageal adenocarcinoma in randomized trials. Although dysplasia is an imperfect biomarker for the development of subsequent malignancy, random sampling of esophageal tissue for dysplasia remains the clinical standard. There have been no studies to establish that endoscopic screening/surveillance programs decrease the rates of death from cancer. Fit patients with Barrett's esophagus and high-grade dysplasia should undergo esophagectomy to prevent the risk of developing esophageal adenocarcinoma. For non–operative candidates, endoscopic ablative approaches may represent a reasonable therapeutic alternative.

Barrett's esophagus represents replacement of normal distal esophageal squamous epithelium with specialized columnar epithelium containing goblet cells. Typically arising in the setting of chronic gastroesophageal reflux disease, the presence of Barrett's esophagus carries a 50- to 100-fold increased risk of developing esophageal cancer. Risk factors include male sex, smoking history, obesity, Caucasian ethnicity, age > 50 and > 5-year history of reflux symptoms. Aggressive medical or surgical antireflux therapy may ameliorate symptoms, but have not yet been proven to affect the risk of developing esophageal adenocarcinoma in randomized trials. Although dysplasia is an imperfect biomarker for the development of subsequent malignancy, random sampling of esophageal tissue for dysplasia remains the clinical standard. There have been no studies to establish that endoscopic screening/surveillance programs decrease the rates of death from cancer. Fit patients with Barrett's esophagus and high-grade dysplasia should undergo esophagectomy to prevent the risk of developing esophageal adenocarcinoma. For non–operative candidates, endoscopic ablative approaches may represent a reasonable therapeutic alternative.

Paclitaxel injected directly into esophageal tumors in conjunction with radiotherapy (RT) proved safe and technically feasible in a small phase IIa, dose-escalation trial

Early metabolic imaging with positron emission tomography (PET) identifies responders to neoadjuvant chemotherapy for advanced adenocarcinoma of the esophagogastric junction

Early metabolic imaging with positron emission tomography (PET) identifies responders to neoadjuvant chemotherapy for advanced adenocarcinoma of the esophagogastric junction

The patient is referred for evaluation of this chronic progressive dysphagia. Upper gastrointestinal endoscopy is performed. The photograph is taken in the esophagus.

Esophageal, gastroesophageal junction, and gastric cancers are underpublicized but are frequently lethal, and gastroesophageal junction adenocarcinomas are increasingly common diseases in the United States and around the world. Although often grouped together in studies of chemotherapy, clear distinctions can be made in the locoregional therapy of these diseases. Esophageal squamous cell carcinomas may be treated with surgery or radiation with concurrent chemotherapy, whereas esophageal adenocarcinomas and gastroesophageal junction adenocarcinomas are often treated with all three treatment modalities. Over the past several years, it has become increasingly evident that gastric cancer is a disease that is potentially sensitive to chemotherapy. In the perioperative setting—at least in the Western world—chemotherapy and sometimes radiation are applied. However, the optimal chemotherapy for advanced gastric or esophageal cancer remains unsettled, and there is no single standard regimen. Several new chemotherapy agents have demonstrated activity in these diseases, but the best chemotherapy remains to be determined. This paper will review the role of chemotherapy in gastroesophageal cancers.

Esophageal, gastroesophageal junction, and gastric cancers are underpublicized but are frequently lethal, and gastroesophageal junction adenocarcinomas are increasingly common diseases in the United States and around the world. Although often grouped together in studies of chemotherapy, clear distinctions can be made in the locoregional therapy of these diseases. Esophageal squamous cell carcinomas may be treated with surgery or radiation with concurrent chemotherapy, whereas esophageal adenocarcinomas and gastroesophageal junction adenocarcinomas are often treated with all three treatment modalities. Over the past several years, it has become increasingly evident that gastric cancer is a disease that is potentially sensitive to chemotherapy. In the perioperative setting—at least in the Western world—chemotherapy and sometimes radiation are applied. However, the optimal chemotherapy for advanced gastric or esophageal cancer remains unsettled, and there is no single standard regimen. Several new chemotherapy agents have demonstrated activity in these diseases, but the best chemotherapy remains to be determined. This paper will review the role of chemotherapy in gastroesophageal cancers.

Esophageal, gastroesophageal junction, and gastric cancers are underpublicized but are frequently lethal, and gastroesophageal junction adenocarcinomas are increasingly common diseases in the United States and around the world. Although often grouped together in studies of chemotherapy, clear distinctions can be made in the locoregional therapy of these diseases. Esophageal squamous cell carcinomas may be treated with surgery or radiation with concurrent chemotherapy, whereas esophageal adenocarcinomas and gastroesophageal junction adenocarcinomas are often treated with all three treatment modalities. Over the past several years, it has become increasingly evident that gastric cancer is a disease that is potentially sensitive to chemotherapy. In the perioperative setting—at least in the Western world—chemotherapy and sometimes radiation are applied. However, the optimal chemotherapy for advanced gastric or esophageal cancer remains unsettled, and there is no single standard regimen. Several new chemotherapy agents have demonstrated activity in these diseases, but the best chemotherapy remains to be determined. This paper will review the role of chemotherapy in gastroesophageal cancers.

Updated Varian Brachytherapy Applicator Receives Clearance

Barrett's esophagus and documented high-grade dysplasia (HGD)

There is sufficient evidence to show that asbestos exposure can cause cancer of the larynx.

Confocal laser endomicroscopy, a new technology that permits high-resolution subsurface microscopic imaging of living tissue during routine endoscopy, can facilitate the diagnosis of esophageal and gastric cancers, according to a recent report. "Endomicroscopy allows you to make an in vivo histology during ongoing endoscopy," Ralf Kiesslich, MD, PhD, said at the 2006 Gastrointestinal Cancers Symposium (General Session I).

Based on positive results from the Radiation Therapy Oncology Group (RTOG) 85-01 trial, the conventional nonsurgical treatment of esophageal carcinoma is combined-modality therapy. Dose intensification of the RTOG 85-01 regimen, examined in the Intergroup (INT)-0123/RTOG 94-05 trial, did not improve local control or survival. Areas of clinical investigation include the development of combined-modality therapy regimens with newer systemic agents, the use of 18F-fluorodeoxyglucose positron-emission tomography to assist in the development of innovative radiation treatment planning techniques, and the identification of prognostic molecular markers. The addition of surgery following primary combined-modality therapy apparently does not improve survival, but this finding is controversial.

Based on positive results from the Radiation Therapy Oncology Group (RTOG) 85-01 trial, the conventional nonsurgical treatment of esophageal carcinoma is combined-modality therapy. Dose intensification of the RTOG 85-01 regimen, examined in the Intergroup (INT)-0123/RTOG 94-05 trial, did not improve local control or survival. Areas of clinical investigation include the development of combined-modality therapy regimens with newer systemic agents, the use of 18F-fluorodeoxyglucose positron-emission tomography to assist in the development of innovative radiation treatment planning techniques, and the identification of prognostic molecular markers. The addition of surgery following primary combined-modality therapy apparently does not improve survival, but this finding is controversial.

Based on positive results from the Radiation Therapy Oncology Group (RTOG) 85-01 trial, the conventional nonsurgical treatment of esophageal carcinoma is combined-modality therapy. Dose intensification of the RTOG 85-01 regimen, examined in the Intergroup (INT)-0123/RTOG 94-05 trial, did not improve local control or survival. Areas of clinical investigation include the development of combined-modality therapy regimens with newer systemic agents, the use of 18F-fluorodeoxyglucose positron-emission tomography to assist in the development of innovative radiation treatment planning techniques, and the identification of prognostic molecular markers. The addition of surgery following primary combined-modality therapy apparently does not improve survival, but this finding is controversial.

Compared with surgery alone, the triple combination of chemotherapy, radiation therapy, and surgery is associated with a more than doubling of overall survival and a more than tripling of progression-free survival in patients with resectable esophageal cancer, according to a randomized trial presented at the 2006 Gastrointestinal Cancers Symposium (abstract 4).