Esophageal Cancer

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).

ROCHESTER, MINNESOTA-A phase II study from the NorthCentral Cancer Treatment Group(NCCTG) showed that oxaliplatin(Eloxatin) combined with lower-dosecapecitabine (Xeloda) is active as first

Esophageal cancer frequently expresses cyclooxygenase-2 (COX-2)enzyme. In preclinical studies, COX-2 inhibition results in decreasedcell proliferation and potentiation of chemotherapy and radiation. Wereport preliminary results of a phase II study conducted by the HoosierOncology Group in patients with potentially resectable esophageal cancer.All patients received cisplatin at 75 mg/m2 given on days 1 and 29and fluorouracil (5-FU) at 1,000 mg/m2 on days 1 to 4 and 29 to 32with radiation (50.4 Gy beginning on day 1). Celecoxib (Celebrex) wasadministered at 200 mg orally twice daily beginning on day 1 untilsurgery and then at 400 mg orally twice daily until disease progressionor unexpected toxicities, or for a maximum of 5 years. Esophagectomywas performed 4 to 6 weeks after completion of chemoradiation. Theprimary study end point was pathologic complete response (pCR). Secondaryend points included response rate, toxicity, overall survival, andcorrelation between COX-2 expression and pCR. Thirty-one patientswere enrolled from March 2001 to July 2002. Respective grade 3/4 toxicitieswere experienced by 58%/19% of patients, and consisted of granulocytopenia(16%), nausea/vomiting (16%), esophagitis (10%), dehydration(10%), stomatitis (6%), and diarrhea (3%). Seven patients (24%)required initiation of enteral feedings. There have been seven deathsso far, resulting from postoperative complications (2), pulmonary embolism(1), pneumonia (1), and progressive disease (3). Of the 22 patients(71%) who underwent surgery, 5 had pCR (22%). We concludethat the addition of celecoxib to chemoradiation is well tolerated. ThepCR rate of 22% in this study is similar to that reported with the use ofpreoperative chemoradiation in other trials. Further follow-up is necessaryto assess the impact of maintenance therapy with celecoxib onoverall survival.

Esophageal cancer is a rare but highly virulent malignancy in theUnited States, and adenocarcinoma of the esophagus has had the mostrapid rate of increase of any solid tumor malignancy. Systemic metastaticdisease is present in 50% of patients at diagnosis. In the remaining50% presenting with local regional disease, systemic metastatic diseasewill develop in the vast majority of these patients.

From the results of recent studies, it is likely that multimodality therapy with chemotherapy and radiation treatment may improve the overall outcome of locally advanced upper gastrointestinal (GI) malignancies, including esophageal, gastric, pancreatic, and biliary tract carcinomas. However, more effective, more optimal, and less toxic chemotherapy regimen(s) with concomitant radiotherapy are needed beyond the concurrent continuous-infusion fluorouracil (5-FU) with radiation that is commonly applied in general practice. Epirubicin (Ellence), cisplatin, and irinotecan (Camptosar) are all active cytotoxic chemotherapy agents in upper GI cancers. Two phase I studies were designed to test the tolerability of the combination of radiotherapy with infusional 5-FU, epirubicin, and cisplatin (ECF) or 5-FU, irinotecan, and epirubicin (EIF) in the treatment of locally advanced upper GI malignancies.