Clarence K.W. Wong, MD, FRCPC, Gastroenterologist and Clinical Lecturer, Division of Gastroenterology, University of Alberta; Consultant, Cross Cancer Institute, Alberta Cancer Board, Edmonton, AB.

Introduction
Gastrointestinal malignancies collectively account for the greatest number of cancer deaths in Canada.¹ This is particularly evident in the elderly population in which 90% of all new cancers are diagnosed in individuals over the age of 45.² Of these new cancers, one in five are gastrointestinal cancers. As these malignancies are often lethal, improved survival depends on preventive strategies to effectively detect and manage the associated precursor conditions. This paper will review the premalignant conditions associated with three common gastrointestinal cancers. Effective management of conditions leading to esophageal, gastric and colon cancers can greatly reduce the burden of disease among the geriatric population.

Esophageal Cancer
Cancers of the esophagus are lethal, with a death to case ratio of 1.11.¹ Although this estimate is high due to incomplete registration of new cases, it underscores the lack of effective treatment for this disease. Until recently, squamous cell carcinomas were the most common type of esophageal cancer. However, in the last few decades the incidence of esophageal adenocarcinomas has increased exponentially. It is likely that this increase is linked to a rise in incidence of its only known risk factor, Barrett's esophagus.

Historically, the outlook for patients with esophageal cancer who undergo surgical resection with curative intent is poor. Because of the high rates of failure, there is a great deal of interest in the possibility of systemic chemotherapy, combined with local surgical treatment.

The results of a recent randomized trial suggest that there may be a survival benefit for patients who undergo this combined treatment. Researchers compared surgical resection as locally practiced, with or without preoperative chemotherapy to investigate whether chemotherapy lengthens survival and affects dysphagia and performance status. Researchers selected a chemotherapy regimen of cisplatin and fluorouracil, which have been demonstrated to be active for both squamous carcinoma and adenocarcinoma, alone or in combination.

Chemotherapy comprised two 4-day cycles of cisplatin (80 mg/m²) by IV infusion over 4 h on day 1 and fluorouracil (1000 mg/m²) daily as a continuous infusion over 96 h, with an interval of 3 weeks between the first day of each cycle. For patients in this group, surgical resection was performed 3-5 weeks after the start of the second cycle of chemotherapy; for the surgery alone group, procedures were done as soon as possible after randomization. Patients were assessed before the start of treatment, on completion of therapy, and at 3, 6, 9, and 12 months from the date of randomization and then every 6 months until death.

Overall and disease-free survival were both better in the combined treatment group when compared to the surgery alone group (p=0.004; hazard ratio of 0.79; 95% CI 0.67-0.93 and p=0.0014; hazard ratio 0.75; 95% CI 0.63-0.89, respectively), with an estimated reduction in risk of 21% for overall survival. No statistically significant differences were found in dysphagia and performance status.

The authors suggest that this regimen should be considered for patients with resectable cancer of the esophagus, and that it may also serve as an appropriate control for further randomized trials designed to identify other beneficial chemotherapy regimens.

Source

1. Medical Research Council Oesophageal Cancer Working Party. Surgical resection with or without preoperative chemotherapy in oesophageal cancer: a randomised controlled trial. Lancet 2002; 359:1727-33.

Jolie Ringash, MD, MSc
Department of Radiation Oncology,
Princess Margaret Hospital
University Health Network,
Toronto, ON

Background
Esophageal and gastric carcinomas are primarily diseases of older persons. Of 498 new cases of esophageal cancer in Ontario in 1997, 237 (48%) occurred in individuals aged 65 to 79, and 101 (20%) in those over the age of 80. The corresponding numbers for gastric cancer are (of a total of 1,032 cases) 492 (48%) for those aged 65 to 79, and 200 (19%) for those over 80.¹ For all age groups, gastric cancer is decreasing in incidence, with only 2, 800 cases in Canada in the year 2000. In contrast, the incidence of esophageal cancers is gradually increasing (1,350 cases in 2000).^2,3 Adenocarcinoma, primarily of the distal esophagus, has replaced squamous cell carcinoma as the most frequent histology. Tumours of the gastroesophageal junction pose a particular challenge, since management may differ depending on whether the tumour is felt to originate in esophagus or stomach.

Canadian oncologists frequently face difficult treatment decisions in the elderly. Unfortunately, since older patients are usually excluded from clinical trials, evidence for their tolerance of, and response to, therapeutic radiation is limited. Existing reports are limited to retrospective reviews and subgroup analyses, many of which originate in Japan.