Combination Treatment for Esophageal Cancer

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.

Skin Cancer: A Review

John E. Adam MD, FRCPC, Professor of Medicine (Dermatology), University of Ottawa, Ottawa, ON.

The annual number of new cases of skin cancers reported in Canada is estimated to be about 40,000. With the aging of the baby boomer generation, this figure is anticipated to increase because of the ease of travel to the south in winter and increased exposure to the sun during outdoor activities. Dermatoheliosis or photodamage is most prevalent in people over 40 years of age who have had excessive sun exposure over their lifetime (Table 1). Epidemiological studies have identified sunlight exposure as the major risk factor for skin cancer.

There are three major types of skin cancer. The most common non-melanocytic skin cancers are Basal Cell Carcinoma and Squamous Cell Carcinoma. The less frequently occurring melanocytic skin cancer is Malignant Melanoma.

Basal cell carcinoma
Basal Cell Carcinoma (BCC) is the most common form of skin cancer but also the least likely to metastasize. It can be very destructive locally if not diagnosed and treated early.

Clinically it presents in several forms on sun-exposed areas (Table 2). The classic and most common presentation is the nodulo-cystic variety--a shiny elevated dome shaped nodule with a raised border often with telangiectatic blood vessels on the surface. The tumour is described as shiny or of a "mother-of-pearl colour.

Cardiac Tumours: Presentation and Treatment

Nimesh D. Desai¹, MD, Jagdish W . Butany, MBBS MS, FRCPC²
Departments of Cardiac Surgery¹ and Pathology², Toronto General Hospital / University Health Network and University of Toronto, Toronto, ON.

Introduction
Cardiac tumours are uncommon,when compared to other tumours. A few of these are more frequently seen in the young (first and second decade of life),while most are more common in older individuals ( fourth decade of life and later). When they occur they are more likely to be metastatic than primary cardiac neoplasms, the latter more likely benign than malignant, and the former more common in older individuals.Their manifestations are varied and invariably pose a diagnostic challenge. The first pre-mortem diagnosis of an intracardiac myxoma was not made until 1952, using angiography.¹ Today, the accurate clinical diagnosis of cardiac tumours is made with non-invasive techniques such as echocardiography.

Incidence
Autopsy studies have shown an incidence of between 0.0017 and 0.3 percent for primary cardiac tumours.^2,3 In adults the mean age at diagnosis of tumours is: sarcoma 40 years; myxoma 50 years; mesothelioma, 57 years; papillary fibroelastoma, 59 years; and lipomatous hypertrophy, 64 years.⁴ The incidence of secondary or metastatic cardiac tumours is significantly greater than that of primary tumours and is approximately 1.23%.

Clinical Approaches to Male Breast Cancer

Stefan Glück^1,2 MD, PhD and Christine Friedenreich³ PhD
¹Professor, Dept. Oncology, Medicine and Pharmacology & Therapeutics Faculty of Medicine, University of Calgary, Calgary, AB.
²Senior Leader, Clinical Research Program Medical Oncologist, Tom Baker Cancer Centre, Calgary, AB.
³Research Scientist, Division of Epidemiology, Prevention and Screening, Alberta Cancer Board, Calgary, AB.

Introduction
In 1996, the most recent year for which complete statistics for Canadian cancer incidence are available, a total of 118 new cases of breast cancer were diagnosed in men.¹ This incidence rate is approximately 0.7% of the 16,551 cases diagnosed in women.¹ This proportion of male to female breast cancers is typical of western populations, although exceptionally high proportions of male to female breast cancers have been found in countries such as Egypt and Zambia, with studies reporting 6% and 15%, respectively.^2,3

In many aspects, the disease has a similar clinical course in both genders. However, because male breast cancer is so rare, it has been very difficult to accumulate knowledge through research, especially through large prospective trials. Many aspects of the diagnosis and treatment of male breast cancer remain controversial and even in the future, clinical research will be difficult.

Screening for Colorectal Cancer in Older Adults

Peter G. Rossos MD, FRCP(C)
Elaine Yeung MD
Division of Gastroenterology, University Health Network
University of Toronto, Toronto, ON.

Introduction
Colorectal cancer (CRC) is the third most common cause of cancer and second leading cause of cancer death in Canada. It is estimated that there were 17,200 new cases and 6,400 deaths from colorectal cancer in Canada in 2001. When both women and men are considered together, colorectal cancer is the second most frequent cause of death from cancer among Canadians.¹ Most CRC occurs in average risk individuals for whom there are no accepted guidelines for screening.² Higher risk categories include those who have a family history of CRC, a personal history of CRC, colonic adenomas or inflammatory bowel disease, and the familial syndromes including familial adenomatous polyposis (FAP) and hereditary nonpolyposis colon cancer (HNPCC).³ This discussion will focus on average risk older adults, who comprise almost all CRC cases in patients 65 years of age or older.

Epidemiologic Considerations
Although age-standardized incidence and mortality rates have been declining for CRC since 1985, the number of new cases has continued to rise steadily and significantly among both men and women as a result of the growth and aging of the population. Recent data from the National Cancer Institute of Canada is displayed in Figures 1 and 2.

Ovarian Cancer in Older Women: Management and Treatment Options

Natalie S. Gould MD, Fellow and Clinical Instructor
D. Scott McMeekin MD, Assistant Professor Section of Gynecologic Oncology,
Department of Obstetrics and Gynecology
University of Oklahoma Medical Center, Oklahoma City, OK, USA.

Ovarian cancer is a disease of older women, with 48% over the age of 65 at diagnosis.¹ It is also the most deadly of gynecologic malignancies, accounting for more deaths than cervical and endometrial carcinoma combined in the US. An estimated 23,400 new cases of ovarian cancer will be diagnosed in 2001 with 13,900 deaths in the US.² As our population ages, the number of women affected by ovarian cancer will increase. Cancer limited to an ovary is typically silent and discovered incidentally on exam or at surgical exploration for other reasons. Patients with disease that has spread beyond the ovaries may present with vague gastrointestinal symptoms, bloating, diarrhea, pain and changes in bowel or bladder habits. On physical exam, patients will have a pelvic mass and often ascites. Due to the absence of symptoms until the malignancy has spread beyond the ovaries, and the lack of good screening tests, approximately 70% of patients present with advanced disease and overall survival is poor.³ (Table 1).

Initial management involves cytoreductive surgery aimed at removal of the greatest volume of tumour (Table 2).

Pancreatic Cancer in the Elderly

Dr. Carol Townsley, Clinical Research Fellow, Princess Margaret Hospital,
University Health Network, Toronto, ON.
Dr. David Hedley, Staff Medical Oncologist, Princess Margaret Hospital,
University Health Network, Toronto, ON.

Pancreatic cancer is the fourth leading cause of cancer-related death for both men and women in North America (following lung, colon and prostate/breast), and is responsible for 5% of all cancer-related deaths. At two to three percent, pancreatic adenocarcinoma has the worst overall five-year survival rate of any cancer. Due to the extreme difficulty in diagnosing pancreatic cancer when it is still surgically resectable, and because of the lack of effective systemic therapies, incidence rates are, unfortunately, virtually equal to mortality rates. Although the overall survival is quite poor, there is a subgroup of patients with slow growing tumours who may survive for several years with good symptom control.

Epidemiology and Risk Factors
An increased incidence of pancreatic cancer is seen in patients of male gender, advanced age and black race. The risk of developing pancreatic cancer is low in the first three to four decades of life but increases sharply after the age of 50 years, with most patients being between the ages of 60 and 80 at the time of diagnosis. Although exact risk factors for pancreatic cancer are not well defined, there appears to be a clear association with smoking and possibly with chronic pancreatitis.

Driving, Cancer and Discrimination

At the time of the writing of this editorial, there is a 'high profile' inquest going on in Toronto concerning driving and the elderly. Two years ago, an elderly woman making a right hand turn struck and killed a young woman. The young woman was then dragged under the car for almost a kilometre with the driver apparently unaware. There was no suggestion that the elderly driver had any physical or cognitive impairment that affected her driving. However, despite the absence of cognitive impairment, this was felt to be a case that could raise the profile of cognitive impairment and the aging driver. The inquest has not concluded, but fortunately initial testimony has stressed that most elderly drivers are competent to drive.

The same day that my testimony at this inquest was reported in the papers, another story was reported, more gruesome than the first. A 25-year-old Texas woman struck a homeless man, impaled him on her windshield, and then locked him and the car in the garage while he slowly bled to death over two or three days. She and her friends then removed the body and 'dumped' it in a garbage bin. For some reason, the first case has sparked an intense interest in whether or not the elderly should drive, but I have not read or heard any musing about restricting the driving privileges of 25-year-olds. Perhaps all young people should have random drug testing to maintain their driving privileges (a presumed factor in the Texas incident)!

Clearly, the difference in the two cases from a geriatrician's perspective is as follows: The incident with the elderly driver is immediately generalized to reflect all the elderly, whereas the incident with the young driver is a reflection of her actions, and her actions alone. In the first case, the trial judge last year pronounced that the woman's ability to drive was 'impaired by age.' I have yet to identify any evidence that shows age is an independent risk factor for driving. Rather, it is the morbidity that accompanies aging that impairs driving. I suspect that any slowing of reaction time and reflexes in the elderly is more than compensated by better judgment and increased caution. Even though we know that a large number of the over 80 population has cognitive impairment, we do not have accurate information on how many still drive, vital information to have if any screening endeavours are considered.

This issue focuses on cancer and the elderly and, as I have discussed in the past, the presumption is often made that the elderly should be treated less aggressively than should younger patients, even though comorbidity is a more important factor than age alone. The lesson, brought home once again by this inquest, is that management must be tailored to the individual and based on comprehensive assessment, not just a single factor such as age.

Fortunately, in this issue we feature articles by experts who do not fall prey to age bias. Dr. Townsley and Dr. Hedley discuss pancreatic cancer in the elderly, and other articles address the issues of cardiac tumours (Desai and Butany), ovarian cancer (Gould and McMeekin), male breast cancer (Glück and Friedenreich), and screening for colorectal cancer (Rossos and Yeung). As well, we have our usual assortment of other articles, including a special piece on estrogen and the aging brain by Elise Levinoff and Dr. Howard Chertkow, one of Canada's leading investigators in the field of cognitive impairment.

Enjoy this issue.