Robert S. Fontana

Lung cancer screening: the Mayo program.

The National Cancer Institute has sponsored three randomized controlled trials of screening for early lung cancer in large, high-risk populations to determine whether lung cancer detection can be improved by adding sputum cytological screening every 4 months to chest roentgenography done either yearly or every 4 months; and lung cancer mortality can be significantly reduced by this type of screening program, followed by appropriate treatment. Results of the three trials suggest that sputum cytology alone detects 15% to 20% of lung cancers, almost all of which are squamous cancers with a favorable prognosis; and chest roentgenography may be a more effective test for early-stage lung cancer than previous reports have suggested. Nevertheless, results of the randomized trial conducted at the Mayo Clinic showed that offering both procedures to high-risk outpatients every 4 months conferred no mortality advantage over standard medical practice that included recommended annual testing.

Screening for lung cancer. A critique of the Mayo Lung Project.

The National Cancer Institute of the United States recently sponsored three large‐scale, randomized controlled trials of screening for early lung cancer. The trials were conducted at the Johns Hopkins Medical Institutions, the Memorial Sloan‐Kettering Cancer Center, and the Mayo Clinic. Participants were middle‐aged and older men who were chronic heavy cigarette smokers and thus at high risk of developing lung cancer. Screening procedures were chest radiography and sputum cytology, the only screening tests of established value for detecting early stage, asymptomatic lung cancer. In the Hopkins and Memorial trials the study population was offered yearly chest radiography plus sputum cytology every 4 months. The control population was offered yearly chest radiography only. In these trials the addition of sputum cytology appeared to confer no lung cancer mortality rate advantage. The Mayo Clinic trial compared offering chest radiography and sputum cytology every 4 months to offering advice that the two tests be obtained once a year. This trial demonstrated significantly increased lung cancer detection, resectability, and survivorship in the group offered screening every 4 months compared with the control group. However, there was no significant difference in lung cancer mortality rate between the two groups. The statistical power of these trials was somewhat limited. Nevertheless, results do not justify recommending large‐scale radiologic or cytologic screening for early lung cancer at this time.

Anatomic and Pathologic Studies in Ventricular Septal Defect

In a necropsy study of 50 cases of ventricular septal defects, the anatomic position and relations of ventricular septal defects, the causes of and ages at death, and association of ventricular septal defects with other cardiovascular malformations were determined. The present availability of surgical closure of ventricular septal defects makes this information of practical significance.

Hematoporphyrin as a diagnostic tool. A preliminary report of new techniques

Data on the induction of fluorescence in malignant tumors by means of the recrystallized hematoporphyrin derivative (Hp‐D) are currently available. Recent improvements in the quality of available Hp‐D, violet light sources, light carriers, and flexible fiberoptic bronchoscopes appear to warrant further examination of this technique for localization of early cancer. A protocol can be developed for utilization of Hp‐D in the localization of in‐situ and early invasive bronchogenic carcinoma.

The mayo lung project: Preliminary report of “early cancer detection” phase

The Mayo Lung Project has been established to assess the effectiveness of close surveillance in reducing the death rate from bronchogenic carcinoma. Candidates for study are high‐risk patients (men, aged 45 or older, smoking at least one pack of cigarettes daily) with life expectancy of at least 5 years. A lung‐health questionnaire, chest roentgenogram, and 3‐day pooled specimen of sputum provide the basic information. Candidates with positive test results receive appropriate treatment. Those whose initial data are negative are randomized into either a close‐surveillance (participant) group or a control group. Participants are restudied every 4 months. Controls receive whatever medical care they ordinarily would, but no regular restudy except annual follow‐up by letter. This routine will extend over 5 years or more, and tracing 5 to 10 years further. Lung‐cancer death rates in the two groups will be compared. Preliminarily, it appears such programs can be incorporated into private group practices.

Some results of screening for early lung cancer

Screening for lung cancer is somewhat controversial in that very few evaluations of the screening process have been made, and even fewer have involved the use of concomitant, unscreened controls. This report of the Mayo Lung Project provides evaluation of a randomly selected 4500 clinic patients, offered screening for lung cancer at four‐month intervals for six years. Another 4500 randomly selected controls not offered screening were merely observed. Good screening is defined, the Mayo project is evaluated, and puzzling results are presented and discussed.

Biometric design of the mayo lung project for early detection and localization of bronchogenic carcinoma

Several important aspects of the Mayo Lung Project demand evaluation. These are: 1. Acceptance. Will people accept such a screening program? 2. Case finding. Does the screen pick out the people most likely to have or develop bronchogenic carcinoma? 3. Effectiveness. If an early case of bronchogenic carcinoma is found, will prompt treatment extend life beyond the time at which death from this disease would have occurred if treatment had been delayed? Direct measurement of effectiveness is not possible, and indirect methods must be used. A group of patients, all of whom are considered suitable for the screening program, are being divided randomly into two subgroups, one to be screened and the other to be kept as an unscreened control. Mortality in the two groups is to be compared for 5 years, and hopefully for 10 years. We also consider here sample size requirements and reports on some of the characteristics of the first 500 patients.

Benzo(a)pyrene metabolism and blast transformation in peripheral blood mononuclear cells from smoking and nonsmoking populations and lung cancer patients.

Benzo(a)pyrene metabolism and lymphocyte transformation in peripheral blood mononuclear cells were evaluated in 3 groups of male patients. Group I were healthy nonsmokers, Group II were smokers, Group III were lung cancer patients, primarily stage I, evaluated before radiation or chemotherapy. Benzo(a)pyrene metabolism was assayed by a method involving quantitation of water soluble products produced from 3H‐benzo(a)pyrene over an eight hour reaction and lymphocyte transformation was measured by 3H‐thymidine incorporation. The mean level of metabolism of benzo(a)pyrene was significantly higher in the smoking control group, but was not significantly different in the nonsmoking control and the lung cancer groups. Lymphocyte transformation was significantly lower in the lung cancer patients than in either of the control groups despite the fact that 38 out of 57 of the lung cancer patients had stage I disease. Two pieces of evidence derived in this study indicate that the degree of lymphocyte transformation by mitogens influences the benzo(a)pyrene metabolism. First, the mean level of benzo(a)pyrene metabolites in lung cancer patients with lymphocyte stimulation less than 104 cpm was significantly lower than in those cancer patients with lymphocyte stimulation greater than 104 cpm. Secondly, when mononuclear cells from three control patients were stimulated with variable concentrations of mitogens, it was found that water soluble metabolite production and the degree of lymphocyte transformation had a significant correlation coefficient.

Aryl Hydrocarbon Hydroxylase in Man and Lung Cancer

Lung cancer is one of the leading causes of cancer deaths in most Western countries. In the United States it accounts for 33% of the cancer deaths in males and 11% of the cancer deaths in females. More males die from lung cancer than from the four next common cancer sites combined, i. e., colon, prostate, pancreas, and stomach cancer. In females, lung cancer holds third place in cancer deaths, preceded only by breast and colon cancer (Silverberg, 1977). Of all the common cancers it is the one most clearly associated with environmental agents, the most notable of which is cigarette smoking.

Early Bronchogenic Carcinoma: Problems in Detection, Localization, and Treatment

Localization and early surgical resection is the goal in management of in situ bronchogenic carcinoma. Results may be improved if the lesion can be detected and localized while still in its presymptomatic phase.