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Biomedical subjects

R S Fontana

Publications and source records attributed to R S Fontana.

At least 19 recordsLinked to original sources

The Mayo Lung Project: a perspective.

BACKGROUND: The Mayo Lung Project (MLP) was a randomized, controlled, clinical trial designed to determine whether intensive radiologic and cytologic screening for lung carcinoma could reduce lung carcinoma mortality significantly. METHODS: Half the MLP population was encouraged (and reminded) to undergo free chest X-rays and free sputum cytology tests every 4 months for 6 years, whereas the other half of the population was advised to undergo the 2 tests yearly. RESULTS: Lung carcinoma incidence rate, resectability, and survivorship were greater in the intensively screened group compared with the control group, but there was no significant difference in the lung carcinoma mortality rate between the two groups. CONCLUSIONS: The intensive screening program cannot be recommended as a public health measure because it did not appear to result in decreased lung carcinoma mortality, even though it did yield an increased rate of incidence of apparently indolent tumors.

Aged↗

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.

Clinical Trials as Topic↗

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.

Clinical Trials as Topic↗

Roentgenographically occult lung cancer: pathologic findings and frequency of multicentricity during a 10-year period.

During the first 10 years of the Mayo Lung Project, 68 roentgenographically inapparent ("occult") lung cancers were localized and apparently completely resected. A pathologic classification was developed based on depth of tumor infiltration. The five categories were (1) in situ carcinoma confined to surface epithelium or ducts of mucous glands or acini (23 cancers), (2) intramucosal invasion not greater than 0.1 cm from mucosal surface (12 cancers), (3) invasion to bronchial cartilages (11 cancers), (4) invasion to full thickness of bronchial wall (10 cancers), and (5) extrabronchial invasion (12 cancers). Multicentricity of lung cancer was studied in 54 patients, none of whom had a history of cancer of the respiratory tract, and all of whom had had "complete" surgical resection of the initial occult lung cancer (or cancers). Neoplasms that were initially multicentric occurred in 4 patients, and a subsequent primary lung cancer developed in 11. The rate of detection of second primary lesions was 42 per 1,000 person-years of observation. A high incidence of unresectable cancers and a low survival rate were noted among patients who had a subsequent primary tumor. These findings were primarily attributable to invasiveness of the subsequent primary cancer or to respiratory insufficiency that resulted from obstructive lung disease or previous pulmonary resection. Because of the high risk of development of a second primary cancer after initial surgical resection, it is important to treat the initial occult cancer as conservatively as possible consistent with "cure."

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The National Cancer Institute Cooperative Early Lung Cancer Detection Program. Results of the initial screen (prevalence). Early lung cancer detection: Introduction.

This introduction provides a description of 3 cooperating studies on Screening for Early Lung Cancer conducted under the auspices of the National Cancer Institute. The next 3 reports detail the unique aspects and results of the individual screening studies. The final presentation summarizes the initial ("prevalence") screening for all 3 centers (approximately 30,000 men), and gives our conclusions.

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Early lung cancer detection: results of the initial (prevalence) radiologic and cytologic screening in the Mayo Clinic study.

The initial (prevalence) radiologic and cytologic screening for lung cancer in the Mayo Clinic study (Mayo Lung Project) involved 10,933 outpatients. All were men at high risk for lung cancer, but none were suspected of having it when they entered the Mayo Clinic. Screening identified 91 lung cancers (8.3 per 1,000 screened). Nearly two thirds of the prevalence lung cancers were detected by chest roentgenography alone. Half of these cancers were resected. Only a fifth of the cancers were detected by sputum cytologic examination alone; however, all but 1 of these were resected. Compared with a group of lung cancers encountered in contemporary clinical practice at the Mayo Clinic, the prevalence cancers were more than twice as likely to be (1) resectable, (2) postsurgical Stage I or II (AJCC), and (3) associated with survival 5 yr after treatment.

Adenocarcinoma↗

Functional classification of bronchial carinae.

Extensive classifications have been in use to describe the bronchial tree; however, the lack of uniform nomenclature to describe the carinae which separate the various bronchi has led to the use of lengthy and often confusing terminologies in reporting and understanding bronchoscopic findings. We have developed a practical classification of main bronchial carinae and suggest the use of abbreviations to describe them. The newer nomenclature is designed to help improve clinical communication, especially with regard to bronchoscopic findings and their clinical implications, among physicians who specialize in pulmonary diseases.

Bronchi↗

Lung cancer detected during a screening program using four-month chest radiographs.

Ninety-two lung cancers were detected in the Mayo Lung Project in patients undergoing chest radiography every four months for screening. Fifty patients had a peripheral nodule, 16 had a perihilar nodule, 20 had hilar or mediastinal enlargement, and six had pneumonitis. The peripheral cancers grew slowly. Ninety per cent were visible in retrospect for months or even years. Despite this, 70% of the peripheral cancers were classified as postsurgical American Joint Committee (AJC) Stage 1. The central cancers grew rapidly, usually presenting as hilar or mediastinal enlargements after normal findings on the previous radiograph obtained four months earlier. Most were classified as AJC Stage 3 tumors.

Adenocarcinoma↗

Roentgenographically occult lung cancer. A ten-year experience.

During the past 10 years, 54 patients, all men, were found to have roentgenographically occult lung cancer. The mean age was 61 years (range 45 to 76 years). All patients had abnormal findings on sputum cytologic study (carcinoma in 41 patients and squamous cell atypia in 13). The cancer was localized by bronchoscopy in all patients (range one to five examinations, mean 1.5). Seventy-five percent of the tumors were localized within 169 days of the abnormal sputum cytologic examination. Pulmonary resection for cure was performed in all patients: lobectomy in 38, pneumonectomy in nine, and bilobectomy in seven. Operative mortality was 5.6% (three patients). Fifty-eight cancers were resected, all squamous cell carcinomas (two had a component of large cell cancer). Tumor TNM classification (AJC) was TIS N0 M0 in 19 patients, T1 N0 M0 in 25, T1 N1 M0 in five, T2 N1 M0 in four, and T3 N0 M0 in one. Overall 5 year actuarial survival rate (lung cancer deaths only) was 90%. Five-year survival rate for the 44 patients with TIS N0 M0 and T1 N0 M0 neoplasms was 91%. Currently, 21 patients have died, but only 10 of lung cancer. Subsequent additional lung cancer developed in 12 patients (22%). Eleven of these patients had a second primary squamous lung cancer, six of which again were occult. We conclude that patients with occult lung cancer have a strong likelihood of long-term survival if treated early. Close surveillance is indicated because of the high incidence of a second primary lung cancer.

Aged↗

Hematoporphyrin derivative in the detection and localization of radiographically occult lung cancer.

Hematoporphyrin derivative used in conjunction with the Mayo Clinic bronchofiberscopic fluorescence detection system allows accurate localization of radiographically occult early squamous cell carcinoma. Thirteen tumors were localized in 10 patients with radiographically occult lung cancer. Six were in situ with or without microinvasion and were also bronchoscopically occult. Localization of these 6 tumors was expedited by the use of hematoporphyrin derivative and the bronchoscopic fluorescence detection system. Hematoporphyrin-derivative fluorescence was not specific for carcinoma and was also detected in areas of moderate and marked squamous cellular atypia. Thus, although detection of hematoporphyrin-derivative fluorescence suggests the presence of cancer, proof depends on histologic or cytologic confirmation.

Bronchoscopy↗

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. From the screened group, 98 new cases of lung cancer have been detected, 67 by study screening and 31 by spontaneous reporting of symptoms (15) or by x-ray examinations (16) done in other than study circumstances. From the controls, 64 new lung cancer cases have been detected, 43 by symptoms and 1 by other methods. Lung cancer mortality is 39 for study patients and 41 for controls. There is thus no evidence at this time that early case finding hs decreased mortality from lung cancer.

Adenocarcinoma↗

Survival of patients surgically treated for stage I lung cancer.

When the TNM staging system of the American Joint Committee (AJC) for Cancer Staging and End-Results Reporting was applied to 3,912 patients seen during a 6 year period at the Mayo Clinic, 624 (16%) fulfilled the criteria for postsurgical pathological Stage I non-small cell bronchogenic carcinoma. Of these 624 patients, 129 were excluded from further survival analysis for various reasons. The remaining 495 consisted of two groups: 350 patients who were enrolled within 30 days into a prospective postoperative 4 monthly follow-up program and 145 patients who were enrolled later or were followed less frequently. Because no significant difference was noted in survival rates between these groups, data were pooled. Of the combined group of 495 patients, 84% survived lung cancer for 2 years and 69% of 5 years (actuarial estimation). The survival of patients classified T1 N0 M0 (91% alive at 2 years and 80% at 5 years) is so good that it seems unlikely that adjuvant therapy in this group could demonstrate improved survival. In addition to TNM classification, age at operation, sex, and extent of operation were important determinants of survival.

Adult↗

Variation of microsomal mixed function oxidase(s) and human lung cancer.

Animal and human studies on aryl hydrocarbon hydroxylase (AHH) have demonstrated wide inter-individual variation. First attempts to link this variation to the susceptibility to certain cancers have been successful in mice but remained inconclusive in man. In a new approach, saliva antipyrine half-lives and metabolic clearance rates have been used to assess individual rates of benzo]a]pyrene metabolism in human subjects. Saliva antipyrine half-lives and metabolic clearance rates have been measured in 57 patients with lung cancer, 90% of whom had quit smoking more than three months prior to the test, 57 cancer-free matched controls, and 59 healthy smoking controls. The mean antipyrine half-life was significantly shorter (P less than 0.001) in lung cancer patients when compared with the cancer-free matched control group, but differed little from that of the smoking group (P less than 0.05). The data support the previous observation than lung cancer patients have increased oxidation rates which, in addition to smoking, might have predisposed them to developing lung cancer.

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