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Biomedical subjects

B J Flehinger

Publications and source records attributed to B J Flehinger.

At least 19 recordsLinked to original sources
PubMed1999

Factors influencing ten-year survival in resected stages I to IIIa non-small cell lung cancer.

OBJECTIVE: The purpose of this study was to determine (in survivors of 5 years after resection of their lung cancer) whether age, sex, histologic condition, and age have any influence on furthering survival beyond 5 years. METHODS: From 1973 to 1989, 686 patients were alive and well 5 years after complete resection of their lung cancers. Survival analysis was carried out with only deaths from lung cancer treated as deaths. Deaths from other causes were treated as withdrawals. Multivariate Cox regression was used to test the relationship of survival to age, sex, histologic condition, and stage. RESULTS: The population in this study had the following characteristics at the time of operation: The male/female ratio was 1.38:1, and the median age was 61 years. The histologic condition of their lung cancer was adenocarcinoma in 412 patients, squamous cell in 244 patients, large cell carcinoma in 29 patients, and small cell carcinoma in 1 patient. The stage of the disease was stage IA in 263 patients, IB in 261 patients, IIA in 12 patients, IIB in 68 patients, and IIIA in 82 patients. The extent of resection was a lobectomy or bilobectomy in 579 patients, pneumonectomy in 55 patients, and wedge resection or segmentectomy in 52 patients. A recurrence or a new lung primary occurrence was considered as failure to remain free of lung cancer. The median follow-up on all patients was 122 months from initial treatment. Of the 686 patients, 26 patients experienced the development of late recurrence and 36 new cancers, beyond 5 years. Overall survival for 5 additional years after a 5-year check point was 92.4%. Likewise, survival by nodal status was 93% for N0 tumors, 95% for N1 tumors, and 90% for N2 tumors. Survival by stage was 93% for stage I tumors and 91% for stage II or IIIA tumors. CONCLUSIONS: In patients with surgically treated lung cancer, neither age, sex, histologic condition, nor stage is a predictor of the risk of late recurrence or new lung cancer. The only prognostic factor appears to be the survival of the patient free of lung cancer for 5 years from the initial treatment, with a resultant favorable outlook to remain well for 10 or more years.

Adenocarcinoma↗
PubMed1994

Current status of screening for lung cancer.

Three parallel studies on screening for lung cancer, supported by the National Cancer Institute, were carried out by the Mayo Clinic, Johns Hopkins Medical Institutions, and Memorial Sloan-Kettering Center from 1971 to 1982. No significant mortality improvement was established that could be attributed to cytologic screening examinations. Many stage I lung cancers were detected by radiographic screening, with excellent changes for long-term survival. Patients with stage I cancers who were operated on had significantly better survival rates than those who failed to undergo surgery. Statistical modeling, however, indicates that long-term annual screening of a high-risk population would decrease lung cancer mortality by no more than 18%.

Adenocarcinoma↗
PubMed1993

Screening for lung cancer. The Mayo Lung Project revisited.

BACKGROUND: The Mayo Lung Project (MLP) reported lung cancer incidence and mortality in a population offered chest radiographs and sputum cytologic screening examinations every 4 months and a population offered only the Mayo Clinic advice to undergo annual examination. No mortality benefit attributable to screening was observed after 6 years of observation and at least 1 year of follow-up. METHODS: The authors describe a simulation study designed to estimate from Mayo data the parameters in a mathematical model of the natural history of lung cancer and to estimate the potential benefit associated with periodic screening of high-risk people starting at 45 years of age. RESULTS: It was found that the mean duration of Stage I non-small cell lung cancer is at least 4 years and that rates of Stage I detectability and curability are less than 25% and 35%, respectively. CONCLUSIONS: A trial of the magnitude, duration, and contamination of the MLP would have a less than 20% probability of showing significant benefit from screening; however, long-term annual screening might result in a modest decrease in lung cancer mortality, ranging from 0% to 13%. A greater benefit would accrue from improved detection and treatment.

Aged↗
PubMed1993

Screening for colorectal cancer with fecal occult blood testing and sigmoidoscopy.

BACKGROUND: The high incidence of and mortality from colorectal cancer (160,000 new cases and 60,000 deaths in the United States each year) are compelling public health concerns. Following the evolution of effective surgery for this disease since the 1960s, the focus has been on improving methods of detection and integrating them into effective screening programs. PURPOSE: This was the first study to evaluate the effectiveness, in a setting of comprehensive medical examinations, of using the fecal occult blood test in conjunction with sigmoidoscopy, rather than sigmoidoscopy alone, to screen for colorectal cancer. Our end points were extent of compliance with fecal occult blood test and sigmoidoscopy, numbers of cancers detected, and mortality rate. METHODS: From 1975 through 1979, a total of 21,756 patients (aged 40 and older) who presented at the Preventive Medicine Institute-Strang Clinic for routine medical examinations were enrolled by calendar period into study and control groups. Study patients were offered annually both rigid sigmoidoscopy examinations and fecal occult blood tests requiring two stool specimens per day for 3 days, while control patients were offered only annual sigmoidoscopy. The majority of fecal occult blood test cards were not rehydrated before assay. Patients with positive tests were referred for double-contrast barium enema and colonoscopy. Two distinct trials were carried out. Trial I was primarily a demonstration of feasibility of using the fecal occult blood test as a supplemental screening method. Of the 9277 participants, 7168 (77%) were assigned to the study group and offered the fecal occult blood test. In trial II, approximately half of the 12,479 patients were assigned to each group. Patients in both trials had follow-up through 1984. RESULTS: Compliance with the fecal occult blood test was initially high in both trials, but diminished such that only 56% of study patients in trial I and 20% of those in trial II returned for second tests. On the initial (prevalence) screen, a substantial number of early-stage cancers were detected by the fecal occult blood test, primarily in trial II. In trial II, survival probability was significantly greater (P < .001) in the study group than in the controls (70% versus 48%), and colorectal cancer mortality was lower (0.36 versus 0.63) with borderline significance (P = .053, one-sided). CONCLUSIONS AND IMPLICATIONS: The screening of average-risk individuals (aged 50 and older) for colorectal cancer through use of the fecal occult blood test in conjunction with sigmoidoscopy can increase the likelihood of early detection of this disease. This practice, coupled with prompt diagnostic work-up following positive tests, will result in treatment of earlier stage cancers and increased survival after treatment.

Aged↗
PubMed1993

Early lung cancer as a potential target for chemoprevention.

Carcinoma of the lung is the most common cause of death from cancer in the United States. In considering lung cancer for possible chemoprevention trials, we have analyzed the data collected by the collaborative NCI program on early lung cancer. The data indicate that at least 12 years of study of 80,000 people at risk for lung cancer (adult male cigarette smokers) would be required to establish a 25% reduction in squamous carcinoma of the lung. No intermediate markers of developing lung cancer are presently available to shorten the observation period. It is concluded that a study of the magnitude required is not feasible at the present time.

Adult↗
PubMed1993

Preoperative chemotherapy for stage IIIa (N2) lung cancer: the Sloan-Kettering experience with 136 patients.

From 1984 to 1991, 136 patients with histologically confirmed non-small cell lung cancer and stage IIIa (N2) disease received two to three cycles of MVP (mitomycin + vindesine or vinblastine + high-dose cisplatin) chemotherapy. All patients had clinical N2 disease, defined as bulky mediastinal lymph node metastases or multiple levels of lymph node involvement in the ipsilateral mediastinum or subcarinal space on chest roentgenograms, computed tomographic scans, or mediastinoscopy. The overall major response rate to chemotherapy was 77% (105/136). Thirteen patients had a complete response and 92 patients had a partial but major response (> 50%). The overall complete resection rate was 65% (89/136) with a complete resection rate of 78% (82/105) in patients with a major response to chemotherapy. There was no histologic evidence of tumor in the resected specimens of 19 patients. The overall survival was 28% at 3 years and 17% at 5 years (median, 19 months). For patients who had complete resection, the median survival was 27 months and the 3-year and 5-year survivals were 41% and 26%, respectively. There were seven treatment-related deaths, five of which were postoperative deaths. To date, 33 patients, all of whom had complete resection, have had no recurrence after treatment. These results demonstrate that (1) preoperative chemotherapy with MVP produces high response rates in stage IIIa (N2) disease, (2) high complete resection rates occur after response to chemotherapy, and (3) survival is longest in patients who have a complete resection after major response to chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

The effect of surgical treatment on survival from early lung cancer. Implications for screening.

We assessed the effect of surgery on survival from stage I non-small-cell lung cancer based on data collected in these screening programs. The majority of patients diagnosed in each program were treated by surgical resection, but 5 percent of the Sloan-Kettering group, 21 percent of the Hopkins group and 11 percent of the Mayo group failed to receive surgical treatment. Approximately 70 percent of the stage I patients in each program who were treated surgically survived more than five years, but there were only two five-year survivors among those who did not have surgery. We conclude that patients with lung cancers detected in stage I by chest x-ray film and treated surgically have a good chance of remaining free of disease for many years. Those stage I lung cancers which are not resected progress and lead to death within five years. Therefore, every effort should be made to detect and treat lung cancer early in high-risk populations.

Age Factors↗
PubMed1991

Nonparametric estimation of the size-metastasis relationship in solid cancers.

This paper is concerned with the relationship between the occurrence of metastases and the size of primary cancers. We consider two probabilistic characterizations of this relationship. First is the distribution function of tumor sizes at the point of metastatic transition; second is the probability that detectable metastases are present when the cancer comes to medical attention. The equation relating these two functions is developed and conditions for their being identical are explored. Since the tumor size at the point of metastasis is not usually observable, estimation of the first distribution requires the use of the EM algorithm. Nonparametric methods of estimating both functions are explored, with attention to the fact that tumors often fail to be measured, particularly those that are known to be metastatic. The methods are applied to the estimation of primary tumor size at the point of distant metastasis in lung cancer (epidermoid and adenocarcinoma) and colorectal cancer and at the point of nodal metastasis in breast cancer. Monte Carlo experiments confirm that the bias inherent in the methodology is acceptably small.

Adenocarcinoma↗
PubMed1990

Declining serum cholesterol levels prior to diagnosis of colon cancer. A time-trend, case-control study.

We report the results of a 10-year, time-trend, case-control study in which serum cholesterol level was determined at several points in time preceding the diagnosis of colon cancer in a population of individuals who sought general checkups at an ambulatory care screening facility. Each of the 69 patients with colon cancer (32 men and 37 women) was matched with a control patient who was randomly selected. At the time of diagnosis, the patients with colon cancer had significantly lower serum cholesterol values than control patients (5.56 +/- 0.31 mmol/L [SEM] vs 6.47 +/- 0.34 mmol/L). This difference did not vary with sex or Dukes' stage of the cancer. The percent of matched pairs in which the cancer patient had a lower serum cholesterol level increased from 42% at 10 years prior to cancer diagnosis to 77% at diagnosis. The ratio of serum cholesterol at each period to the level at time of diagnosis demonstrated an average decline of 13% during the 10 years prior to diagnosis for case patients vs an average rise of 2% in the same period for control patients. We conclude that individuals in whom colorectal cancer develops share the same level of serum cholesterol as the general population initially, but during the 10 years preceding the cancer demonstrate a decline in serum cholesterol level that is opposite to the rising level seen with age in the general population.

Aged↗
PubMed1988

Natural history of adenocarcinoma-large cell carcinoma of the lung: conclusions from screening programs in New York and Baltimore.

A mathematical model of the progression kinetics of lung cancer was described and used to shed light on the natural history of adenocarcinoma and large cell carcinoma of lung from data collected in screening studies of male smokers by the Memorial Sloan-Kettering Cancer Center and The Johns Hopkins Medical Institutions. In both programs, estimates of the mean duration of early-stage adenocarcinoma or large cell carcinoma of lung ranged upward from 4 years, and estimates of the probability of detecting it in early-stage disease ranged downward from .16. The probabilities of curing early-stage disease through surgical treatment were found to be at most .52 and .13 in the New York and Baltimore studies, respectively. These estimates led to the conclusion that expected reduction in mortality from adenocarcinoma and large cell carcinoma of lung as due to annual x-ray screening from age 45 to 80 years is not greater than 18% in New York and 5% in Baltimore.

Adenocarcinoma↗
PubMed1987

Detection of lung cancer: highlights of the Memorial Sloan-Kettering Study in New York City.

1. Patients with Stage 1 lung cancer detected by cytology or x-ray, and treated by complete resection, have a high probability of survival. 2. Sputum cytology is effective in early detection of slow growing squamous (epidermoid) carcinomas of lung, which in our population account for less than one-third of cases. Without cytologic screening these cancers would be identified by annual chest x-rays at a later date, though still while localized and resectable. Thus, in a program of annual chest x-rays, conscientiously carried out, the addition of cytologic screening has no statistically significant effect on mortality. 3. Nearly half of all lung cancers in our population are adenocarcinoma, and early detection of these tumors is virtually restricted to the chest x-ray. Fifteen percent of cases are oat cell (small cell anaplastic) carcinoma, and these rapidly developing tumors are almost all discovered in an advanced stage with symptoms. 4. All participants in our study were offered annual chest x-rays, and no direct evaluation of the effect of radiographic screening on lung cancer mortality was possible. However, 40% of all lung cancers were detected in Stage 1, and at least two-thirds of patients with Stage 1 lung cancer treated by complete resection do not die of that disease. The overall five-year survival of patients enrolled in this program who developed lung cancer is 35%, in contrast to 13% for lung cancer in the United States as a whole. Survival at 10 years for all lung cancer patients in this screening program is 25%, and for those with Stage 1 lung cancer it is approximately 65%. 5.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1987

Estrogen receptor protein of breast cancer in patients with positive nodes. High recurrence rates in the postmenopausal estrogen receptor-negative group.

In 448 patients with positive axillary lymph nodes who were treated with mastectomy at Memorial Sloan-Kettering Cancer Center, New York, from 1973 to 1978, estrogen receptor (ER) status was associated with survival. With a median follow-up of 75 months, significant differences were noted in the 288 postmenopausal patients; ER-positive patients had better six-year disease-free survival than ER-negative patients (60% vs 45%), as well as better overall survival. These differences were true in subgroups with one to three and four or more involved nodes. The addition of adjuvant systemic therapy had no significant effect on either ER-positive or ER-negative patients. The need for new imaginative systemic programs in the subgroup of ER-negative postmenopausal patients with breast cancer with positive nodes is apparent.

Axilla↗
PubMed1987

Impact of early detection on the clinical course of lung cancer.

The Memorial Sloan-Kettering Lung Cancer Detection Program is described, and data from this study are reported and analyzed. The program enrolled 10,040 cigarette-smoking men who were screened for at least 5 years by annual chest radiographs; half the men randomly selected also had 4-monthly sputum cytologic examinations. Of the 354 lung cancers that developed in these men during the screening period and a 2-year post-screening period, nearly half were adenocarcinomas and nearly one third were epidermoid (or squamous) carcinomas. Lung cancers detected by screening were more likely to be early stage (53 per cent) and resectable (65 per cent) than were those discovered by other means (for example, symptoms) or in the post-screening period (20 per cent early stage, 32 per cent resectable). Sputum cytology was most effective in detecting squamous carcinomas early; chest radiographs were most effective for detecting adenocarcinoma. However, sputum cytology did not reduce lung cancer mortality among these men who were in a program of annual chest radiographic examinations. Overall 5-year survival for all of the men who developed lung cancer was 35 per cent, compared with the national average of 13 per cent.

Carcinoma↗
PubMed1987

The role of surgery in N2 lung cancer.

Whereas most physicians believe that long-term survival is unlikely when mediastinal lymph node metastases are present, a significant number of these patients do have resectable tumors with encouraging long-term survival results. Data are presented to support this view, and steps identified to guide the physicians in selecting the patients who can benefit from this surgical approach.

Adult↗
PubMed1987

The natural history of lung cancer in a periodically screened population.

A mathematical model of the progression kinetics of lung cancer in a periodically screened population is proposed and data collected by the Memorial Sloan-Kettering Cancer Center in New York are used for parameter estimation. It is assumed that the development of adenocarcinoma of lung is a stochastic process with two stages, early and advanced, characterized by mean times, detection probabilities, and cure probabilities. Confidence regions of these parameters are estimated using a number of novel techniques. It is found, surprisingly, that the mean duration of the early stage is at least 4 years, the detectability less than .2, and the curability less than .5. These estimates imply that annual radiographic screening from age 45 to 80 might decrease mortality from adenocarcinoma of lung by something less than 20%.

Adenocarcinoma↗
PubMed1984

A retrospective analysis of 10-year survivors from carcinoma of the lung.

From 1949 to 1972, 4732 patients with carcinomas of the lung were seen. Of these, 118 patients were found alive at 10 years from their initial diagnosis and treatment. This number represents only 2.5% of all lung cancers seen because many have been lost to follow-up within the first ten years, and their true status is not known. The authors attempted to look at the patient characteristics that might have influenced long-term survival. A case-matched study was also done of patients with carcinoma of the lung who lived less than 2 years and who had the same age, sex, histology, and year of diagnosis. In the long-term survivors, the median age was 57 years, 2 of 3 had epidermoid carcinoma, 86% were smokers, 76% were symptomatic, and 70% had one or both parents alive at age 70 years or older. There was no difference in these variables in the case-matched group. Of the 118 long-term survivors, 91 were men and 27 were women. Sixty-seven percent had Stage I disease, 13% Stage II, and 20% Stage III. None had distant metastasis at presentation. Of the 118 patients, 115 had surgery. Eighteen of the 115 surgically treated patients also had postoperative external radiation. Three patients with Stage III disease received radiation without surgery. None had recurrence of their cancer, 27 developed new cancers, and 70% of these were new lung cancers. Although the majority of the long-term survivors had Stage I cancers, a third had Stage II or III disease. No long-term survivor died of his original disease, suggesting that a 10-year survival is adequate proof of cure in carcinoma of the lung.

Adult↗