We determined the influence of the extent of disease on bone scan, serum testosterone, patient age, performance status, method of initial diagnosis, Gleason grade, clinical stage at diagnosis, serum acid phosphatase, serum prostate specific antigen (PSA) and primary hormonal treatment on survival. The clinical and hormonal data were obtained when the presence of metastatic disease was established and treatment was to be initiated in 162 men with metastatic prostate cancer. Mean followup was 16 months (range 1 to 105 months). A total of 70 men (43.2%) died of the metastatic disease during the evaluation period. Log rank analysis revealed that only serum testosterone (p = 0.035) and extent of disease on bone scan (p = 0.003) significantly affected over-all survival. A trend (p = 0.068) towards decreased survival was observed with increasing values of PSA. Increasing values of acid phosphatase positively correlated with extent of disease on bone scan but was not a significant independent prognostic factor. Patient age, performance status, clinical stage, method of initial diagnosis, Gleason grade and type of hormonal treatment did not significantly influence survival. Upon using multivariate Cox analysis, only extent of disease on bone scan was significantly correlated with over-all survival (p less than 0.014). PSA may also be influential but longer duration of followup will be necessary. We conclude that extent of disease on bone scan is the most important prognosticator of the analyzed factors and that serum testosterone may be of value.
Lifetable survival curves have been adapted to measure "time to second primary" and used to compare incidence of second primary in all patients in the Alberta Cancer Registry with a primary malignancy in cervix, endometrium and ovary. Comparisons were also obtained within each diagnostic category between patients treated or not treated with radiation. Results show that there are no statistically significant differences in the 25 years following diagnosis of the first primary in "time to second primaries" in patients with cancer of the cervix, endometrium or ovary. Similarly, within each diagnostic category, there are no differences between radiation treated patients and those not treated by radiation, when adjustments for age differences are made and when patients are selected by length of survival.
Of 2231 women with stage I, II or III breast cancer who were registered and seen between 1971 and 1979 and followed to the end of 1981, 48 (2.2%) had synchronous and 58 (2.6%) asynchronous bilateral breast cancer. The unadjusted incidence rate for a second breast cancer was 6.4/1000 breast-years at risk, compared with a rate of 0.70 for the risk of a first breast cancer in women. When calculated from the date of diagnosis of the first breast cancer the survival rate was better for the group with asynchronous disease than for the group with synchronous disease or for a group with unilateral disease, but when calculated from the date of diagnosis of the second cancer the rate was the same in all three groups. Comparison of known risk factors showed a significant association between the development of bilateral cancer and a later age at the birth of the first child and a longer interval between menarche and that birth. There was a trend towards greater age and more stage III cancer in the group with synchronous disease. There was no correlation between receiving radiotherapy for the first breast cancer and development of the second cancer. Annual mammography and clinical examination of asymptomatic women at a cancer centre resulted in the detection of a significantly higher proportion of minimal breast cancers in the second breast compared with the first. Such screening practices should be even more valuable in the earlier detection of unilateral breast cancer in asymptomatic women who have not had breast cancer.
Analysis of data from 643 breast cancer patients seen between 1971 and 1973 in northern Alberta was undertaken as a preliminary study leading towards a comprehensive breast registry. Age at first treatment and menopausal status were found to be related significantly to the clinical stage of the disease. Other data reported included age at menarche, lymph node involvement and methods of primary treatment. A decline in use of the radical mastectomy was noted. The comprehensive breast registry, which will be used to identify high-risk groups, assess treatment modalities, test hypotheses and generate ideas, has a high probability of success because of compulsory registration of new cases of breast cancer in Alberta and collection of data by the same four individuals.
A review was conducted of 660 cases of cancer of the bladder diagnosed in two periods, 1960--62 and 1968--70. A significant increase in the incidence of bladder cancer in both sexes, paralleling the trends in other parts of North America, was found. During the second period the disease was diagnosed earlier and, once diagnosed, was apparently treated more successfully. Overall 5-year survival rates increased from 57% to 70% for patients with stage O or A disease, but were relatively constant, at about 36%, for patients with stage B1 or B2 disease. The survival rate for patients with stage O or A disease appeared to improve without clearly defined changes in treatment. Prospective randomized treatment trials are needed to properly assess the value of definitive and adjunctive methods of treatment.
OBJECTIVES: This study was conducted to provide a review of the prognostic factors of tonsillar carcinoma. DESIGN: A retrospective analysis. SETTING/PATIENTS: Patients with squamous cell carcinoma of the tonsil, treated in Northern Alberta, at the Cross Cancer Institute from 1975 to 1995 were analyzed using a population-based, head and neck cancer registry. There were 102 patients, 73 male and 29 female, ranging in age from 35 years to 83 years, with a mean of 60 years. The clinical stages were T1: 5 patients; T2: 27 patients, T3: 33 patients; T4: 11 patients; and Tx: 3 patients. The nodal stages were N0: 33 patients, N1: 26 patients; N2: 34 patients, N3: 7 patients; Nx: 2 patients. METHOD: The patients were treated with various modalities: surgery alone: 2 patients; surgery plus radiation: 26 patients; radiation treatment alone: 61 patients; and others: 13 patients. Patients were classified according to the UICC TNM 1992 criteria. The overall 5-year Kaplan-Meier survival in our series was 39%. The cause-specific 4-year survival was 57%. Various prognostic factors and their impact on survival were studied. RESULTS: On univariate analysis, the following factors were found to be significant. Age 50 (p = .02); endophytic growth pattern vs. exophytic growth of the primary (p = .01); ulcerated lesions vs. nonulcerated lesions (p = .000); various T stages (p = .003); clinical extension vs. no extension of primary disease (p = .02); combined modality of treatment (surgery and radiation treatment) had the best chance of survival compared to radiation treatment alone (p = .03). Nodal stages N0 vs. N+ disease (p = .2); sex of the patient, female vs. male (p = .83); and dose of radiation treatment 5000 cGy (p = .41) were found not to be significant. When the above significant factors were stratified according to the stage of the disease, only two were significant; ulcerated lesions vs. nonulcerated lesions (p = .04), and the modality of treatment chosen (e.g., radiation alone vs. radiation plus surgery) (p = .02). CONCLUSIONS: In this series of patients, combined-modity approach using surgery and radiation treatment was found to be the best way to treat carcinoma of the tonsil. However, each treatment strategy should be individualized taking into account various prognostic factors.
In a prospective open study, 61 consecutive patients with terminal cancer admitted to the hospital underwent cognitive assessment using the Mini-Mental State Questionnaire three times a week between admission and discharge or death. Mini-Mental State Questionnaire score upon admission was 28 +/- 1.5 in patients who were discharged (N = 14), and 25 +/- 3 in patients who died in the hospital (N = 47, P less than 0.01). The forty-seven patients who died in the hospital presented a total of 66 episodes of cognitive failure (CF) that were defined as a score of less than 24 or a drop of greater than 30% in the score on the Mini-Mental State Questionnaire. Of these 47 patients, 39 (83%) presented CF an average of 16 days before death. Upon detection of CF, a complete medical examination, laboratory evaluation, computerized tomography of the brain if indicated by abnormal findings on medical examination, and a complete medication review were performed. The cause of CF could not be established in 37 (56%) cases. Drugs, sepsis, and brain metastasis were the most frequently detected causes and were present in 6, 4, and 4 cases, respectively. In addition, 22 episodes (33%) of CF improved (10 episodes spontaneously and 12 episodes as a result of treatment). Our findings suggest that CF is extremely prevalent during the last weeks of life and, consequently, informed consent for therapeutic or research procedures or resuscitation may be impossible to obtain reliably at that stage.
Drawing upon the comprehensive population-based Northern Alberta Breast Cancer Registry containing 704 patients with histologically negative axillary lymph nodes who have been followed for 5-16 years, we have undertaken a retrospective case-control study to evaluate the utility of genomic amplification of specific protooncogenes [c-erbB-2 (nee HER-2/neu), c-erbA, c-myc, int-2, and hst-1] as predictive indicators of clinical outcome in node-negative disease. To this end, 115 women with node-negative breast cancer who had recurred at any time up to 16 years posttreatment (cases) were matched pairwise for appropriate clinicopathological variables (size of primary tumor, menopausal state, estrogen receptor status, anniversary year of treatment, and patient age) with a second group of 115 women (controls) selected from a cohort of 502 node-negative patients who had not relapsed during long-term follow-up. Tumor DNA extracted from archival formalin-fixed, paraffin-embedded tissue blocks were analyzed for protooncogene copy number by slot-blot hybridization. Taking a gene copy number of 3 as the cutoff, 27 of the 230 tumor samples examined contained from 3- to 22-fold elevation in c-erbB-2 genomic equivalents. Twenty-one of the 27 tumors amplified for c-erbB-2 were derived from cases and 6 from controls, signifying that 18% of the node-negative patients who had relapsed harbored excessive copies of the protooncogene in their malignant tissue compared to only 5% for the patients who had remained in remission. Accordingly, the occurrence of amplification of c-erbB-2 proved to be a statistically significant predictor of poor prognosis, especially disease-free interval (P = 0.006). Moreover, this genetic alteration appeared to be independent of and to have greater predictive power than most commonly used prognostic factors. Our findings also indicated that as a clinical test, measurement of c-erbB-2 amplification suffers from low sensitivity; however, when greater than 6 gene copies are present, the test has a positive predictive value for recurrence of 70%. Concurrent analysis of tumor DNA blots with probes for the other four protooncogenes examined revealed that their amplification, which others have reported to arise often, especially in node-positive disease, was seldom found even in our high-risk case group (2-3%). In short, our data strongly suggest that amplification of c-erbB-2 may contribute to the pathogenesis of some forms of node-negative breast cancer and thus may serve as a useful genetic marker to identify a subset of high-risk patients.