Accuracy of basic cancer patient data: results from an extensive recoding survey.

The accuracy of data coded from the medical records of 985 patients from 22 major U.S. cancer centers was checked by recoding during 1978-81. The 29 items covered demographics, diagnosis, and therapy. Original codes were compared to recodes, and disagreements were classified as major or minor. The highest rate of major disagreements, 23%, was for stage of disease, followed by 10% for histology and 7% for site. Major disagreement rates for most other items were under 7%. Only 3% of a large sample of major disagreements involved justifiable differences in interpretation; the others were due to errors in the use of records. Major disagreement rates varied by a factor of 10 across sites, 4 across centers, and 2 across stage of disease. For several items the code "unknown" was overused and led to disagreements. A new procedure is presented for analysis of disagreement rates. The results from this procedure can guide training effort to improve coding accuracy.

U.S. centralized cancer patient data system for uniform communication among cancer centers.

The evolution of the Centralized Cancer Patient Data System, a cooperative venture of the 21 comprehensive cancer centers in the United States, and its structure at the end of 3 years of data collection are described. Functions of the data system are detailed in terms of input and output. It is concluded that the short-run objective of establishing a data system to provide high-quality patient data that ae 21 comprehensive cancer centers in the United States, and its structure at the end of 3 years of data collection are described. Functions of the data system are detailed in terms of input and output. It is concluded that the short-run objective of establishing a data system to provide high-quality patient data that ae 21 comprehensive cancer centers in the United States, and its structure at the end of 3 years of data collection are described. Functions of the data system are detailed in terms of input and output. It is concluded that the short-run objective of establishing a data system to provide high-quality patient data that are comparable among cancer centers has been largely accomplished. Moreover, the very process of setting up the national data system has benefited the participating centers by upgrading their individual cancer registries. For the future, the goal is to realize the research potential of this new cooperative data collection mechanism, as well as the accumulating data themselves. Progress toward the long-term goal is just beginning.

Quality of life end points in cancer clinical trials: review and recommendations.

In this presentation, issues that influenced the development of policies for inclusion of quality of life end points in certain Southwest Oncology Group clinical trials are reviewed. The key policies recommended by us and adopted by the Cancer Control Research Committee of the Southwest Oncology Group are as follows: (a) Begin assessment of quality of life in specific types of phase III protocols. (b) Always measure physical functioning, emotional functioning, symptoms (general and protocol specific), and global quality of life separately. (c) Include measures of social functioning and additional protocol-specific measures if resources permit. (d) Use patient-based questionnaires with psychometric properties that have been documented in published studies. In this review, we also recommend specific questionnaires. Our recommendations may prove useful for other cancer clinical trials groups and for multi-institution trials of treatment for chronic diseases.

Ki-ras mutation and p53 overexpression predict the clinical behavior of colorectal cancer: a Southwest Oncology Group study.

We assessed Ki-ras mutations by single-strand conformation polymorphism followed by DNA sequencing, p53 expression by immunohistochemistry, ploidy status, and S-phase fraction in 66 stage II and 163 stage III colon cancer patients enrolled on a randomized trial of surgery followed by observation or adjuvant levamisole or 5-fluorouracil (5FU) plus levamisole (Intergroup Trial 0035) to see whether these factors were independently associated with survival or with differential effects of adjuvant therapy. A Cox proportional hazards survival model was used to describe marker effects and therapy by marker interactions, with adjustment for the clinical covariates affecting survival. A Bonferroni adjustment was used to account for multiple testing. Mutation of the Ki-ras gene was found in 41% of the cancers and was associated with a poor prognosis in stage II but not stage III. In stage II, 7-year survival was 86% versus 58% in those with wild type versus Ki-ras mutations. After adjustment for treatment and clinical variables, the hazard ratio (HR) for death was 4.5; 95% confidence interval (CI), 1.7-12.1 (P = 0.012). p53 overexpression was found in 63% of cancers and was associated with a favorable survival in stage III but not stage II. Seven-year survival in stage III was 56% with p53 overexpression versus 43% with no p53 expression (HR, 2.2; 95% CI, 1.3-3.6; P = 0.012). Aneuploidy was more common in stage III than in stage II (66 versus 47%; P = 0.009) but was not independently related to survival in either group. The proliferative rate was greater in aneuploid than in diploid cancers but was not related to survival. There was no benefit of adjuvant therapy in stage II nor in any of the stage II subgroups defined by mutational status. In stage III, adjuvant therapy with 5FU plus levamisole improved 7-year survival in patients with wild-type Ki-ras (76 versus 44%; HR, 0.4; 95% CI, 0.2-0.8) and in those without p53 overexpression (64 versus 26%; HR, 0.3; 95% CI, 0.1-0.7). Adjuvant therapy did not benefit those with Ki-ras mutations or p53 overexpression. The effects of adjuvant therapy did not differ according to ploidy status or proliferative rate. Ki-ras mutation is a significant risk factor for death in stage II, and the absence of p53 expression is a significant risk factor for death in stage III colon cancer after adjustment for treatment and clinical covariates. Exploratory analyses suggest that patients with stage III colon cancer with wild-type Ki-ras or no p53 expression benefit from adjuvant 5FU plus levamisole, whereas those with Ki-ras mutations or p53 overexpression do not. An independent study will be required to determine whether response to adjuvant therapy in colon cancer depends on mutational status.

Early detection and control of cancer in clinical practice.

As part of the Community Cancer Care Evaluation, a random-sample survey of practicing physicians in 12 geographic areas was conducted in 1985 to provide information about physician practice patterns with reference to cancer detection, control, and treatment. All respondents were asked whether they routinely performed comprehensive physical examinations, breast palpations, mammography, rectal examinations, chest roentgenography, and stool guaiac examinations on normal healthy patients older than 50 years. Responses were examined in terms of American Cancer Society and National Cancer Institute (Bethesda, Md) recommendations. Conformity with recommendations was dependent on the geographic area, the specific procedure, and the specialty of the physician. Across all procedures, frequency of performance varied with years since graduation from medical school, with more recent graduates more likely to conform to recommended standards.

Chemoprevention of cervical cancer with folic acid: a phase III Southwest Oncology Group Intergroup study.

Several epidemiological reports and experimental investigations have suggested a preventive role for folic acid in the etiology of cervical cancer. The effect of p.o. folic acid supplementation on the natural history of cervical intraepithelial neoplasia (CIN) was evaluated in a multiinstitutional prospective, randomized, double-blind, placebo-controlled trial. Three hundred thirty-one women with biopsy-proven koilocytic atypia, mild CIN, or moderate CIN were randomized to receive oral folic acid (5 mg) or a similar-appearing placebo daily for 6 months following a 1-month run-in placebo period. Colposcopy, Papanicolaou smear, and serum vitamin levels (folate, retinol, alpha-tocopherol, beta-carotene, and retinyl palmitate) were monitored every 3 months. Demographic, medical, dietary, and sexual history data were obtained from personal interviews. The primary end point of the study was improvement in both Papanicolaou smear and colposcopic picture after 3 and 6 months of treatment as compared to the start of treatment. After 6 months of treatment there was no significant difference between the two study groups in the percentage of patients improved. Median serum folate levels in the treatment arm at 3 and 6 months (29.0 and 20.0 micrograms/dl) were significantly higher than those in the placebo arm (7.8 and 7.1 micrograms/dl, respectively). Mean serum levels of retinol, retinyl palmitate, alpha-tocopherol, and beta-carotene did not differ significantly between the two treatment arms. Our data support the conclusion that supplementation with folic acid (5 mg/day) does not enhance the regression of early epithelial abnormalities of the cervix.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of clorazepate (Tranxene) as an anticonvulsant--a pilot study.

Desmethyldiazepam--providing the long-term anticonvulsant effect when diazepam is given orally--is conveniently administered as clorazepate (Tranxene). In this study, clorazepate was compared to phenobarbital as a secondary anticonvulsant in eight ambulatory, adult outpatients. Stable doses of phenytoin were maintained throughout. Drowsiness was present in all on phenobarbital, but there were no clorazepate-related side effects. Seizure control did not differ for each treatment. Addition of common side effects of phenytoin and phenobarbital limited the attained serum levels of each when used together. Clorazepate doses in the 0.56-mg-per-kilogram range gave desmethyldiazepam levels in the 1.0-microgram-per-milliliter range. Induction of metabolism was suggested by falling desmethyldiazepam levels despite increasing doses. Clorazepate is an effective, nontoxic secondary anticonvulsant.

Carbamazepine--a double-blind comparison with phenytoin.

In a double-blind crossover study, carbamazepine and phenytoin were compared as single anticonvulsants in 47 patients with focal and major generalized seizures. Each drug provided superior seizure control in about half the patients, but significantly fewer patients had objective side effects while taking carbamazepine. Neuropsychologic testing showed improved performance in cognitive function and emotional status of patients while and carbamazepine. No hematotoxic complications arose, but vigilant follow-up is advised. Mean serum level of carbamazepine was 9.3 microng per milliliter with a suggested therapeutic range of 8 to 12 microng per milliliter reached by eventual doses of 16 to 20 mg per kilogram. Carbamazepine offers an independent choice of improved seizure control with a possibility of fewer side effects.

Quality of life assessment in Southwest Oncology Group trials.

The Southwest Oncology Group Quality of Life Questionnaire is based on six policy recommendations adopted by the Group: 1. Always measure physical functioning, emotional functioning, symptoms, and global quality of life separately. 2. Include measures of social functioning and additional protocol-specific measures if resources permit. 3. Use patient-based questionnaires. 4. Use categorical rather than visual analogue scales. 5. Select brief questionnaires (not interviews). 6. Select quality of life measures with published psychometric properties. Three additional policy recommendations deal with procedures and issues associated with the assessment of quality of life in a Southwest Oncology Group prostate cancer trial. Communication among investigators and groups can improve access to newly developed QOL measures and assure consistent quality control procedures across cooperative group trials.

Improved three-year disease-free survival in osteogenic sarcoma.

Of 41 consecutive patients with newly diagnosed osteogenic sarcoma admitted to the Children's Orthopedic Hospital and Medical Center in Seattle, Washington, between 1952 and 1977, 19 treated before 1973 did not receive adjunctive chemotherapy (histological group) whereas after 1972 22 have been so treated (chemotherapy group). Chemotherapy consisted primarily of high doses of methotrexate and adriamycin for 16 months after surgical treatment. Patients in the historical group have been observed for a minimum of nine years (six patients) or until death (13 patients). The 13 surviving patients in the chemotherapy group have been followed for a minimum of three years (median five years) and all 12 disease-free patients have been off therapy for between one and a half and five and a half years (median three years). Overall, the chemotherapy group has had a significant increase in both survival (p = 0.03) and disease-free survival (P = 0.02) compared to the historical group. In 35 patients with localised disease at diagnosis, the three-year disease-free survival and the three-year survival rates were 18 per cent and 41 per cent respectively in the historical group, and 67 per cent and 78 per cent (life table estimates) respectively in the chemotherapy group. With adjunctive chemotherapy only one of the seven patients developing pulmonary metastases did so later than nine months after diagnosis. The superior results in the chemotherapy group could not be accounted for by differences in age, sex, presence of metastases at diagnosis, histopathology, location of primary tumour, type of initial or subsequent surgical treatment, or the use of standard or computerised lung tomography. Although the use of historical controls in this study does not exclude other changes as contributing to the observed improvement in outcome, our data support the contention that adjunctive chemotherapy improves both the disease-free survival and the overall survival of patients with osteosarcoma and rarely delays the onset of recurrent or metastatic disease.

Pitfalls in quality-of-life assessment: lessons from a Southwest Oncology Group breast cancer clinical trial.

There is increasing interest in evaluating the impact of cancer treatment and medical intervention on patient quality of life (QOL). This article reports the findings of a substudy that incorporated the Functional Living Index--Cancer in an ongoing adjuvant breast cancer clinical trial sponsored by the Southwest Oncology Group. The companion study had to be terminated prior to the end of the two-armed, randomized trial because of poor reporting rates over time. Problems with missing data items also occurred. Poor reporting rates in this trial motivated several recommendations for conducting QOL assessment in the cooperative group setting: (a) build support for QOL assessment among the group's leadership, (b) involve physicians and oncology nurses in the study design, (c) identify a QOL liaison at each participating institution, and (d) aggressively monitor the quality and timeliness of data submission.

A graphical aid for determining sample size when comparing two independent proportions.

Standard sample size calculations for n, the number of observations per group when comparing two independent proportions, P1 and P2, require the specification of four quantities: P1, one of the two proportions of interest; delta = P2 - P1, the smallest difference which it is important to detect; alpha, the significance level; and beta, the chance of failing to detect a difference as large as delta. In terms of these four quantities, the graphical aid is a series of charts showing isographs of sample size for selected values of n ranging from 35 to 500. The isographs, i.e. curves connecting points of equal sample size, are based on the asymptotic arc sine approximation and are plotted on the grid formed by P1 on the abscissa and delta on the ordinate. Eight separate charts are available for different choices of alpha and beta. These charts are especially useful in situations where the feasible sample size is roughly known, in which case the detectable difference, delta, can be read directly from the graph.

Prostate Cancer Prevention Trial (PCPT) update.

The Prostate Cancer Prevention Trial is an intergroup effort in the USA managed by the Southwest Oncology Group (SWOG) in collaboration with the Eastern Cooperative Oncology Group (ECOG) and the Cancer and Leukemia Group B (CALGB). This 10-year study began approximately 5 years ago and will achieve its primary endpoint in October 2004. At the start of the study, 18,882 men, aged over 55 years, and with normal digital rectal examination (DRE) and serum prostate-specific antigen (PSA) levels of 4.0 ng/ml, a biopsy is recommended. Because of the effect finasteride has on PSA, the PSA value has been indexed to equalize the number of biopsies in both arms. At 7 years all survivors will undergo a sextant biopsy to determine the period prevalence of prostate cancer. The critical assumptions are: (1) finasteride-induced PSA changes result in a simple downward shift; (2) the assessment of adherence is sensitive enough to detect nonadherence affecting PSA level interpretation: (3) factors affecting biopsy loss will be equal in both arms; (4) finasteride does not affect the sensitivity or specificity of DRE on transrectal ultrasound nor the sensitivity of biopsy; (5) bias resulting from transurethral resection of the prostate in benign prostate hyperplasia cases will be negligible.

Reliability of basic cancer patient data.

Pooling patient data from multi-institutional medical chart review occurs commonly in the study of cancer and other diseases. To determine the consistency of reporting among institutions, we presented a test set of 25 standardized medical charts to coders at 18 Comprehensive Cancer Centers and compared their resulting codes. This study measures the reproducibility of coding by different persons, but does not assess the accuracy of the underlying medical record. Among 34 data items, we found high disagreement rates in coding stage of disease (14 per cent) and date of diagnosis (8 per cent). Primary site, histologic type and other key items had good reproducibility (disagreement rates less than or equal to 5 per cent). A number of minor disagreements indicated that detailed distinctions could not be reliably coded from medical charts.

A profile of treatment approaches used at comprehensive cancer centers.

The Centralized Cancer Patient Data System is the system which the 21 comprehensive cancer centers in the U.S. have established in order to report and to analyze demographic, diagnostic, treatment and survival data on all new patients. We propose that this closely monitored standardized 36 item dataset can be used to profile the categories of initial treatment that are given to patients having all types and stages of cancer: the data may be displayed for all centers or used to compare the approaches used at different centers. Differences in the frequency with which surgery, radiation, chemotherapy, and no specific treatment are used for patients having any of three common histologic types of lung cancer serve to illustrate the method. Opportunities now exist to utilize this new resource to study trends in the use of treatment modalities and their relationship to survival, which in turn should enhance the accessibility of treatment information about all patients at cancer centers, rather than only those which are reported from selected treatment protocols. This approach may also be uniquely useful in obtaining treatment and survival information about patients with rare sites or types of cancer.