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C B Begg

Publications and source records attributed to C B Begg.

At least 37 records · Page 2Linked to original sources
PubMed1997

CT detection of retroperitoneal lymph node metastases in patients with clinical stage I testicular nonseminomatous germ cell cancer: assessment of size and distribution criteria.

OBJECTIVE: Patients with nonseminomatous germ cell cancer of the testis with no evidence of metastatic disease after orchiectomy may be managed with either retroperitoneal lymph node dissection or surveillance. The present retrospective study was undertaken to determine the accuracy of CT for revealing retroperitoneal lymph node metastases in patients with newly diagnosed clinical stage 1 testicular nonseminomatous germ cell cancer of the testis when smaller size criteria (smaller than 10 mm) are applied and to test the hypothesis that CT-revealed anterior retroperitoneal lymph nodes are more likely to correlate with metastases than are posterior lymph nodes. MATERIALS AND METHODS: Abdominal CT scans obtained before surgery in 70 patients were reviewed by three observers who were unaware of the results of retroperitoneal lymphadenectomy. The sizes and sites of all lymph nodes measuring larger than or equal to 4 mm were recorded. Each CT scan was judged as positive or negative for retroperitoneal metastasis on the basis of the size of the largest measured lymph node at the expected metastatic site. Diameters of 4, 6, 8, and 10 mm were successively applied to each case as the criteria for a positive scan. RESULTS: Using a criterion of 10 mm or larger for metastases, we calculated a sensitivity of 37% and a specificity of 100%; with a 4-mm criterion, the sensitivity was 93% and the specificity was 58%. Receiver operating characteristic curves comparing the accuracy of CT for revealing similar-sized lymph nodes located anterior or posterior to a line bisecting the aorta differed significantly (p = .04) when the same criteria were applied to lymph nodes in both regions. CONCLUSION: False-negative rates were decreased from 63% using a size criterion of 10 mm to as low as 7% using a size criterion of 4 mm, with a corresponding decrease in specificity. Lymph nodes measuring larger than or equal to 4 mm, especially those located anterior to the mid portion of the aorta, should raise a suspicion of metastases.

Germinoma↗
PubMed1997

A note on the estimation of relative risks of rare genetic susceptibility markers.

The comparison of an incident case series with an incident series of second primary cancers, using either a case-control or follow-up study design, is proposed as an efficient method for evaluating the relative risk of a rare genetic susceptibility marker and its prevalence in the population, and for evaluating gene-environment interactions. The relative efficiency of this design versus a conventional case-control study is highly dependent on the population prevalence of the marker and its relative risk. However, for relatively rare but highly penetrant genes, the relative efficiency can be very high. In an example presented regarding a planned study of the p16 gene and its role in melanoma, a conventional case-control study may require up to 70 times as many subjects to achieve equivalent precision to the study of second primaries. The use of second primary cancers in this way requires assumptions about the validity of the classification of a new tumor as a second primary, the extent to which risk of a second cancer is influenced by treatment of the first cancer, and the nature and extent of surveillance bias. However, the problems of ascertaining a valid series of population controls are avoided. The study of second cancers represents an important and underused tool in molecular and genetic epidemiology.

Bias↗
PubMed1996

The role of meta-analysis in monitoring clinical trials.

The randomized clinical trial is the gold standard methodology for evaluating treatment interventions. The randomized trial is a prospective experimental study, the embodiment of the scientific method applied to the clinic. Both organizational and ethical considerations encourage the use of formal criteria for termination. Such criteria, typically based on an overall 5 per cent significance test, are frequently portrayed as guidelines, but none the less usually succeed in focusing the debate on termination decisions and thus facilitate decision making. The use of the 5 per cent criterion is entirely arbitrary and is not based in any way on optimality considerations. No credible model for optimizing the decision to terminate trials has been developed. Meta-analysis is an evolving technique for evaluating the totality of the evidence on general treatment strategies. It has enjoyed considerable success in influencing medical opinion and treatment practice in selected areas. Its role is in establishing proof of concept of general treatment strategies, and is thus a consensus builder, making use of data from trials which may be heterogeneous in the details of treatment administration and patient selection, but similar in conceptual intent. The level of evidence required for consensus is not well understood and cannot be defined precisely. The retrospective nature of meta-analysis and the risks of biased data acquisition mandate a conservative approach to data analysis and interpretation. Randomized trials and meta-analyses have distinct but complementary goals. Meta-analysis can be used productively in planning new clinical trials, and in supplying updated information to study monitors in the course of a trial. However, it is not advisable to employ meta-analysis in formal statistical procedures for terminating clinical trials.

Bias↗
PubMed1996

Screening for cutaneous melanoma by skin self-examination.

BACKGROUND: Although some evidence indicates that early detection protects against the development of lethal melanoma, no randomized clinical trials have been conducted to measure the efficacy of early detection (or screening) in preventing death from this disease. Since melanoma incidence in the United States is relatively rare, a randomized clinical trial to test the efficacy of screening would be extremely expensive. PURPOSE: As an alternative to a randomized clinical trial, we conducted a population-based, case-control study to investigate whether early detection through skin self-examination (SSE) is associated with a decreased risk of lethal melanoma (includes the presence of advanced disease with distant metastases in addition to death from melanoma). METHODS: SSE (conducting a careful, deliberate, and purposeful examination of the skin) was assessed in all subjects by use of a structured questionnaire and personal interviews. The major exposure variable, SSE, was defined following focus-group interviews with melanoma patients and healthy control subjects. The final study population consisted of 1199 Caucasian residents of the state of Connecticut enrolled from January 15, 1987, through May 15, 1989; 650 individuals were newly diagnosed with cutaneous melanoma, and the remaining 549 individuals were age- and sex-frequency matched control subjects from the general population. During the study interviews, nevi on the arms and backs of subjects were counted. In 5 years of follow-up (through March 1994), 110 lethal cases of melanoma were identified. The study design allowed separate estimation of the impact of SSE on reduced melanoma incidence (primary prevention) and survival among incident cases (secondary prevention). Odds ratios (ORs) were used to measure the associations between SSE and melanoma and between SSE and lethal melanoma. RESULTS: SSE, practiced by only 15% of all subjects, was associated with a reduced risk of melanoma incidence (adjusted OR = 0.66; 95% confidence interval [CI] = 0.44-0.99; comparing case patients with control subjects). The data indicated further that SSE may reduce the risk of advanced disease among melanoma patients (unadjusted risk ratio = 0.58; 95% CI = 0.31-1.11); however, longer follow-up is required to confirm this latter estimate. If both estimates are correct, they suggest, in combination, that SSE may reduce mortality from melanoma by 63% (adjusted OR = 0.37; 95% CI = 0.16-0.84; comparing lethal cases with general population controls). CONCLUSIONS AND IMPLICATIONS: SSE may provide a useful and inexpensive screening method to reduce the incidence of melanoma. SSE may also reduce the development of advanced disease. The results of this study need to be replicated before strategies to increase the practice of SSE are further developed and promoted.

Adult↗
PubMed1996

Role of video-assisted thoracic surgery in the treatment of pulmonary metastases: results of a prospective trial.

BACKGROUND: A retrospective review revealed a 42% error rate between computed tomographic scan reports and thoracotomy findings; therefore, a prospective study was designed to compare the value of computed tomographic scans, video-assisted thoracoscopic exploration, and open thoracotomy in the management of pulmonary metastases. METHODS: Eligibility included any patient with only one or two ipsilateral pulmonary metastases identified on computed tomographic scan who was being considered for surgical resection. Initially video-assisted thoracic surgery was performed and all lesions identified were resected. A thoracotomy adequate for complete lung palpation was then carried out and any additional lesions found were removed. RESULTS: Eighteen patients of a planned 50 were treated before closure of the study. Four patients (22%) had no additional lesions found at thoracotomy. The primary sites of tumor were colon (10), breast (3), and one patient each skin (squamous), cervix, kidney, melanoma, and sarcoma. Four patients (22%) did have additional lesions at thoracotomy, which were benign. In the remaining 10 patients (56%) additional malignant lesions were found at thoracotomy after video-assisted thoracoscopic exploration. After 18 patients were entered, analysis of the early results disclosed a 56% failure rate of a computed tomographic scan and video-assisted thoracic surgery to detect all lesions. Being within the 95% confidence interval (32% to 78%), the study was abandoned. CONCLUSIONS: We conclude that video-assisted thoracic surgery should be used only as a diagnostic tool in managing lung metastasis. A thoracotomy is required to achieve complete resection, which is the major survival prognosticator for satisfactory long-term results.

Breast Neoplasms↗
PubMed1996

Optimal sample size for a series of pilot trials of new agents.

A new approach is presented for determining the appropriate sample sizes for a series of screening trials to identify promising new therapeutic agents. The formulation of the problem is motivated by recognition of the fact that screening of new agents is a continuing process. Consequently, it does not seem ideal to fix the overall total sample size, as previous authors have done. Instead we fix the error rates and optimize the individual sample sizes to minimize the time to identify a promising agent, using an empirical Bayes formulation. When applied to data from the large historical experience of exploratory vaccination trials at Memorial Sloan-Kettering Cancer Center, the method demonstrates that relatively small individual screening trials are optimal in this setting. The reliability of the results is evaluated using bootstrapping techniques.

Bayes Theorem↗
PubMed1995

Methodology for evaluating the incidence of second primary cancers with application to smoking-related cancers from the Surveillance, Epidemiology, and End Results (SEER) program.

The Surveillance, Epidemiology, and End Results (SEER) database is used to estimate the standardized incidence ratios (SIRs) of second primaries for all pairs of smoking-related cancers and to interpret the results in the context of our knowledge of the known effects of smoking on the incidence of each of the individual cancers. In evaluating the simultaneous incidence of two cancers, one must recognize the inherent duality of the two relevant SIRs linking the two cancers (e.g., A and B), namely, the SIRs of A following B and B following A. Under fairly general assumptions, the two SIRs are seen to be equal, and departures from equality suggest changes in risk status or the introduction of new risk factors after the incidence of the first primary. Based on these observations, a methodological strategy is developed. The data reveal several clear patterns. First, short-term incidence is uniformly much greater than long-term incidence. Second, the SIRs are consistently much higher for women than for men, for every pair of cancers studied. Third, the magnitudes of the SIRs are generally high and often substantially higher than would be expected on the basis of the known risks of smoking. Exceptionally high SIRs are observed between kidney and bladder cancer and between head and neck and esophageal cancer. Various influences may affect these high observed SIRs, including artifactual influences such as diagnostic, surveillance, and misclassification biases, and the effect of different exposure prevalences on subsequent SIRs, which may to some extent explain the strong sex differences. However, these artifacts do not appear to explain the magnitude of the observed SIRs, especially the very strong associations between kidney and bladder cancer and between head and neck and esophageal cancer. It seems likely that other factors play a role, including, possibly, host susceptibility factors or additional common risk factors other than smoking. Although multiple primary cancers are rare, they represent an especially fruitful population for detailed epidemiologic study.

Evaluation Studies as Topic↗
PubMed1994

Is Trichomonas vaginalis a cause of cervical neoplasia? Results from a combined analysis of 24 studies.

BACKGROUND: We conducted this combined analysis of available data from studies with information on this issue to clarify the association between Trichomonas vaginalis infection and cervical neoplasia. METHODS: We performed MEDLINE searches (1966-1993) using the key words and phrases 'trichomonas vaginitis' and 'neoplasms, cervix' for articles published in English, and searched citations of the articles obtained from MEDLINE: A total of 24 articles (two cohort studies and 22 case-control) were included in this data analysis. In the analysis, the studies were evaluated for heterogeneity using Breslow-Day tests for homogeneity of the odds ratios and of rate ratios. If the odds ratios from studies are heterogeneous, it is not appropriate to combine them using the Mantel-Haenszel method. Also, publication bias was evaluated by assessing the association between the observed effect size and the variance of the effect size using a rank correlation test. RESULTS: The combined summary relative risk for the two cohort studies was 1.93 (95% confidence interval: 1.22-2.65) indicating an approximate doubling of the risk of cervical neoplasia in the presence of T. vaginalis infection. The attributable risks among exposed subjects and among the source population were 47.4% and 2.1% respectively. Results of the 22 retrospective studies were much less consistent. However, most of them demonstrated a significant positive association. CONCLUSIONS: This combined analysis suggests that there is an association between T. vaginalis and the risk of cervical neoplasia, but that such infections account for only 2% of cervical neoplasia.

Adolescent↗
PubMed1994

ROC curve regression analysis: the use of ordinal regression models for diagnostic test assessment.

Diagnostic tests commonly are characterized by their true positive (sensitivity) and true negative (specificity) classification rates, which rely on a single decision threshold to classify a test result as positive. A more complete description of test accuracy is given by the receiver operating characteristic (ROC) curve, a graph of the false positive and true positive rates obtained as the decision threshold is varied. A generalized regression methodology, which uses a class of ordinal regression models to estimate smoothed ROC curves has been described. Data from a multi-institutional study comparing the accuracy of magnetic resonance (MR) imaging with computed tomography (CT) in detecting liver metastases, which are ideally suited for ROC regression analysis, are described. The general regression model is introduced and an estimate for the area under the ROC curve and its standard error using parameters of the ordinal regression model is given. An analysis of the liver data that highlights the utility of the methodology in parsimoniously adjusting comparisons for covariates is presented.

Algorithms↗
PubMed1994

Operating characteristics of a rank correlation test for publication bias.

An adjusted rank correlation test is proposed as a technique for identifying publication bias in a meta-analysis, and its operating characteristics are evaluated via simulations. The test statistic is a direct statistical analogue of the popular "funnel-graph." The number of component studies in the meta-analysis, the nature of the selection mechanism, the range of variances of the effect size estimates, and the true underlying effect size are all observed to be influential in determining the power of the test. The test is fairly powerful for large meta-analyses with 75 component studies, but has only moderate power for meta-analyses with 25 component studies. However, in many of the configurations in which there is low power, there is also relatively little bias in the summary effect size estimate. Nonetheless, the test must be interpreted with caution in small meta-analyses. In particular, bias cannot be ruled out if the test is not significant. The proposed technique has potential utility as an exploratory tool for meta-analysts, as a formal procedure to complement the funnel-graph.

Bias↗
PubMed1994

Methodological issues in studies of the treatment, diagnosis, and etiology of prostate cancer.

Clinical and epidemiological research on prostate cancer is faced with some unusual methodological challenges. The very high prevalence of latent cancer, much of which never becomes clinically manifest, complicates the approach to screening and the conduct of epidemiological studies. Cost-effectiveness issues are especially relevant regarding screening policies, and these trade-offs are complicated by the absence of definitive results on the effectiveness of the various treatment options. The presentation of advanced disease is also unusual, in that the vast majority of patients do not have measurable disease suitable for traditional studies of new chemotherapy agents. These problems necessitate creative approaches to the design and analysis of research studies in this disease: cost-effectiveness analysis is crucial to the evaluation of screening policies; opportunistic designs will be essential to the valid study of cancer etiology, eg, the use of cystoprostatectomy series for studies of epidemiologic risk factors; and posttreatment changes in PSA levels may be valuable as a criterion for screening new agents in advanced disease. Regardless of these new methods, traditional methodological approaches are essential to the valid study of prostate cancer. Randomization is required for valid comparison of treatments and screening strategies. Statistical analysis should observe the intent-to-treat principle whereby patient groups are analyzed with respect to the planned, rather than the delivered therapy, and studies should have sufficiently large sample sizes to reliably distinguish the true effects of the interventions from random statistical fluctuation. Recently, meta-analysis has become popular as a tool for synthesizing the information from available studies on a specific clinical problem. Its most conspicuous success has been in showing the efficacy of adjuvant therapy in breast cancer, for which many individual studies appeared to give conflicting results.64 In this setting there was a large number of published randomized trials, many of which had large sample sizes and long follow-up, and so the meta-analysis was able to show convincingly a small but clinically meaningful treatment effect on long-term disease recurrence and survival. This is similar to the situation in localized prostate cancer in all respects except for the availability of randomized trials. Unfortunately there is no free lunch. This technique can only be applied if the high quality data are available. One must be similarly cautious in applying decision analytic techniques (and also cost-effectiveness analysis) to try to resolve clinical dilemmas.(ABSTRACT TRUNCATED AT 400 WORDS)

Clinical Trials as Topic↗
PubMed1994

Statistical analysis of molecular epidemiology studies employing case-series.

The case-series design is being used increasingly to explore associations between environmental risk factors and genetic markers. It is demonstrated that the odds ratio derived from a case-series study is the ratio of the relative risk for developing marker-positive disease to the relative risk for developing marker-negative disease. This parameter is an empirical manifestation of etiological heterogeneity with respect to the risk factor under study, and it can be used to construct a statistical significance test. Presence of etiological heterogeneity, as reflected in departures of this parameter from unity, could be a result of either the presence of distinct causal mechanisms for the two categories of cases, or a different strength of effect via the same mechanism. The case-series approach represents an efficient and valid approach for evaluating gene-environment associations, especially in referral centers where it is difficult to identify a valid control group.

Biomarkers, Tumor↗
PubMed1993

Age and Hodgkin's disease: the impact of competing risks and possibly salvage therapy on long term survival: an E.C.O.G. study.

A detailed review of factors associated with survival was carried out in a cohort of 560 patients treated in two successive E.C.O.G. studies on advanced Hodgkin's disease. The study was undertaken to explore the impact of age on survival and to attempt to identify reasons for any observed differences. Data from two E.C.O.G. studies of patients with advanced Hodgkin's disease were examined separately and then pooled together. A special data request form was developed to capture additional information on treatments utilized for patients who were treated at relapse. The complete remission percentages were identical in both studies (72%) with no significant difference between the three age groupings (< 40, 40-59, and > 60 yr). This was true as well for disease-free survival. Nevertheless, overall survival was significantly better for the under aged 40 group and this difference was narrowed but not eliminated by competing risks. Our analysis of salvage therapy revealed a marginally significant difference in the CR% between the three groups, favoring the youngest cohort (< age 40 yr). The identical remission rate is probably a reflection of the entry criteria eliminating poor risk patients. Among the small number of patients who received radiation therapy, the response rate was 75% (9/12) in the young cohort. Elderly patients appeared to receive less salvage therapy and certainly fewer responses. Survival after relapse showed a similar pattern with the best survival in the youngest group of patients followed closely by the 40-59 yr group, with a poor outcome for those over age 60 yr. We conclude that a variety of conditions, both age and non-age dependent, impact on the survival of patients with advanced Hodgkin's disease who fulfill the rigid criteria for entry into cooperative group trials.

Adult↗
PubMed1991

Advances in statistical methodology for diagnostic medicine in the 1980's.

Research on diagnostic medicine has been directed at a number of topics in the past decade. Issues which have received a lot of attention are ROC analysis and the identification and correction of various analytic biases. Other topics of widespread interest include the use of expert systems, the relationship of such systems to statistical data-based systems, and the evaluation of tests using cost-effectiveness analysis. Increasingly there is a sentiment that well-designed, prospective trials are required to provide credible information on the accuracy of diagnostic technologies, and so a consensus on methodological standards is needed, paralleling the earlier development of such standards in clinical trials and epidemiology.

Data Interpretation, Statistical↗
PubMed1991

The effect of local control on metastatic dissemination in carcinoma of the prostate: long-term results in patients treated with 125I implantation.

The study evaluates the effect of the locally recurring tumor on the incidence of metastatic disease in early stage carcinoma of the prostate. The probability of distant metastases was studied in 679 patients with Stage B-C/N0 carcinoma of the prostate treated at MSKCC between 1970 and 1985 (median follow-up of 97 months). Patients were staged with pelvic lymph node dissection and treated with retropubic 125I implantation. The actuarial distant metastases free survival (DMFS) for patients at risk at 15 years after initial therapy was 37%. Cox proportional hazard regression analysis of covariates affecting the metastatic outcome showed that local failure, used in the model as a time dependent variable, was the most significant covariate, although stage, grade, and implant volume were also found to be independent variables. The relative risk of metastatic spread subsequent to local failure was 4-fold increased compared to the risk without evidence of local relapse. The 15-year actuarial DMFS in 351 patients with local control was 77% compared to 24% in 328 patients who developed local relapses (p less than 0.00001). The relation of distant spread to the local outcome was observed regardless of stage, grade, or implant dose. Even stage B1/N0-Grade I patient with local control showed a 15-year actuarial DMFS of 82%, compared to 22% in patients with local relapse; p less than 0.00001). The median local relapse-free survival (LRFS) in the 268 patients with local recurrences who did not receive hormonal therapy before distant metastases were detected was 51 months, compared to a median of 71 months for DMFS in the same patients (p less than 0.001), consistent with the possibility that distant dissemination may develop secondary to local failure. Furthermore, distant metastases in patients with local control, apparently already existing as micrometastases before treatment, were detected earlier (median DMFS of 37 months) than in patients with local relapse (median DMFS of 54 months; p = 0.009). These data suggest that the existence and re-growth of local residual disease in localized prostatic carcinoma promotes an enhanced spread of metastatic disease, and that early and complete eradication of the primary tumor is required if a long term cure is to be achieved, although the clinical expression of secondary metastases may not become apparent for 6.5 years or more in one-half of the patients.

Adenocarcinoma↗
PubMed1991

A model for incorporating historical controls into a meta-analysis.

A method is presented for estimating the treatment effect in a meta-analysis when some of the studies are comparative studies, and the rest are noncomparative, historical control studies. A random-effects model is used in which the baseline effect in each study is random, but the treatment effect is constant. With this model the appropriate contribution of the historical studies can be determined. Extensions of the model are developed to accommodate preliminary tests for bias, and for the possibility that the treatment effect is heterogeneous.

Analysis of Variance↗