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C B Begg

Publications and source records attributed to C B Begg.

At least 19 recordsLinked to original sources
PubMed2000

Influence of hospital procedure volume on outcomes following surgery for colon cancer.

CONTEXT: Survival following high-risk cancer surgery, such as pancreatectomy and esophagectomy, is superior at hospitals where high volumes of these procedures are performed. Conflicting evidence exists as to whether the association between hospital experience and favorable health outcomes also applies to more frequently performed operations, such as those for colon cancer. OBJECTIVE: To determine whether hospital procedure volume predicts survival following colon cancer surgery. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of data from the Surveillance, Epidemiology and End Results-Medicare linked database on 27 986 colon cancer patients aged 65 years and older who had surgical resection for primary adenocarcinoma diagnosed between 1991 and 1996. MAIN OUTCOME MEASURES: Thirty-day postoperative mortality and overall and cancer-specific long-term survival, by hospital procedure volume. RESULTS: We found small differences in 30-day postoperative mortality for patients treated at low- vs high-volume hospitals (3. 5% at hospitals in the top-volume quartile vs 5.5% at hospitals in the bottom-volume quartile). However, the correlation was statistically significant and persisted after adjusting for age at diagnosis, sex, race, cancer stage, comorbid illness, socioeconomic status, and acuity of hospitalization (P<.001). The association was evident for subgroups with stage I, II, and III disease. Hospital volume directly correlated with survival beyond 30 days and also was not attributable to differences in case mix (P<.001). The association between hospital volume and long-term survival was concentrated among patients with stage II and III disease (P<.001 for both). Among stage III patients, variation in use of adjuvant chemotherapy did not explain this finding. CONCLUSION: Our data suggest that hospital procedure volume predicts clinical outcomes following surgery for colon cancer, although the absolute magnitudes of these differences are modest in comparison with the variation observed for higher-risk cancer surgeries.

Adenocarcinoma↗
PubMed2000

Comparing tumour staging and grading systems: a case study and a review of the issues, using thymoma as a model.

We consider the problem of comparing alternative cancer staging and grading systems. Statistical comparisons are on the basis of the ability to predict survival, but more qualitative criteria, such as parsimony, and distinctive prognostic separability of the categories are relevant also. Furthermore, some staging systems are clearly ordinal, while others are not. Three candidate statistical measures are studied and compared: explained variation; area under the ROC curve; and the probability of concordance of stage and survival. Each of these has individual strengths and weaknesses. A data set involving the staging of thymoma is analysed in detail to motivate the problem and illustrate the results.

Classification↗
PubMed1999

Racial differences in the treatment of early-stage lung cancer.

BACKGROUND: If discovered at an early stage, non-small-cell lung cancer is potentially curable by surgical resection. However, two disparities have been noted between black patients and white patients with this disease. Blacks are less likely to receive surgical treatment than whites, and they are likely to die sooner than whites. We undertook a population-based study to estimate the disparity in the rates of surgical treatment and to evaluate the extent to which this disparity is associated with differences in overall survival. METHODS: We studied all black patients and white patients 65 years of age or older who were given a diagnosis of resectable non-small-cell lung cancer (stage I or II) between 1985 and 1993 and who resided in 1 of the 10 study areas of the Surveillance, Epidemiology, and End Results (SEER) program (10,984 patients). Data on the diagnosis, stage of disease, treatment, and demographic characteristics of the patients were obtained from the SEER data base. Information on coexisting illnesses, type of Medicare coverage, and survival was obtained from linked Medicare inpatient-discharge records. RESULTS: The rate of surgery was 12.7 percentage points lower for black patients than for white patients (64.0 percent vs. 76.7 percent, P<0.001), and the five-year survival rate was also lower for blacks (26.4 percent vs. 34.1 percent, P<0.001). However, among the patients undergoing surgery, survival was similar for the two racial groups, as it was among those who did not undergo surgery. Furthermore, analyses in which adjustments were made for factors that are predictive of either candidacy for surgery or survival did not alter the influence of race on these outcomes. CONCLUSIONS: Our analyses suggest that the lower survival rate among black patients with early-stage, non-small-cell lung cancer, as compared with white patients, is largely explained by the lower rate of surgical treatment among blacks. Efforts to increase the rate of surgical treatment for black patients appear to be a promising way of improving survival in this group.

Aged↗
PubMed1999

Phase III multicenter randomized trial of the Dartmouth regimen versus dacarbazine in patients with metastatic melanoma.

PURPOSE: Several single-institution phase II trials have reported that the Dartmouth regimen (dacarbazine, cisplatin, carmustine, and tamoxifen) can induce major tumor responses in 40% to 50% of stage IV melanoma patients. This study was designed to compare the overall survival time, rate of objective tumor response, and toxicity of the Dartmouth regimen with standard dacarbazine treatment in stage IV melanoma patients. PATIENTS AND METHODS: In this multicenter phase III trial, 240 patients with measurable stage IV melanoma were randomized to receive the Dartmouth regimen (dacarbazine 220 mg/m(2) and cisplatin 25 mg/m(2) days 1 to 3, carmustine 150 mg/m(2) day 1 every other cycle, and tamoxifen 10 mg orally bid) or dacarbazine 1, 000 mg/m(2). Treatment was repeated every 3 weeks. Patients were observed for tumor response, survival time, and toxicity. RESULTS: Median survival time from randomization was 7 months; 25% of the patients survived > or = 1 year. There was no difference in survival time between the two treatment arms when analyzed on an intent-to-treat basis or when only the 231 patients who were both eligible and had received treatment were considered. Tumor response was assessable in 226 patients. The response rate to dacarbazine was 10.2% compared with 18.5% for the Dartmouth regimen (P =.09). Bone marrow suppression, nausea/vomiting, and fatigue were significantly more common in the Dartmouth arm. CONCLUSION: There was no difference in survival time and only a small, statistically nonsignificant increase in tumor response for stage IV melanoma patients treated with the Dartmouth regimen compared with dacarbazine. Dacarbazine remains the reference standard treatment for stage IV melanoma.

Adult↗
PubMed1999

Staging of malignant pleural mesothelioma: comparison of CT and MR imaging.

OBJECTIVE: This article compares the accuracy of CT with that of MR imaging in staging of malignant pleural mesothelioma. SUBJECTS AND METHODS: Ninety-five patients were enrolled in a prospective staging protocol based on the International Mesothelioma Interest Group staging system. Sixty-five patients underwent CT and MR imaging and a surgical procedure (excluding percutaneous needle biopsy) to stage and resect the tumor. Receiver operating characteristic analyses were performed. CT and MR scans were interpreted independently by observers who were unaware of the results of the other imaging study; these imaging findings were compared with the results of surgery and pathologic examination. RESULTS: The areas under the receiver operating characteristic curves for eight of 10 features revealed by imaging showed no statistically significant differences between CT and MR imaging. However, MR imaging was superior to CT in revealing invasion of the diaphragm (A(z) = .55 for CT versus .82 for MR imaging) and in revealing invasion of endothoracic fascia or solitary resectable foci of chest wall invasion (A(z) = .46 for CT; A(z) = .69 for MR imaging). Several anatomic regions could not be evaluated because positive findings at surgery were rare. CONCLUSION: CT and MR imaging are of nearly equivalent diagnostic accuracy in staging malignant pleural mesothelioma. MR imaging is superior to CT in revealing solitary foci of chest wall invasion and endothoracic fascia involvement and in showing diaphragmatic muscle invasion; however, this advantage does not affect surgical treatment. For cost reasons, CT should be considered the standard diagnostic study before therapy.

Adult↗
PubMed1998

Impact of hospital volume on operative mortality for major cancer surgery.

CONTEXT: Hospitals that treat a relatively high volume of patients for selected surgical oncology procedures report lower surgical in-hospital mortality rates than hospitals with a low volume of the procedures, but the reports do not take into account length of stay or adjust for case mix. OBJECTIVE: To determine whether hospital volume was inversely associated with 30-day operative mortality, after adjusting for case mix. DESIGN AND SETTING: Retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database in which the hypothesis was prospectively specified. Surgeons determined in advance the surgical oncology procedures for which the experience of treating a larger volume of patients was most likely to lead to the knowledge or technical expertise that might offset surgical fatalities. PATIENTS: All 5013 patients in the SEER registry aged 65 years or older at cancer diagnosis who underwent pancreatectomy, esophagectomy, pneumonectomy, liver resection, or pelvic exenteration, using incident cancers of the pancreas, esophagus, lung, colon, and rectum, and various genitourinary cancers diagnosed between 1984 and 1993. MAIN OUTCOME MEASURE: Thirty-day mortality in relation to procedure volume, adjusted for comorbidity, patient age, and cancer stage. RESULTS: Higher volume was linked with lower mortality for pancreatectomy (P=.004), esophagectomy (P<.001), liver resection (P=.04), and pelvic exenteration (P=.04), but not for pneumonectomy (P=.32). The most striking results were for esophagectomy, for which the operative mortality rose to 17.3% in low-volume hospitals, compared with 3.4% in high-volume hospitals, and for pancreatectomy, for which the corresponding rates were 12.9% vs 5.8%. Adjustments for case mix and other patient factors did not change the finding that low volume was strongly associated with excess mortality. CONCLUSIONS: These data support the hypothesis that when complex surgical oncologic procedures are provided by surgical teams in hospitals with specialty expertise, mortality rates are lower.

Aged↗
PubMed1997

Planning controlled clinical trials. Prostatic cancer.

OBJECTIVE: To address principles in the design and conduct of clinical trials on prostate cancer (PC) with special reference to localized disease. METHODS: In advance of and during the World Health Organization (WHO) conference on Prostate Cancer in Stockholm in September 1996, 6 members of a working group evaluated and reached consensus on key points for the planning and conduction of controlled clinical trials in PC. The key points discussed were 1) hypothesis formulation, 2) general methodological principles, 3) special problems of PC trials, 4) alternatives to randomization, and 5) trial organization. RESULTS: The hypothesis must be clearly formulated and also clinically relevant enough to justify the expenses (in a broad sense) of a randomized clinical trial. Patient selection, definition of endpoints, and sample size calculations must be carefully considered and correspond to the aims of the study. Stratification on important prognostic factors should be contemplated. Maintaining the accrual rate and ensuring compliance are critical for a quality study. Survival is the main endpoint and intention to treat analysis is the standard methodology. Secondary endpoints (eg, quality of life and costs) are important for the evaluation of many treatment modalities. The use of surrogate endpoints for survival, such as prostate-specific antigen (PSA) elevation, may be misleading. Surrogate endpoints require further validation. Special features, such as long natural history in localized disease and difficulties in assessing objective responses in advanced disease, need consideration in PC trials. The controlled randomized trial is the gold standard methodology. Nonrandomized trials are often hampered by severe methodological problems, such as selection bias and biased ascertainment of endpoints due to the doctor's or patient's preferences. For the organization of a successful trial, a well-constructed study protocol is essential. Good clinical practice as defined within the European Community helps define and solve practical problems. CONCLUSIONS: The past 30 years of poorly designed clinical research on PC has left us without reliable answers in key clinical issues regarding, for example, the efficacy of primary treatment of localized PC. It is a stimulating and important challenge to the urological scientific community to conduct well-organized controlled clinical trials.

Controlled Clinical Trials as Topic↗
PubMed1997

The indications, rationale, and results of neoadjuvant androgen deprivation in the treatment of prostatic cancer: Memorial Sloan-Kettering Cancer Center results.

OBJECTIVES: The use of neoadjuvant chemotherapy prior to definitive surgery has been firmly established in other areas of oncology, most notably in the treatment to testis and Wilm's tumors. The use of neoadjuvant androgen deprivation therapy (ADT) in conjunction with radical prostatectomy remains a source of controversy. We have conducted phase II and phase III studies to assess the effects of 3 months of preoperative ADT (goserelin and flutamide) on the pathologic staging and postsurgery prostate-specific antigen (PSA) relapse rate. We also reviewed the data confirming the understaging of clinically localized prostatic cancer and the experimental data providing the conceptual support for ADT. METHODS: We report the results of 141 patients, Stage T0-T0, in a Phase II study with concurrent, nonrandomized controls (N = 72) versus a treatment arm (N = 69) of men receiving 3 months of ADT with 3.6 mg goserelin for 28 days and 750 mg flutamide daily. We also report the interim results in 114 men participating in a prospective, randomized study of ADT versus surgery alone. RESULTS: The 69 patients who received 3 months of goserelin and flutamide followed by radical prostatectomy had a pathologic organ-confined cancer rate of 74%, versus 48% in the control group who received no ADT prior to surgery. The margin-positive rate was 10% in the ADT group versus 33% in the control group. In an interim analysis of 114 patients (59 ADT, 55 control), the organ-confined and margin-positive rates were 73% and 17% in the ADT group versus 56% and 36% in the control arm, respectively. The PSA disease-free rate at a mean follow-up of 28.6 months (range 6.2 to 49.5 months) was 89% in the ADT-treated patients (N = 98) and 84% in the control patients (N = 96). There was no statistical difference demonstrated between the arms with respect to biochemical failure. CONCLUSIONS: While the pathologic staging of tumors following ADT treatment was improved compared with surgical controls, to date the PSA disease-free survival rates are similar. Patients with residual extracapsular (P3) disease after ADT manifest an increased PSA failure rate compared with those with P3 tumors treated by surgery alone. This suggests that ADT may identify a subset of patients with aggressive tumors that may be candidates for additional therapeutic interventions even before PSA failure occurs.

Aged↗
PubMed1997

Pathological staging and biochemical recurrence after neoadjuvant androgen deprivation therapy in combination with radical prostatectomy in clinically localized prostate cancer: results of a phase II study.

OBJECTIVES: To assess the pathological staging and biochemical progression-free survival (assessed using serum prostate-specific antigen level) of patients with clinically localized prostate cancer using neoadjuvant androgen deprivation therapy (ADT) in combination with radical retropubic prostatectomy (RRP). PATIENTS AND METHODS: A prospective study was carried out on 69 patients with localized prostate cancer who were enrolled in a trial of 3 months of ADT followed by RRP (group 1). These patients were compared with 72 patients matched for age and clinical stage who declined ADT therapy and had RRP concurrently (group 2). Assignment to the individual treatment groups was thus determined by the patient's preference and not the physician's selection. Pathological staging and biochemical progression-free recurrence were compared between the groups. RESULTS: The rate of organ-confined (pT2) tumours was 74% in group 1 and 49% in group 2 (P < 0.01), and the rate of margin-negative tumours was 87% in group 1 and 64% in group 2 (P < 0.01). Within a median follow-up of 35 months, there was no significant difference in biochemical failure between the groups (P = 0.37). Patients with pT2 disease, regardless of treatment, had similar biochemical failure rates. In the patients with margin-positive disease, there was a significantly higher biochemical failure rate in group 1 (P = 0.02). CONCLUSIONS: The rates of organ- and specimen-confined disease were higher among the patients treated with ADT. The preliminary follow-up suggested that patients with pT2 disease after ADT have a biochemical progression-free recurrence rate similar to pT2 patients treated with RRP alone. Additionally, high biochemical failure rates in patients with margin-positive disease after ADT may identify a subset of more biologically aggressive tumours in need of early adjuvant treatment.

Aged↗
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↗