Design and evolution of the data management systems in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

This paper describes the design and evolution of the data management systems developed in support of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. These systems span platforms from stand-alone computers to distributed systems on local area networks to mainframes. Allowing all of these systems to share appropriate information electronically introduces integration, synchronization, testing, and support challenges. For each platform, applications were developed to handle data entry, editing, trial management, reporting, telecommunications, and data sharing. Approaches to issues such as level of data access, integration with other, existing applications, and handling the expansion of the protocol are discussed.

Genetic disease in offspring of long-term survivors of childhood and adolescent cancer.

Numerous case series have addressed the concern that cancer therapy may damage germ cells, leading to clinical disease in offspring of survivors. None has documented an increased risk. However, the methodological problems of small series make it difficult to draw firm conclusions regarding the potential of cancer treatments to damage the health of future offspring. We conducted a large interview study of adult survivors of childhood cancer treated before 1976. Genetic disease occurred in 3.4% of 2,198 offspring of survivors, compared with 3.1% of 4,544 offspring of controls (P=.33; not significant); there were no statistically significant differences in the proportion of offspring with cytogenetic syndromes, single-gene defects, or simple malformations. A comparison of survivors treated with potentially mutagenic therapy with survivors not so treated showed no association with sporadic genetic disease (P=.49). The present study provides reassurance that cancer treatment using older protocols does not carry a large risk for genetic disease in offspring conceived many years after treatment. With 80% power to detect an increase as small as 40% in the rate of genetic disease in offspring, this study did not do so. However, we cannot rule out the possibility that new therapeutic agents or specific combinations of agents at high doses may damage germ cells.

Reproductive problems and birth defects in survivors of Wilms' tumor and their relatives.

In a retrospective cohort study of 47 Wilms' tumor survivors and their 77 sibling controls, female survivors had a fourfold excess risk (risk ratio, 4.1; 95% confidence interval, 1.7-10.1) for any adverse livebirth outcome, including birth defects, compared with their sibling controls. Wives of male survivors had no apparent excess risk for problem pregnancies. The families had a number of severe reproductive problems and major birth defects, such as primary amenorrhea in two survivors, bicornuate uterus in two survivors and one control, and mental retardation in one male survivor and a male control. The son of a female survivor died after bilateral Wilms' tumors. Birth defects in the offspring of female survivors are compatible either with intrauterine constraint, possibly due to radiation-induced fibrosis or with the complex of malformations associated with Wilms' tumor. Female survivors of Wilms' tumor appear to be at increased risk for a variety of reproductive problems, from sterility to fetal loss, early delivery, and birth defects in offspring. Furthermore, relatives of survivors of Wilms' tumor may be at risk of having associated birth defects, with clinically significant consequences.

Educational achievement of long-term survivors of childhood and adolescent cancer.

In a retrospective cohort study, the level of education attained by 2,283 long-term survivors of childhood and adolescent cancer was investigated and compared with that of 3,270 sibling controls. Survivors of central nervous system tumors were significantly less likely than controls to complete eight grades of school or, if they completed high school, to enter college. No significant differences in educational achievement were found for survivors of non-central nervous system cancers. The educational deficit of survivors of brain tumors was especially striking for tumors of the ventricles or cerebral hemispheres, and the deficit was more severe for those treated with radiation therapy than by surgery alone. Early age at diagnosis of a central nervous system tumor was associated with a larger educational deficit than late age at diagnosis. These findings are reassuring for the majority of long-term survivors of childhood and adolescent cancers given therapies used prior to 1975.

Effects of treatment on fertility in long-term survivors of childhood or adolescent cancer.

In a retrospective cohort study of survivors of cancer and of controls, we estimated the risk of infertility after treatment for cancer during childhood or adolescence. We interviewed 2283 long-term survivors of childhood or adolescent cancer diagnosed in the period from 1945 through 1975, who were identified at five cancer centers in the United States. Requirements for admission to the study were diagnosis before the age of 20, survival for at least five years, and attainment of the age of 21. In addition, 3270 controls selected from among the survivors' siblings were interviewed. Cox regression analysis showed that cancer survivors who married and were presumed to be at risk of pregnancy were less likely than their sibling controls to have ever begun a pregnancy (relative fertility, 0.85; 95 percent confidence interval, 0.78 to 0.92). Radiation therapy directed below the diaphragm depressed fertility in both sexes by about 25 percent. Chemotherapy with alkylating agents, with or without radiation to sites below the diaphragm, was associated with a fertility deficit of about 60 percent in the men. Among the women, there was no apparent effect of alkylating-agent therapy administered alone (relative fertility, 1.02) and only a moderate fertility deficit when alkylating-agent therapy was combined with radiation below the diaphragm (relative fertility, 0.81). Relative fertility in the survivors varied considerably according to sex, site of cancer, and type of treatment; these factors should be taken into consideration in counseling survivors about the long-term consequences of disease.

Cancer in offspring of long-term survivors of childhood and adolescent cancer.

A multicentre retrospective cohort study of long-term survivors of childhood and adolescent cancer identified 7 cases of cancer among 2308 offspring (0.30%) of 2283 case-survivors and 11 cases among 4719 offspring (0.23%) of 3604 controls. Overall, the observed numbers of cases were not significantly different from those expected in the general population. Among offspring of case-survivors observed for the first 5 years of life, the group with the most person-years of follow-up, 5 cancers were reported (3 confirmed), compared with 1.7 expected, a significant excess due mostly to boys whose mothers survived cancer. Some offspring with cancer had known single-gene traits; others resembled previously recognised patterns of family cancer. The remainder may represent chance occurrences or new cancer family syndromes, such as an association with malignant melanoma. The study had an overall 79% power to detect a 3-fold excess of cancer among offspring of case-survivors, but no excess was observed. The number person-years of follow-up in the second decade of life, when most cases of cancer developed, was small.

Cancer incidence and mortality trends among whites in the United States, 1947-84.

Cancer incidence trends from the late 1940s to 1983-84 were assessed among white residents of five geographic areas (Atlanta, Connecticut, Detroit, Iowa, San Francisco-Oakland) by means of data derived from several National Cancer Institute surveys, the Connecticut Tumor Registry, and the Surveillance, Epidemiology, and End Results Program. Incidence trends were compared with mortality trends for the entire United States and for the same five study areas. This study documented rising incidence and mortality rates for four cancers: lung cancer, melanoma of the skin, multiple myeloma, and non-Hodgkin's lymphomas. Increases in lung cancer continued through the early 1980s, but the rate of increase has been moderating during recent years, particularly among males and at younger ages for whom recent declines are evident. Overall, lung cancer incidence rates increased more than 220 and 400% among males and females, respectively. Although much rarer than lung cancer, melanoma of the skin and multiple myeloma increased greatly until the early 1980s among both males and females. The overall rate of increase in melanoma incidence among males was greater than that for lung cancer, and the rate of increase in multiple myeloma mortality among females was exceeded only by that for lung cancer. Increases of 70-120% were observed for non-Hodgkin's lymphomas. Increases in incidence and mortality rates for pancreatic cancer were apparent during the early years but less conspicuous in recent years. Laryngeal and kidney cancer rates generally increased substantially, although the changes were not remarkable for laryngeal cancer mortality among males and kidney cancer mortality among females. The rates for cancers of the mouth and pharynx increased among females but not males. Prostate, colon, and bladder cancer incidence rates increased more than 65% among males, whereas mortality rates changed only moderately. The incidence of thyroid cancer increased more than 75% among both sexes until the late 1970s, but mortality rates have declined during the period of study. Breast cancer incidence increased 30%, whereas mortality rates remained remarkably constant. The incidence of corpus uteri cancer increased dramatically during the mid-1970s and decreased substantially thereafter; these changes were not reflected in the mortality rates, which continually declined during the entire time period. The incidence of testicular cancer increased more than 90% and that of Hodgkin's disease did not change greatly; however, mortality rates for both cancers declined more than 50% since the late 1960s and early 1970s.(ABSTRACT TRUNCATED AT 400 WORDS)

Demographic patterns for mesothelioma in the United States.

Incidence rates for pleural and peritoneal mesotheliomas in about 10% of the U.S. population were examined by various demographic characteristics based on 1973-84 data from the Surveillance, Epidemiology, and End Results Program. Although pleural mesothelioma was more common than peritoneal mesothelioma, both are rare diseases in this country. Pleural mesothelioma incidence rates among white males increased over time and were highest in seaboard areas where shipyards have been located (Seattle, San Francisco-Oakland, Hawaii). The significant secular change was attributed to both period (date of diagnosis) and cohort (date of birth) effects. Pleural mesothelioma incidence rates among white males were nearly 50% higher in the 1980-84 period compared to those in 1975-79; the cohort effect rose to a peak for the 1905-9 birth cohort and then declined. These effects probably reflect changes in asbestos exposure patterns in the past and more recent changes in clinical awareness and coding rules for mesothelioma. Geographic analysis of U.S. death certificates for pleural cancer among white males and females dying during 1968-78 indicated that mortality rates were significantly elevated in several areas that have had asbestos-manufacturing plants or shipyards. Analyses of mortality rates must be viewed with caution, since mesothelioma is considerably underreported on death certificates.

Hodgkin's disease in the United States: a comparison of patient characteristics and survival in the Centralized Cancer Patient Data System and the Surveillance, Epidemiology, and End Results Program.

Demographic, pathologic, and clinical characteristics as well as subsequent survival were compared between 3,607 Hodgkin's disease (HD) patients registered by the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute and 2,278 HD patients registered by comprehensive cancer centers (CCCs) belonging to the Centralized Cancer Patient Data System (CCPDS). All patients were diagnosed with HD between July 1977 and December 1982. CCPDS cases were slightly younger, more often of the nodular sclerosing histologic type, and presented with Stage II disease at diagnosis more often than did SEER cases. CCPDS and SEER cases were similar regarding the lymph node region of origin, sex, and race. The mortality rate among SEER patients was approximately 1.5 times that among CCPDS patients. This significant survival difference was observed within all stages and within all histologic subtypes and remained after controlling for the effects of age. Late-stage, older age, non-Caucasian race, and a more diffuse histologic appearance were all independent and significant predictors of poor survival. These findings suggest that the management of HD in CCCs results in improved outcome relative to that in the general population. Possible explanations for such effects are explored, and additional lines of pursuit are suggested.

Black/white differences in bladder cancer patient survival.

Black bladder cancer patients have been found to have a substantially poorer survival experience than white patients; the 5-year relative survival rates are 71% for whites and 54% for blacks. To explore this difference in survival, data were analyzed on 4289 white and 380 black bladder cancer patients diagnosed during the period 1977-80 in three geographic areas covered by the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. The orientation of the analysis was to identify variables, using multivariable procedures, that were not only prognostic but which also were important in regard to explaining black/white differences in patient survival. Such variables are referred to as explanatory variables. Three variables were analyzed in regard to their importance as explanatory variables, i.e. histologic type, stage, and histologic grade, and all were found to be of roughly equal importance. The effects of other factors on black/white differences in survival are also discussed including the possible importance of lead-time bias and the possible lack of diagnosis of the more benign forms of bladder cancer in blacks.

The prevalence of cancer. Estimates based on the Connecticut Tumor Registry.

Cancer incidence and mortality do not fully reflect the effect of cancer. To estimate the number of persons alive who have a history of cancer, we derived prevalence rates based on data from the Connecticut Tumor Registry. We did not attempt to distinguish between people who had been cured of cancer and those who still had the disease. In 1982 the age-adjusted prevalence rates of cancer among males and females were 1,789 and 2,222, respectively, per 100,000. Age-specific prevalence rates were highest among the elderly; 12 percent of men and 11 percent of women over 70 had previously been given a diagnosis of cancer. Breast cancer in females and prostate cancer in males were the two most prevalent malignant diseases. We estimate that about 5 million persons alive in the United States today have at one time received a diagnosis of cancer.

Factors associated with survival differences between black women and white women with cancer of the uterine corpus.

Prognostic factors leading to the survival advantage of white women over black women with uterine corpus cancer were evaluated by using a series of patients diagnosed from 1973-1977 in three geographic areas of the United States participating in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Higher survival rates were observed among women under age 55 years, with stage I disease, and living in higher socioeconomic census tracts. Significant survival differences by race for patients with adenocarcinomas were found at almost all factor levels. Within each racial group, patients with adenocarcinomas had better prognosis than did those with sarcomas. A multivariate analysis found stage of disease and age at diagnosis to be the major predictors of survival among women with adenocarcinomas of the uterine corpus, followed by race, median family income, and mean highest education received. Adjustment of the black survival rates for these factors reduced the gap among patients with adenocarcinomas, but significant differences in survival between blacks and whites remained. Race was not a predictive factor for survival of patients with sarcomas, but age at diagnosis, stage of disease, and education were. After adjustment for the significant factors, prognosis was equally poor for black patients and white patients with sarcomas of the uterine corpus. These findings suggest that, even when controlling for known markers of racial differences, there remain other underlying prognostic factors associated with survival of black women and white women with adenocarcinomas of the uterine corpus that have yet to be determined.

Survival of children with brain tumors: SEER Program, 1973-1980.

Eight hundred eighty-seven children with brain tumors were identified by the SEER registries (1973-1980). Twenty-five percent were low-grade supratentorial astrocytomas, medulloblastomas were 23%, cerebellar astrocytomas 12%, high-grade supratentorial astrocytomas 11%, brainstem gliomas 9%, and ependymomas 8%. The worst survivals were in children less than 2 years of age, and the best were in those aged 10 to 14 years. Five-year survivals of children with cerebellar astrocytomas were 91%, low-grade supratentorial astrocytomas 71%, high-grade supratentorial astrocytomas 35%, medulloblastomas 39%, ependymomas 28%, and brainstem gliomas 18%.

Psychosocial consequences of childhood and adolescent cancer survival.

A Connecticut Addendum to a multi-center National Cancer Institute study was developed to investigate psychosocial effects of long-term childhood and adolescent cancer survival. Cases (450), drawn from the files of the Connecticut Tumor Registry and 587 of their siblings were located and interviewed. Overall response rate was 84%. The frequency of lifetime major depression in survivors (males, 15%; females, 22%) did not appear to differ from that of their siblings (males, 12%; females, 24%) and was similar to those reported in the literature for the general population. The usual correlates of depression (sex, marital status, perception of health) were observed, independent of a history of a childhood malignancy. There were no differences in the reported frequencies of suicide attempts, running away or psychiatric hospitalizations for either sex. Eighty percent of the male survivors were rejected from the armed forces, 13% from college and 32% from employment. These values were significantly higher than those of the male siblings. Female survivors were significantly more likely than their sisters to be denied entrance into the military (p less than 0.05), but no differences were observed between females with respect to college or employment. Both sexes had more difficulty obtaining health and life insurance than their siblings (p less than 0.0001). Although survivors of childhood and adolescent cancer do not seem to be at excess risk for major depression, they do appear to have difficulty attaining certain major socioeconomic goals.

Recurrence-free survival time for surgically treated soft tissue sarcoma patients. Multivariate analysis of five prognostic factors.

A staging system, based upon the experience of 1215 patients, was published by the American Joint Committee Task Force on Soft Tissue Sarcoma in 1977. A subset of these patients, 594, was selected to study recurrence-free survival time. The authors found 331 patients with a recurrence within 5 years (100 local only, 123 metastatic only, and 108 local + metastatic); median months to recurrence was 9.7. Within 5 years, recurrence was clearly associated with mortality: among the 331 patients who experienced a recurrence, 245 died, whereas only 31 died among the 263 who had no recurrence. To further evaluate the utility of the published staging system, a multivariate analysis of five factors was carried out for 297 of the 594 patients (patients with unknown information for any one of these factors were excluded). Factors in addition to grade that exerted a significant influence on recurrence were: direct extension, symptoms, and location of tumor when survival was measured to the first of any recurrence, and tumor size, measuring survival to the first metastatic recurrence. It is therefore recommended that these factors be taken into account in staging this disease. Estimates of probable recurrence-free survival time based upon the multivariate model (Weibull) are also presented.

The availability of insurance to long-time survivors of childhood cancer.

The authors identified 100 adults who survived cancer who were diagnosed and treated in childhood between 1945 and 1975. Using standardized interviews, each survivor and matched same-sex sibling was asked about life and health including questions about insurance. Compared with their same-sex siblings, childhood cancer survivors had significantly more difficulty in securing life insurance (P less than 0.001), in having life insurance in force (P less than 0.004), and in obtaining health insurance because of health reasons (P less than 0.001). Survivors were significantly less likely than siblings to be covered by health insurance (P less than 0.04). Cure of childhood cancer has become more common, allowing thousands of survivors to enter adult life. This study suggests that childhood cancer survivors have an unmet need in respect to life and health insurance.

Cancer incidence and survival in patients 65 years of age and older.

The impact of cancer on persons 65 years of age and older has been assessed by examining incidence rates and survival rates. For all cancers combined, the incidence rate shown in Table 4 for males 65 and older (2,468.2 per 100,000) is four times the age-adjusted rate for males 45 to 64 years of age (586.7). For elderly females, the incidence rate is twice that for females aged 45 to 64 (1,401.1 versus 609.7). Ratios of incidence rates for older versus younger males are about four to five for cancers of the stomach, colon, rectum, pancreas, and urinary bladder, and for leukemia; about three for cancers of the lung and kidney, and for non-Hodgkin's lymphomas; and 10 for cancer of the prostate. For females, the corresponding ratios are similar to those for males, although a little lower for cancers of the colon, rectum, and urinary bladder, and for leukemia, and a little higher for cancers of the stomach and pancreas. The ratios for breast, uterine cervix, uterine corpus, ovary, and lung are less than two. The relative survival rates for patients 65 and older are for many cancer sites only a few percentage points lower than rates for those 45 to 64 years of age (Table 5), suggesting that patients in this age group fare only a little worse than younger patients in escaping the effects of cancer once it has been diagnosed. Exceptions are cancer of the urinary bladder and non-Hodgkin's lymphomas for both men and women and cancers of the uterine cervix, uterine corpus, ovary, and kidney for women. For these sites, the survival rates for older patients are considerably lower than for their younger counterparts. For female breast cancer patients, there was no difference in the five-year relative survival rate for those 65 and older compared with those 45 to 64.

Risk of leukemia associated with the first course of cancer treatment: an analysis of the Surveillance, Epidemiology, and End Results Program experience.

The risk of leukemia associated with the first course of cancer treatment was evaluated in over 440,000 patients diagnosed during 1973-80 (average follow-up = 1.91 yr) from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Although the reporting of the first course of therapy probably was incomplete, 34 acute nonlymphocytic leukemias (ANLL) developed compared with 7.6 expected among 70,674 patients known to receive initial chemotherapy [relative risk (RR) = 4.5, 95% confidence interval (Cl) = 3.1-6.3]. Significant ANLL excesses were observed following chemotherapy for breast cancer (RR = 8.1), ovarian cancer (RR = 22.2), and multiple myeloma (RR = 9.5). Patients initially treated with radiation (with no record of chemotherapy) also had a significantly increased ANLL risk; 45 leukemias occurred versus 17.9 expected (RR = 2.5, 95% Cl = 1.8-3.4). In this group, excess ANLL were found following irradiation for uterine corpus cancer (RR = 4.0). Kidney and renal pelvis cancer patients had a twofold leukemia risk (all types) that was unrelated to treatment (RR = 2.2).