Accuracy of clinical criteria for AD in the Honolulu-Asia Aging Study, a population-based study.

OBJECTIVE: To determine diagnostic accuracy for AD in a population-based study of Japanese-American men. AD is neuropathologically confirmed for more than 80% of cases at major referral centers (primarily Caucasians); however, information on diagnostic accuracy in population-based studies and studies of different ethnic groups is limited. METHODS: There were 3,734 men who participated in the Honolulu-Asia Aging Study 1991 through 1993 dementia examination and 2,603 in the 1994 through 1996 examination. Diagnoses were based on published criteria. Neuropathologists blinded to clinical data quantified neurofibrillary tangles (NFT) and neuritic plaques (NP). RESULTS: Of 220 autopsied subjects, clinical evaluation revealed 68 with normal cognition, 73 intermediate, and 79 with dementia: 20 AD, 27 vascular dementia, 19 AD + other, and 13 other dementia. Among 20 cases with pure AD, the median value for maximum neocortical NFT density was 6.9/mm(2) and for neocortical NP density was 8.0/mm2. Corresponding densities for other groups were <3.0/mm2. Using established neuropathologic criteria, 25% (5/20) of clinical AD cases had enough NP to meet definite AD criteria, whereas 65% (13/20) had sufficient NP to meet neuropathologic definite or probable AD criteria. Among nine AD cases with moderately severe dementia, only two (22%) had NP densities great enough to meet definite neuropathologic criteria, whereas seven (78%) met neuropathologic criteria for probable AD. CONCLUSIONS: Neuropathologic confirmation and NP density among decedents with clinical AD in this population-based study were lower than reported by referral centers and similar to reports from two other community studies. Ethnic differences in propensity for amyloid deposition as well as differences in clinical severity and representativeness of cases might contribute to these findings.

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.

Marriage and divorce after childhood and adolescent cancer.

As part of a study of long-term survivors of childhood and adolescent cancer, we interviewed 2170 survivors and 3138 sibling control subjects about their marital histories. In a proportional hazards analysis, both male and female survivors were less likely to be ever married than control subjects (rate ratio [RR] for males, 0.87; 99% confidence interval, 0.76 to 0.99; RR for females, 0.86; 99% confidence interval, 0.76 to 0.97). Survivors of brain and central nervous system tumors accounted for most of the marriage deficit, which was greater in men than in women (RRs, 0.48 and 0.73, respectively). Survivors married at the same average age as control subjects, except for survivors of central nervous system tumors, who married slightly later. The average length of first marriages was shorter in survivors than in control subjects. Men who had survived central nervous system tumors diagnosed before 10 years of age and male survivors of retinoblastoma had higher divorce rates than male control subjects (RRs, 2.9 and 1.9, respectively). In this cohort (which received less intense therapy than given in current practice), altered marriage practices are substantial only among survivors of central nervous system tumors.

Improved survival among children with acute leukemia in the United States.

Statistically significant increases in 3- and 5-year survival rates were observed for white children under 15 years of age diagnosed with acute lymphocytic leukemia (ALL) from 1973-1976 to 1977-1980 in 9 geographic areas of the United States. Survival for the cohort diagnosed in 1977-1980 was 78% at 3 years, 68% at 5 years, and 42% at 10 years from diagnosis. For the cohort diagnosed in 1981-1984, however, slight but not significant decreases in survival rates were seen. Improvements in 3- and 5-year survival for children with acute granulocytic leukemia (AGL) were found between the cohort diagnosed in 1973-1976 as compared to 1977-1980, but these rates stabilized as well in the 1980s. While the age-adjusted incidence rate for all childhood leukemias fluctuated slightly between 1973 and 1985, age-adjusted mortality continued to decline, dropping from 2.5 per 100,000 white population under 15 years of age in 1973 to 1.4 per 100,000 in 1985, an average annual decrease of approximately 4%.

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.

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.

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.

Inflammatory breast cancer: the experience of the surveillance, epidemiology, and end results (SEER) program.

The current status of inflammatory breast cancer (IBC) among U.S. females was reviewed with the use of data abstracted from medical records of patients diagnosed with breast cancer between 1975 and 1981 in nine geographic areas covered by the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program. Patients were selected on the basis of reported clinical and pathologic features of IBC and were divided into 3 groups: I) both clinical and pathologic features of IBC; II) clinical features without pathologic confirmation; and III) pathologic evidence only. The age distribution of pathologically defined IBC, in general, showed younger ages than those for other breast cancers in both the white and black populations. Further analysis was restricted to white females due to the relatively small numbers of black and other nonwhite patients with IBC. The disease presentations of both clinically and pathologically defined IBC were similar with regard to the likelihood of the presence of metastases at initial staging. Survival was evaluated by comparison of patients with nonmetastatic (MO) disease. Three years after diagnosis, the relative survival rates among patients in groups I, II, and III were observed to be 34, 60, and 52%, respectively. Survival of patients with all other types of breast cancer was 90% at 3 years. The management of IBC appeared to differ from the treatment of other forms of breast cancer; chemotherapy was given more frequently as the first course of cancer-directed therapy in white SEER females with evidence of MO IBC compared with the group with MO non-IBC. When all possible combinations of initial therapy were considered, the treatment for IBC was more variable than the treatment for non-IBC.

Improved survival among children with acute leukemia diagnosed in the 1970s.

Improvements in survival were observed among white children less than 15 years of age diagnosed with acute lymphocytic leukemia (ALL) between 1973 and 1978 in nine of the areas covered by the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program. Significant increases were noted between the 3-year survival rate for children diagnosed in 1973-1975 (59%) and the rate for those diagnosed in 1976-1978 (74%). The 5-year survival rate for children diagnosed with ALL in 1973-1975 was nearly 50%. Survival of female children exceeded that for males, and younger children 1-4 years of age diagnosed with ALL had a better prognosis than older children 5-14 years of age. Both sexes and age groups showed increases in survival between 1973-1975 and 1976-1978. Improvements in survival during these time periods were not observed for children diagnosed with acute granulocytic (myelogenous) leukemia. Between 1973 and 1979, the age-adjusted incidence rate for all childhood leukemias remained fairly constant in the SEER areas, ranging from 3.7 per 100,000 population less than 15 years of age in 1973 to 3.5 per 100,000 in 1979. Reflecting observed improvements in childhood leukemia survival, the corresponding mortality rates fell from 2.2 to 1.7 per 100,000 in this same time period.

Characteristics of colon cancer patients reported in population-based tumor registries and Comprehensive Cancer Centers.

The characteristics of colon cancer tumors diagnosed in patients seen at hospitals participating in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program and at Comprehensive Cancer Centers (CCC's) belonging to the Centralized Cancer Patient Data System (CCPDS) are compared. There were identified among cases diagnosed between July 1, 1977 and December 31, 1978, the first 18 months of registration for the CCPDS centers. A higher proportion of CCPDS colon tumors were diagnosed in black patients, 15.4% versus 6.8% for SEER, reflecting the urban location of many CCC's. The CCPDS has proportionally fewer patients aged 75 years or older, and a median age of 67.5 years versus 70 years for the SEER cases. Although surgery alone was the major form of therapy for both CCPDS and SEER patients with colon tumors, higher percentages of CCPDS patients than SEER patients were treated by chemotherapy alone or by modalities other than surgery, chemotherapy, and radiotherapy, particularly those with later stages of the disease. Few disagreements existed between the 2 groups in distribution by segment of the colon, stage, and histologic type. Few differences were found that would render invalid future comparative analyses of patient survival between the two data systems once adequate follow-up information is available. Such an evaluation may be a valuable instrument in measuring whether improvements in cancer patient management being developed at CCC's are, in fact, "filtering down" to the general series of colon cancer patients.

Long-term patient survival for some of the more frequently occurring cancers.

Conditional five-year relative survival rates were calculated for patients diagnosed during 1950-1959 to examine long-term survival patterns for some of the more frequently occurring cancers. The data on the patients studied were collected as part of the national cancer institute's End Results Program. Breast cancer patients with localized disease were found to have only slightly increasing conditional rates for 20 years subsequent to diagnosis beginning at 85% at diagnosis and exceeding 90% at 20 years subsequent to diagnosis. Conditional five-year rates for patients with distant involvement approached the conditional rates for patients with regional involvement 15 years after diagnosis. Conditional rates by stage for patients with cancer of the cervix or cancer of the corpus increased initially and then became somewhat constant at a level related to stage of disease at diagnosis. For cancer of the colon, the conditional rates for female patients in each stage of disease category approached the same value 7-8 years subsequent to diagnosis. These observations may provide additional insight into the biological behavior of these cancers.

Changing patterns of Hodgkin's disease at autopsy: a 25-year experience at the National Cancer Institute, 1953--1978.

The pathologic findings at autopsy in 124 patients with an initial diagnosis of Hodgkin's disease (HD) were evaluated to assess the effects of treatment on the anatomic extent and histologic appearance of residual HD. Further, the effects of duration of disease, vascular invasion, and histologic subtype at diagnosis on sites of involvement were considered. The 124 autopsied cases came from a cohort of 345 patients admitted for treatment at the National Cancer Institute between 1953 and 1969, with followup extended to 1978. The pathologic review included extensive organ sampling; greater than 12,000 slides were reviewed. The study period spans 25 years, ranging from a period of palliative therapy (81 cases, pre-1965) to the modern curative treatment era (43 cases, 1965 or later). A distinct reduction in the extent of disease at autopsy was noted in the group treated with curative intent. Reduced involvement was the rule for most, but not all, organ sites, with the reduction greater for certain histologic types. Some organs had a comparable incidence of involvement with early and late deaths. Histologic assessment identified an atypical monomorphic form of residual HD (treatment-altered HD) in patients from both treatment eras but most consistently in the post-1965 group. Vascular invasion occurred in 43% of cases. The incidence of extranodal involvement was considerably higher in patients with vascular invasion, indicating that vascular spread is a factor in extranodal spread and in lethal cases of HD.

Progress in the treatment of childhood acute leukemia: a review.

The dramatic improvements in the survival experience for children diagnosed with acute leukemia are analyzed using data collected through hospitals participating in the National Cancer Institute's End Results Group Program between 1950 and 1973. Children under 15 years of age who were diagnosed with both acute lymphocytic leukemia (ALL) and acute nonlymphocytic leukemia (ANLL) showed moderate improvements in the 1950s, but beginning in the 1960s those with ALL did far better. Statistically significant differences at the 0.05 level were noted between their three-year survival rates for all cohorts analyzed between 1960 and 1973. For the 1970-1973 cohort, three-year survival rates were 49% and 20% for ALL and ANLL, respectively, and five-year survival rates were 34% and 12%. Between 1950 and 1976 the age-adjusted incidence rate for all childhood leukemias remained relatively stable in a sample of five geographic areas, changing from 4.6 per 100,000 children under 15 years of age to 4.3 per 100,000. In contrast, the corresponding age-adjusted mortality rate fell approximately 45% over the same period, from 4.4 per 100,000 to 2.4 per 100,000.

Survival rates after enucleation of eyes with malignant melanoma.

We investigated the rates of mortality for several types of malignant melanomas for evidence that surgery accelerates metastasis. Additionally, we reanalyzed uveal melanoma survival rates from the Armed Forces Institute of Pathology. Our computations showed higher death rates in years two to five after diagnosis than in years one or six to ten. The same pattern of a peak mortality in the early years after diagnosis and lower rates six to ten years thereafter was seen in all tumor types studied. Our analysis of survival rates produced no evidence to alter the existing pattern of treatment for malignant melanoma of the uvea.