Max H. Myers

Early menopause in long-term survivors of cancer during adolescence

Objective: We attempted to investigate the risk of early menopause after treatment for cancer during childhood or adolescence. Study Design: We interviewed 1067 women in whom cancer was diagnosed before age 20, who were at least 5-year survivors, and who were still menstruating at age 21. Self-reported menopause status in survivors was compared with that in 1599 control women. Results: Cancer survivors, with disease diagnosed between ages 13 and 19, had a risk of menopause four times greater than that of controls during the ages 21 to 25; the risk relative to controls declined thereafter. Significantly increased relative risks of menopause during the early 20s occurred after treatment with either radiotherapy alone (relative risk 3.7) or alkylating agents alone (relative risk 9.2). During ages 21 to 25 the risk of menopause increased 27-fold for women treated with both radiation below the diaphragm and alkylating agent chemotherapy. By age 31, 42% of these women had reached menopause compared with 5% for controls. Conclusions: Treatment for cancer during adolescence carries a substantial risk for early menopause among women still menstruating at age 21. Increasing use of radiation and chemotherapy, together with the continued trend toward delayed childbearing, suggests that these women should be made aware of their smaller window of fertility so that they can plan their families accordingly.

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.

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.

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.

Statistical methods for studying multiple primary malignant neoplasms.

Case reports and case series dealing with multiple primary malignant neoplasms provided useful criteria for defining and documenting this phenomenon. The formation of tumor registries greatly aided in identifying a sufficient number of multiple primary cancer patients and facilitated case‐control comparisons. Reports of two or more neoplasms occurring together in the same individual do not constitute proof of a significant association; the tumors must be shown to occur together more frequently than expected by chance. The person‐years approach applied to data derived from a well‐defined population makes it possible to compare the observed and expected number of subsequent primary cancers. The results of the most sophisticated procedures are no better than the quality of the data, however, and one must critically examine possible sources of bias before accepting statistical significance as representing biologic significance.

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.

Implications from seer data on breast cancer management

From the SEER files of the NCI, 8,587 cases of breast cancer diagnosed in 1975 were analyzed. Of these cases, 5.3% were noninvasive. Of the invasive cancers under 0.5 cm in diameter, 17.2% had positive axillary lymph nodes. Where the physician recorded no palpable axillary lymph nodes, 34.5% were found to be positive.

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.

Trends in survival rates of patients with cancer.

Reports on survival of patients with cancer issued by the National Cancer Institute indicate marked improvement for almost all forms of cancer from the 1940s to 1950s. Subsequently, prognosis for patients with forms of cancer accounting for approximately 42 per cent of all cancers continued to improve, although at a slower rate. For cancers of the lung, colon, rectum, stomach and pancreas, little improvement in patient survival during the 1960s was observed, and for women with invasive cervical cancer, survival rates decreased slightly. One-year survival results for patients with diagnoses made during 1970-71 suggest that improvement in five-year survival observed during the 1960s for many forms of cancer will be sustained. Continued reporting of survival of patients treated in the 1970s would ultimately demonstrate the degree of effectiveness of recently introduced therapeutic procedures.