A collaborative group of cancer registries and hospitals carried out a case-control study of tumours of the bladder in women who had previously been treated for ovarian cancer. A total of 63 cases of bladder tumours were identified, and 188 controls were selected matching for age, year of ovarian cancer diagnosis and survival time. Full details of the treatment for ovarian cancer were sought for both cases and for controls. The risk of bladder tumours was increased for patients who had been treated by radiotherapy alone (1.9; 95% confidence interval, 0.77-4.9), by chemotherapy alone (3.2; 0.97-10), and by chemotherapy and radiotherapy (5.2; 1.6-16), when comparison was made with patients treated only by surgery. Patients treated by chemotherapy were separated into 2 groups according to whether they had received cyclophosphamide. Among those who had, there was a clear increase in risk (approximately 4-fold) regardless of whether or not they had also received radiotherapy. For those who received only other drugs, risk was increased substantially among patients who had also been treated by radiation, as compared with patients treated by surgery alone, and those who had received radiotherapy only. Both melphalan and thiotepa were implicated as potential bladder carcinogens on the basis of these results. The estimated risk of bladder tumours due to cyclophosphamide was more than twice the risk following radiation to the bladder, and it appeared substantially earlier. For both agents, the risk continued to increase more than 10 years after treatment began.

SUMMARY The presence of a pregnancy at the time of the initial diagnosis of an intracranial neoplasm was studied using material from a population-based tumour registry. Seventeen malignant neoplasms of the brain (ICD 191), three meningiomas, three acoustic neurinomas and a pituitary adenoma associated with pregnancy were reported to the National Cancer Registry of the GDR from [1961][1962][1963][1964][1965][1966][1967][1968][1969][1970][1971][1972][1973][1974][1975][1976][1977][1978][1979]. Observed cases were compared with those expected based on the number of births and the incidence rates for intracranial tumours among women of childbearing age during the same time period. Observed to expected ratios were substantially reduced for malignancy of the brain and meningioma but not for acoustic neurinoma. Review of this uniformly collected material did not provide support for the view that intracranial neoplasms present more often during pregnancy.The diagnosis of a brain tumour in a pregnant patient is a dramatic event for the patient, her family and for the attending physicians. The nature and timing of therapy directed at the brain tumour are affected by the existence of the pregnancy. Similarly, decisions about whether to continue the pregnancy and the selection of the best means of delivery are critically influenced by the nature and prognosis of the mother's intracranial lesion. In addition the question of a causal link between pregnancy and the development or progression of the tumour is inevitably raised. The present work approached the problem of the association of brain tumour with pregnancy from the epidemiologic point of view.The literature concerning pregnancy and intracranial neoplasms consists largely of case reports, case series and reviews of previously collected material.' Cases may have come from one or several referral centres and, in some instances, have been collected over decades.2 Different definitions are used by each author in the selection and review of cases. Depending on the criteria, patients may be included in whom brain tumour symptoms or diagnosis occurred before, during or after pregnancy. Given such diverse methods of case selection, the assessAddress for reprint requests: Prof. Dr W Janisch,

Summary A case-control study was conducted to determine whether the development of leukaemia was associated with chemotherapy for neoplasms of the ovary or breast, in a population where most such chemotherapy consisted of cyclophosphamide alone. Cases and controls were identified from the National Cancer Registry of the German Democratic Republic. Cases were women who had developed leukaemia as a second primary after an initial diagnosis, at least one year before, of an ovarian or breast tumour. Controls were patients with an ovarian tumour or breast cancer who had survived to the year when the case developed a leukaemia but who had not themselves developed a second malignancy. Controls were matched to cases by the site of the first primary and its year of diagnosis, as well as year of birth. The relative risk for acute leukaemia following treatment with cyclophosphamide alone was significantly elevated (P<0.05), at 14.6 for ovarian tumour patients and 2.7 for breast cancer patients. Among breast cancer patients the increased risk of leukaemia associated with chemotherapy was confined to women who had been under 50 years of age at the time of diagnosis of the breast cancer (for whom the relative risk was 13.1). No excess risk of leukaemia was observed in association with radiotherapy for either ovarian or breast cancer patients. The present findings strongly suggest that cyclophosphamide as a single chemotherapeutic agent is capable of inducing leukaemia in humans.Cyclophosphamide is carcinogenic by several routes of administration in rats and mice (Schmahl & Habs, 1979; IARC, 1981). In humans there is also strong evidence that it is a carcinogen (Plotz et al., 1979;Elliot et al., 1982), producing tumours of the bladder and possibly other sites.There are a number of case reports of acute leukaemia following treatment with cyclophosphamide of nonmalignant diseases including rheumatoid arthritis, Wegener's granulomatosis, chronic glomerulonephritis, idiopathic thrombocytopaenia purpura, and Sj6gren's syndrome (Grunwald & Rosner, 1979). While cyclophosphamide is suspected to be a leukaemogen, it is widely believed to be less potent than many other nitrogen mustard-derived alkylating agents, and it is recommended as a component of adjuvant therapy following surgery for breast cancer (National Institutes of Health, 1986).Studies of leukaemia in cancer patients treated with cyclophosphamide have been difficult to interpret, because it is often given in combination with other agents known to be leukaemogenic. Although an increase in the risk of acute non-lymphocytic leukaemia (ANLL) following Hodgkin's disease has been appreciated for some time (Brody et al., 1977) it has not been possible to implicate directly cyclophosphamide, even though it has been widely used in Hodgkin's disease therapy (Boivin & Hutchison, 1984). Acute leukaemia also occurs in excess in patients with nonHodgkin's lymphoma who have undergone chemotherapy including cyclophosphamide (Pedersen-Bjergaard et al., 1985). In a study of multiple myeloma...

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The incidence of malignant tumors of the eye (ICD 172.1, 173.1 and 190) was calculated from the data of the National Cancer Registry of the GDR. Malignant tumors of the lid represent 1.4% and malignant tumors of the eye 0.3% of all malignant tumors registered. This corresponds to an incidence of intraocular tumors of about 1.0 per 100 000 inhabitants, and an incidence of lid tumors of approx. 4.7 per 100 000. The standardized incidence of malignant tumors of the eye shows no statistically significant change, at 0.85 (1966-1970) and 0.93 (1971-1980) in men and 0.70 and 0.73 in women. The incidence of melanomas of the lid is also unchanged in both sexes. The mean incidence of retinoblastoma in both boys and girls is 0.54 (1961-1980) based on 100 000 children less than 10 years old. The diminution in the incidence of retinoblastoma in recent years is not statistically significant.