Among a cohort of British survivors of childhood cancer, excess mortality from second primary cancers and circulatory diseases continued to occur beyond 25 years from diagnosis.

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This population-based study provides grounds for reassurance of the majority of survivors in that their risk of developing bone cancer within 20 years of 3-year survival did not exceed 0.9%. The higher risks found for bone cancer following the other specific rare types of childhood cancer provide a rational basis for surveillance. The RRs reported for bone cancer after specified levels of exposure to radiation should help in making decisions concerning future treatment protocols.

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Radiotherapy and ACTH deficiency are significantly associated with increased mortality in patients with acromegaly. In ACTH-deficient patients, a daily dose of more than 25 mg hydrocortisone is associated with increased mortality compared to lower doses. These results have important implications for the treatment of patients with acromegaly and also raise issues as to the optimum hydrocortisone treatment regimens for ACTH-deficient patients.

Summary Among a cohort of 10,106 three-year survivors of childhood cancer, 90 second primary tumours (SPTs) were observed. Within 25 years of 3-year survival about 4% developed a SPT, about 6-fold expected, the relative risk not varying much with increasing follow-up.Following genetic retinoblastoma we observed 30-fold the expected number of SPTs, and over 400-fold the expected number of osteosarcomas. The risk of SPT in the absence of radiotherapy and chemotherapy (inherent risk) following genetic retinoblastoma was 13-fold expected and over 200-fold the expected number of osteosarcomas were observed. There was evidence that both radiotherapy and cyclophosphamide were associated with an increased risk of SPT.After all first primary tumours (FPTs) excluding retinoblastoma we observed almost 5-fold the expected number of SPTs. The inherent risk was 4-fold expected, the relative risks associated with radiotherapy but no chemotherapy, and both radiotherapy and chemotherapy were 6-and 9-fold expected respectively. There were about 20-fold the number of malignant bone tumours expected, most were osteosarcoma; also 7-fold the number of central nervous system tumours expected. There were 8 basal cell carcinomas and it seems likely that radiotherapy was involved in the development of some of these. Radiotherapy appears to have been involved in the development of many of the SPTs observed following all FPTs excluding retinoblastoma, particularly after CNS tumours, Wilms' tumour and Hodgkin's disease. Currently there is insufficient followup to examine the risk following chemotherapy. After acute leukaemia there was 20-fold the expected number of central nervous system tumours, though this is based on only 3 cases; whether therapy is directly involved in their development is uncertain.The risks we report are rarely greater than those reported in previous large-scale studies; in most instances they are substantially less. It is very unlikely that many SPTs were missed with our follow-up system so alternative explanations require further investigation; in particular it is possible the lower risks in our data compared to series treated in the United States may be explained, in part, by less combination therapy and lower doses of radiotherapy.At least half of the children who develop cancer now survive beyond three years (Stiller, pers. comm.); thus we expect in excess of 600 such survivors each year from among individuals currently treated in Britain. The intensive therapy given to achieve the improvement in survival contributes towards late effects generally, and second primary tumours in particular. The duration of survival for many individuals includes the latent periods characteristic of radiation and chemical carcinogenesis (Boice, 1981

The findings from this population-based cohort confirm the predictive power of microalbuminuria as a risk factor for mortality in NIDDM. In contrast to prospective studies of conventional cardiovascular risk factors in NIDDM, consistent evidence indicates that microalbuminuria is an independent predictor of excess mortality regardless of the collection procedure used.

Purpose CNS tumours are the most common second primary neoplasm observed after childhood cancer in Britain, but the relationship of risk to dose of previous radiotherapy and chemotherapy is uncertain. Methods The British Childhood Cancer Survivor Study is a national population-based cohort study of 17980 individuals surviving at least 5 years after diagnosis of childhood cancer. Linkage to national population-based cancer registries identified 247 second primary neoplasms of the CNS. Cohort and nested case-control studies were undertaken. Results There were 137 meningiomas, 73 gliomas and 37 other CNS neoplasms included in the analysis. The risk of meningioma increased strongly, linearly and independently with each of dose of radiation to meningeal tissue and dose of intrathecal methotrexate. Those whose meningeal tissue received 0.01-9.99,10.00-19.99,20.00-29.99,30.00-39.99 and ≥40Gy had a risk 2,8,52,568 and 479-fold that experienced by those whose meningeal tissue was unexposed, respectively. The risk of meningioma among individuals receiving 1-39,40-69 and at least 70mg/m2 of intrathecal methotrexate was 15,11 and 36-fold that experienced by those unexposed, respectively. The standardised incidence ratio for gliomas was 10·8 (95% confidence interval: 8·5, 13·6). The risk of glioma/primitive neuroectodermal tumours increased linearly with dose of radiation and those with CNS tissue exposed to at least 40Gy experienced a risk 4-fold that experienced by those with CNS tissue unexposed. Conclusion The largest ever study of CNS tumours in childhood cancer survivors indicates the risk of meningioma increases rapidly with increased dose of radiation to meningeal tissue and increased dose of intrathecal methotrexate.