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.

Among a cohort of British childhood cancer survivors, the greatest excess risk associated with subsequent primary neoplasms at older than 40 years was for digestive and genitourinary neoplasms.

Overall mortality in CD is double that of the general population. However, patients with CD in remission fare much better than those with persistence of hypercortisolism, and they appear not to have an increased mortality rate. Hypertension and diabetes mellitus are risk factors for worse outcome. Because diagnosis and treatment of patients are at a young age, much longer follow-up of patients in remission is required before one can be confident that their mortality outcome is no different from that of the general population, especially because cardiovascular risk factors may persist after successful biochemical control of the disease.

This is the largest available population-based cohort of childhood cancer survivors to have included investigation of a wide spectrum of adverse outcomes (the risk of which might be increased as a result of childhood cancer or its treatment). The study should provide useful information for counselling survivors, planning long-term clinical follow-up and evaluating the long-term risks likely to be associated with proposed treatment strategies.

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.

Purpose: We used data from the first large-scale overwhelmingly population-based study (a) to quantify the risk of adverse pregnancy outcomes in survivors of childhood cancer in relation to cancer type and treatment and (b) to assess live birth rates relative to the general population. Methods: A questionnaire, including questions inquiring about pregnancy outcomes, was completed by 10,483 survivors. A total of 7,300 pregnancies were reported. Odds ratios (OR) for live birth, miscarriage, termination, stillbirth, premature birth, and low birth weight were calculated for different types of childhood cancer and by whether initial treatment involved chemotherapy and abdominal or brain irradiation. For females, the observed number of live births was compared with that expected based on the general population of England and Wales. Results: Female survivors exposed to abdominal irradiation had a significantly increased OR of delivering preterm [OR, 3.2; 95% confidence interval (95% CI), 2.1-4.7] and producing offspring with a low birth weight (OR, 1.9; 95% CI, 1.1-3.2). An increased OR of miscarriage was also associated with abdominal radiotherapy (OR, 1.4; 95% CI, 1.0-1.9). The number of live births observed from all female survivors was two thirds of that expected (O/E, 0.64; 95% CI, 0.62-0.66) and lowest among survivors treated with brain (O/E, 0.52; 95% CI, 0.48-0.56) and abdominal radiotherapy (O/E, 0.55; 95% CI, 0.50-0.61). Conclusion: Female survivors of childhood cancer treated with abdominal radiotherapy are at 3-fold increased risk of delivering preterm, 2-fold increased risk of low birth weight, and a small increased risk of miscarriage. Overall, female survivors produce considerably fewer offspring than expected, particularly those treated with abdominal or brain radiotherapy.

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.

Specific groups of childhood cancer survivors achieve lower-than-expected educational attainment. Detailed educational support and implementation of regular cognitive assessment may be indicated for some groups to maximize long-term function.