Second and subsequent tumours among 1927 retinoblastoma patients diagnosed in Britain 1951-2004.

BACKGROUND: Retinoblastoma is an eye tumour of childhood that occurs in heritable and non-heritable forms. In the heritable form, there is a predisposition to the development of non-ocular subsequent primary tumours (SPTs). METHODS: This study included 1927 retinoblastoma patients diagnosed in Britain from 1951 to 2004. Ascertainment was through the (UK) National Registry of Childhood Tumours; cases were followed-up for the occurrence of SPTs. Standardised incidence ratios (SIRs) were calculated. RESULTS: We identified 169 SPTs in 152 patients. The SIR analysis included 145 SPTs with cancer registrations from the years 1971 to 2009. These tumours occurred in 132 patients: 112 of the 781 heritable and 20 of the 1075 (presumed) non-heritable cases under surveillance at the start of this period developed at least one registered SPT. The SIRs for all tumours combined were 13.7 (95% confidence interval 11.3-16.5) in heritable cases and 1.5 (0.9-2.3) in non-heritable cases. The main types of SPT in the heritable cases were leiomyosarcoma, (31 cases; SIR 1018.7 (692.2-1446.0)), osteosarcoma (26 cases; SIR 444.6 (290.4-651.4)), and skin melanoma (12 cases; SIR 18.6 (9.6-32.4)). CONCLUSION: The risk of SPTs in heritable retinoblastoma is extremely high. This has important implications for the clinical follow-up and counselling of survivors and their families.

Patterns of care and survival for patients aged under 40 years with bone sarcoma in Britain, 1980-1994.

The purpose of the study was to calculate population-based survival rates for osteosarcoma (OS) and Ewing's sarcoma (ES) in Great Britain during 1980-1994, determine proportions of patients treated at specialist centres or entered in national and international clinical trials, and investigate effects of these factors on survival. Data on a population-based series of 1349 patients with OS and 849 with ES were compiled from regional and national cancer registries, UK Children's Cancer Study Group, regional bone tumour registries and clinical trials. Follow-up was through population registers. Survival was analysed by actuarial analysis with log-rank tests and by Cox's proportional hazards analysis. Five-year survival rates during 1980-1984, 1985-1989 and 1990-1994 were 42% (95% CI: 37, 46), 54% (95% CI: 50, 59) and 53% (95% CI: 48, 57), respectively, for OS and 31% (95% CI: 26, 37), 46% (95% CI: 40, 51) and 51% (95% CI: 45, 57) for ES. Proportions of patients treated at a supraregional bone tumour centre or a paediatric oncology centre in the three quinquennia were 36, 56 and 67% for OS and 41, 60 and 69% for ES. In 1983-1992, 48% of OS patients were entered in a national trial; for ES, 27% were entered in 1980-1986 and 54% in 1987-1994. Survival was similar for trial and nontrial patients with OS. For ES, trial patients had consistently higher 5-year survival than nontrial patients: 1980-1986, 42 vs 30%; 1987-1992, 59 vs 42%; 1993-1994, 54 vs 43%. During 1985-1994, patients with OS or ES whose main treatment centre was a nonteaching hospital had lower survival rates. In multivariate analyses of patients diagnosed during 1985-1994 that also included age, sex, primary site, surgical treatment centre, the results relating to main treatment centre for both OS and ES retained significance but the survival advantage of trial entry for ES became nonsignificant. For both OS and ES diagnosed since 1985, patients whose main treatment centre was a nonspecialist hospital had a lower survival rate.

Patterns of childhood cancer among siblings.

The National Registry of Childhood Tumours contains over 51000 records of children born in Great Britain who developed cancer under the age of 15 years. Patterns of childhood cancer among families containing more than one child with cancer have been studied. A total of 225 "sib pair' families have been ascertained from interviews with parents of affected children, from hospital and general practitioner records and from manual and computer searches of names and addresses of patients. A number of special groups have been identified, including those with a known genetic aetiology such as retinoblastoma, twins and families with three or more affected children. A further 148 families not in any of the above groups contain two children with cancer: in 46 families the children had tumours of the same type, most commonly leukaemia. Some of the families are examples of the Li-Fraumeni syndrome; some are associated with other conditions, including Down's syndrome. There is clearly a genetic element in the aetiology of cancer in some families discussed here; shared exposure to environmental causes may account for others and some will be simply due to chance.

Patterns of risk of hereditary retinoblastoma and applications to genetic counselling.

A registry including information about nearly 1,600 cases of retinoblastoma diagnosed in Britain has been created at the Childhood Cancer Research Group. Cases have been classified as 'old germ cell mutation', 'new germ cell mutation' or 'sporadic non-hereditary'. For a population-based group of 918 cases diagnosed between 1962 and 1985 we have calculated the proportions of unilateral/bilateral and hereditary/non-hereditary cases. Bilateral cases represent 40% of the total number over this period; the proportion known to be hereditary is 44%, a higher proportion than has been reported elsewhere. By following up selected groups of cases, an estimate has been made of the proportions of siblings of retinoblastoma patients and offspring of survivors from retinoblastoma who are themselves affected with the disease. Where there is no previous family history, the risk for siblings of retinoblastoma patients of developing the disease is approximately 2% if the disease in the affected child is bilateral and 1% if it is unilateral, assuming that there are no other siblings; if there are unaffected siblings the risks for subsequent children are lower. Children of patients with hereditary retinoblastoma have a one in two chance of carrying the germ cell mutation and for those who are carriers the probability of developing retinoblastoma is very close to the accepted figure of 90% if the parents have bilateral retinoblastoma but probably less if they have the unilateral form. For children of patients not known to be carriers, the probability of developing retinoblastoma is estimated to be about 1%, considerably lower than the previously accepted figure of about 5%. Retinoblastoma kindreds consist mainly of bilateral cases but there is evidence that some kindreds have a high proportion of unilateral cases. The ways in which these findings may be used in conjunction with modern techniques of molecular biology for prenatal and postnatal genetic counselling are discussed.