Retinoblastoma incidence and survival in European children (1978–1997). Report from the Automated Childhood Cancer Information System project
Introduction
In developed countries, retinoblastoma usually accounts for approximately 3–4% of all childhood cancers occurring during the age range 0–14 years.1, 2 Retinoblastoma is an embryonal tumour of the retina. More than 90% of cases are diagnosed during the first 5 years of life.3 In approximately 60% of cases only one eye is affected.3 There are two forms of the disease: heritable and non-heritable. Approximately 15% of the unilateral,4 and all bilateral cases, have the heritable form. Only a minority of the heritable cases will have a previous family history and it appears that most of the heritable cases are the result of de novo mutations.5 Heritable retinoblastoma behaves as an autosomal dominant condition with a variable, but usually high, degree of penetrance. The RB1 gene acts as a tumour suppressor gene and loss or mutation of both alleles is necessary for a tumour to develop. There is a 50% chance that a parent with a germline mutation in the RB1 gene will pass on the mutation to an offspring. There is then a very high probability that the offspring will develop a tumour following a further mutation or deletion leading to loss of function of the remaining RB1 allele in one or more retinal cells.6
The survival rate for retinoblastoma has been high since the 1970s.7, 8, 9 In the majority of children with unilateral disease, excellent survival rates can be achieved by enucleation (removal of the eye) followed by adjuvant chemotherapy for those children found to have adverse histological features.10 However, for children with bilateral disease, treatment is directed at saving vision as well as life. Depending on the size and location of tumours within each eye, preservation of the eye with useful vision can often be achieved by chemotherapy alone or by a combination of chemotherapy and focal therapies such as laser, cryotherapy or radioactive scleral plaque therapy.10, 11 External beam radiotherapy is reserved for children with bilateral retinoblastoma who develop recurrent disease after chemotherapy and can salvage vision in a good proportion of these children.12
As with all childhood cancers, it is essential that survivors of retinoblastoma should have long-term follow-up. In the case of heritable retinoblastoma this is particularly necessary because the mutant RB1 gene acts as a cancer susceptibility gene predisposing to the risk of a subsequent, histologically distinct cancer.13 Clinicians are acutely aware of this increased risk and the possibility that certain treatments, such as radiotherapy and chemotherapy, may increase the risk. If possible, external beam radiotherapy should be avoided during the first year of life as this seems to be the period when radiation is most likely to increase the risk of second malignancies.14 There is also a risk of leukaemias following certain chemotherapeutic agents, particularly alkylating agents and the epidopodophyllotoxins.15
This paper reports the incidence and survival rates of children with retinoblastoma in Europe, and the changes in these rates over the 20 year period 1978–1997. The results are based on the large European database of the Automated Childhood Cancer Information System (ACCIS).16
Section snippets
Data sources
All cases of retinoblastoma, as defined in group V of the International Classification of Childhood Cancer17 were extracted from the ACCIS database. The 60 data-sets included are listed in Table 1, which gives the period of coverage, quality indicators and extent of follow-up for each. The populations-at-risk given for sex, calendar year and age group in each registration area originate from official national statistics and were supplied by the cancer registries. Any missing population figures
Incidence
Table 3 shows numbers of cases, sex ratios and incidence rates for retinoblastoma in Europe for the period 1988–1997. Cumulative incidence ranged from 44.2 to 67.9 per million. The age-specific rates are roughly three times as high in infants (children under 1 year of age) as in the age group 1–4, except in the East, where the corresponding ratio is approximately two. Less than 1 retinoblastoma per million person-years occurs in the age group 5–9 years, and after 10 years of age this tumour is
Incidence
From the data collected by ACCIS, there appears to be some variation in the incidence of retinoblastoma across European regions. The higher incidence of retinoblastoma for the North as compared with the rest of Europe is similar to the greater rate for all cancers in the North shown in Table 2 of the paper by Stiller, Marcos-Gragera, Ardanaz and colleagues [this issue] on the ACCIS data. Incidence showed an increase of 1% per year after adjustment for factors including type of registry but was
Conclusions and recommendations
From the data collected by ACCIS, there appears to be some variation in the incidence of retinoblastoma across European countries. The 5-year survival rate improved from 89% to 95% during the period covered by the study, an improvement being seen for both unilateral and bilateral cases. There were relatively small differences in survival between the five regions (British Isles, East, North, South, West) covered by the study though the 5-year survival rate appeared to be lower in the East region.
Conflict of interest statement
None declared.
Acknowledgement
The ACCIS project was funded by the European Commission from the Europe Against Cancer programme (contracts SI2.126875, SI2.321970 and SPC.2002303), jointly with the International Agency for Research on Cancer. Data analyses were partly funded by the French Ligue Nationale contre le Cancer, Comité du Rhône. This work was undertaken with the help of a research grant for epidemiological studies of retinoblastoma from the Childhood Eye Cancer Trust (CHECT). We are grateful to colleagues at the
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