Dr Jan Alsner told ECCO12 - The European Cancer Conference today (Wednesday 24 September) that this finding was independent of whether the children had been treated with radiotherapy or not; none of them had had chemotherapy, thus enabling Dr Alsner and his colleagues to make reliable calculations about the effect of radiotherapy. (Previous research had suggested radiotherapy could be the reason for a greater number of second primary tumours).
In the world's longest-running, complete population-based study, the researchers tracked down data on 266 retinoblastoma patients, covering a 57-year period from 1943 to 2000**. Much of the data came from the Danish Cancer Registry, which is the oldest registry in the world; it was able to give details on the treatment of every retinoblastoma case in Denmark, and family details of all the cases tracked (identifying parents, siblings, children etc).
They found that 22 of the 236 retinoblastoma survivors had gone on to develop a second, primary tumour. Among the 148 patients with non-hereditary retinoblastoma, there were seven cases of a second, primary cancer; but among the 88 patients with hereditary retinoblastoma, there were 15 cases of a second, primary cancer.
Dr Alsner, an associate professor at the Department of Experimental Clinical Oncology at Aarhus University Hospital, Denmark, said: "Forty years after treatment for retinoblastoma, the cumulative risk of developing - and dying from - a second primary cancer in the non-hereditary group during that time was similar to the general population at five and three per cent respectively. However, among the hereditary group, the cumulative risk was significantly higher, at 25 and 12 per cent respectively. Among the hereditary patients, their increased risk was the same, whether or not their original retinoblastoma had been treated with radiotherapy."
The second cancers were of the same type and occurred at the same sort of time or age as the cancers in the general population. The only exception was that there was a slightly higher incidence of malignant melanomas and sarcomas amongst the second cancers in the hereditary group of patients.
Dr Alsner said: "We can only speculate as to why there is this increased incidence of melanomas and sarcomas. They are amongst the most frequent tumours in the normal population with the same age distribution as the people in our study (3 to 55 years old). Furthermore, one of the critical steps in the development of these tumours is the inactivation of the RB (retinoblastoma) pathway, which includes a number of genes that make (or code for) proteins that are involved in the normal control of cell division. At least one of these genes needs to be inactivated before a cell starts to develop into a melanoma or sarcoma. In some of these genes, including the retinoblastoma gene, both the maternal and paternal copies of the gene have to be inactivated by two independent events before cancer starts. If someone already has an inactivated copy of the gene because they have inherited it, it will increase their risk of a tumour developing because there is only one gene left to be inactivated, rather than two."
He concluded: "In the past 40 years, the treatment of retinoblastoma has improved dramatically, resulting in nearly 100% cure rate if the cancer is recognized at an early stage. The ways of treating retinoblastoma still need to be improved, especially in order to minimize the side effects of the therapy. Our study shows that there is an increased risk of developing a second, primary tumour in patients with hereditary retinoblastoma. This risk is not linked to the use of radiotherapy in treating the retinoblastomas, but strictly to the genetic status of the patient. We need to focus more on these second tumours. However, since they can occur at almost any age and be of several different types, it is difficult at the moment to set up efficient screening programmes for these affected families."
Abstract no: 721 (Wednesday 24 September, 10.45hrs CET, Paediatric Oncology session)
* Retinoblastoma is a rare, but highly malignant tumour of the retina, affecting babies and young children. It occurs in approximately one in 20,000 children and represents about three per cent of all childhood malignancies. If recognised early, it has a 95% survival rate, but treatment often involves removal of the affected eye.
** The work was supported by the Danish Cancer Society.
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