Incidence of second primary tumours among childhood cancer survivors

Abstract

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

A study of soft tissue sarcomas after childhood cancer in Britain

“…The well-recognised increased risk of a second malignant neoplasm (SMN) (Meadows et al, 1985) may represent the greatest challenge to long-term survival (Robison and Mertens, 1993). Further study of their causes, which include both exposure to chemotherapy (CT), radiotherapy (RT) and genetic predisposition (Kony et al, 1997), requires follow-up of large numbers of survivors with a wide spectrum of treatments.Soft tissue sarcoma (STS) represents an important risk of SMN following childhood cancer, particularly heritable retinoblastoma (Draper et al, 1986;Hawkins et al, 1987;Westermeier et al, 1998; Menu-Branthomme et al, 2004). The one published case -control study of STS following childhood cancer demonstrated an independent association with exposure to RT and CT with procarbazine (Menu-Branthomme et al, 2004).…”

“…Soft tissue sarcoma (STS) represents an important risk of SMN following childhood cancer, particularly heritable retinoblastoma (Draper et al, 1986;Hawkins et al, 1987;Westermeier et al, 1998; Menu-Branthomme et al, 2004). The one published case -control study of STS following childhood cancer demonstrated an independent association with exposure to RT and CT with procarbazine (Menu-Branthomme et al, 2004).…”

Patterns of multiple primary tumours in patients treated for cancer during childhood

“…Abramson et al (1984), we have not included them as second tumour cases as in our opinion the intracranial lesion in these cases is not histologically distinct from the primary retinoblastoma. Further details of the ascertainment of cases will be given by Hawkins et al (1987).…”

“…In this report we describe 161 patients who have developed more than one primary neoplasm and examine the various factors which may have influenced the development of the second primary tumour. We have not attempted to estimate the risk of developing a second tumour in this paper as an analysis of incidence rates is the subject of a separate communication (Hawkins et al, 1987). Our main purpose here is to describe the patterns of multiple tumours that have been observed and to identify the possible influence of genetic factors and previous therapy in the pathogenesis of the second tumour.…”

“…A large proportion of these survivors will reach adulthood, potentially 'cured' of their tumours. Recently however, the considerable optimism engendered amongst clinicians by this improvement in survival has been tempered by a growing awareness that patients who have been successfully treated for one cancer appear to be at greater risk than the general population of developing a second histologically distinct malignancy (Li, 1977;Mike et al, 1982;Meadows et al, 1985;Hawkins et al, 1987). Although the occurrence of multiple primary tumours in any individual may reflect an inherent predisposition to cancer, it is likely that the therapies given to eradicate the first tumour are significant factors in the pathogenesis of many, perhaps most, second primary tumours.…”