Long-term population-based risks of second malignant neoplasms after childhood cancer in Britain

Abstract

In a population-based, retrospective cohort study of 16 541 3-year survivors of childhood cancer treated in Britain up to the end of 1987, 278 second malignant neoplasms (SMNs) were identified against 39.4 expected giving a standardised incidence ratio (SIR) of 6.2. The overall cumulative risk of an SMN by 25 years from 3-year survival from childhood cancer was 4.2%. Analysis of the cohort of nonretinoblastoma childhood cancers combined revealed a significant decline in SIR of SMN with increasing duration of follow-up. There was a greater risk of developing a SMN, particularly secondary acute myeloid leukaemia, in those diagnosed with childhood cancer from 1980 onwards. However, on multivariate modeling, this was not an independent risk factor. There was significant heterogeneity (Po0.001) in SIR of SMN across different treatment groups, the greatest risk observed in the group exposed to both radiotherapy and chemotherapy. The risks of SMN observed were comparable with those in other population-based studies. While the decline in SIR with duration of follow-up and the small excess numbers of cancers observed over later decades after diagnosis are reassuring, the high excess risk, particularly of leukaemia, associated with recent more intense therapy is of concern. British Journal of Cancer (2004) Survival after childhood cancer has greatly improved over the last three decades and most recent figures indicate that over 70% of children with cancer are likely to survive at least 5 years (National Registry of Childhood Tumours, unpublished). This growing population of survivors, estimated at 1 in every 1000 young adults (Hawkins and Stevens, 1996), is at risk of certain adverse late effects of both the cancer and its treatment including second malignant neoplasms (SMN). This long recognised increased risk (Meadows et al, 1985) represents perhaps the greatest challenge to long-term survival (Robison and Mertens, 1993). Of multifactorial aetiology, risk has been associated with the primary malignancy, exposure to chemotherapy and radiotherapy and genetic predisposition (Kony et al, 1997). A major difficulty in the analysis of SMNs is the assembling of large numbers of survivors who have been followed up over sufficiently long periods of time with a wide spectrum of treatments.We have investigated the risks of SMNs after childhood cancer using a large UK population-based cohort of patients with substantially longer average follow-up than that in previous comparable studies.

Risk of thyroid cancer in survivors of childhood cancer: Results from the British Childhood Cancer Survivor Study

“…Overall SIR was 18.0 (13.4-23.8) with 50 observed cases and 2.77 expected after a median follow up per survivor of 17.4 years from 5-year survival. These results appear slightly higher than those reported by Jenkinson et al 5 using a similar British populationbased cohort of 3-year childhood cancer survivors: SIR 13.4 (7.3-22.5) for thyroid and endocrine SPN (n 5 14). However, in the study by Jenkinson et al, the SIR included other endocrine SPNs, in addition to thyroid cancer, and so precise comparison is not possible.…”

“…2 Approximately 1,500 children are diagnosed each year with cancer in the United Kingdom 3 and 1 in 640 young adults (aged 20-39 years) becomes a survivor of childhood cancer. 4 Childhood cancer survivors are at an increased risk of late effects of treatment, including the development of second primary neoplasms (SPNs) 5 including thyroid cancer. The thyroid gland is a highly radiosensitive organ.…”

Secondary hematopoietic malignancies in survivors of childhood cancer

“…2,18,19 It also demonstrates that the incidence, risk trends, and outcome of childhood cancer survivors who develop secondary hematological malignancies vary by primary cancer type and treatment periods.…”

A study of soft tissue sarcomas after childhood cancer in Britain

“…However, the numbers were too small for the CT model to converge. (Jenkinson et al, 2004). The greatest STS risk followed Wilms' tumour (SIR ¼ 45.9) and heritable retinoblastoma (SIR ¼ 41.3), based on four and two cases respectively.…”