A study of soft tissue sarcomas after childhood cancer in Britain

Abstract

Among 16 541 3-year survivors of childhood cancer in Britain, 39 soft tissue sarcomas (STSs) occurred and 1.1 sarcomas were expected, yielding a standardised incidence ratio (SIR) of 16.1. When retinoblastomas were excluded from the cohort, the SIR for STSs was 15.9, and the cumulative risk of developing a soft tissue tumour after childhood cancer within 20 years of 3-year survival was 0.23%. In the case -control study, there was a significant excess of STSs in those patients exposed to both radiotherapy (RT) and chemotherapy, which was five times that observed among those not exposed (P ¼ 0.02). On the basis of individual radiation dosimetry, there was evidence of a strong dose -response effect with a significant increase in the risk of STS with increasing dose of RT (Po0.001). This effect remained significant in a multivariate model. The adjusted risk in patients exposed to RT doses of over 3000 cGy was over 50 times the risk in the unexposed. There was evidence of a dose -response effect with exposure to alkylating agents, the risk increasing substantially with increasing cumulative dose (P ¼ 0.05). This effect remained after adjusting for the effect of radiation exposure. British Journal of Cancer (2007) Survival after childhood cancer has greatly improved over the last three decades and most recent figures indicate that about 75% of children diagnosed with cancer are likely to survive at least 5 years (Toms, 2004). Thus a growing number of survivors, estimated at 1 in every 1000 young adults (Hawkins and Stevens, 1996), are at risk of various adverse late effects of both the cancer and its treatment. 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).We here examined the incidence of STS in a population-based cohort of 3-year survivors of childhood cancer in Britain, and explored their aetiological factors in a much larger case -control analysis than previously reported. For present purposes, STS occurring as an SMN will be referred to simply as STS. MATERIALS AND METHODS Cohort studyA cohort of 3-year survivors of childhood cancer was selected from the National Register of Childhood Tumours (NRCT), a population-based national register covering the whole of Great Britain, which is maintained by the Childhood Cancer Research Group (CCRG), at the Univ...

Solid cancers after allogeneic hematopoietic cell transplantation

“…For the majority of these sites, risks were greater among those who survived 5 or more years after initial radiotherapy, in keeping with the latent period typical for radiationrelated solid cancers. 22 These findings are consistent with prior studies that evaluated the risks of radiation-induced solid cancers among cancer survivors [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] as well as atomic bomb survivors and other radiation-exposed populations. 22,39,40 Our finding of a nearly 6-fold increased risk for radiation-associated breast cancer after HCT confirms a recent report linking breast cancer excesses with young age at transplantation (younger than 18 years) and use of TBI, with the risk increasing sharply among those followed for 10 or more years.…”

Second malignancies after childhood noncentral nervous system solid cancer: Results from 13 cancer registries

“…The main known risk factors for second cancers are the type and dose of the therapy received for the treatment of the childhood cancer, host factors such as genetic predispositions and the interaction between these two. The incidence of second cancers after a malignant neoplasm in the pediatric ages has been estimated in several studies, [3][4][5][6][7][8][9][10] especially for the most frequent malignancies (lymphohaematopoietic and brain neoplasms) and for short or intermediate follow-up times. On the other hand, information on the longterm risk of second malignancies after the rarest types of childhood cancer is more limited because large groups of patients have to be followed up for more than three or four decades.…”

“…On the other hand, information on the longterm risk of second malignancies after the rarest types of childhood cancer is more limited because large groups of patients have to be followed up for more than three or four decades. 3,4,9,11 We have estimated the risk of second malignancies after childhood NCNSSC by taking advantage of a unique source of data consisting of a large cohort of survivors from 13 population-based registries located in Europe, North America, Asia and Oceania. The aim of our study is to investigate the magnitude of risk and type of second cancer in relation to the type of childhood NCNSSC, calendar period of NCNSSC diagnosis and time elapsed since NCNSSC diagnosis.…”

Case–control study on the therapy of childhood cancer and the occurrence of second malignant neoplasms in Germany

“…Our study like others had shown before that patients undergoing radiotherapy, especially at the highest dose levels, have a markedly increased risk to develop second solid tumors (e.g., [36,37]). …”