Search

Purpose: To assess the specific role of treatment and type of first cancer (FC) in the risk of long-term subsequent breast cancer (BC) among childhood cancer survivors., Patients and Methods: In a cohort of 1,814 3-year female survivors treated between 1946 and 1986 in eight French and English centers, data on chemotherapy and radiotherapy were collected. Individual estimation of radiation dose to each breast was performed for the 1,258 patients treated by external radiotherapy; mean dose to breast was 5.06 Gy (range, 0.0 to 88.0 Gy) delivered in 20 fractions (mean)., Results: Mean follow-up was 16 years; 16 patients developed a clinical BC, 13 after radiotherapy. The cumulative incidence of BC was 2.8% (95% CI, 1.0% to 4.5%) 30 years after the FC and 5.1% (95% CI, 2.1% to 8.2%) at the age of 40 years. The annual excess incidence increased as age increased, whereas the standardized incidence ratio decreased. On average, each Gray unit received by any breast increased the excess relative risk of BC by 0.13 (< 0.0 to 0.75). After stratification on castration and attained age, and adjusting for radiation dose, FC type, and chemotherapy, a higher risk of a subsequent BC was associated with Hodgkin's disease (relative risk, 7.0; 95% CI, 1.4 to 30.9)., Conclusion: The reported high risk of BC after childhood Hodgkin's disease treatment seems to be due not only to a higher radiation dose to the breasts, but also to a specific susceptibility.

Soft tissue sarcoma (STS) is one of the most frequent second primary cancer that occurs during the first 20 years following treatment for a solid cancer in childhood. Our aim was to quantify the risk of STS as a second malignant neoplasm and to investigate its relationship with radiotherapy and chemotherapy. A cohort study of 4,400 3-year survivors of a first solid cancer diagnosed during childhood in France or the United Kingdom, between 1942 and 1985, was followed 15 years on average. In a partially nested case-control study, we matched 25 cases of STS and 121 controls for sex, type of first cancer, age at first cancer and duration of follow-up. Sixteen STS occurred in the cohort, as compared to 0.3 expected from the general population (Standardized Incidence Radio, SIR = 54 (95%CI: 34-89)). The SIR was 113 (95% CI: 62-185) after chemotherapy plus radiotherapy (13 STS), whereas it was 28 (95%CI: 2-125) after chemotherapy alone (1 STS) and 19 (95%CI: 3-60) after radiotherapy alone (2 STS). After adjustment for treatment, there was no evidence of variation in the annual excess of incidence or in the SIR with either age at first cancer or time since 1st cancer. In the case-control study, the risk of a STS was increased with the square of the dose of radiation to the site of STS development and with the administration of Procarbazine. The increased risk of soft tissue sarcoma that occurred after childhood cancer is independently related to exposure to radiotherapy and Procarbazine. A closer surveillance of children treated with this treatment combination is strongly recommended., (Copyright 2004 Wiley-Liss, Inc.)

Background: The thyroid gland is among the most radiosensitive organs. However, little is known about the long-term risk of developing a thyroid tumor after fractionated external radiotherapy for cancer during childhood., Objective: To study the long-term risk of developing a thyroid tumor in 4096 three-year survivors of childhood cancer treated between May 1942 and December 1985 in 8 centers in France and the United Kingdom, 2827 of whom had received external radiotherapy., Methods: A wide range of radiation doses were given to the thyroid: 1164 children received less than 0.5 Gy and 812 received more than 5.0 Gy, the average dose being 7.0 Gy., Results: After mean follow-up of 15 years (range, 3-45 years), 14 patients-all of whom had received radiotherapy-developed a clinical thyroid carcinoma. Within the cohort, the relation between radiation dose to the thyroid and risk of thyroid carcinoma and adenoma was similar to that observed in patients who received radiotherapy during childhood for other reasons, such as an excess relative risk per gray of 4 to 8, up to a few gray. In contrast, compared with thyroid cancer incidence in the general population, the standardized incidence of thyroid carcinoma was much higher than expected from the dose-response relationship estimated within the cohort and from patients who received radiotherapy during childhood for other reasons: a dose of 0.5 Gy was associated with a standardized incidence ratio of 35 (90% confidence interval, 10-87) and a dose of 3.6 Gy with a standardized incidence ratio of 73 (90% confidence interval, 28-153). We did not show a reduction in excess relative risk per gray with use of an increasing number of fractions., Conclusion: Although we cannot estimate the exact proportion, it is probable that some or all children who are treated for cancer are predisposed to developing a thyroid carcinoma.

The variation in the risk of solid second malignant neoplasms (SMN) with time since first cancer during childhood has been previously reported. However, no study has been performed that controls for the distribution of radiation dose and the aggressiveness of past chemotherapy, which could be responsible for the observed temporal variation of the risk. The purpose of this study was to investigate the influence of the treatment on the long-term pattern of the incidence of solid SMN after a first cancer in childhood. We studied a cohort of 4400 patients from eight centres in France and the UK. Patients had to be alive 3 years or more after a first cancer treated before the age of 17 years and before the end of 1985. For each patient in the cohort, the complete clinical, chemotherapy and radiotherapy history was recorded. For each patient who had received external radiotherapy, the dose of radiation received by 151 sites of the body were estimated. After a mean follow-up of 15 years, 113 children developed a solid SMN, compared to 12.3 expected from general population rates. A similar distribution pattern was observed among the 1045 patients treated with radiotherapy alone and the 2064 patients treated with radiotherapy plus chemotherapy; the relative risk, but not the excess absolute risk, of solid SMN decreased with time after first treatment; the excess absolute risk increased during a period of at least 30 years after the first cancer. This pattern remained after controlling for chemotherapy and for the average dose of radiation to the major sites of SMN. It also remained when excluding patients with a first cancer type or an associated syndrome known to predispose to SMN. When compared with radiotherapy alone, the addition of chemotherapy increases the risk of solid SMN after a first cancer in childhood, but does not significantly modify the variation of this risk during the time after the first cancer.

A cohort of 4,400 persons treated for various cancers of childhood in France and the UK was followed up over an extended period to assess risks of subsequent brain tumour in relation to the radiotherapy and chemotherapy that the children received for their first cancer. Elevated risks of subsequent brain tumours were associated with first central nervous system (CNS) tumour (two-sided p = 0.0002) and neurofibromatosis (two-sided p = 0.001). There was also elevated brain tumour risk (two-sided p = 0.003) associated with ionising radiation exposure, the risk being concentrated among benign and unspecified brain tumours. The radiation-related risk of benign and unspecified brain tumours was significantly higher than that of malignant brain tumours (two-sided p< or =0.05); there was no significant change of malignant brain tumour risk with ionising radiation dose (two-sided p > 0.2). In general, there were no strong associations between alkylating agent dose and brain tumour risk. The only significant association between brain tumour risk and alkylating agent dose was in relation to compounds used (bleomycin, chloraminophen) that are thought not to deliver substantial doses to the brain; the statistical significance of the trend with dose depended on a single case, and thus must be considered a weak result.

Osteosarcoma is the most frequent second primary cancer occurring during the first 20 years following treatment for a solid cancer in childhood. Using a cohort study of children treated for a solid cancer, we investigated the incidence and etiology of osteosarcoma as a second malignant neoplasm after childhood cancer in a cohort and a case-control study. We analysed the relationship between the local dose of radiation and the risk of osteosarcoma, taking into account chemotherapy received. A cohort study of 4,400 3-year survivors of a first solid cancer during childhood diagnosed in France or the United Kingdom, between 1942 and 1986, revealed 32 subsequent osteosarcomas. In a nested case-control study, we matched 32 cases and 160 controls for sex, type of first cancer, age at first cancer and the duration of follow-up. Parameters studied were the incidence of osteosarcoma, the cumulative local dose of irradiation and the cumulative dose of chemotherapy received by cases and controls. The risk of a osteosarcoma was found to be a linear function of the local dose of radiation (excess relative risk per gray=1.8), and was found to increase with the number of moles of electrophilic agents per square meter but not with other drugs. No interaction was noted between radiotherapy and chemotherapy. Bilateral retinoblastoma, Ewing's sarcoma and soft tissue sarcoma were found to render patients susceptible to a higher risk of developing an osteosarcoma as a second malignant neoplasm. We recommend long-term surveillance of patients who were treated during childhood for bilateral retinoblastoma, Ewing's sarcoma, soft tissue sarcoma, as well as other first cancer treated with radiotherapy plus high doses of chemotherapy, without focusing exclusively on the radiation field.

Background: Radiotherapy and chemotherapy are associated with an increased risk of second malignant neoplasm (SMN). An association between SMN and familial aggregation has also been shown. The aim of this study was to investigate the role of familial factors in the risk of SMN and their potential interaction with the effect of treatment., Methods: We devised a case-control study of 25 children with SMN (cases) and 96 children with no SMN after a cancer treatment (controls), taken from a cohort of 649 children treated at our institution between 1953 and 1985. A complete family history was obtained for patients and controls and a familial index defined to evaluate the degree of familial aggregation. The radiation dose given at 151 sites in the body was estimated for each radiotherapy course for each child., Findings: Among family members of the 25 SMN cases, there were ten with early-onset (< or = 45 years) cancer, compared with eight among relatives of the 96 controls. Compared with patients who had no family history of early-onset cancer, those with one or more affected family members had an odds ratio for SMN of 4.7 (95% CI 1.3-17.1; p = 0.02). Adjustment for local radiation dose and exclusion of patients known to be predisposed to SMN (carriers of p53 mutation and those with Recklinghausen's disease) did not affect this risk substantially., Interpretation: Both genetic factors and exposure to ionising radiation have independent effects on the risk of SMN. Follow-up of children treated for cancer should be especially vigilant when there is a family history of early-onset cancer.

Because genetic predisposition probably plays an important role in the aetiology of most of childhood cancers, studies of second primaries occurring after these cancers may be particularly informative about possible common genetic mechanisms in both of these cancers. We have studied the incidence of thyroid tumours occurring after cancer in childhood in a cohort of 592 children treated before 1970. Among these children, six later developed a thyroid carcinoma, and 18 developed a thyroid adenoma. Radiation doses received to the thyroid by each of the irradiated children have been estimated using individual radiotherapeutic technical records. Thyroid carcinomas and thyroid adenomas were five times more frequent after irradiation for neuroblastoma than after irradiation for any other first cancer. This ratio did not depend on sex, nor on time elapsed since irradiation, nor on dose of radiation received for the thyroid gland. This result suggests that there is a common mechanism for the occurrence of neuroblastoma and of differentiated thyroid tumour.