Radiation dose, chemotherapy and risk of soft tissue sarcoma after solid tumours during childhood

Abstract

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.

Concomitant chemo‐radiotherapy and local dose of radiation as risk factors for second malignant neoplasms after solid cancer in childhood: A case–control study

“…18 The risk of an osteosarcoma was found to increase with the number of moles of electrophilic agents per square meter while the risk of STS increased with the administration of Procarbazine. 12 Similar results were found in sub-cohort analysis studying the risk of developing a thyroid carcinoma 20 or any SMN after neuroblastoma in childhood. 29 In contrast, no significant increased risk of a malignant brain tumor or a breast tumor was observed with ionizing radiation dose in the respective 2 following cohort studies.…”

“…This result is at variance with that reported in most other casecontrol studies of SMN after childhood cancer. 8,9,12,17,24 One explanation might be over-matching in our study: each case and the matched controls were treated for the same type of cancer, at the same age and during the same calendar year; however, these 3 variables are known to be strongly correlated to type of treatment. Over-matching to radiotherapy data is less of an issue as there is more variation of radiotherapy modalities and doses.…”

“…Three case-control studies, including 36% of cases of the present case-control study, have previously shown the role of the local dose of radiation received at the site of the second cancer on the risk of an osteosarcoma, 8 a soft tissue sarcoma (STS) 12 and a melanoma. 18 The risk of an osteosarcoma was found to increase with the number of moles of electrophilic agents per square meter while the risk of STS increased with the administration of Procarbazine.…”

“…1 The onset of a second malignant neoplasm (SMN) is one of the most devastating events in these patients. 2 Most of the studies addressing this issue have dealt either with a SMN after a specific first malignant neoplasm (FMN), most often Hodgkin's disease [3][4][5][6] or with specific types of SMN such as bone cancer [7][8][9][10] or soft tissue sarcoma 11,12 after any FMN. Several studies have addressed the role of radiotherapy and chemotherapy in the development of any SMN after cancer in childhood [13][14][15][16][17] but only a few of them have investigated the risk according to the local dose of radiation received at different body sites.…”

RB1 and TP53 pathways in radiation-induced sarcomas

“…Radiation-induced tumours are rare in adults (Travis, 2002), but are among the most frequent secondary cancers for patients treated by radiotherapy for a first cancer during childhood (Menu-Branthomme et al, 2004). The risk of radiation-induced tumour is especially elevated for patients with some germline mutations predisposing to sporadic cancers.…”