EVALUATION DES PERTURBATIONS INDUITES SUR LA MESURE DE LA DOSE ABSORBEE AVEC DES CHAMBRES D'IONISATION, DES DOSIMETRES CHIMIQUES ET DES DOSIMETRES THERMOLUMINESCENTS DANS DES FAISCEAUX D'ELECTRONS DE HAUTE ENERGIE

TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF

Quantified relationship between cellular radiosensitivity, DNA repair defects and chromatin relaxation: a study of 19 human tumour cell lines from different origin.

International audienceBACKGROUND AND PURPOSE: There is still confusion in the choice of the molecular assays to predict the radiation response of human cells. The case of tumours appears to be particularly complex, may be because of their instability and heterogeneity. The aim of this study was to investigate quantitatively the relationships between DNA double-strand breaks (DSB) repair, chromatin relaxation and cellular radiosensitivity. Nineteen human tumour cell lines, representing a large spectrum of radiation responses and tissues, were examined. MATERIALS AND METHODS: Intrinsic radiosensitivity was quantified with surviving fraction at 2 Gy (SF2) as an endpoint. Standard and modified pulsed-field gel electrophoresis techniques were employed to assess DSB repair rate and chromatin relaxation. A cell-free assay was chosen to estimate DSB repair activity, independently of chromatin impairment. RESULTS AND CONCLUSIONS: Surviving fraction at 2 Gy (SF2) decreases linearly with the amount of unrepaired DSB and the extent of chromatin relaxation: one additional unrepaired DSB per cell or 1% chromatin decondensation produce a loss of about 1.5% surviving fraction. However, all the cell lines did not obey both correlations, suggesting that DSB repair and chromatin impairments contribute separately to increase the severity of DNA damage involved in cell lethality. Four cell lines groups showing different DSB repair and/or chromatin impairments were defined. Cell lines exhibiting both DSB repair defect and chromatin relaxation are the most radiosensitive

Retrospective Reconstructions of Active Bone Marrow Dose-Volume Histograms

International audiencePurpose: To present a method for calculating dose-volume histograms (DVH's) to the active bone marrow (ABM) of patients who had undergone radiation therapy (RT) and subsequently developed leukemia.Methods and materials: The study focuses on 15 patients treated between 1961 and 1996. Whole-body RT planning computed tomographic (CT) data were not available. We therefore generated representative whole-body CTs similar to patient anatomy. In addition, we developed a method enabling us to obtain information on the density distribution of ABM all over the skeleton. Dose could then be calculated in a series of points distributed all over the skeleton in such a way that their local density reflected age-specific data for ABM distribution. Dose to particular regions and dose-volume histograms of the entire ABM were estimated for all patients.Results: Depending on patient age, the total number of dose calculation points generated ranged from 1,190,970 to 4,108,524. The average dose to ABM ranged from 0.3 to 16.4 Gy. Dose-volume histograms analysis showed that the median doses (D50%) ranged from 0.06 to 12.8 Gy. We also evaluated the inhomogeneity of individual patient ABM dose distribution according to clinical situation. It was evident that the coefficient of variation of the dose for the whole ABM ranged from 1.0 to 5.7, which means that the standard deviation could be more than 5 times higher than the mean.Conclusions: For patients with available long-term follow-up data, our method provides reconstruction of dose-volume data comparable to detailed dose calculations, which have become standard in modern CT-based 3-dimensional RT planning. Our strategy of using dose-volume histograms offers new perspectives to retrospective epidemiological studies

Frequency Distribution of Second Solid Cancer Locations in Relation to the Irradiated Volume Among 115 Patients Treated for Childhood Cancer

International audiencePurpose: To provide better estimates of the frequency distribution of second malignant neoplasm (SMN) sites in relation to previous irradiated volumes, and better estimates of the doses delivered to these sites during radiotherapy (RT) of the first malignant neoplasm (FMN).Methods and materials: The study focused on 115 patients who developed a solid SMN among a cohort of 4581 individuals. The homemade software package Dos_EG was used to estimate the radiation doses delivered to SMN sites during RT of the FMN. Three-dimensional geometry was used to evaluate the distances between the irradiated volume, for RT delivered to each FMN, and the site of the subsequent SMN.Results: The spatial distribution of SMN relative to the irradiated volumes in our cohort was as follows: 12% in the central area of the irradiated volume, which corresponds to the planning target volume (PTV), 66% in the beam-bordering region (i.e., the area surrounding the PTV), and 22% in regions located more than 5 cm from the irradiated volume. At the SMN site, all dose levels ranging from almost zero to >75 Gy were represented. A peak SMN frequency of approximately 31% was identified in volumes that received <2.5 Gy.Conclusion: A greater volume of tissues receives low or intermediate doses in regions bordering the irradiated volume with modern multiple-beam RT arrangements. These results should be considered for risk-benefit evaluations of RT

Malignant breast tumors after radiotherapy for a first cancer during childhood.

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

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

International audienceSoft 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