Frequency distribution of second solid cancer locations in relation to the irradiated volume among 115 patients treated for childhood cancer.

PURPOSE: 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.

Role of radiotherapy and chemotherapy in the risk of secondary leukaemia after a solid tumour in childhood.

The aim of this study was to determine the therapy-related risk factors for the occurrence of leukaemia after childhood solid cancer. Among 4204 3-year survivors of a childhood cancer treated in eight French and British centres before 1986, 11 patients developed leukaemia as a second malignant neoplasm (SMN). Compared with the leukaemia incidence in the general French and British populations, the standardised incidence ratio (SIR) of leukaemia was 7.8 (95% CI 4.0-13.4). It decreased from 20.3 (95% CI 8.3-41.2) during the first years of follow-up, to 2.2 (95% CI 0.1-9.7) between 10 and 20 years, but rose again to 14.8 (95% CI 3.7-38.3) 20 or more years after the first cancer. Radiotherapy appeared to increase the risk of leukaemia at moderate weighted doses to active bone marrow; the relative risk (RR) was 4.2 (95% CI 0.8-20.7) for doses ranging from 3 to 6.6 Gy. A greater RR was observed for epipodophyllotoxins and for vinca alkaloids. No specific type of first malignant neoplasm (FMN) was found to lead to a higher risk of secondary leukaemia. Epipodophyllotoxins and vinca alkaloids at high doses and moderate weighted radiation doses to active bone marrow may contribute independently to an increased risk of leukaemia for patients treated for childhood cancer. Our results suggest that the long-term risk of secondary leukaemia could be higher than previously reported.