Higher Reported Lung Dose Received During Total Body Irradiation for Allogeneic Hematopoietic Stem Cell Transplantation in Children With Acute Lymphoblastic Leukemia Is Associated With Inferior Survival: A Report from the Children's Oncology Group

Abstract

To examine the relationship between lung radiation dose and survival outcomes in children undergoing total body irradiation (TBI)-based hematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukemia on the Children's Oncology Group trial. TBI (1200 or 1320cGy given twice daily in 6 or 8 fractions) was used as part of 3 HSCT preparative regimens, allowing institutional flexibility regarding TBI techniques, including lung shielding. Lung doses as reported by each participating institution were calculated for different patient setups, with and without shielding, with a variety of dose calculation techniques. The association between lung dose and transplant-related mortality, relapse-free survival, and overall survival (OS) was examined using the Cox proportional hazards regression model controlling for the following variables: TBI dose rate, TBI fields, patient position during TBI, donor type, and pre-HSCT minimal residual disease level. Of a total of 143 eligible patients, 127 had lung doses available for this analysis. The TBI techniques were heterogeneous. The mean lung dose was reported as 904.5cGy (standard deviation, ±232.3). Patients treated with lateral fields were more likely to receive lung doses ≥800cGy(P<.001). The influence of lung dose ≥800cGy on transplant-related mortality was not significant (hazard ratio [HR], 1.78; P=.21). On univariate analysis, lung dose ≥800cGy was associated with inferior relapse-free survival (HR, 1.76; P=.04) and OS (HR, 1.85; P=.03). In the multivariate analysis, OS maintained statistical significance (HR, 1.85; P=.04). The variability in TBI techniques resulted in uncertainty with reported lung doses. Lateral fields were associated with higher lung dose, and thus they should be avoided. Patients treated with lung dose <800cGy in this study had better outcomes. This approach is currently being investigated in the Children's Oncology Group AALL1331 study. Additionally, the Imaging and Radiation Oncology Core Group is evaluating effects of TBI techniques on lung doses using a phantom.