TY - JOUR
T1 - 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
T2 - A Report from the Children's Oncology Group
AU - Esiashvili, Natia
AU - Lu, Xiaomin
AU - Ulin, Ken
AU - Laurie, Fran
AU - Kessel, Sandy
AU - Kalapurakal, John A.
AU - Merchant, Thomas E.
AU - Followill, David S.
AU - Sathiaseelan, Vythialinga
AU - Schmitter, Mary K.
AU - Devidas, Meenakshi
AU - Chen, Yichen
AU - Wall, Donna A.
AU - Brown, Patrick A.
AU - Hunger, Stephen P.
AU - Grupp, Stephan A.
AU - Pulsipher, Michael A.
N1 - Funding Information:
This work was supported in part by National Institutes of Health grants (National Heart, Lung, and Blood Institute N01 HC-45220/HHSN268200425220C; Children's Oncology Group Chair's grant U10 CA098543, and National Cancer Institute R01CA11166600). Pediatric Bone & Marrow Transplant Consortium activities were supported by National Heart, Lung, and Blood Institute 2U01HL069254 and the St. Baldrick's Foundation. Imaging and Radiation Oncology Rhode Island (QARC) activities were supported by grant U10CA29511 and Imaging and Radiation Oncology Houston activities by grant CA180803. This work was supported in part by National Institutes of Health grants ( National Heart, Lung, and Blood Institute N01 HC-45220/ HHSN268200425220C; Children's Oncology Group Chair's grant U10 CA098543, and National Cancer Institute R01CA11166600). Pediatric Bone & Marrow Transplant Consortium activities were supported by National Heart, Lung, and Blood Institute 2U01HL069254 and the St. Baldrick's Foundation. Imaging and Radiation Oncology Rhode Island (QARC) activities were supported by grant U10CA29511 and Imaging and Radiation Oncology Houston activities by grant CA180803.
Funding Information:
This work was supported in part by National Institutes of Health grants (National Heart, Lung, and Blood Institute N01 HC-45220/HHSN268200425220C; Children's Oncology Group Chair's grant U10 CA098543, and National Cancer Institute R01CA11166600). Pediatric Bone & Marrow Transplant Consortium activities were supported by National Heart, Lung, and Blood Institute 2U01HL069254 and the St. Baldrick's Foundation. Imaging and Radiation Oncology Rhode Island (QARC) activities were supported by grant U10CA29511 and Imaging and Radiation Oncology Houston activities by grant CA180803. This work was supported in part by National Institutes of Health grants (National Heart, Lung, and Blood Institute N01 HC-45220/ HHSN268200425220C; Children's Oncology Group Chair's grant U10 CA098543, and National Cancer Institute R01CA11166600). Pediatric Bone & Marrow Transplant Consortium activities were supported by National Heart, Lung, and Blood Institute 2U01HL069254 and the St. Baldrick's Foundation. Imaging and Radiation Oncology Rhode Island (QARC) activities were supported by grant U10CA29511 and Imaging and Radiation Oncology Houston activities by grant CA180803.
Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/7/1
Y1 - 2019/7/1
N2 - Purpose: 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. Methods and Materials: TBI (1200 or 1320 cGy 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. Results: 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 904.5 cGy (standard deviation, ±232.3). Patients treated with lateral fields were more likely to receive lung doses ≥800 cGy (P < .001). The influence of lung dose ≥800 cGy on transplant-related mortality was not significant (hazard ratio [HR], 1.78; P = .21). On univariate analysis, lung dose ≥800 cGy 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). Conclusions: 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 <800 cGy 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.
AB - Purpose: 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. Methods and Materials: TBI (1200 or 1320 cGy 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. Results: 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 904.5 cGy (standard deviation, ±232.3). Patients treated with lateral fields were more likely to receive lung doses ≥800 cGy (P < .001). The influence of lung dose ≥800 cGy on transplant-related mortality was not significant (hazard ratio [HR], 1.78; P = .21). On univariate analysis, lung dose ≥800 cGy 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). Conclusions: 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 <800 cGy 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.
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U2 - 10.1016/j.ijrobp.2019.02.034
DO - 10.1016/j.ijrobp.2019.02.034
M3 - Article
C2 - 30807822
AN - SCOPUS:85063549988
SN - 0360-3016
VL - 104
SP - 513
EP - 521
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 3
ER -