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

Natia Esiashvili, Xiaomin Lu, Ken Ulin, Fran Laurie, Sandy Kessel, John A. Kalapurakal, Thomas E. Merchant, David S. Followill, Vythialinga Sathiaseelan, Mary K. Schmitter, Meenakshi Devidas, Yichen Chen, Donna A. Wall, Patrick A Brown, Stephen P. Hunger, Stephan A. Grupp, Michael A. Pulsipher

Research output: Contribution to journalArticle

Abstract

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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transplantation
leukemias
stem cells
Whole-Body Irradiation
Hematopoietic Stem Cell Transplantation
Precursor Cell Lymphoblastic Leukemia-Lymphoma
lungs
dosage
Lung
irradiation
Survival
hazards
mortality
shielding
Transplants
Recurrence
Radiation Oncology
Mortality
Residual Neoplasm
radiation

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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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. / Esiashvili, Natia; Lu, Xiaomin; Ulin, Ken; Laurie, Fran; Kessel, Sandy; Kalapurakal, John A.; Merchant, Thomas E.; Followill, David S.; Sathiaseelan, Vythialinga; Schmitter, Mary K.; Devidas, Meenakshi; Chen, Yichen; Wall, Donna A.; Brown, Patrick A; Hunger, Stephen P.; Grupp, Stephan A.; Pulsipher, Michael A.

In: International Journal of Radiation Oncology Biology Physics, 01.01.2019.

Research output: Contribution to journalArticle

Esiashvili, Natia ; Lu, Xiaomin ; Ulin, Ken ; Laurie, Fran ; Kessel, Sandy ; Kalapurakal, John A. ; Merchant, Thomas E. ; Followill, David S. ; Sathiaseelan, Vythialinga ; Schmitter, Mary K. ; Devidas, Meenakshi ; Chen, Yichen ; Wall, Donna A. ; Brown, Patrick A ; Hunger, Stephen P. ; Grupp, Stephan A. ; Pulsipher, Michael A. / 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. In: International Journal of Radiation Oncology Biology Physics. 2019.
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title = "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 = "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.",
author = "Natia Esiashvili and Xiaomin Lu and Ken Ulin and Fran Laurie and Sandy Kessel and Kalapurakal, {John A.} and Merchant, {Thomas E.} and Followill, {David S.} and Vythialinga Sathiaseelan and Schmitter, {Mary K.} and Meenakshi Devidas and Yichen Chen and Wall, {Donna A.} and Brown, {Patrick A} and Hunger, {Stephen P.} and Grupp, {Stephan A.} and Pulsipher, {Michael A.}",
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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.

PY - 2019/1/1

Y1 - 2019/1/1

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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