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

• Type of Material: Article
• Authors: Natia Esiashvili, Emory University; X. Lu, University of Florida; K. Ulin, Rhode Island QA Center; F. Laurie, Rhode Island QA Center; S. Kessel, Rhode Island QA Center; J. A. Kalapurakal, Northwestern University; T. E. Merchant, St Jude Childrens Research Hospital; D. S. Followill, Rhode Island QA Center; V. Sathiaseelan, Northwestern University; M. K. Schmitter, Rhode Island QA Center; Meenakshi Devidas, University of Florida; Yichen Chen, University of Florida; D. A. Wall, Manitoba Blood & Marrow Transplant Program; P. A. Brown, Johns Hopkins University; S. P. Hunger, University of Pennsylvania; S. A. Grupp, University of Pennsylvania; M. A. Pulsipher, University of Southern California
• Language: English
• Date: 2019-07-01
• Publisher: Elsevier Science Inc.
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.ijrobp.2019.02.034
• Title of Journal or Parent Work: International Journal of Radiation Oncology, Biology, Physics
• Volume: 104
• Issue: 3
• Start Page: 513
• End Page: 521
• Grant/Funding Information: COG Chair’s grant U10 CA098543; (National Cancer Institute) R01CA1116660; ROC Rhode Island (QARC) activities is supported by grant U10CA29511 and IROC 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; PBMTC activities were supported by (National Heart, Lung and Blood Institute) 2U01HL069254 and the St. Baldrick’s Foundation.
• Keywords: Oncology; Single; Life Sciences & Biomedicine; Bone marrow transplantation; Interstitial pneumonitis; Pulmonary complications; Science & Technology; Experience; Idiopathic pneumonia; Uniformity; Conditioning patients; Radiology, Nuclear Medicine & Medical Imaging; Radiotherapy; Computed tomography
• Research Categories: Health Sciences, Oncology; Health Sciences, Rehabilitation and Therapy; Health Sciences, Radiology

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 (ALL) on Children’s Oncology Group (COG) trial. Patients and Methods: 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 (TRM), relapse-free (RFS) and overall-survival (OS) was examined using Cox proportional hazard regression model controlling for the following variables: TBI dose rate, TBI fields, patient position during TBI, donor type, and pre-HSCT minimal residual disease (MRD) level. Results: From a total of 143 eligible patients127 had lung doses available for this analysis. The TBI techniques were heterogeneous. The mean lung dose was reported as 904.5cGy (SD ±232.3). Patients treated with lateral fields were more likely to receive lung doses ≥800cGy (p<0.001). Lung dose ≥800cGy influence on TRM was not significant (HR 1.78; p=0.21). On univariate analysis, lung dose ≥800cGy was associated with inferior RFS (HR 1.76; p=0.04) and OS (HR 1.85; p=0.03); in the multivariate analysis, OS maintained statistical significance (HR 1.85; p=0.04). Conclusion: The variability in TBI techniques result in an uncertainty with reported lung doses. Lateral fields were associated with higher lung dose, hence better be avoided. Patients treated with lung dose <800 cGy in this study had better outcome. This approach is currently been investigated in COG AALL1331 study. Additionally, the Imaging and Radiation Oncology Core (IROC) Group is evaluating effects of TBI techniques on lung doses using a phantom.