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Title: Statistical analysis of dose heterogeneity in circulating blood: Implications for sequential methods of total body irradiation

Abstract

Purpose: Improvements in delivery techniques for total body irradiation (TBI) using Tomotherapy and intensity modulated radiation therapy have been proven feasible. Despite the promise of improved dose conformality, the application of these ''sequential'' techniques has been hampered by concerns over dose heterogeneity to circulating blood. The present study was conducted to provide quantitative evidence regarding the potential clinical impact of this heterogeneity. Methods: Blood perfusion was modeled analytically as possessing linear, sinusoidal motion in the craniocaudal dimension. The average perfusion period for human circulation was estimated to be approximately 78 s. Sequential treatment delivery was modeled as a Gaussian-shaped dose cloud with a 10 cm length that traversed a 183 cm patient length at a uniform speed. Total dose to circulating blood voxels was calculated via numerical integration and normalized to 2 Gy per fraction. Dose statistics and equivalent uniform dose (EUD) were calculated for relevant treatment times, radiobiological parameters, blood perfusion rates, and fractionation schemes. The model was then refined to account for random dispersion superimposed onto the underlying periodic blood flow. Finally, a fully stochastic model was developed using binomial and trinomial probability distributions. These models allowed for the analysis of nonlinear sequential treatment modalities and treatment designsmore » that incorporate deliberate organ sparing. Results: The dose received by individual blood voxels exhibited asymmetric behavior that depended on the coherence among the blood velocity, circulation phase, and the spatiotemporal characteristics of the irradiation beam. Heterogeneity increased with the perfusion period and decreased with the treatment time. Notwithstanding, heterogeneity was less than {+-}10% for perfusion periods less than 150 s. The EUD was compromised for radiosensitive cells, long perfusion periods, and short treatment times. However, the EUD was unaffected (within 10%) for perfusion periods of less than 150 s or treatment times of 20 min or greater. Treatment over six fractions improved the EUD per fraction such that all parametric combinations resulted in unaffected EUD. The stochastic models confirmed these results. Conclusions: Dose heterogeneity in circulating blood cells is clinically acceptable for typical treatment times, perfusion rates, and cell types. Development of conformal, sequential TBI treatment techniques should not be withheld based on concerns over circulating blood dose heterogeneity.« less

Authors:
 [1]
  1. Department of Radiation Medicine, University of Kentucky, Markey Cancer Center, Rm. CC061, 800 Rose Street, Lexington, Kentucky 40536 (United States)
Publication Date:
OSTI Identifier:
22096801
Resource Type:
Journal Article
Journal Name:
Medical Physics
Additional Journal Information:
Journal Volume: 37; Journal Issue: 11; Other Information: (c) 2010 American Association of Physicists in Medicine; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0094-2405
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; 61 RADIATION PROTECTION AND DOSIMETRY; 71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSICS; 60 APPLIED LIFE SCIENCES; BLOOD CELLS; BLOOD CIRCULATION; BLOOD FLOW; COMPUTERIZED TOMOGRAPHY; CT-GUIDED RADIOTHERAPY; DOSIMETRY; FRACTIONATION; PATIENTS; RADIATION DOSES; STOCHASTIC PROCESSES; VELOCITY; WHOLE-BODY IRRADIATION

Citation Formats

Molloy, Janelle A. Statistical analysis of dose heterogeneity in circulating blood: Implications for sequential methods of total body irradiation. United States: N. p., 2010. Web. doi:10.1118/1.3495816.
Molloy, Janelle A. Statistical analysis of dose heterogeneity in circulating blood: Implications for sequential methods of total body irradiation. United States. https://doi.org/10.1118/1.3495816
Molloy, Janelle A. 2010. "Statistical analysis of dose heterogeneity in circulating blood: Implications for sequential methods of total body irradiation". United States. https://doi.org/10.1118/1.3495816.
@article{osti_22096801,
title = {Statistical analysis of dose heterogeneity in circulating blood: Implications for sequential methods of total body irradiation},
author = {Molloy, Janelle A.},
abstractNote = {Purpose: Improvements in delivery techniques for total body irradiation (TBI) using Tomotherapy and intensity modulated radiation therapy have been proven feasible. Despite the promise of improved dose conformality, the application of these ''sequential'' techniques has been hampered by concerns over dose heterogeneity to circulating blood. The present study was conducted to provide quantitative evidence regarding the potential clinical impact of this heterogeneity. Methods: Blood perfusion was modeled analytically as possessing linear, sinusoidal motion in the craniocaudal dimension. The average perfusion period for human circulation was estimated to be approximately 78 s. Sequential treatment delivery was modeled as a Gaussian-shaped dose cloud with a 10 cm length that traversed a 183 cm patient length at a uniform speed. Total dose to circulating blood voxels was calculated via numerical integration and normalized to 2 Gy per fraction. Dose statistics and equivalent uniform dose (EUD) were calculated for relevant treatment times, radiobiological parameters, blood perfusion rates, and fractionation schemes. The model was then refined to account for random dispersion superimposed onto the underlying periodic blood flow. Finally, a fully stochastic model was developed using binomial and trinomial probability distributions. These models allowed for the analysis of nonlinear sequential treatment modalities and treatment designs that incorporate deliberate organ sparing. Results: The dose received by individual blood voxels exhibited asymmetric behavior that depended on the coherence among the blood velocity, circulation phase, and the spatiotemporal characteristics of the irradiation beam. Heterogeneity increased with the perfusion period and decreased with the treatment time. Notwithstanding, heterogeneity was less than {+-}10% for perfusion periods less than 150 s. The EUD was compromised for radiosensitive cells, long perfusion periods, and short treatment times. However, the EUD was unaffected (within 10%) for perfusion periods of less than 150 s or treatment times of 20 min or greater. Treatment over six fractions improved the EUD per fraction such that all parametric combinations resulted in unaffected EUD. The stochastic models confirmed these results. Conclusions: Dose heterogeneity in circulating blood cells is clinically acceptable for typical treatment times, perfusion rates, and cell types. Development of conformal, sequential TBI treatment techniques should not be withheld based on concerns over circulating blood dose heterogeneity.},
doi = {10.1118/1.3495816},
url = {https://www.osti.gov/biblio/22096801}, journal = {Medical Physics},
issn = {0094-2405},
number = 11,
volume = 37,
place = {United States},
year = {Mon Nov 15 00:00:00 EST 2010},
month = {Mon Nov 15 00:00:00 EST 2010}
}