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Title: Stochastic Predictions of Cell Kill During Stereotactic Ablative Radiation Therapy: Do Hypoxia and Reoxygenation Really Matter?

Abstract

Purpose: To simulate stereotactic ablative radiation therapy on hypoxic and well-oxygenated in silico tumors, incorporating probabilistic parameter distributions and linear-quadratic versus linear-quadratic-cubic methodology and the evaluation of optimal fractionation schemes using biological effective dose (BED{sub α/β=10} {sub or} {sub 3}) comparisons. Methods and Materials: A temporal tumor growth and radiation therapy algorithm simulated high-dose external beam radiation therapy using stochastic methods. Realistic biological proliferative cellular hierarchy and pO{sub 2} histograms were incorporated into the 10{sup 8}-cell tumor model, with randomized radiation therapy applied during continual cell proliferation and volume-based gradual tumor reoxygenation. Dose fractions ranged from 6-35 Gy, with predictive outcomes presented in terms of the total doses (converted to BED) required to eliminate all cells that could potentially regenerate the tumor. Results: Well-oxygenated tumor control BED{sub 10} outcomes were not significantly different for high-dose versus conventional radiation therapy (BED{sub 10}: 79-84 Gy; Equivalent Dose in 2 Gy fractions with α/β of 10: 66-70 Gy); however, total treatment times decreased from 7 down to 1-3 weeks. For hypoxic tumors, an additional 28 Gy (51 Gy BED{sub 10}) was required, with BED{sub 10} increasing with dose per fraction due to wasted dose in the final fraction. Fractions of 9 Gy compromised well for total treatment time and BED, withmore » BED{sub 10}:BED{sub 3} of 84:176 Gy for oxic and 132:278 Gy for non-reoxygenating hypoxic tumors. Initial doses of 12 Gy followed by 6 Gy further increased the therapeutic ratio. When delivering ≥9 Gy per fraction, applying reoxygenation and/or linear-quadratic-cubic cell survival both affected tumor control doses by a significant 1-2 fractions. Conclusions: The complex temporal dynamics of tumor oxygenation combined with probabilistic cell kinetics in the modeling of radiation therapy requires sophisticated stochastic modeling to predict tumor cell kill. For stereotactic ablative radiation therapy, high doses in the first week followed by doses that are more moderate may be beneficial because a high percentage of hypoxic cells could be eradicated early while keeping the required BED{sub 10} relatively low and BED{sub 3} toxicity to tolerable levels.« less

Authors:
 [1];  [2];  [3];  [2];  [2];  [4];  [2]
  1. Department of Medical Physics, Royal Adelaide Hospital, Adelaide, South Australia (Australia)
  2. (Australia)
  3. School of Chemistry and Physics, University of Adelaide, Adelaide, South Australia (Australia)
  4. Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide, South Australia (Australia)
Publication Date:
OSTI Identifier:
22648748
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 95; Journal Issue: 4; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; CELL PROLIFERATION; DOSE EQUIVALENTS; EXTERNAL BEAM RADIATION THERAPY; FORECASTING; NEOPLASMS; PROBABILISTIC ESTIMATION; SIMULATION; STOCHASTIC PROCESSES; TUMOR CELLS

Citation Formats

Harriss-Phillips, Wendy M., E-mail: wharrphil@gmail.com, School of Chemistry and Physics, University of Adelaide, Adelaide, South Australia, Bezak, Eva, International Centre for Allied Health Evidence, University of South Australia, Adelaide, South Australia, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Potter, Andrew, and Adelaide Radiotherapy Centre, Genesis CancerCare, Adelaide, South Australia. Stochastic Predictions of Cell Kill During Stereotactic Ablative Radiation Therapy: Do Hypoxia and Reoxygenation Really Matter?. United States: N. p., 2016. Web. doi:10.1016/J.IJROBP.2016.03.014.
Harriss-Phillips, Wendy M., E-mail: wharrphil@gmail.com, School of Chemistry and Physics, University of Adelaide, Adelaide, South Australia, Bezak, Eva, International Centre for Allied Health Evidence, University of South Australia, Adelaide, South Australia, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Potter, Andrew, & Adelaide Radiotherapy Centre, Genesis CancerCare, Adelaide, South Australia. Stochastic Predictions of Cell Kill During Stereotactic Ablative Radiation Therapy: Do Hypoxia and Reoxygenation Really Matter?. United States. doi:10.1016/J.IJROBP.2016.03.014.
Harriss-Phillips, Wendy M., E-mail: wharrphil@gmail.com, School of Chemistry and Physics, University of Adelaide, Adelaide, South Australia, Bezak, Eva, International Centre for Allied Health Evidence, University of South Australia, Adelaide, South Australia, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Potter, Andrew, and Adelaide Radiotherapy Centre, Genesis CancerCare, Adelaide, South Australia. Fri . "Stochastic Predictions of Cell Kill During Stereotactic Ablative Radiation Therapy: Do Hypoxia and Reoxygenation Really Matter?". United States. doi:10.1016/J.IJROBP.2016.03.014.
@article{osti_22648748,
title = {Stochastic Predictions of Cell Kill During Stereotactic Ablative Radiation Therapy: Do Hypoxia and Reoxygenation Really Matter?},
author = {Harriss-Phillips, Wendy M., E-mail: wharrphil@gmail.com and School of Chemistry and Physics, University of Adelaide, Adelaide, South Australia and Bezak, Eva and International Centre for Allied Health Evidence, University of South Australia, Adelaide, South Australia and Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia and Potter, Andrew and Adelaide Radiotherapy Centre, Genesis CancerCare, Adelaide, South Australia},
abstractNote = {Purpose: To simulate stereotactic ablative radiation therapy on hypoxic and well-oxygenated in silico tumors, incorporating probabilistic parameter distributions and linear-quadratic versus linear-quadratic-cubic methodology and the evaluation of optimal fractionation schemes using biological effective dose (BED{sub α/β=10} {sub or} {sub 3}) comparisons. Methods and Materials: A temporal tumor growth and radiation therapy algorithm simulated high-dose external beam radiation therapy using stochastic methods. Realistic biological proliferative cellular hierarchy and pO{sub 2} histograms were incorporated into the 10{sup 8}-cell tumor model, with randomized radiation therapy applied during continual cell proliferation and volume-based gradual tumor reoxygenation. Dose fractions ranged from 6-35 Gy, with predictive outcomes presented in terms of the total doses (converted to BED) required to eliminate all cells that could potentially regenerate the tumor. Results: Well-oxygenated tumor control BED{sub 10} outcomes were not significantly different for high-dose versus conventional radiation therapy (BED{sub 10}: 79-84 Gy; Equivalent Dose in 2 Gy fractions with α/β of 10: 66-70 Gy); however, total treatment times decreased from 7 down to 1-3 weeks. For hypoxic tumors, an additional 28 Gy (51 Gy BED{sub 10}) was required, with BED{sub 10} increasing with dose per fraction due to wasted dose in the final fraction. Fractions of 9 Gy compromised well for total treatment time and BED, with BED{sub 10}:BED{sub 3} of 84:176 Gy for oxic and 132:278 Gy for non-reoxygenating hypoxic tumors. Initial doses of 12 Gy followed by 6 Gy further increased the therapeutic ratio. When delivering ≥9 Gy per fraction, applying reoxygenation and/or linear-quadratic-cubic cell survival both affected tumor control doses by a significant 1-2 fractions. Conclusions: The complex temporal dynamics of tumor oxygenation combined with probabilistic cell kinetics in the modeling of radiation therapy requires sophisticated stochastic modeling to predict tumor cell kill. For stereotactic ablative radiation therapy, high doses in the first week followed by doses that are more moderate may be beneficial because a high percentage of hypoxic cells could be eradicated early while keeping the required BED{sub 10} relatively low and BED{sub 3} toxicity to tolerable levels.},
doi = {10.1016/J.IJROBP.2016.03.014},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 4,
volume = 95,
place = {United States},
year = {Fri Jul 15 00:00:00 EDT 2016},
month = {Fri Jul 15 00:00:00 EDT 2016}
}