Variations in the RBE for cell killing along the depth-dose profile of a modulated proton therapy beam

Richard A. Britten, Vahagn Nazaryan, Leslie K. Davis, Susan B. Klein, Dmitri Nichiporov, Marc Mendonca, Mark Wolanski, Xiliang Nie, Jerry George, Cynthia Keppel

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Considerable evidence now exists to show that that the relative biological effectiveness (RBE) changes considerably along the proton depth-dose distribution, with progressively higher RBE values at the distal part of the modulated, or spread out Bragg peak (SOBP) and in the distal dose fall-off (DDF). However, the highly variable nature of the existing studies (with regards to cell lines, and to the physical properties and dosimetry of the various proton beams) precludes any consensus regarding the RBE weighting factor at any position in the depth-dose profile. We have thus conducted a systematic study on the variation in RBE for cell killing for two clinical modulated proton beams at Indiana University and have determined the relationship between the RBE and the dose-averaged linear energy transfer (LETd) of the protons at various positions along the depth-dose profiles. Clonogenic assays were performed on human Hep2 laryngeal cancer cells and V79 cells at various positions along the SOBPs of beams with incident energies of 87 and 200 MeV. There was a marked variation in the radiosensitivity of both cell lines along the SOBP depth-dose profile of the 87 MeV proton beam. Using Hep2 cells, the D0.1 isoeffect dose RBE values (normalized against 60Co) were 1.46 at the middle of SOBP, 2.1 at the distal end of the SOBP and 2.3 in the DDF. For V79 cells, the D0.1 isoeffect RBE for the 87 MEV beam were 1.23 for the proximal end of the SOBP: 1.46 for the distal SOBP and 1.78 for the DDF. Similar D0.1 isoeffect RBE values were found for Hep2 cells irradiated at various positions along the depth-dose profile of the 200 MeV beam. Our experimentally derived RBE values were significantly correlated (P = 0.001) with the mean LETd of the protons at the various depths, which confirmed that proton RBE is highly dependent on LETd. These in vitro data suggest that the RBE of the proton beam at certain depths is greater than 1.1, a value currently used in most treatment planning algorithms. Thus, the potential for increased cell killing and normal tissue damage in the distal regions of the proton SOBP may be greater than originally thought.

Original languageEnglish
Pages (from-to)21-28
Number of pages8
JournalRadiation Research
Volume179
Issue number1
DOIs
StatePublished - Jan 2013

Fingerprint

Relative Biological Effectiveness
Proton Therapy
therapy
Protons
dosage
protons
profiles
proton beams
cultured cells
cells
Linear Energy Transfer
Cell Line
linear energy transfer (LET)
Laryngeal Neoplasms
Radiation Tolerance
radiation tolerance
dosimeters
planning

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Biophysics
  • Radiation

Cite this

Britten, R. A., Nazaryan, V., Davis, L. K., Klein, S. B., Nichiporov, D., Mendonca, M., ... Keppel, C. (2013). Variations in the RBE for cell killing along the depth-dose profile of a modulated proton therapy beam. Radiation Research, 179(1), 21-28. https://doi.org/10.1667/RR2737.1

Variations in the RBE for cell killing along the depth-dose profile of a modulated proton therapy beam. / Britten, Richard A.; Nazaryan, Vahagn; Davis, Leslie K.; Klein, Susan B.; Nichiporov, Dmitri; Mendonca, Marc; Wolanski, Mark; Nie, Xiliang; George, Jerry; Keppel, Cynthia.

In: Radiation Research, Vol. 179, No. 1, 01.2013, p. 21-28.

Research output: Contribution to journalArticle

Britten, RA, Nazaryan, V, Davis, LK, Klein, SB, Nichiporov, D, Mendonca, M, Wolanski, M, Nie, X, George, J & Keppel, C 2013, 'Variations in the RBE for cell killing along the depth-dose profile of a modulated proton therapy beam', Radiation Research, vol. 179, no. 1, pp. 21-28. https://doi.org/10.1667/RR2737.1
Britten, Richard A. ; Nazaryan, Vahagn ; Davis, Leslie K. ; Klein, Susan B. ; Nichiporov, Dmitri ; Mendonca, Marc ; Wolanski, Mark ; Nie, Xiliang ; George, Jerry ; Keppel, Cynthia. / Variations in the RBE for cell killing along the depth-dose profile of a modulated proton therapy beam. In: Radiation Research. 2013 ; Vol. 179, No. 1. pp. 21-28.
@article{2f821f39830347709f3fe23236e67c82,
title = "Variations in the RBE for cell killing along the depth-dose profile of a modulated proton therapy beam",
abstract = "Considerable evidence now exists to show that that the relative biological effectiveness (RBE) changes considerably along the proton depth-dose distribution, with progressively higher RBE values at the distal part of the modulated, or spread out Bragg peak (SOBP) and in the distal dose fall-off (DDF). However, the highly variable nature of the existing studies (with regards to cell lines, and to the physical properties and dosimetry of the various proton beams) precludes any consensus regarding the RBE weighting factor at any position in the depth-dose profile. We have thus conducted a systematic study on the variation in RBE for cell killing for two clinical modulated proton beams at Indiana University and have determined the relationship between the RBE and the dose-averaged linear energy transfer (LETd) of the protons at various positions along the depth-dose profiles. Clonogenic assays were performed on human Hep2 laryngeal cancer cells and V79 cells at various positions along the SOBPs of beams with incident energies of 87 and 200 MeV. There was a marked variation in the radiosensitivity of both cell lines along the SOBP depth-dose profile of the 87 MeV proton beam. Using Hep2 cells, the D0.1 isoeffect dose RBE values (normalized against 60Co) were 1.46 at the middle of SOBP, 2.1 at the distal end of the SOBP and 2.3 in the DDF. For V79 cells, the D0.1 isoeffect RBE for the 87 MEV beam were 1.23 for the proximal end of the SOBP: 1.46 for the distal SOBP and 1.78 for the DDF. Similar D0.1 isoeffect RBE values were found for Hep2 cells irradiated at various positions along the depth-dose profile of the 200 MeV beam. Our experimentally derived RBE values were significantly correlated (P = 0.001) with the mean LETd of the protons at the various depths, which confirmed that proton RBE is highly dependent on LETd. These in vitro data suggest that the RBE of the proton beam at certain depths is greater than 1.1, a value currently used in most treatment planning algorithms. Thus, the potential for increased cell killing and normal tissue damage in the distal regions of the proton SOBP may be greater than originally thought.",
author = "Britten, {Richard A.} and Vahagn Nazaryan and Davis, {Leslie K.} and Klein, {Susan B.} and Dmitri Nichiporov and Marc Mendonca and Mark Wolanski and Xiliang Nie and Jerry George and Cynthia Keppel",
year = "2013",
month = "1",
doi = "10.1667/RR2737.1",
language = "English",
volume = "179",
pages = "21--28",
journal = "Radiation Research",
issn = "0033-7587",
publisher = "Radiation Research Society",
number = "1",

}

TY - JOUR

T1 - Variations in the RBE for cell killing along the depth-dose profile of a modulated proton therapy beam

AU - Britten, Richard A.

AU - Nazaryan, Vahagn

AU - Davis, Leslie K.

AU - Klein, Susan B.

AU - Nichiporov, Dmitri

AU - Mendonca, Marc

AU - Wolanski, Mark

AU - Nie, Xiliang

AU - George, Jerry

AU - Keppel, Cynthia

PY - 2013/1

Y1 - 2013/1

N2 - Considerable evidence now exists to show that that the relative biological effectiveness (RBE) changes considerably along the proton depth-dose distribution, with progressively higher RBE values at the distal part of the modulated, or spread out Bragg peak (SOBP) and in the distal dose fall-off (DDF). However, the highly variable nature of the existing studies (with regards to cell lines, and to the physical properties and dosimetry of the various proton beams) precludes any consensus regarding the RBE weighting factor at any position in the depth-dose profile. We have thus conducted a systematic study on the variation in RBE for cell killing for two clinical modulated proton beams at Indiana University and have determined the relationship between the RBE and the dose-averaged linear energy transfer (LETd) of the protons at various positions along the depth-dose profiles. Clonogenic assays were performed on human Hep2 laryngeal cancer cells and V79 cells at various positions along the SOBPs of beams with incident energies of 87 and 200 MeV. There was a marked variation in the radiosensitivity of both cell lines along the SOBP depth-dose profile of the 87 MeV proton beam. Using Hep2 cells, the D0.1 isoeffect dose RBE values (normalized against 60Co) were 1.46 at the middle of SOBP, 2.1 at the distal end of the SOBP and 2.3 in the DDF. For V79 cells, the D0.1 isoeffect RBE for the 87 MEV beam were 1.23 for the proximal end of the SOBP: 1.46 for the distal SOBP and 1.78 for the DDF. Similar D0.1 isoeffect RBE values were found for Hep2 cells irradiated at various positions along the depth-dose profile of the 200 MeV beam. Our experimentally derived RBE values were significantly correlated (P = 0.001) with the mean LETd of the protons at the various depths, which confirmed that proton RBE is highly dependent on LETd. These in vitro data suggest that the RBE of the proton beam at certain depths is greater than 1.1, a value currently used in most treatment planning algorithms. Thus, the potential for increased cell killing and normal tissue damage in the distal regions of the proton SOBP may be greater than originally thought.

AB - Considerable evidence now exists to show that that the relative biological effectiveness (RBE) changes considerably along the proton depth-dose distribution, with progressively higher RBE values at the distal part of the modulated, or spread out Bragg peak (SOBP) and in the distal dose fall-off (DDF). However, the highly variable nature of the existing studies (with regards to cell lines, and to the physical properties and dosimetry of the various proton beams) precludes any consensus regarding the RBE weighting factor at any position in the depth-dose profile. We have thus conducted a systematic study on the variation in RBE for cell killing for two clinical modulated proton beams at Indiana University and have determined the relationship between the RBE and the dose-averaged linear energy transfer (LETd) of the protons at various positions along the depth-dose profiles. Clonogenic assays were performed on human Hep2 laryngeal cancer cells and V79 cells at various positions along the SOBPs of beams with incident energies of 87 and 200 MeV. There was a marked variation in the radiosensitivity of both cell lines along the SOBP depth-dose profile of the 87 MeV proton beam. Using Hep2 cells, the D0.1 isoeffect dose RBE values (normalized against 60Co) were 1.46 at the middle of SOBP, 2.1 at the distal end of the SOBP and 2.3 in the DDF. For V79 cells, the D0.1 isoeffect RBE for the 87 MEV beam were 1.23 for the proximal end of the SOBP: 1.46 for the distal SOBP and 1.78 for the DDF. Similar D0.1 isoeffect RBE values were found for Hep2 cells irradiated at various positions along the depth-dose profile of the 200 MeV beam. Our experimentally derived RBE values were significantly correlated (P = 0.001) with the mean LETd of the protons at the various depths, which confirmed that proton RBE is highly dependent on LETd. These in vitro data suggest that the RBE of the proton beam at certain depths is greater than 1.1, a value currently used in most treatment planning algorithms. Thus, the potential for increased cell killing and normal tissue damage in the distal regions of the proton SOBP may be greater than originally thought.

UR - http://www.scopus.com/inward/record.url?scp=84872119582&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84872119582&partnerID=8YFLogxK

U2 - 10.1667/RR2737.1

DO - 10.1667/RR2737.1

M3 - Article

VL - 179

SP - 21

EP - 28

JO - Radiation Research

JF - Radiation Research

SN - 0033-7587

IS - 1

ER -