Uncertainties in the relative biological effectiveness of therapeutic proton beams associated with bias towards high doses per fraction in radiobiological experiments

Oleg N Vassiliev

Abstract


Most data supporting the widely accepted relative biological effectiveness (RBE) value of 1.1 for therapeutic proton beams are from radiobiological experiments with relatively high doses per fraction. The purpose of this study was to estimate bias in RBE that differences in dose levels between these experiments and proton radiotherapy treatments may cause. The linear quadratic model was applied to calculate, using prior experimental data, RBE variations with dose and a/b ratio for doses delivered in a standard fractionation regimen. The results suggest that the RBE measured at relatively high doses per fraction typical for a radiobiological experiment underestimates the RBE of proton radiotherapy with a standard fractionation. The bias increases with decreasing radiation dose and decreasing a/b ratio, suggesting that, if differences in dose levels are not accounted for, there may be a large underestimation of biological effects in late-responding tissues exposed to low doses of radiation.


Keywords


Proton beam therapy, Proton RBE, Hadron therapy, Dose fractionation

Full Text:

PDF

References


Wambersie A, Hendry JH, Andreo P, et al. The RBE issues in ion-beam therapy: conclusions of a joint IAEA/ICRU working group regarding quantities and units. Radiat Protect Dosim. 2006;122:463-70.

Green LM, Murray DK, Tran DT, et al. Response of thyroid follicular cells to gamma irradiation compared to proton irradiation. Initial characterization of DNA damage, micronucleus formation, apoptosis, cell survival, and cell cycle phase redistribution. Radiat Res. 2001;155:32-42.

Hada M, Sutherland BM. Spectrum of complex DNA damages depends on the incident radiation. Radiat Res. 2006;165:223-30.

Di Pietro C, Piro S, Tabbi G, et al. Cellular and molecular effects of protons: Apoptosis induction and potential implications for cancer therapy. Apoptosis. 2006;11:57–66.

Paganetti H, Niemierko A, Ancukiewicz M, et al. Relative biological effectiveness (RBE) values for proton beam therapy. Int J Radiat Oncol Biol Phys. 2002;53:407–21.

Williams SG, Taylor JMG, Liu N, et al. 2007 Use of individual fraction size data from 3756 patients to directly determine the / ratio of prostate cancer. Int J Radiat Oncol Biol Phys. 2007;68:24–33.

Gerweck LE, Kozin SV. Relative biological effectiveness of proton beams in clinical therapy. Radiother Oncol. 1999;50:135-42.

Gueulette J, Bohm L, De Coster B-M, et al. RBE variation as a function of depth in the 200-MeV proton beam produced at the National Accelerator Centre in Faure (South Africa). Radiother Oncol. 1997;42:303-9.

Fowler JF. The linear-quadratic formula and progress in fractionated radiotherapy. Br J Radiol. 1989;62:679-94.

Kellerer AM, Rossi HH. A generalized formulation of dual radiation action. Radiat Res. 1978;75:471-88.

Coutrakon G, Cortese J, Ghebremedhin A, et al. Microdosimetry spectra of the Loma Linda proton beam and relative biological effectiveness comparisons. Med Phys. 1997;24:1499-506.

Barendsen GW. RBE as a function of dose for effects on tissues and tumors assessed by the linear-quadratic model. Int J Radiat Oncol Biol Phys. 1997;46:684–5.

Wambersie A, Gahbauer RA, Menzel HG. RBE and weighting of absorbed dose in ion-beam therapy. Radiother Oncol. 2004;73:S176-82.

Blomquist E, Russell KR, Stenerlöw B, et al. Relative biological effectiveness of intermediate energy protons. Comparisons with 60Co gamma-radiation using two cell lines. Radiother Oncol. 1993;28:44-51.

Tang JT, Inoue T, Inoue T, et al. Comparison of radiobiological effective depths in 65-MeV modulated proton beams Br. J. Cancer. 1997;76:220-5.

Wouters BG, Lam GKY, Oelfke K, et al. Measurements of relative biological effectiveness of the 70 MeV proton beam at TRIUMPH using Chinese hamster V79 cells and the high-precision cell sorter assay. Radiat Res. 1996;146:159-70.

Tepper J, Verhey L, Goitein M, et al. In vivo determinations of RBE in a high energy modulated proton beam using normal tissue reactions and fractionated dose schedules. Int J Radiat Oncol Biol Phys. 1977;2:1115-22.

Urano M, Goitein M, Verhey L, et al. Relative biological effectiveness of a high energy modulated proton beam using a spontaneous murine tumor in vivo. Int J Radiat Oncol Biol Phys. 1980;6:1187-93.

Urano M, Verhey LJ, Goitein M, et al. Relative biological effectiveness of modulated proton beams in various murine tissues. Int J Radiat Oncol Biol Phys. 1984;10:509-14.

Gueulette J, Slabbert JP, Bohm L, et al. Proton RBE for early intestinal tolerance in mice after fractionated irradiation. Radiother Oncol. 2001;61:177–84.

Newhauser W, Smith A, Burns J, et al. A report on the change in the proton absorbed dose measurement protocol for the clinical trials conducted at the Harvard Cyclotron Laboratory (abstract). Med Phys. 1998;25:A144–5.

Verhey LJ, Koehler AM, McDonald JC, et al. The Determination of Absorbed Dose in a Proton Beam for Purposes of Charged-Particle Radiation Therapy. Radiat Res. 1979;79:34-54.

Slater JD, Rossi CJ, Yonemoto LT, et al. Proton therapy for prostate cancer: the initial Loma Linda University experience. Int J Radiat Oncol Biol Phys. 2004;59:348–52.




DOI: http://dx.doi.org/10.14319/ijcto.44.6

Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.

------------------------------------------------------------

International Journal of Cancer Therapy and Oncology (ISSN 2330-4049)

© International Journal of Cancer Therapy and Oncology (IJCTO)

To make sure that you can receive messages from us, please add the 'ijcto.org' domain to your e-mail 'safe list'. If you do not receive e-mail in your 'inbox', check your 'bulk mail' or 'junk mail' folders.

------------------------------------------------------------

Number of visits since October, 2013
AmazingCounters.com