Volume 3, Issue 3

Case study

Radiotherapy

STUDY OF THE DISCREPANCY BETWEEN ANALYTICAL CALCULATIONS AND THE OBSERVED BIOLOGICAL EFFECTIVENESS IN PROTON BORON CAPTURE THERAPY (PBCT)

G.A.P. Cirrone, G. Petringa, A. Attili, D. Chiappara, L. Manti, V. Bravatà, D. Margarone, M. Mazzocco, G. Cuttone

Pages: 147–151

DOI: 10.21175/RadJ.2018.03.025

Received: 13 OCT 2018, Received revised: 8 JAN 2019, Accepted: 12 JAN 2019, Published online: 28 FEB 2019

A work recently published experimentally demonstrates an increase in the radiobiological efficacy of clinical proton beams when a tumour is treated in the presence of a concentration of 11B. For the first time, this paper demonstrates the potential role of the p+11B —> 3α (for brevity, p-B) reaction in the biological enhancement of proton therapy effectiveness. The work reports robust experimental data in terms of clonogenic cell survival and chromosomal aberrations and unambiguously shows the presence of an enhancement when cells were exposed to a clinical proton beam subject to treatment with sodium boroncaptate (BSH). Moreover, the greater occurrence of complex-type chromosomal exchanges points to the effect in terms of radiation of a LET (Linear Energy Transfer) greater than that of protons alone, possibly the alpha particles generated by the reaction. At the same time, we emphasized that analytical calculations, performed on the basis of the well-known total production cross-section data, are not able to explain the effect in a macroscopic way, i.e., solely in terms of a trivial increase in the total dose released in the cells by the alpha-particles. In this paper, thanks to simulations and analytical calculations, we will discuss the theoretically expected alpha-particle yield and the corresponding LET and RBE (Relative Biological Effectiveness) increase related to the 11B presence. We conclude that a mere calculation based on the classical concepts of integral dose and average LET and RBE cannot be used to justify the observed radiobiological phenomena. We therefore suggest that micro- and nano-dosimetric aspects must be taken into account.
  1. D-K. Yoon, J-Y. Jung, T. S. Suh, “Application of proton boron fusion reaction to radiation therapy: A Monte Carlo simulation study,” Appl. Phys. Lett., vol. 105, no. 22, 223507, 2014, Dec. 2014.
    DOI: 10.1063/1.4903345
  2. L. Giuffrida et al., “Prompt gamma ray diagnostics and enhanced hadron-therapy using neutron-free nuclear reactions,” AIP Advances, vol.6, no. 10, pp. 105 – 204, Oct. 2016.
    DOI: 10.1063/1.4965254
  3. G. Petringa et al., “Study of gamma-ray emission by proton beam interaction with injected boron atoms for future medical imaging applications,” J. Instrumentation, vol.12, no. 3, C03049, Mar. 2017.
    DOI: 10.1088/1748-0221/12/03/C03049
  4. G. A. P. Cirrone et al., “First experimental proof of Proton Boron Capture Therapy (PBCT) to enhance protontherapy effectiveness,” Sci. Rep., vol. 8, 1141, Jan. 2018.
    DOI: 10.1038/s41598-018-19258-5
    PMid: 29348437
    PMCid: PMC5773549
  5. S. Xuan et al., “Synthesis and in vitro studies of a series of carborane-containing boron dipyrromethenes (bodipys),” J. Med. Chem. vol. 59, no. 5, pp. 2109 – 2117, Feb. 2016.
    DOI: 10.1021/acs.jmedchem.5b01783
    PMid: 26849474
    PMCid: PMC4893941
  6. N. Otuka et al., “Towards a More Complete and Accurate Experimental Nuclear Reaction Data Library (EXFOR): International Collaboration Between Nuclear Reaction Data Centres (NRDC),” Nucl. Data Sheets, vol. 120, pp. 272 – 276, Jun. 2014.
    DOI: 10.1016/j.nds.2014.07.065
  7. A. Koning et al., “Modern Nuclear Data Evaluation with the TALYS Code System,” Nucl. Data Sheets, vol. 113, no. 12, pp. 2841 – 2934, Dec. 2012.
    DOI: 10.1016/j.nds.2012.11.002
  8. S. Agostinelli et al., “Geant4-a simulation toolkit,” Nucl. Instrum. Methods A, vol. 506 pp. 250 – 303, 2003.
    DOI: 10.1016/S0168-9002(03)01368-8
  9. G. A. P. Cirrone et al., “Hadrontherapy: a Geant4-Based Tool for Proton/Ion-Therapy-studies,” Prog. Nucl. Sci. Technol., vol. 2, pp. 207 – 212, 2011.
    DOI: 10.15669/pnst.2.207
  10. Geant4, A Simulation Toolkit: Physics Reference Manual Release 10.4, CERN, Geneva, Switzerland, 2017.
    Retrieved from: http://geant4-userdoc.web.cern.ch/geant4-userdoc/UsersGuides/PhysicsReferenceManual/fo/Physics ReferenceManual.pdf;
    Retrieved on: Aug. 10, 2018
  11. Physics List EM constructors in Geant4 10.4, CERN, Geneva, Switzerland, 2018.
    Retrieved from: https://geant4.web.cern.ch/node/1731#opt4;
    Retrieved on: Aug. 10, 2018
  12. D. Sanchez-Parcherisa et al., “Analytical calculation of proton linear energy transfer in voxelized geometries including secondary protons,” Phys. Med. Biol., vol. 61, no. 4, pp. 1705 – 1721, Feb. 2016.
    DOI: 10.1088/0031-9155/61/4/1705
    PMid: 26840945