Dokument

Summary:
Treatment planning in ion beam therapy requires a reliable estimation of the relative biological effectiveness (RBE) of the irradiated tissue. For the pilot project at GSI Helmholtzzentrum für Schwerionenforschung GmbH and at other European ion beam therapy centers RBE prediction is based on a biophysical model, the Local Effect Model (LEM). The model version in use, LEM I, is optimized to give a reliable estimation of RBE in the target volume for carbon ion irradiation. However, systematic deviations are observed for the entrance channel of carbon ions and in general for lighter ions. Thus, the LEM has been continuously developed to improve accuracy. The recent version LEM IV has proven to better describe in-vitro cell experiments. Thus, for the clinical application of LEM IV it is of interest to analyze potential differences compared to LEM I under treatment-like conditions. The systematic analysis presented in this work is aiming at the comparison of RBE-weighted doses resulting from different approaches and model versions for protons and carbon ions. This will facilitate the assessment of consequences for clinical application and the interpretation of clinical results from different institutions. In the course of this thesis it has been shown that the RBE-weighted doses predicted on the basis of LEM IV for typical situations representing chordoma treatments differ on average by less than 10 % to those based on LEM I and thus also allow a consistent interpretation of the clinical results. At Japanese ion beam therapy centers the RBE is estimated using their clinical experience from neutron therapy in combination with in-vitro measurements for carbon ions (HIMAC approach). The methods presented in this work allow direct comparison of the HIMAC approach and the LEM and thus of the clinical results obtained at Japanese and European ion beam therapy centers. Furthermore, the sensitivity of the RBE on the model parameters was evaluated. Among all parameters the characterization of the photon dose-response curve has been found to be of particular importance for the determination of RBE. The application of the LEM IV for proton beams more correctly represents the experimentally observed increase of RBE towards the distal end of the irradiation field compared to the clinically considered constant value of 1.1. It further allowed a better systematic characterization of the increased effective range of proton beams that is a consequence of the RBE enhancement at the distal edge of the treatment field. The results of this work underline the importance of detailed RBE modeling for a long-term improvement of treatment planning in particle therapy and the better exploitation of advantages inherent to this radiation modality.

Bibliographie / References

1. Scholz M, Kellerer A M, Kraft-Weyrather W and Kraft G 1997 Computation of cell survival in heavy ion beams for therapy: the model and its approximation Radiat. Environ. Biophys. 36 59–66
2. A. Cucinotta, R. Katz, J. W. Wilson, L. W. Townsend, J. Shinn, and F. Hajnal, " Biological effectiveness of high-energy protons: Target frag- mentation, " Radiat. Res. 127, 130–137 (1991).
3. Shao C, Saito M and Yu Z 1999 Formation of single-and double-strand breaks of pBR322 plasmid irradiated in the presence of scavengers Radiat. Environ. Biophys. 38 105–9
4. Brenner D J 1993 Dose, volume, and tumor-control predictions in radiotherapy Int. J. Radiat. Oncol. Biol. Phys. 26 171–9
5. I. Yock and N. J. Tarbell, " Technology insight: Proton beam radiotherapy for treatment in pediatric brain tumors, " Nat. Clin. Pract. Oncol. 1, 97–103 (2004).
6. Mozumder A 2007 Track-core radius of charged particles at relativistic speed in condensed media J. Chem. Phys. 60 1145–48
7. Carabe-Fernandez A, Dale R G and Jones B 2007 The incorporation of the concept of minimum RBE (RBEmin) into the linear-quadratic model and the potential for improved radiobiological analysis of high-LET treatments Int. J. Radiat. Biol. 83 27–39
8. Larsson and B. A. Kihlman, " Chromosome aberrations following irra- diation with high-energy protons and their secondary radiation: A study of dose distribution and biological efficiency using root-tips of Vicia faba and Allium cepa, " Int. J. Radiat. Biol. 2, 8–19 (1960).
9. Nikjoo H, O'Neill P, Goodhead D T and Terrissol M 1997 Computational modelling of low-energy electron-induced DNA damage by early physical and chemical events Int. J. Radiat. Biol. 71 467–83
10. Paganetti, " Nuclear interactions in proton therapy: Dose and relative biological effect distributions originating from primary and secondary par- ticles, " Phys. Med. Biol. 47, 747–764 (2002).
11. Carlone M, Wilkins D and Raaphorst P 2005 The modified linear-quadratic model of Guerrero and Li can be derived from a mechanistic basis and exhibits linear-quadratic-linear behaviour Phys. Med. Biol. 50 L9–15
12. Inaniwa T et al 2010 Treatment planning for a scanned carbon beam with a modified microdosimetric kinetic model Phys. Med. Biol. 55 6721–37
13. Böhlen T T et al 2012 Investigating the robustness of ion beam therapy treatment plans to uncertainties in biological treatment parameters Phys. Med. Biol. 57 7983–8004
14. Goodhead D T 2006 Energy deposition stochastics and track structure: what about the target? Radiat. Prot. Dosim. 122 3–15
15. Astrahan M 2008 Some implications of linear-quadratic-linear radiation dose-response with regard to hypofractionation Med. Phys. 35 4161–72
16. Dasu and I. Toma-Dasu, " Impact of variable RBE on proton fractiona- tion, " Med. Phys. 40, 011705 (9pp.) (2013).
17. Goitein, " Calculation of the uncertainty in the dose delivered during radiation therapy, " Med. Phys. 12, 608–612 (1985).
18. Krämer and M. Durante, " Ion beam transport calculations and treatment plans in particle therapy, " Eur. Phys. J. D 60, 195–202 (2010).
19. Paganetti, " Significance and implementation of RBE variations in pro- ton beam therapy, " Technol. Cancer Res. Treat. 2, 413–426 (2003).
20. Sato T and Furusawa Y 2012 Cell survival fraction estimation based on the probability densities of domain and cell nucleus specific energies using improved microdosimetric kinetic models Radiat. Res. 178 341–56
21. Curtis S B 1986 Lethal and potentially lethal lesions induced by radiation—a unified repair model Radiat. Res. 106 252–70
22. Hawkins R B 1994 A statistical theory of cell killing by radiation of varying linear energy transfer Radiat. Res. 140 366–74
23. Tobias CA 1985 The repair–misrepair model in radiobiology: comparison to other models Radiat. Res. Suppl. 8 S77–95
24. H. Sweet, R. N. Kjellberg, R. A. Field, A. M. Koehler, and W. M. Preston, " Time-intensity data in solar cosmic-ray events: Biological data relevant to their effects in man, " Radiat. Res. Suppl. 7, 369–383 (1967).
25. Combs S E et al 2010 Heidelberg ion therapy center (HIT): initial clinical experience in the first 80 patients Acta Oncol. 49 1132–40
26. Friedrich T, Scholz U, Elsässer T, Durante M and Scholz M 2012b Calculation of the biological effects of ion beams based on the microscopic spatial damage distribution pattern Int. J. Radiat. Biol. 88 103–7
27. Hawkins R B 1996 A microdosimetric-kinetic model of cell death from exposure to ionizing radiation of any LET, with experimental and clinical applications Int. J. Radiat. Biol. 69 739–55
28. Kiefer J and Straaten H 1986 A model of ion track structure based on classical collision dynamics Phys. Med. Biol. 31 1201–9
29. Dasu A, Toma-Dasu I and Fowler J F 2003 Should single or distributed parameters be used to explain the steepness of tumour control probability curves? Phys. Med. Biol. 48 387–97
30. Grün R et al 2012 Impact of enhancements in the local effect model (LEM) on the predicted RBE-weighted target dose distribution in carbon ion therapy Phys. Med. Biol. 57 7261–74
31. Carabe, M. Moteabbed, N. Depauw, J. Schuemann, and H. Paganetti, " Range uncertainty in proton therapy due to variable biological effective- ness, " Phys. Med. Biol. 57, 1159–1172 (2012).
32. . Friedrich, R. Grün, U. Scholz, T. Elsässer, M. Durante, and M. Scholz, " Sensitivity analysis of the relative biological effectiveness predicted by the local effect model, " Phys. Med. Biol. 58, 6827–6849 (2013).
33. Gunzert-Marx K, Iwase H, Schardt D and Simon R S 2008 Secondary beam fragments produced by 200 MeVu −112 C ions in water and their dose contributions in carbon ion radiotherapy New J. Phys. 10 075003
34. Elsässer T, Cunrath R, Krämer M and Scholz M 2008 Impact of track structure calculations on biological treatment planning in ion radiotherapy New J. Phys. 10 075005
35. Moiseenko V V, Hamm R N, Waker A J and Prestwich W V 2001 Calculation of radiation-induced DNA damage from photons and tritium beta-particles: part II. Tritium RBE and damage complexity Radiat. Environ. Biophys. 40 23–31
36. Cucinotta F A, Nikjoo H and Goodhead D T 1999 Applications of amorphous track models in radiation biology Radiat. Environ. Biophys. 38 81–92
37. Tsujii H and Kamada T 2012 A review of update clinical results of carbon ion radiotherapy Japan J. Clin. Oncol. 42 670–85
38. Elsässer T, Krämer M and Scholz M 2008 Accuracy of the local effect model for the prediction of biologic effects of carbon ion beams in vitro and in vivo Int. J. Radiat. Oncol. Biol. Phys. 71 866–72
39. Garcia L M, Wilkins D E and Raaphorst G P 2007 Alpha/beta ratio: a dose range dependence study Int. J. Radiat. Oncol. Biol. Phys. 67 587–93
40. Prise K M, Pinto M, Newman H C and Michael B D 2001 A review of studies of ionizing radiation-induced double- strand break clustering Radiat. Res. 156 572–76
41. 31 H. Paganetti, P. Olko, H. Kobus, R. Becker, T. Schmitz, M. P. R. Waligorski, D. Filges, and H. W. Müller-Gärtner, " Calculation of relative biological effectiveness for proton beams using biological weighting functions, " Int. J. Radiat. Oncol., Biol., Phys. 37, 719–729 (1997).
42. Johansson, " Comparative treatment planning in radiotherapy and clinical impact of proton relative biological effectiveness, " Ph.D. dissertation, Acta Universitatis Upsaliensis, Uppsala, 2006.
43. Bassler N, Jäkel O, Søndergaard C S and Petersen J B 2010 Dose-and LET-painting with particle therapy Acta Oncol. 49 1170–6
44. Schulz-Ertner D et al 2007 Effectiveness of carbon ion radiotherapy in the treatment of skull-base chordoma Int. J. Radiat. Oncol. Biol. Phys. 68 449–57
45. Kanai T et al 2006 Examination of GyE system for HIMAC carbon therapy Int. J. Radiat. Oncol. Biol. Phys. 64 650–6
46. Pedroni, S. Scheib, T. Böhringer, A. Coray, M. Grossmann, S. Lin, and A. Lomax, " Experimental characterization and physical modelling of the dose distribution of scanned proton pencil beams, " Phys. Med. Biol. 50, 541–561 (2005).
47. Guerrero M and Li A X 2004 Extending the linear-quadratic model for large fraction doses pertinent to stereotactic radiotherapy Phys. Med. Biol. 49 4825–35
48. Fertil B and Malaise E P 1985 Intrinsic radiosensitivity of human cell lines is correlated with radioresponsiveness of human tumors: analysis of 101 published survival curves Int. J. Radiat. Oncol. Biol. Phys. 11 1699–707
49. F. Gensheimer, T. I. Yock, N. J. Liebsch, G. C. Sharp, H. Paganetti, N. Madan, P. E. Grant, and T. Bortfeld, " In vivo proton beam range veri- fication using spine MRI changes, " Int. J. Radiat. Oncol., Biol., Phys. 78, 268–275 (2010).
50. John Eley for careful reading and suggestions to the paper. a) Author to whom correspondence should be addressed. Electronic mail: M.Scholz@gsi.de 1 ICRU, " Prescribing, recording and reporting proton-beam therapy, " ICRU Report No. 78 (International Commission on Radiation Units and Measure- ments, Bethesda, MD, 2007).
51. Haberer, W. Becher, D. Schardt, and G. Kraft, " Magnetic scanning sys- tem for heavy ion therapy, " Nucl. Instrum. Methods Phys. Res. A330, 296– 305 (1993).
52. Stenerlöw B, Karlsson K H, Cooper B and Rydberg B 2003 Measurement of prompt DNA double-strand breaks in mammalian cells without including heat-labile sites: results for cells deficient in nonhomologous end joining Radiat. Res. 159 502–10
53. G. Wouters, G. K. Y. Lam, U. Oelfke, K. Gardey, R. E. Durand, and L. D. Skarsgard, " Measurements of relative biological effectiveness of the 70 MeV proton beam at TRIUMF using Chinese hamster V79 cells and the high-precision cell sorter assay, " Radiat. Res. 146, 159–170 (1996).
54. B. Robertson, J. R. Williams, R. A. Schmidt, J. B. Little, D. F. Flynn, and H. D. Suit, " Radiobiological studies of a high-energy modulated proton beam utilizing cultured mammalian cells, " Cancer 35, 1664–1677 (1975).
55. Bettega, P. Calzolari, P. Chauvel, A. Courdi, J. Herault, N. Iborra, R. Marchesini, P. Massariello, G. L. Poli, and L. Tallone, " Radiobiologi- cal studies on the 65 MeV therapeutic proton beam at Nice using human tumour cells, " Int. J. Radiat. Biol. 76, 1297–1303 (2000).
56. Krämer and M. Scholz, " Rapid calculation of biological effects in ion radiotherapy, " Phys. Med. Biol. 51, 1959–1970 (2006).
57. Gerweck L E and Kozin S V 1999 Relative biological effectiveness of proton beams in clinical therapy Radiother. Oncol. 50 135–42
58. Sensitivity analysis of RBE 6849
59. Gall, L. Verhey, J. Alonso, J. Castro, J. M. Collier, W. Chu, I. Daftari, M. Goitein, H. Kubo, B. Ludewigt, J. Munzenrider, P. Petti, T. Renner, S. Rosenthal, A. Smith, J. Staples, H. Suit, and A. Thornton, " State of the art? New proton medical facilities for the Massachusetts General Hospital and the University of California Davis Medical Center, " Nucl. Instrum.
60. Courdi, N. Brassart, J. Hérault, and P. Chauvel, " The depth-dependent radiation response of human melanoma cells exposed to 65 MeV protons, " Br. J. Radiol. 67, 800–804 (1994).
61. Paganetti and T. Schmitz, " The influence of the beam modulation tech- nique on dose and RBE in proton radiation therapy, " Phys. Med. Biol. 41, 1649–1663 (1996).
62. Neary G J, Evans H J, Tonkinson S M and Williamson F S 1959 The relative biological efficiency of single doses of fast neutrons and gamma-rays on Vicia faba roots and the effect of oxygen: part III. Mitotic delay Int. J. Radiat. Biol. 1 230–40
63. Krämer M, Jäkel O, Haberer H, Kraft G, Schardt D and Weber U 2000 Treatment planning for heavy-ion radiotherapy: physical beam model and dose optimization Phys. Med. Biol. 45 3299–317
64. Tilly, J. Johansson, U. Isacsson, J. Medin, E. Blomquist, E. Grusell, and B. Glimelius, " The influence of RBE variations in a clinical proton treatment plan for a hypopharynx cancer, " Phys. Med. Biol. 50, 2765–2777 (2005).
65. C. Frese, J. J. Wilkens, P. E. Huber, A. D. Jensen, U. Oelfke, and Z. Taheri-Kadkhoda, " Application of constant vs. variable relative biologi- cal effectiveness in treatment planning of intensity-modulated proton ther- apy, " Int. J. Radiat. Oncol., Biol., Phys. 79, 80–88 (2011).
66. Lühr A, Hansen D C, Teiwes R, Sobolevsky N, Jäkel O and Bassler N 2012 The impact of modeling nuclear fragmentation on delivered dose and radiobiology in ion therapy Phys. Med. Biol. 57 5169–85
67. Scholz M, Matsufuji N and Kanai T 2006 Test of the local effect model using clinical data: tumour control probability for lung tumours after treatment with carbon ion beams Radiat. Prot. Dosim. 122 478–9
68. Yokota H et al 1995 Evidence for the organization of chromatin in megabase pair-sized loops arranged along a random walk path in the human G0/G1 interphase nucleus J. Cell. Biol. 130 1239–49 ACKNOWLEDGMENTS Work is part of HGS-HIRe. The authors are grateful to
69. M. Koizumi, S. Ozeki, and K. Hatanaka, " Comparison of radiobiological effective depths in 65-MeV modulated proton beams, " Br. J. Cancer 76, 220–225 (1997).
70. Neumaier T et al 2012 Evidence for formation of DNA repair centers and dose-response nonlinearity in human cells Proc. Natl Acad. Sci. USA 109 443–8
71. Paganetti, " Range uncertainties in proton therapy and the role of Monte Carlo simulations, " Phys. Med. Biol. 57, R99–R117 (2012).
72. Jones, T. S. A. Underwood, and R. G. Dale, " The potential impact of relative biological effectiveness uncertainty on charged particle treatment prescriptions, " Br. J. Radiol. 84, S61–S69 (2011) (Special issue).
73. Jones B, Wilson P, Nagano A, Fenwick J and McKenna G 2012 Dilemmas concerning dose distribution and the influence of relative biological effect in proton beam therapy of medulloblastoma Br. J. Radiol. 85 e912–8
74. Friedrich T, Scholz U, Elsässer T, Durante M and Scholz M 2013 Systematic analysis of RBE and related quantities using a database of cell survival experiments with ion beam irradiation J. Radiat. Res. 54 494–514
75. E. Cotter, S. M. McBride, and T. I. Yock, " Proton radiotherapy for solid tumors of childhood, " Technol. Cancer Res. Treat. 11, 267–278 (2012).
76. Elsässer and M. Scholz, " Cluster effects within the local effect model, " Radiat. Res. 167, 319–329 (2007).
77. Friedrich T, Durante M and Scholz M 2012a Modeling cell survival after photon irradiation based on double-strand break clustering in megabase pair chromatin loops Radiat. Res. 178 385–94
78. Fertil B, Reydellet I and Deschavanne P J 1994 A benchmark of cell survival models using survival curves for human cells after completion of repair of potentially lethal damage Radiat. Res. 138 61–9
79. Furusawa Y et al 2000 Inactivation of aerobic and hypoxic cells from three different cell lines by accelerated 3He-, 12C-and 20Ne-Ion beams Radiat. Res. 154 485–96
80. Brusasco, B. Voss, and D. Schardt, " A dosimetry system for fast mea- surement of 3D depth-dose profiles in charged-particle tumor therapy with scanning techniques, " Nucl. Instrum. Methods Phys. Res. B168, 578–592 (2000).
81. Scholz M and Elsässer T 2007 Biophysical models in ion beam radiotherapy Adv. Space Res. 40 1381–91
82. Elsässer T et al 2010 Quantification of the relative biological effectiveness for ion beam radiotherapy: direct experimental comparison of proton and carbon ion beams and a novel approach for treatment planning Int. J. Radiat. Oncol. Biol. Phys. 78 1177–83
83. Calugaru, C. Nauraye, G. Noël, N. Giocanti, V. Favaudon, and F. Mégnin-Chanet, " Radiobiological characterization of two therapeutic proton beams with different initial energy spectra used at the Institut Curie Proton Therapy Center in Orsay, " Int. J. Radiat. Oncol., Biol., Phys. 81, 1136–1143 (2011).
84. Tang, S. Both, H. Bentefour, J. J. Paly, Z. Tochner, J. Efstathiou, and H.-M. Lu, " Improvement of prostate treatment by anterior proton fields, " Int. J. Radiat. Oncol., Biol., Phys. 83, 408–418 (2012).
85. Krämer M and Jäkel O 2005 Biological dose optimization using ramp-like dose gradients in ion irradiation fields Phys. Medica 21 107–11
86. Cirrone, and G. Cuttone, " Response of a radioresistant human melanoma cell line along the proton spread-out Bragg peak, " Int. J. Radiat. Biol. 86, 742–751 (2010).
87. Ando K and Kase Y 2009 Biological characteristics of carbon-ion therapy Int. J. Radiat. Biol. 85 715–28

Das Dokument ist im Internet frei zugänglich - Hinweise zu den Nutzungsrechten