Optimization of radiobiological effects in intensity modulated proton therapy.

Today, inverse treatment planning for intensity modulated proton therapy (IMPT) usually employs a constant relative biological effectiveness (RBE). In this paper, the potential clinical relevance of RBE variations for scanning techniques in IMPT is investigated, and a new strategy to include the RBE into the inverse planning process is presented. Three-dimensional RBE distributions are calculated based on a phenomenological model that describes the RBE as a function of dose, linear energy transfer (LET) and tissue type in the framework of the linear-quadratic model. This RBE model is integrated into the optimization loop of inverse planning by using a modified version of the standard quadratic objective function, where the physical dose is replaced by the biological effect. This system for "biological optimization" was implemented into a research version of the inverse planning software KonRad and allows the direct optimization of the product of RBE and physical dose. Several treatment plans for a prostate case are presented, which compare the biological with the conventional physical dose optimization for IMPT scanning techniques, in particular distal edge tracking (DET) and the full three-dimensional (3D) modulation of beam spots. Mainly due to their different LET distributions, the RBE effects for these two techniques are quite different: while the RBE distribution was more or less homogeneous in the planning target volume (PTV) for 3D modulation, considerable RBE variations within the PTV were observed for DET. These unfavorable effects could be compensated for by employing the new biological objective function, which led to a more homogeneous distribution of the product of RBE and physical dose in the PTV. The computation time increased by a factor of 2 compared to the optimization of the physical dose. In conclusion, the proposed method allows the simultaneous multifield optimization of the biological effect in a reasonable time, and is therefore well suited for studying the influence of a variable RBE in IMPT as well as for minimizing potentially adverse effects.

[1]  U Oelfke,et al.  A phenomenological model for the relative biological effectiveness in therapeutic proton beams. , 2004, Physics in medicine and biology.

[2]  M. Scholz,et al.  Computation of cell survival in heavy ion beams for therapy , 1997, Radiation and environmental biophysics.

[3]  L. Verhey,et al.  In vivo determinations of RBE in a high energy modulated proton beam using normal tissue reactions and fractionated dose schedules. , 1977, International journal of radiation oncology, biology, physics.

[4]  T. Holmes,et al.  A comparison of three inverse treatment planning algorithms. , 1994, Physics in medicine and biology.

[5]  P Lambin,et al.  Low-dose hypersensitivity: current status and possible mechanisms. , 2001, International journal of radiation oncology, biology, physics.

[6]  A. Lomax,et al.  Intensity modulation methods for proton radiotherapy. , 1999, Physics in medicine and biology.

[7]  M Goitein,et al.  Biophysical modelling of proton radiation effects based on amorphous track models , 2001, International journal of radiation biology.

[8]  Harald Paganetti,et al.  Relative biological effectiveness (RBE) values for proton beam therapy. , 2002, International journal of radiation oncology, biology, physics.

[9]  E. Pedroni,et al.  Intensity modulated proton therapy: a clinical example. , 2001, Medical physics.

[10]  A Brahme,et al.  Comparison of cell survival models for mixed LET radiation. , 1999, International journal of radiation biology.

[11]  B. Vojnovic,et al.  Low-Dose Hypersensitivity in Chinese Hamster V79 Cells Targeted with Counted Protons Using a Charged-Particle Microbeam , 2001, Radiation research.

[12]  Uwe Oelfke,et al.  Inverse planning of intensity modulated proton therapy. , 2004, Zeitschrift fur medizinische Physik.

[13]  U. Oelfke,et al.  Three-dimensional LET calculations for treatment planning of proton therapy. , 2004, Zeitschrift fur medizinische Physik.

[14]  S. C. Sharma,et al.  Inactivation of cells by heavy ion bombardment. , 1971, Radiation research.

[15]  H Paganetti,et al.  Nuclear interactions in proton therapy: dose and relative biological effect distributions originating from primary and secondary particles. , 2002, Physics in medicine and biology.

[16]  E. Pedroni,et al.  The 200-MeV proton therapy project at the Paul Scherrer Institute: conceptual design and practical realization. , 1995, Medical physics.

[17]  Uwe Oelfke,et al.  Analytical linear energy transfer calculations for proton therapy. , 2003, Medical physics.

[18]  T. Bortfeld,et al.  Inverse planning for photon and proton beams. , 2001, Medical dosimetry : official journal of the American Association of Medical Dosimetrists.

[19]  Simeon Nill Development and application of a multi-modality inverse treatment planning system , 2001 .

[20]  L. Gerweck,et al.  Relative biological effectiveness of proton beams in clinical therapy. , 1999, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[21]  A. Ruifrok,et al.  Proton RBE for early intestinal tolerance in mice after fractionated irradiation. , 2001, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[22]  A. Ruifrok,et al.  Proton relative biological effectiveness (RBE) for survival in mice after thoracic irradiation with fractionated doses. , 2000, International journal of radiation oncology, biology, physics.

[23]  F Ianzini,et al.  Inactivation and mutation induction in V79 cells by low energy protons: re-evaluation of the results at the LNL facility. , 1993, International journal of radiation biology.

[24]  M Scholz,et al.  Treatment planning for heavy-ion radiotherapy: calculation and optimization of biologically effective dose. , 2000, Physics in medicine and biology.

[25]  G. Kraft,et al.  Tumor therapy with heavy charged particles , 2000 .

[26]  A. Kellerer,et al.  A Generalized Formulation of Dual Radiation Action1 , 1978 .

[27]  T Ogino,et al.  Relative biological effectiveness of the 235 MeV proton beams at the National Cancer Center Hospital East. , 2001, Journal of radiation research.

[28]  G T Chen,et al.  Beam scanning for heavy charged particle radiotherapy. , 1983, Medical physics.

[29]  U Oelfke,et al.  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. , 1996, Radiation research.

[30]  J. Wilkens Evaluation of radiobiological effects in intensity modulated proton therapy: New strategies for inverse treatment planning , 2004 .