Validation of the physical and RBE-weighted dose estimator based on PHITS coupled with a microdosimetric kinetic model for proton therapy

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Abstract

The microdosimetric kinetic model (MKM) is widely used for estimating relative biological effectiveness (RBE)-weighted doses for various radiotherapies because it can determine the surviving fraction of irradiated cells based on only the lineal energy distribution, and it is independent of the radiation type and ion species. However, the applicability of the method to proton therapy has not yet been investigated thoroughly. In this study, we validated the RBE-weighted dose calculated by the MKM in tandem with the Monte Carlo code PHITS for proton therapy by considering the complete simulation geometry of the clinical proton beam line. The physical dose, lineal energy distribution, and RBE-weighted dose for a 155 MeV mono-energetic and spread-out Bragg peak (SOBP) beam of 60 mm width were evaluated. In estimating the physical dose, the calculated depth dose distribution by irradiating the mono-energetic beam using PHITS was consistent with the data measured by a diode detector. A maximum difference of 3.1% in the depth distribution was observed for the SOBP beam. In the RBE-weighted dose validation, the calculated lineal energy distributions generally agreed well with the published measurement data. The calculated and measured RBE-weighted doses were in excellent agreement, except at the Bragg peak region of the mono-energetic beam, where the calculation overestimated the measured data by ~15%. This research has provided a computational microdosimetric approach based on a combination of PHITS and MKM for typical clinical proton beams. The developed RBE-estimator function has potential application in the treatment planning system for various radiotherapies.

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Most cited references 43

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Relative biological effectiveness (RBE) values for proton beam therapy. Variations as a function of biological endpoint, dose, and linear energy transfer.

Harald Paganetti (2014)

Proton therapy treatments are based on a proton RBE (relative biological effectiveness) relative to high-energy photons of 1.1. The use of this generic, spatially invariant RBE within tumors and normal tissues disregards the evidence that proton RBE varies with linear energy transfer (LET), physiological and biological factors, and clinical endpoint. Based on the available experimental data from published literature, this review analyzes relationships of RBE with dose, biological endpoint and physical properties of proton beams. The review distinguishes between endpoints relevant for tumor control probability and those potentially relevant for normal tissue complication. Numerous endpoints and experiments on sub-cellular damage and repair effects are discussed. Despite the large amount of data, considerable uncertainties in proton RBE values remain. As an average RBE for cell survival in the center of a typical spread-out Bragg peak (SOBP), the data support a value of ~1.15 at 2 Gy/fraction. The proton RBE increases with increasing LETd and thus with depth in an SOBP from ~1.1 in the entrance region, to ~1.15 in the center, ~1.35 at the distal edge and ~1.7 in the distal fall-off (when averaged over all cell lines, which may not be clinically representative). For small modulation widths the values could be increased. Furthermore, there is a trend of an increase in RBE as (α/β)x decreases. In most cases the RBE also increases with decreasing dose, specifically for systems with low (α/β)x. Data on RBE for endpoints other than clonogenic cell survival are too diverse to allow general statements other than that the RBE is, on average, in line with a value of ~1.1. This review can serve as a source for defining input parameters for applying or refining biophysical models and to identify endpoints where additional radiobiological data are needed in order to reduce the uncertainties to clinically acceptable levels.

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Relative biological effectiveness (RBE) values for proton beam therapy.

Jay S. Loeffler, L E Gerweck, Marek Ancukiewicz … (2002)

Clinical proton beam therapy has been based on the use of a generic relative biological effectiveness (RBE) of 1.0 or 1.1, since the available evidence has been interpreted as indicating that the magnitude of RBE variation with treatment parameters is small relative to our abilities to determine RBEs. As substantial clinical experience and additional experimental determinations of RBE have accumulated and the number of proton radiation therapy centers is projected to increase, it is appropriate to reassess the rationale for the continued use of a generic RBE and for that RBE to be 1.0-1.1. Results of experimental determinations of RBE of in vitro and in vivo systems are examined, and then several of the considerations critical to a decision to move from a generic to tissue-, dose/fraction-, and LET-specific RBE values are assessed. The impact of an error in the value assigned to RBE on normal tissue complication probability (NTCP) is discussed. The incidence of major morbidity in proton-treated patients at Massachusetts General Hospital (MGH) for malignant tumors of the skull base and of the prostate is reviewed. This is followed by an analysis of the magnitude of the experimental effort to exclude an error in RBE of >or=10% using in vivo systems. The published RBE values, using colony formation as the measure of cell survival, from in vitro studies indicate a substantial spread between the diverse cell lines. The average value at mid SOBP (Spread Out Bragg Peak) over all dose levels is approximately 1.2, ranging from 0.9 to 2.1. The average RBE value at mid SOBP in vivo is approximately 1.1, ranging from 0.7 to 1.6. Overall, both in vitro and in vivo data indicate a statistically significant increase in RBE for lower doses per fraction, which is much smaller for in vivo systems. There is agreement that there is a measurable increase in RBE over the terminal few millimeters of the SOBP, which results in an extension of the bioeffective range of the beam in the range of 1-2 mm. There is no published report to indicate that the RBE of 1.1 is low. However, a substantial proportion of patients treated at approximately 2 cobalt Gray equivalent (CGE)/fraction 5 or more years ago were treated by a combination of both proton and photon beams. Were the RBE to be erroneously underestimated by approximately 10%, the increase in complication frequency would be quite serious were the complication incidence for the reference treatment >or=3% and the slope of the dose response curves steep, e.g., a gamma(50) approximately 4. To exclude >or=1.2 as the correct RBE for a specific condition or tissue at the 95% confidence limit would require relatively large and multiple assays. At present, there is too much uncertainty in the RBE value for any human tissue to propose RBE values specific for tissue, dose/fraction, proton energy, etc. The experimental in vivo and clinical data indicate that continued employment of a generic RBE value and for that value to be 1.1 is reasonable. However, there is a local "hot region" over the terminal few millimeters of the SOBP and an extension of the biologically effective range. This needs to be considered in treatment planning, particularly for single field plans or for an end of range in or close to a critical structure. There is a clear need for prospective assessments of normal tissue reactions in proton irradiated patients and determinations of RBE values for several late responding tissues in laboratory animal systems, especially as a function of dose/fraction in the range of 1-4 Gy.

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Biophysical characteristics of HIMAC clinical irradiation system for heavy-ion radiation therapy.

F Soga, A Fukumura, H Ito … (1999)

The irradiation system and biophysical characteristics of carbon beams are examined regarding radiation therapy. An irradiation system was developed for heavy-ion radiotherapy. Wobbler magnets and a scatterer were used for flattening the radiation field. A patient-positioning system using X ray and image intensifiers was also installed in the irradiation system. The depth-dose distributions of the carbon beams were modified to make a spread-out Bragg peak, which was designed based on the biophysical characteristics of monoenergetic beams. A dosimetry system for heavy-ion radiotherapy was established to deliver heavy-ion doses safely to the patients according to the treatment planning. A carbon beam of 80 keV/microm in the spread-out Bragg peak was found to be equivalent in biological responses to the neutron beam that is produced at cyclotron facility in National Institute Radiological Sciences (NIRS) by bombarding 30-MeV deuteron beam on beryllium target. The fractionation schedule of the NIRS neutron therapy was adapted for the first clinical trials using carbon beams. Carbon beams, 290, 350, and 400 MeV/u, were used for a clinical trial from June of 1994. Over 300 patients have already been treated by this irradiation system by the end of 1997.

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Author and article information

Journal

Journal ID (nlm-ta): J Radiat Res

Journal ID (iso-abbrev): J. Radiat. Res

Journal ID (publisher-id): jrr

Title: Journal of Radiation Research

Publisher: Oxford University Press

ISSN (Print): 0449-3060

ISSN (Electronic): 1349-9157

Publication date (Print): January 2018

Publication date (Electronic): 26 October 2017

Publication date PMC-release: 26 October 2017

Volume: 59

Issue: 1

Pages: 91-99

Affiliations

[1 ] Faculty of Medicine, University of Tsukuba , 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan

[2 ] Japan Atomic Energy Agency, 2-4, Shirakata, Tokai, Ibaraki 319-1195, Japan

[3 ] Proton Beam Therapy Center, University of Tsukuba Hospital , 2-1-1, Amakubo, Tsukuba, Ibaraki, 305-8576, Japan

Author notes

Corresponding author. Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan. Tel: +81-29-853-5600 (ext. 90665); Fax: +81-29-853-3404; Email: k-takada@ 123456md.tsukuba.ac.jp

Article

Publisher ID: rrx057

DOI: 10.1093/jrr/rrx057

PMC ID: 5778494

PubMed ID: 29087492

SO-VID: 5887d41b-6758-4ca9-bf68-d40d09516490

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 30 March 2017

Date revision received : 13 July 2017

Page count

Pages: 9

Funding

Funded by: Japan Society for the Promotion of Science (JSPS) KAKENHI 10.13039/501100001691

Validation of the physical and RBE-weighted dose estimator based on PHITS coupled with a microdosimetric kinetic model for proton therapy

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Karger: Oncology

Most cited references 43

Relative biological effectiveness (RBE) values for proton beam therapy. Variations as a function of biological endpoint, dose, and linear energy transfer.

Relative biological effectiveness (RBE) values for proton beam therapy.

Biophysical characteristics of HIMAC clinical irradiation system for heavy-ion radiation therapy.

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