The relative biological effectiveness (RBE) calculations used during the planning of ion therapy treatments are generally based on the microdosimetric kinetic model (MKM) and the local effect model ...(LEM). The Mayo Clinic Florida MKM (MCF MKM) was recently developed to overcome the limitations of previous MKMs in reproducing the biological data and to eliminate the need for ion-exposed in vitro data as input for the model calculations. Since we are considering to implement the MCF MKM in clinic, this article presents (a) an extensive benchmark of the MCF MKM predictions against corresponding in vitro clonogenic survival data for 4 rodent and 10 cell lines exposed to ions from 1H to 238U, and (b) a systematic comparison with published results of the latest version of the LEM (LEM IV). Additionally, we introduce a novel approach to derive an approximate value of the MCF MKM model parameters by knowing only the animal species and the mean number of chromosomes. The overall good agreement between MCF MKM predictions and in vitro data suggests the MCF MKM can be reliably used for the RBE calculations. In most cases, a reasonable agreement was found between the MCF MKM and the LEM IV.
. To investigate similarities and differences in the formalism, processing, and the results of relative biological effectiveness (RBE) calculations with a biological weighting function (BWF), the ...microdosimetric kinetic model (MKM) and subsequent modifications (non-Poisson MKM, modified MKM). This includes: (a) the extension of the V79-RBE
BWF to model the RBE for other clonogenic survival levels; (b) a novel implementation of MKMs as weighting functions; (c) a benchmark against Chinese Hamster lung fibroblast (V79)
data; (d) a study on the effect of pre- or post- processing the average biophysical quantities used for the RBE calculations; (e) a possible modification of the modified MKM parameters to improve the model accuracy at high linear energy transfer (LET).
. Lineal energy spectra were simulated for two spherical targets (diameter = 0.464 or 1.0
m) using PHITS for
H,
He,
C,
Ne,
Ar,
Fe and
Xe ions. The results of the
calculations were compared with published
data.
. All models appear to underestimate the RBE
of hydrogen ions. All MKMs generally overestimate the RBE
, RBE
and RBE
for ions with an LET greater than ∼200 keV
m
. This overestimation is greater for small surviving fractions and is likely due to the assumption of a radiation-independent quadratic term of clonogenic survival (
). The overall RBE trends seem to be best described by the novel 'post-processing average' implementation of the non-Poisson MKM. In case of calculations with the non-Poisson MKM, pre- or post- processing the average biophysical quantities affects the computed RBE values significantly.
. This study presents a systematic analysis of the formalism and results of widely used microdosimetric models of clonogenic survival for ions relevant for cancer particle therapy and space radiation protection. Points for improvements were highlighted and will contribute to the development of upgraded biophysical models.
. (1) To examine to what extent the cell- and exposure- specific information neglected in the phenomenological proton relative biological effectiveness (RBE) models could influence the computed RBE ...in proton therapy. (2) To explore similarities and differences in the formalism and the results between the linear energy transfer (LET)-based phenomenological proton RBE models and the microdosimetry-based Mayo Clinic Florida microdosimetric kinetic model (MCF MKM). (3) To investigate how the relationship between the RBE and the dose-mean proton LET is affected by the proton energy spectrum and the secondary fragments.
. We systematically compared six selected phenomenological proton RBE models with the MCF MKM in track-segment simulations, monoenergetic proton beams in a water phantom, and two spread-out Bragg peaks. A representative comparison with
data for human glioblastoma cells (U87 cell line) is also included.
. Marked differences were observed between the results of the phenomenological proton RBE models, as reported in previous studies. The dispersion of these models' results was found to be comparable to the spread in the MCF MKM results obtained by varying the cell-specific parameters neglected in the phenomenological models. Furthermore, while single cell-specific correlation between RBE and the dose-mean proton LET seems reasonable above 2 keV
m
, caution is necessary at lower LET values due to the relevant contribution of secondary fragments. The comparison with
data demonstrates comparable agreement between the MCF MKM predictions and the results of the phenomenological models.
. The study highlights the importance of considering cell-specific characteristics and detailed radiation quality information for accurate RBE calculations in proton therapy. Furthermore, these results provide confidence in the use of the MCF MKM for clonogenic survival RBE calculations in proton therapy, offering a more mechanistic approach compared to phenomenological models.
Background
Discrete spot scanning (DSS) is the commonly used method for proton pencil beam scanning (PBS). There is lack of data on the dose‐driven continuous scanning (DDCS).
Purpose
To investigate ...delivery benefits and dosimetric implications of DDCS versus DSS for PBS systems.
Methods
The irradiation duty factor, beam delivery time (BDT), and dose deviation were simulated for eight treatment plans in prostate, head and neck, liver, and lung, with both conventional fractionation and hypofractionation schemes. DDCS results were compared with those of DSS.
Results
The DDCS irradiation duty factor (range, 11%–41%) was appreciably improved compared to DSS delivery (range, 4%–14%), within which, hypofractionation schemes had greater improvement than conventional fractionation. With decreasing stop ratio constraints, the DDCS BDT reduction was greater, but dose deviation also increased. With stop ratio constraints of 2, 1, 0.5, and 0, DDCS BDT reduction reached to 6%, 10%, 12%, and 15%, respectively, and dose deviation reached to 0.6%, 1.7%, 3.0%, and 5.2% root mean square error in PTV DVH, respectively. The 3%/2‐mm gamma passing rate was greater than 99% with stop ratio constraints of 2 and 1, and greater than 95% with a stop ratio of 0.5. When the stop ratio constraint was removed, five of the eight treatment plans had a 3%/2‐mm gamma passing rate greater than 95%, and the other three plans had a 3%/2‐mm gamma passing rate between 90% and 95%.
Conclusions
The irradiation duty factor was considerably improved with DDCS. Smaller stop ratio constraints led to shorter BDTs, but with the cost of larger dose deviations. Our finding suggested that a stop ratio of 1 constraint seems to yield acceptable DDCS dose deviation.
Radiochromic film (RCF) is a valuable dosimetric tool, primarily due to its sub-millimeter spatial resolution. For accurate proton dosimetry, the dependence of film response on linear energy transfer ...(LET) must be characterized and calibrated. In this work, we characterized film under-response, or 'quenching', as a function of dose-weighted linear energy transfer (LETd) in several proton fields and established a simple, linear relationship with LETd. We performed measurements as a function of depth in a PMMA phantom irradiated by a spot-scanning proton beam. The fields had energies of 71.3 MeV, 71.3 MeV with filter, and 159.9 MeV. At each depth (measurements taken in depth step sizes of 0.5-1 mm in the Bragg peak), we measured dose with a PTW Markus ion chamber and EBT3 RCF. EBT3 under-response was characterized by the ratio of dose measured with film to that with ion chamber. LETd values for our experimental setup were calculated using in-house clinical Monte Carlo code. Measured film under-response increased with LETd, from approximately 10% under-response for LETd = 5 keV µm−1 to approximately 20% for LETd = 8 keV µm−1. The under-response for all measurements was plotted versus LETd. A linear fit to the data was performed, yielding a function for under-response, , with respect to LETd: . Finally, the linear under-response relationship was applied to a film measurement within a spread-out Bragg peak (SOBP). Without correcting for LETd-dependence in the SOBP measurement, the discrepancy between film and Monte Carlo profiles was greater than 15% at the distal edge. With correction, the corrected film profile was within 2% and 1 mm of the Monte Carlo profile. RCF response depends on LETd, potentially under-responding by >15% in clinically-relevant scenarios. Therefore, it is insufficient to perform only a dose calibration; LET calibration is also necessary for accurate proton film dosimetry. The LETd-dependence of EBT3 can be described by a single, linear function over a range of clinically-relevant proton therapy LETd values.
Abstract
The Mayo Clinic Florida microdosimetric kinetic model (MCF MKM) is a recently developed clonogenic survival model. Since the MCF MKM relies on novel strategies to a priori determine the ...cell-specific model parameters, the only experiment-specific input values are the α and ß terms of the linear–quadratic model (LQM) of clonogenic survival for the reference photon exposure. Because the two LQM terms are anti-correlated, the fitting process of the reference photon survival curve was found to significantly influence the MCF MKM calculations. This article reports this effect for two clinically relevant cell lines (human brain glioblastoma A-172, human healthy foreskin fibroblasts AG01522) and ions (1H and 12C ions).
Background
Using the pencil beam raster scanning method employed at most carbon beam treatment facilities, spots can be moved without interrupting the beam, allowing for the delivery of a dose ...between spots (move dose). This technique is also known as Dose‐Driven‐Continuous‐Scanning (DDCS). To minimize its impact on HIMAK patient dosimetry, there's an upper limit to the move dose. Spots within a layer are grouped into sets, or “break points,” allowing continuous irradiation. The beam is turned off when transitioning between sets or at the end of a treatment layer or spill. The control system beam‐off is accomplished by turning off the RF Knockout (RFKO) extraction and after a brief delay the High Speed Steering Magnet (HSST) redirects the beam transport away from isocenter to a beam dump.
Purpose
The influence of the move dose and beam on/off control on the dose distribution and irradiation time was evaluated by measurements never before reported and modelled for Hitachi Carbon DDCS.
Method
We conducted fixed‐point and scanning irradiation experiments at three different energies, both with and without breakpoints. For fixed‐point irradiation, we utilized a 2D array detector and an oscilloscope to measure beam intensity over time. The oscilloscope data enabled us to confirm beam‐off and beam‐on timing due to breakpoints, as well as the relative timing of the RFKO signal, HSST signal, and dose monitor (DM) signals. From these measurements, we analyzed and modelled the temporal characteristics of the beam intensity. We also developed a model for the spot shape and amplitude at isocenter occurring after the beam‐off signal which we called flap dose and its dependence on beam intensity. In the case of scanning irradiation, we measured move doses using the 2D array detector and compared these measurements with our model.
Result
We observed that the most dominant time variation of the beam intensity was at 1 kHz and its harmonic frequencies. Our findings revealed that the derived beam intensity cannot reach the preset beam intensity when each spot belongs to different breakpoints. The beam‐off time due to breakpoints was approximately 100 ms, while the beam rise time and fall time (tdecay) were remarkably fast, about 10 ms and 0.2 ms, respectively. Moreover, we measured the time lag (tdelay) of approximately 0.2 ms between the RFKO and HSST signals. Since tdelay ≈ tdecay at HIMAK then the HSST is activated after the residual beam intensity, resulting in essentially zero flap dose at isocenter from the HSST. Our measurements of the move dose demonstrated excellent agreement with the modelled move dose.
Conclusion
We conducted the first move dose measurement for a Hitachi Carbon synchrotron, and our findings, considering beam on/off control details, indicate that Hitachi's carbon synchrotron provides a stable beam at HIMAK. Our work suggests that measuring both move dose and flap dose should be part of the commissioning process and possibly using our model in the Treatment Planning System (TPS) for new facilities with treatment delivery control systems with higher beam intensities and faster beam‐off control.
Abstract
Measurements of the extracted beam current (BC) for a Hitachi Carbon Therapy Synchrotron and a Hitachi Compact Proton Therapy Synchrotron are reported for the nominal extracted beam current ...(BC0) of
10
m
M
U
m
sec
, which was chosen since it is the magnitude of the clinical BC0, and a sample rate of 5
μ
sec (Carbon) and 8
μ
sec (Proton). A Noise Power Spectrum (NPS) analysis identifies the source of variation to be beam or power supply related. The rise time in the BC has been modeled and its effect on beam delivery time simulations have been estimated. The impact of the variation in BC from BC0 is shown to cause potentially significant dosimetric uncertainties in treatment delivery for modern particle therapy accelerators using fast Scanning Magnet (SCM) if plans are not simply beam current moderated or robustly optimized. The variation in beam current is shown to be inconsequential for medical physics quality assurance and commissioning measurements using properly biased ion chambers.
Abstract Background In carbon ion radiation therapy (CIRT) the predominant method of irradiation is raster scanning, called dose driven continuous scanning (DDCS) by Hitachi, allowing for continuous ...synchrotron extraction. The reduction in irradiation time is highly beneficial in minimizing the impact of patient and target movement on dose distribution. The RF knock out (RFKO) slow‐extraction method is commonly used for beam on/off control. When the Hitachi synchrotron receives a beam off signal the control system stops the RFKO and after some delay time (t‐delay) during which the beam intensity declines, a high‐speed steering magnet (HSST) is used to sweep the remaining beam from isocenter to a beam dump for safety reasons. Mayo Clinic Florida (MCF) will use a very short delay of the HSST operation from the RFKO beam OFF signal to minimize the delay time and delayed dose. MCF clinical beam intensity, a tenfold increase over HIMAK, is still less than 100 mMU/ms (approximately 4.9 × 10 9 pps for 430 MeV/u). Purpose The rapid beam off control (RBOC) proposed for MCF is associated with the occurrence of flap dose (FD), which refers to the asymmetric shoulder of the spot dose profile formed from the beam bent by HSST deviating from its planned spot position on the isocenter plane. In this study, we quantitatively assessed FD, proposed a treatment planning system (TPS) implementation using a flap spot (FS) and evaluated its impact on dose distribution. Method The experiments were conducted at the Osaka Heavy Ion Therapy Center (HIMAK) varying the t‐delay from 0.01 to 1 ms in a research environment to simulate the MCF RBOC. We studied the dependence of FD position on beam transport and its dependence on energy and beam intensity. FD was generated by delivering 10000 continuous spots on the central axis that are occasionally triggered by an external 10 Hz gate signal. Measurements were conducted using an oscilloscope, and the nozzle's spot position monitor (SPM) and dose monitor (DM). Result All spot profile data were corrected for the gain of the SPM's beam intensity dependence. FD was determined by fitting the (SPM) Profile data to a double Gaussian. The position of the FS was found to be transport path dependent, with FS occurring on the opposite sides of the scanning x‐direction for vertical and horizontal ports, respectively, as predicted by transport calculations. It was observed that the FD increases with beam intensity and did not exhibit a significant dependence on energy. The effect of FD on treatment planning is shown to have no significant dose impact on the organs at risk (OARs) near the target for clinical beam intensities and a modest increase for very high intensities. Conclusion Using HIMAK in research mode the implications are that the FD has no clinical impact on the clinical CIRT beam intensities for MCF and maybe planned for higher intensities by incorporating FS into the TPS to predict the modest increased dose to OARs. A method for commissioning and quality assurance of FD has been proposed.
The computation of the relative biological effectiveness (RBE) is a fundamental step in the planning of cancer radiotherapy treatments with accelerated ions. Numerical parameters derived analyzing ...the dose response of the chosen cell line after irradiation to photons (i.e., α and β, namely the linear and quadratic terms of the linear-quadratic model of cell survival) are generally used as input to biophysical models to predict the ion RBE. The α/β ratio for the photon exposure is generally regarded as an indicator of cell radiosensitivity. However, previous studies suggest that α/β might not be a sufficient parameter to model the RBE of relatively high linear energy transfer (LET) radiation such as carbon ions. For a fixed α/β, the effect of the absolute values of α and β on the computed RBE is underexplored. Furthermore, since α and β are anticorrelated during the fit of the photon-exposed in vitro survival data, different linear-quadratic fits could produce different sets of α and β, thus affecting the RBE calculations. This article reports the combined effect of the α/β ratio and the absolute values α and β on the RBE computed with the Mayo Clinic Florida microdosimetric kinetic model (MCF MKM) for 12C ions of different LET. Furthermore, we introduce a theory-based strategy to potentially mitigate the anticorrelation between α and β during the fit of the photon dose-response biological data.