Evaluation of the uncertainty associated with the ion recombination correction in high dose-per-pulse electron beam dosimetry: an MC approach.

The high dose and dose-per-pulse rates (up to 130 mGy/pulse) produced by some intraoperative radiation therapy (IORT) accelerators pose specific dosimetric problems due to the high density of electric charge per pulse produced in the ionization chamber cavity. In particular, the correction factor for ion recombination, ks , calculated with the traditional two-voltage method is significantly overestimated and three alternative models have been proposed in the literature allowing for the presence of a free-electron component. However, at present there is no general consensus on the best model to assess the ion recombination correction and controversy remains on the uncertainty associated with k s . In the present work we adopted a Monte Carlo (MC) approach to assess the uncertainty associated with the ion recombination correction in plane-parallel chambers used in high dose-per-pulse electron beam dosimetry. The uncertainty associated with k s was calculated for the following plane-parallel ionization chambers: Scanditronix/Wellhofer Parallel Plate Chamber PPC05 and PPC40, PTW Advanced Markus Model 34 045 and PTW Roos Model 34 001. Input variables for MC calculations were derived from experimental data at 28 and 73 mGy/pulse. Taken together, the results of this study indicate that ks values calculated according to the three ion recombination models do not overlap within their standard uncertainties, suggesting that an additional type-B uncertainty component would be necessary to take into account possible differences between the models. Our results indicate that the combined relative standard uncertainty in k s should be calculated as the sum in quadrature of a (type-A) MC-based uncertainty component and a (type-B) uncertainty contribution evaluated assuming a uniform distribution between k s values obtained from the two extreme models.

Absorbed dose measurements from a 90Y radionuclide liquid solution using LiF:Mg,Cu,P thermoluminescent dosimeters.

In the last few years there has been an increasing interest in the measurement of the absorbed dose from radionuclides, with special attention devoted to molecular radiotherapy treatments. In particular, the determination of the absorbed dose from beta emitting radionuclides in liquid solution poses a number of issues when dose measurements are performed using thermoluminescent dosimeters (TLD). Finite volume effect, i.e. the exclusion of radioactivity from the volume occupied by the TLD is one of these. Furthermore, TLDs need to be encapsulated into some kind of waterproof envelope that unavoidably contributes to beta particle attenuation during the measurement. The purpose of this study is twofold: I) to measure the absorbed dose to water, Dw, using LiF:Mg,Cu,P chips inside a PMMA cylindrical phantom filled with a homogenous 90YCl3 aqueous solution II) to assess the uncertainty budget related to Dw measurements. To this purpose, six cylindrical PMMA phantoms were manufactured at ENEA. Each phantom can host a waterproof PMMA stick containing 3 TLD chips encapsulated by a polystyrene envelope. The cylindrical phantoms were manufactured so that the radioactive liquid environment surrounds the whole stick. Finally, Dw measurements were compared with Monte Carlo (MC) calculations. The measurement of absorbed dose to water from 90YCl3 radionuclide solution using LiF:Mg,Cu,P TLDs turned out to be a viable technique, provided that all necessary correction factors are applied. Using this method, a relative combined standard uncertainty in the range 3.1-3.7% was obtained on each Dw measurement. The major source of uncertainty was shown to be TLDs calibration, with associated uncertainties in the range 0.7-2.2%. Comparison of measured and MC-calculated absorbed dose per emitted beta particle provided good results, with the two quantities being in the ratio 1.08.

Calculation of kQ factors for Farmer-type ionization chambers following the recent recommendations on new key dosimetry data.

PURPOSE: To calculate by Monte Carlo simulations kQ factors for Farmer-type ionization chambers in megavoltage photon beams using the new key dosimetry data recommended by the International Commission on Radiation Units and Measurements (ICRU) Report 90. METHODS: Monte Carlo calculations were performed with the EGSnrc code system using both the ICRU 90 and the ICRU 37 data. Farmer-type ionization chambers with graphite and plastic walls and with graphite wall and a plastic waterproofing sleeve were considered (Nuclear Enterprise NE 2571, IBA FC65-G and FC65-P). kQ factors were calculated for photon beams in the range 6-25 MV using phase-space files as input radiation sources. The photon beam qualities in terms of TPR20,10 and %dd(10)x were established by simulating the depth-dose curves in water. Absorbed doses to the air cavity and to water were calculated using the egs_chamber user code with a target statistical uncertainty below 0.1%. RESULTS: The update of key dosimetry data according to the ICRU report 90 had an impact of -0.2% in the absorbed dose to water and up to 0.5% in the absorbed dose to the air cavity. Nevertheless, changes partially offset each other when entering in kQ as ratio, and the final impact on the kQ values was below 0.3%. CONCLUSIONS: The calculated values of kQ tend to be lower than the current values in the IAEA TRS-398 protocol with differences up to about 0.5%. A slightly better agreement (within 0.3%) is observed with the Monte-Carlo calculated values provided by the addendum to the AAPM's TG-51 protocol.

Community approach for reducing small field measurement errors: Experience over 24 centres.

PURPOSE: The complexity of the modern Stereotactic Body Radiation Therapy (SBRT) techniques requires comprehensive quality assurance programs, to ensure the right treatment to the patient. Dosimetry of small radiation fields is a challenge especially for radiotherapy centres starting to work on this issue. The matter to be discussed here concerns the need of detailed measurement procedures and cross checks to be paired to the usual recommendations on detectors and correction factors. MATERIALS AND METHODS: The presented work involved 24 Italian radiotherapy centres, with the specific purpose to minimize systematic errors in output factor measurements over different radiotherapy centres. Using the unshielded silicon diode IBA Razor, reference curves for the relative signal ratio (RSR) as a function of beam size were created for each Linac family. RESULTS: With this study we have demonstrated consistency of small field dosimetry on all the centres involved, moreover all radiotherapy centres using Razor are allowed to compare measurements amongst each other and centres with values deviating more than 5% from the reference curve are advised to repeat their measurements. With this procedure, some critical issues were detected from two centres in RSR measurements, that, if implemented into the own treatment planning system, would induce an unwanted overdosage larger than 5%. CONCLUSIONS: The proposed approach could allow one to envision high-skilled therapy centres providing support to those featuring minor experience and could represent an important strategy for the clinical implementation of emerging technologies at high quality levels. The methodology adopted exploits crowd knowledge methods which could be applied in others areas of radiation dosimetry.

Feasibility of using a dose-area product ratio as beam quality specifier for photon beams with small field sizes.

PURPOSE: To investigate the feasibility of using the ratio of dose-area product at 20 cm and 10 cm water depths (DAPR20,10) as a beam quality specifier for radiotherapy photon beams with field diameter below 2 cm. METHODS: Dose-area product was determined as the integral of absorbed dose to water (Dw) over a surface larger than the beam size. 6 MV and 10 MV photon beams with field diameters from 0.75 cm to 2 cm were considered. Monte Carlo (MC) simulations were performed to calculate energy-dependent dosimetric parameters and to study the DAPR20,10 properties. Aspects relevant to DAPR20,10 measurement were explored using large-area plane-parallel ionization chambers with different diameters. RESULTS: DAPR20,10 was nearly independent of field size in line with the small differences among the corresponding mean beam energies. Both MC and experimental results showed a dependence of DAPR20,10 on the measurement setup and the surface over which Dw is integrated. For a given setup, DAPR20,10 values obtained using ionization chambers with different air-cavity diameters agreed with one another within 0.4%, after the application of MC correction factors accounting for effects due to the chamber size. DAPR20,10 differences among the small field sizes were within 1% and sensitivity to the beam energy resulted similar to that of established beam quality specifiers based on the point measurement of Dw. CONCLUSIONS: For a specific measurement setup and integration area, DAPR20,10 proved suitable to specify the beam quality of small photon beams for the selection of energy-dependent dosimetric parameters.

Phantom validation of quantitative Y-90 PET/CT-based dosimetry in liver radioembolization.

BACKGROUND: PET/CT has recently been shown to be a viable alternative to traditional post-infusion imaging methods providing good quality images of 90Y-laden microspheres after selective internal radiation therapy (SIRT). In the present paper, first we assessed the quantitative accuracy of 90Y-PET using an anthropomorphic phantom provided with lungs, liver, spine, and a cylindrical homemade lesion located into the hepatic compartment. Then, we explored the accuracy of different computational approaches on dose calculation, including (I) direct Monte Carlo radiation transport using Raydose, (II) Kernel convolution using Philips Stratos, (III) local deposition algorithm, (IV) Monte Carlo technique (MCNP) considering a uniform activity distribution, and (V) MIRD (Medical Internal Radiation Dose) analytical approach. Finally, calculated absorbed doses were compared with those obtained performing measurements with LiF:Mg,Cu,P TLD chips in a liquid environment. RESULTS: Our results indicate that despite 90Y-PET being likely to provide high-resolution images, the 90Y low branch ratio, along with other image-degrading factors, may produce non-uniform activity maps, even in the presence of uniform activity. A systematic underestimation of the recovered activity, both for the tumor insert and for the liver background, was found. This is particularly true if no partial volume correction is applied through recovery coefficients. All dose algorithms performed well, the worst case scenario providing an agreement between absorbed dose evaluations within 20%. Average absorbed doses determined with the local deposition method are in excellent agreement with those obtained using the MIRD and the kernel-convolution dose calculation approach. Finally, absorbed dose assessed with MC codes are in good agreement with those obtained using TLD in liquid solution, thus confirming the soundness of both calculation approaches. This is especially true for Raydose, which provided an absorbed dose value within 3% of the measured dose, well within the stated uncertainties. CONCLUSIONS: Patient-specific dosimetry is possible even in a scenario with low true coincidences and high random fraction, as in 90Y-PET imaging, granted that accurate absolute PET calibration is performed and acquisition times are sufficiently long. Despite Monte Carlo calculations seeming to outperform all dose estimation algorithms, our data provide a strong argument for encouraging the use of the local deposition algorithm for routine 90Y dosimetry based on PET/CT imaging, due to its simplicity of implementation.

Use of PTW-microDiamond for relative dosimetry of unflattened photon beams.

PURPOSE: The increasing interest in SBRT treatments encourages the use of flattening filter free (FFF) beams. Aim of this work was to evaluate the performance of the PTW60019 microDiamond detector under 6MV and 10MVFFF beams delivered with the EDGE accelerator (Varian Medical System, Palo Alto, USA). A flattened 6MV beam was also considered for comparison. METHODS: Short term stability, dose linearity and dose rate dependence were evaluated. Dose per pulse dependence was investigated in the range 0.2-2.2mGy/pulse. MicroDiamond profiles and output factors (OFs) were compared to those obtained with other detectors for field sizes ranging from 40×40cm2 to 0.6×0.6cm2. In small fields, volume averaging effects were evaluated and the relevant correction factors were applied for each detector. RESULTS: MicroDiamond short term stability, dose linearity and dependence on monitor unit rate were less than 0.8% for all energies. Response variations with dose per pulse were found within 1.8%. MicroDiamond output factors (OF) values differed from those measured with the reference ion-chamber for less than 1% up to 40×40cm2 fields where silicon diodes overestimate the dose of ≈3%. For small fields (<3×3cm2) microDiamond and the unshielded silicon diode were in good agreement. CONCLUSIONS: MicroDiamond showed optimal characteristics for relative dosimetry even under high dose rate beams. The effects due to dose per pulse dependence up to 2.2mGy/pulse are negligible. Compared to other detectors, microDiamond provides accurate OF measurements in the whole range of field sizes. For fields <1cm correction factors accounting for fluence perturbation and volume averaging could be required.

Small field output factors evaluation with a microDiamond detector over 30 Italian centers.

PURPOSE: The aim of the study was a multicenter evaluation of MLC&jaws-defined small field output factors (OF) for different linear accelerator manufacturers and for different beam energies using the latest synthetic single crystal diamond detector commercially available. The feasibility of providing an experimental OF data set, useful for on-site measurements validation, was also evaluated. METHODS: This work was performed in the framework of the Italian Association of Medical Physics (AIFM) SBRT working group. The project was subdivided in two phases: in the first phase each center measured OFs using their own routine detector for nominal field sizes ranging from 10×10cm2 to 0.6×0.6cm2. In the second phase, the measurements were repeated in all centers using the PTW 60019 microDiamond detector. RESULTS: The project enrolled 30 Italian centers. Micro-ion chambers and silicon diodes were used for OF measurements in 24 and 6 centers respectively. Gafchromic films and TLDs were used for very small field OFs in 3 and 1 centers. Regarding the measurements performed with the user's detectors, OF standard deviations (SD) for field sizes down to 2×2cm2 were in all cases <2.7%. In the second phase, a reduction of around 50% of the SD was obtained using the microDiamond detector. CONCLUSIONS: The measured values presented in this multicenter study provide a consistent dataset for OFs that could be a useful tool for improving dosimetric procedures in centers. The microDiamond data present a small variation among the centers confirming that this detector can contribute to improve overall accuracy in radiotherapy.

CyberKnife beam output factor measurements: A multi-site and multi-detector study.

PURPOSE: New promising detectors are available for measuring small field size output factors (OFs). This study focused on a multicenter evaluation of two new generation detectors for OF measurements on CyberKnife systems. METHODS: PTW-60019 microDiamond and W1 plastic scintillation detector (PSD) were used to measure OFs on eight CyberKnife units of various generations for 5-60mm fixed cones. MicroDiamond and PSD OF were compared to routinely used silicon diodes data corrected applying published Monte Carlo (MC) factors. PSD data were corrected for Cerenkov Light Ratio (CLR). The uncertainties related to CLR determination were estimated. RESULTS: Considering OF values averaged over all centers, the differences between MC corrected diode and the other two detectors were within 1.5%. MicroDiamond exhibited an over-response of 1.3% at 7.5mm and a trend inversion at 5mm with a difference of 0.2%. This behavior was consistent among the different units. OFs measured by PSD slightly under-responded compared to MC corrected diode for the smaller cones and the differences were within 1%. The observed CLR variability was 2.5% and the related variation in OF values was 1.9%. CONCLUSION: This study indicates that CyberKnife microDiamond OF require corrections below 2%. The results are enhanced by the consistency observed among different units. Scintillator shows a good agreement to MC corrected diode but CLR determination remains critical requiring further investigations. The results emphasized the value of a multi-center validation over a single center approach.

Multicenter evaluation of a synthetic single-crystal diamond detector for CyberKnife small field size output factors.

PURPOSE: The aim of the present work was to evaluate small field size output factors (OFs) using the latest diamond detector commercially available, PTW-60019 microDiamond, over different CyberKnife systems. OFs were measured also by silicon detectors routinely used by each center, considered as reference. METHODS: Five Italian CyberKnife centers performed OFs measurements for field sizes ranging from 5 to 60mm, defined by fixed circular collimators (5 centers) and by Iris(™) variable aperture collimator (4 centers). Setup conditions were: 80cm source to detector distance, and 1.5cm depth in water. To speed up measurements two diamond detectors were used and their equivalence was evaluated. MonteCarlo (MC) correction factors for silicon detectors were used for comparing the OF measurements. RESULTS: Considering OFs values averaged over all centers, diamond data resulted lower than uncorrected silicon diode ones. The agreement between diamond and MC corrected silicon values was within 0.6% for all fixed circular collimators. Relative differences between microDiamond and MC corrected silicon diodes data for Iris(™) collimator were lower than 1.0% for all apertures in the totality of centers. The two microDiamond detectors showed similar characteristics, in agreement with the technical specifications. CONCLUSIONS: Excellent agreement between microDiamond and MC corrected silicon diode detectors OFs was obtained for both collimation systems fixed cones and Iris(™), demonstrating the microDiamond could be a suitable detector for CyberKnife commissioning and routine checks. These results obtained in five centers suggest that for CyberKnife systems microDiamond can be used without corrections even at the smallest field size.

Comparison between small radiation therapy electron beams collimated by Cerrobend and tubular applicators.

The purpose of this study was to compare the dosimetric properties of small field electron beams shaped by circular Cerrobend blocks and stainless steel tubular applicators. Percentage depth dose curves, beam profiles, and output factors of small-size circular fields from 2 to 5 cm diameter, obtained either by tubular applicators and Cerrobend blocks, were measured for 6, 10, and 15 MeV electron beam energies. All measurements were performed using a PTW microDiamond 60019 premarket prototype. An overall similar behavior between the two collimating systems can be observed in terms of PDD and beam profiles. However, Cerrobend collimators produce a higher bremsstrahlung background under irradiation with high-energy electrons. In such irradiation condition, larger output factors are observed for tubular applicators. Similar dosimetric properties are observed using circular Cerrobend blocks and stainless steel tubular applicators at lower beam energies. However, Cerrobend collimators allow the delivery of specific beam shapes, conformed to the target area. On the other hand, in high-energy irradiation conditions, tubular applicators produce a lower bremsstrahlung contribution, leading to lower doses outside the target volume. In addition, the higher output factors observed at high energies for tubular applicators lead to reduced treatment times.

Oncogenic bystander radiation effects in Patched heterozygous mouse cerebellum.

The central dogma of radiation biology, that biological effects of ionizing radiation are a direct consequence of DNA damage occurring in irradiated cells, has been challenged by observations that genetic/epigenetic changes occur in unexposed "bystander cells" neighboring directly-hit cells, due to cell-to-cell communication or soluble factors released by irradiated cells. To date, the vast majority of these effects are described in cell-culture systems, while in vivo validation and assessment of biological consequences within an organism remain uncertain. Here, we describe the neonatal mouse cerebellum as an accurate in vivo model to detect, quantify, and mechanistically dissect radiation-bystander responses. DNA double-strand breaks and apoptotic cell death were induced in bystander cerebellum in vivo. Accompanying these genetic events, we report bystander-related tumor induction in cerebellum of radiosensitive Patched-1 (Ptch1) heterozygous mice after x-ray exposure of the remainder of the body. We further show that genetic damage is a critical component of in vivo oncogenic bystander responses, and provide evidence supporting the role of gap-junctional intercellular communication (GJIC) in transmission of bystander signals in the central nervous system (CNS). These results represent the first proof-of-principle that bystander effects are factual in vivo events with carcinogenic potential, and implicate the need for re-evaluation of approaches currently used to estimate radiation-associated health risks.