J DeMarco

Report of the AAPM Task Group No. 105: Issues associated with clinical implementation of Monte Carlo‐based photon and electron external beam treatment planning

The Monte Carlo (MC) method has been shown through many research studies to calculate accurate dose distributions for clinical radiotherapy, particularly in heterogeneous patient tissues where the effects of electron transport cannot be accurately handled with conventional, deterministic dose algorithms. Despite its proven accuracy and the potential for improved dose distributions to influence treatment outcomes, the long calculation times previously associated with MC simulation rendered this method impractical for routine clinical treatment planning. However, the development of faster codes optimized for radiotherapy calculations and improvements in computer processor technology have substantially reduced calculation times to, in some instances, within minutes on a single processor. These advances have motivated several major treatment planning system vendors to embark upon the path of MC techniques. Several commercial vendors have already released or are currently in the process of releasing MC algorithms for photon and/or electron beam treatment planning. Consequently, the accessibility and use of MC treatment planning algorithms may well become widespread in the radiotherapy community. With MC simulation, dose is computed stochastically using first principles; this method is therefore quite different from conventional dose algorithms. Issues such as statistical uncertainties, the use of variance reduction techniques, theability to account for geometric details in the accelerator treatment head simulation, and other features, are all unique components of a MC treatment planning algorithm. Successful implementation by the clinical physicist of such a system will require an understanding of the basic principles of MC techniques. The purpose of this report, while providing education and review on the use of MC simulation in radiotherapy planning, is to set out, for both users and developers, the salient issues associated with clinical implementation and experimental verification of MC dose algorithms. As the MC method is an emerging technology, this report is not meant to be prescriptive. Rather, it is intended as a preliminary report to review the tenets of the MC method and to provide the framework upon which to build a comprehensive program for commissioning and routine quality assurance of MC-based treatment planning systems.

A CT-based Monte Carlo simulation tool for dosimetry planning and analysis.

The Los Alamos code MCNP4A (Monte Carlo N-Particle version 4A) is currently used to simulate a variety of problems ranging from nuclear reactor analysis to boron neutron capture therapy. A graphical user interface has been developed that automatically sets up the MCNP4A geometry and radiation source requirements for a three-dimensional Monte Carlo simulation using computed tomography data. The major drawback for this dosimetry system is the amount of time to obtain a statistically significant answer. A specialized patch file has been developed that optimizes photon particle transport and dose scoring within the standard MCNP4A lattice geometry. The transport modifications produce a performance increase (number of histories per minute) of approximately 4.7 based upon a 6 MV point source centered within a 30 x 30 x 30 cm3 lattice water phantom and 1 x 1 x 1 mm3 voxels. The dose scoring modifications produce a performance increase of approximately 470 based upon a tally section of greater than 1 x 10(4) lattice elements and a voxel size of 5 mm3. Homogeneous and heterogeneous benchmark calculations produce good agreement with measurements using a standard water phantom and a high- and low-density heterogeneity phantom. The dose distribution from a typical mediastinum treatment planning setup is presented for qualitative analysis and comparison versus a conventional treatment planning system.

A Monte Carlo based method to estimate radiation dose from multidetector CT (MDCT): cylindrical and anthropomorphic phantoms

The purpose of this work was to extend the verification of Monte Carlo based methods for estimating radiation dose in computed tomography (CT) exams beyond a single CT scanner to a multidetector CT (MDCT) scanner, and from cylindrical CTDI phantom measurements to both cylindrical and physical anthropomorphic phantoms. Both cylindrical and physical anthropomorphic phantoms were scanned on an MDCT under the specified conditions. A pencil ionization chamber was used to record exposure for the cylindrical phantom, while MOSFET (metal oxide semiconductor field effect transistor) detectors were used to record exposure at the surface of the anthropomorphic phantom. Reference measurements were made in air at isocentre using the pencil ionization chamber under the specified conditions. Detailed Monte Carlo models were developed for the MDCT scanner to describe the x-ray source (spectra, bowtie filter, etc) and geometry factors (distance from focal spot to isocentre, source movement due to axial or helical scanning, etc). Models for the cylindrical (CTDI) phantoms were available from the previous work. For the anthropomorphic phantom, CT image data were used to create a detailed voxelized model of the phantoms geometry. Anthropomorphic phantom material compositions were provided by the manufacturer. A simulation of the physical scan was performed using the mathematical models of the scanner, phantom and specified scan parameters. Tallies were recorded at specific voxel locations corresponding to the MOSFET physical measurements. Simulations of air scans were performed to obtain normalization factors to convert results to absolute dose values. For the CTDI body (32 cm) phantom, measurements and simulation results agreed to within 3.5% across all conditions. For the anthropomorphic phantom, measured surface dose values from a contiguous axial scan showed significant variation and ranged from 8 mGy/100 mAs to 16 mGy/100 mAs. Results from helical scans of overlapping pitch (0.9375) and extended pitch (1.375) were also obtained. Comparisons between the MOSFET measurements and the absolute dose value derived from the Monte Carlo simulations demonstrate agreement in terms of absolute dose values as well as the spatially varying characteristics. This work demonstrates the ability to extend models from a single detector scanner using cylindrical phantoms to an MDCT scanner using both cylindrical and anthropomorphic phantoms. Future work will be extended to voxelized patient models of different sizes and to other MDCT scanners.

Radiation Enhances Regulatory T Cell Representation

PURPOSE Immunotherapy could be a useful adjunct to standard cytotoxic therapies such as radiation in patients with micrometastatic disease, although successful integration of immunotherapy into treatment protocols will require further understanding of how standard therapies affect the generation of antitumor immune responses. This study was undertaken to evaluate the impact of radiation therapy (RT) on immunosuppressive T regulatory (Treg) cells. METHODS AND MATERIALS Treg cells were identified as a CD4(+)CD25(hi)Foxp3(+) lymphocyte subset, and their fate was followed in a murine TRAMP C1 model of prostate cancer in mice with and without RT. RESULTS CD4(+)CD25(hi)Foxp3(+) Treg cells increased in immune organs after local leg or whole-body radiation. A large part, but not all, of this increase after leg-only irradiation could be ascribed to radiation scatter and Treg cells being intrinsically more radiation resistant than other lymphocyte subpopulations, resulting in their selection. Their functional activity on a per-cell basis was not affected by radiation exposure. Similar findings were made with mice receiving local RT to murine prostate tumors growing in the leg. The importance of the Treg cell population in the response to RT was shown by systemic elimination of Treg cells, which greatly enhanced radiation-induced tumor regression. CONCLUSIONS We conclude that Treg cells are more resistant to radiation than other lymphocytes, resulting in their preferential increase. Treg cells may form an important homeostatic mechanism for tissues injured by radiation, and in a tumor context, they may assist in immune evasion during therapy. Targeting this population may allow enhancement of radiotherapeutic benefit through immune modulation.

A Monte Carlo-based method to estimate radiation dose from spiral CT: from phantom testing to patient-specific models

The purpose of this work is to develop and test a method to estimate the relative and absolute absorbed radiation dose from axial and spiral CT scans using a Monte Carlo approach. Initial testing was done in phantoms and preliminary results were obtained from a standard mathematical anthropomorphic model (MIRD V) and voxelized patient data. To accomplish this we have modified a general purpose Monte Carlo transport code (MCNP4B) to simulate the CT x-ray source and movement, and then to calculate absorbed radiation dose in desired objects. The movement of the source in either axial or spiral modes was modelled explicitly while the CT system components were modelled using published information about x-ray spectra as well as information provided by the manufacturer. Simulations were performed for single axial scans using the head and body computed tomography dose index (CTDI) polymethylmethacrylate phantoms at both central and peripheral positions for all available beam energies and slice thicknesses. For comparison, corresponding physical measurements of CTDI in phantom were made with an ion chamber. To obtain absolute dose values, simulations and measurements were performed in air at the scanner isocentre for each beam energy. To extend the verification, the CT scanner model was applied to the MIRD V model and compared with published results using similar technical factors. After verification of the model, the generalized source was simulated and applied to voxelized models of patient anatomy. The simulated and measured absolute dose data in phantom agreed to within 2% for the head phantom and within 4% for the body phantom at 120 and 140 kVp; this extends to 8% for the head and 9% for the body phantom across all available beam energies and positions. For the head phantom, the simulated and measured absolute dose data agree to within 2% across all slice thicknesses at 120 kVp. Our results in the MIRD phantom agree within 11% of all the different organ dose values published by the UKs ImPACT group for a scan using an equivalent scanner, kVp, collimation, pitch and mAs. The CT source model was shown to calculate both a relative and absolute radiation dose distribution throughout the entire volume in a patient-specific matrix geometry. Results of initial testing are promising and application to patient models was shown to be feasible.

Dose distributions using kilovoltage x-rays and dose enhancement from iodine contrast agents

In x-ray phototherapy of brain tumours, the tumour is loaded with iodine and exposed to kilovoltage x-rays. Due to the high photoelectric cross sections of iodine, substantial photoelectric interactions occur. The flux of photoelectrons, characteristic x-rays and Auger electrons produce a localized dose enhancement. A modified computed tomography scanner, CTRx, can be used both for tumour localization and delivery of the dose enhancement therapy. Monte Carlo methods were employed to simulate the treatment of iodinated brain tumours with a CTRx. The calculated results reveal the effect of tumour iodine concentration on dose distribution, the degree of skull bone sparing with the application of multiple arcs, and the homogeneity of tumour dose distribution versus iodine concentration. A comparison with 10 MV stereotactic radiosurgery treatment shows the potential of CTRx treatment relative to conventional treatment modalities.

Radiation dose to the fetus for pregnant patients undergoing multidetector CT imaging: Monte carlo simulations estimating fetal dose for a range of gestational age and patient size1

PURPOSE To use Monte Carlo simulations of a current-technology multidetector computed tomographic (CT) scanner to investigate fetal radiation dose resulting from an abdominal and pelvic examination for a range of actual patient anatomies that include variation in gestational age and maternal size. MATERIALS AND METHODS Institutional review board approval was obtained for this HIPAA-compliant retrospective study. Twenty-four models of maternal and fetal anatomy were created from image data from pregnant patients who had previously undergone clinically indicated CT examination. Gestational age ranged from less than 5 weeks to 36 weeks. Simulated helical scans of the abdominal and pelvic region were performed, and a normalized dose (in milligrays per 100 mAs) was calculated for each fetus. Stepwise multiple linear regression was performed to analyze the correlation of dose with gestational age and anatomic measurements of maternal size and fetal location. Results were compared with several existing fetal dose estimation methods. RESULTS Normalized fetal dose estimates from the Monte Carlo simulations ranged from 7.3 to 14.3 mGy/100 mAs, with an average of 10.8 mGy/100 mAs. Previous methods yielded values of 10-14 mGy/100 mAs. The correlation between gestational age and fetal dose was not significant (P = .543). Normalized fetal dose decreased linearly with increasing patient perimeter (R(2) = 0.681, P < .001), and a two-factor model with patient perimeter and fetal depth demonstrated a strong correlation with fetal dose (R(2) = 0.799, P < .002). CONCLUSION A method for the estimation of fetal dose from models of actual patient anatomy that represented a range of gestational age and patient size was developed. Fetal dose correlated with maternal perimeter and varied more than previously recognized. This correlation improves when maternal size and fetal depth are combined.

The feasibility of a scanner-independent technique to estimate organ dose from MDCT scans: Using CTDIvol to account for differences between scanners

PURPOSE Monte Carlo radiation transport techniques have made it possible to accurately estimate the radiation dose to radiosensitive organs in patient models from scans performed with modern multidetector row computed tomography (MDCT) scanners. However, there is considerable variation in organ doses across scanners, even when similar acquisition conditions are used. The purpose of this study was to investigate the feasibility of a technique to estimate organ doses that would be scanner independent. This was accomplished by assessing the ability of CTDIvol measurements to account for differences in MDCT scanners that lead to organ dose differences. METHODS Monte Carlo simulations of 64-slice MDCT scanners from each of the four major manufacturers were performed. An adult female patient model from the GSF family of voxelized phantoms was used in which all ICRP Publication 103 radiosensitive organs were identified. A 120 kVp, full-body helical scan with a pitch of 1 was simulated for each scanner using similar scan protocols across scanners. From each simulated scan, the radiation dose to each organ was obtained on a per mA s basis (mGy/mA s). In addition, CTDIvol values were obtained from each scanner for the selected scan parameters. Then, to demonstrate the feasibility of generating organ dose estimates from scanner-independent coefficients, the simulated organ dose values resulting from each scanner were normalized by the CTDIvol value for those acquisition conditions. RESULTS CTDIvol values across scanners showed considerable variation as the coefficient of variation (CoV) across scanners was 34.1%. The simulated patient scans also demonstrated considerable differences in organ dose values, which varied by up to a factor of approximately 2 between some of the scanners. The CoV across scanners for the simulated organ doses ranged from 26.7% (for the adrenals) to 37.7% (for the thyroid), with a mean CoV of 31.5% across all organs. However, when organ doses are normalized by CTDIvoI values, the differences across scanners become very small. For the CTDIvol, normalized dose values the CoVs across scanners for different organs ranged from a minimum of 2.4% (for skin tissue) to a maximum of 8.5% (for the adrenals) with a mean of 5.2%. CONCLUSIONS This work has revealed that there is considerable variation among modern MDCT scanners in both CTDIvol and organ dose values. Because these variations are similar, CTDIvol can be used as a normalization factor with excellent results. This demonstrates the feasibility of establishing scanner-independent organ dose estimates by using CTDIvol to account for the differences between scanners.

Irradiation of the potential cancer stem cell niches in the adult brain improves progression-free survival of patients with malignant glioma

BackgroundGlioblastoma is the most common brain tumor in adults. The mechanisms leading to glioblastoma are not well understood but animal studies support that inactivation of tumor suppressor genes in neural stem cells (NSC) is required and sufficient to induce glial cancers. This suggests that the NSC niches in the brain may harbor cancer stem cells (CSCs), Thus providing novel therapy targets. We hypothesize that higher radiation doses to these NSC niches improve patient survival by eradicating CSCs.Methods55 adult patients with Grade 3 or Grade 4 glial cancer treated with radiotherapy at UCLA between February of 2003 and May of 2009 were included in this retrospective study. Using radiation planning software and patient radiological records, the SVZ and SGL were reconstructed for each of these patients and dosimetry data for these structures was calculated.ResultsUsing Kaplan-Meier analysis we show that patients whose bilateral subventricular zone (SVZ) received greater than the median SVZ dose (= 43 Gy) had a significant improvement in progression-free survival if compared to patients who received less than the median dose (15.0 vs 7.2 months PFS; P = 0.028). Furthermore, a mean dose >43 Gy to the bilateral SVZ yielded a hazard ratio of 0.73 (P = 0.019). Importantly, similarly analyzing total prescription dose failed to illustrate a statistically significant impact.ConclusionsOur study leads us to hypothesize that in glioma targeted radiotherapy of the stem cell niches in the adult brain could yield significant benefits over radiotherapy of the primary tumor mass alone and that damage caused by smaller fractions of radiation maybe less efficiently detected by the DNA repair mechanisms in CSCs.

An analysis of MCNP cross-sections and tally methods for low-energy photon emitters

Monte Carlo calculations are frequently used to analyse a variety of radiological science applications using low-energy (10-1000 keV) photon sources. This study seeks to create a low-energy benchmark for the MCNP Monte Carlo code by simulating the absolute dose rate in water and the air-kerma rate for monoenergetic point sources with energies between 10 keV and 1 MeV. The analysis compares four cross-section datasets as well as the tally method for collision kerma versus absorbed dose. The total photon attenuation coefficient cross-section for low atomic number elements has changed significantly as cross-section data have changed between 1967 and 1989. Differences of up to 10% are observed in the photoelectric cross-section for water at 30 keV between the standard MCNP cross-section dataset (DLC-200) and the most recent XCOM/NIST tabulation. At 30 keV, the absolute dose rate in water at 1.0 cm from the source increases by 7.8% after replacing the DLC-200 photoelectric cross-sections for water with those from the XCOM/NIST tabulation. The differences in the absolute dose rate are analysed when calculated with either the MCNP absorbed dose tally or the collision kerma tally. Significant differences between the collision kerma tally and the absorbed dose tally can occur when using the DLC-200 attenuation coefficients in conjunction with a modern tabulation of mass energy-absorption coefficients.