Mohammad Salehpour

Validation of a new grid-based Boltzmann equation solver for dose calculation in radiotherapy with photon beams

A new grid-based Boltzmann equation solver, Acuros, was developed specifically for performing accurate and rapid radiotherapy dose calculations. In this study we benchmarked its performance against Monte Carlo for 6 and 18 MV photon beams in heterogeneous media. Acuros solves the coupled Boltzmann transport equations for neutral and charged particles on a locally adaptive Cartesian grid. The Acuros solver is an optimized rewrite of the general purpose Attila software, and for comparable accuracy levels, it is roughly an order of magnitude faster than Attila. Comparisons were made between Monte Carlo (EGSnrc) and Acuros for 6 and 18 MV photon beams impinging on a slab phantom comprising tissue, bone and lung materials. To provide an accurate reference solution, Monte Carlo simulations were run to a tight statistical uncertainty (sigma approximately 0.1%) and fine resolution (1-2 mm). Acuros results were output on a 2 mm cubic voxel grid encompassing the entire phantom. Comparisons were also made for a breast treatment plan on an anthropomorphic phantom. For the slab phantom in regions where the dose exceeded 10% of the maximum dose, agreement between Acuros and Monte Carlo was within 2% of the local dose or 1 mm distance to agreement. For the breast case, agreement was within 2% of local dose or 2 mm distance to agreement in 99.9% of voxels where the dose exceeded 10% of the prescription dose. Elsewhere, in low dose regions, agreement for all cases was within 1% of the maximum dose. Since all Acuros calculations required less than 5 min on a dual-core two-processor workstation, it is efficient enough for routine clinical use. Additionally, since Acuros calculation times are only weakly dependent on the number of beams, Acuros may ideally be suited to arc therapies, where current clinical algorithms may incur long calculation times.

Dosimetric comparison of Acuros XB deterministic radiation transport method with Monte Carlo and model‐based convolution methods in heterogeneous media

PURPOSE The deterministic Acuros XB (AXB) algorithm was recently implemented in the Eclipse treatment planning system. The goal of this study was to compare AXB performance to Monte Carlo (MC) and two standard clinical convolution methods: the anisotropic analytical algorithm (AAA) and the collapsed-cone convolution (CCC) method. METHODS Homogeneous water and multilayer slab virtual phantoms were used for this study. The multilayer slab phantom had three different materials, representing soft tissue, bone, and lung. Depth dose and lateral dose profiles from AXB v10 in Eclipse were compared to AAA v10 in Eclipse, CCC in Pinnacle3, and EGSnrc MC simulations for 6 and 18 MV photon beams with open fields for both phantoms. In order to further reveal the dosimetric differences between AXB and AAA or CCC, three-dimensional (3D) gamma index analyses were conducted in slab regions and subregions defined by AAPM Task Group 53. RESULTS The AXB calculations were found to be closer to MC than both AAA and CCC for all the investigated plans, especially in bone and lung regions. The average differences of depth dose profiles between MC and AXB, AAA, or CCC was within 1.1, 4.4, and 2.2%, respectively, for all fields and energies. More specifically, those differences in bone region were up to 1.1, 6.4, and 1.6%; in lung region were up to 0.9, 11.6, and 4.5% for AXB, AAA, and CCC, respectively. AXB was also found to have better dose predictions than AAA and CCC at the tissue interfaces where backscatter occurs. 3D gamma index analyses (percent of dose voxels passing a 2%/2 mm criterion) showed that the dose differences between AAA and AXB are significant (under 60% passed) in the bone region for all field sizes of 6 MV and in the lung region for most of field sizes of both energies. The difference between AXB and CCC was generally small (over 90% passed) except in the lung region for 18 MV 10 x 10 cm2 fields (over 26% passed) and in the bone region for 5 x 5 and 10 x 10 cm2 fields (over 64% passed). With the criterion relaxed to 5%/2 mm, the pass rates were over 90% for both AAA and CCC relative to AXB for all energies and fields, with the exception of AAA 18 MV 2.5 x 2.5 cm2 field, which still did not pass. CONCLUSIONS In heterogeneous media, AXB dose prediction ability appears to be comparable to MC and superior to current clinical convolution methods. The dose differences between AXB and AAA or CCC are mainly in the bone, lung, and interface regions. The spatial distributions of these differences depend on the field sizes and energies.

Intensity-modulated radiotherapy following extrapleural pneumonectomy for the treatment of malignant mesothelioma: clinical implementation

PURPOSE New insight into the extent of the target volume for the postoperative irradiation of malignant pleural mesothelioma as determined during surgery has indicated that standard conformal radiotherapy (IMRT) is not sufficient for curative treatment. We describe a novel technique for implementing intensity-modulated radiotherapy (IMRT) to deliver higher doses to treat the full extent of these complex target volumes. METHODS AND MATERIALS After extrapleural pneumonectomy, 7 patients underwent simulation, treatment planning, and treatment with IMRT to the involved hemithorax and adjacent abdomen. The target volumes encompassed the entire operative bed, including the ipsilateral mediastinum, anterior pleural reflection, and ipsilateral pericardium and the insertion of the diaphragm and crura. These were extensively marked during surgery with radiopaque markers to facilitate target delineation. RESULTS Setup uncertainty and respiratory-dependent motion were found to be small. Coverage of the planning target volume was very good, with the crus of the diaphragm the most difficult volume to irradiate. The radiation doses to normal structures were acceptable. CONCLUSION IMRT for treatment of malignant mesothelioma after extrapleural pneumonectomy results in more potentially curative doses to large, complex target volumes with acceptable doses to normal tissues.

CERVIX REGRESSION AND MOTION DURING THE COURSE OF EXTERNAL BEAM CHEMORADIATION FOR CERVICAL CANCER

PURPOSE To evaluate the magnitude of cervix regression and motion during external beam chemoradiation for cervical cancer. METHODS AND MATERIALS Sixteen patients with cervical cancer underwent computed tomography scanning before, weekly during, and after conventional chemoradiation. Cervix volumes were calculated to determine the extent of cervix regression. Changes in the center of mass and perimeter of the cervix between scans were used to determine the magnitude of cervix motion. Maximum cervix position changes were calculated for each patient, and mean maximum changes were calculated for the group. RESULTS Mean cervical volumes before and after 45 Gy of external beam irradiation were 97.0 and 31.9 cc, respectively; mean volume reduction was 62.3%. Mean maximum changes in the center of mass of the cervix were 2.1, 1.6, and 0.82 cm in the superior-inferior, anterior-posterior, and right-left lateral dimensions, respectively. Mean maximum changes in the perimeter of the cervix were 2.3 and 1.3 cm in the superior and inferior, 1.7 and 1.8 cm in the anterior and posterior, and 0.76 and 0.94 cm in the right and left lateral directions, respectively. CONCLUSIONS Cervix regression and internal organ motion contribute to marked interfraction variations in the intrapelvic position of the cervical target in patients receiving chemoradiation for cervical cancer. Failure to take these variations into account during the application of highly conformal external beam radiation techniques poses a theoretical risk of underdosing the target or overdosing adjacent critical structures.

Patient-specific point dose measurement for IMRT monitor unit verification

PURPOSE To review intensity-modulated radiation therapy (IMRT) monitor unit verification in a phantom for 751 clinical cases. METHODS AND MATERIALS A custom water-filled phantom was used to measure the integral dose with an ion chamber for patient-specific quality assurance. The Corvus IMRT planning system was used for all cases reviewed. The 751 clinical cases were classified into 9 treatment sites: central nervous system (27 cases), gastrointestinal (24 cases), genitourinary (447 cases), gynecologic (18 cases), head and neck (200 cases), hematology (12 cases), pediatric (3 cases), sarcoma (8 cases), and thoracic (12 cases). Between December 1998 and January 2002, 1591 measurements were made for these 751 IMRT quality assurance plans. RESULTS The mean difference (MD) in percent between the measurements and the calculations was +0.37% (with the measurement being slightly higher). The standard deviation (SD) was 1.7%, and the range of error was from -4.5% to 9.5%. The MD and SD were +0.49% and 1.4% for MIMiC treatments delivered in 2-cm mode (261 cases) and -0.33% and 2.7% for those delivered in 1-cm mode (36 cases). Most treatments (420) were delivered using the step-and-shoot multileaf collimator with a 6-MV photon beam; the MD and SD were +0.31% and 1.8%, respectively. Among the 9 treatment sites, the prostate IMRT (in genitourinary site) was most consistent with the smallest SD (1.5%). There were 23 cases (3.1% of all cases) in which the measurement difference was greater than 3.5%; of those, 6 cases used the MIMiC in 1-cm mode, and 14 of the cases were from the head-and-neck treatment site. CONCLUSION IMRT monitor unit calculations from the Corvus planning system agreed within 3.5% with the point-dose ion chamber measurement in 97% of 751 cases representing 9 different treatment sites. A good consistency was observed across sites.

Hematologic Toxicity in RTOG 0418: A Phase 2 Study of Postoperative IMRT for Gynecologic Cancer

PURPOSE Intensity modulated radiation therapy (IMRT), compared with conventional 4-field treatment, can reduce the volume of bone marrow irradiated. Pelvic bone marrow sparing has produced a clinically significant reduction in hematologic toxicity (HT). This analysis investigated HT in Radiation Therapy Oncology Group (RTOG) 0418, a prospective study to test the feasibility of delivering postoperative IMRT for cervical and endometrial cancer in a multiinstitutional setting. METHODS AND MATERIALS Patients in the RTOG 0418 study were treated with postoperative IMRT to 50.4 Gy to the pelvic lymphatics and vagina. Endometrial cancer patients received IMRT alone, whereas patients with cervical cancer received IMRT and weekly cisplatin (40 mg/m(2)). Pelvic bone marrow was defined within the treatment field by using a computed tomography density-based autocontouring algorithm. The volume of bone marrow receiving 10, 20, 30, and 40 Gy and the median dose to bone marrow were correlated with HT, graded by Common Terminology Criteria for Adverse Events, version 3.0, criteria. RESULTS Eighty-three patients were eligible for analysis (43 with endometrial cancer and 40 with cervical cancer). Patients with cervical cancer treated with weekly cisplatin and pelvic IMRT had grades 1-5 HT (23%, 33%, 25%, 0%, and 0% of patients, respectively). Among patients with cervical cancer, 83% received 5 or more cycles of cisplatin, and 90% received at least 4 cycles of cisplatin. The median percentage volume of bone marrow receiving 10, 20, 30, and 40 Gy in all 83 patients, respectively, was 96%, 84%, 61%, and 37%. Among cervical cancer patients with a V40 >37%, 75% had grade 2 or higher HT compared with 40% of patients with a V40 less than or equal to 37% (P =.025). Cervical cancer patients with a median bone marrow dose of >34.2 Gy also had higher rates of grade ≥ 2 HT than did those with a dose of ≤ 34.2 Gy (74% vs 43%, P=.049). CONCLUSIONS Pelvic IMRT with weekly cisplatin is associated with low rates of HT and high rates of weekly cisplatin use. The volume of bone marrow receiving 40 Gy and the median dose to bone marrow correlated with higher rates of grade ≥ 2 toxicity among patients receiving weekly cisplatin (cervical cancer patients). Evaluation and limitation of the volume of bone marrow treated with pelvic IMRT is warranted in patients receiving concurrent chemotherapy.

A Monte Carlo model for calculating out-of-field dose from a Varian 6 MV beam

Dose to the patient outside of the treatment field is important when evaluating the outcome of radiotherapy treatments. However, determining out-of-field doses for any particular treatment plan currently requires either time-consuming measurements or calculated estimations that may be highly uncertain. A Monte Carlo model may allow these doses to be determined quickly, accurately, and with a great degree of flexibility. MCNPX was used to create a Monte Carlo model of a Varian Clinac 2100 accelerator head operated at 6MV. Simulations of the dose out-of-field were made and measurements were taken with thermoluminescent dosimeters in an acrylic phantom and with an ion chamber in a water tank to validate the Monte Carlo model. Although local differences between the out-of-field doses calculated by the model and those measured did exceed 50% at some points far from the treatment field, the average local difference was only 16%. This included a range of doses as low as 0.01% of the central axis dose, and at distances in excess of 50cm from the central axis of the treatment field. The out-of-field dose was found to vary with field size and distance from the central axis, but was almost independent of the depth in the phantom except where the dose increased substantially at depths less than dmax. The relationship between dose and kerma was also investigated, and kerma was found to be a good estimate of dose (within 3% on average) except near the surface and in the field penumbra. Our Monte Carlo model was found to well represent typical Varian 2100 accelerators operated at 6MV.

Dosimetric accuracy of Kodak EDR2 film for IMRT verifications

Patient-specific intensity-modulated radiotherapy (IMRT) verifications require an accurate two-dimensional dosimeter that is not labor-intensive. We assessed the precision and reproducibility of film calibrations over time, measured the elemental composition of the film, measured the intermittency effect, and measured the dosimetric accuracy and reproducibility of calibrated Kodak EDR2 film for single-beam verifications in a solid water phantom and for full-plan verifications in a Rexolite phantom. Repeated measurements of the film sensitometric curve in a single experiment yielded overall uncertainties in dose of 2.1% local and 0.8% relative to 300 cGy. 547 film calibrations over an 18-month period, exposed to a range of doses from 0 to a maximum of 240 MU or 360 MU and using 6 MV or 18 MV energies, had optical density (OD) standard deviations that were 7%-15% of their average values. This indicates that daily film calibrations are essential when EDR2 film is used to obtain absolute dose results. An elemental analysis of EDR2 film revealed that it contains 60% as much silver and 20% as much bromine as Kodak XV2 film. EDR2 film also has an unusual 1.69:1 silver:halide molar ratio, compared with the XV2 films 1.02:1 ratio, which may affect its chemical reactions. To test EDR2s intermittency effect, the OD generated by a single 300 MU exposure was compared to the ODs generated by exposing the film 1 MU, 2 MU, and 4 MU at a time to a total of 300 MU. An ion chamber recorded the relative dose of all intermittency measurements to account for machine output variations. Using small MU bursts to expose the film resulted in delivery times of 4 to 14 minutes and lowered the films OD by approximately 2% for both 6 and 18 MV beams. This effect may result in EDR2 film underestimating absolute doses for patient verifications that require long delivery times. After using a calibration to convert EDR2 films OD to dose values, film measurements agreed within 2% relative difference and 2 mm criteria to ion chamber measurements for both sliding window and step-and-shoot fluence map verifications. Calibrated film results agreed with ion chamber measurements to within 5 % /2 mm criteria for transverse-plane full-plan verifications, but were consistently low. When properly calibrated, EDR2 film can be an adequate two-dimensional dosimeter for IMRT verifications, although it may underestimate doses in regions with long exposure times.

A Monte Carlo model for out-of-field dose calculation from high-energy photon therapy.

As cancer therapy becomes more efficacious and patients survive longer, the potential for late effects increases, including effects induced by radiation dose delivered away from the treatment site. This out-of-field radiation is of particular concern with high-energy radiotherapy, as neutrons are produced in the accelerator head. We recently developed an accurate Monte Carlo model of a Varian 2100 accelerator using MCNPX for calculating the dose away from the treatment field resulting from low-energy therapy. In this study, we expanded and validated our Monte Carlo model for high-energy (18 MV) photon therapy, including both photons and neutrons. Simulated out-of-field photon doses were compared with measurements made with thermoluminescent dosimeters in an acrylic phantom up to 55 cm from the central axis. Simulated neutron fluences and energy spectra were compared with measurements using moderated gold foil activation in moderators and data from the literature. The average local difference between the calculated and measured photon dose was 17%, including doses as low as 0.01% of the central axis dose. The out-of-field photon dose varied substantially with field size and distance from the edge of the field but varied little with depth in the phantom, except at depths shallower than 3 cm, where the dose sharply increased. On average, the difference between the simulated and measured neutron fluences was 19% and good agreement was observed with the neutron spectra. The neutron dose equivalent varied little with field size or distance from the central axis but decreased with depth in the phantom. Neutrons were the dominant component of the out-of-field dose equivalent for shallow depths and large distances from the edge of the treatment field. This Monte Carlo model is useful to both physicists and clinicians when evaluating out-of-field doses and associated potential risks.

Quantifying tumor-selective radiation dose enhancements using gold nanoparticles: a monte carlo simulation study.

Gold nanoparticles can enhance the biological effective dose of radiation delivered to tumors, but few data exist to quantify this effect. The purpose of this project was to build a Monte Carlo simulation model to study the degree of dose enhancement achievable with gold nanoparticles. A Monte Carlo simulation model was first built using Geant4 code. An Ir-192 brachytherapy source in a water phantom was simulated and the calculation model was first validated against previously published data. We then introduced up to 1013 gold nanospheres per cm3 into the water phantom and examined their dose enhancement effect. We compared this enhancement against a gold-water mixture model that has been previously used to attempt to quantify nanoparticle dose enhancement. In our benchmark test, dose-rate constant, radial dose function, and two-dimensional anisotropy function calculated with our model were within 2% of those reported previously. Using our simulation model we found that the radiation dose was enhanced up to 60% with 1013 gold nanospheres per cm3 (9.6% by weight) in a water phantom selectively around the nanospheres. The comparison study indicated that our model more accurately calculated the dose enhancement effect and that previous methodologies overestimated the dose enhancement up to 16%. Monte Carlo calculations demonstrate that biologically-relevant radiation dose enhancement can be achieved with the use of gold nanospheres. Selective tumor labeling with gold nanospheres may be a strategy for clinically enhancing radiation effects.