In Vitro and In Vivo Synergetic Radiotherapy with Gold Nanoparticles and Docetaxel for Pancreatic Cancer.

This research underscores the potential of combining nanotechnology with conventional therapies in cancer treatment, particularly for challenging cases like pancreatic cancer. We aimed to enhance pancreatic cancer treatment by investigating the synergistic effects of gold nanoparticles (GNPs) and docetaxel (DTX) as potential radiosensitizers in radiotherapy (RT) both in vitro and in vivo, utilizing a MIA PaCa-2 monoculture spheroid model and NRG mice subcutaneously implanted with MIA PaCa-2 cells, respectively. Spheroids were treated with GNPs (7.5 µg/mL), DTX (100 nM), and 2 Gy of RT using a 6 MV linear accelerator. In parallel, mice received treatments of GNPs (2 mg/kg), DTX (6 mg/kg), and 5 Gy of RT (6 MV linear accelerator). In vitro results showed that though RT and DTX reduced spheroid size and increased DNA DSBs, the triple combination of DTX/RT/GNPs led to a significant 48% (p = 0.05) decrease in spheroid size and a 45% (p = 0.05) increase in DNA DSBs. In vivo results showed a 20% (p = 0.05) reduction in tumor growth 20 days post-treatment with (GNPs/RT/DTX) and an increase in mice median survival. The triple combination exhibited a synergistic effect, enhancing anticancer efficacy beyond individual treatments, and thus could be employed to improve radiotherapy and potentially reduce adverse effects.

Volume staging for arteriovenous malformation SRS treatment using VMAT.

Volume staging involves dividing the target volume into smaller parts and treating each part separately. In this study, the feasibility of volume-staged stereotactic radiosurgery (VS-SRS) on a linear accelerator using volumetric modulated arc therapy (VMAT) and a frameless patient positioning system is investigated. Ten patients, previously treated with hypofractionated stereotactic radiotherapy with arteriovenous malformation (AVM) sized from 1.6 to 4.0 cm in diameter, were selected. VS-SRS plans were created with the VMAT technique on the Varian Eclipse treatment planning system (TPS) using the TrueBeam STx linear accelerator. For each patient, an AVM-VMAT set was planned with the AVM as the target and a PTV-VMAT set using the (PTV = AVM+1 mm) as the target. All targets were divided into two sub-volumes. The TPS data from the AVM-VMAT plans was compared to Gamma Knife (GK) VS-SRS plan data available in the literature. The AVM-VMAT and PTV-VMAT plans were compared to investigate the effect of a 1 mm PTV margin on normal brain (NB) dose. End-to-end testing was performed using a GaFchromic EBT3 film and point-dose measurements. Dosimetric effects of multiple setups were investigated through film-to-film comparisons. Median target dose coverage, NB V12Gy , and conformity index for the AVM-VMAT plans were 97.5%, 17 cm3 , and 0.8, respectively. PTV-VMAT plans attained comparable target dose coverage, but the average NB V12Gy increased by 48.9% when compared to the AVM-VMAT plans. Agreement of point-dose measurements with TPS calculations was -0.6% when averaged over all patients. Gamma analysis passing rates were above 90% for all film-to-film comparisons (2%/1 mm criteria), and for the film to TPS comparison (5%/1 mm). This work suggests that VMAT is capable of producing VS-SRS plans with similar dose falloff characteristics as GK plans. NB dose depends on PTV margin size, and two-stage treatment setups do not appear to contribute additional uncertainty to treatment delivery.

Monte Carlo simulation of 6-MV dynamic wave VMAT deliveries by Vero4DRT linear accelerator using EGSnrc moving sources.

The commissioning and benchmark of a Monte Carlo (MC) model of the 6-MV Brainlab-Mitsubishi Vero4DRT linear accelerator for the purpose of quality assurance of clinical dynamic wave arc (DWA) treatment plans is reported. Open-source MC applications based on EGSnrc particle transport codes are used to simulate the medical linear accelerator head components. Complex radiotherapy irradiations can be simulated in a single MC run using a shared library format combined with BEAMnrc "source20." Electron energy tuning is achieved by comparing measured vs simulated percentage depth doses (PDDs) for MLC-defined field sizes in a water phantom. Electron spot size tuning is achieved by comparing measured and simulated inplane and crossplane beam profiles. DWA treatment plans generated from RayStation (RaySearch) treatment planning system (TPS) are simulated on voxelized (2.5 mm3 ) patient CT datasets. Planning target volume (PTV) and organs at risk (OAR) dose-volume histograms (DVHs) are compared to TPS-calculated doses for clinically deliverable dynamic volumetric modulated arc therapy (VMAT) trajectories. MC simulations with an electron beam energy of 5.9 MeV and spot size FWHM of 1.9 mm had the closest agreement with measurement. DWA beam deliveries simulated on patient CT datasets results in DVH agreement with TPS-calculated doses. PTV coverage agreed within 0.1% and OAR max doses (to 0.035 cc volume) agreed within 1 Gy. This MC model can be used as an independent dose calculation from the TPS and as a quality assurance tool for complex, dynamic radiotherapy treatment deliveries. Full patient CT treatment simulations are performed in a single Monte Carlo run in 23 min. Simulations are run in parallel using the Condor High-Throughput Computing software1 on a cluster of eight servers. Each server has two physical processors (Intel Xeon CPU E5-2650 0 @2.00 GHz), with 8 cores per CPU and two threads per core for 256 calculation nodes.

Visual Outcomes and Local Control After Fractionated Stereotactic Radiotherapy for Optic Nerve Sheath Meningioma.

PURPOSE: To review the outcomes of patients with optic nerve sheath meningiomas (ONSM) treated with fractionated stereotactic radiotherapy. METHODS: Patient characteristics, treatment, and outcomes were analyzed for all patients with primary and secondary ONSM treated from 2001 to 2012. Clinically significant visual acuity change was defined as a 2-line change on the Snellen eye chart from pre-fractionated stereotactic radiotherapy. RESULTS: Forty-one patients were treated: 23 patients with primary ONSM and 18 patients with secondary ONSM. The median age at diagnosis was 56 years. The median visual follow up was 3.8 years and the median radiologic follow up was 4.4 years. At diagnosis, 36% had normal vision (20/20-20/40), 10% had mild impairment (<20/40-20/60), 20% had moderate visual impairment (<20/60-20/200), 27% had severe impairment (<20/200), and 7% had no light perception. Common acute side effects were headache (32%) and nausea (15%); 15% of patients required corticosteroids during stereotactic radiotherapy. Chronic toxicities included retinopathy (7%), pituitary dysfunction (13%), chronic ocular pain (5%), and cataracts (2%). Visual acuity was stable in 65%, improved in 27%, and decreased in 8% of patients. Visual fields were stable in 70%, improved in 21%, and reduced in 9%. Actuarial 5-year local control rates were 100% for primary ONSM and 88% for secondary ONSM. Actuarial 5-year visual preservation rates were 100% for primary ONSM and 86% for secondary ONSM. CONCLUSIONS: Fractionated stereotactic radiotherapy for primary and secondary ONSM was well tolerated and provides excellent local control and visual preservation. Longer follow up is required to determine the risk of late ocular and pituitary sequelae.

Population-Based Study of Stereotactic Radiosurgery or Fractionated Stereotactic Radiation Therapy for Vestibular Schwannoma: Long-Term Outcomes and Toxicities.

PURPOSE: To examine long-term local control of vestibular schwannoma and side effects in patients treated with stereotactic radiosurgery (SRS) and fractionated stereotactic radiation therapy (SRT) in British Columbia. METHODS AND MATERIALS: From August 1998 to May 2009, 207 patients were treated with radiation therapy (RT) at British Columbia Cancer Agency. 136 (66%) received SRS, and 71 (34%) received SRT. Dose prescriptions were 50 Gy/25 fractions for SRT and 12 Gy/1 fraction for SRS. Our multidisciplinary provincial neuro-stereotactic conference recommended SRT for tumors >3 cm and for patients with serviceable hearing (Gardner-Robertson classes I and II). RESULTS: Median follow-up was 7.7 years to the last MRI and 6.4 years to the last clinical assessment. Local control for SRS versus SRT was 94% versus 87% at 5 years and 90% versus 85% at 10 years (P=.2). Five- and 10-year actuarial rates of RT-induced trigeminal nerve dysfunction were 25% and 25% after SRS, compared with 7% and 12% after SRT (P=.01). Five- and 10-year actuarial rates of RT-induced facial nerve dysfunction were 15% and 15% after SRS, versus 13% and 15% after SRT (P=.93). In the 49 patients with serviceable hearing at baseline who were treated with SRT, hearing preservation was 55% at 3 years, 37% at 5 years, and 29% at 7 years. In multivariable analysis, better pretreatment ipsilateral pure tone average was significantly associated with hearing preservation (hazard ratio 1.03; 95% confidence interval 1.00-1.07; P=.04). CONCLUSIONS: Both SRS and SRT provided excellent long-term local control of vestibular schwannoma. Stereotactic radiosurgery was associated with higher rates of trigeminal nerve dysfunction. Even with a fractionated course, hearing preservation declined steadily with long-term audiometric follow-up.

Machine-specific quality assurance procedure for stereotactic treatments with dynamic couch rotations.

OBJECTIVE: We present a method in which the treatment couch's accuracy is measured using the electronic portal imaging device (EPID) and a phantom of our own construction. Using this phantom, we were able to quantify the treatment couch walkout, and the rotation angle accuracy for both static and dynamic couch treatments. These measurements were used to provide an accurate measure of the treatment couch isocenter as well as to verify the couch rotation angle recorded in the trajectory log. METHODS: The phantom was constructed using a polystyrene slab in which five ball bearings of 4 mm diameter are placed on the same plane at varying radii (0, 2.8, 4.4, 5.6, and 6.7 cm). The couch was rotated through its full extent (-90, 90 degrees) while MV images were acquired continuously. The couch rotational accuracy was calculated using a least squares minimization which fit the locations of the BBs to their expected locations relative to reference setup conditions. Using this approach, rotation angle and isocenter walkout was calculated in three dimensions. These measurements were used to quantify the accuracy of the couch as well as to validate the Varian TrueBeam trajectory logs. Additionally, a method for an EPID-based couch star-shot measurement was developed and compared with the traditional film-based method. RESULTS: The measured couch center of rotation consisted of a cloud of points clustered around the room isocenter within 0.7 mm distance. The trajectory log couch angle values agreed with those recorded in the DICOM header of the EPID images to the third significant digit and the couch rotation angles recorded in the trajectory log and DICOM header agreed with the calculated values to 0.08 degrees. Comparison of couch star-shot measurement developed in this study with film-based star-shot measurements gave an agreement to within 0.2 mm. CONCLUSION: We have developed a quality assurance method for the treatment couch which is simple, accurate, and enables the user to access a multitude of consistent data with a single measurement. Using this method, we have shown that the treatment couch is accurate for both static and dynamic stereotactic deliveries.

A simple and robust trajectory-based stereotactic radiosurgery treatment.

INTRODUCTION: We present a Trajectory-based Volumetric Modulated Arc Therapy (TVMAT) technique for Stereotactic Radiosurgery (SRS) that takes advantage of a modern linacs ability to modulate dose rate and move the couch dynamically. In addition, we investigate the quality of the developed TVMAT method and the dosimetric accuracy of the technique. METHODS: The main feature of the TVMAT technique is a standard beam trajectory formed by dynamic motion of the treatment couch and the linac gantry. The couch rotates slowly through 180 degrees while the gantry delivers radiation through continuous sweeps of the gantry. The number of partial arcs that constitute the trajectory can be varied between two and eight and as the number of partial arcs increases, the trajectory more finely samples 4π geometry. Along these trajectories, the multi-leaf collimator (MLC) and dose rate are optimized through an inverse planning framework. The TVMAT method was tested on ten cranial SRS patients who were previously treated with the Dynamic Conformal Arc (DCA) technique. The plans were compared with the DCA and a four- arc VMAT technique with regards to dose to the OAR, dose falloff, V12Gy, and V4Gy. Validation measurements were performed using ion-chamber and Gafchromic film. In addition, the trajectory-log files were analyzed and compared with the treatment plan beam data. RESULTS: The TVMAT treatment plans were successfully delivered with a treatment time between 3-8 min which mostly depended on total cumulated dose. Ion chamber measurements had an average measured error of 1.1 ± 0.6% and a maximum value of 2.2% of the delivered dose. The 2%, 2 mm gamma pass rates for the film measurements were 96% or greater. In a preliminary comparison of ten patients who underwent SRS treatments with the DCA technique, the TVMAT and VMAT techniques were able to produce plans with comparable dose falloff and OAR doses, while achieving better dose conformality, V4Gy and V12Gy when compared to the original DCA plans. The improvement of the TVMAT plans were as follows (mean % improvement ± standard err): Conformity (10 ± 2%), V4 (20 ± 20%), V12 (27 ± 10%), volume weighted mean dose to organs at risk (13 ± 13%), homogeneity index (2 ± 2%) and falloff (4 ± 2%). CONCLUSION: We have developed and validated a trajectory-based dose delivery method which has dose distribution improvements while having a treatment time of 3-8 min. In addition, it has the potential for a simpler planning experience while maintaining an accurate delivery on the Varian Truebeam Linac.

Monte Carlo validation of the TrueBeam 10XFFF phase-space files for applications in lung SABR.

PURPOSE: To establish the clinical acceptability of universal Monte Carlo phase-space data for the 10XFFF (flattening filter free) photon beam on the Varian TrueBeam Linac, including previously unreported data for small fields, output factors, and inhomogeneous media. The study was particularly aimed at confirming the suitability for use in simulations of lung stereotactic ablative radiotherapy treatment plans. METHODS: Monte Carlo calculated percent depth doses (PDDs), transverse profiles, and output factors for the TrueBeam 10 MV FFF beam using generic phase-space data that have been released by the Varian MC research team were compared with in-house measurements and published data from multiple institutions (ten Linacs from eight different institutions). BEAMnrc was used to create field size specific phase-spaces located underneath the jaws. Doses were calculated with DOSXYZnrc in a water phantom for fields ranging from 1 × 1 to 40 × 40 cm(2). Particular attention was paid to small fields (down to 1 × 1 cm(2)) and dose per pulse effects on dosimeter response for high dose rate 10XFFF beams. Ion chamber measurements were corrected for changes in ion collection efficiency (P(ion)) with increasing dose per pulse. MC and ECLIPSE ANISOTROPIC ANALYTICAL ALGORITHM (AAA) calculated PDDs were compared to Gafchromic film measurement in inhomogeneous media (water, bone, lung). RESULTS: Measured data from all machines agreed with Monte Carlo simulations within 1.0% and 1.5% for PDDs and in-field transverse profiles, respectively, for field sizes >1 × 1 cm(2) in a homogeneous water phantom. Agreements in the 80%-20% penumbra widths were better than 2 mm for all the fields that were compared. For all the field sizes considered, the agreement between their measured and calculated output factors was within 1.1%. Monte Carlo results for dose to water at water/bone, bone/lung, and lung/water interfaces as well as within lung agree with film measurements to within 2.8% for 10 × 10 and 3 × 3 cm(2) field sizes. This represents a significant improvement over the performance of the ECLIPSE AAA. CONCLUSIONS: The 10XFFF phase-space data offered by the Varian Monte Carlo research team have been validated for clinical use using measured, interinstitutional beam data in water and with film dosimetry in inhomogeneous media.

Amplitude gating for a coached breathing approach in respiratory gated 10 MV flattening filter-free VMAT delivery.

The purpose of this study was to investigate amplitude gating combined with a coached breathing strategy for 10 MV flattening filter-free (FFF) volumetric-modulated arc therapy (VMAT) on the Varian TrueBeam linac. Ten patient plans for VMAT SABR liver were created using the Eclipse treatment planning system (TPS). The verification plans were then transferred to a CT-scanned Quasar phantom and delivered on a TrueBeam linac using a 10 MV FFF beam and Varian's real-time position management (RPM) system for respiratory gating based on breathing amplitude. Breathing traces were acquired from ten patients using two kinds of breathing patterns: free breathing and an interrupted (~ 5 s pause) end of exhale coached breathing pattern. Ion chamber and Gafchromic film measurements were acquired for a gated delivery while the phantom moved under the described breathing patterns, as well as for a nongated stationary phantom delivery. The gate window was set to obtain a range of residual target motion from 2-5 mm. All gated deliveries on a moving phantom have been shown to be dosimetrically equivalent to the nongated deliveries on a static phantom, with differences in point dose measurements under 1% and average gamma 2%/2 mm agreement above 98.7%. Comparison with the treatment planning system also resulted in good agreement, with differences in point-dose measurements under 2.5% and average gamma 3%/3 mm agreement of 97%. The use of a coached breathing pattern significantly increases the duty cycle, compared with free breathing, and allows for shorter treatment times. Patients' free-breathing patterns contain considerable variability and, although dosimetric results for gated delivery may be acceptable, it is difficult to achieve efficient treatment delivery. A coached breathing pattern combined with a 5 mm amplitude gate, resulted in both high-quality dose distributions and overall shortest gated beam delivery times.

Monte Carlo modeling of HD120 multileaf collimator on Varian TrueBeam linear accelerator for verification of 6X and 6X FFF VMAT SABR treatment plans.

A Monte Carlo (MC) validation of the vendor-supplied Varian TrueBeam 6 MV flattened (6X) phase-space file and the first implementation of the Siebers-Keall MC MLC model as applied to the HD120 MLC (for 6X flat and 6X flattening filter-free (6X FFF) beams) are described. The MC model is validated in the context of VMAT patient-specific quality assurance. The Monte Carlo commissioning process involves: 1) validating the calculated open-field percentage depth doses (PDDs), profiles, and output factors (OF), 2) adapting the Siebers-Keall MLC model to match the new HD120-MLC geometry and material composition, 3) determining the absolute dose conversion factor for the MC calculation, and 4) validating this entire linac/MLC in the context of dose calculation verification for clinical VMAT plans. MC PDDs for the 6X beams agree with the measured data to within 2.0% for field sizes ranging from 2 × 2 to 40 × 40 cm2. Measured and MC profiles show agreement in the 50% field width and the 80%-20% penumbra region to within 1.3 mm for all square field sizes. MC OFs for the 2 to 40 cm2 square fields agree with measurement to within 1.6%. Verification of VMAT SABR lung, liver, and vertebra plans demonstrate that measured and MC ion chamber doses agree within 0.6% for the 6X beam and within 2.0% for the 6X FFF beam. A 3D gamma factor analysis demonstrates that for the 6X beam, > 99% of voxels meet the pass criteria (3%/3 mm). For the 6X FFF beam, > 94% of voxels meet this criteria. The TrueBeam accelerator delivering 6X and 6X FFF beams with the HD120 MLC can be modeled in Monte Carlo to provide an independent 3D dose calculation for clinical VMAT plans. This quality assurance tool has been used clinically to verify over 140 6X and 16 6X FFF TrueBeam treatment plans.

Intensity-modulated stereotactic radiosurgery for arteriovenous malformations: guidance for treatment planning.

BACKGROUND: Stereotactic Radiosurgery (SRS) is a common tool used to treat Arteriovenous Malformations (AVMs) in anatomical locations associated with a risk of surgical complications. Despite high rates of clinical effectiveness, SRS carries a risk of toxicity as a result of radiation injury to brain tissue. The use of intensity-modulated radiotherapy (IMRT) has increased because it may lead to improved PTV conformity and better Normal Tissue (NT) sparing compared to 3D Conformal Radiotherapy (3DCRT). The aim of this study was twofold: 1) to develop simple patient stratification rules for the recommendation of IMRT planning strategies over 3DCRT in the treatment of AVMs with SRS; and 2) to estimate the impact of IMRT in terms of toxicity reduction using retrospectively reported data for symptomatic radiation injury following SRS. METHODS: Thirty-one AVM patients previously treated with 3DCRT were replanned in a commercial treatment planning system using 3DCRT and static gantry IMRT with identical beam arrangements. The radiotherapy planning metrics analyzed included AVM volume, diameter, and volume to surface area ratio. The dosimetric endpoints analyzed included conformity index improvements and NT sparing measured by the maximum NT dose, and the volume of surrounding tissue that received 7Gy and 12Gy. RESULTS: Our analysis revealed stratified subsets of patients for IMRT that were associated with improved conformity, and those that were associated with decreased doses to normal tissue. The stratified patients experienced an improvement in conformity index by -6-68%, a reduction in the maximum NT dose by -0.5-12.3%, a reduction in the volume of NT receiving 7Gy by 1-8 cc, and a reduction in the volume of NT receiving 12Gy by 0-3.7 cc. The reduction in NT receiving 12Gy translated to a theoretical decrease in the probability of symptomatic injury by 0-9.3%. CONCLUSIONS: This work indicates the potential for significant patient improvements when treating AVMs and provides rules to predict which patients are likely to benefit from IMRT.

Long-term outcomes of fractionated stereotactic radiation therapy for pituitary adenomas at the BC Cancer Agency.

PURPOSE: To assess the long-term disease control and toxicity outcomes of fractionated stereotactic radiation therapy (FSRT) in patients with pituitary adenomas treated at the BC Cancer Agency. METHODS AND MATERIALS: To ensure a minimum of 5 years of clinical follow-up, this study identified a cohort of 76 patients treated consecutively with FSRT between 1998 and 2007 for pituitary adenomas: 71% (54/76) had nonfunctioning and 29% (22/76) had functioning adenomas (15 adrenocorticotrophic hormone-secreting, 5 growth hormone-secreting, and 2 prolactin-secreting). Surgery was used before FSRT in 96% (73/76) of patients. A median isocenter dose of 50.4 Gy was delivered in 28 fractions, with 100% of the planning target volume covered by the 90% isodose. Patients were followed up clinically by endocrinologists, ophthalmologists, and radiation oncologists. Serial magnetic resonance imaging was used to assess tumor response. RESULTS: With a median follow-up time of 6.8 years (range, 0.6 - 13.1 years), the 7-year progression-free survival was 97.1% and disease-specific survival was 100%. Of the 2 patients with tumor progression, both had disease control after salvage surgery. Of the 22 patients with functioning adenomas, 50% (11/22) had complete and 9% (2/22) had partial responses after FSRT. Of the patients with normal pituitary function at baseline, 48% (14/29) experienced 1 or more hormone deficiencies after FSRT. Although 79% (60/76) of optic chiasms were at least partially within the planning target volumes, no patient experienced radiation-induced optic neuropathy. No patient experienced radionecrosis. No secondary malignancy occurred during follow-up. CONCLUSION: In this study of long-term follow-up of patients treated for pituitary adenomas, FSRT was safe and effective.

A Monte Carlo approach to validation of FFF VMAT treatment plans for the TrueBeam linac.

PURPOSE: To commission and benchmark a vendor-supplied (Varian Medical Systems) Monte Carlo phase-space data for the 6 MV flattening filter free (FFF) energy mode on a TrueBeam linear accelerator for the purpose of quality assurance of clinical volumetric modulated arc therapy (VMAT) treatment plans. A method for rendering the phase-space data compatible with BEAMnrc/DOSXYZnrc simulation software package is presented. METHODS: Monte Carlo (MC) simulations were performed to benchmark the TrueBeam 6 MV FFF phase space data that have been released by the Varian MC Research team. The simulations to benchmark the phase space data were done in three steps. First, the original phase space which was created on a cylindrical surface was converted into a format that was compatible with BEAMnrc. Second, BEAMnrc was used to create field size specific phase spaces located underneath the jaws. Third, doses were calculated with DOSXYZnrc in a water phantom for fields ranging from 1 × 1 to 40 × 40 cm(2). Calculated percent depth doses (PDD), transverse profiles, and output factors were compared with measurements for all the fields simulated. After completing the benchmarking study, three stereotactic body radiotherapy (SBRT) VMAT plans created with the Eclipse treatment planning system (TPS) were calculated with Monte Carlo. Ion chamber and film measurements were also performed on these plans. 3D gamma analysis was used to compare Monte Carlo calculation with TPS calculations and with film measurement. RESULTS: For the benchmarking study, MC calculated and measured values agreed within 1% and 1.5% for PDDs and in-field transverse profiles, respectively, for field sizes >1 × 1 cm(2). Agreements in the 80%-20% penumbra widths were better than 2 mm for all the fields that were compared. With the exception of the 1 × 1 cm(2) field, the agreement between measured and calculated output factors was within 1%. It is of note that excellent agreement in output factors for all field sizes including highly asymmetric fields was achieved without accounting for backscatter into the beam monitor chamber. For the SBRT VMAT plans, the agreement between Monte Carlo and ion chamber point dose measurements was within 1%. Excellent agreement between Monte Carlo, treatment planning system and Gafchromic film dose distribution was observed with over 99% of the points in the high dose volume passing the 3%, 3 mm gamma test. CONCLUSIONS: The authors have presented a method for making the Varian IAEA compliant 6 MV FFF phase space file of the TrueBeam linac compatible with BEAMnrc/DOSXYZnrc. After benchmarking the modified phase space against measurement, they have demonstrated its potential for use in MC based quality assurance of complex delivery techniques.

Factors predictive of symptomatic radiation injury after linear accelerator-based stereotactic radiosurgery for intracerebral arteriovenous malformations.

PURPOSE: To investigate predictive factors in the development of symptomatic radiation injury after treatment with linear accelerator-based stereotactic radiosurgery for intracerebral arteriovenous malformations and relate the findings to the conclusions drawn by Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC). METHODS AND MATERIALS: Archived plans for 73 patients who were treated at the British Columbia Cancer Agency were studied. Actuarial estimates of freedom from radiation injury were calculated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards models were used for analysis of incidence of radiation injury. Log-rank test was used to search for dosimetric parameters associated with freedom from radiation injury. RESULTS: Symptomatic radiation injury was exhibited by 14 of 73 patients (19.2%). Actuarial rate of symptomatic radiation injury was 23.0% at 4 years. Most patients (78.5%) had mild to moderate deficits according to Common Terminology Criteria for Adverse Events, version 4.0. On univariate analysis, lesion volume and diameter, dose to isocenter, and a V(x) for doses ≥8 Gy showed statistical significance. Only lesion diameter showed statistical significance (p < 0.05) in a multivariate model. According to the log-rank test, AVM volumes >5 cm(3) and diameters >30 mm were significantly associated with the risk of radiation injury (p < 0.01). The V(12) also showed strong association with the incidence of radiation injury. Actuarial incidence of radiation injury was 16.8% if V(12) was <28 cm(3) and 53.2% if >28 cm(3) (log-rank test, p = 0.001). CONCLUSIONS: This study confirms that the risk of developing symptomatic radiation injury after radiosurgery is related to lesion diameter and volume and irradiated volume. Results suggest a higher tolerance than proposed by QUANTEC. The widely differing findings reported in the literature, however, raise considerable uncertainties.

Evaluation of the AAA Treatment Planning Algorithm for SBRT Lung Treatment: Comparison with Monte Carlo and Homogeneous Pencil Beam Dose Calculations.

PURPOSE: To evaluate the dose calculation accuracy of the Varian Eclipse anisotropic analytical algorithm (AAA) for stereotactic body radiation therapy (SBRT), and to investigate the dosimetric consequences of not applying tissue heterogeneity correction on complex SBRT lung plans. MATERIALS AND METHODS: Nine cases of non-small-cell lung cancer (NSCLC) that were previously treated with SBRT at our center were selected for this study. Following Radiation Therapy Oncology Group 0236, the original plans were calculated using pencil beam without heterogeneity correction (PBNC). For this study, these plans were recalculated by applying tissue heterogeneity correction with the AAA algorithm and with the Monte Carlo (MC) method, keeping the number of monitor units the same as the original plans. Two kinds of plan comparison were made. First, the AAA calculations were compared with MC. Second, the treatment plans that were calculated with AAA were compared with the original PBNC calculations. The following dose-volume parameters were used for the comparison: V100%; V90%; the maximum, the minimum, and the mean planning target volume (PTV) doses (Dmax, Dmin, and Dmean, respectively); V20Gy, V15Gy, V10Gy, V5Gy; Dmean for the lung; and Dmax for the critical organs. RESULTS: Comparable results were obtained for AAA and MC calculations: except for Dmax, Dmin, and Dmean, the differences in the patient-average values of all of the PTV dose parameters were less than 2%. The largest average difference was observed for Dmin (3.8 ± 5.4%). Average differences in all the lung dose parameters were under 0.2%, and average differences in normal tissue Dmax were under 0.3 Gy, except for the skin dose. There were appreciable differences in the PTV and normal tissue dose-volume parameters when comparing AAA and PBNC calculations. Except for V100% and V90%, PBNC calculations on average underestimated the dose to the PTV. The largest discrepancy was in the PTV maximum dose, with a patient-averaged difference of 11.1 ± 4.6%. CONCLUSIONS: Based on our MC investigation, we conclude that the Eclipse AAA algorithm is sufficiently accurate for dose calculations of lung SBRT plans involving small 6-MV photon fields. Our results also demonstrate that, although dose calculations at the periphery of the PTV showed good agreement when comparing PBNC with both AAA and MC calculations, there is a potential to significantly underestimate the dose inside the PTV and doses to critical structures if tissue heterogeneity correction is not applied to lung SBRT plans.

Whole brain radiotherapy with hippocampal avoidance and simultaneous integrated boost for 1-3 brain metastases: a feasibility study using volumetric modulated arc therapy.

PURPOSE: To evaluate the feasibility of using volumetric modulated arc therapy (VMAT) to deliver whole brain radiotherapy (WBRT) with hippocampal avoidance and a simultaneous integrated boost (SIB) for one to three brain metastases. METHODS AND MATERIALS: Ten patients previously treated with stereotactic radiosurgery for one to three brain metastases underwent repeat planning using VMAT. The whole brain prescription dose was 32.25 Gy in 15 fractions, and SIB doses to brain metastases were 63 Gy to lesions >or=2.0 cm and 70.8 Gy to lesions <2.0 cm in diameter. The mean dose to the hippocampus was kept at <6 Gy(2). Plans were optimized for conformity and target coverage while minimizing hippocampal and ocular doses. Plans were evaluated on target coverage, prescription isodose to target volume ratio, conformity number, homogeneity index, and maximum dose to prescription dose ratio. RESULTS: Ten patients had 18 metastases. Mean values for the brain metastases were as follows: conformity number = 0.73 +/- 0.10, target coverage = 0.98 +/- 0.01, prescription isodose to target volume = 1.34 +/- 0.19, maximum dose to prescription dose ratio = 1.09 +/- 0.02, and homogeneity index = 0.07 +/- 0.02. For the whole brain, the mean target coverage and homogeneity index were 0.960 +/- 0.002 and 0.39 +/- 0.06, respectively. The mean hippocampal dose was 5.23 +/- 0.39 Gy(2). The mean treatment delivery time was 3.6 min (range, 3.3-4.1 min). CONCLUSIONS: VMAT was able to achieve adequate whole brain coverage with conformal hippocampal avoidance and radiosurgical quality dose distributions for one to three brain metastases. The mean delivery time was under 4 min.

Optimization of stereotactic radiotherapy treatment delivery technique for base-of-skull meningiomas.

This study compares static conformal field (CF), intensity modulated radiotherapy (IMRT), and dynamic arcs (DA) for the stereotactic radiotherapy of base-of-skull meningiomas. Twenty-one cases of base-of-skull meningioma (median planning target volume [PTV] = 21.3 cm3) previously treated with stereotactic radiotherapy were replanned with each technique. The plans were compared for Radiation Therapy Oncology Group conformity index (CI) and homogeneity index (HI), and doses to normal structures at 6 dose values from 50.4 Gy to 5.6 Gy. The mean CI was 1.75 (CF), 1.75 (DA), and 1.66 (IMRT) (p < 0.05 when comparing IMRT to either CF or DA plans). The CI (IMRT) was inversely proportional to the size of the PTV (Spearman's rho = -0.53, p = 0.01) and at PTV sizes above 25 cm3, the CI (IMRT) was always superior to CI (DA) and CI (CF). At PTV sizes below 25 cm3, there was no significant difference in CI between each technique. There was no significant difference in HI between plans. The total volume of normal tissue receiving 50.4, 44.8, and 5.6 Gy was significantly lower when comparing IMRT to CF and DA plans (p < 0.05). There was significantly improved dose sparing for the brain stem and ipsilateral temporal lobe with IMRT but no significant difference for the optic chiasm or pituitary gland. These results demonstrate that stereotactic IMRT should be considered to treat base-of-skull meningiomas with a PTV larger than 25 cm3, due to improved conformity and normal tissue sparing, in particular for the brain stem and ipsilateral temporal lobe.