Jan Hrbacek

Commissioning of Photon Beams of a Flattening Filter-Free Linear Accelerator and the Accuracy of Beam Modeling Using an Anisotropic Analytical Algorithm

PURPOSE To investigate dosimetric characteristics of a new linear accelerator designed to deliver flattened, as well as flattening filter-free (FFF), beams. To evaluate the accuracy of beam modeling under physical conditions using an anisotropic analytical algorithm. METHODS AND MATERIALS Dosimetric data including depth dose curves, profiles, surface dose, penumbra, out-of-field dose, output, total and scatter factors were examined for four beams (X6, X6FFF, X10, and X10FFF) of Varians TrueBeam machine. Beams modeled by anisotropic analytical algorithm were compared with measured dataset. RESULTS FFF beams have lower mean energy (tissue-phantom ratio at the depths of 20 and 10 cm (TPR 20/10): X6, 0.667; X6FFF, 0.631; X10, 0.738; X10FFF, 0.692); maximum dose is located closer to the surface; and surface dose increases by 10%. FFF profiles have sharper but faster diverging penumbra. For small fields and shallow depths, dose outside a field is lower for FFF beams; however, the advantage fades with increasing phantom scatter. Output increases 2.26 times for X6FFF and 4.03 times for X10FFF and is less variable with field size; collimator exchange effect is reduced. A good agreement between modeled and measured data is observed. Criteria of 2% depth-dose and 2-mm distance-to-agreement are always met. CONCLUSION Reference dosimetric characteristics of TrueBeam photon bundles were obtained, and successful modeling of the beams was achieved.

Effect of high dose per pulse flattening filter-free beams on cancer cell survival.

PURPOSE To investigate if there is a statistically significant difference in cancer cell survival using a high dose per pulse flattening filter-free (FFF) beam compared to a standard flattened beam. MATERIAL AND METHODS To validate the radiobiological effect of the flattened and FFF beam, two glioblastoma cell lines were treated with either 5 or 10 Gy using different dose rates. Dose verification was performed and colony formation assays were carried out. To compare the predictability of our data, radiobiological models were included. RESULTS The results presented here demonstrate that irradiation of glioblastoma cell lines using the FFF beam is more efficient in reducing clonogenic cell survival than the standard flattened beam, an effect which becomes more significant the higher the single dose. Interestingly, in our experimental setting, the radiobiological effect of the FFF beam is dependent on dose per pulse rather than on delivery time. The used radiobiological models are able to describe the observed dose rate dependency between 6 and 24 Gy/min. CONCLUSION The results presented here show that dose per pulse might become a crucial factor which influences cancer cell survival. Using high dose rates, currently used radiobiological models as well as molecular mechanisms involved urgently need to be re-examined.

Clinical application of flattening filter free beams for extracranial stereotactic radiotherapy.

PURPOSE To investigate the clinical application of flattening filter free (FFF) beams at maximum dose rate for stereotactic body radiotherapy (SBRT). METHODS AND MATERIALS Patients with tumors in the lung or abdomen were subjected to SBRT using 6 MV FFF or 10 MV FFF beams. For each patient, three plans were calculated using 6 MV flattened, 6 MV FFF, and 10 MV FFF beams. Treatment times were recorded and analyzed, and tumor displacements were assessed by pre- and post-treatment cone beam computed tomography (CBCT). RESULTS Altogether, 26 patients (16 lung, 10 abdominal tumors) were treated. The average dose rate per patient ranged from 442 to 1860 MU/min. Beam-on time was on average 1.6 min (1SD=0.6 min), with the total treatment times recorded at 18.5 min (1SD=3.5 min). The time advantage of using FFF beams was dose-dependent and started at 4 Gy for 6 MV FFF and at 10 Gy for 10 MV FFF beams. The average of the tumor displacements during treatment was 2.0mm (1SD = 1.0mm). CONCLUSIONS SBRT using FFF beams is time efficient and associated with excellent patient stability. According to Van Herks formula, ITV-PTV margins of 6mm are sufficient in our patient cohort. Further studies are necessary to assess clinical outcome and toxicity.

Pretreatment quality assurance of flattening filter free beams on 224 patients for intensity modulated plans: A multicentric study

PURPOSE Pretreatment quality assurance data from four centers, members of the European TrueBeam council were analyzed with different verification devices to assess reliability of flattening filter free beam delivery for intensity modulated radiotherapy (IMRT) and RapidArc (RA) techniques. METHODS TrueBeam(®) (Varian Medical System) is a new linear accelerator designed for delivering flattened, as well as flattening filter free beams. Pretreatment dosimetric validation of plan delivery was performed with different verification devices and responses to high dose rates were tested. Treatment planning was done in Eclipse planning system (PRO 8.9, AAA 8.9). γ evaluation was performed with (dose difference) = 3% and (distance to agreement) = 3 mm scoring the gamma agreement index (GAI, % of field area passing the test). Two hundred and twenty-four patients with 1-6 lesions in various anatomical regions and dose per fraction ranging from 1.8 Gy to 25 Gy were included in the study; 88 were treated with 6 MV flattening filter free (X6FFF) beam energy and 136 with 10 MV flattening filter free (X10FFF) beam. Gafchromic films in solid water, delta(4), arccheck, and matrixx phantom were used to verify the dose distributions. Additionally, point measurements were performed using a PinPoint chamber and a Farmer chamber. RESULTS Dose calculation as well as dose delivery was equally accurate for IMRT and RA delivery (IMRT: GAI = 99.3% (±1.1); RA: GAI = 98.8% (±1.1) as well as for the two beams evaluated (X6FFF: GAI = 99.1% (±1.0); X10FFF: GAI = 98.8% (±1.2). Only small differences were found for the four verification devices. A point dose verification was performed on 52 cases, obtaining a dose deviation of 0.34%. The GAI variations with number of monitor units were statistically significant. CONCLUSIONS The TrueBeam FFF modality, analyzed with a variety of verification devices and planned with Eclipse planning system is dosimetrically accurate (within the specified limits 3 mm/3%) for both X6FFF and X10FFF beam energy.

Ion-recombination correction for different ionization chambers in high dose rate flattening-filter-free photon beams.

Recently, there has been an increased interest in flattening-filter-free (FFF) linear accelerators. Removal of the filter results in available dose rates up to 24 Gy min(-1) (for nominal energy 10 MV in depth of maximum dose, a source-surface distance of 100 cm and a field size of 10×10 cm2). To guarantee accurate relative and reference dosimetry for the FFF beams, we investigated the charge collection efficiency of multiple air-vented and one liquid ionization chamber for dose rates up to 31.9 Gy min(-1). For flattened beams, the ion-collection efficiency of all air-vented ionization chambers (except for the PinPoint chamber) was above 0.995. By removing the flattening filter, we found a reduction in collection efficiency of approximately 0.5-0.9% for a 10 MV beam. For FFF beams, the Markus chamber showed the largest collection efficiency of 0.994. The observed collection efficiencies were dependent on dose per pulse, but independent of the pulse repetition frequency. Using the liquid ionization chamber, the ion-collection efficiency for flattened beams was above 0.990 for all dose rates. However, this chamber showed a low collection efficiency of 0.940 for the FFF 10 MV beam at a dose rate of 31.9 Gy min(-1). All investigated air-vented ionization chambers can be reliably used for relative dosimetry of FFF beams. The order of correction for reference dosimetry is given in the manuscript. Due to their increased saturation in high dose rate FFF beams, liquid ionization chambers appear to be unsuitable for dosimetry within these contexts.

Practice Patterns Analysis of Ocular Proton Therapy Centers: The International OPTIC Survey.

PURPOSE To assess the planning, treatment, and follow-up strategies worldwide in dedicated proton therapy ocular programs. METHODS AND MATERIALS Ten centers from 7 countries completed a questionnaire survey with 109 queries on the eye treatment planning system (TPS), hardware/software equipment, image acquisition/registration, patient positioning, eye surveillance, beam delivery, quality assurance (QA), clinical management, and workflow. RESULTS Worldwide, 28,891 eye patients were treated with protons at the 10 centers as of the end of 2014. Most centers treated a vast number of ocular patients (1729 to 6369). Three centers treated fewer than 200 ocular patients. Most commonly, the centers treated uveal melanoma (UM) and other primary ocular malignancies, benign ocular tumors, conjunctival lesions, choroidal metastases, and retinoblastomas. The UM dose fractionation was generally within a standard range, whereas dosing for other ocular conditions was not standardized. The majority (80%) of centers used in common a specific ocular TPS. Variability existed in imaging registration, with magnetic resonance imaging (MRI) rarely being used in routine planning (20%). Increased patient to full-time equivalent ratios were observed by higher accruing centers (P=.0161). Generally, ophthalmologists followed up the post-radiation therapy patients, though in 40% of centers radiation oncologists also followed up the patients. Seven centers had a prospective outcomes database. All centers used a cyclotron to accelerate protons with dedicated horizontal beam lines only. QA checks (range, modulation) varied substantially across centers. CONCLUSIONS The first worldwide multi-institutional ophthalmic proton therapy survey of the clinical and technical approach shows areas of substantial overlap and areas of progress needed to achieve sustainable and systematic management. Future international efforts include research and development for imaging and planning software upgrades, increased use of MRI, development of clinical protocols, systematic patient-centered data acquisition, and publishing guidelines on QA, staffing, treatment, and follow-up parameters by dedicated ocular programs to ensure the highest level of care for ocular patients.

With Gaze Tracking Toward Noninvasive Eye Cancer Treatment

We present a new gaze tracking-based navigation scheme for proton beam radiation of intraocular tumors and we show the technical integration into the treatment facility. Currently, to treat a patient with such a tumor, a medical physicist positions the patient and the affected eye ball such that the radiation beam targets the tumor. This iterative eye positioning mechanism requires multiple X-rays, and radio-opaque clips previously sutured on the target eyeball. We investigate a possibility to replace this procedure with a noninvasive approach using a 3-D model-based gaze tracker. Previous work does not cover a comparably extensive integration of a gaze tracking device into a state-of-the-art proton beam facility without using additional hardware, such as a stereo optical tracking system. The integration is difficult because of limited available physical space, but only this enables to quantify the overall accuracy. We built a compact gaze tracker and integrated it into the proton beam radiation facility of the Paul Scherrer Institute in Villigen, Switzerland. Our results show that we can accurately estimate a healthy volunteers point of gaze, which is the basis for the determination of the desired initial eye position. The proposed method is the first crucial step in order to make the proton therapy of the eye completely noninvasive.

Range resolution and reproducibility of a dedicated phantom for proton PBS daily quality assurance

PURPOSE Wedge phantoms coupled with a CCD camera are suggested as a simple means to improve the efficiency of quality assurance for pencil beam scanning (PBS) proton therapy, in particular to verify energy/range consistency on a daily basis. The method is based on the analysis of an integral image created by a pencil beam (PB) pattern delivered through a wedge. We have investigated the reproducibility of this method and its dependence on setup and positional beam errors for a commercially available phantom (Sphinx®, IBA Dosimetry) and CCD camera (Lynx®, IBA Dosimetry) system. MATERIAL AND METHODS The phantom includes 4 wedges of different thickness, allowing verification of the range for 4 energies within one integral image. Each wedge was irradiated with a line pattern of clinical energies (120, 150, 180 and 230MeV). The equipment was aligned to the isocenter using lasers, and the delivery was repeated for 5 consecutive days, 4 times each day. Range was computed using the myQA software (IBA Dosimetry) and inter- and intra-setup uncertainty were calculated. Dependence of range on energy was investigated delivering the same pencil beam pattern but with energy variations in steps of ±0.2MeV for all the nominal energies, up to ±1.0MeV. Possible range uncertainties, caused by setup and positional errors, were then simulated including inclination of the phantom, pencil beam and couch shifts. RESULTS Intra position setup (based on in-room laser system) shows a maximum in plane difference within 1.5mm. Range reproducibility (standard deviation) was less than 0.14mm. Setup and beam errors did not affect significantly the results, except for a vertical shift of 10mm which leads to an error in the range computation. CONCLUSION Taking into account different day-to-day setup and beam errors, day-to-day determination of range has been shown to be reproducible using the proposed system.

Experimental validation of a deforming grid 4D dose calculation for PBS proton therapy

The aim of this study was to verify the temporal accuracy of the estimated dose distribution by a 4D dose calculation (4DDC) in comparison to measurements. A single-field plan (0.6 Gy), optimised for a liver patient case (CTV volume: 403cc), was delivered to a homogeneous PMMA phantom and measured by a high resolution scintillating-CCD system at two water equivalent depths. Various motion scenarios (no motion and motions with amplitude of 10 mm and two periods: 3.7 s and 4.4 s) were simulated using a 4D Quasar phantom and logged by an optical tracking system in real-time. Three motion mitigation approaches (single delivery, 6[Formula: see text] layered and volumetric rescanning) were applied, resulting in 10 individual measurements. 4D dose distributions were retrospectively calculated in water by taking into account the delivery log files (retrospective) containing information on the actually delivered spot positions, fluences, and time stamps. Moreover, in order to evaluate the sensitivity of the 4DDC inputs, the corresponding prospective 4DDCs were performed as a comparison, using the estimated time stamps of the spot delivery and repeated periodical motion patterns. 2D gamma analyses and dose-difference-histograms were used to quantify the agreement between measurements and calculations for all pixels with [Formula: see text]5% of the maximum calculated dose. The results show that a mean gamma score of 99.2% with standard deviation 1.0% can be achieved for 3%/3 mm criteria and all scenarios can reach a score of more than 95%. The average area with more than 5% dose difference was 6.2%. Deviations due to input uncertainties were obvious for single scan deliveries but could be smeared out once rescanning was applied. Thus, the deforming grid 4DDC has been demonstrated to be able to predict the complex patterns of 4D dose distributions for PBS proton therapy with high dosimetric and geometric accuracy, and it can be used as a valid clinical tool for 4D treatment planning, motion mitigation selection, and eventually 4D optimisation applications if the correct temporal information is available.

Personalized Anatomic Eye Model From T1-Weighted Volume Interpolated Gradient Echo Magnetic Resonance Imaging of Patients With Uveal Melanoma

PURPOSE We present a 3-dimensional patient-specific eye model from magnetic resonance imaging (MRI) for proton therapy treatment planning of uveal melanoma (UM). During MRI acquisition of UM patients, the point fixation can be difficult and, together with physiological blinking, can introduce motion artifacts in the images, thus challenging the model creation. Furthermore, the unclear boundary of the small objects (eg, lens, optic nerve) near the muscle or of the tumors with hemorrhage and tantalum clips can limit model accuracy. METHODS AND MATERIALS A dataset of 37 subjects, including 30 healthy eyes of volunteers and 7 eyes of UM patients, was investigated. In our previous work, active shape model was successfully applied to retinoblastoma eye segmentation in T1-weighted 3T MRI. Here, we evaluate this method in a more challenging setting, based on 1.5T MRI acquisition and different datasets of awake adult eyes with UM. The lens and cornea together with the sclera, vitreous humor, and optic nerve were automatically segmented and validated against manual delineations of a senior ocular radiation oncologist, in terms of the Dice similarity coefficient and Hausdorff distance. RESULTS Leave-one-out cross validation (mixing both volunteers and UM patients) yielded median Dice similarity coefficient values (respective of Hausdorff distance) of 94.5% (1.64 mm) for the sclera, 92.2% (1.73 mm) for the vitreous humor, 88.3% (1.09 mm) for the lens, and 81.9% (1.86 mm) for the optic nerve. The average computation time for an eye was 10 seconds. CONCLUSIONS To our knowledge, our work is the first attempt to automatically segment adult eyes, including patients with UM. Our results show that automated active shape model segmentation can succeed in the presence of motion, tumors, and tantalum clips. These results are promising for inclusion in clinical practice.