C Duzenli

In vitro study of cell survival following dynamic MLC intensity-modulated radiation therapy dose delivery.

The possibility of reduced cell kill following intensity-modulated radiation therapy (IMRT) compared to conventional radiation therapy has been debated in the literature. This potential reduction in cell kill relates to prolonged treatment times typical of IMRT dose delivery and consequently increased repair of sublethal lesions. While there is some theoretical support to this reduction in cell kill published in the literature, direct experimental evidence specific to IMRT dose delivery patterns is lacking. In this study we present cell survival data for three cell lines: Chinese hamster V79 fibroblasts, human cervical carcinoma, SiHa and colon adenocarcinoma, WiDr. Cell survival was obtained for 2.1 Gy delivered as acute dose with parallel-opposed pair (POP), irradiation time 75 s, which served as a reference; regular seven-field IMRT, irradiation time 5 min; and IMRT with a break for multiple leaf collimator (MLC) re-initialization after three fields were delivered, irradiation time 10 min. An actual seven-field dynamic MLC IMRT plan for a head and neck patient was used. The IMRT plan was generated for a Varian EX or iX linear accelerator with 120 leaf Millenium MLC. Survival data were also collected for doses 1X, 2X, 3X, 4X, and 5x 2.1 Gy to establish parameters of the linear-quadratic equation describing survival following acute dose delivery. Cells were irradiated inside an acrylic cylindrical phantom specifically designed for this study. Doses from both IMRT and POP were validated using ion chamber measurements. A reproducible increase in cell survival was observed following IMRT dose delivery. This increase varied from small for V79, with a surviving fraction of 0.8326 following POP vs 0.8420 following uninterrupted IMRT, to very pronounced for SiHa, with a surviving fraction of 0.3903 following POP vs 0.5330 for uninterrupted IMRT. When compared to IMRT or IMRT with a break for MLC initialization, cell survival following acute dose delivery was significantly different, p < 0.05, in three out of six cases. In contrast, when cell survival following IMRT was compared to that following IMRT with a break for MLC initialization the difference was always statistically insignificant. When projected to a 30 fraction treatment, dose deficit to bring cell survival to the same value as in POP was calculated as 4.1, 24.9, and 31.1 Gy for V79, WiDr, and SiHa cell lines, respectively. The dose deficit did not relate to the alpha/beta ratio obtained in this study for the three cell lines. Clinical data do not show reduction in local control following IMRT. Possible reasons for this are discussed. The obtained data set can serve as a test data set for models designed to explore the effect of dose delivery prolongation/fractionation in IMRT on radiation therapy outcome.

Technical considerations for implementation of x-ray CT polymer gel dosimetry

Gel dosimetry is the most promising 3D dosimetry technique in current radiation therapy practice. X-ray CT has been shown to be a feasible method of reading out polymer gel dosimeters and, with the high accessibility of CT scanners to cancer hospitals, presents an exciting possibility for clinical implementation of gel dosimetry. In this study we report on technical considerations for implementation of x-ray CT polymer gel dosimetry. Specifically phantom design, CT imaging methods, imaging time requirements and gel dose response are investigated. Where possible, recommendations are made for optimizing parameters to enhance system performance. The dose resolution achievable with an optimized system is calculated given voxel size and imaging time constraints. Results are compared with MRI and optical CT polymer gel dosimetry results available in the literature.

Are neutrons responsible for the dose discrepancies between Monte Carlo calculations and measurements in the build-up region for a high-energy photon beam?

This study presents measured neutron dose using a neutron dosimeter in a water phantom and investigates a hypothesis that neutrons in a high-energy photon beam may be responsible for the reported significant dose discrepancies between Monte Carlo calculations and measurements at the build-up region in large fields. Borated polyethylene slabs were inserted between the accelerator head and the phantom in order to remove neutrons generated in the accelerator head. The thickness of the slab ranged from 2.5 cm to 10 cm. A lead slab of 3 mm thickness was also used in the study. The superheated drop neutron dosimeter was used to measure the depth-dose curve of neutrons in a high-energy photon beam and to verify the effectiveness of the slab to remove these neutrons. Total dose measurements were performed in water using a WELLHOFER WP700 beam scanner with an IC-10 ionization chamber. The Monte Carlo code BEAM was used to simulate an 18 MV photon beam from a Varian Clinac-2100EX accelerator. Both EGS4/DOSXYZ and EGSnrc/DOSRZnrc were used in the dose calculations. Measured neutron dose equivalents as a function of depth per unit total dose in water were presented for 10 x 10 and 40 x 40 cm2 fields. The measured results have shown that a 5-10 cm thick borated polyethylene slab can reduce the neutron dose by a factor of 2 when inserted between the accelerator head and the detector. In all cases the measured neutron dose equivalent was less than 0.5% of the photon dose. In order to study if the ion chamber was highly sensitive to the neutron dose, we have investigated the disagreement between the Monte Carlo calculated and measured central-axis depth-dose curves in the build-up region when different shielding materials were used. The result indicated that the IC-10 chamber was not highly sensitive to the neutron dose. Therefore, neutrons present in a high-energy photon beam were unlikely to be responsible for the reported discrepancies in the build-up region for large fields.

Complexity and accuracy of image registration methods in SPECT-guided radiation therapy.

The use of functional imaging in radiotherapy treatment (RT) planning requires accurate co-registration of functional imaging scans to CT scans. We evaluated six methods of image registration for use in SPECT-guided radiotherapy treatment planning. Methods varied in complexity from 3D affine transform based on control points to diffeomorphic demons and level set non-rigid registration. Ten lung cancer patients underwent perfusion SPECT-scans prior to their radiotherapy. CT images from a hybrid SPECT/CT scanner were registered to a planning CT, and then the same transformation was applied to the SPECT images. According to registration evaluation measures computed based on the intensity difference between the registered CT images or based on target registration error, non-rigid registrations provided a higher degree of accuracy than rigid methods. However, due to the irregularities in some of the obtained deformation fields, warping the SPECT using these fields may result in unacceptable changes to the SPECT intensity distribution that would preclude use in RT planning. Moreover, the differences between intensity histograms in the original and registered SPECT image sets were the largest for diffeomorphic demons and level set methods. In conclusion, the use of intensity-based validation measures alone is not sufficient for SPECT/CT registration for RTTP. It was also found that the proper evaluation of image registration requires the use of several accuracy metrics.

Effect of prolonging radiation delivery time on retention of gammaH2AX

Background and purposeCompared to conventional external beam radiotherapy, IMRT requires significantly more time to deliver the dose. Prolonging dose delivery potentially increases DNA repair which would reduce the biological effect. We questioned whether retention of γH2AX, a measure of lack of repair of DNA damage, would decrease when dose delivery was protracted.Materials and methodsExponentially growing SiHa cervical carinoma cells were irradiated with 6 MV photons in a water tank using a VarianEX linear accelerator. Cells held at 37°C received 2 Gy in 0.5 min and 4 Gy in 1 min. To evaluate effect of dose delivery prolongation, 2 and 4 Gy were delivered in 30 and 60 min. After 24 h recovery, cells were analyzed for clonogenic survival and for residual γH2AX as measured using flow cytometry.ResultsIncreasing the dose delivery time from 0.5 or 1 min to 30 or 60 min produced a signficant increase in cell survival from 0.45 to 0.48 after 2 Gy, and from 0.17 to 0.20 after 4 Gy. Expression of residual γH2AX decreased from 1.27 to 1.22 relative to background after 2 Gy and 1.46 to 1.39 relative to background after 4 Gy, but differences were not statistically significant. The relative differences in the slopes of residual γH2AX versus dose for acute versus prolonged irradiation bordered on significant (p = 0.055), and the magnitude of the change was consistent with the observed increase in surviving fraction.ConclusionThese results support the concept that DNA repair underlies the increase in survival observed when dose delivery is prolonged. They also help to establish the limits of sensitivity of residual γH2AX, as measured using flow cytometry, for detecting differences in response to irradiation.

A Monte Carlo model of the Varian IGRT couch top for RapidArc QA

The objectives of this study are to evaluate the effect of couch attenuation on quality assurance (QA) results and to present a couch top model for Monte Carlo (MC) dose calculation for RapidArc treatments. The IGRT couch top is modelled in Eclipse as a thin skin of higher density material with a homogeneous fill of foam of lower density and attenuation. The IGRT couch structure consists of two longitudinal sections referred to as thick and thin. The Hounsfield Unit (HU) characterization of the couch structure was determined using a cylindrical phantom by comparing ion chamber measurements with the dose predicted by the treatment planning system (TPS). The optimal set of HU for the inside of the couch and the surface shell was found to be respectively -960 and -700 HU in agreement with Vanetti et al (2009 Phys. Med. Biol. 54 N157-66). For each plan, the final dose calculation was performed with the thin, thick and without the couch top. Dose differences up to 2.6% were observed with TPS calculated doses not including the couch and up to 3.4% with MC not including the couch and were found to be treatment specific. A MC couch top model was created based on the TPS geometrical model. The carbon fibre couch top skin was modelled using carbon graphite; the density was adjusted until good agreement with experimental data was observed, while the density of the foam inside was kept constant. The accuracy of the couch top model was evaluated by comparison with ion chamber measurements and TPS calculated dose combined with a 3D gamma analysis. Similar to the TPS case, a single graphite density can be used for both the thin and thick MC couch top models. Results showed good agreement with ion chamber measurements (within 1.2%) and with TPS (within 1%). For each plan, over 95% of the points passed the 3D gamma test.

Incorporating Quantitative Single Photon Emission Computed Tomography into Radiation Therapy Treatment Planning for Lung Cancer: Impact of Attenuation and Scatter Correction on the Single Photon Emission Computed Tomography–Weighted Mean Dose and Functional Lung Segmentation

PURPOSE To assess the impact of attenuation and scatter corrections on the calculation of single photon emission computed tomography (SPECT)-weighted mean dose (SWMD) and functional volume segmentation as applied to radiation therapy treatment planning for lung cancer. METHODS AND MATERIALS Nine patients with lung cancer underwent a SPECT lung perfusion scan. For each scan, four image sets were reconstructed using the ordered subsets expectation maximization method with attenuation and scatter corrections ranging from none to a most comprehensive combination of attenuation corrections and direct scatter modeling. Functional volumes were segmented in each reconstructed image using 10%, 20%, …, 90% of maximum SPECT intensity as a threshold. Systematic effects of SPECT reconstruction methods on treatment planning using functional volume were studied by calculating size and spatial agreements of functional volumes, and V(20) for functional volume from actual treatment plans. The SWMD was calculated for radiation beams with a variety of possible gantry angles and field sizes. RESULTS Functional volume segmentation is sensitive to the particular method of SPECT reconstruction used. Large variations in functional volumes, as high as >50%, were observed in SPECT images reconstructed with different attenuation/scatter corrections. However, SWMD was less sensitive to the type of scatter corrections. SWMD was consistent within 2% for all reconstructions as long as computed tomography-based attenuation correction was used. CONCLUSION When using perfusion SPECT images during treatment planning optimization/evaluation, the SWMD may be the preferred figure of merit, as it is less affected by reconstruction technique, compared with threshold-based functional volume segmentation.

Equivalent doses for gynecological patients undergoing IMRT or RapidArc with kilovoltage cone beam CT

PURPOSE To investigate in-field and peripheral kilovoltage cone beam CT (CBCT) doses in gynecological patients in comparison with IMRT or RapidArc scatter and linac leakage doses. MATERIALS AND METHODS Monte Carlo codes BEAMnrc/DOSXYZnrc were used to simulate dose for daily use of kV CBCT in patients undergoing adjuvant pelvic radiotherapy for uterine or ovarian malignancies. Biological effectiveness was accounted for using a lineal energy based quality factor. Organ equivalent doses (OED) within the treatment field were modeled with linear-exponential, plateau and linear dose response curves. CBCT doses in peripheral regions were compared with IMRT and RapidArc scatter doses as well as linac leakage doses. RESULTS CBCT doses in peripheral regions were on the order of linac leakage doses and one order of magnitude lower than IMRT or RapidArc scatter doses. OEDs increased slightly, leveled off or even decreased within the treatment field with the addition of CBCT doses according to different dose response models. CONCLUSION The results of this study indicate that patients undergoing IMRT or RapidArc treatments with daily use of kV CBCT imaging are not subjected to additional risk due to CBCT imaging doses.

Automated segmentation and dose-volume analysis with DICOMautomaton

Purpose: Exploration of historical data for regional organ dose sensitivity is limited by the effort needed to (sub-)segment large numbers of contours. A system has been developed which can rapidly perform autonomous contour sub-segmentation and generic dose-volume computations, substantially reducing the effort required for exploratory analyses. Methods: A contour-centric approach is taken which enables lossless, reversible segmentation and dramatically reduces computation time compared with voxel-centric approaches. Segmentation can be specified on a per-contour, per-organ, or per-patient basis, and can be performed along either an embedded plane or in terms of the contours bounds (e.g., split organ into fractional-volume/dose pieces along any 3D unit vector). More complex segmentation techniques are available. Anonymized data from 60 head-and-neck cancer patients were used to compare dose-volume computations with Varians EclipseTM (Varian Medical Systems, Inc.). Results: Mean doses and Dose-volume-histograms computed agree strongly with Varians EclipseTM. Contours which have been segmented can be injected back into patient data permanently and in a Digital Imaging and Communication in Medicine (DICOM)-conforming manner. Lossless segmentation persists across such injection, and remains fully reversible. Conclusions: DICOMautomaton allows researchers to rapidly, accurately, and autonomously segment large amounts of data into intricate structures suitable for analyses of regional organ dose sensitivity.

SU‐D‐105‐03: Developing QA Procedures for Gated VMAT SABR Treatments

PURPOSE To develop a QA procedure for gated VMAT SABR liver cancer treatments and investigate the gating parameters for acceptable plan delivery in terms of the dose to a moving volume and treatment delivery time. METHODS 10 patient plans for VMAT SABR liver were created using the Eclipse™ TPS. The verification plans were then transferred to a CT-scanned Quasar™ phantom and delivered on a TrueBeam™ linac using a 10FFF beam and Varians RPM system for respiratory gating. Two kinds of breathing patterns were used: free breathing (FB) and an interrupted (∼5s pause) end of exhale coached breathing (CB) pattern. Ion chamber and Gafchromic™ film measurements were acquired for a gated delivery while the phantom moved under the described breathing patterns and a non-gated, stationary phantom delivery. The gate window was set to obtain a range of residual target motion from 2-10 mm. RESULTS Preliminary chamber measurements indicate that the dose to the center of the PTV can vary considerably under gated delivery compared to the static case. The effect can be significant for free breathing; ∼4-12% over the selected range of residual target motion. The agreement was more consistent with CB pattern at ∼1-4%. Gamma analysis (3%, 3mm) showed an agreement above 99.74% for all gated deliveries compared to the static delivery. The treatment time with a gate width of 2 mm was ∼265s for the CB pattern compared to ∼740s under a typical FB pattern. A non-gated delivery of the same plan took ∼100s. CONCLUSION Gated VMAT treatments have been delivered successfully to a motorized phantom. FB patterns contain considerable variability and it is difficult to achieve acceptable results even with very small gate windows. However, a CB pattern combined with a sufficiently small gate, resulted in acceptable dose distributions that can be delivered in a reasonable amount of time. Francis Viel received funding from the Natural Sciences and Engineering Research Council of Canada. This work has been supported by the Varian Research Collaborations Program.