Dosimetric and mechanical equivalency of Varian TrueBeam linear accelerators.

PURPOSE: To investigate and improve the level of equivalency of Varian TrueBeam linear accelerators (linacs) in energy-, dosimetric leaf gap- (DLG) and jaw calibration. METHODS: Eight linacs with four photon energies: 6 MV, 6 MV FFF, 10 MV FFF, and 15 MV, and three electron energies (on two linacs): 6, 9, and 12 MeV were commisioned and beam-matched. Initially, symmetry of lateral profiles was calibrated for maximum field size. Energy-matching was then performed for photons by adjusting diagonal profiles at maximum field size and depth of maximum dose to coincide with the reference linac, and for electrons by matching the range at percentage depth of ionization of 90%, 80%, and 50%. Calibration of DLG was performed for 6 MV and evaluated among the linacs. The relationship between DLG and the Gap value was investigated. A method using electronic portal imaging device (EPID) was developed and implemented for jaw calibration. RESULTS: Symmetry calibration for photons (electrons) was within 1% (0.7%), further improving the vendor's acceptance criteria. Photon and electron energy-matching was within 0.5% and 0.1 mm, respectively. Calibration of DLG was within 0.032 mm among the linacs and utilizing the relationship between DLG and the Gap value resulted in an empirical calibration method which was implemented to simplify DLG adjustment. Using EPID-based method of calibration, evaluation of the jaw-positioning among the linacs for 30 cm × 30 cm field size was within 0.4 mm and in the junction area within 0.2 mm. Dose delivery error of VMAT-plans were at least 99.2% gamma pass rate (1%, 1 mm). CONCLUSIONS: High level of equivalency, beyond clinically accepted criteria, of TrueBeam linacs could be achieved which reduced dose delivery systematic errors and increased confidence in interchanging patients among linacs.

Technical Note: In silico and experimental evaluation of two leaf-fitting algorithms for MLC tracking based on exposure error and plan complexity.

PURPOSE: Multileaf collimator (MLC) tracking is being clinically pioneered to continuously compensate for thoracic and pelvic motion during radiotherapy. The purpose of this work was to characterize the performance of two MLC leaf-fitting algorithms, direct optimization and piecewise optimization, for real-time motion compensation with different plan complexity and tumor trajectories. METHODS: To test the algorithms, both in silico and phantom experiments were performed. The phantom experiments were performed on a Trilogy Varian linac and a HexaMotion programmable motion platform. High and low modulation VMAT plans for lung and prostate cancer cases were used along with eight patient-measured organ-specific trajectories. For both MLC leaf-fitting algorithms, the plans were run with their corresponding patient trajectories. To compare algorithms, the average exposure errors, i.e., the difference in shape between ideal and fitted MLC leaves by the algorithm, plan complexity and system latency of each experiment were calculated. RESULTS: Comparison of exposure errors for the in silico and phantom experiments showed minor differences between the two algorithms. The average exposure errors for in silico experiments with low/high plan complexity were 0.66/0.88 cm2 for direct optimization and 0.66/0.88 cm2 for piecewise optimization, respectively. The average exposure errors for the phantom experiments with low/high plan complexity were 0.73/1.02 cm2 for direct and 0.73/1.02 cm2 for piecewise optimization, respectively. The measured latency for the direct optimization was 226 ± 10 ms and for the piecewise algorithm was 228 ± 10 ms. In silico and phantom exposure errors quantified for each treatment plan demonstrated that the exposure errors from the high plan complexity (0.96 cm2 mean, 2.88 cm2 95% percentile) were all significantly different from the low plan complexity (0.70 cm2 mean, 2.18 cm2 95% percentile) (P < 0.001, two-tailed, Mann-Whitney statistical test). CONCLUSIONS: The comparison between the two leaf-fitting algorithms demonstrated no significant differences in exposure errors, neither in silico nor with phantom experiments. This study revealed that plan complexity impacts the overall exposure errors significantly more than the difference between the algorithms.

Simulating intrafraction prostate motion with a random walk model.

PURPOSE: Prostate motion during radiation therapy (ie, intrafraction motion) can cause unwanted loss of radiation dose to the prostate and increased dose to the surrounding organs at risk. A compact but general statistical description of this motion could be useful for simulation of radiation therapy delivery or margin calculations. We investigated whether prostate motion could be modeled with a random walk model. METHODS AND MATERIALS: Prostate motion recorded during 548 radiation therapy fractions in 17 patients was analyzed and used for input in a random walk prostate motion model. The recorded motion was categorized on the basis of whether any transient excursions (ie, rapid prostate motion in the anterior and superior direction followed by a return) occurred in the trace and transient motion. This was separately modeled as a large step in the anterior/superior direction followed by a returning large step. Random walk simulations were conducted with and without added artificial transient motion using either motion data from all observed traces or only traces without transient excursions as model input, respectively. RESULTS: A general estimate of motion was derived with reasonable agreement between simulated and observed traces, especially during the first 5 minutes of the excursion-free simulations. Simulated and observed diffusion coefficients agreed within 0.03, 0.2 and 0.3 mm2/min in the left/right, superior/inferior, and anterior/posterior directions, respectively. A rapid increase in variance at the start of observed traces was difficult to reproduce and seemed to represent the patient's need to adjust before treatment. This could be estimated somewhat using artificial transient motion. CONCLUSIONS: Random walk modeling is feasible and recreated the characteristics of the observed prostate motion. Introducing artificial transient motion did not improve the overall agreement, although the first 30 seconds of the traces were better reproduced. The model provides a simple estimate of prostate motion during delivery of radiation therapy.

A dosimetric comparison of real-time adaptive and non-adaptive radiotherapy: A multi-institutional study encompassing robotic, gimbaled, multileaf collimator and couch tracking.

PURPOSE: A study of real-time adaptive radiotherapy systems was performed to test the hypothesis that, across delivery systems and institutions, the dosimetric accuracy is improved with adaptive treatments over non-adaptive radiotherapy in the presence of patient-measured tumor motion. METHODS AND MATERIALS: Ten institutions with robotic(2), gimbaled(2), MLC(4) or couch tracking(2) used common materials including CT and structure sets, motion traces and planning protocols to create a lung and a prostate plan. For each motion trace, the plan was delivered twice to a moving dosimeter; with and without real-time adaptation. Each measurement was compared to a static measurement and the percentage of failed points for γ-tests recorded. RESULTS: For all lung traces all measurement sets show improved dose accuracy with a mean 2%/2mm γ-fail rate of 1.6% with adaptation and 15.2% without adaptation (p<0.001). For all prostate the mean 2%/2mm γ-fail rate was 1.4% with adaptation and 17.3% without adaptation (p<0.001). The difference between the four systems was small with an average 2%/2mm γ-fail rate of <3% for all systems with adaptation for lung and prostate. CONCLUSIONS: The investigated systems all accounted for realistic tumor motion accurately and performed to a similar high standard, with real-time adaptation significantly outperforming non-adaptive delivery methods.

Dose painting based on tumor uptake of Cu-ATSM and FDG: a comparative study.

BACKGROUND: Hypoxia and increased glycolytic activity of tumors are associated with poor prognosis. The purpose of this study was to investigate differences in radiotherapy (RT) dose painting based on the uptake of 2-deoxy-2-[(18) F]-fluorodeoxyglucose (FDG) and the proposed hypoxia tracer, copper(II)diacetyl-bis(N(4))-methylsemithiocarbazone (Cu-ATSM) using spontaneous clinical canine tumor models. METHODS: Positron emission tomography/computed tomography scans of five spontaneous canine sarcomas and carcinomas were obtained; FDG on day 1 and (64)Cu-ATSM on day 2 and 3 (approx. 3 and 24 hours pi.). Sub-volumes for dose escalation were defined by a threshold-based method for both tracers and five dose escalation levels were formed in each sub-volume. Volumetric modulated arc therapy plans were optimized based on the dose escalation regions for each scan for a total of three dose plans for each dog. The prescription dose for the GTV was 45 Gy (100%) and it was linearly escalated to a maximum of 150%. The correlations between dose painting plans were analyzed with construction of dose distribution density maps and quality volume histograms (QVH). Correlation between high-dose regions was investigated with Dice correlation coefficients. RESULTS: Comparison of dose plans revealed varying degree of correlation between cases. Some cases displayed a separation of high-dose regions in the comparison of FDG vs. (64)Cu-ATSM dose plans at both time points. Among the Dice correlation coefficients, the high dose regions showed the lowest degree of agreement, indicating potential benefit of using multiple tracers for dose painting. QVH analysis revealed that FDG-based dose painting plans adequately covered approximately 50% of the hypoxic regions. CONCLUSION: Radiotherapy plans optimized with the current approach for cut-off values and dose region definitions based on FDG, (64)Cu-ATSM 3 h and 24 h uptake in canine tumors had different localization of the regional dose escalation levels. This indicates that (64)Cu-ATSM at two different time-points and FDG provide different biological information that has to be taken into account when using the dose painting strategy in radiotherapy treatment planning.

Motion management during IMAT treatment of mobile lung tumors--a comparison of MLC tracking and gated delivery.

PURPOSE: To compare real-time dynamic multileaf collimator (MLC) tracking, respiratory amplitude and phase gating, and no compensation for intrafraction motion management during intensity modulated arc therapy (IMAT). METHODS: Motion management with MLC tracking and gating was evaluated for four lung cancer patients. The IMAT plans were delivered to a dosimetric phantom mounted onto a 3D motion phantom performing patient-specific lung tumor motion. The MLC tracking system was guided by an optical system that used stereoscopic infrared (IR) cameras and five spherical reflecting markers attached to the dosimetric phantom. The gated delivery used a duty cycle of 35% and collected position data using an IR camera and two reflecting markers attached to a marker block. RESULTS: The average gamma index failure rate (2% and 2 mm criteria) was <0.01% with amplitude gating for all patients, and <0.1% with phase gating and <3.7% with MLC tracking for three of the four patients. One of the patients had an average failure rate of 15.1% with phase gating and 18.3% with MLC tracking. With no motion compensation, the average gamma index failure rate ranged from 7.1% to 46.9% for the different patients. Evaluation of the dosimetric error contributions showed that the gated delivery mainly had errors in target localization, while MLC tracking also had contributions from MLC leaf fitting and leaf adjustment. The average treatment time was about three times longer with gating compared to delivery with MLC tracking (that did not prolong the treatment time) or no motion compensation. For two of the patients, the different motion compensation techniques allowed for approximately the same margin reduction but for two of the patients, gating enabled a larger reduction of the margins than MLC tracking. CONCLUSIONS: Both gating and MLC tracking reduced the effects of the target movements, although the gated delivery showed a better dosimetric accuracy and enabled a larger reduction of the margins in some cases. MLC tracking did not prolong the treatment time compared to delivery with no motion compensation while gating had a considerably longer delivery time. In a clinical setting, the optical monitoring of the patients breathing would have to be correlated to the internal movements of the tumor.

A treatment planning and delivery comparison of volumetric modulated arc therapy with or without flattening filter for gliomas, brain metastases, prostate, head/neck and early stage lung cancer.

BACKGROUND: Flattening filter-free (FFF) beams are an emerging technology that has not yet been widely implemented as standard practice in radiotherapy centers. To facilitate the clinical implementation of FFF, we attempted to elucidate the difference in plan quality and treatment delivery time compared to flattening filter beams (i.e. standard, STD) for several patient groups. We hypothesize that the treatment plan quality is comparable while the treatment delivery time of volumetric modulated arc therapy (VMAT) is considerably shorter using FFF beams, especially for stereotactic treatments. METHODS: A total of 120 patients treated for head and neck (H&N) tumors, high-grade glioma, prostate cancer, early stage lung cancer and intra-cranial metastatic disease (both single and multiple metastases) were included in the study. For each cohort, 20 consecutive patients were selected. The plans were generated using STD- and FFF-VMAT for both 6 MV and 10 MV, and were compared with respect to plan quality, monitor units and delivery time using Wilcoxon signed rank tests. RESULTS: For H&N and high-grade gliomas, there was a significant difference in homogeneity index in favor for STD-VMAT (p < 0.001). For the stereotactic sites there were no differences in plan conformity. Stereotactic FFF-VMAT plans required significantly shorter delivery time compared to STD-VMAT plans (p < 0.001) for higher dose per fraction, on average 54.5% for 6 MV and 71.4% for 10 MV. FFF-VMAT generally required a higher number of MU/Gy (p < 0.001), on average 7.0% for 6 MV and 8.4% for 10 MV. CONCLUSION: It was generally possible to produce FFF-VMAT plans with the same target dose coverage and doses to organs at risk as STD-VMAT plans. Target dose homogeneity tended to be somewhat inferior for FFF-VMAT for the larger targets investigated. For stereotactic radiotherapy, FFF-VMAT resulted in a considerable time gain while maintaining similar plan quality compared to STD beams.

Improvement in toxicity in high risk prostate cancer patients treated with image-guided intensity-modulated radiotherapy compared to 3D conformal radiotherapy without daily image guidance.

BACKGROUND: Image-guided radiotherapy (IGRT) facilitates the delivery of a very precise radiation dose. In this study we compare the toxicity and biochemical progression-free survival between patients treated with daily image-guided intensity-modulated radiotherapy (IG-IMRT) and 3D conformal radiotherapy (3DCRT) without daily image guidance for high risk prostate cancer (PCa). METHODS: A total of 503 high risk PCa patients treated with radiotherapy (RT) and endocrine treatment between 2000 and 2010 were retrospectively reviewed. 115 patients were treated with 3DCRT, and 388 patients were treated with IG-IMRT. 3DCRT patients were treated to 76 Gy and without daily image guidance and with 1-2 cm PTV margins. IG-IMRT patients were treated to 78 Gy based on daily image guidance of fiducial markers, and the PTV margins were 5-7 mm. Furthermore, the dose-volume constraints to both the rectum and bladder were changed with the introduction of IG-IMRT. RESULTS: The 2-year actuarial likelihood of developing grade > = 2 GI toxicity following RT was 57.3% in 3DCRT patients and 5.8% in IG-IMRT patients (p < 0.001). For GU toxicity the numbers were 41.8% and 29.7%, respectively (p = 0.011). On multivariate analysis, 3DCRT was associated with a significantly increased risk of developing grade > = 2 GI toxicity compared to IG-IMRT (p < 0.001, HR = 11.59 [CI: 6.67-20.14]). 3DCRT was also associated with an increased risk of developing GU toxicity compared to IG-IMRT.The 3-year actuarial biochemical progression-free survival probability was 86.0% for 3DCRT and 90.3% for IG-IMRT (p = 0.386). On multivariate analysis there was no difference in biochemical progression-free survival between 3DCRT and IG-IMRT. CONCLUSION: The difference in toxicity can be attributed to the combination of the IMRT technique with reduced dose to organs-at-risk, daily image guidance and margin reduction.

The impact of leaf width and plan complexity on DMLC tracking of prostate intensity modulated arc therapy.

PURPOSE: Intensity modulated arc therapy (IMAT) is commonly used to treat prostate cancer. The purpose of this study was to evaluate the impact of leaf width and plan complexity on dynamic multileaf collimator (DMLC) tracking for prostate motion management during IMAT treatments. METHODS: Prostate IMAT plans were delivered with either a high-definition MLC (HDMLC) or a Millennium MLC (M-MLC) (0.25 and 0.50 cm central leaf width, respectively), with and without DMLC tracking, to a dosimetric phantom that reproduced four prostate motion traces. The plan complexity was varied by applying leaf position constraints during plan optimization. A subset of the M-MLC plans was converted for delivery with the HDMLC, isolating the effect of the different leaf widths. The gamma index was used for evaluation. Tracking errors caused by target localization, leaf fitting, and leaf adjustment were analyzed. RESULTS: The gamma pass rate was significantly improved with DMLC tracking compared to no tracking (p < 0.001). With DMLC tracking, the average gamma index pass rate was 98.6% (range 94.8%-100%) with the HDMLC and 98.1% (range 95.4%-99.7%) with the M-MLC, using 3%, 3 mm criteria and the planned dose as reference. The corresponding pass rates without tracking were 87.6% (range 76.2%-94.7%) and 91.1% (range 81.4%-97.6%), respectively. Decreased plan complexity improved the pass rate when static target measurements were used as reference, but not with the planned dose as reference. The main cause of tracking errors was leaf fitting errors, which were decreased by 42% by halving the leaf width. CONCLUSIONS: DMLC tracking successfully compensated for the prostate motion. The finer leaf width of the HDMLC improved the tracking accuracy compared to the M-MLC. The tracking improvement with limited plan complexity was small and not discernible when using the planned dose as reference.

Dosimetric benefit of DMLC tracking for conventional and sub-volume boosted prostate intensity-modulated arc radiotherapy.

This study investigated the dosimetric impact of uncompensated motion and motion compensation with dynamic multileaf collimator (DMLC) tracking for prostate intensity modulated arc therapy. Two treatment approaches were investigated; a conventional approach with a uniform radiation dose to the target volume and an intraprostatic lesion (IPL) boosted approach with an increased dose to a subvolume of the prostate. The impact on plan quality of optimizations with a leaf position constraint, which limited the distance between neighbouring adjacent MLC leaves, was also investigated. Deliveries were done with and without DMLC tracking on a linear acceleration with a high-resolution MLC. A cylindrical phantom containing two orthogonal diode arrays was used for dosimetry. A motion platform reproduced six patient-derived prostate motion traces, with the average displacement ranging from 1.0 to 8.9 mm during the first 75 s. A research DMLC tracking system was used for real-time motion compensation with optical monitoring for position input. The gamma index was used for evaluation, with measurements with a static phantom or the planned dose as reference, using 2% and 2 mm gamma criteria. The average pass rate with DMLC tracking was 99.9% (range 98.7-100%, measurement as reference), whereas the pass rate for untracked deliveries decreased distinctly as the average displacement increased, with an average pass rate of 61.3% (range 32.7-99.3%). Dose-volume histograms showed that DMLC tracking maintained the planned dose distributions in the presence of motion whereas traces with >3 mm average displacement caused clear plan degradation for untracked deliveries. The dose to the rectum and bladder had an evident dependence on the motion direction and amplitude for untracked deliveries, and the dose to the rectum was slightly increased for IPL boosted plans compared to conventional plans for anterior motion with large amplitude. In conclusion, optimization using a leaf position constraint had minimal dosimetric effect, DMLC tracking improved the target and normal tissue dose distributions compared to no tracking for target motion >3 mm, with the DMLC tracking distributions showing generally good agreement between the planned and delivered doses.

Photon activation therapy of RG2 glioma carrying Fischer rats using stable thallium and monochromatic synchrotron radiation.

75 RG2 glioma-carrying Fischer rats were treated by photon activation therapy (PAT) with monochromatic synchrotron radiation and stable thallium. Three groups were treated with thallium in combination with radiation at different energy; immediately below and above the thallium K-edge, and at 50 keV. Three control groups were given irradiation only, thallium only, or no treatment at all. For animals receiving thallium in combination with radiation to 15 Gy at 50 keV, the median survival time was 30 days, which was 67% longer than for the untreated controls (p = 0.0020) and 36% longer than for the group treated with radiation alone (not significant). Treatment with thallium and radiation at the higher energy levels were not effective at the given absorbed dose and thallium concentration. In the groups treated at 50 keV and above the K-edge, several animals exhibited extensive and sometimes contra-lateral edema, neuronal death and frank tissue necrosis. No such marked changes were seen in the other groups. The results were discussed with reference to Monte Carlo calculated electron energy spectra and dose enhancement factors.