Four-dimensional treatment planning strategies for dynamic tumor tracking.

INTRODUCTION: Dynamic tumor tracking (DTT) is a motion management technique where the radiation beam follows a moving tumor in real time. Not modelling DTT beam motion in the treatment planning system leaves an organ at risk (OAR) vulnerable to exceeding its dose limit. This work investigates two planning strategies for DTT plans, the "Boolean OAR Method" and the "Aperture Sorting Method," to determine if they can successfully spare an OAR while maintaining sufficient target coverage. MATERIALS AND METHODS: A step-and-shoot intensity modulated radiation therapy (sIMRT) treatment plan was re-optimized for 10 previously treated liver stereotactic ablative radiotherapy patients who each had one OAR very close to the target. Two planning strategies were investigated to determine which is more effective at sparing an OAR while maintaining target coverage: (1) the "Boolean OAR Method" created a union of an OAR's contours from two breathing phases (exhale and inhale) on the exhale phase (the planning CT) and protected this combined OAR during plan optimization, (2) the "Aperture Sorting Method" assigned apertures to the breathing phase where they contributed the least to an OAR's maximum dose. RESULTS: All 10 OARs exceeded their dose constraints on the original plan four-dimensional (4D) dose distributions and average target coverage was V100%  = 91.3% ± 2.9% (ranging from 85.1% to 94.8%). The "Boolean OAR Method" spared 7/10 OARs, and mean target coverage decreased to V100%  = 87.1% ± 3.8% (ranging from 80.7% to 93.7%). The "Aperture Sorting Method" spared 9/10 OARs and the mean target coverage remained high at V100%  = 91.7% ± 2.8% (ranging from 84.9% to 94.5%). CONCLUSIONS: 4D planning strategies are simple to implement and can improve OAR sparing during DTT treatments. The "Boolean OAR Method" improved sparing of OARs but target coverage was reduced. The "Aperture Sorting Method" further improved sparing of OARs and maintained target coverage.

Upfront Versus Delayed Systemic Therapy in Patients With Oligometastatic Cancer Treated With SABR in the Phase 2 SABR-5 Trial.

PURPOSE: The optimal sequencing of local and systemic therapy for oligometastatic cancer has not been established. This study retrospectively compared progression-free survival (PFS), overall survival (OS), and SABR-related toxicity between upfront versus delay of systemic treatment until progression in patients in the SABR-5 trial. METHODS AND MATERIALS: The single-arm phase 2 SABR-5 trial accrued patients with up to 5 oligometastases across SABR-5 between November 2016 and July 2020. Patients received SABR to all lesions. Two cohorts were retrospectively identified: those receiving upfront systemic treatment along with SABR and those for whom systemic treatment was delayed until disease progression. Patients treated for oligoprogression were excluded. Propensity score analysis with overlap weighting balanced baseline characteristics of cohorts. Bootstrap sampling and Cox regression models estimated the association of delayed systemic treatment with PFS, OS, and grade ≥2 toxicity. RESULTS: A total of 319 patients with oligometastases underwent treatment on SABR-5, including 121 (38%) and 198 (62%) who received upfront and delayed systemic treatment, respectively. In the weighted sample, prostate cancer was the most common primary tumor histology (48%) followed by colorectal (18%), breast (13%), and lung (4%). Most patients (93%) were treated for 1 to 2 metastases. The median follow-up time was 34 months (IQR, 24-45). Delayed systemic treatment was associated with shorter PFS (hazard ratio [HR], 1.56; 95% CI, 1.15-2.13; P = .005) but similar OS (HR, 0.90; 95% CI, 0.51-1.59; P = .65) compared with upfront systemic treatment. Risk of grade 2 or higher SABR-related toxicity was reduced with delayed systemic treatment (odds ratio, 0.35; 95% CI, 0.15-0.70; P < .001). CONCLUSIONS: Delayed systemic treatment is associated with shorter PFS without reduction in OS and with reduced SABR-related toxicity and may be a favorable option for select patients seeking to avoid initial systemic treatment. Efforts should continue to accrue patients to histology-specific trials examining a delayed systemic treatment approach.

Markerless dynamic tumor tracking (MDTT) radiotherapy using diaphragm as a surrogate for liver targets.

PURPOSE: To assess the feasibility of using the diaphragm as a surrogate for liver targets during MDTT. METHODS: Diaphragm as surrogate for markers: a dome-shaped phantom with implanted markers was fabricated and underwent dual-orthogonal fluoroscopy sequences on the Vero4DRT linac. Ten patients participated in an IRB-approved, feasibility study to assess the MDTT workflow. All images were analyzed using an in-house program to back-project the diaphragm/markers position to the isocenter plane. ExacTrac imager log files were analyzed. Diaphragm as tracking structure for MDTT: The phantom "diaphragm" was contoured as a markerless tracking structure (MTS) and exported to Vero4DRT/ExacTrac. A single field plan was delivered to the phantom film plane under static and MDTT conditions. In the patient study, the diaphragm tracking structure was contoured on CT breath-hold-exhale datasets. The MDTT workflow was applied until just prior to MV beam-on. RESULTS: Diaphragm as surrogate for markers: phantom data confirmed the in-house 3D back-projection program was functioning as intended. In patients, the diaphragm/marker relative positions had a mean ± RMS difference of 0.70 ± 0.89, 1.08 ± 1.26, and 0.96 ± 1.06 mm in ML, SI, and AP directions. Diaphragm as tracking structure for MDTT: Building a respiratory-correlation model using the diaphragm as surrogate for the implanted markers was successful in phantom/patients. During the tracking verification imaging step, the phantom mean ± SD difference between the image-detected and predicted "diaphragm" position was 0.52 ± 0.18 mm. The 2D film gamma (2%/2 mm) comparison (static to MDTT deliveries) was 98.2%. In patients, the mean difference between the image-detected and predicted diaphragm position was 2.02 ± 0.92 mm. The planning target margin contribution from MDTT diaphragm tracking is 2.2, 5.0, and 4.7 mm in the ML, SI, and AP directions. CONCLUSION: In phantom/patients, the diaphragm motion correlated well with markers' motion and could be used as a surrogate. MDTT workflows using the diaphragm as the MTS is feasible using the Vero4DRT linac and could replace the need for implanted markers for liver radiotherapy.

Late Toxicity of Prostate Ultrahypofractionated Radiation Therapy Compared With Moderate Hypofractionation in a Randomized Trial.

PURPOSE: We report late toxicity, quality of life (QOL), and urinary symptom score with prostate cancer radiation therapy in a randomized trial comparing moderate hypofractionation and ultrahypofrationation. METHODS AND MATERIALS: Patients with intermediate and high-risk prostate cancer were randomized to either Arm 1 (70 Gy/28 fractions) or Arm 2 (36.25 Gy/5 weekly fractions). Late toxicity was evaluated using the Common Terminology Criteria for Adverse Events and Radiation Therapy Oncology Group/Subjective, Objective, Management, Analytical scales. QOL was assessed with the Expanded Prostate Inventory Composite-26 Short Form and urinary function with the International Prostate Symptom Score. RESULTS: Eighty participants were randomized. Two from Arm 1 withdrew, leaving 36 patients in Arm 1 and 42 in Arm 2. There were no significant differences in baseline characteristics, except for worse International Prostate Symptom Score in Arm 2. No difference was observed in freedom from grade 3 or worse toxicity between treatments (P = .921), with only a single grade 3 event in each arm. There was no significant difference in freedom from grade 2 or worse toxicity (P = .280). No difference was observed in freedom from grade 2 or worse genitorurinary toxicity, with cumulative probabilities of 69.0% and 87.0% at 5 years for Arms 1 and 2, respectively (0.132). No difference was observed in freedom from grade 2 or worse gastrointestinal toxicity, with cumulative probabilities of 74.0% in Arm 1 and 80.0% in Arm 2 (P = .430). There were no significant differences in Expanded Prostate Inventory Composite-26 Short Form QOL between arms. CONCLUSIONS: Ultrahypofrationation, delivered weekly, is well tolerated with no significant differences in freedom from late toxicity compared with moderate hypofractionation.

Monte Carlo Modeling of Dynamic Tumor Tracking on a Gimbaled Linear Accelerator.

Purpose and Aim: The Vero4DRT (Brainlab AG) linear accelerator is capable of dynamic tumor tracking (DTT) by panning/tilting the radiation beam to follow respiratory-induced tumor motion in real time. In this study, the panning/tilting motion is modeled in Monte Carlo (MC) for quality assurance (QA) of four-dimensional (4D) dose distributions created within the treatment planning system (TPS). Materials and Methods: Step-and-shoot intensity-modulated radiation therapy plans were optimized for 10 previously treated liver patients. These plans were recalculated on multiple phases of a 4D computed tomography (4DCT) scan using MC while modeling panning/tilting. The dose distributions on each phase were accumulated to create a respiratory-weighted 4D dose distribution. Differences between the TPS and MC modeled doses were examined. Results: On average, 4D dose calculations in MC showed the maximum dose of an organ at risk (OAR) to be 10% greater than the TPS' three-dimensional dose calculation (collapsed cone [CC] convolution algorithm) predicted. MC's 4D dose calculations showed that 6 out of 24 OARs could exceed their specified dose limits, and calculated their maximum dose to be 4% higher on average (up to 13%) than the TPS' 4D dose calculations. Dose differences between MC and the TPS were greatest in the beam penumbra region. Conclusion: Modeling panning/tilting for DTT has been successfully modeled with MC and is a useful tool to QA respiratory-correlated 4D dose distributions. The dose differences between the TPS and MC calculations highlight the importance of using 4D MC to confirm the safety of OAR doses before DTT treatments.

In-vivo quality assurance of dynamic tumor tracking (DTT) for liver SABR using EPID images.

PURPOSE: To assess dynamic tumor tracking (DTT) target localization uncertainty for in-vivo marker-based stereotactic ablative radiotherapy (SABR) treatments of the liver using electronic-portal-imaging-device (EPID) images. The Planning Target Volume (PTV) margin contribution for DTT is estimated. METHODS: Phantom and patient EPID images were acquired during non-coplanar 3DCRT-DTT delivered on a Vero4DRT linac. A chain-code algorithm was applied to detect Multileaf Collimator (MLC)-defined radiation field edges. Gold-seed markers were detected using a connected neighbor algorithm. For each EPID image, the absolute differences between the measured center-of-mass (COM) of the markers relative to the aperture-center (Tracking Error, (ET )) was reported in pan, tilt, and 2D-vector directions at the isocenter-plane. PHANTOM STUDY: An acrylic cube phantom implanted with gold-seed markers was irradiated with non-coplanar 3DCRT-DTT beams and EPID images collected. Patient Study: Eight liver SABR patients were treated with non-coplanar 3DCRT-DTT beams. All patients had three to four implanted gold-markers. In-vivo EPID images were analyzed. RESULTS: Phantom Study: On the 125 EPID images collected, 100% of the markers were identified. The average ± SD of ET were 0.24 ± 0.21, 0.47 ± 0.38, and 0.58 ± 0.37 mm in pan, tilt and 2D directions, respectively. Patient Study: Of the 1430 EPID patient images acquired, 78% had detectable markers. Over all patients, the average ± SD of ET was 0.33 ± 0.41 mm in pan, 0.63 ± 0.75 mm in tilt and 0.77 ± 0.80 mm in 2D directions The random 2D-error, σ, for all patients was 0.79 mm and the systematic 2D-error, Σ, was 0.20 mm. Using the Van Herk margin formula 1.1 mm planning target margin can represent the marker based DTT uncertainty. CONCLUSIONS: Marker-based DTT uncertainty can be evaluated in-vivo on a field-by-field basis using EPID images. This information can contribute to PTV margin calculations for DTT.

Should organs at risk (OARs) be prioritized over target volume coverage in stereotactic ablative radiotherapy (SABR) for oligometastases? a secondary analysis of the population-based phase II SABR-5 trial.

BACKGROUND AND PURPOSE: Stereotactic ablative radiotherapy (SABR) for oligometastases may improve survival, however concerns about safety remain. To mitigate risk of toxicity, target coverage was sacrificed to prioritize organs-at-risk (OARs) during SABR planning in the population-based SABR-5 trial. This study evaluated the effect of this practice on dosimetry, local recurrence (LR), and progression-free survival (PFS). METHODS: This single-arm phase II trial included patients with up to 5 oligometastases between November 2016 and July 2020. Theprotocol-specified planning objective was to cover 95 % of the planning target volume (PTV) with 100 % of the prescribed dose, however PTV coverage was reduced as needed to meet OAR constraints. This trade-off was measured using the coverage compromise index (CCI), computed as minimum dose received by the hottest 99 % of the PTV (D99) divided by the prescription dose. Under-coverage was defined as CCI < 0.90. The potential association between CCI and outcomes was evaluated. RESULTS: 549 lesions from 381 patients were assessed. Mean CCI was 0.88 (95 % confidence interval [CI], 0.86-0.89), and 196 (36 %) lesions were under-covered. The highest mean CCI (0.95; 95 %CI, 0.93-0.97) was in non-spine bone lesions (n = 116), while the lowest mean CCI (0.71; 95 % CI, 0.69-0.73) was in spine lesions (n = 104). On multivariable analysis, under-coverage did not predict for worse LR (HR 0.48, p = 0.37) or PFS (HR 1.24, p = 0.38). Largest lesion diameter, colorectal and 'other' (non-prostate, breast, or lung) primary predicted for worse LR. Largest lesion diameter, synchronous tumor treatment, short disease free interval, state of oligoprogression, initiation or change in systemic treatment, and a high PTV Dmax were significantly associated with PFS. CONCLUSION: PTV under-coverage was not associated with worse LR or PFS in this large, population-based phase II trial. Combined with low toxicity rates, this study supports the practice of prioritizing OAR constraints during oligometastatic SABR planning.

Treatment With Stereotactic Ablative Radiotherapy for Up to 5 Oligometastases in Patients With Cancer: Primary Toxic Effect Results of the Nonrandomized Phase 2 SABR-5 Clinical Trial.

Importance: After the publication of the landmark SABR-COMET trial, concerns arose regarding high-grade toxic effects of treatment with stereotactic ablative body radiotherapy (SABR) for oligometastases. Objective: To document toxic effects of treatment with SABR in a large cohort from a population-based, provincial cancer program. Design, Setting, and Participants: From November 2016 to July 2020, 381 patients across all 6 cancer centers in British Columbia were treated in this single-arm, phase 2 trial of treatment with SABR for patients with oligometastatic or oligoprogressive disease. During this period, patients were only eligible to receive treatment with SABR in these settings in trials within British Columbia; therefore, this analysis is population based, with resultant minimal selection bias compared with previously published SABR series. Interventions: Stereotactic ablative body radiotherapy to up to 5 metastases. Main Outcomes and Measures: Rate of grade 2, 3, 4, and 5 toxic effects associated with SABR. Findings: Among 381 participants (122 women [32%]), the mean (SD; range) age was 68 (11.1; 30-97) years, and the median (range) follow-up was 25 (1-54) months. The most common histological findings were prostate cancer (123 [32%]), colorectal cancer (63 [17%]), breast cancer (42 [11%]), and lung cancer (33 [9%]). The number of SABR-treated sites were 1 (263 [69%]), 2 (82 [22%]), and 3 or more (36 [10%]). The most common sites of SABR were lung (188 [34%]), nonspine bone (136 [25%]), spine (85 [16%]), lymph nodes (78 [14%]), liver (29 [5%]), and adrenal (15 [3%]). Rates of grade 2, 3, 4, and 5 toxic effects associated with SABR (based on the highest-grade toxic effect per patient) were 14.2%; (95% CI, 10.7%-17.7%), 4.2% (95% CI, 2.2%-6.2%), 0%, and 0.3% (95% CI, 0%-0.8%), respectively. The cumulative incidence of grade 2 or higher toxic effects associated with SABR at year 2 by Kaplan-Meier analysis was 8%, and for grade 3 or higher, 4%. Conclusions and Relevance: This single-arm, phase 2 clinical trial found that the incidence of grade 3 or higher SABR toxic effects in this population-based study was less than 5%. Furthermore, the rates of grade 2 or higher toxic effects (18.6%) were lower than previously published for SABR-COMET (29%). These results suggest that SABR treatment for oligometastases has acceptable rates of toxic effects and potentially support further enrollment in randomized phase 3 clinical trials. Trial Registration: ClinicalTrials.gov Identifier: NCT02933242.

Four-dimensional dose calculations for dynamic tumour tracking with a gimbal-mounted linear accelerator.

PURPOSE: In this study we present a novel method for re-calculating a treatment plan on different respiratory phases by accurately modeling the panning and tilting beam motion during DTT (the "rotation method"). This method is used to re-calculate the dose distribution of a plan on multiple breathing phases to accurately assess the dosimetry. METHODS: sIMRT plans were optimized on a breath hold computed tomography (CT) image taken at exhale (BHexhale ) for 10 previous liver stereotactic ablative radiotherapy patients. Our method was used to re-calculate the plan on the inhale (0%) and exhale (50%) phases of the four-dimensional CT (4DCT) image set. The dose distributions were deformed to the BHexhale CT and summed together with proper weighting calculated from the patient's breathing trace. Subsequently, the plan was re-calculated on all ten phases using our method and the dose distributions were deformed to the BHexhale CT and accumulated together. The maximum dose for certain organs at risk (OARs) was compared between calculating on two phases and all ten phases. RESULTS: In total, 26 OARs were examined from 10 patients. When the dose was calculated on the inhale and exhale phases six OARs exceeded their dose limit, and when all 10 phases were used five OARs exceeded their limit. CONCLUSION: Dynamic tumor tracking plans optimized for a single respiratory phase leave an OAR vulnerable to exceeding its dose constraint during other respiratory phases. The rotation method accurately models the beam's geometry. Using deformable image registration to accumulate dose from all 10 breathing phases provides the most accurate results, however it is a time consuming procedure. Accumulating the dose from two extreme breathing phases (exhale and inhale) and weighting them properly provides accurate results while requiring less time. This approach should be used to confirm the safety of a DTT treatment plan prior to 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.

Real-time interactive planning for radiotherapy of head and neck cancer with volumetric modulated arc therapy.

BACKGROUND AND PURPOSE: Planning complex radiotherapy treatments can be inefficient, with large variation in plan quality. In this study we evaluated plan quality and planning efficiency using real-time interactive planning (RTIP) for head and neck (HN) volumetric modulated arc therapy (VMAT). MATERIALS AND METHODS: RTIP allows manipulation of dose volume histograms (DVHs) in real-time to assess achievable planning target volume (PTV) coverage and organ at risk (OAR) sparing. For 20 HN patients previously treated with VMAT, RTIP was used to minimize OAR dose while maintaining PTV coverage. RTIP DVHs were used to guide VMAT optimization. Dosimetric differences between RTIP-assisted plans and original clinical plans were assessed. Five blinded radiation oncologists indicated their preference for each PTV, OAR and overall plan. To assess efficiency, ten patients were planned de novo by experienced and novice planners and a RTIP user. RESULTS: The average planning time with RTIP was <20 min, and most plans required only one optimization. All 20 RTIP plans were preferred by a majority of oncologists due to improvements in OAR sparing. The average maximum dose to the spinal cord was reduced by 10.5 Gy (from 49.5 to 39.0 Gy), and the average mean doses for the oral cavity, laryngopharynx, contralateral parotid and submandibular glands were reduced by 3.5 Gy (39.1-35.7 Gy), 6.8 Gy (42.5-35.7 Gy), 1.7 Gy (17.0-15.3 Gy) and 3.3 Gy (22.9-19.5 Gy), respectively. CONCLUSIONS: Incorporating RTIP into clinical workflows may increase both planning efficiency and OAR sparing.

Population-based phase II trial of stereotactic ablative radiotherapy (SABR) for up to 5 oligometastases: SABR-5.

BACKGROUND: Oligometastases refer to a state of disease where cancer has spread beyond the primary site, but is not yet widely metastatic, often defined as 1-3 or 1-5 metastases in number. Stereotactic ablative radiotherapy (SABR) is an emerging radiotherapy technique to treat oligometastases that require further prospective population-based toxicity estimates. METHODS: This is a non-randomized phase II trial where all participants will receive experimental SABR treatment to all sites of newly diagnosed or progressing oligometastatic disease. We will accrue 200 patients to assess toxicity associated with this experimental treatment. The study was powered to give a 95% confidence on the risk of late grade 4 toxicity, anticipating a < 5% rate of grade 4 toxicity. DISCUSSION: SABR treatment of oligometastases is occurring off-trial at a high rate, without sufficient evidence of its efficacy or toxicity. This trial will provide necessary toxicity data in a population-based cohort, using standardized doses and organ at risk constraints, while we await data on efficacy from randomized phase III trials. TRIAL REGISTRATION: Registered through clinicaltrials.gov NCT02933242 on October 14, 2016 prospectively before patient accrual.

Treatment planning for spinal radiosurgery : A competitive multiplatform benchmark challenge.

PURPOSE: To investigate the quality of treatment plans of spinal radiosurgery derived from different planning and delivery systems. The comparisons include robotic delivery and intensity modulated arc therapy (IMAT) approaches. Multiple centers with equal systems were used to reduce a bias based on individual's planning abilities. The study used a series of three complex spine lesions to maximize the difference in plan quality among the various approaches. METHODS: Internationally recognized experts in the field of treatment planning and spinal radiosurgery from 12 centers with various treatment planning systems participated. For a complex spinal lesion, the results were compared against a previously published benchmark plan derived for CyberKnife radiosurgery (CKRS) using circular cones only. For two additional cases, one with multiple small lesions infiltrating three vertebrae and a single vertebra lesion treated with integrated boost, the results were compared against a benchmark plan generated using a best practice guideline for CKRS. All plans were rated based on a previously established ranking system. RESULTS: All 12 centers could reach equality (n = 4) or outperform (n = 8) the benchmark plan. For the multiple lesions and the single vertebra lesion plan only 5 and 3 of the 12 centers, respectively, reached equality or outperformed the best practice benchmark plan. However, the absolute differences in target and critical structure dosimetry were small and strongly planner-dependent rather than system-dependent. Overall, gantry-based IMAT with simple planning techniques (two coplanar arcs) produced faster treatments and significantly outperformed static gantry intensity modulated radiation therapy (IMRT) and multileaf collimator (MLC) or non-MLC CKRS treatment plan quality regardless of the system (mean rank out of 4 was 1.2 vs. 3.1, p = 0.002). CONCLUSIONS: High plan quality for complex spinal radiosurgery was achieved among all systems and all participating centers in this planning challenge. This study concludes that simple IMAT techniques can generate significantly better plan quality compared to previous established CKRS benchmarks.

Stereotactic ablative radiation therapy with volumetric modulated arc therapy in flattening filter-free mode for low-, intermediate-, and high-risk prostate cancer patients: Are 2 arcs better than 1?

PURPOSE: In preparation for a phase 2 clinical trial of prostate cancer treatment with stereotactic ablative radiation therapy (SABR), the quality of volumetric modulated arc therapy (VMAT) plans was investigated to determine the preferred delivery technique. METHODS AND MATERIALS: VMAT treatment plans were generated with version 11 of the Eclipse treatment planning system for a Varian TrueBeam linear accelerator operating with 10-MV x-rays in flattening filter-free mode (FFFM). Plans were designed with pelvic computed tomography scans from 10 patients with prostate cancer with an assumption of low-, intermediate-, and high-risk target volumes. The prescription dose was set to 36.25 Gy to be delivered in 5 fractions of 7.25 Gy each. Dose-volume constraints imposed during optimization to protect organs at risk (OARs) were based on data from published studies and current SABR clinical trials. One-arc and 2-arc plans were compared in terms of dose homogeneity and conformity to the target volumes, dose to the OAR and to the surrounding normal tissue, the total number of monitor units required, and overall treatment time. RESULTS: Clinically acceptable VMAT-FFFM-based SABR regimens were produced for all low-, intermediate-, and high-risk target volumes using both 1-arc and 2-arc deliveries. No significant dosimetric differences in terms of homogeneity, conformity, or dose to the OAR were observed between 1-arc and 2-arc deliveries, but treatment times were twice as long for 2-arc deliveries and consistently required more monitor units. CONCLUSIONS: Given the similar dosimetry between 1- and 2-arc plans, single-arc delivery of VMAT-FFFM may be preferable to minimize the risk of intrafraction motion and reduce leakage and scatter radiation to the patient.

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.

Integration of on-line imaging, plan adaptation and radiation delivery: proof of concept using digital tomosynthesis.

The main objective of this manuscript is to propose a new approach to on-line adaptive radiation therapy (ART) in which daily image acquisition, plan adaptation and radiation delivery are integrated together and performed concurrently. A method is described in which on-line ART is performed based on intra-fractional digital tomosynthesis (DTS) images. Intra-fractional DTS images were reconstructed as the gantry rotated between treatment positions. An edge detection algorithm was used to automatically segment the DTS images as the gantry arrived at each treatment position. At each treatment position, radiation was delivered based on the treatment plan re-optimized for the most recent DTS image contours. To investigate the feasibility of this method, a model representing a typical prostate, bladder and rectum was used. To simulate prostate deformations, three clinically relevant, non-rigid deformations (small, medium and large) were modeled by systematically deforming the original anatomy. Using our approach to on-line ART, the original treatment plan was successfully adapted to arrive at a clinically acceptable plan for all three non-rigid deformations. In conclusion, we have proposed a new approach to on-line ART in which plan adaptation is performed based on intra-fractional DTS images. The study findings indicate that this approach can be used to re-optimize the original treatment plan to account for non-rigid anatomical deformations. The advantages of this approach are 1) image acquisition and radiation delivery are integrated in a single gantry rotation around the patient, reducing the treatment time, and 2) intra-fractional DTS images can be used to detect and correct for patient motion prior to the delivery of each beam (intra-fractional patient motion).

Direct aperture optimization for online adaptive radiation therapy.

This paper is the first investigation of using direct aperture optimization (DAO) for online adaptive radiation therapy (ART). A geometrical model representing the anatomy of a typical prostate case was created. To simulate interfractional deformations, four different anatomical deformations were created by systematically deforming the original anatomy by various amounts (0.25, 0.50, 0.75, and 1.00 cm). We describe a series of techniques where the original treatment plan was adapted in order to correct for the deterioration of dose distribution quality caused by the anatomical deformations. We found that the average time needed to adapt the original plan to arrive at a clinically acceptable plan is roughly half of the time needed for a complete plan regeneration, for all four anatomical deformations. Furthermore, through modification of the DAO algorithm the optimization search space was reduced and the plan adaptation was significantly accelerated. For the first anatomical deformation (0.25 cm), the plan adaptation was six times more efficient than the complete plan regeneration. For the 0.50 and 0.75 cm deformations, the optimization efficiency was increased by a factor of roughly 3 compared to the complete plan regeneration. However, for the anatomical deformation of 1.00 cm, the reduction of the optimization search space during plan adaptation did not result in any efficiency improvement over the original (nonmodified) plan adaptation. The anatomical deformation of 1.00 cm demonstrates the limit of this approach. We propose an innovative approach to online ART in which the plan adaptation and radiation delivery are merged together and performed concurrently-adaptive radiation delivery (ARD). A fundamental advantage of ARD is the fact that radiation delivery can start almost immediately after image acquisition and evaluation. Most of the original plan adaptation is done during the radiation delivery, so the time spent adapting the original plan does not increase the overall time the patient has to spend on the treatment couch. As a consequence, the effective time allotted for plan adaptation is drastically reduced. For the 0.25, 0.5, and 0.75 cm anatomical deformations, the treatment time was increased by only 2, 4, and 6 s, respectively, as compared to no plan adaptation. For the anatomical deformation of 1.0 cm the time increase was substantially larger. The anatomical deformation of 1.0 cm represents an extreme case, which is rarely observed for the prostate, and again demonstrates the limit of this approach. ARD shows great potential for an online adaptive method with minimal extension of treatment time.

Geometric parameter analysis to predetermine optimal radiosurgery technique for the treatment of arteriovenous malformation.

PURPOSE: To develop a method of predicting the values of dose distribution parameters of different radiosurgery techniques for treatment of arteriovenous malformation (AVM) based on internal geometric parameters. METHODS AND MATERIALS: For each of 18 previously treated AVM patients, four treatment plans were created: circular collimator arcs, dynamic conformal arcs, fixed conformal fields, and intensity-modulated radiosurgery. An algorithm was developed to characterize the target and critical structure shape complexity and the position of the critical structures with respect to the target. Multiple regression was employed to establish the correlation between the internal geometric parameters and the dose distribution for different treatment techniques. The results from the model were applied to predict the dosimetric outcomes of different radiosurgery techniques and select the optimal radiosurgery technique for a number of AVM patients. RESULTS: Several internal geometric parameters showing statistically significant correlation (p < 0.05) with the treatment planning results for each technique were identified. The target volume and the average minimum distance between the target and the critical structures were the most effective predictors for normal tissue dose distribution. The structure overlap volume with the target and the mean distance between the target and the critical structure were the most effective predictors for critical structure dose distribution. The predicted values of dose distribution parameters of different radiosurgery techniques were in close agreement with the original data. CONCLUSIONS: A statistical model has been described that successfully predicts the values of dose distribution parameters of different radiosurgery techniques and may be used to predetermine the optimal technique on a patient-to-patient basis.