Clinical applicability of Linac-integrated CBCT based NIPAM 3D dosimetry: a dual-institutional investigation.

OBJECTIVE: To develop and benchmark a novel 3D dose verification technique consisting of polymer-gel-dosimeter (PGD) with cone-beam-CT (CBCT) readout through a two-institution study. The technique has potential for wide and robust applicability through reliance on CBCT readout. Approach: Three treatment plans (3-Field, TG119-C-shape spine, 4-target SRS) were created by two independent institutions (Institution A and B). A Varian Truebeam LINAC was used to deliver the plans to NIPAM polymer gel dosimeters produced at both institutions using an identical approach. For readout, a slow CBCT scan mode was used to acquire pre- and post-irradiation images of the gel (1 mm slice thickness). Independent gel analysis tools were used to process the PGD images (A: VistaAce software, B: in-house MATLAB code). Comparing planned and measured doses, the analysis involved a combination of 1D line profiles, 2D contour plots, and 3D global gamma maps (criteria ranging between 2%1mm and 5%2mm, with a 10% dose threshold). Main Results: For all gamma criteria tested, the 3D gamma pass rates were all above 90% for 3-field and 88% for the SRS plan. For the C-shape spine plan, we benchmarked our 2% 2mm result against previously published work using film analysis (93.4%). For 2%2mm, 99.4% (Institution A data), and 89.7% (Institution B data) were obtained based on VistaAce software analysis, 83.7% (Institution A data), and 82.9% (Institution B data) based on MATLAB. Significance: The benchmark data demonstrate that when two institutions follow the same rigorous procedures gamma passing rates up to 99%, for 2%2mm criteria can be achieved for substantively different treatment plans. The use of different software and calibration techniques may have contributed to the variation in the 3D gamma results. By sharing the data across institutions, we observe the gamma passing rate is more consistent within each pipeline, indicating the need for standardized analysis methods.

A deep learning-based framework (Co-ReTr) for auto-segmentation of non-small cell-lung cancer in computed tomography images.

PURPOSE: Deep learning-based auto-segmentation algorithms can improve clinical workflow by defining accurate regions of interest while reducing manual labor. Over the past decade, convolutional neural networks (CNNs) have become prominent in medical image segmentation applications. However, CNNs have limitations in learning long-range spatial dependencies due to the locality of the convolutional layers. Transformers were introduced to address this challenge. In transformers with self-attention mechanism, even the first layer of information processing makes connections between distant image locations. Our paper presents a novel framework that bridges these two unique techniques, CNNs and transformers, to segment the gross tumor volume (GTV) accurately and efficiently in computed tomography (CT) images of non-small cell-lung cancer (NSCLC) patients. METHODS: Under this framework, input of multiple resolution images was used with multi-depth backbones to retain the benefits of high-resolution and low-resolution images in the deep learning architecture. Furthermore, a deformable transformer was utilized to learn the long-range dependency on the extracted features. To reduce computational complexity and to efficiently process multi-scale, multi-depth, high-resolution 3D images, this transformer pays attention to small key positions, which were identified by a self-attention mechanism. We evaluated the performance of the proposed framework on a NSCLC dataset which contains 563 training images and 113 test images. Our novel deep learning algorithm was benchmarked against five other similar deep learning models. RESULTS: The experimental results indicate that our proposed framework outperforms other CNN-based, transformer-based, and hybrid methods in terms of Dice score (0.92) and Hausdorff Distance (1.33). Therefore, our proposed model could potentially improve the efficiency of auto-segmentation of early-stage NSCLC during the clinical workflow. This type of framework may potentially facilitate online adaptive radiotherapy, where an efficient auto-segmentation workflow is required. CONCLUSIONS: Our deep learning framework, based on CNN and transformer, performs auto-segmentation efficiently and could potentially assist clinical radiotherapy workflow.

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.

Radiomic analysis for early differentiation of lung cancer recurrence from fibrosis in patients treated with lung stereotactic ablative radiotherapy.

Objective. The development of radiation-induced fibrosis after stereotactic ablative radiotherapy (SABR) can obscure follow-up images and delay detection of a local recurrence in early-stage lung cancer patients. The objective of this study was to develop a radiomics model for computer-assisted detection of local recurrence and fibrosis for an earlier timepoint (<1 year) after the SABR treatment.Approach. This retrospective clinical study included CT images (n= 107) of 66 patients treated with SABR. A z-score normalization technique was used for radiomic feature standardization across scanner protocols. The training set for the radiomics model consisted of CT images (66 patients; 22 recurrences and 44 fibrosis) obtained at 24 months (median) follow-up. The test set included CT-images of 41 patients acquired at 5-12 months follow-up. Combinations of four widely used machine learning techniques (support vector machines, gradient boosting, random forests (RF), and logistic regression) and feature selection methods (Relief feature scoring, maximum relevance minimum redundancy, mutual information maximization, forward feature selection, and LASSO) were investigated. Pyradiomics was used to extract 106 radiomic features from the CT-images for feature selection and classification.Main results. An RF + LASSO model scored the highest in terms of AUC (0.87) and obtained a sensitivity of 75% and a specificity of 88% in identifying a local recurrence in the test set. In the training set, 86% accuracy was achieved using five-fold cross-validation. Delong's test indicated that AUC achieved by the RF+LASSO is significantly better than 11 other machine learning models presented here. The top three radiomic features: interquartile range (first order), Cluster Prominence (GLCM), and Autocorrelation (GLCM), were revealed as differentiating a recurrence from fibrosis with this model.Significance. The radiomics model selected, out of multiple machine learning and feature selection algorithms, was able to differentiate a recurrence from fibrosis in earlier follow-up CT-images with a high specificity rate and satisfactory sensitivity performance.

Measurement of neutron yield for a medical linear accelerator below 10 MV.

BACKGROUND: The recent trend toward 10 MV for volumetric radiotherapy treatment such as volumetric modulated arc therapy (VMAT), stereotactic radiosurgery (SRS), and stereotactic ablative body radiotherapy (SABR) introduces photoneutron production, with implications for non-therapeutic patient dose and additional shielding requirements for treatment room design. The sharply nonlinear drop-off in photoneutron production below 10 MV to negligible at 6 MV has scarcely been characterized quantitatively, yet can elucidate important practical insights. PURPOSE: To measure photoneutron yields in a medical linac at 8 MV, which may strike a reasonable balance between usefully increased beam penetration and dose rate as compared to 6 MV while reducing photoneutron production which is present at 10 MV. METHODS: A Varian iX linear accelerator undergoing decommissioning at our clinic was made to operate over a range of photon energies between 6 and 15 MV by calibrating the bending magnet and adjusting other beam generation parameters. Neutron dose within the treatment room was measured using an Anderson-Braun type detector over a continuum of intermediate energies. RESULTS: The photoneutron production for energies below 10 MV was measured, adding to data that is otherwise scarce in the literature. Our results are consistent with previously published results for neutron yield. We found that the photoneutron production at 8 MV was about 1/10 of the value at 10 MV, and about 10 times higher than detector background at 6 MV. CONCLUSIONS: Photoneutron production drops off below 10 MV, but is still present at 8 MV. An 8 MV beam is more penetrating than a 6 MV beam, and may offer a suitable tradeoff for modern radiotherapy techniques such as VMAT, SRS, and SABR. Further studies are needed to better understand the impact on treatment plan quality between 8 and 10 MV beams considering the benefits to facility requirements and non-therapeutic patient dose.

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.

Radiomics-guided radiation therapy: opportunities and challenges.

Radiomics is an advanced image-processing framework, which extracts image features and considers them as biomarkers towards personalized medicine. Applications include disease detection, diagnosis, prognosis, and therapy response assessment/prediction. As radiation therapy aims for further individualized treatments, radiomics could play a critical role in various steps before, during and after treatment. Elucidation of the concept of radiomics-guided radiation therapy (RGRT) is the aim of this review, attempting to highlight opportunities and challenges underlying the use of radiomics to guide clinicians and physicists towards more effective radiation treatments. This work identifies the value of RGRT in various steps of radiotherapy from patient selection to follow-up, and subsequently provides recommendations to improve future radiotherapy using quantitative imaging features.

Assessment of intrafraction motion for spine and non-spine bone metastases treated with image-guided stereotactic body radiotherapy without 6 degrees-of-freedom couch correction.

Stereotactic body radiotherapy (SBRT) planning target volume (PTV) margins are influenced by multiple factors. Data is limited on intrafraction motion in bone SBRT, particularly non-spine lesions. We analyzed intrafraction motion in bone SBRT patients treated on a standard treatment couch without 6 degrees-of-freedom (6-DOF) correction. Extracranial bone SBRT patients were included. Patients were treated using two volumetric-modulated arcs and targets were localized using daily cone-beam computed tomography (CBCT) prior to each arc. Alignments between the first and second CBCT images yielded intrafraction positional shift values used to compute translational 3-dimensional vector shifts. 125 fractions from 43 patients were reviewed. Median vector shift for all SABR fractions was 0.7 mm (range 0-6.6 mm); spine 0.7 mm (range:0-2.3 mm) and non-spine 0.9 mm (range:0-6.6 mm). Of the 125 fractions, 95% had IFM vectors within the prescribed PTV margin. Intrafraction motion is small for bone SBRT patients treated on a standard couch without 6-DOF correction capabilities. Intrafraction motion was slightly larger for non-spine sites and may require treatment with larger PTV margins than spine cases.

Implementation of Single-Fraction Lung Stereotactic Ablative Radiotherapy in a Multicenter Provincial Cancer Program During the COVID-19 Pandemic.

Background During the novel coronavirus disease 2019 (COVID-19) pandemic, cancer centers considered shortened courses of radiotherapy to minimize the risk of infectious exposure of patients and staff members. Amidst a pandemic, the process of implementing new treatment approaches can be particularly challenging in larger institutions with multiple treatment centers. We describe the implementation of single-fraction (SF) lung stereotactic ablative radiotherapy (SABR) in a multicenter provincial cancer program. Materials and Methods British Columbia, Canada has a provincial cancer program with six geographically distributed radiotherapy centers serving a population of 5.1 million, over 944,735 square kilometers. In March 2020, provincial mitigation strategies were developed in case of reduced access to radiotherapy due to the COVID-19 pandemic. SF lung SABR was identified by the provincial lung radiation oncology group as a mitigation measure supported by high-quality randomized evidence that could provide comparable outcomes and toxicity to existing fractionated SABR protocols. A working group consisting of radiation oncologists and medical physicists reviewed the medical literature and drafted consensus guidelines that were reviewed by a group of center representatives as a component of provincial lung radiotherapy mitigation strategic planning. Individual centers were encouraged to implement SF lung SABR as their resources and staffing would allow. Centers were then surveyed about barriers to implementation. Results On March 24, 2020, a working group was created and consensus guidelines for SF lung SABR were drafted. The final version was approved and distributed by the working group on March 26, 2020. The provincial lung radiotherapy mitigation strategy group adopted the guidelines for implementation on April 1, 2020. Implementation was completed at the first center on April 27, 2020. Barriers to implementation were identified at five of six centers. Two centers in regions with disproportionately high COVID-19 cases described inadequate staffing as a barrier to implementation. One center encountered delays due to pre-scheduled commissioning of new treatment techniques. Three centers cited competing priorities as reasons for delay. As of May 2021, two centers had active SF lung SABR programs in place, three centers were in the process of implementation, and one center had no immediate plans for implementation due to ongoing resource issues. Conclusion SF lung SABR was adopted by a provincial cancer program within weeks of conception through rapid communication during the development of COVID-19 pandemic mitigation strategies for radiotherapy. Although consensus guidelines were written and approved in an expedited timeframe, the completion of implementation by individual centers was variable due to differences in resource allocation and staffing among the centers. Strong organizational structures and early identification of potential barriers may improve the efficiency of implementing new treatment initiatives in large multicenter radiotherapy programs.

Acute Radiation-Induced Hematopoietic Depletion Does Not Alter the Onset or Severity of Pneumonitis in Mice.

Survival from partial-body irradiation (PBI) may be limited by the development of the late lung injury response of pneumonitis. Herein we investigated the hypothesis that acute hematopoietic depletion alters the onset and severity of lung disease in a mouse model. To establish depletion, C3H/HeJ mice received 8 Gy PBI with shielding of only the tibiae, ankles and feet. One week after irradiation, blood lymphocyte and neutrophil counts were each significantly reduced (P < 0.04) in these mice compared to levels in untreated controls or in mice receiving 16 Gy to the whole thorax only. All 8 Gy PBI mice survived to the experimental end point of 16 weeks postirradiation. To determine whether the hematopoietic depletion affects lung disease, groups of mice received 8 Gy PBI plus 8 Gy whole-thorax irradiation (total lung dose of 16 Gy) or 16 Gy whole-thorax irradiation only. The weight loss, survival to onset of respiratory distress (P = 0.17) and pneumonitis score (P = 0.96) of mice that received 8 Gy PBI plus 8 Gy whole-thorax irradiation were not significantly different from those of mice receiving 16 Gy whole-thorax irradiation only. Mice in respiratory distress from PBI plus whole-thorax irradiation had significantly reduced (P = 0.02) blood monocyte counts compared to levels in distressed, whole-thorax irradiated mice, and symptomatic pneumonitis was associated with increased blood neutrophil counts (P = 0.04) relative to measures from irradiated, non-distressed mice. In conclusion, survivable acute hematopoietic depletion by partial-body irradiation did not alter the onset or severity of lethal pneumonitis in the C3H/HeJ mouse model.

Assessment of the Sun Nuclear ArcCHECK to detect errors in 6MV FFF VMAT delivery of brain SABR using ROC analysis.

Institutions use a range of different detector systems for patient-specific quality assurance (QA) measurements conducted to assure that the dose delivered by a patient's radiotherapy treatment plan matches the calculated dose distribution. However, the ability of different detectors to detect errors from different sources is often unreported. This study contains a systematic evaluation of Sun Nuclear's ArcCHECK in terms of the detectability of potential machine-related treatment errors. The five investigated sources of error were multileaf collimator (MLC) leaf positions, gantry angle, collimator angle, jaw positions, and dose output. The study encompassed the clinical treatment plans of 29 brain cancer patients who received stereotactic ablative radiotherapy (SABR). Six error magnitudes were investigated per source of error. In addition, the Eclipse AAA beam model dosimetric leaf gap (DLG) parameter was varied with four error magnitudes. Error detectability was determined based on the area under the receiver operating characteristic (ROC) curve (AUC). Detectability of DLG errors was good or excellent (AUC >0.8) at an error magnitude of at least ±0.4 mm, while MLC leaf position and gantry angle errors reached good or excellent detectability at error magnitudes of at least 1.0 mm and 0.6°, respectively. Ideal thresholds, that is, gamma passing rates, to maximize sensitivity and specificity ranged from 79.1% to 98.7%. The detectability of collimator angle, jaw position, and dose output errors was poor for all investigated error magnitudes, with an AUC between 0.5 and 0.6. The ArcCHECK device's ability to detect errors from treatment machine-related sources was evaluated, and ideal gamma passing rate thresholds were determined for each source of error. The ArcCHECK was able to detect errors in DLG value, MLC leaf positions, and gantry angle. The ArcCHECK was unable to detect the studied errors in collimator angle, jaw positions, and dose output.

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.

Positional Accuracy of Treating Multiple Versus Single Vertebral Metastases With Stereotactic Body Radiotherapy.

The aim of this study is to determine whether stereotactic body radiotherapy for multiple vertebral metastases treated with a single isocenter results in greater intrafraction errors than stereotactic body radiotherapy for single vertebral metastases and to determine whether the currently used spinal cord planning organ at risk volume and planning target volume margins are appropriate. Intrafraction errors were assessed for 65 stereotactic body radiotherapy treatments for vertebral metastases. Cone beam computed tomography images were acquired before, during, and after treatment for each fraction. Residual translational and rotational errors in patient positioning were recorded and planning organ at risk volume and planning target volume margins were calculated in each direction using this information. The mean translational residual errors were smaller for single (0.4 (0.4) mm) than for multiple vertebral metastases (0.5 (0.7) mm; P = .0019). The mean rotational residual errors were similar for single (0.3° (0.3°) and multiple vertebral metastases (0.3° (0.3°); P = .862). The maximum calculated planning organ at risk volume margin in any direction was 0.83 mm for single and 1.22 for multiple vertebral metastases. The maximum calculated planning target volume margin in any direction was 1.4 mm for single and 1.9 mm for multiple vertebral metastases. Intrafraction errors were small for both single and multiple vertebral metastases, indicating that our strategy for patient immobilization and repositioning is robust. Calculated planning organ at risk volume and planning target volume margins were smaller than our clinically employed margins, indicating that our clinical margins are appropriate.

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.

Spine stereotactic body radiotherapy utilizing cone-beam CT image-guidance with a robotic couch: intrafraction motion analysis accounting for all six degrees of freedom.

PURPOSE: To evaluate the residual setup error and intrafraction motion following kilovoltage cone-beam CT (CBCT) image guidance, for immobilized spine stereotactic body radiotherapy (SBRT) patients, with positioning corrected for in all six degrees of freedom. METHODS AND MATERIALS: Analysis is based on 42 consecutive patients (48 thoracic and/or lumbar metastases) treated with a total of 106 fractions and 307 image registrations. Following initial setup, a CBCT was acquired for patient alignment and a pretreatment CBCT taken to verify shifts and determine the residual setup error, followed by a midtreatment and posttreatment CBCT image. For 13 single-fraction SBRT patients, two midtreatment CBCT images were obtained. Initially, a 1.5-mm and 1° tolerance was used to reposition the patient following couch shifts which was subsequently reduced to 1 mm and 1° degree after the first 10 patients. RESULTS: Small positioning errors after the initial CBCT setup were observed, with 90% occurring within 1 mm and 97% within 1°. In analyzing the impact of the time interval for verification imaging (10 ± 3 min) and subsequent image acquisitions (17 ± 4 min), the residual setup error was not significantly different (p > 0.05). A significant difference (p = 0.04) in the average three-dimensional intrafraction positional deviations favoring a more strict tolerance in translation (1 mm vs. 1.5 mm) was observed. The absolute intrafraction motion averaged over all patients and all directions along x, y, and z axis (± SD) were 0.7 ± 0.5 mm and 0.5 ± 0.4 mm for the 1.5 mm and 1 mm tolerance, respectively. Based on a 1-mm and 1° correction threshold, the target was localized to within 1.2 mm and 0.9° with 95% confidence. CONCLUSION: Near-rigid body immobilization, intrafraction CBCT imaging approximately every 15-20 min, and strict repositioning thresholds in six degrees of freedom yields minimal intrafraction motion allowing for safe spine SBRT delivery.

Stereotactic body radiotherapy is an effective treatment in reirradiating spinal metastases: current status and practical considerations for safe practice.

Spinal metastases are a relatively common manifestation in advanced cancer patients. Low-dose conventional radiotherapy has long been the mainstay of treatment under the assumption that patients have a limited life expectancy in the order of 3-6 months. However, with new developments in systemic therapies, patients are surviving longer than expected. As the spinal retreatment rates, secondary to conventional radiation, can approach 20-50%, retreatments are likely to be more frequent. Rather than a second course of even lower-dose conventional radiation, spine stereotactic body radiotherapy (SBRT) has been developed predominantly to overcome the limitations of conventional reirradiation. Spine SBRT permits a second course of high-dose radiation aimed at local tumor control while sparing the spinal cord, and other surrounding normal tissues, of a toxic dose. The focus of this review is to provide an overview of reirradiation spine SBRT, and address key issues surrounding safe and effective practice.

Technique for stereotactic body radiotherapy for spinal metastases.

Stereotactic body radiotherapy (SBRT) is an emerging technique for spinal tumours that is a natural succession to brain radiosurgery. The spine is an ideal site for SBRT due to its relative immobility and the potential clinical benefits of high dose delivery, particularly to optimise local control and avoid disease progression that can result in spinal cord compression. However, the proximity of the tumour to the spinal cord, with the potential for radiation myelopathy if the dose is delivered inaccurately or if the spinal cord dose limit is set too high, demands technical accuracy with radiation myelopathy a feared complication. Spine SBRT has been delivered with either a robotic-based linac system such as the Cyberknife, or with linac-based systems equipped with a multileaf collimator and image guidance system. Regardless of the technology, spine SBRT demands sophisticated treatment planning and delivery. This case-based technical review outlines the SBRT apparatus, planning and treatment delivery in use at the University of Toronto, Toronto, Canada.

Apparatus-dependent dosimetric differences in spine stereotactic body radiotherapy.

The purpose of this investigation was to study apparatus-dependent dose distribution differences specific to spine stereotactic body radiotherapy (SBRT) treatment planning. This multi-institutional study was performed evaluating an image-guided robotic radiosurgery system (CK), intensity modulated protons (IMP), multileaf collimator (MLC) fixed-field IMRT with 5 mm (11 field), 4 mm (9 field), and 2.5 mm (8- and 9-field) leaf widths and intensity modulated volumetric arc therapy (IMVAT) with a 2.5 mm MLC. Treatment plans were systematically developed for targets consisting of one, two and three consecutive thoracic vertebral bodies (VBs) with the esophagus and spinal cord contoured as the organs at risk. It was found that all modalities achieved acceptable treatment planning constraints. However, following normalization fixed field IMRT with a 2.5 mm MLC, IMVAT and IMP systems yielded the smallest ratio of maximum dose divided by the prescription dose (MD/PD) for one-, two- and three-VB PTVs (ranging from 1.1-1.16). The 2.5 mm MLC 9-field IMRT, IMVAT and CK plans resulted in the least dose to 0.1 cc volumes of spinal cord and esophagus. CK plans had the greatest degree of target dose inhomogeneity. As the level of complexity increased with an increasing number of vertebral bodies, distinct apparatus features such as the use of a high number of beams and a finer leaf size MLC were favored. Our study quantified apparatus-dependent dose-distribution differences specific to spine SBRT given strict, but realistic, constraints and highlights the need to benchmark physical dose distributions for multi-institutional clinical trials.