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 dosimetry (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 (Institutions A and B). A Varian Truebeam linear accelerator 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%1 mm and 5%2 mm, 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% 2 mm result against previously published work using film analysis (93.4%). For 2%2 mm, 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%2 mm 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.

Independent Monte Carlo dose calculation identifies single isocenter multi-target radiosurgery targets most likely to fail pre-treatment measurement.

PURPOSE: For individual targets of single isocenter multi-target (SIMT) Stereotactic radiosurgery (SRS), we assess dose difference between the treatment planning system (TPS) and independent Monte Carlo (MC), and demonstrate persistence into the pre-treatment Quality Assurance (QA) measurement. METHODS: Treatment plans from 31 SIMT SRS patients were recalculated in a series of scenarios designed to investigate sources of discrepancy between TPS and independent MC. Targets with > 5% discrepancy in DMean[Gy] after progressing through all scenarios were measured with SRS MapCHECK. A matched pair analysis was performed comparing SRS MapCHECK results for these targets with matched targets having similar characteristics (volume & distance from isocenter) but no such MC dose discrepancy. RESULTS: Of 217 targets analyzed, individual target mean dose (DMean[Gy]) fell outside a 5% threshold for 28 and 24 targets before and after removing tissue heterogeneity effects, respectively, while only 5 exceeded the threshold after removing effect of patient geometry (via calculation on StereoPHAN geometry). Significant factors affecting agreement between the TPS and MC included target distance from isocenter (0.83% decrease in DMean[Gy] per 2 cm), volume (0.15% increase per cc), and degree of plan modulation (0.37% increase per 0.01 increase in modulation complexity score). SRS MapCHECK measurement had better agreement with MC than with TPS (2%/1 mm / 10% threshold gamma pass rate (GPR) = 99.4 ± 1.9% vs. 93.1 ± 13.9%, respectively). In the matched pair analysis, targets exceeding 5% for MC versus TPS also had larger discrepancies between TPS and measurement with no GPR (2%/1 mm / 10% threshold) exceeding 90% (71.5% ± 16.1%); whereas GPR was high for matched targets with no such MC versus TPS difference (96.5% ± 3.3%, p = 0.01). CONCLUSIONS: Independent MC complements pre-treatment QA measurement for SIMT SRS by identifying problematic individual targets prior to pre-treatment measurement, thus enabling plan modifications earlier in the planning process and guiding selection of targets for pre-treatment QA measurement.

Effects of Ataxia-Telangiectasia Mutated Variants on Radionecrosis and Local Control After Stereotactic Radiation Surgery for Non-Small Cell Lung Cancer Brain Metastases.

Purpose: Genetic variants affecting the radiation response protein ataxia-telangiectasia mutated (ATM) have been associated with increased adverse effects of radiation but also with improved local control after conventional radiation therapy. However, it is unknown whether ATM variants affect rates of radionecrosis (RN) and local intracranial progression (LIP) after stereotactic radiosurgery (SRS) for brain metastases. Methods and Materials: Patients undergoing an initial course of SRS for non-small cell lung cancer (NSCLC) brain metastases at a single institution were retrospectively identified. Kaplan-Meier estimates were calculated and Cox proportional hazards testing was performed based on ATM variant status. Results: A total of 541 patients completed SRS for brain metastasis secondary to NSCLC, of whom 260 completed molecular profiling. Variants of ATM were identified in 36 cases (13.8%). Among patients who completed molecular profiling, RN incidence was 4.9% (95% CI, 1.6%-8.2%) at 6 months and 9.9% (95% CI, 4.8%-15.0%) at 12 months. Incidence of RN was not significantly increased among patients with ATM variants, with an RN incidence of 5.3% (95% CI, 0.0%-15.3%) at both 6 and 12 months (P = .46). For all patients who completed genomic profiling, LIP was 5.4% (95% CI, 2.4%-8.4%) at 6 months and 9.8% (5.5%-14.1%) at 12 months. A significant improvement in LIP was not detected among patients with ATM variants, with an LIP incidence of 3.1% (0.0%-9.1%) at both 6 and 12 months (P = .26). Although differences according to ATM variant type (pathologic variant or variant of unknown significance) did not reach significance, no patients with ATM pathologic variants experienced LIP. Conclusions: We did not detect significant associations between ATM variant status and RN or LIP after SRS for NSCLC brain metastases. The current data set allows estimation of patient cohort sizes needed to power future investigations to identify genetic variants that associate with significant differences in outcomes after SRS.

Generation, validation, and benchmarking of a commercial independent Monte Carlo calculation beam model for multi-target SRS.

BACKGROUND: Dosimetric validation of single isocenter multi-target radiosurgery plans is difficult due to conditions of electronic disequilibrium and the simultaneous irradiation of multiple off-axis lesions dispersed throughout the volume. Here we report the benchmarking of a customizable Monte Carlo secondary dose calculation algorithm specific for multi-target radiosurgery which future users may use to guide their commissioning and clinical implementation. PURPOSE: To report the generation, validation, and clinical benchmarking of a volumetric Monte Carlo (MC) dose calculation beam model for single isocenter radiosurgery of intracranial multi-focal disease. METHODS: The beam model was prepared within SciMoCa (ScientificRT, Munich Germany), a commercial independent dose calculation software, with the aim of broad availability via the commercial software for use with single isocenter radiosurgery. The process included (1) definition & acquisition of measurement data required for beam modeling, (2) tuning model parameters to match measurements, (3) validation of the beam model via independent measurements and end-to-end testing, and finally, (4) clinical benchmarking and validation of beam model utility in a patient specific QA setting. We utilized a 6X Flattening-Filter-Free photon beam from a TrueBeam STX linear accelerator (Siemens Healthineers, Munich Germany). RESULTS: In addition to the measured data required for standard IMRT/VMAT (depth dose, central axis profiles & output factors, leaf gap), beam modeling and validation for single-isocenter SRS required central axis and off axis (5 cm & 9 cm) small field output factors and comparison between measurement and simulation of backscatter with aperture for jaw much greater than MLCs. Validation end-to-end measurements included SRS MapCHECK in StereoPHAN geometry (2%/1 mm Gamma = 99.2% ±â€¯2.2%), and OSL & scintillator measurements in anthropomorphic STEEV phantom (6 targets, volume = 0.1-4.1cc, distance from isocenter = 1.2-7.9 cm) for which mean difference was -1.9% ±â€¯2.2%. For 10 patient cases, MC for individual PTVs was -0.8% ±â€¯1.5%, -1.3% ±â€¯1.7%, and -0.5% ±â€¯1.8% for mean dose, D95%, and D1%, respectively. This corresponded to custom passing rates action limits per AAPM TG-218 guidelines of ±5.2%, ±6.4%, and ±6.3%, respectively. CONCLUSIONS: The beam modeling, validation, and clinical action criteria outlined here serves as a benchmark for future users of the customized beam model within SciMoCa for single isocenter radiosurgery of multi-focal disease.

A radiomics-incorporated deep ensemble learning model for multi-parametric MRI-based glioma segmentation.

Objective.To develop a deep ensemble learning (DEL) model with radiomics spatial encoding execution for improved glioma segmentation accuracy using multi-parametric magnetic resonance imaging (mp-MRI).Approach.This model was developed using 369 glioma patients with a four-modality mp-MRI protocol: T1, contrast-enhanced T1 (T1-Ce), T2, and FLAIR. In each modality volume, a 3D sliding kernel was implemented across the brain to capture image heterogeneity: 56 radiomic features were extracted within the kernel, resulting in a fourth-order tensor. Each radiomic feature can then be encoded as a 3D image volume, namely a radiomic feature map (RFM). For each patient, all RFMs extracted from all four modalities were processed using principal component analysis for dimension reduction, and the first four principal components (PCs) were selected. Next, a DEL model comprised of four U-Net sub-models was trained for the segmentation of a region-of-interest: each sub-model utilizes the mp-MRI and one of the four PCs as a five-channel input for 2D execution. Last, four softmax probability results given by the DEL model were superimposed and binarized using Otsu's method as the segmentation results. Three DEL models were trained to segment the enhancing tumor (ET), tumor core (TC), and whole tumor (WT), respectively. The segmentation results given by the proposed ensemble were compared to the mp-MRI-only U-Net results.Main Results.All three radiomics-incorporated DEL models were successfully implemented: compared to the mp-MRI-only U-net results, the dice coefficients of ET (0.777 → 0.817), TC (0.742 → 0.757), and WT (0.823 → 0.854) demonstrated improvement. The accuracy, sensitivity, and specificity results demonstrated similar patterns.Significance.The adopted radiomics spatial encoding execution enriches the image heterogeneity information that leads to the successful demonstration of the proposed DEL model, which offers a new tool for mp-MRI-based medical image segmentation.

A structured FMEA approach to optimizing combinations of plan-specific quality assurance techniques for IMRT and VMAT QA.

BACKGROUND: Many commercial tools are available for plan-specific quality assurance (QA) of radiotherapy plans, with their functionality assessed in isolation. However, multiple QA tools are required to review the full range of potential errors. It is important to assess their effectiveness in combination with each other to look for ways to both streamline the QA process and to make certain that errors of high impact and/or high occurrence are caught before reaching patient treatment. PURPOSE: To develop a structured method to assess the effective risk reduction of combinations of QA methods for IMRT/VMAT treatments. METHODS: First, a structured prospective risk assessment was performed to establish the major failure modes (FMs) of IMRT/VMAT QA, and assign occurrence (O), severity (S), and baseline detectability (BD) rankings to them. The baseline assumed that chart checks and linear accelerator QA was performed, but no plan-specific secondary dose calculation or measurement was done. Second, the detectability of each FM for two secondary dose calculation methods and four plan measurement methods (point-based dose calculation, Monte-Carlo-based dose calculation, 2D fluence-based measurement, 2.5D phantom-based measurement, log file analysis with dose recalculation, and log file analysis combined with MLC QA) was determined. Third, we used a minimum detectability approach in addition to each FM's occurrence and severity to determine the optimal combination of QA methods. We analyzed the cumulative risk priority number of eight combinations of QA methods. The analysis was done on (1) all FMs, (2) FMs with high severity, (3) FMs with high-risk priority numbers (RPN) of O*S*BD, and (4) on FMs with both high severity and high RPN. RESULTS: Our analysis resulted in 54 FMs, including commissioning, planning, data transfer, and linear accelerator failures. 1D secondary dose calculation plus measurement provided a 19%-22% risk reduction from baseline. 1D/3D secondary dose calculation plus log files created a 25%-32% reduction. 3D secondary dose calculation plus measurement resulted in a 27%-34% reduction. 3D secondary dose calculation plus log files with additional machine QA provided the greatest reduction of 31%-42%. CONCLUSION: This novel structured approach to comparing combinations of QA methods will allow us to optimize our procedures, with the goal of detecting all clinically significant FMs. Our results show that log-file QA with 3D dose recalculation and supplemental machine QA provides better risk reduction than measurement-based QA. This work builds evidence to justify reducing or eliminating measurement-based PSQA with an independent 3D dose verification, log-file measurement, and appropriate supplementation of machine QA. The process also highlights FMs that cannot be caught by pre-treatment QA, prompting us to consider future directions for on-treatment QA.

Investigation of a 3D dosimetry system utilizing radio-chromic gel and telecentric optical-CT readout.

BACKGROUND: Sophisticated modern radiation therapy treatments require comprehensive validation in 3D. PURPOSE: Investigation and characterization of a novel 3D dosimetry system consisting of ClearView radiochromic gel dosimeters (commercially available from Modus Inc) and an in-house telecentric optical CT scanner DLOS (the Duke Large Field of View Optical-CT Scanner). METHODS: Spectrophotometry measurements were made on small volumes of ClearView gel irradiated with 6X photon doses up to 40 Gy to determine linearity and temporal stability of dose response. Clinical evaluation of Clearview/DLOS system was conducted in two phases. Phase one involved simple photon and electron benchmark irradiations, delivered to 15 and 10 cm diameter dosimeters, at various energies and doses. Phase 2 investigated application to the verification of two single isocenter multi-target (SIMT) stereotactic radiosurgery (SRS) deliveries. These were patient treatments for two and five brain lesions, respectively, and delivered to 15 cm diameter dosimeters. SIMT treatments were delivered by Varian TrueBeam 6X with doses of 40 Gy. For dose read-out, dosimeters were optically scanned in the DLOS both pre- and post- irradiation (within 24 h). 3D reconstructions (1 mm3 resolution) of the change in linear-optical- attenuation (proportional to dose) was obtained using in-house software and 3D Slicer. Measured and predicted (Eclipse TPS) doses were compared through percent depth-dose (PDD), cross plane and in-plane profiles, and relative 3D gamma analysis (performed at a range of 7%/4 mm down to 2%/2 mm). Regions of known artifacts were excluded from analysis (jar base, neck, and wall). The SIMT SRS deliveries were additionally compared to SciMoca, an independent Monte Carlo second check software. RESULTS: Linearity of dose response was confirmed with R2 ≥ 0.9986 at both 520 and 630 nm wavelengths and at three post-irradiation time points: 21 h, 6 and 10 days. Dose profiles of all benchmark irradiations, in both 15 and 10 cm dosimeters, show good agreement in useable areas of the gel compared to Eclipse dose calculations, with root mean square errors (RMSE) ≤ 0.0054, and R2 ≥ 0.9808. Gamma pass rates for the 15 cm dosimeter benchmark irradiations were ≥ 94% at 2%/2 mm (central axis), ≥ 90% at 3%/3 mm (left lateral), ≥ 90% at 2%/2 mm (electron), and ≥ 94% at 3%/2 mm (stacking field). Similar high passing rates were observed for benchmark irradiations to the smaller 10 cm diameter dosimeters. Very high Gamma pass rates were found for SIMT SRS deliveries, with 99.82% and 97.80% at 3%/2 mm, for the two and five target plans, respectively. CONCLUSION: This work presents the first investigation of ClearView dosimeters in combination with a telecentric optical-CT scanner (DLOS). Simple benchmark irradiations demonstrate ClearView/DLOS can accurately recreate and measure relative 3D dose within non-artifact regions (i.e., > 1 cm away from walls). Application to SIMT SRS deliveries demonstrated the viability of the system as a means for comprehensive 3D verification of complex treatment deliveries as well as confirming the treatment planning system dose distribution. The results indicate that DLOS/ClearView system is a highly effective 3D verification tool for SIMT irradiations and can be applied with 3%/2 mm gamma criteria where passing rates of > 95% are to be expected.

Erratum to "E.C. Lerner, E.S. Srinivasan, G. Broadwater, et al. Factors Associated With New-Onset Seizures Following Stereotactic Radiosurgery for Newly Diagnosed Brain Metastases. Adv Radiat Oncol. 2022;7:101054."

[This corrects the article DOI: 10.1016/j.adro.2022.101054.].

Outcomes in Patients with Intact and Resected Brain Metastasis Treated with 5-Fraction Stereotactic Radiosurgery.

Purpose: Hypofractionated stereotactic radiosurgery (HF-SRS) with or without surgical resection is potentially a preferred treatment for larger or symptomatic brain metastases (BMs). Herein, we report clinical outcomes and predictive factors following HF-SRS. Methods and Materials: Patients undergoing HF-SRS for intact (iHF-SRS) or resected (rHF-SRS) BMs from 2008 to 2018 were retrospectively identified. Linear accelerator-based image-guided HF-SRS consisted of 5 fractions at 5, 5.5, or 6 Gy per fraction. Time to local progression (LP), time to distant brain progression (DBP), and overall survival (OS) were calculated. Cox models assessed effect of clinical factors on OS. Fine and Gray's cumulative incidence model for competing events examined effect of factors on LP and DBP. The occurrence of leptomeningeal disease (LMD) was determined. Logistic regression examined predictors of LMD. Results: Among 445 patients, median age was 63.5 years; 87% had Karnofsky performance status ≥70. Fifty-three % of patients underwent surgical resection, and 75% received 5 Gy per fraction. Patients with resected BMs had higher Karnofsky performance status (90-100, 41 vs 30%), less extracranial disease (absent, 25 vs 13%), and fewer BMs (multiple, 32 vs 67%). Median diameter of the dominant BM was 3.0 cm (interquartile range, 1.8-3.6 cm) for intact BMs and 4.6 cm (interquartile range, 3.9-5.5 cm) for resected BMs. Median OS was 5.1 months (95% confidence interval [CI], 4.3-6.0) following iHF-SRS and 12.8 months (95% CI, 10.8-16.2) following rHF-SRS (P < .01). Cumulative LP incidence was 14.5% at 18 months (95% CI, 11.4-18.0%), significantly associated with greater total GTV (hazard ratio, 1.12; 95% CI, 1.05-1.20) following iFR-SRS, and with recurrent versus newly diagnosed BMs across all patients (hazard ratio, 2.28; 95% CI, 1.01-5.15). Cumulative DBP incidence was significantly greater following rHF-SRS than iHF-SRS (P = .01), with respective 24-month rates of 50.0 (95% CI, 43.3-56.3) and 35.7% (95% CI, 29.2-42.2). LMD (57 events total; 33% nodular, 67% diffuse) was observed in 17.1% of rHF-SRS and 8.1% of iHF-SRS cases (odds ratio, 2.46; 95% CI, 1.34-4.53). Any radionecrosis and grade 2+ radionecrosis events were observed in 14 and 8% of cases, respectively. Conclusions: HF-SRS demonstrated favorable rates of LC and radionecrosis in postoperative and intact settings. Corresponding LMD and RN rates were comparable to those of other studies.

Uncertainties in the dosimetric heterogeneity correction and its potential effect on local control in lung SBRT.

Objective. Dose calculation in lung stereotactic body radiation therapy (SBRT) is challenging due to the low density of the lungs and small volumes. Here we assess uncertainties associated with tissue heterogeneities using different dose calculation algorithms and quantify potential associations with local failure for lung SBRT.Approach. 164 lung SBRT plans were used. The original plans were prepared using Pencil Beam Convolution (PBC, n = 8) or Anisotropic Analytical Algorithm (AAA, n = 156). Each plan was recalculated with AcurosXB (AXB) leaving all plan parameters unchanged. A subset (n = 89) was calculated with Monte Carlo to verify accuracy. Differences were calculated for the planning target volume (PTV) and internal target volume (ITV) Dmean[Gy], D99%[Gy], D95%[Gy], D1%[Gy], and V100%[%]. Dose metrics were converted to biologically effective doses (BED) usingα/ß= 10Gy. Regression analysis was performed for AAA plans investigating the effects of various parameters on the extent of the dosimetric differences. Associations between the magnitude of the differences for all plans and outcome were investigated using sub-distribution hazards analysis.Main results. For AAA cases, higher energies increased the magnitude of the difference (ΔDmean of -3.6%, -5.9%, and -9.1% for 6X, 10X, and 15X, respectively), as did lung volume (ΔD99% of -1.6% per 500cc). Regarding outcome, significant hazard ratios (HR) were observed for the change in the PTV and ITV D1% BEDs upon univariate analysis (p = 0.042, 0.023, respectively). When adjusting for PTV volume and prescription, the HRs for the change in the ITV D1% BED remained significant (p = 0.039, 0.037, respectively).Significance. Large differences in dosimetric indices for lung SBRT can occur when transitioning to advanced algorithms. The majority of the differences were not associated with local failure, although differences in PTV and ITV D1% BEDs were associated upon univariate analysis. This shows uncertainty in near maximal tumor dose to potentially be predictive of treatment outcome.

Factors Associated With New-Onset Seizures Following Stereotactic Radiosurgery for Newly Diagnosed Brain Metastases.

Purpose: Stereotactic radiosurgery (SRS) is a highly effective therapy for newly diagnosed brain metastases. Prophylactic antiepileptic drugs are no longer routinely used in current SRS practice, owing to a perceived low overall frequency of new-onset seizures and potential side effects of medications. It is nonetheless desirable to prevent unwanted side effects following SRS. Risk factors for new-onset seizures after SRS have not been well established. As such, we aimed to characterize variables associated with increased seizure risk. Methods and Materials: Patients treated with SRS for newly diagnosed brain metastases between 2013 and 2016 were retrospectively reviewed at a single institution. Data on baseline demographics, radiation parameters, and clinical courses were collected. Results: The cohort consisted of 305 patients treated with SRS without prior seizure history. Median age and baseline Karnofsky Performance Scale score were 64 years (interquartile range, 55-70) and 80 (interquartile range, 80-90), respectively. Twenty-six (8.5%) patients developed new-onset seizures within 3 months of SRS. There was no association between new-onset seizures and median baseline Karnofsky Performance Scale score, prior resection, or prior whole brain radiation therapy. There were significant differences in the combined total irradiated volume (12.5 vs 3.7 cm3, P < .001), maximum single lesion volume (8.8 vs 2.8 cm3, P = .003), lesion diameter (3.2 vs 2.0 cm, P = .003), and number of lesions treated (3 vs 1, P = .018) between patients with and without new-onset seizures, respectively. On multivariate logistic regression, total irradiated volume (odds ratio, 1.09 for every 1-cm1 increase in total volume; confidence interval, 1.02-1.17; P = .016) and pre-SRS neurologic symptoms (odds ratio, 3.08; 95% confidence interval, 1.19-7.99; P = .020) were both significantly correlated with odds of seizures following SRS. Conclusions: Our data suggest that larger total treatment volume and the presence of focal neurologic deficits at presentation are associated with new-onset seizures within 3 months of SRS. High-risk patients undergoing SRS may benefit from counseling or prophylactic antiseizure therapy.

Virtual patient-specific QA with DVH-based metrics.

We demonstrate a virtual pretreatment patient-specific QA (PSQA) procedure that is capable of quantifying dosimetric effect on patient anatomy for both intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT). A machine learning prediction model was developed to use linear accelerator parameters derived from the DICOM-RT plan to predict delivery discrepancies at treatment delivery (defined as the difference between trajectory log file and DICOM-RT) and was coupled with an independent Monte Carlo dose calculation algorithm for dosimetric analysis. Machine learning models for IMRT and VMAT were trained and validated using 120 IMRT and 206 VMAT fields of prior patients, with 80% assigned for iterative training and testing, and 20% for post-training validation. Various prediction models were trained and validated, with the final models selected for clinical implementation being a boosted tree and bagged tree for IMRT and VMAT, respectively. After validation, these models were then applied clinically to predict the machine parameters at treatment delivery for 7 IMRT plans from various sites (61 fields) and 10 VMAT multi-target intracranial radiosurgery plans (35 arcs) and compared to the dosimetric effect calculated directly from trajectory log files. Dose indices tracked for targets and organs at risk included dose received by 99%, 95%, and 1% of the volume, mean dose, percent of volume receiving 25%-100% of the prescription dose. The average coefficient of determination (r2 ) when comparing intra-field predicted and actual delivery error was 0.987 ± 0.012 for IMRT and 0.895 ± 0.095 for VMAT, whereas r2 when comparing inter-field predicted versus actual delivery error was 0.982 for IMRT and 0.989 for VMAT. Regarding dosimetric analysis, r2 when comparing predicted versus actual dosimetric changes for all dose indices was 0.966 for IMRT and 0.907 for VMAT. Prediction models can be used to anticipate the dosimetric effect calculated from trajectory files and have potential as a "delivery-free" pretreatment analysis to enhance PSQA.

The Effect of Various Dose Normalization Strategies When Implementing Linear Boltzmann Transport Equation Dose Calculation for Lung Stereotactic Body Radiation Therapy Planning.

PURPOSE: To explore implications of various plan normalizations when implementing a linear Boltzmann transport equation solver dose calculation algorithm (LBTE) for lung stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: Eighty-seven plans originally calculated with a convolution-superposition algorithm (CS) were recalculated with LBTE and normalized in 3 ways: prescription covering 95% of planning target volume (PTV), 99% of internal target volume (ITV), and keeping the original planned PTV coverage. Effect on delivered dose after implementing the new algorithm was quantified using change in total monitor units for each renormalization strategy. Treatment planning system-reported changes in PTV, ITV, and organ at risk (OAR) doses were also quantified, along with the feasibility of LBTE plans to meet institutional OAR planning objectives. RESULTS: LBTE renormalization resulted in monitor unit increases of 7.0 ± 8.8%, 0.31 ± 5.8%, and 7.9 ± 8.6% when normalizing to the PTV D95%, ITV D99%, and planned coverage, respectively. When normalizing to PTV D95%, the LBTE reported increased PTV and ITV D1% (Gy) relative to CS (median, 3.4% and 3.2%, respectively), and normalizing to ITV D99% showed a median 1.9% decrease. For LBTE plans, reported OAR doses were increased when normalizing to PTV D95% or planned coverage (median chest wall V30 Gy [cc] increase of 0.85 and 1.7 cc, respectively) and normalizing to ITV D99% resulted in decreased dose (median chest wall V30 Gy [cc] decrease of 1.8 cc). LBTE plans normalized to PTV D95% showed inferior ability to meet the OAR objectives, but reoptimizing kept the objectives manageable while maintaining PTV coverage. CONCLUSIONS: When transitioning from CS to LBTE dose calculation for lung SBRT, maintaining a PTV coverage-based normalization generally results in increased dose delivered relative to CS and increased reported target and OAR dose. In cases where PTV normalization results in unacceptably high doses to targets or OARs, normalizing based on ITV coverage can be considered to maintain similar target dose as CS.

Outcomes in Patients With 4 to 10 Brain Metastases Treated With Dose-Adapted Single-Isocenter Multitarget Stereotactic Radiosurgery: A Prospective Study.

PURPOSE: To examine the effectiveness and safety of single-isocenter multitarget stereotactic radiosurgery using a volume-adapted dosing strategy in patients with 4 to 10 brain metastases. METHODS AND MATERIALS: Adult patients with 4 to 10 brain metastases were eligible for this prospective trial. The primary endpoint was overall survival. Secondary endpoints were local recurrence, distant brain failure, neurologic death, and rate of adverse events. Exploratory objectives were neurocognition, quality of life, dosimetric data, salvage rate, and radionecrosis. Dose was prescribed in a single fraction per RTOG 90-05 or as 5 Gy × 5 fractions for lesions ≥3 cm diameter, lesions involving critical structures, or single-fraction brain V12Gy >20 mL. RESULTS: Forty patients were treated with median age of 61 years, Karnofsky performance status 90, and 6 brain metastases. Twenty-two patients survived longer than expected from the time of protocol SRS, with 1 living patient who has not reached that milestone. Median overall survival was 8.1 months with a 1-year overall survival of 35.7%. The 1-year local recurrence rate was 5% (10 of 204 of evaluable lesions) in 12.5% (4 of 32) of the patients. Distant brain failure was observed in 19 of 32 patients with a 1-year rate of 35.8%. Grade 1-2 headache was the most common complaint, with no grade 3-5 treatment-related adverse events. Radionecrosis was observed in only 5 lesions, with a 1-year rate of 1.5%. Rate of neurologic death was 20%. Neurocognition and quality of life did not significantly change 3 months after SRS compared with pretreatment. CONCLUSIONS: These results suggest that volume-adapted dosing single-isocenter multitarget stereotactic radiosurgery is an effective and safe treatment for patients with 4 to 10 brain metastases.

Hippocampal Avoidance in Multitarget Radiosurgery.

Brain metastases are a common complication for patients diagnosed with cancer. As stereotactic radiosurgery (SRS) becomes a more prevalent treatment option for patients with many brain metastases, further research is required to better characterize the ability of SRS to treat large numbers of metastases (≥4) and the impact on normal brain tissue and, ultimately, neurocognition and quality of life (QOL). This study serves first as an evaluation of the feasibility of hippocampal avoidance for SRS patients, specifically receiving single-isocenter multitarget treatments (SIMT) planned with volumetric modulated arc therapy (VMAT). Second, this study analyzes the effects of standard-definition (SD) multileaf collimators (MLCs) (5 mm width) on plan quality and hippocampal avoidance. The 40 patients enrolled in this Institutional Review Board (IRB)-approved study had between four and 10 brain metastases and were treated with SIMT using VMAT. From the initial 40 patients, eight hippocampi across seven patients had hippocampal doses exceeding the maximum biologically effective dose (BED) constraint given by RTOG 0933. With the addition of upper constraints in the optimization objectives and one arc angle adjustment in one patient plan, four out of seven patient plans were able to meet the maximum hippocampal BED constraint, avoiding five out of eight total hippocampi at risk. High-definition (HD) MLCs allowed for an average decrease of 29% ± 23% (p = 0.007) in the maximum BED delivered to all eight hippocampi at risk. The ability to meet dose constraints depended on the distance between the hippocampus and the nearest planning target volume (PTV). Meeting the maximum hippocampal BED constraint in re-optimized plans was equally likely with the use of SD-MLCs (five out of eight hippocampi at risk were avoided) but resulted in increased dose to normal tissue volumes (23.67% ± 16.3% increase in V50%[cc] of normal brain tissue, i.e., brain volume subtracted by the total PTV) when compared to the HD-MLC re-optimized plans. Comparing the effects of SD-MLCs on plans not optimized for hippocampal avoidance resulted in increases of 48.2% ± 32.2% (p = 0.0056), 31.5% ± 16.3% (p = 0.024), and 16.7% ± 8.5% (p = 0.022) in V20%[cc], V50%[cc], and V75%[cc], respectively, compared to the use of HD-MLCs. The conformity index changed significantly neither when plans were optimized for hippocampal avoidance nor when SD-MLC leaves were used for treatment. In plans not optimized for hippocampal avoidance, mean hippocampal dose increased with the use of SD-MLCs by 38.0% ± 37.5% (p = 0.01). However, the use of SD-MLCs did not result in an increased number of hippocampi at risk.

Single isocenter SRS using CAVMAT offers improved robustness to commissioning and treatment delivery uncertainty compared to VMAT.

PURPOSE: In this study, we evaluate and compare single isocenter multiple target VMAT (SIMT) and Conformal Arc Informed VMAT (CAVMAT) radiosurgery's sensitivity to uncertainties in dosimetric leaf gap (DLG) and treatment delivery. CAVMAT is a novel planning technique that uses multiple target conformal arcs as the starting point for limited inverse VMAT optimization. METHODS: All VMAT and CAVMAT plans were recalculated with DLG values of 0.4, 0.8, and 1.2 mm. DLG effect on V6Gy [cc], V12Gy [cc], and V16Gy [cc], and target dose was evaluated. Plans were delivered to a Delta4 (ScandiDos, Madison, WI) phantom and gamma analysis performed with varying criteria. Log file analysis was performed to evaluate MLC positional error. Sixteen targets were delivered to a SRS MapCHECK (Sun Nuclear Corp., Melbourne, FL) to evaluate VMAT and CAVMAT's dose difference (DD) as a function of DLG. RESULTS: VMAT's average maximum and minimum target dose sensitivity to DLG was 9.08 ±3.50%/mm and 9.50 ± 3.30%/mm, compared to 3.20 ± 1.60%/mm and 4.72 ± 1.60%/mm for CAVMAT. For VMAT, V6Gy [cc], V12Gy [cc], and V16Gy [cc] sensitivity was 35.83 ± 9.50%/mm, 34.12 ± 6.60%/mm, and 39.23 ± 8.40%/mm. In comparison, CAVMAT's sensitivity was 23.19 ± 4.50%/mm, 22.45 ± 4.40%/mm, and 24.88 ± 4.90%/mm, respectively. Upon delivery to the Delta4 , CAVMAT offered superior dose agreement compared to VMAT. For a 1%/1 mm gamma analysis, VMAT and CAVMAT had a passing rate of 94.53 ± 4.40% and 99.28 ± 1.70%, respectively. CAVMAT was more robust to DLG variation, with the SRS MapCHECK plans yielding an absolute average DD sensitivity of 2.99 ± 1.30%/mm compared to 5.07 ± 1.10%/mm for VMAT. Log files demonstrated minimal differences in MLC positional error for both techniques. CONCLUSIONS: CAVMAT remains robust to delivery uncertainties while offering a target dose sensitivity to DLG less than half that of VMAT, and 65% of that of VMAT for V6Gy [cc], V12Gy [cc], and V16Gy [cc]. The superior dose agreement and reduced sensitivity of CAVMAT to DLG uncertainties indicate promise as a robust alternative to VMAT for SIMT SRS.

A tool for patient-specific prediction of delivery discrepancies in machine parameters using trajectory log files.

PURPOSE: Multileaf collimator (MLC) delivery discrepancy between planned and actual (delivered) positions have detrimental effect on the accuracy of dose distributions for both IMRT and VMAT. In this study, we evaluated the consistency of MLC delivery discrepancies over the course of treatment and over time to verify that a predictive machine learning model would be applicable throughout the course of treatment. Next, the MLC and gantry positions recorded in prior trajectory log files were analyzed to build a machine learning algorithm to predict MLC positional discrepancies during delivery for a new treatment plan. An open source tool was developed and released to predict the MLC positional discrepancies at treatment delivery for any given plan. METHODS: Trajectory log files of 142 IMRT plans and 125 VMAT plans from 9 Varian TrueBeam linear accelerators were collected and analyzed. The consistency of delivery discrepancy over patient-specific quality assurance (QA) and patient treatment deliveries was evaluated. Data were binned by treatment site and machine type to determine their relationship with MLC and gantry angle discrepancies. Motion-related parameters including MLC velocity, MLC acceleration, control point, dose rate, and gravity vector, gantry velocity and gantry acceleration, where applicable, were analyzed to evaluate correlations with MLC and gantry discrepancies. Several regression models, such as simple/multiple linear regression, decision tree, and ensemble method (boosted tree and bagged tree model) were used to develop a machine learning algorithm to predict MLC discrepancy based on MLC motion parameters. RESULTS: MLC discrepancies at patient-specific QA differed from those at patient treatment deliveries by a small (mean = 0.0021 ± 0.0036 mm, P = 0.0089 for IMRT; mean = 0.0010 ± 0.0016 mm, P = 0.0003 for VMAT) but statistically significant amount, likely due to setting the gantry angle to zero for QA in IMRT. MLC motion parameters, MLC velocity and gravity vector, showed significant correlation (P < 0.001) with MLC discrepancy, especially MLC velocity, which had an approximately linear relationship (slope = -0.0027, P < 0.001, R2  = 0.79). Incorporating MLC motion parameters, the final generalized model trained by data from all linear accelerators can predict MLC discrepancy to a high degree of accuracy with high correlation (R2  = 0.86) between predicted and actual MLC discrepancies. The same prediction results were found across different treatment sites and linear accelerators. CONCLUSION: We have developed a machine learning model using trajectory log files to predict the MLC discrepancies during delivery. This model has been a released as a research tool in which a DICOM-RT with predicted MLC positions can be generated using the original DICOM-RT file as input. This tool can be used to simulate radiotherapy treatment delivery and may be useful for studies evaluating plan robustness and dosimetric uncertainties from treatment delivery.

Radiosurgery treatment planning using conformal arc informed volumetric modulated arc therapy.

Linac based radiosurgery to multiple metastases is commonly planned with volumetric modulated arc therapy (VMAT) as it effectively achieves high conformality to complex target arrangements. However, as the number of targets increases, VMAT can struggle to block between targets, which can lead to highly modulated and/or nonconformal multi-leaf collimator (MLC) trajectories that unnecessarily irradiation of healthy tissue. In this study we introduce, describe, and evaluate a treatment planning technique called Conformal Arc Informed VMAT (CAVMAT), which aims to reduce the dose to healthy tissue while generating highly conformal treatment plans. CAVMAT is a hybrid technique which combines the conformal MLC trajectories of dynamic conformal arcs with the MLC modulation and versatility of inverse optimization. CAVMAT has 3 main steps. First, targets are assigned to subgroups to maximize MLC blocking between targets. Second, arc weights are optimized to achieve the desired target dose, while minimizing MU variation between arcs. Third, the optimized conformal arc plan serves as the starting point for limited inverse optimization to improve dose conformity to each target. Twenty multifocal VMAT cases were replanned with CAVMAT with 20Gy applied to each target. The total volume receiving 2.5Gy[cm3], 6Gy[cm3], 12Gy[cm3], and 16Gy[cm3], conformity index, treatment delivery time, and the total MU were used to compare the VMAT and CAVMAT plans. In addition, CAVMAT was compared to a broad range of planning strategies from various institutions (108 linear accelerator based plans, 14 plans using other modalities) for a 5-target case utilized in a recent plan challenge. For the linear accelerator-based plans, a plan complexity metric based on aperture opening area and perimeter, total monitor units (MU), and MU for a given aperture opening was utilized in the plan challenge scoring algorithm to compare the submitted plans to CAVMAT. After re-planning the 20 VMAT cases, CAVMAT reduced the average V2.5Gy[cm3] by 25.25 ± 19.23%, V6Gy[cm3] by 13.68 ± 18.97%, V12Gy[cm3] by 11.40 ± 19.44%, and V16Gy[cm3] by 6.38 ± 19.11%. CAVMAT improved conformity by 3.81 ± 7.57%, while maintaining comparable target dose. MU for the CAVMAT plans increased by 24.35 ± 24.66%, leading to an increased treatment time of 2 minutes. For the plan challenge case, CAVMAT was 1 of 12 linac based plans that met all plan challenge scoring criteria. Compared to the average submitted VMAT plan, CAVMAT increased the V10%Gy[%] of healthy tissue (Brain-PTV) by roughly 3.42%, but in doing so was able to reduce the V25%Gy[%] by roughly 3.73%, while also reducing V50%Gy[%], V75%Gy[%], and V100%Gy[%]. The CAVMAT technique successfully eliminated insufficient MLC blocking between targets prior to the inverse optimization, leading to less complex treatment plans and improved tissue sparing. Tissue sparing, improved conformity, and decreased plan complexity at the cost of slight increase in treatment delivery time indicates CAVMAT to be a promising method to treat brain metastases.

Application of TG-218 action limits to SRS and SBRT pre-treatment patient specific QA.

AAPM TG-218 provides recommendations for standard IMRT pre-treatment QA without giving specifics for stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT). In light of this, our purpose is to report our experience with applying TG-218 recommendations to a large multicenter clinical SRS and SBRT program for a range of diverse clinical pre-treatment QA systems. Pre-treatment QA systems included Delta4 (Scandidos), Portal Dosimetry (Varian Medical Systems), ArcCHECK (SunNuclear), and SRS MapCHECK (SunNuclear). Plans were stratified by technique for each QA system, and included intracranial and extracranial IMRT and VMAT (total QA cases n=275). Gamma analysis was re-analyzed with spatial/dose criteria combinations ranging from 1 to 3 mm and 1% to 4%, and action and tolerance limits were calculated per plan type and compared to the "universal" TG-218 action limit of 90%. The analysis indicated that spatial tolerance criteria could be tightened to 1 mm while still maintaining an in-control QA process for all QA systems evaluated.