Volumetric Modulated Arc Therapy Radiosurgery Research Articles

Understanding the Effect of Prescription Isodose in Single-Fraction Stereotactic Radiosurgery on Plan Quality and Clinical Outcomes for Solid Brain Metastases.

There is wide variation in treatment planning strategy for central nervous system (CNS) stereotactic radiosurgery. We sought to understand what relationships exist between intratumor maximum dose and local control (LC) or CNS toxicity, and dosimetric effects of constraining hotspots on plan quality of multiple metastases volumetric modulated arc therapy radiosurgery plans. We captured brain metastases from 2015 to 2017 treated with single-isocenter volumetric modulated arc therapy radiosurgery. Included tumors received single-fraction stereotactic radiosurgery, had no previous surgery or radiation, and available follow-up imaging. Our criterion for local failure was 25% increase in tumor diameter on follow-up MRI or pathologic confirmation of tumor recurrence. We defined significant CNS toxicity as Radiation Therapy Oncology Group irreversible Grade 3 or higher. We performed univariate and multivariate analyses evaluating factors affecting LC. We examined 10 stereotactic radiosurgery plans with prescriptions of 18 Gy to all targets originally planned without constraints on the maximum dose within the tumor. We replanned each with a constraint of Dmax 120%. We compared V50%, mean brain dose, and Dmax between plans. Five hundred and thirty tumors in 116 patients were available for analysis. Median prescription dose was 18 Gy, and median prescription isodose line (IDL) was 73%. Kaplan-Meier estimate of 12-month LC only tumor volume (HR 1.43 [1.22-1.68] P < .001) was predictive of local failure on univariate analysis; prescription IDL and histology were not. In multivariate analysis, tumor volume impacted local failure (HR 1.43 [1.22-1.69] P < .001) but prescription IDL did not (HR 0.95 [0.86-1.05] P = .288). Only a single grade 3 and 2 grade 4 toxicities were observed; tumor volume was predictive of CNS toxicity (HR 1.58 [1.25-2.00]; P < .001), whereas prescription IDL was not (HR 1.01 [0.87-1.17] P = .940). The prescription isodose line had no impact on local tumor control or CNS toxicity. Penalizing radiosurgery hotspots resulted in worse radiosurgery plans with poorer gradient. Limiting maximum dose in gross tumor causes increased collateral exposure to surrounding tissue and should be avoided.

Antiseizure medication for brain metastasis-related epilepsy: Findings of optimal choice from a retrospective cohort

ObjectiveTo analyze the prevalence of antiseizure medication (ASM) in patients with brain metastasis-related epilepsy (BMRE) treated with radiosurgery and the relationship between ASM and psychiatric comorbidity. Material and methodsThis is a cross-sectional observational design study with retrospective review of medical records of all patients with brain metastases treated with volumetric modulated arc therapy radiosurgery (VMAT-RS) between 2012 and 2018 in a tertiary oncology center. We included those patients with BMRE, analyzing the clinical and demographic data, with special attention to psychiatric comorbidities and the use of ASM. ResultsOf the 121 patients with brain metastases included for treatment with VMAT-RS, a total of 38 presented BMRE. The most widely used ASM as first-line treatment was levetiracetam (89%). Only 8% of the patients received sodium channel blockers. The most common psychiatric comorbidity was depression (42.1%). ConclusionsLevetiracetam is the most widely used ASM in patients with BMRE treated with VMAT-RS. Nevertheless, common psychiatric comorbidities in this population might change the decision-making of ASM choice.

170. Implementing single-isocenter volumetric modulated arc therapy radiosurgery treatment for multiple intracranial metastases

PurposeRecently an increase in radiosurgery treatments for multiple metastases has been observed. Traditionally these lesions were treated using one isocenter for each target and the patient had to be shifted during a single session for repositioning.The implementation of single-isocenter volumetric modulated arc therapy (VMAT) radiosurgery technique for multiple intracranial lesions allows a significant reduction of treatment times, as well as enhancing accuracy by reducing the potential intrafraction motion [1]. MethodsFor 20 patients treated with VMAT for multiple brain metastases we have analyzed the treatment process. Each case had different number and distribution of metastases. We performed a CT simulation scan with 1.25 mm thickness slice for all patients. The simulation images were registered with a MR in order to define the targets. For each case we compared the VMAT single-isocenter technique plan with the sums of the plans of every single lesion. Plans were evaluated using Dose Volume Histograms, Conformity and Uniformity Indexes. All the plans were optimized with 6 MV flattened filter free arcs. Set up checks were performed using both BrainLAB ExacTrac and Varian Cone Beam CT (CBCT). For 10 patients we also evaluated the intrafraction motion. ResultsNo significant difference was detected between the two techniques. The single-isocenter technique comes out better for the dose distributions especially for low doses. We discovered a good agreement between ExacTrac and CBCT and a minimum intrafraction movement (<1 mm) which was dosimetrically insignificant also for peripheral lesions. We underline a very significant reduction of treatment times. ConclusionsBoth methods achieve good dosimetric results. Single-isocenter VMAT radiosurgery treatment for multiple metastases is a faster technique and could be performed safely using image guided radiotherapy treatment thus relieving patient discomfort.

First experience and clinical results using a new non-coplanar mono-isocenter technique (HyperArc™) for Linac-based VMAT radiosurgery in brain metastases.

Radiosurgery (SRS) or stereotactic fractionated radiotherapy (SFRT) is increasing in the treatment of brain metastases (BMs). Aim of the present study was to evaluate the safety and effectiveness of SRS/SFRT for BMs, using a new mono-isocenter non-coplanar solution (HyperArc™ Varian Medical System). BMs patients with a diameter inferior to 3cm, a life expectancy of more than 3months and a good performance status, were eligible for Linac-based volumetric modulated arc therapy (VMAT) SFRT/SRS with HyperArc™. A retrospective analysis of patients and BMs was performed. From August 2017 to May 2018, 381BMs in 64 patients were treated and 246BMs (43 patients, median number of BMs: 5) of them were suitable for analysis. With a median FU time of 6 months, 244 out 246 (99%) BMs were controlled (18% complete response; 41% partial response, 40% stable disease), 2BMs showed a progression, at the first control. No acute or late toxicities were reported. Median overall survival (OS) has not yet been achieved, while median time to progression was 5months. In univariate analysis, statistically negative prognostic factors for OS were histology of primary tumor (p = 0.009): lung/breast cancer had better survival rates as compared to others. Cumulative intracranial volume disease ≥ 15cc and systemic progression disease were independent prognostic factors for OS at univariate (p = 0.04; p = 0.005) and multivariate (p = 0.04; p = 0.009) analysis, respectively. The present first clinical data show that SFRT/SRS with HyperArc™ is safe and effective for BMs patients. The utilization of SFRT/SRS for BMs is promising and should be further explored in randomized trials.

Linac-based VMAT radiosurgery for multiple brain lesions: comparison between a conventional multi-isocenter approach and a new dedicated mono-isocenter technique

BackgroundLinac-based stereotactic radiosurgery or fractionated stereotactic radiotherapy (SRS/FSRT) of multiple brain lesions using volumetric modulated arc therapy (VMAT) is typically performed by a multiple-isocenter approach, i.e. one isocenter per lesion, which is time-demanding for the need of independent setup verifications of each isocenter. Here, we present our initial experience with a new dedicated mono-isocenter technique with multiple non-coplanar arcs (HyperArc™, Varian Inc.) in terms of a plan comparison with a multiple-isocenter VMAT approach.MethodsFrom August 2017 to October 2017, 20 patients with multiple brain metastases (mean 5, range 2–10) have been treated by HyperArc in 1–3 fractions. The prescribed doses (Dp) were 18–25 Gy in single-fraction, and 21–27 Gy in three-fractions. Planning Target Volume (PTV), defined by a 2 mm isotropic margin from each lesion, had mean dimension of 9.6 cm3 (range 0.5–27.9 cm3). Mono-isocenter HyperArc VMAT plans (HA) with 5 non-coplanar 180°-arcs (couch at 0°, ±45°, ±90°) were generated and compared to multiple-isocenter VMAT plans (RA) with 2 coplanar 360°-arcs per isocenter. A dose normalization of 100%Dp at 98%PTV was adopted, while D2%(PTV) < 150%Dp was accepted. All plans had to respect the constraints on maximum dose to the brainstem (D0.5cm3 < 18 Gy) as well as to the optical nerves/chiasm, eyes and lenses (D0.5cm3 < 15 Gy). HA and RA plans were compared in terms of dose-volume metrics, by Paddick conformity (CI) and gradient (GI) index and by V12 and mean dose to the brain-minus-PTV, and in terms of MU and overall treatment time (OTT) per fraction. OTT was measured for HA treatments, whereas for RA plans OTT was estimated by assuming 3 min. For initial patient setup plus 5 min. For each CBCT-guided setup correction per isocenter.ResultsSignificant variations in favour of HA plans were computed for both target dose indexes, CI (p < .01) and GI (p < .01). The lower GI in HA plans was the likely cause of the significant reduction in V12 to the brain-minus-PTV (p = .023). Although at low doses, below 2–5 Gy, the sparing of the brain-minus-PTV was in favour of RA plans, no significant difference in terms of mean doses to the brain-minus-PTV was observed between the two groups (p = .31). Finally, both MU (p < .01) and OTT (p < .01) were significantly reduced by HyperArc plans.ConclusionsFor linac-based SRS/FSRT of multiple brain lesions, HyperArc plans assured a higher CI and a lower GI than standard multiple-isocenter VMAT plans. This is consistent with the computed reduction in V12 to the brain-minus-PTV. Finally, HyperArc treatments were completed within a typical 20 min. time slot, with a significant time reduction with respect to the expected duration of multiple-isocenters VMAT.

Comparison of Plan Quality Between Stereotactic and Volumetric Modulated Arc Therapy Radiosurgery for Many Brain Metastases

The objective of this study was to compare radiation dose distributions created by two radiosurgery modalities for treating a large number (≥7) brain metastases: single-isocenter volumetric modulated arc therapy (VMAT) and GammaKnife Perfexion (GK). We examined 103 brain metastases (range 0.01- 19.95 cc) from twelve patients. The mean number of targets per patient was 9 (range 7-14). Highly-optimized GK plans were compared to highly-optimized single-isocenter, multiple non-coplanar arc VMAT plans using both 6FFF (1400 MU/min) and 10FFF (2400 MU/min) high intensity modes from a Truebeam linear accelerator equipped with a high-definition multileaf collimator. Three layers of ‘tuning rinds’ were used in VMAT planning to control dose-volume constraints corresponding to high (Rx of each target), medium (12 Gy), and low-dose levels (6 Gy) [1-4]. Dosimetric parameters analyzed included RTOG conformity index (CI), 12 Gy (a known predictor of radiation necrosis [5]), 6 Gy, 3 Gy isodose volumes (V12Gy, V6Gy, V3Gy), mean and maximum hippocampus dose, maximum skin dose, and beam-on time. Each lesion had > 99.5% volume covered by the Rx dose. Direct comparison was performed using a Kruskal-Wallis test with Dunn’s post hoc comparisons (significance criteria: p < 0.05). There was a significant CI difference between GK and both 6FFF and 10FFF (2.52 ± 1.64 vs 1.59 ± 0.81 and 1.68 ± 0.87, p < 0.001). For V12Gy, there was a significant difference between GK and both 6FFF and 10FFF (2.79 ± 6.13 cc vs 2.97 ± 5.22 cc and 3.13 ± 5.39 cc, p <0.001). For V6Gy, there was no significant difference between GK and 6FFF, however, GK was significantly smaller compared to 10FFF (81.12 ± 72.86 cc vs 167.55 ± 87.55 cc, p=0.011). For V3Gy, GK was significantly smaller compared to both 6FFF and 10FFF (323 ± 295 cc vs, 880 ± 369 cc and 938 ± vs 362 cc, p < 0.001). For mean hippocampus dose, there was no significant difference between GK and 6 FFF, however, GK was significantly smaller compared to 10FFF (1.88 ± 1.35 Gy vs 3.59 ± 1.36 Gy, p = 0.013). No significant differences existed for maximum hippocampus or skin doses. There was a significant beam-on time difference between GK and both 6FFF and 10 FFF (148 ± 49 min vs 11 ± 2 min and 6 ± 1 min, p < 0.001). This study focused on cases with at least 7 brain metastases. Highly-optimized VMAT produced improved conformity at the expense of a higher V12Gy and V3Gy volume when compared to highly-optimized GK. However, the increased V12Gy with VMAT may not be clinically significant while increased V3Gy is comparable to a single fraction of whole-brain radiotherapy. [1] Liu et al. Front. Oncol. 6:26 (2016) [2] Thomas et al. Neurosurgery. 75(4): 409-418 (2014) [3] McDonald et al. J Neurosurg (Suppl 2) 121: 51-59 (2014) [4] Clark et al. Pract. Radiat. Oncol. 2: 306-313 (2012) [5] Minniti et al. Radiat. Oncol. J. 6: 48 (2011).

Interinstitutional Dosimetric Comparison Between Stereotactic Radiosurgery and Volumetric Modulated Arc Therapy Radiosurgery for Difficult Intracranial Cases

Interinstitutional Dosimetric Comparison Between Stereotactic Radiosurgery and Volumetric Modulated Arc Therapy Radiosurgery for Difficult Intracranial Cases

Is a single isocenter sufficient for volumetric modulated arc therapy radiosurgery when multiple intracranial metastases are spatially dispersed?

Previous work demonstrated improved dosimetry of single isocenter volumetric modulated arc therapy (VMAT) of multiple intracranial targets when they are located ≤ 4cm from isocenter because of narrower multileaf collimators (MLCs). In follow-up, we sought to determine if decreasing isocenter-target distance (diso) by using 2 to 3 isocenters would improve dosimetry for spatially dispersed targets. We also investigated the effect of a maximum dose constraint during VMAT optimization, and the dosimetric effect of the number of VMAT arcs used for a larger number of targets (i.e., 7 to 9). We identified radiosurgery cases that had multiple intracranial targets with diso of at least 1 target > 5cm. A single isocenter VMAT plan was created using a standardized 4-arc technique with 18Gy per target. Each case was then replanned (1) using 2 to 3 isocenters, (2) including a maximum dose constraint per target, and in the case of 7 to 9 targets, (3) using 3 to 6 arcs. Dose evaluation included brain V6Gy and V12Gy, and conformity index (CI), gradient index (GI), and heterogeneity index (HI) per target. Two isocenters were sufficient to limit diso to ≤ 4cm and ≤ 5cm for 11/15 and 13/15 cases, respectively; after replanning with 2 to 3 isocenters, diso decreased from 5.8 ± 2.8cm (2.3 14.9) to 2.5 ± 1.4cm (0 5.2). All dose statistics improved on average, albeit modestly: V6Gy = 6.9 ± 7.1%, V12Gy = 0.9% ± 4.4%, CI = 2.6% ± 4.6%, GI = 0.9% ± 12.7%, and HI = 2.6% ± 5.2%; however, the number of arcs doubled and monitor units increase by nearly 2-fold. A maximum dose constraint had a negative effect on all dose indices, increasing V12Gy by 9.7 ± 6.9%. For ≥ 7 targets, increasing number of arcs to > 3 improved CI, V12Gy, and V6Gy. A single isocenter is likely sufficient for VMAT radiosurgery of multiple intracranial metastases. Optimal treatment plan quality is achieved when no constraint is placed on the maximum target dose; for cases with many targets at least 4 arcs are needed for optimal plan quality.

Knowledge-based prediction of plan quality metrics in intracranial stereotactic radiosurgery.

The objective of this work was to develop a comprehensive knowledge-based methodology for predicting achievable dose-volume histograms (DVHs) and highly precise DVH-based quality metrics (QMs) in stereotactic radiosurgery/radiotherapy (SRS/SRT) plans. Accurate QM estimation can identify suboptimal treatment plans and provide target optimization objectives to standardize and improve treatment planning. Correlating observed dose as it relates to the geometric relationship of organs-at-risk (OARs) to planning target volumes (PTVs) yields mathematical models to predict achievable DVHs. In SRS, DVH-based QMs such as brain V10Gy (volume receiving 10 Gy or more), gradient measure (GM), and conformity index (CI) are used to evaluate plan quality. This study encompasses 223 linear accelerator-based SRS/SRT treatment plans (SRS plans) using volumetric-modulated arc therapy (VMAT), representing 95% of the institution's VMAT radiosurgery load from the past four and a half years. Unfiltered models that use all available plans for the model training were built for each category with a stratification scheme based on target and OAR characteristics determined emergently through initial modeling process. Model predictive accuracy is measured by the mean and standard deviation of the difference between clinical and predicted QMs, δQM = QMclin - QMpred, and a coefficient of determination, R(2). For categories with a large number of plans, refined models are constructed by automatic elimination of suspected suboptimal plans from the training set. Using the refined model as a presumed achievable standard, potentially suboptimal plans are identified. Predictions of QM improvement are validated via standardized replanning of 20 suspected suboptimal plans based on dosimetric predictions. The significance of the QM improvement is evaluated using the Wilcoxon signed rank test. The most accurate predictions are obtained when plans are stratified based on proximity to OARs and their PTV volume sizes. Volumes are categorized into small (VPTV < 2 cm(3)), medium (2 cm(3) < VPTV < 25 cm(3)), and large (25 cm(3) < VPTV). The unfiltered models demonstrate the ability to predict GMs to ∼1 mm and fractional brain V10Gy to ∼25% for plans with large VPTV and critical OAR involvements. Increased accuracy and precision of QM predictions are obtained when high quality plans are selected for the model training. For the small and medium VPTV plans without critical OAR involvement, predictive ability was evaluated using the refined model. For training plans, the model predicted GM to an accuracy of 0.2 ± 0.3 mm and fractional brain V10Gy to 0.04 ± 0.12, suggesting highly accurate predictive ability. For excluded plans, the average δGM was 1.1 mm and fractional brain V10Gy was 0.20. These δQM are significantly greater than those of the model training plans (p < 0.001). For CI, predictions are close to clinical values and no significant difference was observed between the training and excluded plans (p = 0.19). Twenty outliers with δGM > 1.35 mm were identified as potentially suboptimal, and replanning these cases using predicted target objectives demonstrates significant improvements on QMs: on average, 1.1 mm reduction in GM (p < 0.001) and 23% reduction in brain V10Gy (p < 0.001). After replanning, the difference of δGM distribution between the 20 replans and the refined model training plans was marginal. The results demonstrate the ability to predict SRS QMs precisely and to identify suboptimal plans. Furthermore, the knowledge-based DVH predictions were directly used as target optimization objectives and allowed a standardized planning process that bettered the clinically approved plans. Full clinical application of this methodology can improve consistency of SRS plan quality in a wide range of PTV volume and proximity to OARs and facilitate automated treatment planning for this critical treatment site.

Feasibility of single-isocenter, multi-arc non-coplanar volumetric modulated arc therapy for multiple brain tumors using a linear accelerator with a 160-leaf multileaf collimator: a phantom study.

The feasibility of single isocenter, multi-arc non-coplanar volumetric modulated arc therapy (VMAT) for multiple brain tumors was studied using an Elekta Synergy linear accelerator with an Agility multileaf collimator and a Monaco treatment planning system. Two VMAT radiosurgery plans consisting of a full arc and three half arcs were created with a prescribed dose of 20 Gy in a single fraction. After dose delivery to a phantom, ionization chambers and radiochromic films were used for dose measurement. The first VMAT radiosurgery plan had nine targets inside the phantom, and the doses were measured by the chambers at two different points and by the films on three sagittal and three coronal planes. The differences between the calculated dose and the dose measured by a Farmer ionization chamber and a pinpoint ionization chamber were <1.00% and <2.30%, respectively, and the average pass rates of gamma indices among the six planes under each of 3%/3 mm and 2%/2 mm criteria were 98.6% and 92.6%, respectively. The second VMAT radiosurgery plan was based on a clinical 14 brain metastases. Differences between calculated and film-measured doses were evaluated on two sagittal planes. The average pass rates of the gamma indices on the planes under each of 3%/3 mm and 2%/2 mm criteria were 97.8% and 88.8%, respectively. It was confirmed that single-isocenter, non-coplanar multi-arc VMAT radiosurgery for multiple brain metastases was feasible using Elekta Synergy with Agility and Monaco treatment planning systems. It was further shown that film dosimetry was accurately performed for a dose of up to nearly 25 Gy.

A comprehensive investigation of the accuracy and reproducibility of a multitarget single isocenter VMAT radiosurgery technique

Recent trends in stereotactic radiosurgery use multifocal volumetric modulated arc therapy (VMAT) plans to simultaneously treat several distinct targets. Conventional verification often involves low resolution measurements in a single plane, a cylinder, or intersecting planes of diodes or ion chambers. This work presents an investigation into the consistency and reproducibility of this new treatment technique using a comprehensive commissioned high-resolution 3D dosimetry system (PRESAGE(®)∕Optical-CT). A complex VMAT plan consisting of a single isocenter but five separate targets was created in Eclipse for a head phantom containing a cylindrical PRESAGE(®) dosimetry insert of 11 cm diameter and height. The plan contained five VMAT arcs delivering target doses from 12 to 20 Gy. The treatment was delivered to four dosimeters positioned in the head phantom and repeated four times, yielding four separate 3D dosimetry verifications. Each delivery was completely independent and was given after image guided radiation therapy (IGRT) positioning using Brainlab ExacTrac and cone beam computed tomography. A final delivery was given to a modified insert containing a pin-point ion chamber enabling calibration of PRESAGE(®) 3D data to dose. Dosimetric data were read out in an optical-CT scanner. Consistency and reproducibility of the treatment technique (including IGRT setup) was investigated by comparing the dose distributions in the four inserts, and with the predicted treatment planning system distribution. Dose distributions from the four dosimeters were registered and analyzed to determine the mean and standard deviation at all points throughout the dosimeters. A dose standard deviation of <3% was found from dosimeter to dosimeter. Global 3D gamma maps show that the predicted and measured dose matched well [3D gamma passing rate was 98.0% (3%, 2 mm)]. The deliveries of the irradiation were found to be consistent and matched the treatment plan, demonstrating high accuracy and reproducibility of both the treatment machine and the IGRT procedure. The complexity of the treatment (multiple arcs) and dosimetry (multiple strong gradients) pose a substantial challenge for comprehensive verification. 3D dosimetry can be uniquely effective in this scenario.

EP-1121: Volumetric Modulated Arc Therapy Radiosurgery for liver metastases: feasibility and early clinical experience

EP-1121: Volumetric Modulated Arc Therapy Radiosurgery for liver metastases: feasibility and early clinical experience

Feasibility of Single-Isocenter Volumetric Modulated Arc Radiosurgery for Treatment of Multiple Brain Metastases

To evaluate the relative plan quality of single-isocenter vs. multi-isocenter volumetric modulated arc therapy (VMAT) for radiosurgical treatment of multiple central nervous system metastases. VMAT plans were created using RapidArc technology for treatment of simulated patients with three brain metastases. The plans consisted of single-arc/single-isocenter, triple-arc (noncoplanar)/single-isocenter, and triple-arc (coplanar)/triple-isocenter configurations. All VMAT plans were normalized to deliver 100% of the 20-Gy prescription dose to all lesions. The plans were evaluated by calculation of Paddick and Radiation Therapy Oncology Group conformity index scores, Paddick gradient index scores, and 12-Gy isodose volumes. All plans were judged clinically acceptable, but differences were observed in the dosimetric parameters, with the use of multiple noncoplanar arcs showing small improvements in the conformity indexes compared with the single-arc/single-isocenter and triple-arc (coplanar)/triple-isocenter plans. Multiple arc plans (triple-arc [noncoplanar]/single-isocenter and triple-arc [coplanar]/triple-isocenter) showed smaller 12-Gy isodose volumes in scenarios involving three metastases spaced closely together, with only small differences noted among all plans involving lesions spaced further apart. Our initial results suggest that single-isocenter VMAT plans can be used to deliver conformity equivalent to that of multiple isocenter VMAT techniques. For targets that are closely spaced, multiple noncoplanar single-isocenter arcs might be required. VMAT radiosurgery for multiple targets using a single isocenter can be efficiently delivered, requiring less than one-half the beam time required for multiple isocenter set ups. VMAT radiosurgery will likely replace multi-isocenter techniques for linear accelerator-based treatment of multiple targets.