Radiosurgery for ventricular tachycardia (RAVENTA): interim analysis of a multicenter multiplatform feasibility trial.

BACKGROUND: Single-session cardiac stereotactic radiation therapy (SBRT) has demonstrated promising results for patients with refractory ventricular tachycardia (VT). However, the full safety profile of this novel treatment remains unknown and very limited data from prospective clinical multicenter trials are available. METHODS: The prospective multicenter multiplatform RAVENTA (radiosurgery for ventricular tachycardia) study assesses high-precision image-guided cardiac SBRT with 25 Gy delivered to the VT substrate determined by high-definition endocardial and/or epicardial electrophysiological mapping in patients with refractory VT ineligible for catheter ablation and an implanted cardioverter defibrillator (ICD). Primary endpoint is the feasibility of full-dose application and procedural safety (defined as an incidence of serious [grade ≥ 3] treatment-related complications ≤ 5% within 30 days after therapy). Secondary endpoints comprise VT burden, ICD interventions, treatment-related toxicity, and quality of life. We present the results of a protocol-defined interim analysis. RESULTS: Between 10/2019 and 12/2021, a total of five patients were included at three university medical centers. In all cases, the treatment was carried out without complications. There were no serious potentially treatment-related adverse events and no deterioration of left ventricular ejection fraction upon echocardiography. Three patients had a decrease in VT episodes during follow-up. One patient underwent subsequent catheter ablation for a new VT with different morphology. One patient with local VT recurrence died 6 weeks after treatment in cardiogenic shock. CONCLUSION: The interim analysis of the RAVENTA trial demonstrates early initial feasibility of this new treatment without serious complications within 30 days after treatment in five patients. Recruitment will continue as planned and the study has been expanded to further university medical centers. TRIAL REGISTRATION NUMBER: NCT03867747 (clinicaltrials.gov). Registered March 8, 2019. Study start: October 1, 2019.

STereotactic Arrhythmia Radioablation (STAR): the Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary consortium (STOPSTORM.eu) and review of current patterns of STAR practice in Europe.

The EU Horizon 2020 Framework-funded Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary (STOPSTORM) consortium has been established as a large research network for investigating STereotactic Arrhythmia Radioablation (STAR) for ventricular tachycardia (VT). The aim is to provide a pooled treatment database to evaluate patterns of practice and outcomes of STAR and finally to harmonize STAR within Europe. The consortium comprises 31 clinical and research institutions. The project is divided into nine work packages (WPs): (i) observational cohort; (ii) standardization and harmonization of target delineation; (iii) harmonized prospective cohort; (iv) quality assurance (QA); (v) analysis and evaluation; (vi, ix) ethics and regulations; and (vii, viii) project coordination and dissemination. To provide a review of current clinical STAR practice in Europe, a comprehensive questionnaire was performed at project start. The STOPSTORM Institutions' experience in VT catheter ablation (83% ≥ 20 ann.) and stereotactic body radiotherapy (59% > 200 ann.) was adequate, and 84 STAR treatments were performed until project launch, while 8/22 centres already recruited VT patients in national clinical trials. The majority currently base their target definition on mapping during VT (96%) and/or pace mapping (75%), reduced voltage areas (63%), or late ventricular potentials (75%) during sinus rhythm. The majority currently apply a single-fraction dose of 25 Gy while planning techniques and dose prescription methods vary greatly. The current clinical STAR practice in the STOPSTORM consortium highlights potential areas of optimization and harmonization for substrate mapping, target delineation, motion management, dosimetry, and QA, which will be addressed in the various WPs.

Stereotactic arrhythmia radioablation (STAR)-A systematic review and meta-analysis of prospective trials on behalf of the STOPSTORM.eu consortium.

Stereotactic arrhythmia radioablation (STAR) is a noninvasive treatment of refractory ventricular tachycardia (VT). In this study, we aimed to systematically review prospective trials on STAR and pool harmonized outcome measures in a meta-analysis. After registration in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42023439666), we searched OVID Medline, OVID Embase, Web of Science Core Collection, the Cochrane Central Register of Controlled Trials, and Google Scholar on November 9, 2023, to identify reports describing results of prospective trials evaluating STAR for VT. Risk of bias was assessed using the Risk Of Bias In Non-randomized Studies of Interventions tool. Meta-analysis was performed using generalized linear mixed models. We identified 10 prospective trials in which 82 patients were treated with STAR between 2016 and 2022. The 90-day rate of treatment-related grade ≥3 adverse events was 0.10 (95% confidence interval [CI] 0.04-0.2). The proportions of patients achieving given VT burden reductions were 0.61 (95% CI 0.45-0.74) for ≥95%, 0.80 (95% CI 0.62-0.91) for ≥75%, and 0.9 (95% CI 0.77-0.96) for ≥50% in 63 evaluable patients. The 1-year overall survival rate was 0.73 (95% CI 0.61-0.83) in 81 patients, 1-year freedom from recurrence was 0.30 (95% CI 0.16-0.49) in 61 patients, and 1-year recurrence-free survival was 0.21 in 60 patients (95% CI 0.08-0.46). Limitations include methodological heterogeneity across studies and moderate to significant risk of bias. In conclusion, STAR is a promising treatment method, characterized by moderate toxicity. We observed 1-year mortality of ≈27% in this population of critically ill patients suffering from refractory VT. Most patients experience a significant reduction in VT burden; however, 1-year recurrence rates are high. STAR should still be considered an investigational approach and recommended to patients primarily within the context of prospective trials.

Semi-automated reproducible target transfer for cardiac radioablation - A multi-center cross-validation study within the RAVENTA trial.

BACKGROUND: Stereotactic arrhythmia radioablation (STAR) is a therapeutic option for ventricular tachycardia (VT) where catheter-based ablation is not feasible or has previously failed. Target definition and its transfer from electro-anatomic maps (EAM) to radiotherapy treatment planning systems (TPS) is challenging and operator-dependent. Software solutions have been developed to register EAM with cardiac CT and semi-automatically transfer 2D target surface data into 3D CT volume coordinates. Results of a cross-validation study of two conceptually different open-source software solutions using data from the RAVENTA trial (NCT03867747) are reported. METHODS: Clinical Target Volumes (CTVs) were created from target regions delineated on EAM using two conceptually different approaches by separate investigators on data of 10 patients, blinded to each other's results. Targets were transferred using 3D-3D registration and 2D-3D registration, respectively. The resulting CTVs were compared in a core-lab using two complementary analysis software packages for structure similarity and geometric characteristics. RESULTS: Volumes and surface areas of the CTVs created by both methods were comparable: 14.88 ±â€¯11.72 ml versus 15.15 ±â€¯11.35 ml and 44.29 ±â€¯33.63 cm2 versus 46.43 ±â€¯35.13 cm2. The Dice-coefficient was 0.84 ±â€¯0.04; median surface-distance and Hausdorff-distance were 0.53 ±â€¯0.37 mm and 6.91 ±â€¯2.26 mm, respectively. The 3D-center-of-mass difference was 3.62 ±â€¯0.99 mm. Geometrical volume similarity was 0.94 ±â€¯0.05 %. CONCLUSION: The STAR targets transferred from EAM to TPS using both software solutions resulted in nearly identical 3D structures. Both solutions can be used for QA (quality assurance) and EAM-to-TPS transfer of STAR-targets. Semi-automated methods could potentially help to avoid mistargeting in STAR and offer standardized workflows for methodically harmonized treatments.

Refining Treatment Planning in STereotactic Arrhythmia Radioablation: Benchmark Results and Consensus Statement From the STOPSTORM.eu Consortium.

PURPOSE: STereotactic Arrhythmia Radioablation (STAR) showed promising results in patients with refractory ventricular tachycardia. However, clinical data are scarce and heterogeneous. The STOPSTORM.eu consortium was established to investigate and harmonize STAR in Europe. The primary goal of this benchmark study was to investigate current treatment planning practice within the STOPSTORM project as a baseline for future harmonization. METHODS AND MATERIALS: Planning target volumes (PTVs) overlapping extracardiac organs-at-risk and/or cardiac substructures were generated for 3 STAR cases. Participating centers were asked to create single-fraction treatment plans with 25 Gy dose prescriptions based on in-house clinical practice. All treatment plans were reviewed by an expert panel and quantitative crowd knowledge-based analysis was performed with independent software using descriptive statistics for International Commission on Radiation Units and Measurements report 91 relevant parameters and crowd dose-volume histograms. Thereafter, treatment planning consensus statements were established using a dual-stage voting process. RESULTS: Twenty centers submitted 67 treatment plans for this study. In most plans (75%) intensity modulated arc therapy with 6 MV flattening filter free beams was used. Dose prescription was mainly based on PTV D95% (49%) or D96%-100% (19%). Many participants preferred to spare close extracardiac organs-at-risk (75%) and cardiac substructures (50%) by PTV coverage reduction. PTV D0.035cm3 ranged from 25.5 to 34.6 Gy, demonstrating a large variety of dose inhomogeneity. Estimated treatment times without motion compensation or setup ranged from 2 to 80 minutes. For the consensus statements, a strong agreement was reached for beam technique planning, dose calculation, prescription methods, and trade-offs between target and extracardiac critical structures. No agreement was reached on cardiac substructure dose limitations and on desired dose inhomogeneity in the target. CONCLUSIONS: This STOPSTORM multicenter treatment planning benchmark study not only showed strong agreement on several aspects of STAR treatment planning, but also revealed disagreement on others. To standardize and harmonize STAR in the future, consensus statements were established; however, clinical data are urgently needed for actionable guidelines for treatment planning.

Stereotactic Arrhythmia Radioablation (STAR): Assessment of cardiac and respiratory heart motion in ventricular tachycardia patients - A STOPSTORM.eu consortium review.

AIM: To identify the optimal STereotactic Arrhythmia Radioablation (STAR) strategy for individual patients, cardiorespiratory motion of the target volume in combination with different treatment methodologies needs to be evaluated. However, an authoritative overview of the amount of cardiorespiratory motion in ventricular tachycardia (VT) patients is missing. METHODS: In this STOPSTORM consortium study, we performed a literature review to gain insight into cardiorespiratory motion of target volumes for STAR. Motion data and target volumes were extracted and summarized. RESULTS: Out of the 232 studies screened, 56 provided data on cardiorespiratory motion, of which 8 provided motion amplitudes in VT patients (n = 94) and 10 described (cardiac/cardiorespiratory) internal target volumes (ITVs) obtained in VT patients (n = 59). Average cardiac motion of target volumes was < 5 mm in all directions, with maximum values of 8.0, 5.2 and 6.5 mm in Superior-Inferior (SI), Left-Right (LR), Anterior-Posterior (AP) direction, respectively. Cardiorespiratory motion of cardiac (sub)structures showed average motion between 5-8 mm in the SI direction, whereas, LR and AP motions were comparable to the cardiac motion of the target volumes. Cardiorespiratory ITVs were on average 120-284% of the gross target volume. Healthy subjects showed average cardiorespiratory motion of 10-17 mm in SI and 2.4-7 mm in the AP direction. CONCLUSION: This review suggests that despite growing numbers of patients being treated, detailed data on cardiorespiratory motion for STAR is still limited. Moreover, data comparison between studies is difficult due to inconsistency in parameters reported. Cardiorespiratory motion is highly patient-specific even under motion-compensation techniques. Therefore, individual motion management strategies during imaging, planning, and treatment for STAR are highly recommended.

Quality assurance process within the RAdiosurgery for VENtricular TAchycardia (RAVENTA) trial for the fusion of electroanatomical mapping and radiotherapy planning imaging data in cardiac radioablation.

A novel quality assurance process for electroanatomical mapping (EAM)-to-radiotherapy planning imaging (RTPI) target transport was assessed within the multi-center multi-platform framework of the RAdiosurgery for VENtricular TAchycardia (RAVENTA) trial. A stand-alone software (CARDIO-RT) was developed to enable platform independent registration of EAM and RTPI of the left ventricle (LV), based on pre-generated radiotherapy contours (RTC). LV-RTC were automatically segmented into the American-Heart-Association 17-segment-model and a manual 3D-3D method based on EAM 3D-geometry data and a semi-automated 2D-3D method based on EAM screenshot projections were developed. The quality of substrate transfer was evaluated in five clinical cases and the structural analyses showed substantial differences between manual target transfer and target transport using CARDIO-RT.

Stereotactic arrhythmia radioablation: A multicenter pre-post intervention safety evaluation of the implantable cardioverter-defibrillator function.

BACKGROUND: Stereotactic arrhythmia radioablation (STAR) appears to be beneficial in selected patients with therapy-refractory ventricular tachycardia (VT). However, high-dose radiotherapy used for STAR-treatment may affect functioning of the patients' implantable cardioverter defibrillator (ICD) by direct effects of radiation on ICD components or cardiac tissue. Currently, the effect of STAR on ICD functioning remains unknown. METHODS: A retrospective pre-post multicenter study evaluating ICD functioning in the 12-month before and after STAR was performed. Patients with (non)ischemic cardiomyopathies with therapy-refractory VT and ICD who underwent STAR were included and the occurrence of ICD-related adverse events was collected. Evaluated ICD parameters included sensing, capture threshold and impedance. A linear mixed-effects model was used to investigate the association between STAR, radiotherapy dose and changes in lead parameters over time. RESULTS: In total, 43 patients (88% male) were included in this study. All patients had an ICD with an additional right atrial lead in 34 (79%) and a ventricular lead in 17 (40%) patients. Median ICD-generator dose was 0.1 Gy and lead tip dose ranged from 0-32 Gy. In one patient (2%), a reset occurred during treatment, but otherwise, STAR and radiotherapy dose were not associated with clinically relevant alterations in ICD leads parameters. CONCLUSIONS: STAR treatment did not result in major ICD malfunction. Only one radiotherapy related adverse event occurred during the study follow-up without patient harm. No clinically relevant alterations in ICD functioning were observed after STAR in any of the leads. With the reported doses STAR appears to be safe.

Refining critical structure contouring in STereotactic Arrhythmia Radioablation (STAR): Benchmark results and consensus guidelines from the STOPSTORM.eu consortium.

BACKGROUND AND PURPOSE: In patients with recurrent ventricular tachycardia (VT), STereotactic Arrhythmia Radioablation (STAR) shows promising results. The STOPSTORM.eu consortium was established to investigate and harmonise STAR treatment in Europe. The primary goals of this benchmark study were to standardise contouring of organs at risk (OAR) for STAR, including detailed substructures of the heart, and accredit each participating centre. MATERIALS AND METHODS: Centres within the STOPSTORM.eu consortium were asked to delineate 31 OAR in three STAR cases. Delineation was reviewed by the consortium expert panel and after a dedicated workshop feedback and accreditation was provided to all participants. Further quantitative analysis was performed by calculating DICE similarity coefficients (DSC), median distance to agreement (MDA), and 95th percentile distance to agreement (HD95). RESULTS: Twenty centres participated in this study. Based on DSC, MDA and HD95, the delineations of well-known OAR in radiotherapy were similar, such as lungs (median DSC = 0.96, median MDA = 0.1 mm and median HD95 = 1.1 mm) and aorta (median DSC = 0.90, median MDA = 0.1 mm and median HD95 = 1.5 mm). Some centres did not include the gastro-oesophageal junction, leading to differences in stomach and oesophagus delineations. For cardiac substructures, such as chambers (median DSC = 0.83, median MDA = 0.2 mm and median HD95 = 0.5 mm), valves (median DSC = 0.16, median MDA = 4.6 mm and median HD95 = 16.0 mm), coronary arteries (median DSC = 0.4, median MDA = 0.7 mm and median HD95 = 8.3 mm) and the sinoatrial and atrioventricular nodes (median DSC = 0.29, median MDA = 4.4 mm and median HD95 = 11.4 mm), deviations between centres occurred more frequently. After the dedicated workshop all centres were accredited and contouring consensus guidelines for STAR were established. CONCLUSION: This STOPSTORM multi-centre critical structure contouring benchmark study showed high agreement for standard radiotherapy OAR. However, for cardiac substructures larger disagreement in contouring occurred, which may have significant impact on STAR treatment planning and dosimetry evaluation. To standardize OAR contouring, consensus guidelines for critical structure contouring in STAR were established.

Treatment Planning for Cardiac Radioablation: Multicenter Multiplatform Benchmarking for the RAdiosurgery for VENtricular TAchycardia (RAVENTA) Trial.

PURPOSE: Cardiac radioablation is a novel treatment option for patients with refractory ventricular tachycardia unsuitable for catheter ablation. The quality of treatment planning depends on dose specifications, platform capabilities, and experience of the treating staff. To harmonize the treatment planning, benchmarking of this process is necessary for multicenter clinical studies such as the RAdiosurgery for VENtricular TAchycardia trial. METHODS AND MATERIALS: Planning computed tomography data and consensus structures from 3 patients were sent to 5 academic centers for independent plan development using a variety of platforms and techniques with the RAdiosurgery for VENtricular TAchycardia study protocol serving as guideline. Three-dimensional dose distributions and treatment plan details were collected and analyzed. In addition, an objective relative plan quality ranking system for ventricular tachycardia treatments was established. RESULTS: For each case, 3 coplanar volumetric modulated arc (VMAT) plans for C-arm linear accelerators (LINAC) and 3 noncoplanar treatment plans for robotic arm LINAC were generated. All plans were suitable for clinical applications with minor deviations from study guidelines in most centers. Eleven of 18 treatment plans showed maximal one minor deviation each for target and cardiac substructures. However, dose-volume histograms showed substantial differences: in one case, the planning target volume ≥30 Gy ranged from 0.0% to 79.9% and the ramus interventricularis anterior V14Gy ranged from 4.0% to 45.4%. Overall, the VMAT plans had steeper dose gradients in the high-dose region, while the plans for the robotic arm LINAC had smaller low-dose regions. Thereby, VMAT plans required only about half as many monitor units, resulting in shorter delivery times, possibly an important factor in treatment outcome. CONCLUSIONS: Cardiac radioablation is feasible with robotic arm and C-arm LINAC systems with comparable plan quality. Although cross-center training and best practice guidelines have been provided, further recommendations, especially for cardiac substructures, and ranking of dose guidelines will be helpful to optimize cardiac radioablation outcomes.

A New Phantom for Individual Verification of the Dose Distribution in Precision Radiotherapy for Head-and-Neck Cancer.

BACKGROUND/AIM: Many patients with head-and-neck cancers receive radiotherapy. Treatment planning can be very complex in case of dental fillings or implants that cause metal artefacts. Verification of dose distributions may be performed using specific phantoms. This study aimed to develop a 3D-printed phantom that can be produced easily and cost-effectively. PATIENTS AND METHODS: The phantom was designed to allow fast adaption to a patient's individual situation with a particular focus on metal artefacts due to dental fillings. Bone and soft-tissue shells were 3D-printed and filled with tissue-equivalent materials. RESULTS: Attenuation properties of the tissue-equivalent structures in the phantom corresponded well to the structures of real human anatomy. In magnetic resonance (MR)-imaging, useful signals of the materials in the phantom were obtained. CONCLUSION: The phantom met the requirements including equivalence with human tissues and can be useful for highly individual treatment planning in precision-radiotherapy of head-and-neck cancers. It can be also used for scientific issues related to MR-imaging.

Dosimetric Implications of Residual Tracking Errors During Robotic SBRT of Liver Metastases.

PURPOSE: Although the metric precision of robotic stereotactic body radiation therapy in the presence of breathing motion is widely known, we investigated the dosimetric implications of breathing phase-related residual tracking errors. METHODS AND MATERIALS: In 24 patients (28 liver metastases) treated with the CyberKnife, we recorded the residual correlation, prediction, and rotational tracking errors from 90 fractions and binned them into 10 breathing phases. The average breathing phase errors were used to shift and rotate the clinical tumor volume (CTV) and planning target volume (PTV) for each phase to calculate a pseudo 4-dimensional error dose distribution for comparison with the original planned dose distribution. RESULTS: The median systematic directional correlation, prediction, and absolute aggregate rotation errors were 0.3 mm (range, 0.1-1.3 mm), 0.01 mm (range, 0.00-0.05 mm), and 1.5° (range, 0.4°-2.7°), respectively. Dosimetrically, 44%, 81%, and 92% of all voxels differed by less than 1%, 3%, and 5% of the planned local dose, respectively. The median coverage reduction for the PTV was 1.1% (range in coverage difference, -7.8% to +0.8%), significantly depending on correlation (P=.026) and rotational (P=.005) error. With a 3-mm PTV margin, the median coverage change for the CTV was 0.0% (range, -1.0% to +5.4%), not significantly depending on any investigated parameter. In 42% of patients, the 3-mm margin did not fully compensate for the residual tracking errors, resulting in a CTV coverage reduction of 0.1% to 1.0%. CONCLUSIONS: For liver tumors treated with robotic stereotactic body radiation therapy, a safety margin of 3 mm is not always sufficient to cover all residual tracking errors. Dosimetrically, this translates into only small CTV coverage reductions.