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.

Background and Aims: Stereotactic arrhythmia radioablation (STAR) is increasingly used for refractory ventricular tachycardia (VT), yet prospective multicentre outcome data remain limited. Here, the planned interim analysis of the prospective Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary (STOPSTORM) registry is reported. Methods: STOPSTORM is a European prospective, international, multicentre registry of patients treated with STAR. The primary efficacy endpoint was the change in sustained VT episode burden comparing the 6 months before versus the 6 months after STAR. The primary safety endpoint was the occurrence of serious adverse events (SAEs) adjudicated as possibly or probably treatment-related. Overall survival was assessed using time-to-event methods. Results: Across 28 centres, 193 patients were included (mean age 68±9 years; 88% male; 53% non-ischaemic cardiomyopathy). Median follow-up was 19 months. Among 107 evaluable patients with ≥6-month follow-up, the median VT episode burden was reduced by 80% after STAR. Among patients surviving ≥6 months, 72% were free from implantable cardioverter-defibrillator (ICD) shock. In the full cohort, 12 SAEs were adjudicated as possibly or probably treatment-related, including pericardial effusion, coronary events, and early post-treatment ventricular arrhythmia. Overall survival probability was 77% at 12 months. Conclusions: In the largest prospective multicentre cohort reported to date, STAR was associated with a substantial reduction in VT burden and ICD shocks, with a low frequency of possibly or probably treatment-related SAEs.

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. 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. 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. 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.

Breast cancer (BC) is one of the most diagnosed malignant carcinomas in women with a triple-negative breast cancer (TNBC) phenotype being correlated with poorer prognosis. Fractionated radiotherapy (RT) is a central component of breast cancer management, especially after breast conserving surgery and is increasingly important for TNBC subtype prognosis. In recent years, moderately hypofractionated radiation schedules are established as a standard of care, but many professionals remain skeptical and are concerned about their efficiency and side effects. In the present study, two different triple-negative breast cancer cell lines, a non-malignant breast epithelial cell line and fibroblasts, were irradiated daily under normofractionated and hypofractionated schedules to evaluate the impact of different irradiation regimens on radiation-induced cell-biological effects. During the series of radiotherapy, proliferation, growth rate, double-strand DNA break-repair (DDR), cellular senescence, and cell survival were measured. Investigated normal and cancer cells differed in their responses and receptivity to different irradiation regimens, indicating cell line/cell type specificity of the effect. At the end of both therapy concepts, normal and malignant cells reach almost the same endpoint of cell count and proliferation inhibition, confirming the clinical observations in the follow-up at the cellular level. These result in cell lines closely replicating the irradiation schedules in clinical practice and, to some extent, contributing to the understanding of growth rate or remission of tumors and the development of fibrosis.

Purpose: For adjuvant radiotherapy of low-risk breast cancer after breast-conserving surgery, there have been many trials of hypofractionation and partial breast irradiation (PBI) over the years, with proven mild long-term toxicity. The aim of this study was to introduce a short-course dose-adapted concept, proven in whole breast irradiation (WBI) for use in accelerated partial breast irradiation (APBI), while monitoring dosimetric data and toxicity. Methods: From April 2020 to March 2022, 61 patients with low-risk breast cancer or ductal carcinoma in situ (DCIS) were treated at a single institution with percutaneous APBI of 26 Gy in five fractions every other day after breast-conserving surgery. Dosimetric data for target volume and organs at risk were determined retrospectively. Acute toxicity was evaluated. Results: The target volume of radiotherapy comprised an average of 19% of the ipsilateral mamma. The burden on the heart and lungs was very low. The mean cardiac dose during irradiation of the left breast was only 0.6 Gy. Two out of three patients remained without any acute side effects. Conclusions: Linac-based APBI is an attractive treatment option for patients with low-risk breast cancer in whom neither WBI nor complete omission of radiotherapy appears to be an adequate alternative.

BE following RT after breast-conserving surgery is a common concern, impacting patients’ quality of life. This study introduces a clinically meaningful classification system for BE and retrospectively evaluates its incidence among patients treated with normofractionated (nfRT) and hypofractionated (hfRT) regimens. Data from 1156 patients treated between 2011 and 2021 were analyzed. BE was graded according to the CTC and a so-called “WST classification” (grade 1: lymphatic drainage performed by the patient; grade 2: professional lymphatic drainage; grade 3: surgery). A total of 33%/17% developed BE according to the WST classification/CTC. Grade III BE was not reported. About 70% experienced a remission of BE during follow-up. Risk factors for the development of BE included RT of lymphatic drainage, complete axillary dissection compared to sentinel node dissection, and CTX. CTX was not confirmed in multivariate analysis. The incidence of BE did not differ significantly between the nfRT and hfRT groups, affirming the safety and comparability of hfRT regarding BE risk (HR: 0.833, p = 0.1219). This study emphasizes the importance of precise and standardized BE classification for improved treatment outcomes. Given its comparable risk profile and potential for enhanced therapy adherence, the findings support hfRT as a preferred regimen aligned with the current guidelines.