# Protocol of the RADIO-STAR trial: a phase 1 safety and dose finding study of hypofractionated radiotherapy to the stellate ganglia for the treatment of ventricular arrhythmia

## TL;DR

This study explores using non-invasive radiotherapy to treat ventricular arrhythmia by targeting the stellate ganglia, aiming to improve safety and reduce complications compared to surgery.

## Contribution

The study introduces a novel non-invasive approach using hypofractionated radiotherapy for cardiac sympathetic denervation in patients with refractory ventricular arrhythmia.

## Key findings

- The study will assess the safety of radiotherapy targeting the stellate ganglia in patients with recurrent ventricular arrhythmia.
- It will evaluate changes in biomarkers like catecholamines and heart rate variability to determine treatment efficacy.
- MRI imaging will be used to monitor structural changes in the stellate ganglia following radiotherapy.

## Abstract

Sympathetic activation is the hallmark of cardiac disease, driving disease progression and triggering ventricular arrhythmia (VA). Despite optimal medical therapy, many patients experience recurrent VAs refractory to medical therapy, leading to repetitive implantable cardioverter defibrillator (ICD) therapy, worse quality of life and adverse outcomes. Cardiac sympathetic denervation (CSD) through surgical removal of the stellate ganglia is an effective treatment for refractory VAs but carries a high complication rate. We hypothesise that high precision image guided radiotherapy can be used to target the stellate ganglia to achieve CSD non-invasively.

RADIO-STAR (hypofractionated radiotherapy to the stellate ganglia for ventricular arrhythmia) is a first-in-human, phase 1 safety and dose finding study of radiotherapy to the stellate ganglia in patients with recurrent VAs. Patients with structural heart disease requiring recurrent ICD therapy for VAs are invited to undergo radiotherapy bilaterally to their stellate ganglia with a predetermined sample size of n=13. Radiotherapy dose will be determined by a prespecified dose escalation protocol. The primary outcome is safety defined as any treatment-related grade 3–5 toxicity occurring within 6 months of radiotherapy treatment, as defined by the Common Terminology Criteria for Adverse Events or any treatment-related side effects detected on patient symptom questionnaires and clinical examination during study visits. Secondary outcome measures to evaluate feasibility and efficacy include ability to safely deliver radiotherapy and consequent changes in circulating catecholamines and neuropeptide-Y, heart rate variability, structural changes in the stellate ganglia on MRI imaging and ICD therapy burden.

This study has received ethical approval by the South Central—Oxford B Research Ethics Committee (REC/SC/0005). Study findings will be submitted for publication in peer-reviewed scientific journals and presented at national and/or international scientific conferences.

ISRCTN49861434.