Lower dose radiotherapy did not alter cardiac function and was not pro-arrhythmic: results of the small prospective HALO trial
Authors: Hoeksema W F , Belderbos J S A , Dieleman E M T , Hopman L H G , Van Doorn C J , De Bruin H A C M , Van Der Ree M H , Visser J , Van Kesteren Z , Postema P G , Boekholdt S M , Planken R N , Sonke J J , Stam B 
Published: May 2024

Abstract

Background
Stereotactic arrhythmia radiotherapy (STAR) is a highly promising bail-out treatment for patients with therapy-refractory ventricular tachycardia (VT). Despite precise, noninvasive targeting of the pro-arrhythmic area, surrounding healthy cardiac tissue inadvertently receives low-dose radiation. There is a historical notion that collateral cardiac damage from radiation of extra-cardiac structures can cause heart failure and arrhythmias. In the HALO trial, where non-small cell lung cancer (NSCLC) patients treated with stereotactic ablative radiotherapy (SABR) received relatively low-dose radiotherapy to the heart, detailed cardiac safety after radiotherapy was therefore evaluated.

Objective
The aim of this study was to prospectively evaluate cardiac function after collateral radiotherapy on the heart in patients with NSCLC treated with SABR.

Methods
The HALO trial was a prospective observational trial evaluating cardiac adverse effects in patients treated with SABR for early stage NSCLC. Patients with a tumour within 3cm of the pericardium were eligible to participate. The mean radiotherapy dose per segment was calculated by semi-automated angulation and segmentation using an in-house developed tool. The heart was segmented according to the AHA 17-segment model. Patients underwent cardiac magnetic resonance imaging (CMR) pre-treatment, 3 and 12 months after treatment. CMR strain-analysis was conducted by two independent observers using cvi42 software. Longitudinal, radial and circumferential strain were measured both globally and segmentally and evaluated for dose-dependent effects.

Results
Ten patients were included in this study. Two patients dropped out before first follow-up and were not included in this analysis. Median age was 66 years (range 58-81) and four were male (50%). Median distance between the tumour and pericardium was 0.46cm (range 0.00-2.80). Patients were treated with 8 fractions of 7.0-7.5 Gy (n=6), 5 fractions of 11.0 Gy (n=1) or 3 fractions of 18.0 Gy (n=1). Median global cardiac radiotherapy dose was 6.7 Gy (range 0.1-17.9). Pre-treatment, median left ventricular ejection fraction as measured on CMR was 65% (range 40-75), global longitudinal strain was -15% (-20 - -9), global circumferential strain was -17% (-26 - -9) and global radial strain was 28% (11-60). These did not significantly change comparing 3 months and 12 months after treatment with pre-treatment. As can be appreciated from Table 1, there were no dose-dependent effects on segmental longitudinal, radial and circumferential strain both 3 months or 12 months after SABR. There were no ventricular arrhythmias observed during follow-up.

Conclusion
In this small study, collateral radiotherapy in patients with NSCLC treated with SABR did not significantly alter cardiac function as measured on CMR, and no relevant pro-arrhythmic effects were observed during short term follow-up. Extending the research into a larger dataset is warranted.