# Assessment of Early Cardiotoxicity and Cardiac Dysfunction of Radioligand Therapy in Patients with Neuroendocrine Tumors

## TL;DR

This study shows that radioligand therapy for neuroendocrine tumors does not cause heart damage, even in high-risk patients.

## Contribution

The study provides the first large-scale evidence of the cardiac safety of radioligand therapy in neuroendocrine tumor patients.

## Key findings

- No significant increases in cardiac biomarkers were observed in the overall population after RLT.
- High-risk subgroups, including those with heart failure or carcinoid heart disease, showed no signs of cardiotoxicity.
- RLT was found to be safe in terms of cardiotoxicity and cardiac dysfunction.

## Abstract

Radioligand therapy (RLT) with [177Lu]Lu-DOTA-TATE, alone or in combination with [90Y]Y-DOTA-TATE, is an established treatment option for patients with neuroendocrine tumors (NETs). Although highly effective, concerns remain regarding its potential impact on cardiac injury, particularly in subgroups with increased susceptibility to such injury. This study evaluated potential cardiotoxicity by measuring serum concentrations of troponin I, CK-MB, and NT-proBNP before and after RLT. A total of 60 patients undergoing 228 treatment courses were included, representing the largest cohort analyzed to date. No significant increases in cardiac biomarkers were observed, either in the overall population or in high-risk subgroups such as those with heart failure, carcinoid heart disease, or prior chemotherapy. These findings provide the first evidence from a large patient population that RLT is not associated with cardiotoxicity or cardiac dysfunction. Our results therefore support the cardiac safety of RLT in NET patients, including those at increased risk of cardiotoxicity.

Background: Cardiotoxicity remains a concern across cancer therapies. To date, there is a lack of extensive studies evaluating the potential impact of radioligand therapy (RLT) on myocardial injury in patients with neuroendocrine tumors (NETs), particularly in subgroups with increased susceptibility to such injury. This study aimed to assess the potential cardiotoxic effects and myocardial dysfunction associated with RLT using both [177Lu]Lu-DOTA-TATE and tandem therapy with [177Lu]Lu-DOTA-TATE/[90Y]Y-DOTA-TATE in patients with NETs, including specific high-risk subgroups such as patients with pre-existing heart failure, carcinoid heart disease or those previously treated with chemotherapy, by monitoring serum concentration of troponin I, CK-MB, and NT-proBNP before and after RLT. Methods: We conducted a retrospective observational analysis of 60 consecutive NET patients who underwent 228 RLT courses. A comprehensive cardiac assessment, including a detailed medical history, was performed. Additionally, serum troponin I, CKMB and NT-proBNP concentrations were measured prior to treatment and 48 h post-therapy. Fifty-two patients received [177Lu]Lu-DOTA-TATE monotherapy, while eight patients were treated with tandem therapy. Results: No increase in cardiotoxicity markers was observed in the overall study population following RLT administration (ΔTroponin −0.2 [−1.4–0.3]ng/L, p = 0.007; ∆CKMB 0.0 [−4.0–3.0]U/L, p = 0.90; ΔNT-proBNP 4.0 [−45.6–33.6]pg/mL) as well as in the subgroup receiving tandem therapy (ΔTroponin 0.7 [−1.7–013]ng/L, p = 0.68; ΔCKMB −0.5 [−10.7–3.0]U/L, p = 0.21; ΔNT-proBNP −21.6 [−44.1–16.7]pg/mL). Furthermore, none of the predefined patient subgroups exhibited signs of cardiotoxicity or evidence of myocardial dysfunction. Conclusions: RLT is a safe anticancer treatment option for patients with NETs in terms of cardiotoxicity and cardiac dysfunction, including those at higher risk of cardiovascular complications.