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

<b>Background</b>: 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. <b>Methods</b>: 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. <b>Results</b>: No increase in cardiotoxicity markers was observed in the overall study population following RLT administration (ΔTroponin -0.2 [-1.4-0.3]ng/L, <i>p</i> = 0.007; ∆CKMB 0.0 [-4.0-3.0]U/L, <i>p</i> = 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, <i>p</i> = 0.68; ΔCKMB -0.5 [-10.7-3.0]U/L, <i>p</i> = 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. <b>Conclusions</b>: 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.