Long-term Safety and Cumulative Efficacy of Multicycle 177Lu-DOTA-IBA Therapy in Bone Metastases: A Retrospective Cohort Study

PURPOSE: To evaluate the long-term efficacy, safety, and survival outcomes of at least 4 treatment cycles of 177Lu-DOTA-IBA therapy in patients with bone metastases. PATIENTS AND METHODS: This single-center retrospective cohort study enrolled patients with bone metastases who initiated therapy between November 2021 and May 2024 and completed ≥4 cycles of 177Lu-DOTA-IBA. The primary endpoints were symptom improvement [Numerical Rating Scale (NRS) and Karnofsky Performance Status (KPS)], safety (Common Terminology Criteria for Adverse Events v5.0), and overall survival. Longitudinal efficacy changes were analyzed using linear mixed-effects models. RESULTS: Fifty-six patients were included: 31 completed 4-5 cycles and 25 completed 6-10 cycles. Pharmacokinetic analysis (n=20) demonstrated a longer effective half-life in lesions than in the whole body, with progressively increasing target-to-nontarget uptake ratios over time. Treatment-related myelosuppression of any grade occurred in 8 patients (14.3%), renal toxicity in 4 (7.1%), and grade 3 thrombocytopenia in 1 (1.8%); no other grade 3-4 adverse events were observed. Increasing treatment cycles were not associated with increased hematological or renal toxicity. The best overall pain response rate (NRS reduction ≥50%) was 88.5%, and KPS improvement was observed in 79.6% of patients. Longitudinal analysis demonstrated cumulative therapeutic benefit, with continuous NRS reduction and KPS improvement across cycles. Disease progression during treatment independently predicted shorter survival. CONCLUSIONS: For patients with bone metastases who can tolerate multicycle therapy, long-term 177Lu-DOTA-IBA treatment yields cumulative symptom improvement with no significant increase in cumulative toxicity risk, supporting its use as a long-term therapeutic strategy.