Chandekar Kunal Ramesh, Satapathy Swayamjeet, Ballal Sanjana, Yadav Madhav Prasad, Ravindra Shubha Gadde, Rastogi Sameer, Sahoo Ranjit Kumar, Bal Chandrasekhar
Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India; and.
Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India.
J Nucl Med. 2025 Jul 1;66(7):1046-1053. doi: 10.2967/jnumed.125.269456.
Skeletal metastases portend a poor prognosis for patients with neuroendocrine tumors (NETs). Literature on peptide receptor radionuclide therapy (PRRT) specific to patients with skeletal metastases from NETs is scarce. This study assessed real-world clinical outcomes of Lu-DOTATATE PRRT in this patient subgroup. Data from consecutive patients with well-differentiated NETs and skeletal metastases treated with Lu-DOTATATE at our center from January 2014 until August 2024 were retrospectively reviewed. Safety, efficacy, progression-free survival (PFS), and overall survival (OS) outcomes were analyzed. In total, 288 PRRT cycles were administered to 74 patients. The median number of PRRT cycles was 4 (interquartile range, 2-6), and the median cumulative activity was 21.3 GBq (interquartile range, 11.1-33.3 GBq). The best objective response rates, evaluated using modified M.D. Anderson criteria (bone metastases) and RECIST 1.1 (overall response), were 31% and 23%, respectively, for 62 evaluable patients. The skeletal metastases burden (≤10 vs. >10 sites) did not significantly affect objective response rates. Among the 23 patients with bone pain (31%), 39% reported complete resolution and 52% experienced a partial reduction after treatment. Grade 4 or 5 adverse events occurred in 12% of patients, with anemia, thrombocytopenia, leukopenia, and neutropenia each occurring in fewer than 5% of patients. Skeletal-related events were noted in 20% of patients. The median PFS and OS were 29 mo (95% CI, 18.0-39.9 mo) and 44 mo (95% CI, 32.8-55.2 mo), respectively. Multivariate Cox regression analysis revealed that higher cumulative activity (≥29.6 GBq) was the strongest independent predictor of improved PFS (hazard ratio [HR], 0.15; < 0.001) and OS (HR, 0.11; < 0.001), whereas serum alkaline phosphatase elevation (HR, 2.68; = 0.048) and male sex (HR, 3.48; = 0.007) were associated with worse OS rates. Lu-DOTATATE PRRT is an effective treatment modality for patients with skeletal metastases from NETs (regardless of metastatic burden), with a favorable safety profile and favorable survival outcomes. Serum alkaline phosphatase monitoring is essential in this patient cohort. Achieving an optimal cumulative activity is crucial to maximizing the survival benefit of patients receiving PRRT.
骨转移预示着神经内分泌肿瘤（NETs）患者的预后不良。关于NETs骨转移患者特异性的肽受体放射性核素治疗（PRRT）的文献很少。本研究评估了镥-奥曲肽PRRT在该患者亚组中的真实世界临床疗效。回顾性分析了2014年1月至2024年8月在我们中心接受镥-奥曲肽治疗的连续的高分化NETs和骨转移患者的数据。分析了安全性、疗效、无进展生存期（PFS）和总生存期（OS）结果。总共对74例患者进行了288个PRRT周期。PRRT周期的中位数为4（四分位间距，2 - 6），累积活度中位数为21.3 GBq（四分位间距，11.1 - 33.3 GBq）。根据改良的MD安德森标准（骨转移）和RECIST 1.1（总体缓解）评估，62例可评估患者的最佳客观缓解率分别为31%和23%。骨转移负担（≤10个部位与>10个部位）对客观缓解率没有显著影响。在23例有骨痛的患者（31%）中，39%报告治疗后疼痛完全缓解，52%疼痛部分减轻。12%的患者发生4级或5级不良事件，贫血、血小板减少、白细胞减少和中性粒细胞减少的发生率均低于5%。20%的患者出现骨相关事件。PFS和OS的中位数分别为29个月（95%CI，18.0 - 39.9个月）和44个月（95%CI，32.8 - 55.2个月）。多因素Cox回归分析显示，较高的累积活度（≥29.6 GBq）是PFS改善（风险比[HR]，0.15；P < 0.001）和OS改善（HR，0.11；P < 0.001）的最强独立预测因素，而血清碱性磷酸酶升高（HR，2.68；P = 0.048）和男性（HR, 3.48；P = = 0.007）与较差的OS率相关。镥-奥曲肽PRRT是NETs骨转移患者（无论转移负担如何）的一种有效治疗方式，具有良好的安全性和生存结局。在该患者队列中，监测血清碱性磷酸酶至关重要。实现最佳累积活度对于使接受PRRT的患者生存获益最大化至关重要。
