Therapy-related myeloid neoplasms in 177Lu-DOTATATE treated neuroendocrine tumor patients: how great is the risk?

Yael Kusne, Mrinal M Patnaik, Thorvardur R Halfdanarson, Mohamad Bassam Sonbol
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Abstract

Peptide receptor radionuclide therapy (PRRT) with lutetium-177-Dotatate (177Lu-DOTATATE) has transformed neuroendocrine tumor (NET) treatment, improving progression-free survival, symptom control, and quality of life. However, long-term hematologic toxicities, including therapy-related myeloid neoplasms (tMN), are increasingly recognized. These rare but severe complications, such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), appear multifactorial, influenced by prior cytotoxic therapies, radiation exposure, clonal hematopoiesis, and germline predispositions. This review synthesizes data on PRRT-related hematologic toxicities, including findings from pivotal studies and real-world evidence. We explore risk factors, underlying mechanisms, and the potential role of biomarkers such as clonal hematopoiesis and germline mutations in predicting toxicity. Emerging approaches, including alpha particle radioligand therapy and advanced dosimetry are explored as strategies to optimize patient selection and minimize adverse outcomes. To maximize the benefits of PRRT while safeguarding patient safety, future efforts should focus on integrating predictive biomarkers, refining treatment sequencing, and developing personalized, risk-stratified approaches to therapy.

177例lu - dotatate治疗的神经内分泌肿瘤患者的治疗相关性髓系肿瘤:风险有多大?
肽受体放射性核素治疗(PRRT)与lutetium-177-Dotatate (177Lu-DOTATATE)已经改变了神经内分泌肿瘤(NET)的治疗,改善了无进展生存,症状控制和生活质量。然而,长期血液学毒性,包括治疗相关髓系肿瘤(tMN),越来越被认识到。这些罕见但严重的并发症,如骨髓增生异常综合征(MDS)和急性髓性白血病(AML),似乎是多因素的,受先前的细胞毒性治疗、辐射暴露、克隆造血和种系易感的影响。这篇综述综合了prrt相关血液学毒性的数据,包括关键研究的发现和真实世界的证据。我们探讨危险因素,潜在的机制,以及生物标志物如克隆造血和种系突变在预测毒性中的潜在作用。新兴的方法,包括α粒子放射配体治疗和先进的剂量学被探索作为优化患者选择和减少不良后果的策略。为了在保障患者安全的同时最大化PRRT的益处,未来的努力应集中在整合预测性生物标志物、完善治疗序列、开发个性化、风险分层的治疗方法上。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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