Division of Medical Oncology, Department of Internal Medicine, The Ohio State University and Arthur G. James Cancer Center, Columbus, Ohio, United States of America.
Department of Pharmacy, The Ohio State University, Columbus, Ohio, United States of America.
PLoS One. 2024 May 15;19(5):e0298824. doi: 10.1371/journal.pone.0298824. eCollection 2024.
Peptide receptor radionucleotide therapy (PRRT) with 177Lu-dotatate is widely used for the treatment of patients with neuroendocrine tumors (NETs). We analyzed data from 104 patients with NETs treated with 177Lu -dotatate at a US academic center between December 2017 and October 2020 to better understand patterns of long-term efficacy, safety, and toxicity in the real-world setting. 177Lu-dotatate (200 mCi) was administered every eight weeks for four doses. The most common sites of primary disease were small intestine NETs (n = 49, 47%), pancreatic NETs (n = 32, 31%), and lung NETs (n = 7, 7%). Twenty-seven percent had Ki-67 <3%, 49% had Ki-67 between 3-20%, and 13.5% had Ki-67 >20%. The cohort had been pretreated with a median of two prior lines of treatment. Forty percent had received prior liver-directed treatment. Seventy-four percent of patients completed all four doses of treatment. The objective response rate was 18%. The median time-to-treatment failure/death was significantly longer for small-bowel NETs when compared to pancreatic NETs (37.3 months vs. 13.2 months, p = 0.001). In a multivariate model, Ki-67, primary site, and liver tumor burden ≥50% were found to independently predict time-to-treatment failure/death. Around 40% of patients experienced adverse events of ≥grade 3 severity. Treatment-related adverse events leading to discontinuation of therapy happened in 10% of patients. Preexisting mesenteric/peritoneal disease was present in 33 patients; seven of these patients developed bowel-related toxicities including two grade 5 events. We also report two cases of delayed-onset minimal change nephrotic syndrome, which occurred 14 and 27 months after the last dose of PRRT. Lastly, we describe six patients who developed rapid tumor progression in the liver leading to terminal liver failure within 7.3 months from the start of PRRT, and identify potential risk factors associated with this occurrence, which will need further study.
镥 177 放射性核素肽受体治疗（PRRT）联合 177Lu- DOTATATE 已广泛用于治疗神经内分泌肿瘤（NETs）患者。我们分析了 2017 年 12 月至 2020 年 10 月期间在美国一家学术中心接受 177Lu-DOTATATE 治疗的 104 例 NET 患者的数据，以更好地了解真实环境中这种治疗的长期疗效、安全性和毒性模式。每 8 周给予 177Lu-DOTATATE（200mCi），共 4 个剂量。原发疾病最常见的部位为小肠 NET（n=49，47%）、胰腺 NET（n=32，31%）和肺 NET（n=7，7%）。27%的患者 Ki-67<3%，49%的患者 Ki-67 在 3%-20%之间，13.5%的患者 Ki-67>20%。该队列患者之前接受过中位数为 2 线的治疗。40%的患者接受过肝定向治疗。74%的患者完成了所有 4 个剂量的治疗。客观缓解率为 18%。与胰腺 NET 相比，小肠 NET 的治疗失败/死亡时间明显更长（37.3 个月 vs. 13.2 个月，p=0.001）。在多变量模型中，Ki-67、原发部位和肝脏肿瘤负荷≥50%被发现是独立预测治疗失败/死亡时间的因素。约 40%的患者出现≥3 级严重不良事件。10%的患者因治疗相关不良事件而停止治疗。33 例患者存在肠系膜/腹膜疾病，其中 7 例发生与肠道相关的毒性，包括 2 例 5 级事件。我们还报告了两例迟发性微小变化肾病综合征病例，分别发生在 PRRT 最后一次剂量后 14 个月和 27 个月。最后，我们描述了 6 例患者在 PRRT 开始后 7.3 个月内肝脏内肿瘤迅速进展导致终末期肝功能衰竭，确定了与这种情况相关的潜在危险因素，需要进一步研究。
