Durma Adam Daniel, Saracyn Marek, Kołodziej Maciej, Jóźwik-Plebanek Katarzyna, Dmochowska Beata, Mróz Adrianna, Żmudzki Wawrzyniec, Kamiński Grzegorz
Department of Endocrinology and Radioisotope Therapy, Military Institute of Medicine-National Research Institute, Szaserów 128, 04-141 Warsaw, Poland.
Pharmaceuticals (Basel). 2023 Aug 24;16(9):1205. doi: 10.3390/ph16091205.
Neuroendocrine neoplasms (NENs) are a rare group of tumors with a different clinical course, prognosis and location. Radioligand therapy (RLT) can be used as a first or second line of treatment. It is registered in gastroenteropancreatic NENs (GEP-NENs) as grades G1 and G2. Tumors with an unknown point of origin, diagnosed outside the gastrointestinal tract and pancreas (non-GEP) or at the G3 grade, remain in the "grey area" of treatment.
Analysis of 51 patients with NENs who underwent RLT in a single highest reference center from 2018 to 2023 was performed. Treatment was administrated to the patients with neoplasms of unknown origin, non-GEP-NENs, and ones with G3 grade. In total, 35 patients received 177-Lutetium (7.4 GBq), while 16 received 177-Lutetium and 90-Yttrium with equal activities (1.85 + 1.85 GBq).
The progression-free survival (PFS) before RLT qualification was 34.39 ± 35.88 months for the whole study group. In subgroups of patients with an unknown tumor location ( = 25), the median PFS was 19 months (IQR = 23), with "other" locations ( = 21) at 31 months (IQR = 28), and with NEN G3 ( = 7) at 18 months (IQR = 40). After RLT, disease stabilization or regression was observed in 42 (87.5% of) patients. RLT did not cause statistical changes in creatinine or GFR values. Hematological parameters (RBC, WBC, PLT, HGB) as well as chromogranin A concentration decreased significantly. There were no statistical differences between both subgroups regarding the type of radioisotope (177-Lutetium vs. 177-Lutetium and 90-Yttrium). After RLT in long-term observation, the median observation time (OT) was 14 months (IQR = 18 months). In patients with progression ( = 8), the median PFS was 20 months (IQR = 16 months), while in patients with confirmed death ( = 9), the median overall survival (OS) was 8 months (IQR = 14 months).
Our study showed that 87.5% of NEN patients with unknown origin, non-GEP-NENs, and those with GEP-NEN G3 grade had benefited from the radioligand therapy. There were no significantly negative impacts on renal parameters. The decrease of bone marrow parameters was acceptable in relation to beneficial disease course. The decrease of chromogranin concentration was confirmed as a predictive factor for disease stabilization or regression.
神经内分泌肿瘤（NENs）是一组罕见的肿瘤，具有不同的临床病程、预后和发病部位。放射性配体疗法（RLT）可作为一线或二线治疗方法。它已在胃肠胰神经内分泌肿瘤（GEP-NENs）中注册用于G1和G2级肿瘤。起源不明、在胃肠道和胰腺以外部位诊断出的肿瘤（非GEP）或G3级肿瘤，仍处于治疗的“灰色地带”。
对2018年至2023年在单个最高参考中心接受RLT治疗的51例NENs患者进行了分析。对起源不明的肿瘤患者、非GEP-NENs患者以及G3级肿瘤患者进行了治疗。总共有35例患者接受了177-镥（7.4GBq）治疗，而16例患者接受了等量活度（1.85 + 1.85GBq）的177-镥和90-钇联合治疗。
整个研究组在接受RLT治疗前的无进展生存期（PFS）为34.39±35.88个月。在肿瘤位置不明的患者亚组（n = 25）中，中位PFS为19个月（四分位间距[IQR] = 23），“其他”位置的患者（n = 21）为31个月（IQR = 28），NEN G3级患者（n = 7）为18个月（IQR = 40）。RLT治疗后，42例（87.5%）患者病情稳定或缓解。RLT未引起肌酐或肾小球滤过率（GFR）值的统计学变化。血液学参数（红细胞、白细胞、血小板、血红蛋白）以及嗜铬粒蛋白A浓度显著下降。两个亚组在放射性同位素类型（177-镥与177-镥和90-钇联合）方面无统计学差异。RLT治疗后的长期观察中，中位观察时间（OT）为14个月（IQR = 18个月）。病情进展的患者（n = 8）中位PFS为20个月（IQR = 16个月），确诊死亡的患者（n = 9）中位总生存期（OS）为8个月（IQR = 14个月）。
我们的研究表明，87.5%的起源不明、非GEP-NENs以及GEP-NEN G3级的NEN患者从放射性配体疗法中获益。对肾脏参数无明显负面影响。与有益的疾病进程相关，骨髓参数的下降是可以接受的。嗜铬粒蛋白浓度的下降被确认为疾病稳定或缓解的预测因素。
