Galler Markus, Rogasch Julian M M, Huang Kai, Jann Henning, Plehm Kristina, Wetz Christoph, Amthauer Holger
Department of Nuclear Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
Cancers (Basel). 2022 Mar 31;14(7):1768. doi: 10.3390/cancers14071768.
(1) Background: retreatment with radionuclide-labeled somatostatin analogues following disease progression after initial treatment cycles is often referred to as salvage peptide receptor radionuclide therapy (salvage PRRT). Salvage PRRT is shown to have a favorable safety profile in patients with metastatic neuroendocrine tumors (NETs), but numerous questions about the efficacy and prognostic or predictive factors remain to be answered. The purpose of this study was to evaluate two parameters that have shown prognostic significance in progression-free survival (PFS) in initial PRRT treatment, namely the size of the largest lesion (LLS) and the De Ritis ratio (aspartate aminotransferase (AST)/alanine aminotransferase (ALT)), as prognostic factors in the context of salvage PRRT. In addition, the PFS after initial PRRT was evaluated as a predictor of the PFS following salvage PRRT. (2) Methods: retrospective, monocentric analysis in 32 patients with NETs (gastroenteropancreatic, 23; unknown primary, 7; kidney, 1; lung, 1) and progression after initial PRRT undergoing retreatment with [Lu]Lu-DOTATOC. The prognostic values of LLS, the De Ritis ratio, and PFS after initial treatment cycles regarding PFS following salvage PRRT were evaluated with univariable and multivariable Cox regression. PFS was defined as the time from treatment start until tumor progression according to RECIST 1.1 criteria, death from any cause or start of a new treatment due to progression of cancer-related symptoms (namely carcinoid syndrome). (3) Results: progression after salvage PRRT was observed in 29 of 32 patients with median PFS of 10.8 months (95% confidence interval (CI), 8.0-15.9 months). A higher LLS (hazard ratio (HR): 1.03; = 0.002) and a higher De Ritis ratio (HR: 2.64; = 0.047) were associated with shorter PFS after salvage PRRT in univariable Cox regression. PFS after initial PRRT was not associated with PFS following salvage PRRT. In multivariable Cox regression, only LLS remained a significant predictor. (4) Conclusions: the size of the largest lesion is easy to obtain and might help identify patients at risk of early disease progression after salvage PRRT. Validation is required.
(1) 背景：在初始治疗周期后疾病进展时，用放射性核素标记的生长抑素类似物进行再治疗通常被称为挽救性肽受体放射性核素治疗（挽救性PRRT）。挽救性PRRT在转移性神经内分泌肿瘤（NETs）患者中显示出良好的安全性，但关于其疗效以及预后或预测因素仍有许多问题有待解答。本研究的目的是评估在初始PRRT治疗中已显示出对无进展生存期（PFS）具有预后意义的两个参数，即最大病灶大小（LLS）和德瑞蒂斯比值（天冬氨酸转氨酶（AST）/丙氨酸转氨酶（ALT）），作为挽救性PRRT背景下的预后因素。此外，将初始PRRT后的PFS评估为挽救性PRRT后PFS的预测指标。(2) 方法：对32例NETs患者（胃肠胰，23例；原发灶不明，7例；肾脏，1例；肺，1例）进行回顾性单中心分析，这些患者在初始PRRT后进展，接受[Lu]Lu - DOTATOC再治疗。采用单变量和多变量Cox回归评估LLS、德瑞蒂斯比值以及初始治疗周期后的PFS对挽救性PRRT后PFS的预后价值。PFS定义为从治疗开始至根据RECIST 1.1标准出现肿瘤进展、任何原因导致的死亡或因癌症相关症状（即类癌综合征）进展而开始新治疗的时间。(3) 结果：32例患者中有29例在挽救性PRRT后出现进展，中位PFS为10.8个月（95%置信区间（CI），8.0 - 15.9个月）。在单变量Cox回归中，较高的LLS（风险比（HR）：1.03；P = 0.002）和较高的德瑞蒂斯比值（HR：2.64；P = 0.047）与挽救性PRRT后较短的PFS相关。初始PRRT后的PFS与挽救性PRRT后的PFS无关。在多变量Cox回归中，只有LLS仍然是一个显著的预测指标。(4) 结论：最大病灶大小易于获取，可能有助于识别挽救性PRRT后有早期疾病进展风险的患者。需要进行验证。
