Herr Felix L, Dascalescu Christian, Ebner Ricarda, Schnitzer Moritz L, Fabritius Matthias P, Schmid-Tannwald Christine, Zacherl Mathias J, Wenter Vera, Unterrainer Lena M, Brendel Matthias, Holzgreve Adrien, Werner Rudolf A, Auernhammer Christoph J, Spitzweg Christine, Knösel Thomas, Burkard Tanja, Ricke Jens, Heimer Maurice M, Sheikh Gabriel T, Cyran Clemens C
Department of Radiology, LMU University Hospital, LMU Munich, Munich, Germany.
Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany.
Theranostics. 2025 May 25;15(13):6444-6453. doi: 10.7150/thno.112588. eCollection 2025.
Integrated biomarkers that predict survival in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NET) receiving peptide receptor radionuclide therapy (PRRT) are still limited. This study aims to identify predictors of progression-free survival (PFS) in patients with GEP-NET undergoing two cycles of PRRT. This single-center retrospective study included 178 patients with GEP-NET (G1 and G2) who received at least two consecutive cycles of PRRT with [177Lu]Lu-DOTA-TATE and underwent somatostatin receptor (SSTR)-PET/CT before and after therapy. At baseline, Krenning score (KS) > 2, clinical, pathological and laboratory parameters were collected and correlated to PFS. Survival predictors were analyzed using univariate and multivariate models. For goodness-of-fit analysis, the Akaike information criterion and Harrell concordance index were determined. To determine the impact on the regression model the Wald-Test was performed. In univariate analysis, KS 3 (vs. KS 4; HR, 2.02; 95% CI, 1.27-3.22; p = 0.012), Ki-67 > 5 % (HR, 2.00; 95% CI, 1.31-3.04; p = 0.008), CgA > 200 ng/mL (HR, 1.77; 95% CI, 1.14-2.76; p = 0.027) and NSE > 35 ng/mL (HR, 2.37; 95% CI, 1.44-3.89; p < 0.008) were significantly associated with shorter PFS, with CgA providing the highest C-index (0.6). In multivariate analysis , KS 3 (vs. KS 4; HR, 1.94; 95% CI, 1.17-3.21; p = 0.01), CgA > 200 ng/mL (HR, 1.76; CI, 1.08-2.87; p = 0.024), NSE > 35 ng/mL (HR, 1.98; 95% CI, 1.17-3.36; p = 0.011), and Ki-67 > 5 % (HR, 1.89; 95% CI, 1.18-3.02; p = 0.008) were significantly associated with reduced PFS. Including KS into multivariate analysis significantly improved the Cox regression model performance, as shown by a reduction in Akaike Information Criterion (592/596) and an increase in concordance index (0.66/0.65). The Wald test for individual variables supported the significance of both Ki-67 (7.1) and KS (6.7) as independent predictors of PFS. NSE, CgA, KS and Ki-67 emerged as independent predictors of PFS in GEP-NET patients scheduled for two cycles of PRRT, thereby emphasizing the importance of integrated diagnostics including in- and ex-vivo biomarkers to identify high-risk individuals prone to disease progression.
预测接受肽受体放射性核素治疗（PRRT）的胃肠胰神经内分泌肿瘤（GEP-NET）患者生存情况的综合生物标志物仍然有限。本研究旨在确定接受两个周期PRRT的GEP-NET患者无进展生存期（PFS）的预测因素。这项单中心回顾性研究纳入了178例GEP-NET（G1和G2）患者，他们接受了至少两个连续周期的[177Lu]Lu-DOTA-TATE PRRT治疗，并在治疗前后接受了生长抑素受体（SSTR）-PET/CT检查。在基线时，收集了Krenning评分（KS）>2、临床、病理和实验室参数，并将其与PFS进行关联分析。使用单变量和多变量模型分析生存预测因素。为了进行拟合优度分析，确定了赤池信息准则和哈雷尔一致性指数。为了确定对回归模型的影响，进行了Wald检验。在单变量分析中，KS 3（与KS 4相比；HR，2.02；95%CI，1.27-3.22；p = 0.012）、Ki-67>5%（HR，2.00；95%CI，1.31-3.04；p = 0.008）、嗜铬粒蛋白A（CgA）>200 ng/mL（HR，1.77；95%CI，1.14-2.76；p = 0.027）和神经元特异性烯醇化酶（NSE）>35 ng/mL（HR，2.37；95%CI，1.44-3.89；p < 0.008）与较短的PFS显著相关，其中CgA的C指数最高（0.6）。在多变量分析中，KS 3（与KS 4相比；HR，1.94；95%CI，1.17-3.21；p = 0.01）、CgA>200 ng/mL（HR，1.76；CI，1.08-2.87；p = 0.024）、NSE>35 ng/mL（HR，1.98；95%CI，1.17-3.36；p = 0.011）和Ki-67>5%（HR，1.89；95%CI，1.18-3.0
