Ezziddin Samer, Attassi Mared, Yong-Hing Charlotte J, Ahmadzadehfar Hojjat, Willinek Winfried, Grünwald Frank, Guhlke Stefan, Biersack Hans-Jürgen, Sabet Amir
Department of Nuclear Medicine, University Hospital, Bonn, Germany.
J Nucl Med. 2014 Feb;55(2):183-90. doi: 10.2967/jnumed.113.125336. Epub 2014 Jan 16.
Outcome analyses for patients with gastroenteropancreatic neuroendocrine tumors (GEP NET) after peptide receptor radionuclide therapy (PRRT) are still limited, especially with regard to the impact of the Ki-67 index. Using a single-center analysis, we aimed to establish predictors of survival.
We retrospectively analyzed a consecutive cohort of 74 patients who had metastatic GEP NET and underwent PRRT with (177)Lu-octreotate (mean activity of 7.9 GBq per cycle, aimed at 4 treatment cycles at standard intervals of 3 mo). Patients (33 with pancreatic NET and 41 with nonpancreatic GEP NET) had unresectable metastatic disease graded as G1 or G2 (G1/G2) and documented morphologic or clinical progression within less than 12 mo or uncontrolled disease under somatostatin analog treatment. Responses were evaluated according to modified Southwest Oncology Group criteria. Potential predictors of survival were analyzed with the Kaplan-Meier curve method (log-rank test) and multivariate analysis (P < 0.05).
The response rates were 36.5% partial response, 17.6% minor response, 35.1% stable disease, and 10.8% progressive disease for the entire cohort; 54.5% partial response, 18.2% minor response, 18.2% stable disease, and 9.1% progressive disease for pancreatic NET; and 22.0% partial response, 17.1% minor response, 48.8% stable disease, and 12.2% progressive disease for nonpancreatic GEP NET. The median progression-free survival and overall survival were 26 mo (95% confidence interval, 18.3-33.7) and 55 mo (95% confidence interval, 48.8-61.2), respectively. Besides the Ki-67 index, a Karnofsky performance score of less than or equal to 70%, a hepatic tumor burden of greater than or equal to 25%, and a baseline plasma level of neuron-specific enolase of greater than 15 ng/mL independently predicted shorter overall survival (hazard ratio, 2.1-3.1). Patients with a Ki-67 index of greater than 10% still had median progression-free survival and overall survival of 19 and 34 mo, respectively.
The results of this study demonstrated the favorable response and long-term outcome of patients with G1/G2 GEP NET after PRRT. Independent predictors of survival were the Ki-67 index, the patient's performance status (Karnofsky performance scale score), the tumor burden, and the baseline neuron-specific enolase level. Even patients with a Ki-67 index of greater than 10% seemed to benefit from PRRT, with a good response and a notable long-term outcome. We present the first evidence, to our knowledge, that even in patients with metastatic disease the distinction between G1 and G2-in particular, between G1 (Ki-67 index of 1%-2%) and low-range G2 (Ki-67 index of 3%-10%)-provides prognostic stratification.
肽受体放射性核素治疗（PRRT）后胃肠胰神经内分泌肿瘤（GEP NET）患者的疗效分析仍然有限，尤其是关于Ki-67指数的影响。通过单中心分析，我们旨在确定生存预测因素。
我们回顾性分析了连续74例转移性GEP NET患者的队列，这些患者接受了（177）Lu-奥曲肽PRRT（每个周期平均活度为7.9 GBq，计划按3个月的标准间隔进行4个周期治疗）。患者（33例胰腺NET和41例非胰腺GEP NET）患有不可切除的转移性疾病，分级为G1或G2（G1/G2），并记录在不到12个月内有形态学或临床进展，或在生长抑素类似物治疗下疾病未得到控制。根据改良的西南肿瘤协作组标准评估反应。用Kaplan-Meier曲线法（对数秩检验）和多变量分析（P<0.05）分析生存的潜在预测因素。
整个队列的反应率为部分缓解36.5%、轻微缓解17.6%、疾病稳定35.1%、疾病进展10.8%；胰腺NET为部分缓解54.5%、轻微缓解18.2%、疾病稳定18.2%、疾病进展9.1%；非胰腺GEP NET为部分缓解22.0%、轻微缓解17.1%、疾病稳定48.8%、疾病进展12.2%。无进展生存期和总生存期的中位数分别为26个月（95%置信区间，18.3 - 33.7）和55个月（95%置信区间，48.8 - 61.2）。除Ki-67指数外，卡诺夫斯基体能状态评分小于或等于７０％、肝肿瘤负荷大于或等于25％以及神经元特异性烯醇化酶基线血浆水平大于15 ng/mL独立预测总生存期较短（风险比，2.1 - 3.1）。Ki-67指数大于10%的患者无进展生存期和总生存期的中位数分别仍为19个月和34个月。
本研究结果表明G1/G2 GEP NET患者PRRT后反应良好且长期预后较好。生存的独立预测因素为Ki-67指数、患者的体能状态（卡诺夫斯基体能量表评分）、肿瘤负荷和基线神经元特异性烯醇化酶水平。即使是Ki-67指数大于10%的患者似乎也能从PRRT中获益，反应良好且有显著的长期预后。据我们所知，我们首次提供证据表明，即使在转移性疾病患者中，G1和G2之间的区分——特别是G1（Ki-67指数为1% - 2%）和低范围G2（Ki-67指数为3% - 10%）之间——可提供预后分层。
