Sabet Amir, Khalaf Feras, Haslerud Torjan, Al-Zreiqat Abdullah, Sabet Amin, Simon Birgit, Pöppel Thorsten D, Biersack Hans-Jürgen, Ezziddin Samer
Department of Nuclear Medicine, University Hospital Bonn, Germany.
Am J Nucl Med Mol Imaging. 2013 Sep 19;3(5):437-45. eCollection 2013.
Bone metastases of gastroenteropancreatic neuroendocrine tumors (GEP NET) can be associated with pain and a poor prognosis. Peptide receptor radionuclide therapy (PRRT) has been shown to be effective against this tumor manifestation. This study represents an update of the therapeutic assessment of PRRT with (177)Lu-octreotate in GEP NET patients with bone metastases focusing on potential predictors for impaired outcome and overall survival.We retrospectively analyzed a consecutive subgroup of n=68 patients with bone metastases (BM) of GEP NET treated with (177)Lu-octreotate (4 intended cycles at 3 monthly intervals; mean activity per cycle, 8.1 GBq). Baseline characteristics, including age, performance status, tumor origin, tumor load, plasma chromogranin A (CgA), and neuron-specific enolase (NSE) were analyzed regarding the impact on tumor regression (modified M.D. Anderson criteria) and survival of the patients. Survival analyses were performed using Kaplan-Meier curves, log-rank test at a significance level of p <0.05, and Cox proportional hazards model for uni- and multivariate analyses. Median follow-up was 48 months. The observed response of BMs consisted of complete remission in 2 (2.9%), partial remission in 23 (33.8%), minor response in 8 (11.8%), stable disease in 26 (38.2%), and progressive disease in 8 (13.2%) patients. Median time-to-progression (TTP) of BMs and overall survival (OS) were 35 mo (95% CI: 25-45) and 51 mo (95% CI: 38-64), respectively. Patients with responding BMs survived significantly longer than other patients (median 56 mo vs. 39 mo, p=0.034). NSE >15 ng/ml (p=0.002) and Ki67 index >10% (p=0.008) were associated with shorter overall survival. BM of GEP NET are effectively controlled by PRRT with a long median progression-free survival of approx. 3 years. Non-regression of BM, high proliferation rate and increased plasma NSE at baseline are predictive of shorter survival. However, this study confirms that poor patient condition (Karnofsky-Index ≤70%) and multifocality of BM (>10 lesions) do not affect outcome efficacy, further encouraging the use of PRRT in advanced bone metastatic disease.
胃肠胰神经内分泌肿瘤（GEP NET）的骨转移可能与疼痛和预后不良相关。肽受体放射性核素治疗（PRRT）已被证明对这种肿瘤表现有效。本研究是对使用（177）Lu - 奥曲肽进行PRRT治疗GEP NET骨转移患者的治疗评估的更新，重点关注预后受损和总生存的潜在预测因素。我们回顾性分析了连续的68例接受（177）Lu - 奥曲肽治疗的GEP NET骨转移（BM）患者亚组（每3个月1个周期，共4个预期周期；每个周期平均活度8.1 GBq）。分析了基线特征，包括年龄、体能状态、肿瘤起源、肿瘤负荷、血浆嗜铬粒蛋白A（CgA）和神经元特异性烯醇化酶（NSE）对肿瘤消退（改良的MD安德森标准）和患者生存的影响。使用Kaplan - Meier曲线、显著性水平p <0.05的对数秩检验以及单因素和多因素分析的Cox比例风险模型进行生存分析。中位随访时间为48个月。观察到的BM反应包括2例（2.9%）完全缓解、23例（33.8%）部分缓解、8例（11.8%）轻度反应、26例（38.2%）疾病稳定和8例（13.2%）疾病进展。BM的中位疾病进展时间（TTP）和总生存（OS）分别为35个月（95%CI：25 - 45）和51个月（95%CI：38 - 64）。BM有反应的患者生存时间明显长于其他患者（中位56个月对39个月，p = 0.034）。NSE>15 ng/ml（p = 0.002）和Ki67指数>10%（p = 0.008）与较短的总生存相关。GEP NET的BM通过PRRT得到有效控制，中位无进展生存期约为3年。BM无消退、高增殖率和基线时血浆NSE升高预示着较短的生存。然而，本研究证实患者状况差（卡诺夫斯基指数≤70%）和BM多灶性（>10个病灶）不影响疗效，进一步鼓励在晚期骨转移性疾病中使用PRRT。
