Walter T, Tougeron D, Baudin E, Le Malicot K, Lecomte T, Malka D, Hentic O, Manfredi S, Bonnet I, Guimbaud R, Coriat R, Lepère C, Desauw C, Thirot-Bidault A, Dahan L, Roquin G, Aparicio T, Legoux J-L, Lombard-Bohas C, Scoazec J-Y, Lepage C, Cadiot G
University Hospital, Lyon, France.
University Hospital, Poitiers, France.
Eur J Cancer. 2017 Jul;79:158-165. doi: 10.1016/j.ejca.2017.04.009. Epub 2017 May 11.
Diagnosis and management of poorly differentiated gastro-entero-pancreatic (GEP) neuroendocrine carcinomas (NECs) remain challenging. Recent studies suggest prognostic heterogeneity. We designed within the French Group of Endocrine Tumours a prospective cohort to gain insight in the prognostic stratification and treatment of GEP-NEC.
All patients with a diagnosis of GEP-NEC between 1st January 2010 and 31st December 2013 could be included in this national cohort. Adenoneuroendocrine tumours were excluded.
253 patients from 49 centres were included. Median age was 66 years. Main primary locations were pancreas (21%), colorectal (27%), oesophagus-stomach (18%); primary location was unknown in 20%. Tumours were metastatic at diagnosis in 78% of cases. Performance status (PS) at diagnosis was 0-1 in 79% of patients. Among the 147 (58%) cases reviewed by an expert pathological network, 39% were classified as small cell NEC and 61% as large cell NEC. Median Ki67 index was 75% (range, 20-100). Median overall survival was 15.6 (13.6-17.0) months. Significant adverse prognostic factors in univariate analysis were PS > 1 (hazard ratio [HR] = 2.5), metastatic disease (HR = 1.6), NSE>2 upper limit of normal [ULN]; HR = 3.2), CgA>2 ULN (HR = 1.7) and lactate dehydrogenase >2 ULN (HR = 2.1). After first-line palliative chemotherapy (CT1) with platinum-etoposide (n = 152), objective response, progression-free survival and overall survival were 50%, 6.2 and 11.6 months; they were 24%, 2.9 and 5.9, respectively, after post-CT1 FOLFIRI regimen (n = 72).
We report a large prospective series of GEP-NEC which show the predominance of large cell type and advanced stage at diagnosis. Prognosis was found more homogeneous than previously reported, mainly impacted by PS and tumour burden.
低分化胃肠胰（GEP）神经内分泌癌（NEC）的诊断和管理仍然具有挑战性。最近的研究表明存在预后异质性。我们在法国内分泌肿瘤研究组内设计了一项前瞻性队列研究，以深入了解GEP-NEC的预后分层和治疗。
2010年1月1日至2013年12月31日期间所有诊断为GEP-NEC的患者均可纳入该全国性队列研究。腺神经内分泌肿瘤被排除在外。
纳入了来自49个中心的253例患者。中位年龄为66岁。主要原发部位为胰腺（21%）、结直肠（27%）、食管-胃（18%）；20%的患者原发部位不明。78%的病例在诊断时已有转移。79%的患者诊断时的体能状态（PS）为0-1。在由专家病理网络审查的147例（58%）病例中，39%被分类为小细胞NEC，61%为大细胞NEC。中位Ki67指数为75%（范围20%-100%）。中位总生存期为15.6（13.6-17.0）个月。单因素分析中显著的不良预后因素为PS>1（风险比[HR]=2.5）、转移性疾病（HR=1.6）、神经元特异性烯醇化酶（NSE）>2倍正常上限（ULN）；HR=3.2）、嗜铬粒蛋白A（CgA）>2倍ULN（HR=1.7）和乳酸脱氢酶>2倍ULN（HR=2.1）。在接受铂类-依托泊苷一线姑息化疗（CT1）（n=152）后，客观缓解率、无进展生存期和总生存期分别为50%、6.2个月和11.6个月；在CT1后接受FOLFIRI方案（n=72）后，分别为24%、2.9个月和5.9个月。
我们报告了一个大型的GEP-NEC前瞻性系列研究，该研究显示诊断时大细胞类型和晚期占主导地位。发现预后比先前报道的更具同质性，主要受PS和肿瘤负荷影响。
