High-Grade Gastrointestinal Neuroendocrine Carcinoma Management and Outcomes: A National Cancer Database Study
High-Grade Gastrointestinal Neuroendocrine Carcinoma Management and Outcomes: A National Cancer Database Study
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DOI：
10.1634/theoncologist.2018-0382
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发表时间：
2019-07-01
期刊：
影响因子：
5.8
通讯作者：
El-Raycs, Bassel F.
中科院分区：
文献类型：
--
作者：
Alese, Olatunji B.;Jiang, Renjian;El-Raycs, Bassel F.
背景胃肠道高度恶性神经内分泌癌是罕见的。然而，治疗模式和结果尚未得到很好的描述。研究对象、材料和方法：对美国国家癌症数据库进行分析。主要目的是描述临床结果并确定预后因素。进行单变量和多变量分析以确定与患者结局相关的因素。结果2004年至2013年期间，共确定了1，861例患者。平均年龄为63岁（标准差+/- 13）。大多数患者（78.1%）为非西班牙裔白人。最常见的原发部位为胰腺（胰腺神经内分泌肿瘤[PNET] = 19.4%）、大肠（18.1%）、食管（17.8%）和直肠（15.5%）。临床分期为I期（6.6%）、II期（10.5%）、III期（18%）和IV期（64.6%）。只有1.6%的患者有脑转移。手术切除是27.9%的主要治疗方法，其中位总生存期（OS）为13.3个月。姑息化疗患者的中位OS为11.2个月，而未治疗患者为1.7个月。高级别PNET的中位OS为6个月，而其他高级别胃肠道神经内分泌癌（HG GI NEC）为9.9个月。在单变量分析中，年龄< 65岁（风险比[HR] 0.72; 0.66-0.8; p <0.001）和在学术中心治疗（HR 0.88; 0.79-0.99; p <0.034）与生存率改善相关。多变量分析证实了在学术中心治疗的预后优势。结论本组病例为最大的HG GI NEC病例。大多数患者存在转移性疾病，总体生存率仍然很差。在学术中心接受治疗、年龄较小和使用化疗与生存率提高相关。与单药化疗相比，多药化疗与上级生存率相关，单药化疗上级生存率优于不化疗。在多变量分析中，化疗、手术和放疗的时间顺序与生存差异无关。高级别胃肠道神经内分泌癌（HG GI NEC）患者的实践管理的意义是基于小细胞肺癌的经验。在这项回顾性研究中，大多数患者患有晚期疾病，胰腺原发性疾病的结局更差。在学术中心接受治疗、年龄较小和使用化疗与生存率提高相关。与接受新辅助治疗或辅助治疗的患者相比，仅接受切除治疗的早期疾病患者的结局较差，这表明微转移导致手术结局较差。相对较高的手术切缘阳性比例有利于通过新辅助治疗降低分期，以改善切除率并降低全身复发风险。
Background High-grade neuroendocrine carcinomas are rare in the gastrointestinal tract. However, treatment patterns and outcomes have not been well described. Subjects, Materials, and Methods The National Cancer Database was analyzed. The primary objective was to describe the clinical outcomes and identify prognostic factors. Univariate and multivariate analyses were done to identify factors associated with patient outcome. Results A total of 1,861 patients were identified between 2004 and 2013. The mean age was 63 years (standard deviation +/- 13). The majority of the patients (78.1%) were non-Hispanic whites. The most common primary sites were pancreas (pancreatic neuroendocrine tumor [PNET] = 19.4%), large intestine (18.1%), esophagus (17.8%), and rectum (15.5%). Stage at presentation was I (6.6%), II (10.5%), III (18%) and IV (64.6%). Only 1.6% of the patients had brain metastases. Surgical resection was the primary therapy in 27.9%, and their median overall survival (OS) was 13.3 months. Patients treated with palliative chemotherapy had a median OS of 11.2 months, compared with 1.7 months for untreated patients. The median OS for high-grade PNET was 6 months, compared with 9.9 months for other high-grade gastrointestinal neuroendocrine carcinomas (HG GI NEC). On univariable analysis, age < 65 years (hazard ratio [HR] 0.72; 0.66-0.8; p < .001) and treatment at an academic center (HR 0.88; 0.79-0.99; p < .034) were associated with improved survival. Multivariable analysis confirmed prognostic advantage of treatment at an academic center. Conclusion This is the largest series of HG GI NEC. Most patients present with metastatic disease, and overall survival remains poor. Treatment at an academic center, younger age, and use of chemotherapy were associated with improved survival. Multiagent chemotherapy was found to be associated with superior survival compared with single-agent chemotherapy, which was superior to no chemotherapy. Temporal sequences of chemotherapy, surgery, and radiation administration were not found to be associated with survival differences on multivariable analysis. Implications for Practice Management of patients with high-grade gastrointestinal neuroendocrine carcinomas (HG GI NEC) is based on experience with small-cell lung cancer. In this retrospective review, most patients had advanced disease and pancreatic primary had worse outcomes. Treatment at an academic center, younger age, and use of chemotherapy are associated with improved survival. Patients with early-stage disease treated with resection alone had inferior outcomes compared with patients who received neoadjuvant or adjuvant therapy, suggesting that micrometastases contribute to poor surgical outcomes. The relatively high proportion of positive surgical margin favors downstaging with neoadjuvant therapy to improve resection and lower the risk of systemic recurrence.