小细胞肺癌NCCN指南2017第二版讨论（第六部分）

Small Cell Lung Cancer 小细胞肺癌

NCCN Guidelines Version 2.2017
NCCN指南2017第2版山东省肿瘤医院呼吸肿瘤内科张品良

Discussion
讨论

Lung Neuroendocrine Tumors
肺神经内分泌肿瘤

LNTs encompass a wide spectrum of disease. Using the 2015 WHO criteria, LNTs are characterized as: 1) high-grade neuroendocrine carcinomas (SCLC and LCNEC); 2) intermediate-grade neuroendocrine carcinomas (atypical carcinoids); or 3) low-grade neuroendocrine carcinomas (typical carcinoids). SCLC and LCNEC are poorly differentiated tumors that often have a poor prognosis, whereas typical carcinoid is a well-differentiated neuroendocrine tumor that usually has a good prognosis. Atypical carcinoid is a moderately differentiated neuroendocrine cancer and, as such, carries an intermediate prognosis. Although many carcinoids occur in the GI tract (68%), they also occur in the bronchopulmonary system (25%). Carcinoids are rare tumors, but a SEER analysis suggests that their incidence is increasing.
肺神经内分泌肿瘤（LNTs）包括多种疾病。按照2015年WHO标准，肺神经内分泌肿瘤（LNTs）的特征为：1）高分级神经内分泌癌（小细胞肺癌和大细胞神经内分泌癌[LCNEC]）；2）中分级神经内分泌癌（不典型类癌）；3）低分级神经内分泌癌（典型类癌）。小细胞肺癌和大细胞神经内分泌癌（LCNEC）是分化差的肿瘤，通常预后很差，而典型类癌是一种分化良好的神经内分泌肿瘤，一般预后良好。非典型类癌是一种分化中等的神经内分泌癌，因此，预后中等。虽然许多类癌发生在胃肠道（68%），但是也可出现在支气管肺系统（25%）。类癌是罕见肿瘤，但SEER分析表明，其发病率正在上升。

Diagnosis and Staging
诊断与分期

Most LNTs are SCLCs, which are managed using the NCCN Guidelines for SCLC. LCNEC is associated with smoking and is managed using the NCCN Guidelines for NSCLC, because the conceptual algorithm used to manage these patients is the same as that for patients with NSCLC. However, data suggest that chemotherapy regimens used for SCLC may be a better option for LCNEC if systemic therapy is indicated. Low-grade lung neuroendocrine carcinomas (typical carcinoids) and intermediate-grade lung neuroendocrine carcinomas (atypical carcinoids) account for 1% to 2% of lung cancers and are managed using the NCCN Guidelines for Lung Neuroendocrine Tumors. Both histologic and cytologic features can be useful for distinguishing LNTs from SCLC and LCNEC, although diagnosis can be difficult (see the NCCN Guidelines for Neuroendocrine Tumors and the NCCN Guidelines for NSCLC, available at NCCN.org). CD56, chromogranin, and synaptophysin are useful immunohistochemical markers for identifying neuroendocrine tumors. The proliferative marker Ki-67 may also be useful. Larger surgical specimens are often needed to diagnose atypical carcinoids or LCNEC, which may be difficult to diagnose using small biopsies or cytology.
大多数肺神经内分泌肿瘤（LNTs）是小细胞肺癌，使用小细胞肺癌NCCN指南管理。大细胞神经内分泌癌（LCNEC）与吸烟有关，使用非小细胞肺癌NCCN指南管理，因为管理这些患者的工作步骤概念与非小细胞肺癌患者相同。然而，数据表明，对于大细胞神经内分泌癌（LCNEC），如果有全身治疗的适应症，用于小细胞肺癌的化疗方案可能是一个更好的选择。分化良好的肺神经内分泌癌（典型类癌）与分化中等的肺神经内分泌癌（非典型类癌）占肺癌的1%-2%，使用肺神经内分泌肿瘤的NCCN指南管理。组织学和细胞学特征二者均有助于从小细胞肺癌和大细胞神经内分泌癌（LCNEC）中鉴别肺神经内分泌肿瘤（LNTs），尽管诊断困难（见神经内分泌肿瘤NCCN指南和非小细胞肺癌NCCN指南，可在NCCN.org获得）。CD56、嗜铬素和突触素是识别神经内分泌肿瘤有用的免疫组化标记。增殖标志物Ki-67也可能有用。诊断非典型类癌或大细胞神经内分泌癌（LCNEC）通常需要更大的手术标本，使用小活检或细胞学检查可能难以诊断。

LNTs are staged using the 7th edition of the AJCC staging system for lung tumors (see Tables 2 and 3 in the NCCN Guidelines for SCLC). Both low-grade and intermediate-grade LNTs are usually stage I at diagnosis, although lymph node metastases (stages II–III) are more commonly seen in intermediate-grade tumors. Compared with other lung carcinomas, the prognosis is excellent for many patients with low-grade and intermediate-grade LNTs.
肺神经内分泌肿瘤（LNTs）使用第7版AJCC肺肿瘤分期系统进行分期（见小细胞肺癌NCCN指南中的表2和表3）。分化良好与分化中等的肺神经内分泌肿瘤（LNTs）在诊断时通常均是I期，虽然淋巴结转移（II–III期）在分化中等的肿瘤中更常见。与其他肺癌相比，许多分化良好与分化中等的肺神经内分泌肿瘤（LNTs）患者的预后极佳。

Treatment
治疗

Surgery is recommended for patients with stage I, II, or IIIA low-grade or intermediate-grade LNTs (ie, typical or atypical carcinoids) (see Primary Treatment in the NCCN Guidelines for Lung Neuroendocrine Tumors). After surgical resection, 5- and 10-year survival rates are more than 90% for patients with typical carcinoids, whereas 5- and 10-year survival rates are 70% and 50% to 60% for patients with atypical carcinoids. Lymph node involvement decreases long-term survival in both typical and atypical carcinoid. Recently, the NCCN Panel slightly revised the primary treatment guidelines for patients with stage IIIA LNTs. If surgery is not feasible, external-beam radiotherapy is recommended for stage IIIA typical carcinoids, and cisplatin/etoposide plus radiotherapy is recommended for stage IIIA atypical carcinoids. Cisplatin/etoposide with or without RT is recommended for stage IIIB LNTs except for T4 due to multiple lung nodules. Systemic therapy (eg, cisplatin/etoposide [preferred for atypical carcinoids], temozolomide ± capecitabine, sunitinib, everolimus) is recommended for patients with unresectable or advanced disease, although response rates are modest and there is no evidence for a preferred regimen for low-grade typical carcinoids. Octreotide (including long-acting release [LAR]) or lanreotide may be considered for select patients with positive octreotide scans or symptoms of carcinoid syndrome.
对于I、II或IIIA期分化良好或分化中等的肺神经内分泌肿瘤（LNTs）（即典型或非典型类癌）患者，推荐手术（见肺神经内分泌肿瘤NCCN指南中的初始治疗）。手术切除后，典型类癌患者5年与10年生存率超过90%，而不典型类癌患者分别为70%和50%-60%。在典型和不典型类癌患者中淋巴结受累均降低二者的长期生存。最近，NCCN小组略微修改了IIIA期肺神经内分泌肿瘤（LNTs）患者的初始治疗指南。对于IIIA期典型类癌，如果手术不可行，则推荐外放疗，而对于IIIA期非典型类癌推荐顺铂/依托泊苷加放疗。除了多发肺结节T4的IIIB期肺神经内分泌肿瘤（LNTs），推荐顺铂/依托泊苷加或不加放疗。对于不能手术切除或晚期患者，推荐全身治疗（如顺铂/依托泊苷[非典型类癌]、替莫唑胺±卡培他滨、舒尼替尼、依维莫司），虽然有效率中等，但是，对于低级别的典型类癌没有证据推荐首选方案。对于选择性奥曲肽扫描阳性或有类癌综合征症状的患者，可考虑奥曲肽（包括长效缓释[LAR]）或兰瑞肽。