非小细胞肺癌 NCCN指南2016v4 概述

NSCLC NCCN2016V4 Discussion
讨论

Overview
概述山东省肿瘤医院呼吸肿瘤内科张品良

Lung cancer is the leading cause of cancer death in the United States.
在美国，肺癌是癌症死亡的最主要原因。

In 2015, an estimated 221,200 new cases (115,610 in men and 105,590 in women) of lung and bronchial cancer will be diagnosed, and 158,040 deaths (86,380 in men and 71,660 in women) are estimated to occur because of the disease.
在2015年，估计有221200个新病例（男性115610例和女性105590例）将被诊断为肺癌和支气管癌，估计有158040例因为该疾病死亡（男性86380例和女性71660例）。

Only 17.4% of all patients with lung cancer are alive 5 years or more after diagnosis.
在所有的肺癌患者中只有17.4%在诊断后存活5年或以上。

However, much progress has been made recently for lung cancer such as screening, minimally invasive techniques for diagnosis and treatment, advances in radiation therapy (RT) including stereotactic ablative radiotherapy (SABR), targeted therapies, and immunotherapies.
然而，最近肺癌已经取得了很大进步，如筛查、诊疗的微创技术、放射治疗（RT）进展包括立体定向消融放疗（SABR）、靶向治疗和免疫疗法。

Common symptoms of lung cancer include cough, dyspnea, weight loss, and chest pain; patients with symptoms are more likely to have chronic obstructive pulmonary disease.
肺癌的常见症状包括咳嗽、呼吸困难、体重减轻和胸痛；有症状的患者很可能有慢性阻塞性肺疾病。

The NCCN Guidelines(R) for Non-Small Cell Lung Cancer (NSCLC) are updated at least once a year by the NCCN Panel (eg, there were 7 updates from January to December 2015).
非小细胞肺癌（NSCLC）NCCN指南®由NCCN小组每年至少更新一次（例如，自2015年1月到12月有7次更新）。

These NCCN Guidelines were first published in 1996.
这些NCCN指南于1996年首次公布。

The Summary of the Guidelines Updates describes the most recent revisions to the algorithms, which have been incorporated into this updated Discussion text.
指南更新概要描述了最新修订的工作步骤，已纳入这个更新的讨论正文中。

By definition, the NCCN Guidelines cannot incorporate all possible clinical variations and are not intended to replace good clinical judgment or individualization of treatments.
按照定义，NCCN指南无法体现所有可能的临床变化并且不打算代替良好的临床判断或个体化治疗。

Literature Search Criteria and Guidelines Update Methodology
文献检索标准与指南更新方法

Before the update of this version of the NCCN Guidelines for NSCLC, an electronic search of the PubMed database was performed to obtain key literature in NSCLC, published between June 1, 2014 and July 1, 2015 using the following search term: NSCLC.
在更新本版本的NSCLC NCCN指南之前，使用以下搜索词：NSCLC电子搜索PubMed数据库中在2014年6月1日与2015年7月1日之间发表的文献以获取NSCLC的关键文献。

The PubMed database was chosen, because it is the most widely used resource for medical literature and indexes only peer-reviewed biomedical literature.
选择PubMed数据库是因为它是使用最广泛的医学文献资源并且只有同行评议过的生物医学文献。

The search results were narrowed by selecting studies in humans published in English.
挑选的用英语发表的研究搜索结果是有限的。

Results were confined to the following article types: Clinical Trial, Phase 2; Clinical Trial, Phase 3; Clinical Trial, Phase 4; Guideline; Meta-Analysis; Randomized Controlled Trial; Systematic Reviews; and Validation Studies.
结果限于以下文章类型：2期临床试验；3期临床试验；4期临床试验；指南；荟萃分析；随机对照试验；系统综述；和验证研究。

The PubMed search resulted in 245 citations and their potential relevance was examined.
PubMed检索结果中检出245篇参考文献及其关联文献。

The data from key PubMed articles selected by the NCCN Panel for review during the NCCN Guidelines update meeting, as well as articles from additional sources deemed as relevant to these Guidelines and discussed by the NCCN Panel, have been included in this version of the Discussion section (eg, e-publications ahead of print, meeting abstracts).
NCCN小组在NCCN指南更新会议期间评审挑选的PubMed关键文献数据以及其他来源的、认为与这些指南相关的文献（如印刷前的电子出版物、会议摘要）并由NCCN小组进行讨论，已收录到这个版本的讨论部分。

If high-level evidence is lacking, recommendations are based on the panel’s review of lower-level evidence and expert opinion.
如果缺乏高级别证据，推荐是基于较低级别证据的小组评审和专家意见。

The complete details of the development and update of the NCCN Guidelines are available on the NCCN webpage.
NCCN指南发展与更新的全部细节可在NCCN网页上获得。

Risk Factors
危险因素

The primary risk factor for lung cancer is smoking tobacco, which accounts for most lung cancer-related deaths.
肺癌的主要危险因素是吸食烟草，占肺癌死亡的大多数。

Cigarette smoke contains many carcinogenic chemicals (eg, nitrosamines, benzo(a)pyrene diol epoxide).
香烟烟雾中含有许多致癌的化学物质（如亚硝胺、苯并芘二醇环氧化物）。

The risk for lung cancer increases with the number of packs of cigarettes smoked per day and with the number of years spent smoking (ie, pack-years of smoking history).
肺癌的风险随着每天吸烟的包数和吸烟的年数（即吸烟史的包年）增加而增加。

Exposed nonsmokers also have an increased relative risk (RR = 1.24) of developing lung cancer from secondhand smoke; other studies have reported a modest risk (hazard ratio [HR] = 1.05).
非吸烟者的暴露也增加患二手烟肺癌的相对风险（RR = 1.24）；其他研究报告风险并不大（风险比[HR] = 1.05）。

Other possible risk factors for lung cancer include disease history (eg, COPD), cancer history, family history of lung cancer, and exposure to other carcinogens (see the NCCN Guidelines for Lung Cancer Screening, available at NCCN.org).
其他可能的肺癌危险因素包括病史（如COPD）、恶性肿瘤史、肺癌家族史和暴露于其他致癌物质（见肺癌筛查NCCN指南，在NCCN.org可得到）。

The International Agency for Research on Cancer lists several agents known to cause lung cancer, including arsenic, chromium, asbestos, nickel, cadmium, beryllium, silica, and diesel fumes.
国际癌症研究机构列出了一些已知的导致肺癌的物质，包括砷、铬、石棉、镍、镉、铍、二氧化硅和柴油烟气。

Asbestos is a known carcinogen that increases the risk for lung cancer in people exposed to airborne fibers, especially in individuals who smoke.
石棉是一种已知的致癌物质，在暴露于空气中纤维的人群中、特别是吸烟者中，增加肺癌的风险。

It is estimated that about 3% to 4% of lung cancers are caused by asbestos exposure.
据估计，约3%-4%的肺癌是由石棉暴露引起的。

Asbestos also causes malignant pleural mesothelioma (see the NCCN Guidelines for Malignant Pleural Mesothelioma, available at NCCN.org).
石棉还导致恶性胸膜间皮瘤（见恶性胸膜间皮瘤NCCN指南，在NCCN.org可得到）。

Radon gas, a radioactive gas that is produced by the decay of radium 226, also seems to cause lung cancer.
氡气，一种放射性气体，是由镭226衰变产生的，似乎也导致肺癌。

It is not clear whether hormone replacement therapy (HRT) affects the risk for lung cancer in women.
目前尚不清楚是否激素替代疗法（HRT）影响女性肺癌的风险。

More than 20 studies have been published, but the results have been inconsistent.
已经发表了20多篇，但结果却不一致。

In a large randomized controlled study, no increase in the incidence of lung cancer was found among postmenopausal women treated with estrogen plus progestin HRT; however, the risk of death from NSCLC increased.
在一项大型随机对照研究中，在雌激素加孕酮HRT治疗的绝经后妇女中发现肺癌的发病率没有增加；然而，NSCLC的死亡风险增加。

In women who received estrogen alone, the incidence or risk of death from lung cancer did not increase.
在单独使用雌激素的妇女中，肺癌的发病率或死亡风险没有增加。

Smoking Cessation
戒烟

Approximately 85% to 90% of cases of lung cancer are caused by cigarette smoking.
约85%至90%的肺癌是由吸烟引起的。

Active smoking and secondhand smoke both cause lung cancer.
主动吸烟和二手烟都会导致肺癌。

There is a causal relationship between active smoking and lung cancer and also between other cancers (eg, esophageal, oral cavity, laryngeal, pharyngeal, bladder, pancreatic, gastric, kidney, ovarian cancer, colorectal, and cervical cancers) and other diseases and conditions.
主动吸烟不仅与肺癌之间有因果关系，而且与其他癌症（如食道、口腔、喉、咽、膀胱、胰腺、胃、肾、卵巢癌、结直肠癌和宫颈癌）以及其他疾病与情况也有因果关系。

Smoking harms nearly every organ in the body; smokers have increased mortality compared with nonsmokers.
吸烟几乎危害体内的所有器官；与非吸烟者相比吸烟者死亡率增加。

Those who live with someone who smokes have an increased risk for lung cancer.
那些与吸烟者共同生活的人患肺癌的风险增加。

Further complicating this problem, cigarettes also contain nicotine, which is a highly addictive substance.
香烟中还含有尼古丁，这是一种很容易上瘾的物质，使这一问题更加复杂。

Oncologists should encourage smoking cessation, especially in patients with cancer.
肿瘤学家应该鼓励戒烟，特别是癌症患者。

The 5 A’s framework is a useful tool (that is, Ask, Advise, Assess, Assist, Arrange).
5A准则是一个有用的工具（即Ask询问、Advise建议、 Assess评估、 Assist辅助、Arrange安排）。

It is in the best interest of patients to quit smoking.
戒烟最好是使患者感兴趣。

Persistent smoking is associated with second primary cancers, treatment complications, and decreased survival.
持续吸烟与第二原发癌、治疗并发症以及生存率降低有关。

Some surgeons will not operate on a current smoker.
一些外科医生不会对当前吸烟者进行手术。

Programs using behavioral counseling combined with medications that promote smoking cessation (approved by the FDA) can be very useful.
使用行为咨询计划和结合促进戒烟的药物（经FDA批准的）可能是非常有用的。

For example, the American Cancer Society (ACS) has a Guide to Quitting Smoking as well as The E-Quit Study, which uses email to help smokers quit smoking.
例如，美国癌症协会（ACS）有一个戒烟指导和E-Quit研究，使用电子邮件来帮助吸烟者戒烟。

Agents that can be used to promote smoking cessation include nicotine replacement (eg, gum, inhaler, lozenge, nasal spray, patch), bupropion sustained release, and varenicline.
可用药物促进戒烟包括尼古丁替代（如口香糖、吸入剂、含片、鼻喷剂、贴剂）、安非他酮缓释制剂和伐尼克兰。

A recent study suggests that cytisine is more efficacious than nicotine replacement therapy, although more side effects were reported with cytisine such as nausea, vomiting, and sleep disorders.
最近一项研究表明，金雀花碱比尼古丁替代疗法更有效，尽管报道的金雀花碱副作用如恶心、呕吐和睡眠障碍更多。

Studies have shown that varenicline is better than bupropion or nicotine patch for smoking cessation.
研究已证明，伐尼克兰戒烟优于安非他酮或尼古丁贴剂。

The effectiveness of varenicline for preventing relapse has not been clearly established.
伐尼克兰预防复吸的效果尚未明确。

The FDA has issued an alert for varenicline regarding neuropsychiatric symptoms.
FDA发布了关于伐尼克兰神经精神症状的警告。

Varenicline has also been associated with other disorders (eg, visual disturbances, movement disorders, unconsciousness, cardiovascular disorders) and, therefore, is banned in truck and bus drivers, pilots, and air traffic controllers.
伐尼克兰也与其他异常（如视觉障碍、运动障碍、意识丧失、心血管疾病）有关，因此，禁用于卡车和巴士司机、飞行员和空中交通管制员。

Other side effects with varenicline include nausea, abnormal dreams, insomnia, and headache.
伐尼克兰的其他副作用包括恶心、异常梦境、失眠和头痛。

Bupropion may also be associated with similar serious neuropsychiatric symptoms.
安非他酮也可能与类似的严重神经精神症状有关。

Nicotine replacement has fewer adverse effects than varenicline or bupropion.
与伐尼克兰或安非他酮相比尼古丁替代疗法具有更少的副作用。

However, in spite of the potential adverse effects, it is probably more beneficial for motivated patients to use agents to promote smoking cessation.
然而，尽管有潜在的不良反应，它可能是更有利于激发患者积极使用的促进戒烟的药物。

Lung Cancer Screening
肺癌筛查

Lung cancer is the leading cause of cancer death worldwide, and late diagnosis is a major obstacle to improving lung cancer outcomes.
肺癌是全球癌症死亡的最主要原因，延迟诊断是改善肺癌预后的主要障碍。

Because localized cancer can be managed with curative intent, and because the mortality rate in other solid tumors (eg, cervix, colon) seems to be decreased by screening and early detection, lung cancer is an appropriate candidate for a population-based screening approach.
因为限局性肿瘤是可以根治性处理的，并且因为在其他实体瘤（如，宫颈癌、结肠癌）中通过筛查和早期发现，死亡率似乎是下降的，基于群体的筛查方法肺癌是合适的。

The National Lung Screening Trial (NLST) (ACRIN Protocol A6654) was a randomized controlled study involving more than 53,000 current or former heavy smokers that assessed the risks and benefits of low-dose CT scans compared with chest radiographs for detecting lung cancer.
国家肺癌筛查试验（NLST）（ACRIN协议A6654）是一项随机对照研究，包括53000多名目前或既往重度吸烟者，评估与胸片检测肺癌相比较，低剂量CT扫描的风险与收益。

Data from the NLST showed that screening individuals with high-risk factors using low-dose CT decreased the mortality rate from lung cancer by 20%.
NLST数据显示，使用低剂量CT筛查具有高危因素的个体，降低20%的肺癌死亡率。

Individuals with high-risk factors were either current or former smokers with a 30 or more pack-year smoking history (former smokers had quit up to 15 years before enrollment), were 55 to 74 years of age, and had no evidence of lung cancer.
具有高危因素的个体是，吸烟史≥30包年的目前或既往吸烟者（既往吸烟者入组前戒烟达15年）、年龄55至74岁且没有肺癌证据。

The NCCN, ACS, U.S. Preventive Services Task Force, American College of Chest Physicians, European Society for Medical Oncology (ESMO), and other organizations recommend lung cancer screening using low-dose CT for select high-risk current and former smokers (see the NCCN Guidelines for Lung Cancer Screening, available at NCCN.org).
对于选择的当前和既往吸烟的高危人群，NCCN、ACS、美国预防服务工作组、美国胸内科医师学会、欧洲肿瘤内科学会（ESMO）以及其他组织推荐使用低剂量CT肺癌筛查（见肺癌筛查NCCN指南，可在NCCN.org获得）。

It is important to note that low-dose CT screening and follow-up is not a substitute for smoking cessation; patients should be offered smoking cessation counseling (see NCCN Guidelines for Smoking Cessation, available at NCCN.org).
重要的是注意到，低剂量CT筛查与随访并不能代替戒烟；应为患者提供戒烟咨询（见戒烟NCCN指南，可在NCCN.org获得）。

Classification and Prognostic Factors
分类及预后因素

The WHO divides lung cancer into 2 major classes based on its biology, therapy, and prognosis: NSCLC (discussed in this guideline) and small cell lung cancer (SCLC) (see the NCCN Guidelines for Small Cell Lung Cancer, available at NCCN.org).
基于生物学、治疗和预后，WHO将肺癌分为两个主要类型：NSCLC（在本指南讨论）和小细胞肺癌（SCLC）（见小细胞肺癌NCCN指南，可在NCCN.org获得）。

NSCLC accounts for more than 83% of all lung cancer cases, and it includes 2 major types: 1) non-squamous carcinoma (including adenocarcinoma, large-cell carcinoma, and other cell types); and 2) squamous cell (epidermoid) carcinoma.
NSCLC占所有肺癌病例的83%以上，包括两大类：1）非鳞癌（包括腺癌、大细胞癌和其他细胞类型的癌）；和2）鳞状细胞（表皮样）癌。

Adenocarcinoma is the most common type of lung cancer seen in the United States and is also the most frequently occurring histology in nonsmokers.
在美国腺癌是最常见的肺癌类型，也是非吸烟者中最常见的组织学类型。

In 2011, an international panel revised the classification of lung adenocarcinoma (see the Pathologic Evaluation of Lung Cancer in this Discussion).
在2011年，一个国际小组修订了肺腺癌的分类（见此讨论中的肺癌病理评价）。

Certain prognostic factors are predictive of survival in patients with NSCLC.
某些预后因素可以预测NSCLC患者的生存。

Good prognostic factors include early-stage disease at diagnosis, good performance status (PS) (ECOG 0, 1, or 2), no significant weight loss (not more than 5%), and female gender.
预后良好的因素包括诊断时早期疾病、功能状态（PS）良好（ECOG 0、1或2）、无明显的体重减轻（不超过5%）以及女性。