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肿瘤医学

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小细胞肺癌NCCN指南2019第2版

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楼主 圣手阿良
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更新不是太多

主要是免疫化疗

讨论部分的翻译见跟帖



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2019-08-13 16:01 浏览 : 5593 回复 : 28
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Discussion
讨论

Overview
概述

Neuroendocrine tumors account for approximately 20% of lung cancers; most (approximately 14%) are small cell lung cancer (SCLC). In 2019, an estimated 29,660 new cases of SCLC will occur in the United States. Nearly all cases of SCLC are attributable to cigarette smoking. Although the incidence of SCLC has been decreasing, the incidence in women is increasing and the male-to-female incidence ratio is now 1:1. Management of SCLC is described in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ) for Small Cell Lung Cancer, which includes the algorithm and this supporting Discussion text. Management of other lung neuroendocrine tumors (LNTs) is described in a different guideline (see Lung Neuroendocrine Tumors in the NCCN Guidelines for Neuroendocrine and Adrenal Tumors, available at www.NCCN.org).
神经内分泌肿瘤约占肺癌的20%;大多数(约14%)是小细胞肺癌(SCLC)。2019年,美国估计将有29,660例新发SCLC病例。几乎所有的SCLC病例都是由吸烟引起的。虽然SCLC的发病率一直呈下降趋势,但是在女性中的发病率升高,男女发病率之比现在是1:1。SCLC的管理在小细胞肺癌NCCN肿瘤学临床实践指南(NCCN指南)中描述,包括工作步骤和此支持讨论文本。其他肺神经内分泌肿瘤(LNT)的管理在一个不同的指南中描述(参见神经内分泌和肾上腺肿瘤NCCN指南中的肺神经内分泌肿瘤,可在www.NCCN.org获得)。

The NCCN Guidelines for Small Cell Lung Cancer were originally published 20 years ago and have been subsequently updated at least once every year (see www.NCCN.org). The Summary of the Guidelines Updates section in the SCLC algorithm describes the most recent revisions for 2019, which are described in greater detail in this revised Discussion text; recent references have been added (see Summary in this Discussion and the algorithm). For example, new immunotherapy options have been added for patients with SCLC. Additional supplemental material in the SCLC algorithm includes the Signs and Symptoms of Small Cell Lung Cancer, Principles of Pathologic Review, Principles of Surgical Resection, Principles of Supportive Care, Principles of Systemic Therapy, Principles of Radiation Therapy, and staging tables.
小细胞肺癌的NCCN指南最初发表于20年前,随后至少每年更新一次(参见www.NCCN.org)。SCLC工作步骤中的指南更新部分概述了2019年的最新修订版,在本修订后的讨论中对此进行了更详细的描述;添加了最新的参考文献(参见本讨论和工作步骤中的概要)。例如,为SCLC患者添加了新的免疫治疗选择。SCLC工作步骤中的其他补充材料包括小细胞肺癌的症状和体征、病理检查原则、手术切除原则、支持治疗原则、系统治疗原则、放射治疗原则和分期表。

SCLC is characterized by a rapid doubling time, high growth fraction, and early development of widespread metastases. Most patients with SCLC present with hematogenous metastases; approximately one third present with limited disease confined to the chest. SCLC is highly sensitive to initial chemotherapy and radiotherapy; however, most patients eventually die of recurrent disease. In patients with limited-stage SCLC, the goal of treatment is cure using chemotherapy plus thoracic radiotherapy; some patients are eligible for curative surgery followed by systemic therapy with or without mediastinal radiotherapy. In patients with extensive-stage disease, systemic therapy alone can palliate symptoms and prolong survival in most patients; however, long-term survival is rare. Note that the definitions for limited-stage and extensive-stage SCLC incorporate TNM staging (see the algorithm and Staging in this Discussion). Surgery is only recommended for certain patients with surgically resectable stage I to IIA SCLC; stereotactic ablative radiotherapy (SABR) is an option for certain patients with medically inoperable stage I to IIA SCLC. Clinical trials generally represent state-of-the-art treatment for patients with SCLC. Despite recent advances, the recommended therapy for SCLC as outlined in these NCCN Guidelines still needs to be improved. Thus, participation in clinical trials should be strongly encouraged.
SCLC的特点是倍增时间短、增殖比率高以及广泛转移发生早。大多数SCLC患者有血行转移;约三分之一的局限期疾病局限于胸部。SCLC对初始化疗和放疗高度敏感;然而,大多数患者最终死于复发性疾病。局限期SCLC患者,治疗的目标是采用化疗+胸部放疗治愈;一些患者适于接受根治性手术,然后进行全身治疗,加或不加纵隔放疗。广泛期疾病患者,单纯系统治疗可减轻大多数患者的症状、延长生存;然而,长期生存罕见。请注意,局限期和广泛期SCLC的定义体现了TNM分期(参见本讨论中的工作步骤和分期)。仅推荐对某些手术可切除的I-ⅡA期SCLC患者进行手术治疗;对于某些不宜手术的I-ⅡA期SCLC患者,立体定向消融放疗(SABR)是一种选择。临床试验通常为SCLC患者提供最先进的治疗。虽然最近有进步,但是这些NCCN指南所概括的SCLC推荐治疗还需要改进。因此,应强烈鼓励参与临床试验。

Smoking cessation should be strongly promoted in patients with SCLC and other high-grade neuroendocrine carcinomas (see the NCCN Guidelines for Smoking Cessation, available at www.NCCN.org). Former smokers should be strongly encouraged to remain abstinent. Patients with SCLC who continue to smoke have increased toxicity during treatment and shorter survival. Programs using behavioral counseling combined with FDA-approved medications that promote smoking cessation can be very useful.
应强烈提倡SCLC和其他高级别神经内分泌癌患者戒烟(参见戒烟NCCN指南,可在www.NCCN.org获得)。应该强烈鼓励既往吸烟者保持戒烟。在治疗期间继续吸烟的SCLC患者毒性增加且生存期更短。使用行为咨询计划并结合FDA批准的促进戒烟的药物可能是非常有用的。


2019-08-13 16:01
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楼主 圣手阿良
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Diagnosis
诊断

Screening
筛查

Ideally, a screening test should detect disease at an early stage when it is still curable. Currently, no effective screening test is available to detect early-stage SCLC; the disease is typically diagnosed when patients present with symptoms indicative of advanced-stage disease (see Signs and Symptoms of Small Cell Lung Cancer in the algorithm). The National Lung Screening Trial (NLST) reported that screening with annual, low-dose, spiral CT scans decreased lung cancer-specific mortality in asymptomatic high-risk individuals (see the NCCN Guidelines for Lung Cancer Screening, available at www.NCCN.org). Although low-dose CT screening can detect early-stage non-small cell lung cancer (NSCLC), it does not seem to be useful for detecting early-stage SCLC. Low-dose CT screening is probably not useful for SCLC because of the aggressiveness of the disease, which results in the development of symptomatic disease between annual scans, thereby limiting the potential effect on mortality.
理想情况下,筛查应检出早期仍可治愈的疾病。目前,没有有效的筛选检查可以检出早期SCLC;通常是当患者出现晚期疾病症状时才确诊(参见工作步骤中小细胞肺癌的症状和体征)。国家肺癌筛查试验(NLST)报道,每年1次低剂量螺旋CT扫描筛查,在无症状高危个体中肺癌特异性死亡率下降(参见NCCN肺癌筛查指南,可在www.NCCN.org获得)。虽然低剂量CT筛检可以发现早期非小细胞肺癌(NSCLC),但似乎对检出早期SCLC没有用。对于SCLC低剂量CT筛查可能没有用,因为疾病的侵袭性,导致在每年1次的检查之间发展为有症状的疾病,因此限制了对死亡率的潜在影响。


2019-08-13 16:02
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Manifestations
表现

SCLC typically presents as a large hilar mass and bulky mediastinal lymphadenopathy that cause cough and dyspnea. Frequently, patients present with symptoms of widespread metastatic disease, such as weight loss, debility, bone pain, and neurologic compromise. The NCCN SCLC Panel recently added a new section describing signs and symptoms of SCLC based on the tumor location and type of metastases (see Signs and Symptoms of Small Cell Lung Cancer in the algorithm). It is uncommon for patients to present with a solitary peripheral nodule without central adenopathy. In this situation, fine-needle aspiration (FNA) may not adequately differentiate small cell carcinoma (which is a high-grade neuroendocrine carcinoma) from low-grade (typical carcinoid), intermediate-grade (atypical carcinoid), or large-cell neuroendocrine carcinoma (LCNEC) (which is also a high-grade neuroendocrine carcinoma) (see Lung Neuroendocrine Tumors in the NCCN Guidelines for Neuroendocrine and Adrenal Tumors, available at www.NCCN.org).
SCLC的典型表现为肺门大肿块和纵隔巨大淋巴结,引起咳嗽和呼吸困难。患者常常出现广泛的转移性疾病症状,如体重减轻、乏力、骨痛和神经损害。NCCN SCLC专家组最近增加了一个新章节,根据肿瘤部位和转移类型描述SCLC的症状与体征(参见工作步骤中小细胞肺癌的症状与体征)。无中央淋巴结的孤立性周围型结节患者罕见。在这种情况下,细针穿刺抽吸(FNA)或许不能充分区分小细胞癌(这是一种高级别的神经内分泌癌)、低级别(典型类癌)、中级别(不典型类癌)或大细胞神经内分泌癌(LCNEC)(这也是一种高级别神经内分泌癌)(参见神经内分泌和肾上腺肿瘤NCCN指南中的肺神经内分泌肿瘤,可在www.NCCN.org获得)。

Many neurologic and endocrine paraneoplastic syndromes are associated with SCLC. Neurologic syndromes include Lambert-Eaton myasthenic syndrome, encephalomyelitis, and sensory neuropathy. Patients with the Lambert-Eaton myasthenic syndrome present with proximal leg weakness that is caused by antibodies directed against the voltage-gated calcium channels. Paraneoplastic encephalomyelitis and sensory neuropathy are caused by the production of an antibody (anti-Hu) that cross-reacts with both small cell carcinoma antigens and human neuronal RNA-binding proteins resulting in multiple neurologic deficits; paraneoplastic encephalomyelitis may precede the diagnosis of a tumor. For the 2019 update, the NCCN SCLC Panel now recommends that if neurologic paraneoplastic syndrome is suspected, then obtaining a comprehensive paraneoplastic antibody panel should be considered.
许多神经系统和内分泌副肿瘤综合征与SCLC有关。神经系统症状包括Lambert-Eaton肌无力综合征、脑脊髓炎以及感觉神经病变。合并Lambert-Eaton肌无力综合征的患者表现为近端下肢无力,是由抗电压门控钙通道抗体引起的。副肿瘤性脑脊髓炎和感觉神经病变是由一种抗体(抗-Hu)引起的,该抗体既能与小细胞癌抗原结合,又能与人神经元RNA结合蛋白相互作用导致多神经损伤;副肿瘤性脑脊髓炎可能早于肿瘤的确诊。对于2019年的更新,NCCN SCLC专家组目前推荐如果怀疑神经系统副肿瘤综合征,则应考虑获取全面的副肿瘤抗体组套。

 

SCLC cells sometimes produce polypeptide hormones, including vasopressin (antidiuretic hormone [ADH]) and adrenocorticotropic hormone (ACTH), which cause hyponatremia of malignancy (ie, syndrome of inappropriate ADH secretion [SIADH]) and Cushing syndrome, respectively. In patients with SCLC, SIADH occurs more frequently than Cushing syndrome. Cancer treatment and/or supportive care may also cause hyponatremia (eg, cisplatin, opiates). Primary treatment for SIADH includes fluid restriction (which is difficult for patients because of increased thirst) and demeclocycline; vasopressin receptor inhibitors (ie, conivaptan, tolvaptan) can be used for refractory hyponatremia (see Principles of Supportive Care in the algorithm). Hyponatremia usually improves after successful treatment for SCLC.
SCLC细胞有时会产生多肽激素,包括加压素(抗利尿激素[ADH])和促肾上腺皮质激素(ACTH),分别引起恶性低钠血症(即抗利尿激素分泌异常综合征[SIADH])和库欣综合征。在SCLC患者中,SIADH比库欣综合征更常见。癌症治疗和/或支持治疗也可能导致低钠血症(如顺铂、阿片类)。SIADH的主要治疗包括限制液体(因为口渴,这对患者是困难的)和地美环素;加压素受体拮抗剂(即考尼伐坦、托伐普坦)可用于难治性低钠血症(参见工作步骤中的支持治疗原则)。在SCLC治疗成功后,低钠血症通常改善。


2019-08-13 16:03
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