小细胞肺癌临床特点及预后

美域国际健康是一家跨国治疗癌症的服务机构，从创业初期到现在已经帮助了众多癌症病人，延长了生存期。然而国人对于癌症的认识和预防少之又少，我们有必要了解一些癌症知识，本文从丹娜法伯小细胞肺癌的介绍分别阐述小细胞肺癌的发病率和死亡率，临床特点，诊断，及预后。

  

小细胞肺癌（SCLC）占支气管癌的将近15%。

诊断的时候，将近30%的小细胞肺癌病人肿瘤局限于胸部的原发部位，纵隔，或锁骨上淋巴节点。这些患者被指定为局限期疾病（LD）。[1] 肿瘤病人转移超过锁骨上区被叫做扩散期疾病（ED）。

 

小细胞肺癌相较于其他种肺癌对化疗和放疗更加敏感；然而，很难治愈，因为小细胞肺癌在诊断后有很强很快的广泛传播趋势。

 

1. 发病率和死亡率

 

美国小细胞肺癌的总发病率和死亡率在过去几十年已经下降。[2]

2014年美国肺癌新病例和死亡病例评估（小细胞肺癌[SCLC]和非小细胞肺癌[NSCLC]）

新病例：224,210.

死亡数: 159,260.

 

 

 

2. 临床特点

 

肺癌可能由呈现症状或者偶然在胸腔影像中发现。症状和体征可能是由于原发性局部浸润部位或者相邻胸部结构压迫引起，远处转移，或副肿瘤性现象。表现为常见的现象是很严重的咳嗽，气短，和呼吸困难。其他表现症状包括以下：

 

胸痛

 

声音嘶哑

 

身体不适

 

厌食症

 

体重下降

 

咳血

 

症状可能来自于局部浸润或者临近胸结构压迫，例如涉及食道压迫引起的吞咽困难，喉神经压迫引起声音嘶哑，或者上腔静脉受压区造成面部水肿和头颈部浅静脉扩张。远处转移症状可能表现包括脑部转移后的神经缺损和人格改变或者是骨转移引起的疼痛。

 

偶尔，小细胞肺癌病人也可能呈现如下副肿瘤综合征症状和体征之一：

 

抗利尿激素分泌不当

 

促肾上腺皮质激素分泌导致库欣综合征。

 

副肿瘤性小脑变性。

 

Lambert-Eaton 肌无力综合征。[2]

 

体检可能确定为锁骨上淋巴结肿大，胸腔积液或肺叶塌陷，迁延性肺炎，或者慢性阻塞性肺疾病等相关疾病迹象。

 

3. 诊断

 

病人的治疗选择取决于病人的组织学，病情阶段，并发症和健康状况。疑似小细胞肺癌患者的调查研究关注于诊断的确定及疾病范围的确定。  

 

确定癌症存在的程序包括以下：

 

病史

 

体检

 

常规实验室评估

 

胸腔x-ray

 

造影材料输注胸部计算X线断层扫描。

 

活检。

 

在病人开始肺癌治疗前，有经验的肺癌病理学家必须检查病理材料。这是很严格的。由于小细胞肺癌，对化疗反应很好，一般不用手术治疗，用显微镜检查非小细胞肺癌可能是困惑的。[4] 免疫组化疗法和电子显微镜检查对于诊断和分类是非常宝贵的技术，但是大多数肺癌由光镜标准分类。

 

4. 预后和生存时间

 

不管哪个阶段，即使过去的25年里诊断和治疗有提高，但是小细胞肺癌病人目前预后是不满意的。在无治疗的情况下，小细胞肺癌是任何类型肺肿瘤具侵袭性的临床病程。预后平均生存时间是2到4个月。从开始治疗的两年里，大约百分之十的小细胞肺癌病人总人数免受病害，在此期间，大多数有复发发生。然而即使这样这些病人，有死于肺癌风险（小细胞和非小细胞类型）。[5] 5年总生存率是5%-10%。[1][5][6][7]

 

小细胞肺癌一个重要的预后因素是疾病程度。局限期疾病（LD）病人比扩散期疾病（ED）病人有更好的预后。对于局限期疾病病人，平均生存时间是16-24个月，当前治疗14%的5年生存率已经报道。[1][6][8][9] 诊断为局限期疾病的吸烟病人在综合治疗前被鼓励停止吸烟，因为继续吸烟可能影响生存。[10]

 

已经显示综合治疗改善局限期小细胞肺癌病人的长期生存率。[9][11] [Level of evidence: 1iiA] 虽然报道病人中，长期存活者既接受过手术也单接受过化疗，但是化疗联合胸部放疗被当作标准治疗。 [12] 另外胸腔放疗，比单用化疗增加约5%的绝对生存期。[11][13]  胸腔放疗相对于化疗的佳时机在多个试验中已经评估出来。证据分析显示早期胸腔放射治疗的小益处。[1][14][15][Level of evidence: 1iiA]

 

据报道用现在可用的治疗方法治疗扩散期癌症病人，病人的平均生存期是6-12个月，但是长期无病生存期是少见的。

 

预防性全脑放疗会阻止中枢神经系统复发并提高接受过放化疗完全反应的病人的生存期。[16][17][Level of evidence: 1iiA]

 

所有这种癌症病人在诊断的时候可能适当考虑列入临床试验。更多临床试验信息从国家癌症研究所网站获得。（丹娜法伯癌症研究院 麻省医疗国际赵霞翻译）

 

参考:

 

1. Murray N, Coy P, Pater JL, et al.: Importance of timing for thoracic irradiation in the combined modality treatment of limited-stage small-cell lung cancer. The National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 11 (2): 336-44, 1993.

 

2. Govindan R, Page N, Morgensztern D, et al.: Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol 24 (28): 4539-44, 2006.

 

3. American Cancer Society: Cancer Facts and Figures 2014. Atlanta, Ga: American Cancer Society, 2014. Available online. Last accessed May 21, 2014.

 

4. Travis WD, Colby TV, Corrin B, et al.: Histological typing of lung and pleural tumours. 3rd ed. Berlin: Springer-Verlag, 1999.

 

5. Johnson BE, Grayson J, Makuch RW, et al.: Ten-year survival of patients with small-cell lung cancer treated with combination chemotherapy with or without irradiation. J Clin Oncol 8 (3): 396-401, 1990.

 

6. Fry WA, Menck HR, Winchester DP: The National Cancer Data Base report on lung cancer. Cancer 77 (9): 1947-55, 1996.

 

7. Lassen U, Osterlind K, Hansen M, et al.: Long-term survival in small-cell lung cancer: posttreatment characteristics in patients surviving 5 to 18+ years--an analysis of 1,714 consecutive patients. J Clin Oncol 13 (5): 1215-20, 1995.

 

8. Turrisi AT 3rd, Kim K, Blum R, et al.: Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med 340 (4): 265-71, 1999.

 

9. Jänne PA, Freidlin B, Saxman S, et al.: Twenty-five years of clinical research for patients with limited-stage small cell lung carcinoma in North America. Cancer 95 (7): 1528-38, 2002.

 

10. Videtic GM, Stitt LW, Dar AR, et al.: Continued cigarette smoking by patients receiving concurrent chemoradiotherapy for limited-stage small-cell lung cancer is associated with decreased survival. J Clin Oncol 21 (8): 1544-9, 2003.

 

11. Pignon JP, Arriagada R, Ihde DC, et al.: A meta-analysis of thoracic radiotherapy for small-cell lung cancer. N Engl J Med 327 (23): 1618-24, 1992.

 

12. Chandra V, Allen MS, Nichols FC 3rd, et al.: The role of pulmonary resection in small cell lung cancer. Mayo Clin Proc 81 (5): 619-24, 2006.

 

13. Warde P, Payne D: Does thoracic irradiation improve survival and local control in limited-stage small-cell carcinoma of the lung? A meta-analysis. J Clin Oncol 10 (6): 890-5, 1992.

 

14. Perry MC, Eaton WL, Propert KJ, et al.: Chemotherapy with or without radiation therapy in limited small-cell carcinoma of the lung. N Engl J Med 316 (15): 912-8, 1987.

 

15. Takada M, Fukuoka M, Kawahara M, et al.: Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer: results of the Japan Clinical Oncology Group Study 9104. J Clin Oncol 20 (14): 3054-60, 2002.

 

16. Aupérin A, Arriagada R, Pignon JP, et al.: Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group. N Engl J Med 341 (7): 476-84, 1999.

 

17. Slotman B, Faivre-Finn C, Kramer G, et al.: Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med 357 (7): 664-72, 2007.

 

 

General Information About Small Cell Lung Cancer

 

Small cell lung cancer (SCLC) accounts for approximately 15% of bronchogenic carcinomas.

 

At the time of diagnosis, approximately 30% of patients with SCLC will have tumors confined to the hemithorax of origin, the mediastinum, or the supraclavicular lymph nodes. These patients are designated as having limited-stage disease (LD).[1] Patients with tumors that have spread beyond the supraclavicular areas are said to have extensive-stage disease (ED).

 

SCLC is more responsive to chemotherapy and radiation therapy than other cell types of lung cancer; however, a cure is difficult to achieve because SCLC has a greater tendency to be widely disseminated by the time of diagnosis.

 

Incidence and Mortality

 

The overall incidence and mortality rates of SCLC in the United States have decreased during the past few decades.[2]

 

Estimated new cases and deaths from lung cancer (SCLC and non-small cell lung cancer [NSCLC] combined) in the United States in 2014:[3]

 

New cases: 224,210.

 

Deaths: 159,260.

 

Clinical Features

 

Lung cancer may present with symptoms or be found incidentally on chest imaging. Symptoms and signs may result from the location of the primary local invasion or compression of adjacent thoracic structures, distant metastases, or paraneoplastic phenomena. The most common symptoms at presentation are worsening cough, shortness of breath, and dyspnea. Other presenting symptoms include the following:

 

Chest pain.

 

Hoarseness.

 

Malaise.

 

Anorexia.

 

Weight loss.

 

Hemoptysis.

 

Symptoms may result from local invasion or compression of adjacent thoracic structures, such as compression involving the esophagus causing dysphagia, compression involving the laryngeal nerves causing hoarseness, or compression involving the superior vena cava causing facial edema and distension of the superficial veins of the head and neck. Symptoms from distant metastases may also be present and include neurological defect or personality change from brain metastases or pain from bone metastases.

 

Infrequently, patients with SCLC may present with symptoms and signs of one of the following paraneoplastic syndromes:

 

Inappropriate antidiuretic hormone secretion.

 

Cushing syndrome from secretion of adrenocorticotropic hormone.

 

Paraneoplastic cerebellar degeneration.

 

Lambert-Eaton myasthenic syndrome.[2]

 

Physical examination may identify enlarged supraclavicular lymphadenopathy, pleural effusion or lobar collapse, unresolved pneumonia, or signs of associated disease such as chronic obstructive pulmonary disease.

 

Diagnosis

 

Treatment options for patients are determined by histology, stage, and general health and comorbidities of the patient. Investigations of patients with suspected SCLC focus on confirming the diagnosis and determining the extent of the disease.

 

The procedures used to determine the presence of cancer include the following:

 

History.

 

Physical examination.

 

Routine laboratory evaluations.

 

Chest x-ray.

 

Chest computed tomography scan with infusion of contrast material.

 

Biopsy.

 

Before a patient begins lung cancer treatment, an experienced lung cancer pathologist must review the pathologic material. This is critical because SCLC, which responds well to chemotherapy and is generally not treated surgically, can be confused on microscopic examination with NSCLC.[4] Immunohistochemistry and electron microscopy are invaluable techniques for diagnosis and subclassification, but most lung tumors can be classified by light microscopic criteria.

 

(Refer to the Staging Evaluation section in the Stage Information for Small Cell Lung Cancer section of this summary for more information about tests and procedures used for staging.)

 

Prognosis and Survival

 

Regardless of stage, the current prognosis for patients with SCLC is unsatisfactory despite improvements in diagnosis and therapy made during the past 25 years. Without treatment, SCLC has the most aggressive clinical course of any type of pulmonary tumor, with median survival from diagnosis of only 2 to 4 months. About 10% of the total population of SCLC patients remains free of disease during the 2 years from the start of therapy, which is the time period during which most relapses occur. Even these patients, however, are at risk of dying from lung cancer (both small and non-small cell types).[5] The overall survival at 5 years is 5% to 10%.[1][5][6][7]

 

An important prognostic factor for SCLC is the extent of disease. Patients with LD have a better prognosis than patients with ED. For patients with LD, median survival of 16 to 24 months and 5-year survivals of 14% with current forms of treatment have been reported.[1][6][8][9] Patients diagnosed with LD who smoke should be encouraged to stop smoking before undergoing combined-modality therapy because continued smoking may compromise survival.[10]

 

Improved long-term survival in patients with LD has been shown with combined-modality therapy.[9][11][Level of evidence: 1iiA] Although long-term survivors have been reported among patients who received either surgery or chemotherapy alone, chemotherapy combined with thoracic radiation therapy (TRT) is considered the standard of care.[12] Adding TRT increases absolute survival by approximately 5% over chemotherapy alone.[11][13] The optimal timing of TRT relative to chemotherapy has been evaluated in multiple trials and meta-analyses with the weight of evidence suggesting a small benefit to early TRT.[1][14][15][Level of evidence: 1iiA]

 

In patients with ED, median survival of 6 to 12 months is reported with currently available therapy, but long-term disease-free survival is rare.

 

Prophylactic cranial radiation prevents central nervous system recurrence and can improve survival in patients who have had a complete response to chemoradiation.[16][17][Level of evidence: 1iiA]

 

All patients with this type of cancer may appropriately be considered for inclusion in clinical trials at the time of diagnosis. Information about ongoing clinical trials is available from the NCI Web site.

 

媒体发布：丹娜法伯对小细胞肺癌的研究数据