Small Lung Cancer

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Small lung cancer (SCLC), previously known as oat carcinoma, is considered distinct from other lung cancers, which are called non–small cell lung cancers (NSCLCs) because of their clinical and biologic characteristics. See the image below.

SCLC is a neuroendocrine carcinoma that exhibits aggressive behavior, rapid growth, early spread to distant sites, exquisite sensitivity to chemotherapy and radiation, and frequent association with distinct paraneoplastic syndromes, including hypercalcemia, Eaton-lambert syndrome, syndrome of inappropriate antidiuretic hormone (SIADH) secretion, and many others. (See Pathophysiology, Etiology, and Presentation.) [1, 2, 3]

In patients who present with SCLC, it is important to determine whether the cancer is limited or at an extensive stage. Limited-stage cancer, which is potentially curable, is treated with chemotherapy and radiation, with surgical resection reserved for selected patients with stage I disease. Extensive-stage cancer is incurable; systemic chemotherapy is used to improve quality of life and prolong survival. [4]

See Small Cell Lung Cancer: Beating the Spread, a Critical Images slideshow, to help identify the key clinical and biologic characteristics of small cell lung cancer, the staging criteria, and the common sites of spread.

Also see the Clinical Presentations of Lung Cancer: Slideshow and Lung Cancer Staging — Radiologic Options slideshows for additional information on SCLC staging and treatment.

Small cell lung carcinoma (SCLC) arises in peribronchial locations and infiltrates the bronchial submucosa. Widespread metastases occur early in the course of the disease, with common spread to the mediastinal lymph nodes, liver, bones, adrenal glands, and brain.

In addition, production of various peptide hormones leads to a wide range of paraneoplastic syndromes; the most common of these are the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and the syndrome of ectopic adrenocorticotropic hormone (ACTH) production. In addition, autoimmune phenomena may lead to various neurologic syndromes, such as Lambert-Eaton syndrome.

The predominant cause of small cell lung cancer (SCLC) (and non-SCLC) is tobacco smoking. Of all histologic types of lung cancer, SCLC and squamous cell carcinoma have the strongest correlation to tobacco. [5, 6] Approximately 98% of patients with SCLC have a smoking history. Patients with SCLC should be encouraged to stop smoking, as smoking cessation is associated with improved survival. [7]

All types of lung cancer occur with increased frequency in uranium miners, but SCLC is the most common. The incidence of lung cancer is increased further in these individuals if they also smoke tobacco.

Exposure to radon, an inert gas that is a product of uranium decay, has also been reported to cause SCLC.

Lung cancer overall is the second most common malignancy in both sexes in the United States, exceeded in frequency only by cancer in men and breast cancer in women. [8, 9, 10]  In both sexes, lung cancer is the most common cause of cancer death. Although less than half as many new cases of lung cancer than breast cancer are diagnosed in US women each year, almost twice as many US women die of lung cancer each year than from breast cancer.

The incidence of small cell lung cancer (SCLC) has declined over the last few years, as smoking rates have fallen. [10] SCLC once accounted for 20-25% of all newly diagnosed lung cancers; it now comprises only about 13% of all lung cancers. [11]

For 2019, the estimates for lung cancer overall in the United States are 228,150 new cases and 142,670 deaths. [10]

Globally, lung cancer is the most frequent malignancy in men (in Europe, lung cancer is second only to cancer [12] ) and the fifth most common cancer in women. Although the incidence of lung cancer has been falling in the US, it is increasing at a staggering pace in developing countries due to the rising prevalence of tobacco use. According to World Health Organization (WHO) statistics, about 1.69 million deaths from lung cancer occur annually throughout the world. [13]

Separate worldwide data for small cell carcinoma are not available. The incidence of lung cancer started to decline among men in the early 1980s and has continued to do so over the past 20 years. In contrast, the incidence in women started to increase in the late 1970s and did not begin to decline until the mid-2000s. [8, 10]

As with other histopathologic types of lung cancer, most cases of SCLC occur in individuals aged 60-80 years. 

Over the past two decades, the incidence of lung cancer has generally decreased in both men and women 30 to 54 years of age in all races and ethnic groups. However, the incidence has declined more steeply in men. As a result, lung cancer rates in younger women have become higher than those in younger men. In non-Hispanic whites and Hispanics ages 44 to 49 years, for example, the female-to-male rate ratio for lung cancer incidence rose from 0.88 during 1995-1999 to 1.17 during 2010-2014. [14]

This reversal can be explained in part by increased rates of cigarette smoking in women born since 1965. However, while the difference in smoking rates in that age group has narrowed, rates in women have generally not exceeded the rates in men, so other factors may be playing a role. For example, women may be more susceptible to the oncogenic effects of smoking. [14]

Approximately 60-70% of patients with small cell lung cancer (SCLC) have clinically disseminated or extensive disease at presentation. Extensive-stage SCLC is incurable. When given combination chemotherapy, patients with extensive-stage disease have a complete response rate of more than 20% and a median survival longer than 7 months; however, only 2% are alive at 5 years. [15] For individuals with limited-stage disease that is treated with combination chemotherapy plus chest radiation, a complete response rate of 80% and survival of 17 months have been reported; 12-15% of patients are alive at 5 years. [16]

Genome-wide association studies have identified single-nucleotide polymorphisms (eg, within the promoter region of YAP1 on chromosome 11q22) that may affect survival in patients with SCLC. [17, 18]  

Indicators of poor prognosis include the following:

Because tobacco smoking is the predominant cause of lung cancer, the only means of decreasing the incidence of this disease overall, as well as that of small cell lung cancer (SCLC) specifically, is to decrease the prevalence of smoking. The evidence is clear that the declining incidence of lung cancer in men in the United States has coincided with a decrease in smoking among males.

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Organ System

Syndrome

Mechanism

Frequency

Endocrine

SIADH

Antidiuretic hormone

15% [20]

Ectopic secretion of ACTH

ACTH

2-5% [21]

 

 

 

Neurologic

Eaton-Lambert reverse myasthenic syndrome

 

3% [22]

Subacute cerebellar degeneration

 

 

Subacute sensory neuropathy

 

 

Limbic encephalopathy

Anti-Hu, anti-Yo antibodies

 

ACTH = adrenocorticotropic hormone; SCLC = small cell lung cancer; SIADH = syndrome of inappropriate antidiuretic hormone.

Sources:  (1) Campling BG, Sarda IR, Baer KA, et al. Secretion of atrial natriuretic peptide and vasopressin by small cell lung cancer. Cancer. May 15, 1995;75(10):2442-51 [20] ; (2) Shepherd FA, Laskey J, Evans WK, et al. Cushing’s syndrome associated with ectopic corticotropin production and small-cell lung cancer. J Clin Oncol. Jan 1992;10(1):21-7 [21] ; (3) Sher E, Gotti C, Canal N, et al. Specificity of calcium channel autoantibodies in Lambert-Eaton myasthenic syndrome. Lancet. Sep 16, 1989;2(8664):640-3. [22]

Primary Tumor (T)

Tumor Size

Location of Involvement

TX

Primary tumor can’t be assessed, or sputum cytology reveals tumor cells but the tumor is not seen on radiologic or bronchoscopic evaluation

T0

No evidence of a primary tumor

Tis

Carcinoma in situ

T1

≤3 cm in greatest dimension

Surrounded by lung or visceral pleura; no invasion more proximal than lobar bronchus

T1a

≤1 cm in greatest dimension

T1b

 >1 cm but ≤2 cm in greatest dimension

T1c

>2 cm but ≤3 cm in greatest dimension

T2

>3 cm but ≤5 cm in greatest  dimension, or

(see right column)

Main bronchus, ≥2 cm distal to carina, or

Visceral pleura, or

Hilar region, but not entire lung, associated with atelectasis/obstructive pneumonitis

T2a

>3 cm but ≤4 cm in greatest  dimension

T2b

>5 cm but ≤7 cm in greatest  dimension

T3

>5 cm but ≤7 cm in greatest  dimension, or

(see right column)

Direct invasion of:

Parietal pleural chest wall, diaphragm, phrenic nerve, mediastinal pleura, parietal pericardium, or

Main bronchus < 2 cm distal to carina (but not carina itself), or

Entire lung with associated atelectasis/obstructive pneumonitis, or

Same lobe, separate tumor nodule(s)

T4

>7 cm or

(see right column)

Invasion of:

Mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, or carina

Different ipsilateral lobe, separate tumor nodule(s)

Node (N)

Location of Regional Metastatic Involvement

NX

Regional lymph nodes cannot be assessed

N0

No regional lymph node metastasis

N1

Ipsilateral peribronchial and/or ipsilateral hilar lymph nodes, and

Intrapulmonary nodes, including direct extension

N2

Ipsilateral mediastinal and/or subcarinal lymph node(s)

N3

Contralateral mediastinal, contralateral hilar, ipsilateral/contralateral scalene, or supraclavicular lymph node(s)

Metastasis (M)

Location of Distant Metastatic Involvement

M0

No distant metastasis

M1

Distant metastasis

M1a

Contralateral lobe tumor with separate tumor nodule(s), or

Tumor with pleural nodules or malignant pleural or pericardial effusion

M1b

Single extrathoracic metastasis in a single organ and involvement of a single distant (nonregional) node

M1c

AJCC = American Joint Committee on Cancer.

Adapted from:  (1) Edge SB, Byrd DR, Compton CC, et al, eds. AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer; 2010:299-330 [31] ; (2) National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology:Small Cell Lung Cancer [serial online]. 2018;v.2. Available at: http://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf. [31]

Primary Tumor (T)

Regional Node (N)

Metastasis (M)

Occult Cancer

TX

N0

M0

Stage 0

Tis

N0

M0

Stage IA

IA1

T1a

N0

M0

IA2

T1b

N0

M0

IA3

T1c

N0

M0

Stage IIA

T2b

N0

M0

Stage IIB

T1a,b,c

N1

M0

T2a,b

N1

M0

T3

N0

M0

Stage IIIA

T1a,b,c

N2

M0

T2a,b

N2

M0

T3

N1-2

M0

T4

N0-1

M0

Stage IIIB

T1a,b,c

N3

M0

T2a,b

N3

M0

T3

N2

M0

T4

N2

M0

Stage IIIC

T3-4

N3

M0

Stage IVA

Any T

Any N

M1a,b

Stage IVB

Any T

Any N

M1c

AJCC = American Joint Committee on Cancer.

Adapted from:  (1) Edge SB, Byrd DR, Compton CC, et al, eds. AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer; 2016 [36] ; (2) National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology:Small Cell Lung Cancer [serial online]. 2018;v.2. Available at: http://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf. [31]

Winston W Tan, MD, FACP Associate Professor of , Mayo Medical School; Consultant and Person-in-Charge of Genitourinary Oncology-Medical Oncology, Division of Hematology/Oncology, Department of Internal , Mayo Clinic Jacksonville; Vice Chairman of Education, Division of Hematology/Oncology, Mayo Clinic Florida

Winston W Tan, MD, FACP is a member of the following medical societies: American College of Physicians, American Society of Clinical Oncology, American Society of Hematology, Philippine Medical Association, Texas Medical Association

Disclosure: Nothing to disclose.

Irfan Maghfoor, MD  Oncologist, Department of Oncology, King Faisal Specialist Hospital and Research Center, Saudi Arabia

Irfan Maghfoor, MD is a member of the following medical societies: American Society of Hematology

Disclosure: Nothing to disclose.

Nagla Abdel Karim, MD, PhD Associate Professor of Medicine, Associate Director of Experimental Therapeutics, Division of Hematology/Oncology, University of Cincinnati Cancer Institute, Department of Internal Medicine, University of Cincinnati College of Medicine

Nagla Abdel Karim, MD, PhD is a member of the following medical societies: American Medical Association, American Society of Clinical Oncology, Egyptian American Medical Association, Egyptian Cancer Society, International Association for the Study of Lung Cancer

Disclosure: Nothing to disclose.

Small Cell Lung Cancer

Research & References of Small Cell Lung Cancer|A&C Accounting And Tax Services
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