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{{Non small cell lung cancer}}
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==Overview==
==Overview==


'''Non-small cell lung cancer''' ('''NSCLC''') is any type of epithelial [[lung cancer]] other than [[small-cell lung cancer]] (SCLC). Non-small cell lung cancer may be classified according to the WHO histological classification system into 3 main types: squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. Other less common subtypes, include: adenosquamous lung carcinoma, pulmonary sarcomatoid carcinoma, carcinoid tumors of lung, and carcinomas of the lung of salivary gland type.<ref name="NSCLC">Non-Small Cell Lung Cancer Treatment –for health professionals. National Cancer Institute – Physician Data Query PDQ. http://www.cancer.gov/types/lung/hp/non-small-cell-lung-treatment-pdq#link/_361_toc Accessed on February 3, 2016.</ref> Non-small cell lung cancer arises from the [[epithelial]] cells of the lung of the central [[bronchi]] to terminal [[alveoli]], which are normally involved in the protection of the airways. Non-small cell lung cancer is an invasive and rapidly growing cancer which may metastasize to different organs of the body. [[Genes]] involved in the pathogenesis of non-small cell lung cancer include multiple oncogenes, such as [[EGFR]], [[KRAS]], [[HER2]], [[BRAF]], [[ROS1 (gene)|ROS-1]], [[ALK-1|ALK]] AKT1, MEK1, MET, NRAS, PIK3CA, and RET . The primary cause of non-small cell lung cancer is DNA damage. Non-small cell lung cancer is the leading cause of cancer-related death among both men and women, and the most common cancer among the adult population in the United States.<ref name="NSCLS">SEER Stat Fact Sheets: Lung and Bronchus Cancer. http://seer.cancer.gov/statfacts/html/lungb.html Accessed on February 3 2016</ref><ref name="NsdS">Non-small cell lung cancer. https://en.wikipedia.org/wiki/Non-small-cell_lung_carcinoma Accessed on February 3 2016 <nowiki></ref name="FACTS"></nowiki>American Cancer Society: Cancer Facts and Figures 2016. Atlanta, Ga: American Cancer Society, 2016. Available online. Accessed February 3</ref> Non-small cell lung cancers account for about 85% of all lung cancers. The incidence rate of non-small cell lung cancer is approximately 42.6 per 100 000 individuals in the United States. Common risk factors in the development of non-small cell lung are [[smoking]], family history of [[lung cancer]], high levels of air pollution, [[radiation therapy]] to the chest, radon gas, [[asbestos]], occupational exposure to chemical carcinogens, and previous lung disease.<ref>Lung cancer. Canadian Cancer Society 2015. http://www.cancer.ca/en/cancer-information/cancer-type/lung/risks/?region=ab#Outdoor_air_pollution Accessed February 3, 2016</ref> Non-small cell lung cancer is a locally aggressive tumor, commonly occurs in patients between 65 to 74 years. Common sites of metastasis include [[adrenal gland]], [[Bone tumors|bone]], [[brain]], and [[liver]]. The 5-year relative survival of patients with non-small cell lung cancer is approximately 50%. Features associated with worse prognosis are [[genetic markers]], tumor size, associated conditions, clinical fitness for surgery, presence of lymphatic invasion, location of lesion, presence of satellite lesions, and presence of regional or distant metastases. Prognosis is generally regarded as poor with an all-stage average survival rate of 50%.  The 5-year recurrence rate of non-small cell lung cancer is 24%.<ref name="pmid17356101">{{cite journal |vauthors=Soares M, Darmon M, Salluh JI, Ferreira CG, Thiéry G, Schlemmer B, Spector N, Azoulay E |title=Prognosis of lung cancer patients with life-threatening complications |journal=Chest |volume=131 |issue=3 |pages=840–6 |year=2007 |pmid=17356101 |doi=10.1378/chest.06-2244 |url=}}</ref> Chemotherapy is indicated for non-small cell lung cancer stage (IB, II, and III) as adjuvant therapy. The predominant therapy for non-small cell lung cancer is surgical resection. [[Chemotherapy]] and chemoradiation may be required upon histological subtype of non-small cell lung cancer, location, size, and lymph node involvement.
'''Non-small cell lung cancer''' ('''NSCLC''') is any type of epithelial [[lung cancer]] other than [[small-cell lung cancer]] (SCLC). Non-small cell lung cancer may be classified according to the WHO histological classification system into 3 main types; [[Squamous cell carcinoma]], [[Adenocarcinoma of the lung|adenocarcinoma]], and [[Large cell carcinoma of the lung|large cell carcinoma]]. Other less common subtypes include [[Adenosquamous carcinoma|adenosquamous lung carcinoma]], [[Sarcomatoid carcinoma of the lung|pulmonary sarcomatoid carcinoma]], [[Carcinoid tumor of the lung|carcinoid tumors of the lung]], and carcinomas of the lung of salivary gland type. Non-small cell lung cancer arises from the [[epithelial]] cells of the lung of the [[bronchi]] to the [[alveoli]], which are normally involved in the protection of the airways. Non-small cell lung cancer is an invasive and rapidly growing cancer which may metastasize to different organs of the body. [[Genes]] involved in the pathogenesis of non-small cell lung cancer include multiple [[Oncogene|oncogenes]], such as [[EGFR]], [[KRAS]], [[HER2]], [[BRAF]], [[ROS1 (gene)|ROS-1]], [[ALK-1|ALK]], [[AKT1]], [[MEK1]], MET, [[Neuroblastoma RAS viral oncogene homolog|NRAS]], [[PIK3CA]], and [[RET proto-oncogene|RET]]. The primary cause of non-small cell lung cancer is [[DNA damage]]. Non-small cell lung cancer is the leading cause of cancer-related death among both men and women, and the most common cancer among the adult population in the United States. Non-small cell lung cancers account for about 85% of all [[Lung cancer|lung cancers]]. The incidence rate of non-small cell lung cancer is approximately 42.6 per 100 000 individuals in the United States. Common [[Risk factor|risk factors]] in the development of non-small cell lung are [[smoking]], family history of [[lung cancer]], high levels of [[air pollution]], [[radiation therapy]] to the chest, [[radon|radon gas]], [[asbestos]], occupational exposure to [[Carcinogen|chemical carcinogens]], and [[Lung disease|previous lung disease]]. Non-small cell lung cancer is a locally aggressive [[tumor]], commonly occurs in patients between 65 to 74 years. Common sites of [[metastasis]] include [[adrenal gland]], [[Bone tumors|bone]], [[brain]], and [[liver]]. The 5-year relative [[Survival rate|survival]] of patients with non-small cell lung cancer is approximately 50%. Features associated with worse [[prognosis]] are [[genetic markers]], tumor size, [[Non small cell lung cancer pathophysiology#Associated condition|associated conditions]], clinical fitness for [[surgery]], the presence of [[Lymph node metastases|lymphatic invasion]], the location of the lesion, the presence of satellite lesions, and presence of [[Metastasis|regional]] or [[Metastases|distant metastases.]] [[Prognosis]] is generally regarded as poor with an all-stage average survival rate of 50%.  The 5-year recurrence rate of non-small cell lung cancer is 24%. [[Chemotherapy]] is indicated for non-small cell lung cancer stage (IB, II, and III) as [[adjuvant therapy]]. The main therapy for non-small cell lung cancer is [[Resection|surgical resection]]. [[Chemotherapy]] and [[chemo-radiation]] may be required upon [[Histopathological subtype|histological subtype]] of non-small cell lung cancer, location, size, and [[Lymph node metastases|lymph node involvement]].


==Historical Perspective==
==Historical Perspective==
In 1929, Fritz Lickint a German physican first described the association between [[smoking]] and non small cell lung cancer.<ref name="history">Fritz Lickint. Wikipedia https://en.wikipedia.org/wiki/Fritz_Lickint Accessed on February 19,2016</ref>
[[Lung cancer]] was not identified as a disease until 1700. Morgagni GB, an Italian anatomist, first described [[lung cancer]] in his book "De sedibus et causis morborum per anatomen indagatis (1761). In 1761, Dr. John Hill of London, proved the relationship between the use of [[tobacco]] and [[cancer]] in his case study. In 1879, Harting and Hesse, two German physicians, first described the association between [[lung cancer]] and working in mines, and later radon gas was identified as the cause. In 1929, Fritz Lickint, a German physician first described the association between smoking and [[lung cancer]]. In 1965, U.S. Congress adopted the Federal Cigarette Labeling and Advertising Act and the Public Health Cigarette Smoking Act of 1969 as a preventive measure against [[Lung cancer|lung cancer.]]
 
==Classification==
==Classification==
 
Non-small cell lung cancer may be classified according to the [[World Health Organization|WHO histological classification system]] into 3 main types; [[Squamous cell lung cancer|Squamous cell carcinoma]], [[Adenocarcinoma of the lung|lung adenocarcinoma]], and [[Large cell carcinoma of the lung|large cell carcinoma]]. Other less common subtypes include [[Adenosquamous carcinoma|adenosquamous lung carcinoma]], [[Sarcomatoid carcinoma of the lung|pulmonary sarcomatoid carcinoma]], [[Carcinoid tumor of the lung|carcinoid tumors of the lung]], and carcinomas of the lung of salivary gland type.
Non-small cell lung cancer may be classified according to the WHO histological classification system into 3 main types: [[squamous cell carcinoma]], [[adenocarcinoma]], and [[large cell carcinoma]]. Other less common subtypes, include: adenosquamous lung carcinoma, pulmonary sarcomatoid carcinoma, carcinoid tumors of lung, and carcinomas of the lung of salivary gland type.<ref name="NSCLC">Non-Small Cell Lung Cancer Treatment –for health professionals. National Cancer Institute – Physician Data Query PDQ. http://www.cancer.gov/types/lung/hp/non-small-cell-lung-treatment-pdq#link/_361_toc Accessed on February 3, 2016.</ref>


==Pathophysiology==
==Pathophysiology==
 
Non-small cell lung cancer arises from the [[epithelial cells]] of the [[Bronchiole|bronchioles]] and [[Pulmonary alveolus|alveoli]][[Terminal bronchiole|,]] which are normally involved in the protection of the [[Airway|airways]]. Non-small cell lung cancer is an invasive and rapidly growing [[cancer]] which may [[Metastasis|metastasize]] to different organs of the body. [[Genes]] involved in the pathogenesis of non-small cell lung cancer include [[EGFR]], [[KRAS]], [[HER2]], [[BRAF]], and [[ALK-positive ALCL|ALK]]. Findings on gross pathology depend on the [[Histopathology|histological subtypes]] of non-small cell lung cancer. On microscopic [[Histopathology|histopathological]] analysis non-small cell lung cancer usually demonstrates [[Large cell|large cells]] with abundant [[cytoplasm]] and no stippled [[chromatin]].
Non-small cell lung cancer arises from the [[epithelial]] cells of the lung of the central [[bronchi]] to terminal [[alveoli]], which are normally involved in the protection of the airways. Non-small cell lung cancer is an invasive and rapidly growing cancer which may metastasize to different organs of the body. [[Genes]] involved in the pathogenesis of non-small cell lung cancer include [[EGFR]], [[KRAS]], [[HER2]], [[BRAF]], and ALK. On gross pathology, findings will depend on the histological type. On microscopic histopathological analysis non-small cell lung cancer demonstrate large cells with abundant cytoplasm and no stippled chromatin.


==Causes==
==Causes==
 
Cancers are caused by [[DNA]] changes that turn on [[Oncogene|oncogenes]] or turn off [[Tumor suppressor gene|tumor suppressor genes]]. [[Mutation|DNA mutations]] can be acquired or [[Heredity|hereditary]]. Non-small cell lung cancer may develop by [[Acquired disorder|acquired]] [[Mutation|genetic mutation]] of the ''[[TP53]]'' or [[P16 (gene)|''p16'' tumor suppressor genes]] and the ''[[KRAS|K-RAS]]'' or ''[[ALK-positive ALCL|ALK]]'' oncogenes as result of exposure to environmental factors such as [[smoking]], [[asbestos]] exposure, [[ionizing radiation]], and [[air pollution]], which are considered as [[Non small cell lung cancer risk factors|risk factors for NSCLC]]. [[Heredity|Hereditary]] factors in development of [[lung cancer]] is poorly understood because they are masked by the influence of environmental factors.
Common causes of non-small cell lung cancer include precursor lesions, such as metaplasia or dysplasia induced by smoking, asbestos exposure, ionizing radiation, atmospheric pollution, and chronic interstitial pneumonitis. Less common causes of non-small cell lung cancer include chromium and nickel exposure, vinyl chloride exposure, and inorganic arsenic exposure.<ref name="NSCL"> National Cancer Institute: PDQ® Non-Small Cell Lung Cancer Treatment. Bethesda, MD: National Cancer Institute. Date last modified January 22. http://www.cancer.gov/types/lung/hp/non-small-cell-lung-treatment-pdq. Accessed February 23, 2015</ref>


==Differentiating Non Small Cell Carcinoma of the Lung from other Diseases==
==Differentiating Non Small Cell Carcinoma of the Lung from other Diseases==
 
Non-small cell lung cancer must be differentiated from other diseases that cause chronic [[cough]], [[weight loss]], [[hemoptysis]], and [[dyspnea]] among adults such as [[tuberculosis]], [[Fungal pneumonia|pulmonary fungal disease]], [[lung abscess]], and secondary [[metastases]].
Non-small cell lung cancer must be differentiated from other diseases that cause chronic [[cough]], [[weight loss]], [[hemoptysis]], and [[dyspnea]] among adults such as [[tuberculosis]], pulmonary fungal disease, and secondary [[metastases]].


==Epidemiology and Demographics==
==Epidemiology and Demographics==
 
Non-small cell lung cancer is the most common cancer worldwide and the leading cause of [[Mortality|cancer-related mortality]] in the United States. Non-small cell lung cancer accounted for 1.8 million new cases and 1.6 million deaths of lung cancer in 2012. In the United States, the age-adjusted [[prevalence]] of non-small cell lung cancer is 47.2 per 100,000 individuals. The median age at diagnosis of non-small cell lung cancer is 70 years. Non-small cell lung cancer is most frequently diagnosed among people between 65 to 74 years old. Males are more commonly affected by non-small cell lung cancer than females. The male to female ratio is approximately 1.8 to 1. The rate of new cases in 2011 showed that males develop [[Lung cancer epidemiology and demographics|lung cancer]] more often than females (64.8 and 48.6 per 100,000 individuals). There is a racial preponderance to the development of non-small cell lung cancer, where African American individuals are at a significantly increased risk compared to Caucasian race.
Non-small cell lung cancer is the leading cause of cancer-related death among both men and women, and the most common cancer among the adult population in the United States.<ref name="NSCLS">SEER Stat Fact Sheets: Lung and Bronchus Cancer. http://seer.cancer.gov/statfacts/html/lungb.html Accessed on February 3 2016</ref><ref name="NsdS">Non-small cell lung cancer. https://en.wikipedia.org/wiki/Non-small-cell_lung_carcinoma Accessed on February 3 2016</ref><ref name="FACTS">American Cancer Society: Cancer Facts and Figures 2016. Atlanta, Ga: American Cancer Society, 2016. Available online. Accessed February 3</ref> These tumors account for about 85% of all lung cancers. The incidence rate of non-small cell lung cancer is approximately 42.6 per 100 000 individuals in the United States. The incidence of non-small cell lung cancer increases with age; the median age at diagnosis is between 40 to 75 years. Males are more commonly affected with non-small cell lung cancer than females. The male to female ratio is approximately 1.5 to 1.<ref name="NSCLS">SEER Stat Fact Sheets: Lung and Bronchus Cancer. http://seer.cancer.gov/statfacts/html/lungb.html Accessed on February 3 2016</ref>


==Risk Factors==
==Risk Factors==
 
Common risk factors in the development of non small cell lung are smoking, family history of [[lung cancer]], [[Air pollution|high levels of air pollution]], [[radiation therapy]] to the chest, [[radon|radon gas]], [[asbestos]], [[Occupational safety and health|occupational exposure]] to chemical [[carcinogens]], and previous [[lung disease]].
Common risk factors in the development of non small cell lung are smoking, family history of [[lung cancer]], high levels of air pollution, radiation therapy to the chest, radon gas, [[asbestos]], occupational exposure to chemical carcinogens, and previous lung disease.<ref>Lung cancer. Canadian Cancer Society 2015. http://www.cancer.ca/en/cancer-information/cancer-type/lung/risks/?region=ab#Outdoor_air_pollution Accessed February 3, 2016</ref>


==Screening==
==Screening==
 
According to the [[USPSTF|U.S. Preventive Services Task Force (USPSTF)]], screening for lung cancer by [[Computed tomography|low-dose computed tomography]] is recommended every year among [[smokers]] who are between 55 to 80 years old and who have history of smoke 30 pack-years or more and either continue to [[Smoking|smoke]] or have quit within the past 15 years (grade B recommendation).
According to the U.S. Preventive Services Task Force (USPSTF), screening for lung cancer by low-dose computed tomography is recommended every year among smokers who are between 55 to 80 years old and who have history of smoke 30 pack-years or more and either continue to smoke or have quit within the past 15 years (grade B recommendation).<ref name=“lung screen"> Lung Cancer: Screening  http://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/lung-cancer-screening. Accessed on February 3, 2016 <nowiki></ref></nowiki>


==Natural History, Complications and Prognosis==
==Natural History, Complications and Prognosis==
If left untreated, non-small cell lung cancer progression occurs slowly and is then followed by local invasion to [[lymph nodes]] and distant [[metastasis]]. Non-small cell lung cancer is a locally aggressive tumor, which commonly occurs in adult patients between 65 to 74 years. Common sites of [[metastasis]] include [[adrenal gland|the adrenal gland]], [[Bone tumors|bone]], [[brain]], and [[liver]]. Complications of non-small cell lung cancer include [[respiratory failure|acute respiratory failure]], [[respiratory acidosis]], [[pleural effusion|malignant pleural effusion]], [[metastases]], and [[pneumonia]]. The 5-year relative survival of patients with non-small cell lung cancer is approximately 50%. Features associated with worse prognosis are presence of [[Lymph node metastases|lymphatic invasion]], location of lesion, [[Gene expression|gene expression profile]], performance status,  presence of satellite lesions, and presence of [[Metastasis|regional or distant metastases]]. Prognosis is generally regarded as poor with an all-stage average survival rate of 25%. The 5-year recurrence rate of non-small cell lung cancer is approximately 24%.
==Diagnosis==


If left untreated, non-small cell lung cancer progression occurs slowly and is then followed by local invasion to [[lymph nodes]] and distant [[metastasis]].<ref name="pmid17356101">{{cite journal |vauthors=Soares M, Darmon M, Salluh JI, Ferreira CG, Thiéry G, Schlemmer B, Spector N, Azoulay E |title=Prognosis of lung cancer patients with life-threatening complications |journal=Chest |volume=131 |issue=3 |pages=840–6 |year=2007 |pmid=17356101 |doi=10.1378/chest.06-2244 |url=}}</ref> Non-small cell lung cancer is a locally aggressive tumor, commonly occurs in patients between 65 to 74 years. Common sites of metastasis include [[adrenal gland]], [[Bone tumors|bone]], [[brain]], and [[liver]]. Complications of non-small cell lung cancer are usually related to the site of metastasis. The 5-year relative survival of patients with non-small cell lung cancer is approximately 50%. Features associated with worse prognosis are [[genetic markers]], tumor size, associated conditions, clinical fitness for surgery, presence of lymphatic invasion, location of lesion, presence of satellite lesions, and presence of regional or distant metastases. Prognosis is generally regarded as poor with an all-stage average survival rate of 50%.  The 5-year recurrence rate of non-small cell lung cancer is 24%.<ref name="pmid17356101">{{cite journal |vauthors=Soares M, Darmon M, Salluh JI, Ferreira CG, Thiéry G, Schlemmer B, Spector N, Azoulay E |title=Prognosis of lung cancer patients with life-threatening complications |journal=Chest |volume=131 |issue=3 |pages=840–6 |year=2007 |pmid=17356101 |doi=10.1378/chest.06-2244 |url=}}</ref>
===Diagnostic Study of Choice===
 
[[Chest X-ray|Chest X-Ray]] is the initial study performed when non-small cell lung cancer is suspected. [[Lung]] [[Computed tomography|CT scan]] is the diagnostic study of choice for the diagnosis of non-small cell lung cancer. [[Endoscopic ultrasound|Endobronchial ultrasound]] is a first-line diagnostic modality for [[mediastinal]] staging of the non-small cell lung cancer. The lung [[biopsy]] is the gold standard for the diagnosis of the non-small cell lung cancer. The [[Non small cell lung cancer biopsy|lung biopsy]] helps to differentiate between the various subtypes of [[lung cancer]].
==Diagnosis==


===Staging===
===Staging===
 
[[Lung cancer staging|Staging system]] classifications for non-small cell lung cancer, include: [[American Joint Committee on Cancer|American Joint Committee on Cancer (AJCC)]] staging system and [[International Union Against Cancer|International Union Against Cancer (UICC)]] staging system. According to both institutions, TNM system, which they now develop jointly, classifies cancer by several factors, T for [[tumor]], N for [[Lymph node|nodes]], M for [[metastasis]]. TNM determines the stages of cancer based on the extent of involvement of the [[lung]], [[Lymph node|lymph nodes]], and adjacent structures.
Staging system classifications for non-small cell lung cancer, include: [[American Joint Committee on Cancer|American Joint Committee on Cancer (AJCC)]] staging system and [[International Union Against Cancer|International Union Against Cancer (UICC)]] staging system. According to both institutions, TNM system, which they now develop jointly, classifies cancer by several factors, T for tumor, N for nodes, M for metastasis, and then groups these TNM factors into overall stages.<ref name="canadian">Stages of non–small cell lung cancer. Canadian Cancer Society. http://www.cancer.ca/en/cancer-information/cancer-type/lung/staging/?region=ab</ref>


===History and Symptoms===
===History and Symptoms===
 
The hallmark of non-small cell lung cancer is [[Cough|chronic cough]], [[weight loss]], and [[hemoptysis]]. A positive history of [[smoking]], [[Asbestosis|exposure to asbestos]], [[tuberculosis infection]], or a [[Occupational safety and health|high risk occupation]] may be suggestive of non-small cell lung cancer. Symptoms related with non-small cell lung cancer will vary depending on the size and location of the [[tumor]]. Common symptoms of non-small cell lung cancer may also include [[shortness of breath]], [[fatigue]], and [[chest pain]].
The hallmark of non-small cell lung cancer is [[Cough|chronic cough]], [[weight loss]], and [[hemoptysis]]. A positive history of [[smoking]], [[Asbestosis|exposure to asbestos]], [[tuberculosis infection]], or a [[Occupational safety and health|high risk occupation]] may be suggestive of non-small cell lung cancer. Symptoms related with non-small cell lung cancer will vary depending on the size and location of the tumor. Common symptoms of non-small cell lung cancer may also include [[shortness of breath]], [[fatigue]], and [[chest pain]].<ref name="pain">Non small cell lung cancer. Wikipedia. https://en.wikipedia.org/wiki/Non-small-cell_lung_carcinoma Accessed on February 24, 2016 </ref><ref name="pmid17505036">{{cite journal |vauthors=Raz DJ, Zell JA, Ou SH, Gandara DR, Anton-Culver H, Jablons DM |title=Natural history of stage I non-small cell lung cancer: implications for early detection |journal=Chest |volume=132 |issue=1 |pages=193–9 |year=2007 |pmid=17505036 |doi=10.1378/chest.06-3096 |url=}}</ref>


===Physical Examination===
===Physical Examination===
 
Physical examination findings of non-small cell lung cancer will depend on the location of the tumor. Non-small cell lung cancer with central location may cause [[Crackles|crackling sounds]], [[Wheezing|focal wheezing]], [[Hoarseness|voice hoarseness]], and [[tachypnea]]. Peripheral location can present with [[pleurisy]] findings, such as reduced [[chest expansion]]. Common physical examination of patients with non-small cell lung cancer, include: crackling or bubbling noises, decreased/absent [[breath sounds]], and whispered pectoriloquy.
Physical examination findings of non-small cell lung cancer will depend on the location of the tumor. Non-small cell lung cancer with central location may cause [[Crackles|crackling sounds]], [[Wheezing|focal wheezing]], [[Hoarseness|voice hoarseness]], and [[tachypnea]]. Peripheral location can be consistent with [[pleurisy]] findings, such as reduced [[chest expansion]]. Common physical examination of patients with non-small cell lung cancer, include: crackling or bubbling noises, decreased/absent [[breath sounds]], whispered pectoriloquy, and [[tachypnea]].<ref name="pmid4813837">{{cite journal |vauthors=Hyde L, Hyde CI |title=Clinical manifestations of lung cancer |journal=Chest |volume=65 |issue=3 |pages=299–306 |year=1974 |pmid=4813837 |doi= |url=}}</ref>


===Laboratory Findings===
===Laboratory Findings===
 
The following laboratory tests are required for patients with non-small cell lung carcinoma, including squamous cell carcinoma are [[complete blood count]], [[Electrolyte|electrolytes]], [[calcium]], [[alkaline phosphatase]], [[alanine aminotransferase|alanine aminotransferase (ALT)]], [[aspartate aminotransferase|aspartate aminotransferase (AST)]], [[Bilirubin|total bilirubin]], [[creatinine]], [[albumin]], and [[lactate dehydrogenase]].
Laboratory findings associated with non-small cell lung cancer, include: elevation of LDH or serum tumor markers (CYFRA21-1, p53 antibody and CEA). Routine laboratory studies for non-small cell lung cancer, include: [[complete blood count]], [[Electrolyte|electrolytes]], [[calcium]], [[alkaline phosphatase]], [[alanine aminotransferase]] (ALT), [[aspartate aminotransferase]] (AST), [[Bilirubin|total bilirubin]], [[creatinine]], [[albumin]], and [[lactate dehydrogenase]].<ref name="pmid14736930">{{cite journal |vauthors=Spira A, Ettinger DS |title=Multidisciplinary management of lung cancer |journal=N. Engl. J. Med. |volume=350 |issue=4 |pages=379–92 |year=2004 |pmid=14736930 |doi=10.1056/NEJMra035536 |url=}}</ref> Other laboratory findings, associated with non-small cell lung cancer, include:  [[genetic testing]] for [[EGFR]], [[KRAS]], [[ALK-1|ALK]], and [[ROS1 (gene)|ROS-1]] mutations.


===Imaging===
===Imaging===


Conventional chest radiography is the initial imaging method of choice for the diagnostic evaluation of non-small cell lung cancer.<ref name="radiopedia">Non-small cell lung cancer: Adenocarcinoma of the lung. Radiopedia.http://radiopaedia.org/articles/adenocarcinoma-of-the-lung Accessed on March 1, 2016 </ref> The initial evaluation of suspected non-small cell lung cancer will depend upon the results of the chest X ray. Further evaluation of suspected non-small cell lung cancer, includes: enhanced [[CT scan]] (thorax, upper abdomen, and low neck) and/or [[MRI]] imaging. Imaging features for the evaluation of non-small cell lung cancer, include:  location ( central, peripheral, or pleural lesion), mass characteristics (size, shape, and margins), presence of [[cavitation]], and type of adenopathy ( hiliar or mediastinal). Other imaging and diagnostic modalities, such as [[endoscopic ultrasound]], [[bronchoscopy]], and [[mediastinoscopy]] may help determine and precise staging of non-small cell lung cancer.<ref name="who">WHO: Lung cancer/Tumours of the Lung. https://www.iarc.fr/en/publications/pdfs-online/pat-gen/bb10/bb10-chap1.pdf Accessed on March 1, 2016</ref>
===X Ray===
 
On [[chest X-ray]], characteristic findings of non-small cell lung cancer include rounded or spiculated mass, bulky [[hilum]] (representing the [[tumor]] and local [[Lymph node metastases|nodal involvement]]) and [[Atelactasis|lobar collapse]].
===Chest X Ray===
On conventional radiography, characteristic findings of non-small cell lung cancer, include:  rounded or spiculated mass, bulky [[hilum]] (representing the tumor and local nodal involvement) and lobar collapse.<ref name="pmid8190965">{{cite journal |vauthors=Rosado-de-Christenson ML, Templeton PA, Moran CA |title=Bronchogenic carcinoma: radiologic-pathologic correlation |journal=Radiographics |volume=14 |issue=2 |pages=429–46; quiz 447–8 |year=1994 |pmid=8190965 |doi=10.1148/radiographics.14.2.8190965 |url=}}</ref>
 
===CT===
Computed tomography is the method of choice for the diagnosis of non-small cell lung cancer. On CT, characteristic findings of non-small cell lung cancer, include: ground-glass opacity, rounded or spiculated mass, local nodal involvement, intraluminar obstruction, and lobar collapse.<ref name="pmid8190965">{{cite journal |vauthors=Rosado-de-Christenson ML, Templeton PA, Moran CA |title=Bronchogenic carcinoma: radiologic-pathologic correlation |journal=Radiographics |volume=14 |issue=2 |pages=429–46; quiz 447–8 |year=1994 |pmid=8190965 |doi=10.1148/radiographics.14.2.8190965 |url=}}</ref><ref name="pmid19234288">{{cite journal |vauthors=Parker MS, Chasen MH, Paul N |title=Radiologic signs in thoracic imaging: case-based review and self-assessment module |journal=AJR Am J Roentgenol |volume=192 |issue=3 Suppl |pages=S34–48 |year=2009 |pmid=19234288 |doi=10.2214/AJR.07.7081 |url=}}</ref>


===CT scan===
[[Computed tomography]] is the method of choice for the diagnosis of non-small cell lung cancer. On [[Computed tomography|CT]], characteristic findings of non-small cell lung cancer include [[Ground glass opacification on CT|ground-glass opacity]], rounded or spiculated mass, [[Lymph node metastases|local nodal involvement]], [[Airway obstruction|intraluminal obstruction]], and [[Atelactasis|lobar collapse.]]
===MRI===
===MRI===
On MRI, characteristic features for the diagnosis of non-small cell lung cancer, include: pleural effusion assessment, guidance for [[thoracentesis]], guidance for biopsy of peripheral lung or [[mediastinal mass]].<ref name="pmid25276380">{{cite journal |vauthors=Wang YX, Lo GG, Yuan J, Larson PE, Zhang X |title=Magnetic resonance imaging for lung cancer screen |journal=J Thorac Dis |volume=6 |issue=9 |pages=1340–8 |year=2014 |pmid=25276380 |pmc=4178109 |doi=10.3978/j.issn.2072-1439.2014.08.43 |url=}}</ref>
On [[Magnetic resonance imaging|MRI]], there are no specific findings of non-small cell cancer. MRI may be done for the [[pleural effusion]] assessment, guidance for [[thoracentesis]], and guidance for [[biopsy]] of peripheral [[lung]] or [[mediastinal mass]].


===Ultrasound===
===Ultrasound===
 
On [[Endoscopic ultrasound|endobronchial ultrasound (EBUS)]] and [[endoscopic ultrasound]], characteristic findings of non-small cell lung cancer include [[Lymphadenopathy|enlarged lymph nodes]] and local invasion to adjacent [[bronchial]] structures and [[Mediastinal mass|mediastinum]]. [[Endoscopic ultrasound|Endobronchial ultrasound]] is a first-line diagnostic modality for [[Mediastinal mass|mediastinal staging]].
On endobronchial and endoscopic ultrasound, characteristic findings of non-small cell lung cancer include: enlarged lymph nodes and local invasion to adjacent bronchial structures and mediastinum. Endobronchial ultrasound is a first-line diagnostic modality for mediastinal staging.<ref name="pmid24484269">{{cite journal |vauthors=Kinsey CM, Arenberg DA |title=Endobronchial ultrasound-guided transbronchial needle aspiration for non-small cell lung cancer staging |journal=Am. J. Respir. Crit. Care Med. |volume=189 |issue=6 |pages=640–9 |year=2014 |pmid=24484269 |doi=10.1164/rccm.201311-2007CI |url=}}</ref>


===Other Imaging Findings===
===Other Imaging Findings===
 
Other [[Imaging studies|imaging]] findings of non-small cell lung cancer include [[PET scan|PET]] and [[pulmonary angiography]]. [[Positron emission tomography|PET scan]] is used for general follow-up, monitor treatment response and as a [[Cancer staging|staging]] modality (in the risk of missing [[Occult|occult disease]]).
Other imaging findings of non-small cell lung cancer, include: [[Positron emission tomography|PET/CT]] and [[pulmonary angiography]].<ref name="pmid16014441">{{cite journal |vauthors=Shim SS, Lee KS, Kim BT, Chung MJ, Lee EJ, Han J, Choi JY, Kwon OJ, Shim YM, Kim S |title=Non-small cell lung cancer: prospective comparison of integrated FDG PET/CT and CT alone for preoperative staging |journal=Radiology |volume=236 |issue=3 |pages=1011–9 |year=2005 |pmid=16014441 |doi=10.1148/radiol.2363041310 |url=}}</ref>


===Other Diagnostic Studies===
===Other Diagnostic Studies===
 
Diagnosis of non-small cell lung cancer can be confirmed by [[Histopathology|histopathological]] evaluation and [[immunohistochemical staining]] of the tumor specimen obtained from [[biopsy]]. Different types of lung [[Biopsy|tissue biopsy]] for non-small cell lung cancer include transthoracic [[needle biopsy]], [[Thoracotomy|open biopsy]], and [[Thoracoscopy|video-assisted thoracoscopic surgery (VATS)]]. Specimen for [[Histopathology|histopathological]] evaluation and [[immunohistochemical staining]] can also be obtained by [[bronchoscopy]], [[mediastinoscopy]], transthoracic percutaneous [[fine needle aspiration]] or [[Cytology|sputum cytology]].
Other diagnostic modalities for non-small cell lung cancer, include: [[thoracotomy]], [[bronchoscopy]], [[mediastinoscopy]], and transthoracic percutaneous [[fine needle aspiration]].<ref name="pmid24484269">{{cite journal |vauthors=Kinsey CM, Arenberg DA |title=Endobronchial ultrasound-guided transbronchial needle aspiration for non-small cell lung cancer staging |journal=Am. J. Respir. Crit. Care Med. |volume=189 |issue=6 |pages=640–9 |year=2014 |pmid=24484269 |doi=10.1164/rccm.201311-2007CI |url=}}</ref>
 
===Biopsy===
Biopsy findings associated with non-small cell lung cancer will depend on tumor [[histology]], common findings include: prominent nucleoli, eosinophilic cytoplasm, and intracellular bridges. Different types of lung tissue biopsy for non-small cell lung cancer, includes: needle biopsy, open biopsy, and video-assisted thoracoscopic surgery.<ref name="NSCLS">Non-small cell lung cancer. Libre Pathology http://librepathology.org/wiki/Non-small_cell_lung_carcinoma Accessed on March 1, 2016</ref><ref name="NSCLS1">Lung adenosquamous carcinoma. Libre Pathology. http://librepathology.org/wiki/Adenosquamous_carcinoma_of_the_lung Accessed on March 1, 2016</ref><ref name="NSCLS2">Squamous cell carcinoma of the lung. Libre Pathology http://librepathology.org/wiki/Squamous_cell_carcinoma_of_the_lung Accessed on March 1, 2016</ref>


==Treatment==
==Treatment==
Line 92: Line 72:
===Management Approach===
===Management Approach===


The optimal management approach of non-small cell lung cancer will depend on a series of characteristics, that include: pre-treatment evaluation, location, and adequate [[Cancer staging|staging]]. Different treatment options for management of non-small cell lung cancer, include: [[surgery]], [[neoadjuvant chemotherapy]], [[Adjuvant therapy|adjuvant chemotherapy]], and [[radiation therapy]].<ref name="pmid10185145">{{cite journal |vauthors=Melville A, Eastwood A |title=Management of lung cancer |journal=Qual Health Care |volume=7 |issue=3 |pages=170–7 |year=1998 |pmid=10185145 |pmc=2483609 |doi= |url=}}</ref>
The optimal management approach of non-small cell lung cancer will depend on a series of characteristics, which includes: pre-treatment evaluation, location, and adequate [[Cancer staging|staging]]. Common treatment options for management of non-small cell lung cancer include [[surgery]], [[neoadjuvant chemotherapy]], [[Adjuvant therapy|adjuvant chemotherapy]], and [[radiation therapy]].


===Stage I===
===Stage I===
 
Therapies for non-small cell lung cancer stage I include [[surgery]], [[radiation therapy]], or [[surgery]] and [[chemotherapy]] (if the tumor size is larger than 4cm).
Therapies for non-small cell lung cancer stage I, include: surgery, radiation therapy, or surgery and chemotherapy (if the tumor size is larger than 4cm).<ref name="pmid10185145">{{cite journal |vauthors=Melville A, Eastwood A |title=Management of lung cancer |journal=Qual Health Care |volume=7 |issue=3 |pages=170–7 |year=1998 |pmid=10185145 |pmc=2483609 |doi= |url=}}</ref>
   
   
===Stage II===
===Stage II===
 
Therapies for non-small cell lung cancer stage II include [[surgery]], [[neoadjuvant chemotherapy]], [[adjuvant chemotherapy]], and [[radiation therapy]]. If the [[tumor]] is resectable, the preferred treatment for stage II non small cell lung cancer, includes: surgical resection with [[lymph node]] dissection and pathological evaluation.  If evidence of [[lymph node]] extension of the disease is present adjutant [[Non small cell lung cancer chemotherapy|chemotherapy]] should be administered.
Therapies for non-small cell lung cancer stage II, include: surgery, neoadjuvant chemotherapy, adjuvant chemotherapy, and radiation therapy. If the [[tumor]] is resectable, the preferred treatment for stage II non small cell lung cancer, includes: surgical resection with [[lymph node]] dissection and pathological evaluation.  If evidence of [[lymph node]] extension of the disease is present adjutant [[Non small cell lung cancer chemotherapy|chemotherapy]] should be administered.<ref name="pmid10185145">{{cite journal |vauthors=Melville A, Eastwood A |title=Management of lung cancer |journal=Qual Health Care |volume=7 |issue=3 |pages=170–7 |year=1998 |pmid=10185145 |pmc=2483609 |doi= |url=}}</ref>


===Stage III===
===Stage III===
 
Therapies for non-small cell lung cancer stage III, depends on 4 categories; Resectable tumors, unresectable tumors, superior sulcus tumors, and tumors that invade the chest wall. Therapies for resectable tumors include [[surgery]], [[neoadjuvant therapy]], and [[adjuvant therapy]]. Alternatively, therapies for unresectable disease only include [[radiation therapy]], and [[chemoradiation therapy]]. Therapies for superior sulcus tumors include [[radiation therapy]] alone, [[radiation therapy]] and [[surgery]], concurrent [[chemotherapy]] with [[radiation therapy]] and [[surgery]]. Lastly, therapies for tumors that invade the [[Thoracic cavity|chest wall]] include [[surgery]], [[surgery]] and [[radiation therapy]], [[radiation therapy]] alone, and [[chemotherapy]] combined with [[radiation therapy]] and/or [[surgery]].  The treatment of stage III non-small cell lung cancer will be contingent on the extension of the [[tumor]]. [[Chemotherapy]] and/or [[radiation therapy]] should be considered for patients with stage IIIB.
Therapies for non-small cell lung cancer stage III, will depend on 4 categories: resectable tumors, unresectable tumors, superior sulcus tumors, and tumors that invade the chest wall. Therapies for resectable tumors, include: surgery, neoadjuvant therapy, and adjuvant therapy. Alternatively, therapies for unresectable disease, only include: radiation therapy, and chemoradiation therapy. Therapies for superior sulcus tumors, include: radiation therapy alone, radiation therapy and surgery, concurrent chemotherapy with radiation therapy and surgery. Lastly, therapies for tumors that invade the chest wall, include: surgery, surgery and radiation therapy, radiation therapy alone, and chemotherapy combined with radiation therapy and/or surgery.  The treatment of stage III non-small cell lung cancer will be contingent on the extension of the [[tumor]]. [[Chemotherapy]] and/or [[radiation therapy]] should be considered for patients with stage IIIB.<ref name="pmid10185145">{{cite journal |vauthors=Melville A, Eastwood A |title=Management of lung cancer |journal=Qual Health Care |volume=7 |issue=3 |pages=170–7 |year=1998 |pmid=10185145 |pmc=2483609 |doi= |url=}}</ref>


===Stage IV===
===Stage IV===
 
Therapies for non-small cell lung cancer stage IV include [[cytotoxic]] combination [[chemotherapy]] (first line), combination chemotherapy with bevacizumab or cetuximab, EGFR [[tyrosine kinase inhibitors]], [[EML4]]-[[ALK-positive ALCL|ALK]] inhibitors in patients with [[EML4|EML]]-[[ALK-positive ALCL|ALK]] translocation, and immune checkpoint inhibition with [[nivolumab]] for selected patients with [[Squamous cell|squamous]] or non-squamous metastatic. Maintenance therapy following first-line [[chemotherapy]], include [[Laser therapy|endobronchial laser therapy]] or [[brachytherapy]] (for obstructing lesions) and [[External beam radiotherapy|external beam radiation therapy]] (primarily for palliation of local symptomatic tumor growth). Local therapies (ambulatory catheter drainage, [[pleurodesis]] or mediastinal window) plus therapy for [[Non small cell lung cancer medical therapy metastatic cancer#Medical Therapy for Metastatic Non-Small Cell Lung Cancer|systemic metastasis]] is the preferred combination for patients with stage IV M1a non-small cell lung cancer. Patients with solitary site [[metastasis]] (stage IV M1b) should be treated according to the site of [[metastasis]].
Therapies for non-small cell lung cancer stage IV, include: cytotoxic combination chemotherapy (first line), combination chemotherapy with [[bevacizumab]] or [[cetuximab]], EGFR tyrosine kinase inhibitors, EML4-ALK inhibitors in patients with EML-ALK [[translocations]], and immune checkpoint inhibition with nivolumab for selected patients with squamous or non-squamous metastatic. Maintenance therapy following first-line chemotherapy, include: endobronchial laser therapy or brachytherapy (for obstructing lesions) and external-beam radiation therapy (primarily for palliation of local symptomatic tumor growth). Local therapies (ambulatory catheter drainage, [[pleurodesis]] or mediastinal window) plus therapy for [[Non small cell lung cancer medical therapy metastatic cancer#Medical Therapy for Metastatic Non Small Cell Lung Cancer|systemic metastasis]] is the preferred combination for patients with stage IV M1a non-small cell lung cancer. Patients with solitary site [[metastasis]] (stage IV M1b) should be treated according to the site of [[metastasis]].<ref name="NCCN">http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf</ref>


===Metastatic Cancer===
===Metastatic Cancer===
 
Therapies for non-small cell lung cancer stage IV include [[radiation therapy]] (for palliation) and palliative [[chemotherapy]]. The treatment of [[metastatic]] non-small cell lung cancer depends on the site and extension of the disease. If specific [[mutations]] are diagnosed, targeted treatment should be administered.
Therapies for metastatic non-small cell lung cancer, include: radiation therapy (for palliation) and palliative chemotherapy. The treatment of metastatic non-small cell lung cancer depends on the site and extension of the disease. If specific mutations are diagnosed, targeted treatment should be administered.


==Medical Therapy==
==Medical Therapy==
 
Chemotherapy is indicated for non-small cell lung cancer stage (IB, II, and III) as [[adjuvant therapy]]. The predominant therapy for non-small cell lung cancer is [[Resection|surgical resection]]. [[Chemotherapy]] and [[Chemotherapy|chemo]]-[[Radiation therapy|radiation]] may be required upon [[histological]] subtype of non-small cell lung cancer, location, size, and [[Lymph node metastases|lymph node involvement]]. Commonly used [[Chemotherapeutic agent|chemotherapeutic agents]] include [[gemcitabine]], [[paclitaxel]], [[docetaxel]], [[pemetrexed]], [[etoposide]] or [[vinorelbine]].
Chemotherapy is indicated for non-small cell lung cancer stage (IB, II, and III) as adjuvant therapy. The predominant therapy for non-small cell lung cancer is surgical resection. Chemotherapy and chemoradiation may be required upon histological subtype of non-small cell lung cancer, location, size, and lymph node involvement. Commonly used chemotherapeutic agents, include: [[gemcitabine]], [[paclitaxel]], [[docetaxel]], [[pemetrexed]], [[etoposide]] or [[vinorelbine]].


===Chemotherapeutic Regimen===
===Chemotherapeutic Regimen===
 
[[List of chemotherapy regimens|Chemotherapeutic regimens]] are based on [[Platinum-based antineoplastic|platinum agents]] such as [[cisplatin]], [[carboplatin]], [[oxaliplatin]], and [[satraplatin]]. Alternative regimens include [[paclitaxel]], [[gemcitabine]], or [[etoposide]]. [[List of chemotherapy regimens|Chemotherapeutic regimens]] are adjusted based on individual characteristics and body surface. The regimen adjustment according to tumor evolution has demonstrated longer [[Survival rate|survival rates]], optimal symptom control, and higher quality of life.
Chemotherapeutic regimens are based on platinum agents, such as: [[cisplatin]], [[carboplatin]], [[oxaliplatin]], and [[satraplatin]]. Alternative regimens, include: [[paclitaxel]], [[gemcitabine]], or [[etoposide]]. Chemotherapeutic regimens are adjusted based on individual characteristics and body surface. The regimen adjustment according to tumor evolution has demonstrated longer survival rates, optimal symptom control, and higher quality of life.<ref name="lungcancer">Alberti, W; Anderson, G; Bartolucci, A; Bell, D; et al. Chemotherapy in non-small cell lung cancer: A meta-analysis using updated data on individual patients from 52 randomised clinical trials. British Medical Journal, International edition311.7010 (Oct 7, 1995): 899 </ref>


===Radiation Therapy===
===Radiation Therapy===
 
[[Radiation therapy]] can be applied to any stage of non-small cell lung cancer. In general, [[radiation therapy]] is recommended as [[Palliative care|palliative care treatment]] among patients who develop an advanced stage of non-small cell lung cancer or symptomatic patients with local involvement (pain, [[vocal cord paralysis]], and [[hemoptysis]]). Curative [[radiation therapy]] may be indicated in patients who are not suitable for [[surgery]] with early-stage non-small cell lung cancer. The main goal of radiation therapy for non-small cell lung cancer is maximum [[tumor]] control with minimal [[tissue]] toxicity. The two main types of [[radiation therapy]] for non-small cell lung cancer are [[external beam radiation therapy]] (thoracic radiotherapy), and [[brachytherapy]] (internal radiation therapy).
[[Radiation therapy]] can be applied to any stage of non-small cell lung cancer, according to the individual parameters provided for each stage. In general, radiation therapy is effective and recommended as palliative care among patients who develop advanced stage of non-small cell lung cancer or symptomatic patients with local involvement (pain , vocal cord paralysis, and hemoptysis). Curative radiation therapy may be indicated in patients who are not suitable for surgery with early stage non-small cell lung cancer. The main goal of radiation therapy for non-small cell lung cancer is maximum [[tumor]] control with minimal [[tissue]] toxicity. There are 2 main types of radiation therapy for non-small cell lung cancer: external beam radiation therapy (thoracic radiotherapy), and [[brachytherapy]] (internal radiation therapy).<ref name="radio"> Pattern of use of radiotherapy for lung cancer: a descriptive study. BioMed Central. http://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-14-697#CR6 Accessed on March 1, 2016</ref>


==Surgery==
==Surgery==
Surgery is the mainstay of therapy for early-stage non-small cell lung cancer. Common surgical procedures for the treatment of non-small cell lung cancer, include: lung resection with [[lobectomy]], lung resection with pneumonectomy with or without [[Dissection|lymph node dissection]]. The preferred surgical procedure is [[thoracotomy]] with removal of the entire lung or lobe (lobectomy) along with regional lymph nodes and contiguous structures.
[[Surgery]] is the mainstay of therapy for early-stage non-small cell lung cancer. Common [[List of surgical procedures|surgical procedures]] for the treatment of non-small cell lung cancer, include [[Resection|lung resection]] with [[lobectomy]], lung [[resection]] with [[pneumonectomy]] with or without [[lymph node]] dissection. The preferred surgical procedure is [[thoracotomy]] with the removal of the entire [[lung]] or [[Lobectomy of lung|lobe (lobectomy)]] along with regional [[Lymph node|lymph nodes]] and contiguous structures.


==Primary Prevention==
==Primary Prevention==
 
[[Prevention (medical)|Primary prevention]] of non-small cell lung cancer includes avoidance of [[smoking]], [[Passive smoking|smoking exposure]], exposure to [[asbestos]], and other high-risk occupational jobs.
Primary prevention of non-small cell lung cancer includes avoidance of smoking, smoking exposure, exposure to asbestos, and other [[Occupational health|high risk occupational jobs]].<ref name="pmid14641993">{{cite journal |vauthors=Khuri FR |title=Primary and secondary prevention of non-small-cell lung cancer: the SPORE Trials of Lung Cancer Prevention |journal=Clin Lung Cancer |volume=5 Suppl 1 |issue= |pages=S36–40 |year=2003 |pmid=14641993 |doi= |url=}}</ref>


==Secondary Prevention==
==Secondary Prevention==
 
The [[Prevention (medical)|secondary prevention]] of non-small cell lung cancer is based on the stage of non-small cell lung cancer at diagnosis. [[Prevention (medical)|Secondary prevention]] includes chest [[CT]] along with a periodic evaluation of alert signs in [[Passive smoking|second-hand smokers]] or [[Smoking|active smokers]].
The secondary prevention of non-small cell lung cancer is based on the stage of non-small cell lung cancer at diagnosis. Secondary prevention include [[CT|chest CT imaging]] along with periodic evaluation of alert signs in second-hand smokers or active smokers.<ref name="pmid10824565">{{cite journal |vauthors=Tominaga S |title=[Prevention of lung cancer--primary and secondary prevention] |language=Japanese |journal=Nippon Rinsho |volume=58 |issue=5 |pages=1149–52 |year=2000 |pmid=10824565 |doi= |url=}}</ref>


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}


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Latest revision as of 22:58, 29 July 2020

Non Small Cell Lung Cancer Microchapters

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Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Non Small Cell Lung Cancer from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X-Ray

CT Scan

MRI

Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Management Approach

Stage I
Stage II
Stage III
Stage IV
Metastatic Cancer

Medical Therapy

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Surgery

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Trusha Tank, M.D.[2],Maria Fernanda Villarreal, M.D. [3],Furqan M M. M.B.B.S[4]

Overview

Non-small cell lung cancer (NSCLC) is any type of epithelial lung cancer other than small-cell lung cancer (SCLC). Non-small cell lung cancer may be classified according to the WHO histological classification system into 3 main types; Squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. Other less common subtypes include adenosquamous lung carcinoma, pulmonary sarcomatoid carcinoma, carcinoid tumors of the lung, and carcinomas of the lung of salivary gland type. Non-small cell lung cancer arises from the epithelial cells of the lung of the bronchi to the alveoli, which are normally involved in the protection of the airways. Non-small cell lung cancer is an invasive and rapidly growing cancer which may metastasize to different organs of the body. Genes involved in the pathogenesis of non-small cell lung cancer include multiple oncogenes, such as EGFR, KRAS, HER2, BRAF, ROS-1, ALK, AKT1, MEK1, MET, NRAS, PIK3CA, and RET. The primary cause of non-small cell lung cancer is DNA damage. Non-small cell lung cancer is the leading cause of cancer-related death among both men and women, and the most common cancer among the adult population in the United States. Non-small cell lung cancers account for about 85% of all lung cancers. The incidence rate of non-small cell lung cancer is approximately 42.6 per 100 000 individuals in the United States. Common risk factors in the development of non-small cell lung are smoking, family history of lung cancer, high levels of air pollution, radiation therapy to the chest, radon gas, asbestos, occupational exposure to chemical carcinogens, and previous lung disease. Non-small cell lung cancer is a locally aggressive tumor, commonly occurs in patients between 65 to 74 years. Common sites of metastasis include adrenal gland, bone, brain, and liver. The 5-year relative survival of patients with non-small cell lung cancer is approximately 50%. Features associated with worse prognosis are genetic markers, tumor size, associated conditions, clinical fitness for surgery, the presence of lymphatic invasion, the location of the lesion, the presence of satellite lesions, and presence of regional or distant metastases. Prognosis is generally regarded as poor with an all-stage average survival rate of 50%. The 5-year recurrence rate of non-small cell lung cancer is 24%. Chemotherapy is indicated for non-small cell lung cancer stage (IB, II, and III) as adjuvant therapy. The main therapy for non-small cell lung cancer is surgical resection. Chemotherapy and chemo-radiation may be required upon histological subtype of non-small cell lung cancer, location, size, and lymph node involvement.

Historical Perspective

Lung cancer was not identified as a disease until 1700. Morgagni GB, an Italian anatomist, first described lung cancer in his book "De sedibus et causis morborum per anatomen indagatis (1761). In 1761, Dr. John Hill of London, proved the relationship between the use of tobacco and cancer in his case study. In 1879, Harting and Hesse, two German physicians, first described the association between lung cancer and working in mines, and later radon gas was identified as the cause. In 1929, Fritz Lickint, a German physician first described the association between smoking and lung cancer. In 1965, U.S. Congress adopted the Federal Cigarette Labeling and Advertising Act and the Public Health Cigarette Smoking Act of 1969 as a preventive measure against lung cancer.

Classification

Non-small cell lung cancer may be classified according to the WHO histological classification system into 3 main types; Squamous cell carcinoma, lung adenocarcinoma, and large cell carcinoma. Other less common subtypes include adenosquamous lung carcinoma, pulmonary sarcomatoid carcinoma, carcinoid tumors of the lung, and carcinomas of the lung of salivary gland type.

Pathophysiology

Non-small cell lung cancer arises from the epithelial cells of the bronchioles and alveoli, which are normally involved in the protection of the airways. Non-small cell lung cancer is an invasive and rapidly growing cancer which may metastasize to different organs of the body. Genes involved in the pathogenesis of non-small cell lung cancer include EGFR, KRAS, HER2, BRAF, and ALK. Findings on gross pathology depend on the histological subtypes of non-small cell lung cancer. On microscopic histopathological analysis non-small cell lung cancer usually demonstrates large cells with abundant cytoplasm and no stippled chromatin.

Causes

Cancers are caused by DNA changes that turn on oncogenes or turn off tumor suppressor genes. DNA mutations can be acquired or hereditary. Non-small cell lung cancer may develop by acquired genetic mutation of the TP53 or p16 tumor suppressor genes and the K-RAS or ALK oncogenes as result of exposure to environmental factors such as smoking, asbestos exposure, ionizing radiation, and air pollution, which are considered as risk factors for NSCLC. Hereditary factors in development of lung cancer is poorly understood because they are masked by the influence of environmental factors.

Differentiating Non Small Cell Carcinoma of the Lung from other Diseases

Non-small cell lung cancer must be differentiated from other diseases that cause chronic cough, weight loss, hemoptysis, and dyspnea among adults such as tuberculosis, pulmonary fungal disease, lung abscess, and secondary metastases.

Epidemiology and Demographics

Non-small cell lung cancer is the most common cancer worldwide and the leading cause of cancer-related mortality in the United States. Non-small cell lung cancer accounted for 1.8 million new cases and 1.6 million deaths of lung cancer in 2012. In the United States, the age-adjusted prevalence of non-small cell lung cancer is 47.2 per 100,000 individuals. The median age at diagnosis of non-small cell lung cancer is 70 years. Non-small cell lung cancer is most frequently diagnosed among people between 65 to 74 years old. Males are more commonly affected by non-small cell lung cancer than females. The male to female ratio is approximately 1.8 to 1. The rate of new cases in 2011 showed that males develop lung cancer more often than females (64.8 and 48.6 per 100,000 individuals). There is a racial preponderance to the development of non-small cell lung cancer, where African American individuals are at a significantly increased risk compared to Caucasian race.

Risk Factors

Common risk factors in the development of non small cell lung are smoking, family history of lung cancer, high levels of air pollution, radiation therapy to the chest, radon gas, asbestos, occupational exposure to chemical carcinogens, and previous lung disease.

Screening

According to the U.S. Preventive Services Task Force (USPSTF), screening for lung cancer by low-dose computed tomography is recommended every year among smokers who are between 55 to 80 years old and who have history of smoke 30 pack-years or more and either continue to smoke or have quit within the past 15 years (grade B recommendation).

Natural History, Complications and Prognosis

If left untreated, non-small cell lung cancer progression occurs slowly and is then followed by local invasion to lymph nodes and distant metastasis. Non-small cell lung cancer is a locally aggressive tumor, which commonly occurs in adult patients between 65 to 74 years. Common sites of metastasis include the adrenal gland, bone, brain, and liver. Complications of non-small cell lung cancer include acute respiratory failure, respiratory acidosis, malignant pleural effusion, metastases, and pneumonia. The 5-year relative survival of patients with non-small cell lung cancer is approximately 50%. Features associated with worse prognosis are presence of lymphatic invasion, location of lesion, gene expression profile, performance status, presence of satellite lesions, and presence of regional or distant metastases. Prognosis is generally regarded as poor with an all-stage average survival rate of 25%. The 5-year recurrence rate of non-small cell lung cancer is approximately 24%.

Diagnosis

Diagnostic Study of Choice

Chest X-Ray is the initial study performed when non-small cell lung cancer is suspected. Lung CT scan is the diagnostic study of choice for the diagnosis of non-small cell lung cancer. Endobronchial ultrasound is a first-line diagnostic modality for mediastinal staging of the non-small cell lung cancer. The lung biopsy is the gold standard for the diagnosis of the non-small cell lung cancer. The lung biopsy helps to differentiate between the various subtypes of lung cancer.

Staging

Staging system classifications for non-small cell lung cancer, include: American Joint Committee on Cancer (AJCC) staging system and International Union Against Cancer (UICC) staging system. According to both institutions, TNM system, which they now develop jointly, classifies cancer by several factors, T for tumor, N for nodes, M for metastasis. TNM determines the stages of cancer based on the extent of involvement of the lung, lymph nodes, and adjacent structures.

History and Symptoms

The hallmark of non-small cell lung cancer is chronic cough, weight loss, and hemoptysis. A positive history of smoking, exposure to asbestos, tuberculosis infection, or a high risk occupation may be suggestive of non-small cell lung cancer. Symptoms related with non-small cell lung cancer will vary depending on the size and location of the tumor. Common symptoms of non-small cell lung cancer may also include shortness of breath, fatigue, and chest pain.

Physical Examination

Physical examination findings of non-small cell lung cancer will depend on the location of the tumor. Non-small cell lung cancer with central location may cause crackling sounds, focal wheezing, voice hoarseness, and tachypnea. Peripheral location can present with pleurisy findings, such as reduced chest expansion. Common physical examination of patients with non-small cell lung cancer, include: crackling or bubbling noises, decreased/absent breath sounds, and whispered pectoriloquy.

Laboratory Findings

The following laboratory tests are required for patients with non-small cell lung carcinoma, including squamous cell carcinoma are complete blood count, electrolytes, calcium, alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, creatinine, albumin, and lactate dehydrogenase.

Imaging

X Ray

On chest X-ray, characteristic findings of non-small cell lung cancer include rounded or spiculated mass, bulky hilum (representing the tumor and local nodal involvement) and lobar collapse.

CT scan

Computed tomography is the method of choice for the diagnosis of non-small cell lung cancer. On CT, characteristic findings of non-small cell lung cancer include ground-glass opacity, rounded or spiculated mass, local nodal involvement, intraluminal obstruction, and lobar collapse.

MRI

On MRI, there are no specific findings of non-small cell cancer. MRI may be done for the pleural effusion assessment, guidance for thoracentesis, and guidance for biopsy of peripheral lung or mediastinal mass.

Ultrasound

On endobronchial ultrasound (EBUS) and endoscopic ultrasound, characteristic findings of non-small cell lung cancer include enlarged lymph nodes and local invasion to adjacent bronchial structures and mediastinum. Endobronchial ultrasound is a first-line diagnostic modality for mediastinal staging.

Other Imaging Findings

Other imaging findings of non-small cell lung cancer include PET and pulmonary angiography. PET scan is used for general follow-up, monitor treatment response and as a staging modality (in the risk of missing occult disease).

Other Diagnostic Studies

Diagnosis of non-small cell lung cancer can be confirmed by histopathological evaluation and immunohistochemical staining of the tumor specimen obtained from biopsy. Different types of lung tissue biopsy for non-small cell lung cancer include transthoracic needle biopsy, open biopsy, and video-assisted thoracoscopic surgery (VATS). Specimen for histopathological evaluation and immunohistochemical staining can also be obtained by bronchoscopy, mediastinoscopy, transthoracic percutaneous fine needle aspiration or sputum cytology.

Treatment

Management Approach

The optimal management approach of non-small cell lung cancer will depend on a series of characteristics, which includes: pre-treatment evaluation, location, and adequate staging. Common treatment options for management of non-small cell lung cancer include surgery, neoadjuvant chemotherapy, adjuvant chemotherapy, and radiation therapy.

Stage I

Therapies for non-small cell lung cancer stage I include surgery, radiation therapy, or surgery and chemotherapy (if the tumor size is larger than 4cm).

Stage II

Therapies for non-small cell lung cancer stage II include surgery, neoadjuvant chemotherapy, adjuvant chemotherapy, and radiation therapy. If the tumor is resectable, the preferred treatment for stage II non small cell lung cancer, includes: surgical resection with lymph node dissection and pathological evaluation. If evidence of lymph node extension of the disease is present adjutant chemotherapy should be administered.

Stage III

Therapies for non-small cell lung cancer stage III, depends on 4 categories; Resectable tumors, unresectable tumors, superior sulcus tumors, and tumors that invade the chest wall. Therapies for resectable tumors include surgery, neoadjuvant therapy, and adjuvant therapy. Alternatively, therapies for unresectable disease only include radiation therapy, and chemoradiation therapy. Therapies for superior sulcus tumors include radiation therapy alone, radiation therapy and surgery, concurrent chemotherapy with radiation therapy and surgery. Lastly, therapies for tumors that invade the chest wall include surgery, surgery and radiation therapy, radiation therapy alone, and chemotherapy combined with radiation therapy and/or surgery. The treatment of stage III non-small cell lung cancer will be contingent on the extension of the tumor. Chemotherapy and/or radiation therapy should be considered for patients with stage IIIB.

Stage IV

Therapies for non-small cell lung cancer stage IV include cytotoxic combination chemotherapy (first line), combination chemotherapy with bevacizumab or cetuximab, EGFR tyrosine kinase inhibitors, EML4-ALK inhibitors in patients with EML-ALK translocation, and immune checkpoint inhibition with nivolumab for selected patients with squamous or non-squamous metastatic. Maintenance therapy following first-line chemotherapy, include endobronchial laser therapy or brachytherapy (for obstructing lesions) and external beam radiation therapy (primarily for palliation of local symptomatic tumor growth). Local therapies (ambulatory catheter drainage, pleurodesis or mediastinal window) plus therapy for systemic metastasis is the preferred combination for patients with stage IV M1a non-small cell lung cancer. Patients with solitary site metastasis (stage IV M1b) should be treated according to the site of metastasis.

Metastatic Cancer

Therapies for non-small cell lung cancer stage IV include radiation therapy (for palliation) and palliative chemotherapy. The treatment of metastatic non-small cell lung cancer depends on the site and extension of the disease. If specific mutations are diagnosed, targeted treatment should be administered.

Medical Therapy

Chemotherapy is indicated for non-small cell lung cancer stage (IB, II, and III) as adjuvant therapy. The predominant therapy for non-small cell lung cancer is surgical resection. Chemotherapy and chemo-radiation may be required upon histological subtype of non-small cell lung cancer, location, size, and lymph node involvement. Commonly used chemotherapeutic agents include gemcitabine, paclitaxel, docetaxel, pemetrexed, etoposide or vinorelbine.

Chemotherapeutic Regimen

Chemotherapeutic regimens are based on platinum agents such as cisplatin, carboplatin, oxaliplatin, and satraplatin. Alternative regimens include paclitaxel, gemcitabine, or etoposide. Chemotherapeutic regimens are adjusted based on individual characteristics and body surface. The regimen adjustment according to tumor evolution has demonstrated longer survival rates, optimal symptom control, and higher quality of life.

Radiation Therapy

Radiation therapy can be applied to any stage of non-small cell lung cancer. In general, radiation therapy is recommended as palliative care treatment among patients who develop an advanced stage of non-small cell lung cancer or symptomatic patients with local involvement (pain, vocal cord paralysis, and hemoptysis). Curative radiation therapy may be indicated in patients who are not suitable for surgery with early-stage non-small cell lung cancer. The main goal of radiation therapy for non-small cell lung cancer is maximum tumor control with minimal tissue toxicity. The two main types of radiation therapy for non-small cell lung cancer are external beam radiation therapy (thoracic radiotherapy), and brachytherapy (internal radiation therapy).

Surgery

Surgery is the mainstay of therapy for early-stage non-small cell lung cancer. Common surgical procedures for the treatment of non-small cell lung cancer, include lung resection with lobectomy, lung resection with pneumonectomy with or without lymph node dissection. The preferred surgical procedure is thoracotomy with the removal of the entire lung or lobe (lobectomy) along with regional lymph nodes and contiguous structures.

Primary Prevention

Primary prevention of non-small cell lung cancer includes avoidance of smoking, smoking exposure, exposure to asbestos, and other high-risk occupational jobs.

Secondary Prevention

The secondary prevention of non-small cell lung cancer is based on the stage of non-small cell lung cancer at diagnosis. Secondary prevention includes chest CT along with a periodic evaluation of alert signs in second-hand smokers or active smokers.

References

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