Non small cell lung cancer overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Maria Fernanda Villarreal, M.D. [2]
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.[1] 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, 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.[2][3] 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.[4] 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, 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%.[5] 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.
Historical Perspective
In 1929, Fritz Lickint a German physican first described the association between smoking and non small cell lung cancer.[6]
Classification
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.[1]
Pathophysiology
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
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.[7]
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, and secondary metastases.
Epidemiology and Demographics
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.[2][3][8] 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.[2]
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.[9]
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).[10]</nowiki>
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.[5] 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. 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%.[5]
Diagnosis
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, and then groups these TNM factors into overall stages.[11]
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.[12][13]
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 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.[14]
Laboratory Findings
Laboratory findings associated with non-small cell lung cancer, include: complete blood count, electrolytes, calcium, alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, creatinine, albumin, and lactate dehydrogenase.[15] Other laboratory findings, associated with non-small cell lung cancer, include: genetic testing for EGFR, KRAS, ALK, and ROS-1 mutations.
Imaging
Conventional chest radiography is the initial imaging method of choice for the diagnostic evaluation of non-small cell lung cancer.[16] 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.[17]
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.[18]
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.[18][19]
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.[20]
Ultrasound
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.[21]
Other Imaging Findings
Other imaging findings of non-small cell lung cancer, include: PET/CT and pulmonary angiography.[22]
Other Diagnostic Studies
Other diagnostic modalities for non-small cell lung cancer, include: thoracotomy, bronchoscopy, mediastinoscopy, and transthoracic percutaneous fine needle aspiration.[21]
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.[2][23][24]
Treatment
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 staging. Different treatment options for management of non-small cell lung cancer, include: surgery, neoadjuvant chemotherapy, adjuvant chemotherapy, and radiation therapy.[25]
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).[25]
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.[25]
Stage III
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.[25]
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 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 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.[26]
Metastatic Cancer
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
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 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, 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).[27]
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 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.[28]
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 include chest CT imaging along with periodic evaluation of alert signs in second-hand smokers or active smokers.[29]
References
- ↑ 1.0 1.1 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.
- ↑ 2.0 2.1 2.2 2.3 SEER Stat Fact Sheets: Lung and Bronchus Cancer. http://seer.cancer.gov/statfacts/html/lungb.html Accessed on February 3 2016
- ↑ 3.0 3.1 Non-small cell lung cancer. https://en.wikipedia.org/wiki/Non-small-cell_lung_carcinoma Accessed on February 3 2016 </ref name="FACTS">American Cancer Society: Cancer Facts and Figures 2016. Atlanta, Ga: American Cancer Society, 2016. Available online. Accessed February 3
- ↑ 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
- ↑ 5.0 5.1 5.2 Soares M, Darmon M, Salluh JI, Ferreira CG, Thiéry G, Schlemmer B, Spector N, Azoulay E (2007). "Prognosis of lung cancer patients with life-threatening complications". Chest. 131 (3): 840–6. doi:10.1378/chest.06-2244. PMID 17356101.
- ↑ Fritz Lickint. Wikipedia https://en.wikipedia.org/wiki/Fritz_Lickint Accessed on February 19,2016
- ↑ 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
- ↑ American Cancer Society: Cancer Facts and Figures 2016. Atlanta, Ga: American Cancer Society, 2016. Available online. Accessed February 3
- ↑ 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
- ↑ Lung Cancer: Screening http://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/lung-cancer-screening. Accessed on February 3, 2016 <nowiki>
- ↑ Stages of non–small cell lung cancer. Canadian Cancer Society. http://www.cancer.ca/en/cancer-information/cancer-type/lung/staging/?region=ab
- ↑ Non small cell lung cancer. Wikipedia. https://en.wikipedia.org/wiki/Non-small-cell_lung_carcinoma Accessed on February 24, 2016
- ↑ Raz DJ, Zell JA, Ou SH, Gandara DR, Anton-Culver H, Jablons DM (2007). "Natural history of stage I non-small cell lung cancer: implications for early detection". Chest. 132 (1): 193–9. doi:10.1378/chest.06-3096. PMID 17505036.
- ↑ Hyde L, Hyde CI (1974). "Clinical manifestations of lung cancer". Chest. 65 (3): 299–306. PMID 4813837.
- ↑ Spira A, Ettinger DS (2004). "Multidisciplinary management of lung cancer". N. Engl. J. Med. 350 (4): 379–92. doi:10.1056/NEJMra035536. PMID 14736930.
- ↑ Non-small cell lung cancer: Adenocarcinoma of the lung. Radiopedia.http://radiopaedia.org/articles/adenocarcinoma-of-the-lung Accessed on March 1, 2016
- ↑ 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
- ↑ 18.0 18.1 Rosado-de-Christenson ML, Templeton PA, Moran CA (1994). "Bronchogenic carcinoma: radiologic-pathologic correlation". Radiographics. 14 (2): 429–46, quiz 447–8. doi:10.1148/radiographics.14.2.8190965. PMID 8190965.
- ↑ Parker MS, Chasen MH, Paul N (2009). "Radiologic signs in thoracic imaging: case-based review and self-assessment module". AJR Am J Roentgenol. 192 (3 Suppl): S34–48. doi:10.2214/AJR.07.7081. PMID 19234288.
- ↑ Wang YX, Lo GG, Yuan J, Larson PE, Zhang X (2014). "Magnetic resonance imaging for lung cancer screen". J Thorac Dis. 6 (9): 1340–8. doi:10.3978/j.issn.2072-1439.2014.08.43. PMC 4178109. PMID 25276380.
- ↑ 21.0 21.1 Kinsey CM, Arenberg DA (2014). "Endobronchial ultrasound-guided transbronchial needle aspiration for non-small cell lung cancer staging". Am. J. Respir. Crit. Care Med. 189 (6): 640–9. doi:10.1164/rccm.201311-2007CI. PMID 24484269.
- ↑ Shim SS, Lee KS, Kim BT, Chung MJ, Lee EJ, Han J, Choi JY, Kwon OJ, Shim YM, Kim S (2005). "Non-small cell lung cancer: prospective comparison of integrated FDG PET/CT and CT alone for preoperative staging". Radiology. 236 (3): 1011–9. doi:10.1148/radiol.2363041310. PMID 16014441.
- ↑ Lung adenosquamous carcinoma. Libre Pathology. http://librepathology.org/wiki/Adenosquamous_carcinoma_of_the_lung Accessed on March 1, 2016
- ↑ Squamous cell carcinoma of the lung. Libre Pathology http://librepathology.org/wiki/Squamous_cell_carcinoma_of_the_lung Accessed on March 1, 2016
- ↑ 25.0 25.1 25.2 25.3 Melville A, Eastwood A (1998). "Management of lung cancer". Qual Health Care. 7 (3): 170–7. PMC 2483609. PMID 10185145.
- ↑ http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf
- ↑ 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
- ↑ Khuri FR (2003). "Primary and secondary prevention of non-small-cell lung cancer: the SPORE Trials of Lung Cancer Prevention". Clin Lung Cancer. 5 Suppl 1: S36–40. PMID 14641993.
- ↑ Tominaga S (2000). "[Prevention of lung cancer--primary and secondary prevention]". Nippon Rinsho (in Japanese). 58 (5): 1149–52. PMID 10824565.