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'''Lung cancer''' is the second most frequent cancer, but it causes the most cancer-related deaths worldwide. [[Smoking]] is famously the biggest risk factor, and also the reason that lung cancer incidence increased dramatically during the 1900s. 85 – 90% of cases of lung cancer are attributable to smoking.
<section begin="oncology" />'''Lung cancer''' is the second most frequent cancer, but it causes the most cancer-related deaths worldwide. [[Smoking]] is famously the biggest risk factor, and also the reason that lung cancer incidence increased dramatically during the 1900s. 85 – 90% of cases of lung cancer are attributable to smoking.


Around 95% of all primary lung tumors are carcinomas (epithelial origin), and these four types are most important:
Around 95% of all primary lung tumors are carcinomas (epithelial origin), and these four types are most important:
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* Family history (Genetic susceptibility)
* Family history (Genetic susceptibility)


Smoking is by far the important cause of lung cancer, and it's estimated that 90% of lung cancer cases would be avoided if not for smoking. Lung adenocarcinoma is not as strongly associated with smoking and is actually more common in nonsmokers than in smokers. The other types of lung cancer are very strongly associated with smoking.
Smoking is by far the important cause of lung cancer, and it's estimated that 90% of lung cancer cases would be avoided if not for smoking and 80% of lung cancer deaths are due to tobacco use. Lung adenocarcinoma is not as strongly associated with smoking and is actually more common in nonsmokers than in smokers. The other types of lung cancer are very strongly associated with smoking.


We can compare smoking habits with a measure called “pack-year”. If you have smoked 1 pack of cigarettes (20 pcs) every day for one year you have accumulated 1 pack-year. If you smoke one half pack every day for four years you have accumulated 2 pack-years. This allows us to quantify smoking habits, and it has prognostic significance. Higher pack years means higher risk of smoking-induced cancer, as well as a poorer prognosis in the case of lung cancer.
We can compare smoking habits with a measure called “pack-year”. If you have smoked 1 pack of cigarettes (20 pcs) every day for one year you have accumulated 1 pack-year. If you smoke one half pack every day for four years you have accumulated 2 pack-years. This allows us to quantify smoking habits, and it has prognostic significance. Higher pack years means higher risk of smoking-induced cancer, as well as a poorer prognosis in the case of lung cancer.
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=== Squamous cell carcinoma ===
=== Squamous cell carcinoma ===
SCC are found centrally, where they originate from major bronchi. Well-differentiated tumors will show keratinization, poorly-differentiated tumors won’t. It’s highly associated with smoking, but not with <abbr>[[HPV]]</abbr>, like laryngeal SCC is.
SCC are found centrally, where they originate from major bronchi. Well-differentiated tumors will show keratinization, poorly-differentiated tumors won’t. It’s highly associated with smoking, but not with <abbr>[[HPV]]</abbr>, like laryngeal SCC is.
 
<section end="oncology" />
It follows the following process of development:
It follows the following process of development:


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This development takes many years. The pathohistology slide shows this progression. These tumors usually form cavities because of central necrosis.
This development takes many years. The pathohistology slide shows this progression. These tumors usually form cavities because of central necrosis.
 
<section begin="oncology" />
=== Adenocarcinoma ===
=== Adenocarcinoma ===
Adenocarcinomas are the most common type and are found peripherally. They’re the most common type in women and is ''not'' associated with smoking, but rather with several genetic mutations, like:
Adenocarcinomas are the most common type and are found peripherally. They’re the most common type in women and is ''not'' associated with smoking, but rather with several genetic mutations, like:
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* [[PD-L1]]
* [[PD-L1]]


These mutations are important because we have drugs which target the mutations specifically.
These mutations are important because we have immunotherapy drugs which target the mutations specifically. The higher the cancer cells' expression of the protein, the higher the odds that the immunotherapy will be effective.


TTF-1 is a transcription factor that is expressed in lung adenocarcinomas and small cell carcinomas that is commonly used to distinguish between these types and squamous cell carcinoma, which doesn’t express TTF-1.
TTF-1 is a transcription factor that is expressed in lung adenocarcinomas and small cell carcinomas that is commonly used to distinguish between these types and squamous cell carcinoma, which doesn’t express TTF-1.
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The initial investigation is usually [[chest x-ray]], which may show a solitary nodule. In this case, the patient proceeds to a contrast chest [[CT]].
The initial investigation is usually [[chest x-ray]], which may show a solitary nodule. In this case, the patient proceeds to a contrast chest [[CT]].


For a definite diagnosis, histopathology is required. Ideally, a large enough biopsy should be taken to allow for immunohistochemical and genetic analysis, as this has implications for treatment and prognosis. There exist multiple modalities for obtaining biopsy, including endobronchial ultrasound-guided biopsy, transthoracic needle biopsy, transoesophageal endoscopic ultrasound, mediastinoscopy, etc.
For a definite diagnosis, histopathology is required. Ideally, a large enough biopsy should be taken to allow for immunohistochemical and genetic analysis, as this has implications for treatment and prognosis. There exist multiple modalities for obtaining biopsy, including [[endobronchial ultrasound]]-guided biopsy (EBUS), transthoracic needle biopsy, transoesophageal endoscopic ultrasound, mediastinoscopy, etc.
 
Acquiring tissue specimens is better than acquiring cytologic specimens, as only tissue specimens yield enough material for immunohistochemistry and genetic testing. This is important for prognosis and treatment. However, cytologic specimen is usually sufficient to determine the histological subtype and to confirm the cancer diagnosis. Cytology is most commonly acquired from a malignant pleural effusion, but can also be acquired from sputum analysis and [[bronchoalveolar lavage]].


When the diagnosis is made, several staging and preoperative investigations should be performed:
When the diagnosis is made, several staging and preoperative investigations should be performed:
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* Evaluation of performance status (ECOG)
* Evaluation of performance status (ECOG)
* [[CT]] chest, abdomen, pelvis
* [[CT]] chest, abdomen, pelvis
* Brain [[MRI]]
* [[Pulmonary function test]]
* Pulmonary function test
* Abdominal [[ultrasound]]
* Abdominal [[ultrasound]]
* If CT finds metastases (advanced disease), then perform brain MRI for brain metastases and x-ray/bone scintigraphy for skeletal metastases


== Treatment ==
== Treatment ==
The treatment for NSCLC and SCLC is different.
The treatment for NSCLC and SCLC is different.


=== Non-small cell lung cancer (NSCLC) ===
For NSCLC, tumours up to and including stage IIIb are potentially curable:
For NSCLC, tumours up to and including stage IIIb are potentially curable:


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* Stage IIIc – IV – palliative, any combination of chemo, radio, immunotherapy
* Stage IIIc – IV – palliative, any combination of chemo, radio, immunotherapy


For incurable NSCLC, the genetic and immunohistochemical analysis becomes important. We have specific therapy for PD-L1, KRAS, EGFR, ALK, and <abbr>ROS</abbr> mutations.
For incurable NSCLC, the genetic and immunohistochemical analysis becomes important. We have specific [[targeted therapy]] and [[immunotherapy]] for PD-L1, KRAS, EGFR, ALK, and <abbr>ROS</abbr> mutations, which may provide years of life if there is a good response.
 
The most commonly used chemotherapy drugs are cisplatin and taxanes like paclitaxel.  


For SCLC, the so-called “limited disease” (cancer has not spread beyond the hemithorax, corresponds to stages I – IIIb) is curable. SCLC has a very high turnover and is therefore sensitive to radio and chemotherapy. “Extensive disease” refers to cancer which has spread beyond one hemithorax and is deemed incurable.
=== Small cell lung cancer (SCLC) ===
For SCLC, the so-called “limited disease” (cancer has not spread beyond the hemithorax, corresponds to stages I – IIIb) is curable. SCLC has a very high turnover and is therefore sensitive to radio and chemotherapy, which is the first choice. “Extensive disease” refers to cancer which has spread beyond one hemithorax and is deemed incurable, but chemotherapy may still provide months or years of life.


Prophylactic cranial irradiation is used for SCLC, as it improves survival by killing brain metastases which are often already present but not visible on scans.
Prophylactic cranial irradiation is used for SCLC, as it improves survival by killing brain metastases which are often already present but not visible on scans. This can both be used curatively (for limited disease) and palliatively (for extensive disease).


=== Surgical treatment ===
=== Surgical treatment ===
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Surgical options include wedge resection, segmentectomy, lobectomy, and pneumonectomy. The less invasive options are preferred if they allow for margin negative (R0) resection. Lobectomy is usually preferred over wedge resection or segmentectomy, as the risk for R1 resection is smaller, but the latter may be chosen if the patient is deemed to have insufficient pulmonary function to tolerate a lobectomy.
Surgical options include wedge resection, segmentectomy, lobectomy, and pneumonectomy. The less invasive options are preferred if they allow for margin negative (R0) resection. Lobectomy is usually preferred over wedge resection or segmentectomy, as the risk for R1 resection is smaller, but the latter may be chosen if the patient is deemed to have insufficient pulmonary function to tolerate a lobectomy.


Surgery is preferably performed with video-assisted thoracoscopy (VATS) rather than open surgery.
Surgery is preferably performed with video-assisted thoracoscopy (VATS) rather than open surgery.<section end="oncology" /><noinclude>‎[[Category:Thoracic surgery]]
<noinclude>‎[[Category:Thoracic surgery]]
[[Category:Oncology]]
[[Category:Oncology]]
</noinclude>
</noinclude>