Lung Carcinoma

Lung Carcinoma

Lung cancer is the most common cause of cancer deaths among both men and women in the United States. Lung cancer refers to those cancers, which originates in the respiratory epithelium (bronchi, bronchioles, and alveoli). Mesotheliomas are distinct from epithelial lung cancer and are considered a different type of cancer. Cancerous cells of lung spread into tissue in close proximity and finally into distant organs. Carcinomas, which arise from epithelial cells, are the most common form of lung cancer.

Epidemiology

Every year around 1.61 million new cases of lung cancer are diagnosed. Estimated new cases and deaths from lung cancer (non-small cell and small cell combined) in the United States in 2011: New cases: 221,130, Deaths: 156,940.
NSCLC accounts for approximately 85% of all cases of lung cancer.

The incidence of lung cancer varies widely in different parts of the world. The disease is predominant in elderly population; the median age at which lung cancer is diagnosed is about 70 years. Lung cancer is more common in males compared to females, however as the incidence of smoking in women has increased the incidence of lung cancer is increasing in women.

Types of lung cancer

Classification in details

1. Small cell lung carcinoma (SCLC)

SCLCs are fast growing tumors that spread quickly. They are less frequent. Often, SCLCs are diagnosed late. SCLC accounts for 15-20% of all cases of lung cancer.

2. Non-small cell lung carcinoma (NSCLC)

Non-small cell lung cancer (NSCLC) is the predominant form of lung cancer. It grows and spreads much slower than SCLC. NSCLC accounts for 80-85% of all cases of lung cancer. There are three forms of NSCLC:

  • Adenocarcinomas – Mostly detected in an outer area of the lung and account for 40% of all lung cancers
  • Squamous cell carcinomas or epidermoid carcinoma found in the bronchial tubes (large airways) in the central part of the lungs and account for 30% of all lung cancers
  • Large cell carcinomas or large cell anaplastic cancers. They can develop in any region of the lung and have a tendency to grow and spread faster than the previous two types. They account for 10% of all lung cancers.

Over the past two decades, adenocarcinoma has replaced squamous cell carcinoma as the most common subtype of NSCLC in the United States.

Symptoms

Symptoms that may be associated with lung cancer are the following:

  • shortness of breath or dyspnea
  • blood coming out while coughing
  • chronic coughing or change in regular coughing pattern
  • wheezing
  • chest or abdominal pain
  • dysphonic voice
  • weight loss
  • tiredness and loss of appetite
  • dizziness
  • infections in chest
  • clubbing of the fingernails (rare)
  • dysphagia (difficulty in swallowing)

Causes of lung cancer

Smoking

Smoking is the one of the most important risk factors for lung cancer. Approximately 87 % of all lung cancers are related to cigarette smoking. Passive smoking is also a cause of lung cancer. Therefore, people close to active smokers are also prone to lung cancer.

Occupational causes

Radon in indoor environments is now considered to be a significant cause of lung cancer. The list of human occupational causes of lung cancer also includes asbestos, chromates, arsenic, nickel, polycyclic aromatic hydrocarbons, chloromethyl ethers, radon progeny and other agents. Exposure to radioactive dust and materials such as uranium increases the risk of developing lung cancer.

Outdoor air pollutants

Diesel emissions and combustion-generated carcinogens are a major cause of lung cancer. Exposure to fumes from cooking stoves and fires is associated with lung cancer risk in many developing countries.

Dietary micronutrients

Certain dietary micronutrients can increase the risk of lung cancer in smokers.

Viruses

  • Human papillomavirus infection can be the cause of lung cancer.
  • Inherited genetic susceptibility
  • Germline mutations in certain genes like EGFR can result in genetic susceptibility to lung cancer and can run in the family.

Genes involved in carcinoma in lungs

The role of molecular genetics in lung cancer is well known and continues to be studied. SCLCs do differ significantly from NSCLCs in the specific genetic alterations that occur. In addition, genetic alterations are significantly higher in SCLCs than NSCLCs when smoking is the major cause of carcinoma in lungs.

Diagnosis

  • Chest x-ray: The chest x-ray remains probably the most valuable tool in diagnosing lung cancer.
  • Physical exam and history: In most patients symptoms related to lung cancer are indicative of the patient’s conditions. Lifestyle and previous health problems of the patient can help in diagnosis and plan of treatment.
  • CT scan (CAT scan) and PET scan: These imaging technologies can provide images of the lungs. Carcinoma in the lungs can be detected from these images.
  • Sputum cytology: A sample of sputum (mucus) is examined in the laboratory under a microscope to detect cancer cells when a patient is suspected of having lung cancer. Sputum of a patient is collected by forceful coughing or by using a bronchoscope.
  • Bronchoscopy: This procedure involves the insertion of a tube like instrument with a light and lens at its end (bronchoscope) through the nose or mouth to view abnormal areas in the trachea and large airways in the lung. This instrument can also be used for removing tissue samples, which are examined in the laboratory to detect malignancy.
  • Fine-needle aspiration (FNA) biopsy of the lung: In this technique, a thin needle is inserted through a small incision in the skin into the lungs to obtain a small tissue. An ultrasound or a CT scan guides this process. The tissue is examined in the laboratory with a microscope to detect abnormalities.
  • Thoracoscopy: This process involves insertion of a thin tube like instrument with a light and lens at its end (thoracoscope) through a small incision on the chest. It helps to see the organs inside the chest. It helps to obtain tissues from the abnormal parts, which are then examined under a microscope in the laboratory. If the doctor fails to reach the organ, the size of the incision can be increased.
  • Thoracentesis: Fluid from the space between the lining of the chest and the lung can be obtained using a needle. The fluid can be examined in the laboratory to detect cancer cells.

Additional blood tests: The presence of lung cancer “markers” which are elements in the blood that are associated with the presence of lung cancer can be found in the blood with the help of specific blood tests.

Staging

Staging is critical to the prognosis and treatment. The TNM staging classification can be used in SCLC. But, the disease presents the symptoms only when it has advanced to stage III or IV. SCLC can be classified as limited or extensive. If it remains within hemithorax, it is limited. If it spreads outside hemithorax then it is extensive. Techniques like mediastinoscopy, mediastinotomy, thoracotomy, and video-assisted thoracoscopy (VATS) are used in staging lung carcinoma.

Treatment

Surgery: Surgical resection remains the single most consistent and successful option for cure for patients diagnosed as having lung cancer. For this option to be feasible, the cancer must be completely resectable, and the patient must be able to tolerate the proposed surgical intervention.

Radiation therapy: Radiation therapy can be used for both forms of lung carcinoma, especially when surgical resection is not possible. The purpose for radiation therapy can be curative, palliative or as adjuvant therapy with surgery or chemotherapy. Usually radiation therapy alone can only shrink a tumor or limits its growth. It is performed with high-energy X-rays or other types of radiation.

Chemotherapy: Chemotherapy can also be used for both forms of lung carcinoma. It may be used alone or in combination with surgery and radiation therapy. Platinum-based drugs have been most effective. Many other drugs are in the pipeline for the treatment of lung cancer. Chemotherapy is more effective for SCLC in comparison to NSCLC. It greatly improves the survival period of SCLC patients.

Prophylactic brain radiation: This radiation therapy is given to the brain to prevent the spread of SCLC cells and formation of a secondary tumor in the brain. But this treatment has side effects that can cause memory loss.

Treatment of recurrence: Recurrent lung cancer can be removed by surgery. If it spreads to other organs chemotherapy or radiotherapy can be used. Recurrent cancers do not respond to those drugs which have been already used. Therefore, a second line of chemotherapeutic drugs should be used.

Targeted therapy: Targeted therapy drugs more specifically target cancer cells and therefore cause less damage to other organs. The drugs erlotinib (Tarceva) and gefitinib (Iressa) can be used for the treatment of NSCLC. Epidermal growth factor receptor (EGFR) has proved to be a good target for lung carcinoma in clinical trials. These two drugs have been successful by targeting this protein. Cetuximab is an antibody that binds to the epidermal growth factor receptor (EGFR). Another drug bevacizumab (Avastin) can acts by cutting off the blood supply to the affected area and hence prolongs survival in advanced lung cancer patients.

Other new therapies: Photodynamic therapy (PDT) and Radiofrequency ablation are new ways of treating patients. Both techniques have good precision and less side effects.

Prognosis

The TNM classifications can then be grouped into four stages of NSCLC. Stages I and II indicates that the tumor is localized and therefore surgery can be performed. Stage III is the more advanced form where the cancer cells have spread within the lung. Stage IV indicates that distant metastasis of the cancer cells.

SCLC usually presents itself at an advanced stage and therefore is considered as a stage III or IV disease according to the TNM staging.

References

  1. Dooley AL, Winslow MM, Chiang DY, Banerji S, Stransky N, Dayton TL, Snyder EL, Senna S, Whittaker CA, Bronson RT, Crowley D, Barretina J, Garraway L, Meyerson M, Jacks T. (2011) Nuclear factor I/B is an oncogene in small cell lung cancer. Genes Dev. Jul 15;25(14):1470-5.
  2. Zaba O, Grohe C, Merk J. (2011) Novel therapies in non-small cell lung cancer. Minerva Chir.;66(3):235-44.
  3. Target therapies in lung cancer. (2011) Bearz A, Berretta M, Lleshi A, Tirelli U. J Biomed Biotechnol.;2011:921231. Epub 2011 Mar 30.
  4. Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. (2008) Non-Small Cell Lung Cancer: Epidemiology, Risk Factors, Treatment, and Survivorship. Mayo Clin Proc.; 83(5): 584-94.
  5. Bell DW, Gore I, Okimoto RA, Godin-Heymann N, Sordella R, Mulloy R, Sharma SV, Brannigan BW, Mohapatra G, Settleman J, Haber DA. (2005) Inherited susceptibility to lung cancer may be associated with the T790M drug resistance mutation in EGFR. Nat Genet. Dec;37(12):1315-6.
  6. Wistuba II, Gazdar AF, Minna JD. (2001) Molecular genetics of small cell lung carcinoma. Semin Oncol. 2001 ;28(2 Suppl 4):3-13.
  7. This article was originally published on September 3, 2012 and last revision and update was 9/4/2015.