Sayantika Dhar

LUNG CARCINOMA

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DEFINITION

• Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung.

• If left untreated, this growth can spread

beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body.

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Epidemiology:

Worldwide, lung cancer is the most common cause of cancer-related death in men and women, and is responsible for 1.3 million deaths annually, as of 2004.

Ref: WHO (February 2006). "Cancer". World Health Organization. Retrieved 2007-06-25.

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Signs and symptoms:• dyspnea (shortness of breath)• hemoptysis (coughing up blood)• chronic coughing or change in regular coughing

pattern• wheezing• chest pain or pain in the abdomen• cachexia (weight loss), fatigue, and loss

of appetite• dysphonia (hoarse voice)• clubbing of the fingernails (uncommon)• dysphagia (difficulty swallowing)

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Causes:

Smoking• Smoking, particularly of cigarettes, is by far

the main contributor to lung cancer. Cigarette smoke contains over 60 known carcinogens.

• Additionally, nicotine appears to depress the immune response to malignant growths in exposed tissue.

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• Passive smoking—the inhalation of smoke from another's smoking—is a cause of lung cancer in nonsmokers.

• Studies from the U.S., Europe, the UK, and Australia have consistently shown a significant increase in relative risk among those exposed to passive smoke.

• 10–15% of lung cancer patients have never smoked.

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Radon gas• Radon is a colorless and

odorless gas generated by the breakdown of radioactive radium, found in the Earth's crust.

• The radiation decay products ionize genetic material, causing mutations that sometimes turn cancerous. Radon exposure is the second major cause of lung cancer in the general population, after smoking.

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Asbestos• Asbestos can cause a variety of lung diseases,

including lung cancer. • Asbestos can also cause cancer of the pleura,

called mesothelioma(which is different from lung cancer).

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Viruses• Viruses are known to cause lung cancer in

animals, and recent evidence suggests similar potential in humans.

• These viruses may affect the cell cycle and inhibit apoptosis, allowing uncontrolled cell division.

• Implicated viruses include:– human papillomavirus, – JC virus, simian virus 40 (SV40), – BK virus, and – cytomegalovirus.

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Particulate matter• Studies of the American Cancer Society cohort

directly link the exposure to particulate matter with lung cancer. For example, if the concentration of particles in the air increases by only 1%, the risk of developing a lung cancer increases by 14%.

Krewski D, Burnett R, Jerrett M, Pope CA, Rainham D, Calle E, Thurston G, Thun M (2005 Jul 9-23). "Mortality and long-term exposure to ambient air pollution: ongoing analyses based on the American Cancer Society cohort". J Toxicol Environ Health A 68 (13–14): 1093–109.

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Pathogenesis:

• Oncogenes:–activation of oncogenes or inactivation

of tumor suppressor genes.–Proto-oncogenes are believed to turn into

oncogenes when exposed to particular carcinogens.–Mutations in the K-ras proto-oncogene are

responsible for 10–30% of lung adenocarcinoma.

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• Epidermal Growth Factor Receptor (EGFR)– EGFR regulates cell

proliferation, apoptosis, angiogenesis, and tumor invasion

– Mutations and amplification of EGFR can lead to cancerous growth, esp. non-small-cell lung cancer (basis for the treatment with EGFR-Inhibitors)

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• Chromosomal damage:– Chromosomal damage can lead to loss of

heterozygosity– This can cause inactivation of tumor suppressor

genes.– Damage to chromosomes 3p, 5q, 13q, and 17p are

particularly common in small-cell lung carcinoma.– The p53 tumor suppressor gene, located on

chromosome 17p, is affected in 60-75% of cases.

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• Genetic polymorphisms– People with genetic polymorphisms are more likely

to develop lung cancer after exposure to carcinogens.– These include polymorphisms in genes coding for» interleukin-1, » cytochrome P450, » apoptosis promoters such as caspase-8,and » DNA repair molecules such as XRCC1

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Diagnosis:

• Chest Radiograph:Look for- o An obvious masso Widening of mediastinum(suggestive of spread to lymph nodes there)o atelectasis (collapse)o consolidation (pneumonia), or o pleural effusion.

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• Blood stained sputum present, but radiograph normal, then:– Bronchoscopy– CT Scan– CT Scan guided biopsy(to find the tumor type)– Sputum Cytologic examination

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Differential Diagnosis:

• Abnormalities on chest radiograph:– infectious causes such as tuberculosis or

pneumonia,– inflammatory conditions such as sarcoidosis– mediastinal lymphadenopathy or lung nodules,

sometimes mimic lung cancers

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Classification:

• Lung carcinomas classified according to histological types:

– Non-small-cell Carcinoma– Small-cell carcinoma

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• Non-small-cell carcinoma:– squamous cell lung carcinoma – adenocarcinoma, and – large-cell lung carcinoma.

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Others

• Currently, the most widely recognized and utilized lung cancer classification system is the 4th revision of the Histological Typing of Lung and Pleural Tumours, published in 2004 as a cooperative effort by the World Health Organization and the International Association for the Study of Lung Cancer.

• It recognizes numerous other distinct histopathological entities into several subtypes.

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Metastasis:

• The lung is a common place for metastasis of tumors from other parts of the body.

• Secondary cancers are classified by the site of origin; e.g., breast cancer that has spread to the lung is called breast cancer.

• Metastases often have a characteristic round appearance on chest radiograph.

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• Micrograph of a lung lymph node biopsy showing metastatic colorectal adenocarcinoma. (Field stain).

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Lung Cancer Staging:

• Staging is the process of determining how much cancer there is in the body and where it is located.

• Staging information which is obtained prior to surgery, for example by x-rays and endoscopic ultrasound, is called clinical staging and staging by surgery is known as pathological staging.

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Tumours (TNM):• T describes the size of the tumor and whether

it has invaded nearby tissue,• N describes regional lymph nodes that are

involved,• M describes distant metastasis

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T: size or direct extent of the primary tumor

• T- CIS• T 0• T 1-4

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N: degree of spread to regional lymph nodes

• N0: tumor cells absent from regional lymph nodes• N1: regional lymph node metastasis present; (at

some sites: tumor spread to closest or small number of regional lymph nodes)

• N2: tumor spread to an extent between N1 and N3 (N2 is not used at all sites)

• N3: tumor spread to more distant or numerous regional lymph nodes (N3 is not used at all sites)

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M: presence of metastasis.

• M0: no distant metastasis• M1: metastasis to distant organs (beyond

regional lymph nodes)

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Staging modalities:• CT and PET scans• PFTs• Endoscopic ultrasound (EUS)• Endobronchial ultrasound (EBUS)• Mediastinal staging– Nearly half of lung cancers

have mediastinal disease at diagnosis, involving any of the mediastinal lymph nodes.

– on the same side lymph nodes - N2– if they are on the other side - N3

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Management:

• Non-surgical– Radiotherapy– Chemotherapy

• Surgical

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Radiotherapy:• Radiation therapy works by damaging the DNA of cancerous

cells. • the older, most common form of radiation therapy, Intensity-

modulated radiation therapy (IMRT) or photon radiation therapy.

• Direct damage to cancer cell DNA occurs through high-LET (linear energy transfer) where charged particles such as proton, boron, carbon or neon ions which have an antitumor effect, are used to break DNA strands.

• Brachytherapy (localized radiotherapy) may be given directly inside the airway when cancer affects a short section of bronchus. It is used when inoperable lung cancer causes blockage of a large airway.

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Chemotherapy:• The chemotherapy regimen depends on the tumor type.• Small-cell lung carcinoma– Even if relatively early stage, small-cell lung carcinoma is

treated primarily with chemotherapy and radiation.– Cisplatin and Etoposide are most commonly used.

• Non-small-cell lung carcinoma– Advanced non-small-cell lung carcinoma is often treated

with Cisplatin or Carboplatin, in combination with Gemcitabine.

– For adenocarcinoma and large-cell lung cancer, Cisplatin with Pemetrexed-more beneficial than cisplatin and gemcitabine.

– Bronchoalveolar carcinoma may respond to Gefitinib

and Erlotinib.

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Surgical Management

Wedge resection: If the patient does not have enough functional lung, this technique is preferred.

Segmentectomy Lobectomy: In patients with adequate respiratory

reserve this is preferred, as this minimizes the chance of local recurrence.

Pneumonectomy

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Pneumonectomy specimen containing a squamous cell carcinoma, seen as a white area near the bronchi.

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