Sayantika Dhar 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.
Sayantika Dhar 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.
Sayantika Dhar 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)
Sayantika Dhar 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.
Sayantika Dhar• Passive smoking—the inhalation of smoke from anothers 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.
Sayantika DharRadon gas• Radon is a colorless and odorless gas generated by the breakdown of radioactive radium, found in the Earths 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.
Sayantika DharAsbestos• 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).
Sayantika DharViruses• 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.
Sayantika DharParticulate 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.
Sayantika Dhar 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.
Sayantika Dhar• 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)
Sayantika Dhar• 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.
Sayantika Dhar• 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
Sayantika Dhar 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.
Sayantika Dhar 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
Sayantika Dhar Classification:• Lung carcinomas classified according to histological types: – Non-small-cell Carcinoma – Small-cell carcinoma
Sayantika Dhar 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.
Sayantika Dhar 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.
Sayantika Dhar• Micrograph of a lung lymph node biopsy showing metastatic colorectal adenocarcinoma. (Field stain).
Sayantika Dhar 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.
Sayantika Dhar TNM Classification of Malignant 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
Sayantika DharT: size or direct extent of the primary tumor• T- CIS• T0• T 1-4
Sayantika DharN: 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)
Sayantika DharM: presence of metastasis.• M0: no distant metastasis• M1: metastasis to distant organs (beyond regional lymph nodes)
Sayantika Dhar 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
Sayantika Dhar 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.
Sayantika Dhar 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.
Sayantika Dhar 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
Sayantika DharPneumonectomy specimen containing a squamouscell carcinoma, seen as a white area near thebronchi.