With industrialization increasing the levels of air pollution and widespread cigarette smoking, lung cancer has been one of the most form of diagnosed cancers in the modern world. It is currently the most frequently diagnosed cancer and the most common cause of cancer mortality worldwide. It is found that there is 10 fold increased risk in the development of lung cancer in cigarette smokers when compared to those who never smoked. Lung cancer development is reduced even in those who quit smoking than those who continue. Cigarette smoking has been implied in the development of all major types of lung cancer. Also passive smoking has been associated with the development of lung cancer but it is 20% to 30% low when compared to active smoking. 

The other causes of lung cancer are occupational exposures to some of the chemicals and elements like asbestos, arsenic, bischloromethyl ether, hexavalent chromium, mustard gas, nickel and polycyclic aromatic hydrocarbons. Because of this causality, the mechanism by which lung cancer develops has been studied to a great detail. Low fruit and vegetable intake in adults also make them more vulnerable to the development of lung cancer. This points to the fact that retinoids and carotenoids may have a protective mechanism. Heredity has also been shown to play a role in the development of lung cancer. First degree relatives of lung cancer have a two-to-threefold excess risk of lung cancer and other cancers, many of which are not smoking-related.

The lung cancers are the ones that develop from the epithelial cell lining of the respiratory system which include bronchi, bronchioles and alveoli. The classification by the WHO of epithelial cancers are :

  • Small-cell lung cancer (SCLC)
  • Adenocarcinoma
  • Squamous cell carcinoma
  • Non-small-cell carcinomas (NSCLC)

Of the wide variety of benign and malignant tumors that may arise in the lung, 90% to 95% are carcinomas that arise from the epithelial lining of cells, about 5% are carcinoid tumors, and 2% to 5% are mesenchymal and other miscellaneous neoplasms. 

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Lung cancers are currently the most frequently diagnosed cancer and causes the highest mortality due to cancer worldwide. Cigarette smoking is the main cause apart from other industrial hazards and genetic mutations.
Lung cancer is one of the most insidious and aggressive neoplasm in the realm of oncology. The usual symptoms of lung cancer are :

  • Cough in 50% to 75% of cases. This represent the involvement of central airways.
  • Hemoptysis (coughing up blood) in 25% to 50% of cases. This indicates haemorrhage of tumor in the airway.
  • Chest pain in 20% of cases. This is due to extension of tumor in the mediastinum, pleura or chest wall
  • Pneumonia, abscess and lobar prolapse in some cases. This is due to airway obstruction by tumor.
  • Lipoid pneumonia in some cases. This is due to tumor obstruction and accumulation of cellular lipid in foamy macrophages.
  • Pleural effusion in few cases. This due to the spread of tumor in the pleura.
  • Hoarseness of voice in some cases. This is due to recurrent laryngeal nerve invasion.
  • Dysphagia in few cases. This is due to esophageal invasion.
  • Diaphragm paralysis in some cases. This is due to phrenic nerve invasion.
  • Rib destruction in few cases. This is due to chest wall invasion.
  • SVCS (Superior Vena Cava Syndrome) in some cases. This is due to the compression of superior vena cava by tumor.
  • Horner syndrome in few cases. This is due to sympathetic ganglia invasion.
  • Pericarditis and tamponade is also observed in a few cases. This is due to pericardial involvement.

The other symptoms that might be present are bone pain, clubbing, weakness, unexplained weight loss, and wheezing and stridor. 

The staging of lung cancer is done according to the TNM classification. It is as follows:

Tis: Carcinoma in situ. Adenocarcinoma in situ: adenocarcinoma with pure lepidic pattern, ≤3 cm Squamous cell carcinoma in situ

T1: Tumor ≤3 cm without pleural or mainstem bronchus involvement (T1mi, minimally invasive adenocarcinoma; T1a, <1 cm; T1b, 1–2 cm; T1c, 2–3 cm)

T3: Tumor>5–7 cm or one with involvement of parietal pleura, chest wall (including superior sulcus tumors), diaphragm, phrenic nerve, mediastinal pleura, parietal pericardium, or separate tumor nodules in the same lobe

T4: Tumor>7 cm or any tumor with invasion of mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, or carina, or separate tumor nodules in a different ipsilateral lobe

N0: No metastasis to regional lymph nodes

N1: Ipsilateral intraparenchymal or peribronchial or hilar nodal involvement

N2: Metastasis to ipsilateral mediastinal or subcarinal lymph nodes

N3: Metastasis to contralateral mediastinal or hilar lymph nodes, ipsilateral or contralateral scalene, or supraclavicular lymph nodes

M0: No distant metastasis

M1: Distant metastasis (M1a, separate tumor nodule in contralateral lobe or pleural nodules or malignant pleural or pericardial effusion; M1b, single extrathoracic metastasis in a single organ; M1c, multiple extrathoracic metastases)

Now depending on the parameters defined above, the staging is done as follows:

Biopsies usually confirm the presence of lung cancers. The tissue suspected of tumor may be obtained via minimally invasive techniques such as bronchial or transbronchial biopsy during fiberoptic bronchoscopy, by fine-needle aspiration (FNA) or percutaneous biopsy using image guidance, or via endobronchial ultrasound (EBSU)-guided biopsy. Depending on the location, lymph node sampling may occur via transesophageal endoscopic ultrasound-guided biopsy (EUS), EBUS and blind biopsy. Bronchoscopic specimens include bronchial brush, bronchial wash, bronchioalveolar lavage, transbronchial FNA and core biopsy. 

The treatment of lung cancer depends on the type of cancer and the stage at which it is diagnosed. The overall treatment approach to patients with NSCLC is:

Occult and Stage 0 carcinomas:

Surgical resection of the tumor followed by bronchoscopic localization has been shown to improve survival compared to no treatment.

Solitary pulmonary nodule and “Ground-glass” opacities:

The approach to a patient with solitary pulmonary nodule is based on the estimate of the probability of cancer, determined based on the patient’s smoking history, age and characteristics on imaging. 

MANAGEMENT OF STAGES I AND II NSCLC:

Surgical resection of Stage I and II NSCLC:

A thoracic surgeon is the doctor of choice for performing surgical resection with clinical stage I and II NSCLC who are able to tolerate the procedure. The 5 year survival rates are 60%-80% for patients with stage I NSCLC and 40%-50% for patients with stage II NSCLC.

Radiation therapy in Stages I and II NSCLC:

The patients who are not suitable for surgery should be considered for radiation therapy. Stereotactic treatment body radiation therapy (SBRT) is a technique used to treat patients with isolated pulmonary nodules (<=5 cm). Cryoablation is another technique occasionally used to treat small, isolated tumors (i.e. <= 3 cm).

Chemotherapy in Stages I and II NSCLC:

The main chemotherapeutic agent that work in all forms of lung cancer is cisplatin. Vinorelbine is also used along with cisplatin. .

MANAGEMENT OF STAGE III NSCLC:

A multimodality approach is used for the treatment of the patients with Stage III NSCLC. Neoadjuvant therapy, which involves the use of chemotherapy to shrink the tumor size before surgical resection, is one of the treatment approaches 

MANAGEMENT OF METASTATIC NSCLC:

Approximately 40% of the NSCLC patients present with advanced, stage IV disease at the time of diagnosis. Cisplatin based regimens have proved to be a marginal successful than only supportive care.

TREATMENT OF SMALL CELL LUNG CANCER (SCLC):

Surgery for limited-disease SCLC:

SCLC is a highly aggressive cancer characterized by its rapid doubling time, high growth fraction, early development of disseminated disease, and dramatic response to first-line chemotherapy and radiation. Surgical resection is usually not recommended. 

Chemotherapy:

Chemotherapy significantly increases the survival rate. 4 to 6 cycles of platinum-based chemotherapy with either cisplatin or carboplatin plus either etoposide or irinotecan has been the mainstay of treatment for nearly 3 decades and is recommended over other chemotherapy regimens irrespective of initial stage. Cyclophosphamide, doxorubicin and vincristine (CAV) mzy be an alternative for patients who are unable to tolerate platinum-based regimen. The prognosis is usually poor for patients who relapse within 3 months of treatment. 

Thoracic radiation therapy:

Thoracic radiation therapy (TRT) is a standard component of induction therapy for good performance status and limited-stage SCLC patients. Studies indicate that chemotherapy combined with chest irradiation improves 3-year survival by approximately 5% as compared with chemotherapy alone. The 5 year survival rate is disappointingly low.

Prophylactic cranial irradiation:

Prophylactic cranial irradiation (PCI) should be considered in all patients with either LD-SCLC or ED-SCLC who have responded well to initial therapy.

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