LUNG CANCER
Lung cancer is leading cause of death among cancer disease worldwide and it is the most diagnosed malignant cancer. However, lots of advancement in diagnosis and treatment methods, non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related death worldwide. Approximately 1.8 million deaths (18.7%) of deaths caused by lung cancer. The next most common cancers were breast cancers in women, colorectal cancer, prostate cancer and stomach cancer. Breast cancer is the most common in women whereas lung cancer were the most common cancers in men.
LUNG CANCER SIGN AND SYMPTOMS
Common symptoms
Early lung cancer usually causes no symptoms, and when symptoms appear, they are often vague. When present, common symptoms include cough, shortness of breath, and chest pain. Some individuals develop a new cough or worsening of an existing cough, and about one in four may cough up blood. Shortness of breath affects about half of patients, while many experience persistent chest pain.
Other symptoms may include loss of appetite, weight loss, weakness, fever, and night sweats.
When tumors are located in specific area
Less common symptoms occur when tumors are located in specific areas. Tumors in the thorax may block the trachea or disrupt the nerve supplying the diaphragm, leading to breathing problems. Tumors can compress the esophagus, causing difficulty in swallowing. They may also disrupt the laryngeal nerve, resulting in hoarseness. Disruption of the sympathetic nervous system can lead to Horner’s syndrome.
Horner’s syndrome is commonly associated with tumors at the top of the lung, known as Pancoast tumors. These tumors may also cause shoulder pain that radiates down the little-finger side of the arm and can lead to destruction of the upper ribs.
Advanced lung tumors
Advanced lung tumors can affect lymph nodes, blood flow, and heart function.
Swollen lymph nodes above the collarbone may indicate cancer spread within the chest. Tumors that block blood flow to the heart can cause superior vena cava syndrome, leading to upper-body swelling and shortness of breath. Tumors that spread around the heart region may cause fluid buildup around the heart, irregular heartbeat (arrhythmia), and heart failure.
Lung cancer can metastasize to various parts of the body, and the resulting symptoms depend on the site of spread. Brain metastases may cause headaches, nausea, vomiting, seizures, and neurological deficits. Bone metastases often lead to pain, pathological fractures, and compression of the spinal cord. When cancer spreads to the bone marrow, it can reduce normal blood cell production, resulting in leukoerythroblastosis, characterized by the presence of immature blood cells in circulation. Liver metastases may cause liver enlargement, pain in the right upper abdomen, fever, and weight loss.
Imbalance in minerals
Lung tumors can stimulate the release of hormone-like substances that disrupt normal body functions, leading to a group of unusual symptoms known as paraneoplastic syndromes. Abnormal hormone release can result in significant imbalances in blood mineral levels.
Hypercalcemia (high blood calcium) is the most common effect caused by excessive production of parathyroid hormone related protein or parathyroid hormone. Hypercalcemia can cause nausea, frequent urination, vomiting, constipation, abdominal pain, increased thirst, and altered mental status.
Hypokalemia (low potassium) caused by the secretion of adrenocorticotropic hormone.
Hyponatremia (low sodium) cause due to the overproduction of antidiuretic hormone or atrial natriuretic peptide.
Hypertrophic pulmonary osteoarthropathy
Lung cancer develop nail hypertrophic pulmonary osteoarthropathy, characterized by nail clubbing, joint pain, and skin thickening.
Autoimmune disorder
A wide range of autoimmune disorders may occur as paraneoplastic syndromes in lung cancer, including Lambert–Eaton myasthenic syndrome, which causes muscle weakness, as well as sensory neuropathies, muscle inflammation, brain edema, and autoimmune involvement of the cerebellum, limbic system, or brainstem.
Paraneoplastic blood-clotting disorders: Lung cancer patient also suffering from paraneoplastic blood-clotting disorders that cause migratory venous thrombophlebitis, intracardiac clots, and disseminated intravascular coagulation, which involves widespread clot formation. Paraneoplastic syndromes affecting the skin and kidneys are rare, each occurring in up to 1% of individuals with lung cancer.
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TYPES OF LUNGS CANCER
Lung cancer is classified by the type and appearance of cancer cells, which influences disease behavior and treatment.
At diagnosis, lung cancer is classified based on the cells from which the tumor originates. The two main types are small cell lung cancer (about 15% of cases) and non-small-cell lung cancer (about 85% of cases), which differ in how they progress and respond to treatment.
NSCLCs classified into three cancer types:
- Adenocarcinoma,
- Squamous-cell carcinoma
- large-cell carcinoma
Small Cell Lung Cancer (SCLC)
SCLC tumors are often found in the major airways, near the center of the lungs. SCLC tumors are with small with poorly defined, without cytoplasm, numerous mitochondria. Their nuclei have a distinctive granular chromatin pattern and no visible nucleoli.
Small cell lung cancer has two main subtypes: small cell carcinoma and mixed small cell/large cell cancer or combined small cell lung cancer. These subtypes are named based on the types of cells present and their appearance under microscopic examination. Small cell lung cancer is almost always associated with cigarette smoking.
Non-Small Cell Lung Cancer (NSCLC)
Non-small cell lung cancer is very common types and accounts for 80% of lung cancer. This type of cancer generally grows and spreads to other parts of the body more slowly than small cell lung cancer.
There are three different types of NSCLC:
Adenocarcinoma
Adenocarcinoma is a type of non–small cell lung cancer (NSCLC) that is commonly found in the outer regions of the lung.
Adenocarcinoma is a type of non–small cell lung cancer (NSCLC) that is commonly found in the outer regions of the lung. It develops from epithelial cells, which line body surfaces and cavities and are involved in gland formation. Adenocarcinoma accounts for nearly 40% of all lung cancers. The cancer cells typically grow in three-dimensional clusters, resemble glandular cells, and may produce mucin.
Squamous cell carcinoma
Squamous cell carcinoma is a type of non–small cell lung cancer (NSCLC) that is usually found in the central part of the lung, near the bronchi. It accounts for about 30% of lung cancers and typically develops close to the large airways. These tumors are composed of sheets of malignant cells with characteristic keratin formation. The center of the tumor often develops a hollow cavity as a result of cancer cell death caused by inadequate blood supply.
Large cell carcinoma
Large cell carcinoma is a type of non–small cell lung cancer (NSCLC) that can develop in any region of the lung and generally grows and spreads faster than adenocarcinoma or squamous cell carcinoma. It accounts for less than 10% of all lung cancers. The tumor is characterized by large malignant cells with abundant cytoplasm, large nuclei, and prominent nucleoli.
RARE TYPES OF LUNG CANCER
Approximately 10% of lung cancers consist of rarer types. These include mixed subtypes, such as adenosquamous carcinoma, as well as uncommon forms like carcinoid tumors and sarcomatoid carcinomas.
Pancoast tumors
Pancoast tumors, also known as superior sulcus tumors, arise in the upper portion of the lung and can spread nearby structures. These tumors are rare and are most commonly a form of NSCLC, although similar tumors may also result from other conditions such as lymphoma or tuberculosis.
Neuroendocrine Tumors (NETs) of the Lung
Lung carcinoid tumors, also known as lung neuroendocrine tumors (NETs), are uncommon and generally grow more slowly than other types of lung cancer. They are made from neuroendocrine cells, which are specialized cells found throughout the body that have characteristics of both nerve cells and hormone-producing cells. In the lungs, these cells line the airways and respond to physiological signals.
Neuroendocrine tumors of the lung represent a distinct category of lung cancer and behave differently from the more common lung cancer subtypes. They are typically classified as typical or atypical carcinoid tumors based on their cellular features and growth behavior. Lung carcinoid tumors are rare, usually slow-growing, and are most often treated with surgery.
LUNG CANCER RISK FACTOR
Smoking
Smoking is the most important risk factor for lung cancer, with active smoking posing the greatest risk. However, passive smoking also increases the risk. Smoking accounts for approximately 80–90% of all lung cancer cases.
Smoking is associated with an increased risk of several cancers, including those of the oral cavity, throat, esophagus, stomach, pancreas, bladder, kidney, cervix, and the hematopoietic system. Spectral analysis of cigarette smoke has identified more than 6,000 chemical compounds, over 60 of which are known carcinogens.
In addition to its carcinogenic effects, smoking adversely affects the immune system. It can enhance inflammatory, allergic, and autoimmune responses while simultaneously weakening the body’s ability to defend against infections.
Exposure of toxic substances
Long-term exposure to carcinogenic compounds such as radon, asbestos, polycyclic aromatic hydrocarbons, arsenic, beryllium, cadmium, silica, vinyl chloride, and nickel and chromium compounds, as well as diesel engine exhaust further leads to lung cancer.
Exposure of lung tissue to ionizing radiation during treatment for other cancers, such as early-stage Hodgkin lymphoma or breast cancer, also increases lung cancer risk. Environmental air pollution further contributes to this risk.
Genetic factors and epigenetic changes
Individuals with a family history of lung cancer, particularly among first-degree relatives, have a higher likelihood of developing the disease compared with the general population.
Lung cancer arises from multiple genetic and epigenetic changes that activate growth-promoting pathways and inhibit tumor suppressor mechanisms. Commonly affected tumor suppressor genes include TP53, RB, and p16, while frequently mutated oncogenes belong to the MYC, RAS, and HER families; ALK gene rearrangements also play a significant role. Disruption of growth factor signaling, particularly the EGF–EGFR pathway, is especially important in non–small cell lung cancer.
Tumor progression depends on abnormal angiogenesis driven mainly by vascular endothelial growth factor (VEGF). Continuous activation of VEGF signaling enables tumors to form their own blood supply once they exceed a small size, supporting further growth and metastasis. These newly formed vessels are structurally abnormal and fragile, contributing to symptoms such as hemoptysis.
In addition, impaired apoptosis allows cancer cells to survive despite harmful stimuli. Overall, lung cancer develops through the gradual accumulation of multiple molecular abnormalities.
HOW IS LUNG CANCER DIAGNOSED?
Flexible bronchoscopy and transthoracic sampling are the most commonly used methods to diagnose lung cancer.
Tumors located in the central part of the chest are usually examined using bronchoscopy, while tumors in the outer parts of the lung are sampled through transthoracic techniques.
In India, bronchoscopy services have increased significantly over the past decade, although they are mainly available in major metropolitan cities.
PET-guided biopsy
ET-guided biopsy is promising method used for transthoracic sampling. PET-CT scans show how active a tumor is, which helps doctors target the most viable part of the lesion during biopsy and improves the chances of an accurate diagnosis.
Whole-body PET-CT
Patients with lung cancer usually undergo non-invasive imaging tests to determine how far the disease has spread within the chest and to other parts of the body. This staging is especially important for patients who may be candidates for surgery. A whole-body PET-CT scan is the most accurate test for non-invasive staging of lung cancer.
TREATMENT FOR LUNG CANCER
Surgery
Surgery is the main treatment for early-stage lung cancer, but only a small percentage of patients (about 1.5%–5.3%) are eligible for or undergo surgery. Surgical treatment is usually carried out by thoracic surgeons at major cancer and tertiary care centers, where cases are discussed by multidisciplinary tumor boards.
For non–small cell lung cancer (NSCLC), the standard treatment for stage I and II disease is lobectomy with removal of nearby lymph nodes.
In stage IIIA disease, patients often receive neoadjuvant chemotherapy first, followed by reassessment for surgery.
The choice between lobectomy and pneumonectomy depends on how extensive the cancer is and how well the patient’s lungs function. If a patient has limited lung reserve, a smaller surgery such as segmentectomy may be performed, especially for small tumors with ground-glass appearance.
Radiation Therapy
Radiation therapy is an essential part of lung cancer treatment and is used across most disease stages.
Radiation therapy plays an important role in managing lung cancer at almost all stages. Patients with bulky tumors, poor general health, other serious illnesses, significant weight loss, or advanced age are often treated with sequential chemoradiation.
Systemic Therapy in NSCLC
In advanced non–small cell lung cancer (NSCLC), systemic treatment is mainly guided by biomarkers. For patients with EGFR mutations or ALK rearrangements, targeted therapy is the preferred treatment, especially in advanced or metastatic disease.
EGFR TKIs
EGFR TKIs include erlotinib and gefitinib (first generation), afatinib and dacomatinib (second generation), and osimertinib (third generation). Erlotinib and gefitinib are used most often because affordable generic versions are available. A generic form of afatinib has also recently become available. Osimertinib is mainly used as first-line treatment in patients who can afford it or have insurance or reimbursement support.
ALK TKI
In India, several ALK tyrosine kinase inhibitors (TKIs) are available, including crizotinib (first generation), alectinib and ceritinib (second generation), and lorlatinib (third generation).
OTHER TARGETED THERAPIES
Immunotherapy
Several immune checkpoint inhibitors are approved in India for advanced or metastatic non–small cell lung cancer, including PD-1 inhibitors (nivolumab, pembrolizumab) and PD-L1 inhibitors (atezolizumab, durvalumab). However, due to high cost, immunotherapy as first-line treatment is usually limited to patients who can afford it or have insurance, while most patients receive platinum-based chemotherapy.
Before starting immunotherapy, doctors typically wait for results of genetic tests such as EGFR mutations and ALK rearrangements, especially in nonsquamous NSCLC.
Targeted therapy is preferred when these mutations are present, as such patients respond poorly to immunotherapy and may experience severe toxicities if immunotherapy is given before targeted treatment.
Chemotherapy
Platinum-based doublet chemotherapy remains the standard treatment for NSCLC without targetable mutations.
For patients without oncogenic driver mutations, platinum-based doublet chemotherapy is the main treatment.
Pemetrexed plus platinum is preferred for nonsquamous NSCLC, followed by maintenance pemetrexed in suitable patients.
For squamous NSCLC, common regimens include paclitaxel–carboplatin or gemcitabine–platinum.
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