Advanced Non‐Squamous Non–Small Cell Lung Cancer

What are the risk factors of non-small cell lung cancer?

Risk factors include extrinsic and intrinsic factors.

Although little is known about the causes of each sub-type of lung cancer, there is ample data on the possible factors could put one at risk of lung cancer. This includes extrinsic (smoking, environmental factors) as well as intrinsic (familial and genetic) factors.

I. Smoking

Tobacco smoking, whether active or passive, is by far one of the leading causes of lung cancer incidence. About 80% of smoking-attributable cancer deaths involve lung cancer. Secondhand tobacco smoke exposure also poses significant risk with higher risk at a younger age of exposure.

II. Environmental factors

Some carcinogens are known to act in synergism with tobacco smoking to raise the risk of lung cancer. These carcinogens include arsenic in drinking water, asbestos and radon, a naturally occurring radioactive gas, found in some homes. Air pollution also has been observed to raise risk slightly.

III. Genetic

Genetic and familial factors can predispose a person to getting lung cancer. For example, ras gene mutations occur almost exclusively in adenocarcinoma and are found in 30% of all cases, more predominantly in persons who smoke. Ras gene mutation, along with other mutations can result in overexpression of proteins such as Epidermal Growth Factor Receptor (EGFR), Vascular Endothelial Growth Factor (VEGF), which can then lead to lung cancer. These attributes may make these cancer cases ideal candidates for targeted therapy. To know more on targeted therapy, click here.

What are the symptoms like?

Often, symptoms of NSCLC surface after the cancer is in an advanced stage. Many of the symptoms arise when the grown tumour interferes with air passageways or blood vessels. Also, sometimes paraneoplastic syndromes can be one of the first symptoms of lung cancer, which often go unnoticed as they affect organs other than the lungs (To know more on paraneoplastic syndromes, click here).

Below are some commonly reported symptoms of lung cancer. Every time, only a doctor can confirm presence or absence of cancer.

• Persistent cough that gets worse with time
• Blood or rust-coloured sputum
• Chest pain that gets worse with deep breathing, coughing and laughing
• Hoarseness
• Loss of weight and appetite
• Frequent shortness of breath
• Fatigue and weakness
• Infections such as bronchitis and pneumonia that don’t go away or keep coming back
• New onset of wheezing

In advanced stages, when cancer would have spread to other organs, one may experience:

Bone pain (such as that in the back or hips), jaundice-like symptoms (yellowing of skin and eyes), numbness or weakness of one arm or leg, balance problems, seizures, persistent headache, balance problems, lumps near body surface such as skin and lymph nodes

In addition to the above, there are certain syndromes that may be associated with lung cancer. These include:

I. Horner syndrome

Horner syndrome (due to block in nerve pathway between brain and some parts of the face and eye) results in drooping and weakness of eye lid(s), decrease in pupil size and decreased sweating on affected part of the face, among other symptoms. Tumours arising on top part of the lungs (‘Pancoast tumours’) often result in Horner syndrome and shoulder pain.

II. Superior vena cava syndrome

Superior vena cava (SVC), a major vein in the body, carries blood from head and arms back to heart, passing next to upper part of the right lung. Tumours in this area can press against SVC, obstructing blood flow partially or completely. Symptoms include swelling, with a bluish-red skin colour of the face, neck, arms and upper chest area, headache and dizziness. In many cases, SVC syndrome turns life-threatening, hence calling for urgent treatment.

III. Paraneoplastic syndromes

Even before the cancer could spread outside the lungs, hormone-like substances released from some lung cancers can enter bloodstream and cause discomfort in distant tissues and organs. Problems arising from these changes are collectively termed as ‘Paraneoplastic syndromes’. Sometimes these syndromes can be one of the first symptoms of lung cancer, which are often are mistaken as diseases of organs other than the lungs.

Commonly reported paraneoplastic syndromes associated with NSCLC are:

High blood calcium levels leading to frequent urination, thirst, constipation, nausea, vomiting, belly pain, weakness, fatigue, dizziness, confusion and other nervous system problems, excess painful thickening of certain bones, especially those in the finger tips, blood clots and excessive breast tissue growth in men.

These symptoms can also be a result of disease conditions other than lung cancer. This calls for a person to be vigilant and consult a doctor to clarify a given health condition.