Encyclopedia
Lung cancer is a
cancer of the
lungs characterized by the presence of malignant tumours. Most commonly it is bronchogenic carcinoma . Lung cancer is the most lethal of cancers worldwide, causing up to 3 million deaths annually. Only one in ten patients diagnosed with this disease will survive the next five years. Although lung cancer was previously an illness that affected predominately men, the lung cancer rate for women has been increasing in the last few decades, which has been attributed to the rising ratio of female to male smokers. More women die of lung cancer than any other cancer, including
breast cancer, ovarian cancer and uterine cancers combined.
Current research indicates that the factor with the greatest impact on risk of lung cancer is long-term exposure to inhaled carcinogens. The most common means of such exposure is
tobacco smoke.
Treatment and prognosis depend upon the
histological type of cancer and the stage . Possible treatment modalities include
surgery, chemotherapy, and/or
radiotherapy.
Signs and symptoms
Symptoms that suggest lung cancer include:
- dyspnea
- hemoptysis
- chronic cough or change in regular coughing pattern
- wheezing
- chest pain or pain in the abdomen
- cachexia , fatigue and loss of appetite
- dysphonia
- clubbing of the fingernails
- difficulty swallowing
- Some signs of pneumonia
If the cancer grows into the lumen it may obstruct the airway, causing breathing difficulties. This can lead to accumulation of secretions behind the blockage, predisposing the patient to
pneumonia.
Many lung cancers have a rich blood supply. The surface of the cancer may be fragile, leading to bleeding from the cancer into the airway. This blood may subsequently be coughed up.
Depending on the type of tumor, so-called paraneoplastic phenomena may initially attract attention to the disease. In lung cancer, this may be Lambert-Eaton myasthenic syndrome , hypercalcemia and SIADH. Tumors in the top of the lung, known as Pancoast tumors, may invade the local part of the sympathetic nervous system, leading to changed sweating patterns and eye muscle problems , as well as muscle weakness in the hands due to invasion of the
brachial plexus.
In many patients, the cancer has already spread beyond the original site by the time they have symptoms and seek medical attention. Common sites of metastasis include the
bone, such as the spine and the
brain.
Diagnosis
Performing a
chest X-ray is the first step if a patient reports symptoms that may be suggestive of lung cancer. This may reveal an obvious mass, widening of the
mediastinum , atelectasis , consolidation and
pleural effusion. If there are no X-ray findings but the suspicion is high ,
bronchoscopy and/or a
CT scan may provide the necessary information. In any case, bronchoscopy or CT-guided
biopsy is often necessary to identify the tumor type.
If investigations have confirmed lung cancer, scan results and often
positron emission tomography are used to determine whether the disease is localised and amenable to surgery or whether it has spread to the point it cannot be cured surgically. PET is not useful as screening, as not all malignancies are positive on PET scan , and lung infections may be positive on PET Scan.
Blood tests and
spirometry are also necessary to assess whether the patient is well enough to be operated on. If spirometry reveals a very poor respiratory reserve, as may occur in chronic smokers, surgery may be contraindicated.
Types
There are two main types of lung cancer categorized by the size and appearance of the malignant cells seen by a histopathologist under a
microscope:
non-small cell and
small-cell lung cancer. This classification although based on simple pathomorphological criteria has very important implications for clinical management and prognosis of the disease.
Non-small cell lung cancer
The non-small cell lung cancers are grouped together because their prognosis and management is roughly identical. When it cannot be subtyped, it is frequently coded to 8046/3. The subtypes are:
- Squamous cell carcinoma, accounting for 20% to 25% of NSCLC, also starts in the larger breathing tubes but grows slower meaning that the size of these tumours varies on diagnosis.
- Adenocarcinoma is the most common subtype of NSCLC, accounting for 50% to 60% of NSCLC. It is a form which starts near the gas-exchanging surface of the lung. Most cases of the adenocarcinoma are associated with smoking. However, among non-smokers and in particular female non-smokers, adenocarcinoma is the most common form of lung cancer. A subtype of adenocarcinoma, the bronchioalveolar carcinoma, is more common in female non-smokers and may have different responses to treatment.
- Large cell carcinoma is a fast-growing form that grows near the surface of the lung. It is primarily a diagnosis of exclusion, and when more investigation is done, it is usually reclassified to squamous cell carcinoma or adenocarcinoma.
Small cell lung cancer
- Small cell carcinoma is the less common form of lung cancer. It tends to start in the larger breathing tubes and grows rapidly becoming quite large. The oncogene most commonly involved is L-myc. The "oat" cell contains dense neurosecretory granules which give this an endocrine/paraneoplastic syndrome association. It is more sensitive to chemotherapy, but carries a worse prognosis and is often metastatic at presentation. This type of lung cancer is strongly associated with smoking.
Other types
Metastatic
The lung is a common place for metastasis from tumors in other parts of the body. These cancers, however, are identified by the site of origin, i.e., a breast cancer metastasis to the lung is still known as breast cancer. The adrenal glands, liver, brain, and bone are the most common sites of metastasis from primary lung cancer itself.
Causes
Exposure to carcinogens, such as those present in
tobacco smoke, immediately causes cumulative changes to the tissue lining the bronchi of the lungs and more tissue gets damaged until a tumour develops.
There are four major causes of lung cancer :
The role of smoking
Smoking, particularly of
cigarettes, is by far the main contributor to lung cancer, which at least in theory makes it one of the easiest diseases to prevent. In the United States, smoking is estimated to account for 87% of lung cancer cases , and in the
UK for 90%. Cigarette smoke contains 19 known carcinogens including
radioisotopes from the radon decay sequence, nitrosamine, and
benzopyrene. Additionally, nicotine appears to depress the immune response to malignant growths in exposed tissue. The length of time a person continues to smoke as well as the amount smoked increases the person's chances of contracting lung cancer. If a person stops smoking, these chances steadily decrease as damage to the lungs is repaired and contaminant particles are gradually vacated. More recent work has shown that, across the developed world, almost 90% of lung cancer deaths are caused by smoking.
Passive smoking—the inhalation of smoke from another's smoking— is claimed to be a cause of lung cancer in non-smokers. Studies from the USA , Europe , the UK , and Australia have consistently shown a significant increase in relative risk among those exposed to passive smoke.
The in 1993 claimed that about 3,000 lung cancer-related deaths a year were caused by passive smoking. However, since this report was based on a study that was alleged to be heavily biased and was ruled by a federal judge to be "unscientific", the EPA report was declared null and void by a federal judge in 1998.
Percentage of lung cancer deaths attributable to smoking in the developed world| | 35-69 years | 70 years+ | All ages |
| Men | 93.9 | 90.3 | 92.5 |
|---|
| Women | 68.8 | 68.9 | 68.8 |
|---|
| Both | 88.7 | 84.3 | 86.6 |
|---|
The extensive attempts made by
Philip Morris to delay the release of the 1997 IARC study, to affect the wording of its conclusions, to neutralise its negative results for their business, and to counteract its impact on public and policymakers' opinion has been documented by Ong & Glantz in The Lancet. Their work was based on 32 million pages of documents made public as part of the settlement of the 1998 legal case of State of Minnesota and Blue Cross/Blue Shield of Minnesota vs Philip Morris Inc, et al. and available at Philip Morris' own website.
Recent investigation of sidestream smoke suggests it is more dangerous than direct smoke inhalation.
Asbestos
Asbestos can cause a variety of lung diseases. It increases the risk of developing lung cancer. There is a synergistic effect between tobacco smoking and asbestos in the formation of lung cancer.
Asbestos can also cause cancer of the pleura, called mesothelioma .
Radon gas
Radon is a colorless and odourless gas generated by the breakdown of radioactive radium, which in turn is the decay product of
uranium, found in the earth's crust. Radon exposure is the second major cause of lung cancer after smoking. The radiation ionizes genetic material, causing mutations that sometimes turn cancerous. Radon gas levels vary by locality and the composition of the underlying
soil and rocks. For example, in areas such as
Cornwall in the UK , radon gas is a major problem, and buildings have to be force-ventilated with fans to lower radon gas concentrations. In the US, the EPA estimates that one in 15 homes has radon levels above the recommended standard.
Radon causes lung cancer because it causes arbitrary damage to the
chromosomes and
DNA molecules contained in the
nucleus of the cell.
Genetics and viruses
Oncogenes are genes that are believed make people more susceptible to cancer.
Proto-oncogenes are believed to turn into oncogenes when exposed to particular carcinogens.
Viruses are also suspected of causing cancer in humans, as this link has already been proven in animals. Genetic susceptibility and viral infection are not of major importance in lung cancer, but they may influence pathogenesis.
Lung cancer staging
Lung cancer staging is an important part of the assessment of prognosis and potential treatment for lung cancer.
See non-small cell lung cancer staging.
Treatment
Treatment for lung cancer depends on the cancer's specific cell type, how far it has spread, and the patient's performance status. Common treatments include
surgery, chemotherapy, and
radiation therapy.
See also
Manchester score.
Surgery
Surgery is only an option in NSCLC and if the disease is limited to one lung and has not spread beyond its confines. This is assessed with medical imaging . Furthermore, as stated, a sufficient respiratory reserve needs to be present to allow for the removal of large amounts of lung tissue. Procedures performed include lobectomy , bilobectomy or pneumonectomy .
The role of sub lobar resection continues to be debated for the primary management of NSCLC. Although overall survival appears to be equivalent to that of lobectomy resection, the local recurrence rate has been documented to be over three times more common . Accordingly, sub lobar resection has historically been used as a "compromise resection" approach for the management of small stage I peripheral NSCLC identified in patients with impaired cardiopulmonary reserve.
Recent reports of the use of intraoperative radioactive iodine brachytherapy implants at the margins of sublobar resection suggest that local recurrence can be reduced to that of lobectomy when this is used as a surgical adjunct to sublobar resection.
The role of anatomic segmentectomy with complete lymph node staging has also been found to have potential survival benefits similar to lobectomy. Such resections should be limited to peripheral small stage I NSCLC where a margin of resection equivalent to the diameter of the tumor can be achieved.
Five-year prognosis is often as good as 70% following complete resection of limited disease.
After surgery, adjuvant chemotherapy may be recommended if lymph nodes within the lung tissues resected or the mediastinum are found to be positive for cancer spread. Survival may be improved by up to 15% above patients receiving only surgical resection in these circumstances. The role of adjuvant chemotherapy for patients with large stage 1 NSCLC remains controversial.
The NCI Canada study JBR.10 treated patients with stage 1B to 2B NSCLC with vinorelbine and cisplatin chemotherapy and showed a significant survival benefit of 15% over 5 years. However subgroup analysis of patients in stage IB showed that chemotherapy did not result in any survival gain in them. Similarly, while the Italian ANITA study showed a survival benefit of 8% over 5 years with vinorelbine and cisplatin chemotherapy in stages 1B to 3A patients, subgroup analysis also showed no benefit in the 1B stage.
The Cancer and Leukemia -Group B study was a randomized study which examined the use of carboplatin and paclitaxel chemotherapy in patients with stage 1B disease. Unfortunately, although initial immature result in 2004 was encouraging, an update at the recent American Society of Clinical Oncology meeting reported that the findings are now negative with no survival advantage with the use of adjuvant chemotherapy in patients with this stage of disease. However, exploratory analysis of patients in the CALGB study suggested that perhaps those with tumors equal or greater than 4cm in size may still benefit.
At present, it is standard practice to offer patients with resected stage 2-3A NSCLC adjuvant 3rd generation platinum based chemotherapy . Adjuvant chemotherapy for patients with stage 1B remains controversial as clinical trials have not clearly demonstrated a survival benefit.
Chemotherapy
Small-cell lung cancer is treated primarily with chemotherapy, as surgery has no demonstrable influence on survival. Primary chemotherapy is also given in metastatic NSCLC.
The combination regimen depends on the tumour type:
Targeted therapy
In recent years, various molecular targeted therapies have been developed for the treatment of advanced lung cancer.
Gefitinib is one such drug, which targets the
epidermal growth factor receptor which is expressed in many cases of NSCLC. However despite an exciting start it was not shown to increase survival, although females, Asians, non-smokers and those with the adenocarcinoma cell type appear to be deriving most benefit from gefitinib.
A newer drug called
erlotinib has been shown to increase survival in lung cancer patients and has recently been approved by the FDA for second-line treatment of advanced non-small cell lung cancer.. Similar to gefitinib, it appeared to work best in females, Asians, non-smokers and those with the adenocarcinoma cell type.
Treatment of non-small cell lung cancer is evolving and the next few years could present exciting developments and new targeted therapies for lung cancer.
Radiotherapy
Radiotherapy is often given together with chemotherapy, and may be used with curative intent in patients who are not eligible for surgery. A radiation dose of 40 or more Gy in many fractions is commonly used with curative intent in non-small cell lung cancer; typically in North America, the dose prescribed is 60 or 66 Gy in 30 to 33 fractions given once daily, 5 days a week, for 6 to 6½ weeks. For small cell lung cancer cases that are potentially curable, in addition to chemotherapy, chest radiation is often recommended. For these small cell lung cancer cases, chest radiation doses of 40 Gy or more in many fractions are commonly given; typically in North America, the dose prescribed is 45 to 50 Gy and can be given in either once daily treatments for 5 weeks or twice daily treatments for 3 weeks.
For both non-small cell lung cancer and small cell lung cancer patients, radiation of disease in the chest to smaller doses may be used for symptom control.
Interventional radiology
Radiofrequency ablation is increasing in popularity for this condition as it is nontoxic and causes very little pain. It seems especially effective when combined with chemotherapy as it catches the cells inside a tumor—the ones difficult to get with chemotherapy due to reduced blood supply to the inside of the tumor. It is done by inserting a small heat probe into the tumor to cook the tumor cells. The body then disposes of the cooked cells through its normal eliminative processes.
Epidemiology
The population segment most likely to develop lung cancer is the over-fifties who also have a history of smoking. Lung cancer is the second most commonly occurring form of cancer in most western countries, and it is the leading cancer-related cause of death for men and women. In the US, 175,000 new cases are expected in 2006
- 90,700 in men and 80,000 in women. Although the rate of men dying from lung cancer is declining in western countries, it is actually increasing for women due to the increased takeup of smoking by this group. Among lifetime non-smokers, men who have never smoked have higher age-standardized lung cancer death rates than women. Of the 80,000 women who are diagnosed with lung cancer in 2006, approximately 70,000 are expected to die from it.
The British Doctors Study, published in the
1950s, first offered solid evidence on the link between lung cancer and smoking.
Not all cases of lung cancer are due to smoking, but the role of
passive smoking is increasingly being recognised as a risk factor for lung cancer, leading to policy interventions to decrease undesired exposure of non-smokers to others' tobacco smoke.
In the
Second World and
Third World, smoking-related lung cancer is rising rapidly in incidence. Countries such as
China are expected to see a marked increase in lung cancer cases as smoking is exceedingly common and other causes of death are becoming
less common, revealing an "iceberg" of pulmonary neoplasms. Cheap tobacco products and heavy advertising are seen by health campaigners as a major problem in these countries.
Prevention
Primary prevention
Prevention is the most cost-effective means of fighting lung cancer on the national and global scales. While in most countries industrial and domestic carcinogens have been identified and banned, tobacco smoking is still widespread. Eliminating tobacco smoking is a primary goal in the fight to prevent lung cancer, and
smoking cessation is the most important preventative tool in this process.
Policy interventions to decrease
passive smoking have become more common in various Western countries, with
California taking a lead in banning smoking in public establishments in 1998,
Ireland playing a similar role in
Europe in 2004, followed by
Norway in 2005 and
Scotland as well as several others in 2006.
New Zealand has also recently banned smoking in public places. .
Only the Asian state of
Bhutan has a complete
smoking ban . In many countries pressure groups are campaigning for similar bans. Arguments cited against such bans is criminalisation of smoking, increased risk of
smuggling and the risk that such a ban cannot be enforced.
Screening and secondary prevention
Because prognosis depends heavily on early detection there have been several attempts at secondary prevention. Regular chest radiography and sputum examination programs were not effective in early detection of this cancer and did not result in a reduction of mortality.
Computed tomography scanning is now being actively evaluated as a screening tool for lung cancer, and it is showing promising results. The National Cancer Institute is currently completing a randomized trial comparing CT scans with chest radiographs. Several single-institution trials are ongoing around the world. A large group of investigators are currently collating the results of 26,000 screen-detected lung cancers and are showing excellent preliminary survivals with these patients. More work is needed in this area.
When lung cancer is detected early, the survival rate for affected individuals can go up from 14 precent to over 80 percent. The key to early detection is a
CT scan which can uncover small tumors in the lungs of asymptomatic persons. By the time an individual experiences one or more symptoms of lung cancer, his/her disease is usually in an advanced state. A CT scan can uncover tumors not yet visible on an X-ray. A study published in 2006 by onocologists at New York Cornell-Weil confirmed the wisdom of scans for those in lung cancer risk groups.
At present, there are no official early-detection guidelines for lung cancer as there are for other cancers, although lung cancer claims far more lives. Many oncologists and pulmonologists recommend CT chest scans for people near 50 years of age who have a significant smoking history, even if these smokers quit some time ago. An informal 50-20-10 rule is commonplace: if an individual is age 50 or older and has smoked a pack a day for 10 years, or half a pack a day for 20 years, a CT-scan of the chest is advised.
There are those who argue against such scans on the ground of false positives, yet almost all medical tests show some false positives. Chest scans that indicate tumors are always followed up by cell extraction and biopsy that must confirm a tumorous cancer before treatment begins.
Lung cancer is a woefully underfunded area in the areas of prevention, detection and cure. Little is definitive except that smoking significantly increases an individual's risk of getting lung cancer. Unfortunately, quitting smoking does not necessarily bestow a free pass when it comes to lung cancer. But it is clear that smokers and ex-smokers are at high risk for lung cancer, and that waiting for lung cancer to show itself almost guarantees a poor outcome. CT-scans could saves hundreds of thousands of lives each years in North America alone.
Alerting the public that ex-smokers remain at risk for lung cancer would complicate the public health stop-smoking campaigns.
References
External links
- at the National Cancer Institute.
- by the IARC.
