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Lung cancer is a malignant tumor of the lungs. Most commonly it is bronchogenic carcinoma (about 90%). Lung cancer is the most lethal malignant tumor 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.
The incidence of lung cancer is highly correlated with smoking. The above is an
illustration for the United States incidence of lung cancer.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 (degree of spread). Possible treatment modalities include surgery,
chemotherapy, and/or radiotherapy.
Signs and symptoms
Symptoms that suggest lung cancer include:
dyspnea (shortness of breath)
hemoptysis (coughing up blood)
chronic cough
wheezing
chest pain
cachexia (weight loss), fatigue and loss of appetite
dysphonia (hoarse voice)
clubbing of the fingernails (uncommon)
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 (muscle weakness due to auto-antibodies), hypercalcemia and
SIADH. Tumors in the top (apex) 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 (a combination known as Horner's
syndrome), 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 (causing back pain and occasionally spinal
cord compression) 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 (suggestive of spread to lymph nodes there), atelectasis
(collapse), consolidation (infection) and pleural effusion. If there are no
X-ray findings but the suspicion is high (e.g. a heavy smoker with blood-stained
sputum), 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 (PET) 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 (such as bronchoalveolar carcinoma), and lung infections may be
positive on PET Scan.
Blood tests and spirometry (lung function testing) 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 categorised by the size and appearance
of the malignant cells seen by a histopathologist under a microscope: small-cell
(roughly 20%) and non-small cell (80%) lung cancer. This classification although
based on simple pathomorphological criteria has very important implications for
clinical management and prognosis of the disease.
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Non-small cell lung cancer
The non-small cell lung cancers (NSCLC) 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:
(M8070/3) Squamous cell carcinoma also starts in the larger breathing tubes but
grows slower meaning that the size of these tumours varies when on diagnosis.
(M8140/3) Adenocarcinoma (or for slower growing forms alveolar cell cancer) is a
form which starts near the gas-exchanging surface of the lung. It is less
closely associated with smoking.
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.
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Small cell lung cancer
(M8041/3) Small cell carcinoma (SCLC, also called "oat 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.
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Other types
(M8240/3) carcinoid (the main representatives in this group)
(M8200/3) adenoid cystic carcinoma
cylindroma
mucoepidermoid carcinoma
Metastatic
The lung is a common place for metastasis from tumors in other parts of the
body.
Causes
Exposure to carcinogens, such as those present in tobacco smoke, immediately
causes cumulative changes to the tissue lining the bronchi of the lungs (the
bronchial mucous membrane) and more tissue gets damaged until a tumour develops.
There are four major causes of lung cancer (and, actually, cancer in general):
Carcinogens such as those in cigarette smoke
Radiation exposure
Genetic susceptibility
Viral infection
The role of smoking
Smoking, particularly of cigarettes, is believed to be by far the main cause of
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 in the U.S. (90% in men and 79% in women). There are hundreds of
known carcinogens—such as polynuclear aromatic hydrocarbons—present in cigarette
smoke. 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 the lung damage is repaired.
Passive smoking—the inhalation of smoke from another's smoking—has recently been
identified as a much larger cause of lung cancer in non-smokers than previously
believed. The US Environmental Protection Agency (EPA) in 1993 concluded that
about 3,000 lung cancer-related deaths a year were caused by passive smoking,
however since this report was declared null and void by a federal judge in 1998,
the true extent is still contested by scientists.
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 (which is
distinct from lung cancer).
Radon gas
Radon is a colorless and odourless gas generated by the breakdown of radioactive
radium, which in turn is the decayed 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
(which has granite as substrata), 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.
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.
Treatment
Treatment for lung cancer depends on the cancer's specific form, how far it has
spread, and other factors such as the patient's age and general medical state.
Common treatments include surgery, chemotherapy, and radiation therapy.
Surgery
Surgery is only an option in NSCLC and if the disease is limited to one lobe and
has not spread beyond its confines. This is assessed with medical imaging
(computed tomography, positron emission tomography). 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 (removal of
one lobe), bilobectomy (two lobes) or pneumonectomy (removal of a whole lung).
After surgery, adjuvant chemotherapy is usually recommended to decrease the risk
of recurrence. Five-year prognosis is often as good as 70% in limited disease
with clear resection margins.
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:
NSCLC: cisplatin or carboplatin, in combination with gemcitabine, paclitaxel,
docetaxel, etoposide or vinorelbine. In metastatic lung cancer, the addition of
bevacizumab when added to carboplatin and paclitaxel was found to improve
survival (though in this study, patients with squamous cell lung cancer were
excluded because of problems with pulmonary hemorrhage in this group in the
past).
SCLC: cisplatin or carboplatin, in combination etoposide or ifosfamide;
combinations with gemcitabine, paclitaxel, vinorelbine, topotecan and irinotecan
are being studied
Targeted therapy
In recent years, various molecular targeted therapies have been developed for
the treatment of advanced lung cancer. Gefitinib (Iressa®) is one such drug,
which targets the epidermal growth factor receptor (EGF-R) which is expressed in
many cases of NSCLC. However despite an exciting start it was not shown to
increase survival, although younger females without a smoking history appear to
be deriving most benefit from gefitinib.
A newer drug called erlotinib (Tarceva®) 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.
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 6
1/2 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 (typically 20 Gy in 5
fractions) 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.
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Epidemiology
Lung cancer distribution in the United States.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. It is expected that 2001 will have seen 169,500 new cases of lung cancer
in the US; 90,700 in men and 78,000 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.
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 (such as infections) 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 probably the most important
preventative tool in this process.
Policy interventions to decrease passive smoking (e.g. in restaurants and
workplaces) have become more common in various Western countries, with
California taking a lead in banning smoking in public establishments in 1998,
and Ireland playing a similar role in Europe in 2004.
Only the Asian state of Bhutan has a complete smoking ban (since 2005). 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.
Computerized tomography (CT) scanning is now being actively evaluated as a
screening tool for lung cancer, and it is showing promising results. The
National Cancer Institute (USA) 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 (the International
Early Lung Cancer Action Project) 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.
The source of this article is
Wikipedia, the free encyclopedia. The text of this
article is licensed under the
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