Lung cancer is a
disease of
uncontrolled
cell growth in
tissues of the
lung.
This growth may lead to
metastasis, which
is the invasion of adjacent tissue and infiltration beyond the
lungs. The vast majority of primary lung cancers are
carcinomas of the lung, derived from
epithelial cells. Lung
cancer, the most common cause of cancer-related death
in men and also the most common in women, is responsible for
1.3 million deaths
worldwideannually. The most common
symptoms
are shortness of breath, coughing (including
coughing up blood), and weight loss.
The main types of lung cancer are
small cell lung
carcinoma and
non-small cell lung carcinoma. This
distinction is important, because the treatment varies; non-small
cell lung carcinoma (NSCLC) is sometimes treated with
surgery, while small cell lung carcinoma
(SCLC) usually responds better to
chemotherapy and radiation. The most common
cause of lung cancer is long-term exposure to
tobacco smoke. The occurrence of lung cancer
in nonsmokers, who account for as many as 15% of cases , is often
attributed to a combination of
genetic
factors,
radon gas,
asbestos, and
air
pollution, including
secondhand
smoke.
Lung cancer may be seen on
chest
radiograph and
computed
tomography (CT scan). The
diagnosis is confirmed with a
biopsy. This is usually performed via
bronchoscopy or CT-guided biopsy. Treatment and
prognosis depend upon the
histological type of cancer, the
stage (degree of spread), and the
patient's
performance status.
Possible treatments include surgery, chemotherapy, and
radiotherapy. With treatment, the
five-year
survival rate is 14%.
Classification
The vast majority of lung cancers are
carcinomas—malignancies that arise from
epithelial cells. There are two main types
of lung carcinoma, categorized by the size and appearance of the
malignant cells seen by a
histopathologist under a
microscope:
non-small cell (80.4%) and
small-cell (16.8%) lung carcinoma. This classification,
based on
histological criteria, has
important implications for clinical management and prognosis of the
disease.
Frequency of
histological types of lung cancer
| Histological type |
Frequency (%) |
| Non-small cell lung carcinoma |
80.4 |
| Small cell lung carcinoma |
16.8 |
| Carcinoid |
0.8 |
| Sarcoma |
0.1 |
| Unspecified lung cancer |
1.9 |
Non-small cell lung carcinoma (NSCLC)
The
non-small cell lung
carcinomas are grouped together because their prognosis and
management are similar. There are three main sub-types:
squamous cell lung carcinoma,
adenocarcinoma, and
large cell lung carcinoma.
Sub-types of non-small cell lung cancer in
smokers and never-smokers
|
Histological sub-type |
Frequency of non-small cell lung
cancers (%) |
| Smokers |
Never-smokers |
| Squamous cell lung carcinoma |
42 |
33 |
| Adenocarcinoma |
Adenocarcinoma (not otherwise specified) |
39 |
35 |
| Bronchioloalveolar
carcinoma |
4 |
10 |
| Carcinoid |
7 |
16 |
| Other |
8 |
6 |
Accounting for 25% of lung cancers, squamous cell lung carcinoma
usually starts near a central
bronchus. A
hollow cavity and associated
necrosis are
commonly found at the center of the tumor. Well-differentiated
squamous cell lung cancers often grow more slowly than other cancer
types.
Adenocarcinoma accounts for 40% of lung cancers. It usually
originates in peripheral lung tissue. Most cases of adenocarcinoma
are associated with smoking; however, among people who have never
smoked ("never-smokers"), adenocarcinoma is the most common form of
lung cancer. A subtype of adenocarcinoma, the
bronchioloalveolar carcinoma,
is more common in female never-smokers, and may have different
responses to treatment.
Small cell lung carcinoma (SCLC)
_by_core_needle_biopsy.jpg/180px-Lung_small_cell_carcinoma_(1)_by_core_needle_biopsy.jpg)
Small cell lung carcinoma (microscopic
view of a core needle biopsy).
Small cell lung carcinoma
(SCLC, also called "oat cell carcinoma") is less common. It tends
to arise in the larger airways (primary and secondary
bronchi) and grows rapidly, becoming quite large.
The "oat" cell contains dense neurosecretory granules (
vesicles containing
neuroendocrine hormones), which give this an
endocrine/paraneoplastic syndrome association. While initially more
sensitive to chemotherapy, it ultimately carries a worse prognosis
and is often metastatic at presentation. Small cell lung cancers
are divided into limited stage and extensive stage disease. This
type of lung cancer is strongly associated with smoking.
Others
In infants and children, the most common primary lung cancers are
pleuropulmonary blastoma
and
carcinoid tumor.
Secondary cancers
The lung is a common place for
metastasis
from tumors in other parts of the body. These secondary cancers are
identified by the site of origin; thus, a breast cancer metastasis
to the lung is still known as breast cancer. They often have a
characteristic round appearance on chest radiograph. In children,
the majority of lung cancers are secondary.
Primary lung cancers themselves most commonly metastasize to the
adrenal glands, liver, brain, and
bone.
Staging
Lung
cancer staging is an assessment
of the degree of spread of the cancer from its original source. It
is an important factor affecting the
prognosis and potential treatment of lung cancer.
Non-small cell lung carcinoma is staged from IA ("one A"; best
prognosis) to IV ("four"; worst prognosis). Small cell lung
carcinoma is classified as
limited stage if it is confined
to one half of the chest and within the scope of a single
radiotherapy field; otherwise, it is
extensive stage.
Signs and symptoms
Symptoms that suggest lung cancer include:
If the cancer grows in the
airway, it may
obstruct airflow, 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, these
phenomena may include
Lambert-Eaton myasthenic
syndrome (muscle weakness due to
auto-antibodies),
hypercalcemia, or
syndrome of
inappropriate antidiuretic hormone (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.
Many of the symptoms of lung cancer (
bone
pain,
fever, and
weight loss) are nonspecific; in the elderly,
these may be attributed to
comorbid
illness. 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 brain, bone,
adrenal
glands, contralateral (opposite) lung, liver,
pericardium, and
kidneys.
About 10% of people with lung cancer do not have symptoms at
diagnosis; these cancers are incidentally found on routine chest
radiograph.
Causes
The main causes of lung cancer (and cancer in general) include
carcinogens (such as those in tobacco
smoke),
ionizing radiation, and
viral infection. This exposure
causes cumulative changes to the
DNA in the
tissue lining the
bronchi of the lungs (the
bronchial
epithelium). As more tissue
becomes damaged, eventually a cancer develops.
Smoking
Following an increase in smoking in
the population, the rate of lung cancer death increases.
Smoking, particularly of
cigarettes, is by far the main contributor to lung
cancer. Across the developed world, almost 90% of lung cancer
deaths are caused by smoking. In the United States, smoking is
estimated to account for 87% of lung cancer cases (90% in men and
85% in women). Among male smokers, the lifetime risk of developing
lung cancer is 17.2%; among female smokers, the risk is 11.6%. This
risk is significantly lower in nonsmokers: 1.3% in men and 1.4% in
women. Cigarette smoke contains over 60 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 smokes (as well as rate of smoking)
increases the person's chance of developing lung cancer. If a
person stops smoking, this chance steadily decreases as damage to
the lungs is repaired and contaminant particles are gradually
removed. In addition, there is evidence that lung cancer in
never-smokers has a better prognosis than in smokers, and that
patients who smoke at the time of diagnosis have shorter survival
times than those who have quit.
Passive smoking—the inhalation of
smoke from another's smoking—is a cause of lung cancer in
nonsmokers. A passive smoker can be classified as someone living or
working with a smoker as well. Studies from the U.S.,
*
*
*
*
* Europe, the UK,
* and Australia have consistently shown a significant increase in
relative risk among those exposed to
passive smoke. Recent investigation of
sidestream smoke suggests that it is more
dangerous than direct smoke inhalation.
Roughly ten-fifteen percent of lung cancer patients have never
smoked. That means between 20,000 to 30,000 never-smokers are
diagnosed with lung cancer in the United States each year. Because
of the five-year survival rate, each year in the U.S. more
never-smokers die of lung cancer than do patients of leukemia,
ovarian cancer, or AIDS.
Radon gas
Radon is a colorless and odorless
gas generated by the breakdown of radioactive
radium, which in turn is the decay product of
uranium, found in the Earth's
crust. The radiation decay products
ionize genetic material, causing mutations that
sometimes turn cancerous. Radon exposure is the second major cause
of lung cancer, after smoking. 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. The
United States
Environmental Protection Agency (EPA) estimates that one in 15
homes in the U.S. has radon levels above the recommended guideline
of 4
picocuries per liter (pCi/L) (148
Bq/
m³).
Iowa
has the
highest average radon concentration in the United States; studies
performed there have demonstrated a 50% increased lung cancer risk,
with prolonged radon exposure above the EPA's action level of 4
pCi/L.
Asbestos
Asbestos can cause a variety of lung
diseases, including lung cancer. There is a
synergistic effect between tobacco smoking and
asbestos in the formation of lung cancer. In the UK, asbestos
accounts for 2–3% of male lung cancer deaths. Asbestos can also
cause cancer of the
pleura, called
mesothelioma (which is different from lung
cancer).
Viruses
Viruses are known to cause lung cancer in
animals, and recent evidence suggests similar potential in humans.
Implicated viruses include
human
papillomavirus,
JC virus,
simian virus 40 (SV40),
BK
virus, and
cytomegalovirus.
These viruses may affect the
cell cycle
and inhibit
apoptosis, allowing
uncontrolled cell division.
Pathogenesis
Similar to many other cancers, lung cancer is initiated by
activation of
oncogenes or inactivation of
tumor suppressor genes.
Oncogenes are
genes that are believed to make
people more susceptible to cancer.
Proto-oncogenes are believed to turn into
oncogenes when exposed to particular carcinogens.
Mutations in the
K-ras proto-oncogene are responsible for
10–30% of lung adenocarcinomas. The
epidermal growth factor
receptor (EGFR) regulates cell proliferation,
apoptosis,
angiogenesis, and tumor invasion. Mutations and
amplification of EGFR are common in non-small cell lung cancer and
provide the basis for treatment with EGFR-inhibitors.
Her2/neu is affected less frequently.
Chromosomal damage can lead to
loss of heterozygosity. This can
cause inactivation of tumor suppressor genes. Damage to chromosomes
3p, 5q, 13q, and 17p are particularly common in small cell lung
carcinoma. The
p53 tumor suppressor
gene, located on chromosome 17p, is affected in 60-75% of cases.
Other genes that are often mutated or amplified are
c-MET,
NKX2-1,
LKB1,
PIK3CA, and
BRAF.
Several
genetic polymorphisms
are associated with lung cancer. These include polymorphisms in
genes coding for
interleukin-1,
cytochrome P450,
apoptosis promoters such as
caspase-8, and DNA repair molecules such as
XRCC1. People with these polymorphisms are more likely
to develop lung cancer after exposure to
carcinogens.
A recent study suggested that the
MDM2 309G
allele is a low-penetrant risk factor for
developing lung cancer in
Asians.
Diagnosis
Performing a
chest radiograph 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 (
pneumonia), or
pleural
effusion. If there are no radiographic findings but the
suspicion is high (such as a heavy smoker with blood-stained
sputum),
bronchoscopy and/or a
CT scan may provide the necessary information.
Bronchoscopy or CT-guided
biopsy is often
used to identify the tumor type.
Abnormal findings in cells ("
atypia") in
sputum are associated with an increased risk
of lung cancer. Sputum
cytologic
examination combined with other screening examinations may have a
role in the early detection of lung cancer.
The
differential diagnosis
for patients who present with abnormalities on chest radiograph
includes lung cancer as well as nonmalignant diseases. These
include infectious causes such as
tuberculosis or pneumonia, or inflammatory
conditions such as
sarcoidosis. These
diseases can result in
mediastinal
lymphadenopathy or lung
nodules, and sometimes mimic lung cancers.
Lung cancer can also be an
incidental
finding: a
solitary
pulmonary nodule (also called a coin lesion) on a chest
radiograph or CT scan taken for an unrelated reason.
Prevention
Prevention is the most cost-effective means of fighting lung
cancer. 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
prevention of lung cancer, and
smoking
cessation is an important preventative tool in this process.
Most importantly, are prevention programs that target the young. In
1998 the
Master Settlement
Agreement entitled 46 states in the USA to an annual payout
from the tobacco companies. Between the settlement money and
tobacco taxes, each state's public health department funds their
prevention programs, although none of the states are living up to
the
Center for Disease
Control's recommended amount by spending 15 percent of tobacco
taxes and settlement revenues on these prevention efforts.
Policy interventions to decrease
passive
smoking in public areas such as restaurants and workplaces have
become more common in many Western countries, with California
taking a lead in banning smoking in public establishments in 1998.
Ireland played a similar role in Europe in 2004, followed by Italy
and Norway in 2005, Scotland as well as several others in 2006,
England in 2007, France in 2008 and Turkey in 2009. New Zealand has
banned smoking in public places as of 2004.
The state of Bhutan
has had a
complete smoking ban since 2005. In many countries, pressure
groups are campaigning for similar bans.
In 2007, Chandigarh
became the first city in India
to become
smoke-free. India introduced a total ban on smoking at
public places on Oct 2 2008.
Arguments cited against such bans are
criminalisation of smoking, increased risk
of
smuggling, and the risk that such a ban
cannot be enforced.
The long-term use of supplemental multivitamins—such as vitamin C,
vitamin E, and folate—does not reduce the risk of lung cancer.
Indeed long-term intake of high doses of vitamin E supplements may
even increase the risk of lung cancer.
The
World Health
Organization has called for governments to institute a total
ban on tobacco advertising in order to prevent young people from
taking up smoking. They assess that such bans have reduced tobacco
consumption by 16% where already instituted.
Screening
Screening refers to the use of
medical tests to detect disease in
asymptomatic people. Possible screening tests for lung cancer
include
chest radiograph or
computed tomography (CT) of the
chest. So far, screening programs for lung cancer have not
demonstrated any clear benefit.
Randomized controlled trials are
underway in this area to see if decreased long-term mortality can
be directly observed from CT screening.
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.
Surgery
If investigations confirm lung cancer, CT scan and often
positron emission tomography
(PET) are used to determine whether the disease is localized and
amenable to surgery or whether it has spread to the point where it
cannot be cured surgically.
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 poor respiratory reserve (often
due to
chronic
obstructive pulmonary disease), surgery may be
contraindicated.
Surgery itself has an operative death rate of about 4.4%, depending
on the patient's lung function and other risk factors. Surgery is
usually only an option in non-small cell lung carcinoma limited to
one lung, up to stage IIIA. This is assessed with medical imaging
(
computed tomography,
positron emission tomography).
A sufficient preoperative respiratory reserve must be present to
allow adequate lung function after the tissue is removed.
Procedures include
wedge
resection (removal of part of a lobe), segmentectomy (removal
of an anatomic division of a particular lobe of the lung),
lobectomy (one lobe), bilobectomy (two
lobes), or
pneumonectomy (whole lung).
In patients with adequate respiratory reserve, lobectomy is the
preferred option, as this minimizes the chance of local recurrence.
If the patient does not have enough functional lung for this, wedge
resection may be performed. Radioactive
iodine brachytherapy at
the margins of wedge excision may reduce recurrence to that of
lobectomy.
Video-assisted
thoracoscopic surgery and
VATS
lobectomy have allowed for minimally invasive approaches to
lung cancer surgery that may have the advantages of quicker
recovery, shorter hospital stay and diminished hospital
costs.
Chemotherapy
Small cell lung carcinoma is treated primarily with chemotherapy
and radiation, as surgery has no demonstrable influence on
survival. Primary chemotherapy is also given in metastatic
non-small cell lung carcinoma.
The combination regimen depends on the tumor type. Non-small cell
lung carcinoma is often treated with
cisplatin or
carboplatin, in combination with
gemcitabine,
paclitaxel,
docetaxel,
etoposide, or
vinorelbine. In small cell lung carcinoma,
cisplatin and etoposide are most commonly used. Combinations with
carboplatin, gemcitabine, paclitaxel, vinorelbine,
topotecan, and
irinotecan are also used. in extensive-stage
small-cell lung cancer
celecoxib may
safely be combined with etoposide, this combination showed improve
outcomes.
Adjuvant chemotherapy for NSCLC
Adjuvant chemotherapy refers
to the use of chemotherapy after surgery to improve the outcome.
During surgery, samples are taken from the
lymph nodes. If these samples contain cancer, the
patient has stage II or III disease. In this situation, adjuvant
chemotherapy may improve survival by up to 15%. Standard practice
is to offer platinum-based chemotherapy (including either cisplatin
or carboplatin).
Adjuvant chemotherapy for patients with stage IB cancer is
controversial, as clinical trials have not clearly demonstrated a
survival benefit. Trials of preoperative chemotherapy (
neoadjuvant chemotherapy) in
resectable non-small cell lung carcinoma have been
inconclusive.
Radiotherapy
Radiotherapy is often given
together with chemotherapy, and may be used with curative intent in
patients with non-small cell lung carcinoma who are not eligible
for surgery. This form of high intensity radiotherapy is called
radical radiotherapy. A refinement of this technique is
continuous hyperfractionated accelerated radiotherapy (CHART), in
which a high dose of radiotherapy is given in a short time period.
For small cell lung carcinoma cases that are potentially curable,
chest radiation is often recommended in addition to chemotherapy.
The use of adjuvant thoracic radiotherapy following curative intent
surgery for non-small cell lung carcinoma is not well established
and is controversial. Benefits, if any, may only be limited to
those in whom the tumor has spread to the
mediastinal lymph
nodes.
For both non-small cell lung carcinoma and small cell lung
carcinoma patients, smaller doses of radiation to the chest may be
used for symptom control (
palliative
radiotherapy). Unlike other treatments, it is possible to deliver
palliative radiotherapy without confirming the
histological diagnosis of lung cancer.
Brachytherapy (localized radiotherapy)
may be given directly inside the airway when cancer affects a short
section of bronchus. It is used when inoperable lung cancer causes
blockage of a large airway.
Patients with limited stage small cell lung carcinoma are usually
given prophylactic cranial irradiation (PCI). This is a type of
radiotherapy to the brain, used to reduce the risk of
metastasis. More recently, PCI has also been
shown to be beneficial in those with extensive small cell lung
cancer. In patients whose cancer has improved following a course of
chemotherapy, PCI has been shown to
reduce the cumulative risk of brain
metastases within one year from 40.4% to
14.6%.
Recent improvements in targeting and imaging have led to the
development of extracranial stereotactic radiation in the treatment
of early-stage lung cancer. In this form of radiation therapy, very
high doses are delivered in a small number of sessions using
stereotactic targeting techniques. Its use is primarily in patients
who are not surgical candidates due to medical
comorbidities.
Interventional radiology
Radiofrequency ablation
should currently be considered an investigational technique in the
treatment of bronchogenic carcinoma. It is done by inserting a
small heat probe into the tumor to kill the tumor cells.
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
tyrosine kinase domain of the
epidermal growth factor
receptor (EGFR), expressed in many cases of non-small cell lung
carcinoma. It was not shown to increase survival, although females,
Asians, nonsmokers, and those with
bronchioloalveolar carcinoma
appear to derive the most benefit from gefitinib.
Erlotinib (Tarceva), another tyrosine
kinase inhibitor, 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 carcinoma.
Similar to gefitinib, it also appeared to work best in females,
Asians, nonsmokers, and those with bronchioloalveolar
carcinoma.
The
angiogenesis inhibitor
bevacizumab, (in combination with
paclitaxel and
carboplatin), improves the survival of patients
with advanced non-small cell lung carcinoma. However, this
increases the risk of lung bleeding, particularly in patients with
squamous cell
carcinoma.
Advances in cytotoxic drugs,
pharmacogenetics and targeted drug design
show promise. A number of targeted agents are at the early stages
of clinical research, such as
cyclo-oxygenase-2 inhibitors, the
apoptosis promoter
exisulind,
proteasome inhibitors,
bexarotene, the epidermal growth factor receptor
inhibitor
cetuximab, and vaccines. Future
areas of research include
ras proto-oncogene inhibition,
phosphoinositide 3-kinase
inhibition,
histone deacetylase
inhibition, and
tumor suppressor
gene replacement.
Prognosis
Prognostic factors in non-small cell lung cancer include presence
or absence of pulmonary symptoms,
tumor size,
cell type (
histology), degree of spread
and
metastases to multiple
lymph nodes, and vascular invasion. For patients
with inoperable disease, prognosis is adversely affected by poor
performance status and weight
loss of more than 10%. Prognostic factors in small-cell lung cancer
include
performance status,
gender, stage of disease, and involvement of
the
central nervous system or
liver at the time of
diagnosis.
For non-small cell lung carcinoma, prognosis is generally poor.
Following complete surgical resection of stage IA disease,
five-year survival is 67%. With stage IB disease, five-year
survival is 57%. The five-year survival rate of patients with stage
IV NSCLC is about 1%.
For small cell lung carcinoma, prognosis is also generally poor.
The overall five-year survival for patients with SCLC is about 5%.
Patients with extensive-stage SCLC have an average five-year
survival rate of less than 1%. The
median
survival time for limited-stage disease is 20 months, with a
five-year survival rate of 20%.
According to data provided by the
National Cancer Institute, the
median age of incidence of lung cancer is 70 years, and the median
age of death by lung cancer is 71 years.
Epidemiology
[[Image:Trachea, bronchus, lung cancers world map - Death -
WHO2004.svg|thumb|
Age-standardized
death from tracheal, bronchial, and lung cancers per
100,000 inhabitants in 2004.
]]
Worldwide, lung cancer is the most common cancer in terms of both
incidence and mortality (1.35 million new cases per year and 1.18
million deaths), with the highest rates in Europe and North
America. The population segment most likely to develop lung cancer
is over-fifties who 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. In
contrast to the mortality rate in men, which began declining more
than 20 years ago, women's lung cancer mortality rates have been
rising for over the last decades, and are just recently beginning
to stabilize. The evolution of "
Big
Tobacco" plays a significant role in the smoking culture.
Tobacco companies have focused their efforts since the 1970s at
marketing their product toward women and girls, especially with
"light" and "low-tar" cigarettes
[2719]. Among lifetime nonsmokers, men have higher
age-standardized lung cancer death rates than women.
Not all cases of lung cancer are due to smoking, but the role of
passive smoking is increasingly
being recognized as a risk factor for lung cancer—leading to policy
interventions to decrease undesired exposure of nonsmokers to
others' tobacco smoke. Emissions from automobiles, factories, and
power plants also pose potential risks.
Eastern Europe has the highest lung
cancer mortality among men, while northern Europe and the U.S. have
the highest mortality among women. Lung cancer incidence is
currently less common in developing countries. With increased
smoking in developing countries, the incidence is expected to
increase in the next few years, notably in China and India.
Lung cancer incidence (by country) has an inverse correlation with
sunlight and
UVB
exposure. One possible explanation is a preventative effect of
vitamin D (which is produced in the skin
on exposure to sunlight).
From the 1950s, the incidence of lung adenocarcinoma started to
rise relative to other types of lung cancer. This is partly due to
the introduction of filter cigarettes. The use of filters removes
larger particles from tobacco smoke, thus reducing deposition in
larger airways. However the smoker has to inhale more deeply to
receive the same amount of nicotine, increasing particle deposition
in small airways where adenocarcinoma tends to arise. The incidence
of lung adenocarcinoma in the U.S. has fallen since 1999. This may
be due to reduction in environmental air pollution.
History
Lung cancer was uncommon before the advent of cigarette smoking; it
was not even recognized as a distinct disease until 1761. Different
aspects of lung cancer were described further in 1810. Malignant
lung tumors made up only 1% of all cancers seen at autopsy in 1878,
but had risen to 10–15% by the early 1900s. Case reports in the
medical literature numbered only 374 worldwide in 1912, but a
review of autopsies showed that the incidence of lung cancer had
increased from 0.3% in 1852 to 5.66% in 1952.
In Germany
in 1929,
physician Fritz Lickint recognized the link between smoking and
lung cancer, which led to an aggressive antismoking
campaign. The
British
Doctors Study, published in the 1950s, was the first solid
epidemiological evidence of the link
between lung cancer and smoking. As a result, in 1964 the
Surgeon General of the
United States recommended that smokers should stop
smoking.
The
connection with radon gas was first recognized
among miners in the Ore Mountains
near Schneeberg, Saxony
. Silver has been mined
there since 1470, and these mines are rich in
uranium, with its accompanying
radium and radon gas. Miners developed a
disproportionate amount of lung disease, eventually recognized as
lung cancer in the 1870s. An estimated 75% of former miners died
from lung cancer.
Despite this discovery, mining continued into
the 1950s, due to the USSR
's demand for
uranium.
The first successful
pneumonectomy for
lung cancer was performed in 1933. Palliative
radiotherapy has been used since the 1940s.
Radical radiotherapy, initially used in the 1950s, was an attempt
to use larger radiation doses in patients with relatively early
stage lung cancer but who were otherwise unfit for surgery. In
1997, continuous hyperfractionated accelerated radiotherapy (CHART)
was seen as an improvement over conventional radical
radiotherapy.
With small cell lung carcinoma, initial attempts in the 1960s at
surgical resection and radical radiotherapy were unsuccessful. In
the 1970s, successful chemotherapy regimens were developed.
Gallery
Image:X-ray(Chest)Cancer.jpg|
Chest
radiograph showing lung cancer.
See also
References
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