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Dr. Bhaswat S. Chakraborty
Non-small Cell Lung
Cancer I
(Basics, Diagnosis, Survival Rates)
ļ‚— Lungs are 2 sponge-like organs found in your chest.
The right lung has 3 lobes, while the left lung has 2
lobes only (because the heart takes up more room
on the left).
ļ‚— While breathing, air enters through mouth or nose
into your lungs through the trachea which divides
into bronchi, then into bronchioles. At the end of
each bronchiole, there are tiny air sacs, alveoli.
ļ‚— Tiny blood vessels in alveoli absorb O2 from the
inhaled air into the bloodstream and pass CO2 from
the body into the alveoli, which is then exhaled.
ļ‚— Taking in oxygen and getting rid of carbon dioxide
are the main functions of lungs.
ā€¢ A thin lining layer called the pleura surrounds the lungs. The pleura protects the lungs and
helps them slide back and forth against the chest wall as they expand and contract during
breathing.
ā€¢ Below the lungs, a dome-shaped muscle called the diaphragm separates the chest from the
abdomen. When you breathe, the diaphragm moves up and down, forcing air in and out
of the lungs.
Source: American Cancer Soc.
Start and Spread of Lung
Cancer
ā€¢ Lung cancers can start in the cells lining the bronchi and in bronchioles or
alveoli.
ā€¢ They start as areas of pre-cancerous changes in the lung. The first changes
happen in the genes of the cells themselves and may cause them to grow
faster.
ā€¢ The cells may look a bit abnormal if seen under a microscope, but at this
point they do not form a mass or tumor.
ā€¢ Over time, these pre-cancerous changes in the cells progress to true cancer.
As a cancer develops, the cancer cells may make chemicals that cause new
blood vessels (angiogenesis) nourishing the cancer cells.
ā€¢ At some point, cells from the cancer may break away from the original
tumor and spread (metastasize) to other parts of the body.
ā€¢ Lung cancer is often a life-threatening disease because it tends to spread in
this way even before it can be detected on an imaging test e.g., chest x-ray.
The Lymph (Lymphatic) System
ā€¢ The lymph system is one of the ways in which lung cancers can spread.
ā€¢ Lymph nodes are small, bean-shaped collections of immune system cells (cells that
fight infections) that are connected by lymphatic vessels.
ā€¢ Lymphatic vessels are like small veins, except that they carry a clear fluid called lymph
(instead of blood) away from the lungs.
ā€¢ Lymph contains excess fluid and waste products from body tissues, as well as immune
system cells.
ā€¢ Lung cancer cells can enter lymphatic vessels and begin to grow in lymph nodes
around the bronchi and in the mediastinum.
ā€¢ From lymph nodes, cancer cells spread to other organs of the body.
ā€¢ The stage (extent) of the cancer and decisions about treatment are based on
whether or not the cancer has spread to the nearby lymph nodes in the
mediastinum.
Types of Lung
Cancer
ā€¢ There are 2 major types of lung
cancer:
ā€¢ Small cell lung cancer (SCLC)
ā€¢ Non-small cell lung cancer
(NSCLC)
ā€¢ (If a lung cancer has characteristics
of both types it is called a mixed
small cell/large cell cancer. This
is uncommon.)
ā€¢ These 2 types of lung cancer are
treated very differently.
Non-small Cell Lung Cancer
(NSCLC)
ļ‚—About 85% of all lung cancers are of the non-small cell type. There are 3
sub-types of NSCLC. The cells in these sub-types differ in size, shape, and
chemical make-up.
ļ‚—Squamous cell carcinoma: about 25% to 30% of all lung cancers are of
this kind starting in early versions of squamous cells (flat cells that line the
inside of lungs). They are linked to smoking and tend to be found near the
bronchus.
ļ‚—Adenocarcinoma: this type accounts for about 40% of lung cancers
starting in cells that normally secrete substances such as mucus. It is usually
found in the outer part of the lung
ļ‚—Large-cell undifferentiated carcinoma: about 10% to 15% of lung
cancers are this type. It can start in any part of the lung. It tends to grow and
spread quickly.Ā 
ļ‚—Other subtypes: There are also a few other subtypes of non-small cell lung
cancer, such as adenosquamous carcinoma and sarcomatoid carcinoma. These
are much less common.
Adenocarcinoma (A), squamous cell carcinoma (B), and large cell carcinoma (C).
Immunohistochemical analysis for Ki-67 in an adenocarcinoma (D).
The TNM Staging System
ā€¢ The system used to describe the growth and spread of non-small cell lung
cancer (NSCLC) is the American Joint Committee on Cancer (AJCC) TNM
staging system. The TNM system is based on 3 key pieces of information:
ā€¢ T indicates the size of the main (primary) tumor and whether it has grown
into nearby areas.
ā€¢ N describes the spread of cancer to nearby (regional) lymph nodes. Lymph
nodes are small bean-shaped collections of immune system cells that help
fight infections. Cancers often spread to the lymph nodes before going to
other parts of the body.
ā€¢ M indicates whether the cancer has spread (metastasized) to other organs of
the body (e.g., brain, bones, adrenal glands, liver, kidneys, and the other
lung.)
ā€¢ Numbers or letters appear after T, N, and M to provide more details about
each of these factors. The numbers 0 through 4 indicate increasing severity.
The letter X means "cannot be assessed because the information is not
available.ā€
Stage Grouping for Lung Cancer
ā€¢ Once the T, N, and M categories have been assigned, this information is combined to
assign an overall stage of 0, I, II, III, or IV. This process is called stage grouping.
Some stages are subdivided into A and B. Patients with lower stage numbers tend to
have a better prognosis.
ā€¢ Occult cancer
ā€¢ TX, N0, M0: Cancer cells are seen in a sample of sputum or other lung fluids, but
the cancer isn't found with other tests, so its location can't be determined.
ā€¢ Stage 0
ā€¢ Tis, N0, M0: The cancer is found only in the top layers of cells lining the air
passages. It has not invaded deeper into other lung tissues and has not spread to
lymph nodes or distant sites.
ā€¢ Stage IA
ā€¢ T1a/T1b, N0, M0: The cancer is no larger than 3 cm across, has not reached the
membranes that surround the lungs, and does not affect the main branches of the
bronchi. It has not spread to lymph nodes or distant sites.
ā€¢ Stage IB
ā€¢ T2a, N0, M0: The cancer has 1 or more of the following features:
ā€¢ main tumor is between 3 and 5 cm across; tumor has grown into a main bronchus,
but is not within 2 cm of the carina; grown into the visceral pleura; partially clogging
the airways; in any case, not larger than 5 cm; cancer has not spread to lymph nodes
or distant sites.
Stage Grouping for Lung Cancer..
ā€¢ Stage IIA
ā€¢ T1a/T1b, N1, M0: The cancer is no larger than 3 cm across, has not grown into the membranes that surround the
lungs, and does not affect the main branches of the bronchi; spread to lymph nodes within the lung and/or hilar lymph
nodes); not spread to distant sites. OR
ā€¢ T2a, N1, M0: The main tumor is between 3 and 5 cm across; grown into a main bronchus, but is not within 2 cm of
the carina; tumor has grown into the visceral pleura; it is partially clogging the airways; in any case, not larger than 5
cm; spread to lymph nodes within the lung and/or hilar lymph nodes; cancer has not spread to distant sites. OR
ā€¢ T2b, N0, M0: main tumor is between 5 and 7 cm across; grown into a main bronchus, but is not within 2 cm of the
carina; tumor has grown into the visceral pleura; it is partially clogging the airways; cancer has not spread to lymph
nodes or distant sites.
ā€¢ Stage IIB
ā€¢ T2b, N1, M0: main tumor is between 5 and 7 cm across; grown into a main bronchus, but is not within 2 cm of the
carina; tumor has grown into the visceral pleura; it is partially clogging the airways; The cancer has spread to lymph
nodes within the lung and/or hilar lymph nodes and has not spread to distant sites. OR
ā€¢ T3, N0, M0: The main tumor is larger than 7 cm across; has grown into diaphragm, mediastinal pleura, or parietal
pericardium; invades a main bronchus and is closer than 2 cm (about Ā¾ inch) to the carina, but it does not involve the
carina itself; has grown into the airways enough to cause an entire lung to collapse or to cause pneumonia in the
entire lung; or more separate tumor nodules are present in the same lobe of a lung; cancer has not spread to lymph
nodes or distant sites.
Stage Grouping for Lung Cancerā€¦
ā€¢ Stage IIIA
ļ‚— T1 to T3, N2, M0: The main tumor can be any size; not grown into mediastinum, the heart, the
aorta, trachea, esophagus, the backbone, or the carina; not spread to different lobes of the same
lung; cancer has spread to lymph nodes around the carina or in the mediastinum; cancer has not
spread to distant sites. OR
ļ‚— T3, N1, M0: The cancer is larger than 7 cm across; has grown into the diaphragm, mediastinal
pleura, or parietal pericardium; invades a main bronchus and is closer than 2 cm to the carina,
but it does not involve the carina itself; or more separate tumor nodules are present in the same
lobe of a lung; has grown into the airways enough to cause an entire lung to collapse or to cause
pneumonia in the entire lung; spread to lymph nodes within the lung and/or the hilar lymph
nodes; has not spread to distant sites. OR
ļ‚— T4, N0 or N1, M0: The tumor of any size has grown into the mediastinum, the heart, the aorta
or any other large blood vessels, the trachea, esophagus, the backbone, or the carina; or more
separate tumor nodules are present in different lobes of the same lung; may or may not have
spread to lymph nodes within the lung and/or hilar lymph nodes; affected lymph nodes are on
the same side as the cancer; not spread to distant sites.
Stage Grouping for Lung Cancerā€¦
ā€¢ Stage IIIB
ā€¢ Two combinations of categories make up this stage; any T, N3, M0: The cancer can be of any
size; may or may not have grown into nearby structures or caused pneumonia or lung collapse;
spread to lymph nodes near the collarbone on either side, and/or has spread to hilar or
mediastinal lymph nodes on the side opposite the primary tumor; cancer has not spread to distant
sites; OR
ā€¢ T4, N2, M0: The tumor of any size has grown into the mediastinum; the heart, the aorta; the
trachea; the esophagus, the backbone, or the carina; or more separate tumor nodules are present
in different lobes of the same lung; cancer has also spread to lymph nodes around the carina or in
the mediastinum; affected lymph nodes are on the same side as the main lung tumor; has not
spread to distant sites.
ā€¢ Stage IV
ā€¢ Two combinations of categories make up this stage; any T, any N, M1a: The cancer can be any
size and may or may not have grown into nearby structures or reached nearby lymph nodes; also
cancer has spread to the other lung; malignant pleural effusion; malignant pericardial effusion. OR
ā€¢ Any T, any N, M1b: The cancer can be any size and may or may not have grown into nearby
structures or reached nearby lymph nodes. It has spread to distant lymph nodes or to other
organs such as the liver, bones, or brain.
Risk Factors for NSCLC
ā€¢ A risk factor is anything that affects a person's chance
of getting a disease such as cancer.
ā€¢ Different cancers have different risk factors, e.g.,
unprotected exposure to strong sunlight is a risk factor
for skin cancer.
ā€¢ But risk factors don't tell us everything. Having a risk factor, or even
several risk factors, does not mean that one will get the disease.
ā€¢ And some people who get the disease may not have had any known risk
factors.
ā€¢ Even if a person with lung cancer has a risk factor, it is often very hard
to know how much that risk factor may have contributed to the cancer.
ā€¢ Several risk factors can make you more likely to develop lung cancer.
Tobacco Smoke
ā€¢ Smoking is by far the leading risk factor for lung cancer. About 80% of lung cancer
deaths are thought to result from smoking.
ā€¢ The risk for lung cancer among smokers is many times higher than among non-
smokers. The longer one smokes and the more packs a day, the greater the risk.
ā€¢ Secondhand smoke: If you don't smoke, breathing in the smoke of others (called
secondhand smoke or environmental tobacco smoke) can increase your risk of
developing lung cancer.
ā€¢ A non-smoker who lives with a smoker has about a 20% to 30% greater risk of
developing lung cancer.
Radon
ā€¢ Radon is a naturally occurring radioactive gas that results from the breakdown
of uranium in soil and rocks. It cannot be seen, tasted, or smelled..
ā€¢ Outdoors, there is so little radon that it is not likely to be dangerous. But
indoors, radon can be more concentrated.
ā€¢ When it is breathed in, it enters the lungs, exposing them to small amounts of
radiation. This may increase a person's risk of lung cancer.
Asbestos
ā€¢ Workplace exposure to asbestos fibers is an important risk factor for lung cancer.
ā€¢ Studies have found that people who work with asbestos (in some mines, mills, textile
plants, etc.) are several times more likely to die of lung cancer.
ā€¢ Both smokers and non-smokers exposed to asbestos also have a greater risk of
developing mesothelioma, a type of cancer that starts in the pleura.
Other workplace cancer-causing
agents
ā€¢ Radioactive ores such as uranium
ā€¢ Inhaled chemicals or minerals such as arsenic, beryllium, cadmium, silica, vinyl
chloride, nickel compounds, chromium compounds, coal products, mustard gas, and
chloromethyl ethers
ā€¢ Diesel exhaust
ā€¢ Also radiation therapy to the lungs
ā€¢ People who have had radiation therapy to the chest for other cancers are at
higher risk for lung cancer, particularly if they smoke.
Arsenic
ā€¢ High levels of arsenic in drinking water may increase the risk of lung cancer. This is
even more pronounced in smokers.
ā€¢ Brothers, sisters, and children of those who have had lung cancer may have a slightly
higher risk of lung cancer themselves,
ā€¢ It is not clear how much of this risk might be due to genetics and how much might be
from shared household exposures.
ā€¢ Researchers have found that genetics does seem to play a role in some families with a
strong history of lung cancer.
ā€¢ e.g., people who inherit certain DNA changes in a particular chromosome
(chromosome 6) are more likely to develop lung cancer, even if they only smoke
a little.
Personal or family history of lung cancer
Certain dietary supplements
ā€¢ Possible role of antioxidant supplements in reducing lung cancer risk does not seem
promising so far. In fact, 2 large studies found that smokers who took beta carotene
supplements actually had an increased risk of lung cancer.
ā€¢ Results of these studies suggest that smokers should avoid taking beta carotene
supplements.
Inherited gene changes
ā€¢ Some people inherit DNA mutations (changes) from their parents that greatly
increase their risk for developing certain cancers.
ā€¢ However, inherited mutations are not thought to cause very many lung cancers.
ā€¢ Genes, however, do seem to play a role in some families with a history of lung
cancer.
ā€¢ e.g., some people seem to inherit a reduced ability to break down or get rid of
certain types of cancer-causing chemicals in the body, such as those found in tobacco
smoke putting them at higher risk for lung cancer.
ā€¢ Others may inherit faulty DNA repair mechanisms that make it more likely
they will end up with DNA changes.
ā€¢ e.g., patients with repair enzymes that don't work well might be especially
vulnerable to cancer-causing chemicals and radiation.
ā€¢ Researchers are developing reliable tests for identifying such people, but for
now, physicians recommend that all people avoid tobacco smoke and other
exposures that might increase their cancer risk.
Acquired gene changes
ā€¢ Gene changes related to lung cancer are usually acquired during life
rather than inherited.
ā€¢ Acquired mutations in lung cells often result from exposure to factors
in the environment, such as cancer-causing chemicals in tobacco
smoke.
ā€¢ But some gene changes may just be random events that sometimes
happen inside a cell, without having an external cause.
ā€¢ Acquired changes in certain genes, such as the p53 or p16 tumor
suppressor genes and the K-RAS oncogene, are thought to be
important in the development of non-small cell lung cancer.
ā€¢ Changes in these and other genes may also make some lung cancers
likely to grow and spread more rapidly than others.
ā€¢ Not all lung cancers share the same gene changes
Diagnosis of NSCLCā€¢ Most lung cancers are not found until they start to cause symptoms. Symptoms can suggest that a person
may have lung cancer, but the actual diagnosis is made by looking at lung cells under a microscope.
ā€¢ Common signs and symptoms of lung cancer
ā€¢ Most lung cancers do not cause any symptoms until they have spread too far to be cured, but
symptoms do occur in some people with early lung cancer. The most common symptoms of lung
cancer are:
ā€¢ A cough that does not go away or gets
worse
ā€¢ Chest pain that is often worse with deep
breathing, coughing, or laughing
ā€¢ Hoarseness
ā€¢ Weight loss and loss of appetite
ā€¢ Coughing up blood or rust-colored sputum
(spit or phlegm)
ā€¢ Shortness of breath
ā€¢ Feeling tired or weak
ā€¢ Infections such as bronchitis and pneumonia
that donā€™t go away or keep coming back
ā€¢ New onset of wheezing
ā€¢ When lung cancer spreads to distant organs,
it may cause:
ā€¢ Bone pain (like pain in the back or hips)
Contd..
ā€¢ Neurologic changes (such as headache,
weakness or numbness of an arm or leg,
dizziness, balance problems, or seizures)
ā€¢ Jaundice (yellowing of the skin and eyes)
ā€¢ Lumps near the surface of the body, due to
cancer spreading to the skin or to lymph
nodes (collections of immune system cells) in
the neck or above the collarbone
ā€¢ Most of the symptoms listed above are more
likely to be caused by conditions other than
lung cancer. Still, if you have any of these
problems, it's important to see your doctor
right away so the cause can be found and
treated, if needed.
ā€¢ Some lung cancers can cause a group of very
specific symptoms (syndromes).
Horner syndrome
ā€¢ Cancers of the top part of the lungs (called Pancoast tumors) may damage a nerve that passes
from the upper chest to neck causing Horner syndrome:
ā€¢ Severe shoulder pain.
ā€¢ Drooping or weakness of one eyelid; having a smaller pupil in the same eye
ā€¢ Reduced or absent sweating on the same side of the face
ā€¢ Conditions other than lung cancer can also cause Horner syndrome.
ā€¢ Tumors in upper part of the right lung and the lymph nodes may push on the SVC, which can
cause the blood to back up in the veins. This can cause swelling in the face, neck, arms, and
upper chest (sometimes with a bluish-red skin color).
ā€¢ While SVC syndrome can develop gradually over time, in some cases it can become life-
threatening, and needs to be treated right away.
Superior vena cava (SVC) syndrome
Paraneoplastic syndromes
ā€¢ Some lung cancers may make hormone-like substances that enter the bloodstream and cause
problems with distant tissues and organs, even though the cancer has not spread to those
tissues or organs, viz., paraneoplastic syndromes.
ā€¢ Common paraneoplastic syndromes include: hypercalcemia, constipation, nausea, vomiting,
weakness, dizziness, confusion, and other nervous system problems; excess growth of certain
bones, especially painful finger tip bones, gynecomastia
Horner syndrome
Superior vena cava syndrome
Paraneoplastic syndromes
Diagnosis..
ā€¢ Medical history and physical exam
ā€¢ Any signs or symptoms of lung cancer must be checked by a qualified physician
who will take a medical history to check for risk factors and signs of lung cancer
and other health problems.
ā€¢ If the results of the history and physical exam suggest lung cancer, more
involved tests are done. These might include imaging tests and/or getting
biopsies of lung tissue.
ā€¢ Imaging tests use x-rays, magnetic fields, sound waves, or radioactive
substances to create pictures of the inside of body:
ā€¢ To help find a suspicious area that might be cancerous
ā€¢ To learn how far cancer may have spread
ā€¢ To help determine if treatment has been effective
ā€¢ To look for possible signs of cancer recurrence after treatment
ā€¢ Chest x-ray is often the first test your doctor will do to look for any masses
or spots on the lungs.
ā€¢ If the x-ray is normal, there is no lung cancer
ā€¢ If something suspicious is seen, additional tests may be done
Computed tomography (CT)
scan
ā€¢ The CT or CAT scan uses x-rays to produce detailed cross-sectional images of your
body. Instead of taking one picture, like a regular x-ray, a CT scanner takes many
pictures as it rotates around the patient on a table.
ā€¢ A computer then combines these pictures into images of slices of the part of your
body being studied. Unlike a regular x-ray, a CT scan creates detailed images of the
soft tissues in the body.
ā€¢ Before the CT scan, a drink or injection of a contrast solution can be given.The
contrast may cause some flushing (a feeling of warmth, especially in the face).
ā€¢ CT scans take longer than regular x-rays, and they expose one to a small amount of
radiation. The test itself is painless, other than, perhaps, the insertion of the IV line.
ā€¢ A CT scan can provide precise information about the size, shape, and position of any
tumors and can help find enlarged lymph nodes that might contain cancer that has
spread from the lung. CT scans are more sensitive than routine chest x-rays in
finding early lung cancers.
ā€¢ CT guided needle biopsy (see a later slide): In cases where a suspected area of
cancer lies deep within the body, a CT scan can be used to guide a biopsy needle
precisely into the suspected area.
Magnetic resonance imaging (MRI)
scan
ā€¢ Like CT scans, MRI scans provide detailed images of soft tissues in the body. But MRI scans
use radio waves and strong magnets instead of x-rays. A contrast material called gadolinium is
often injected into a vein before the scan to better see details.
ā€¢ MRI scans are a little more uncomfortable than CT scans. (a) they take longer ā€“ often up to an
hour; (b) patient has to lie inside a narrow tube (difficult for people with claustrophobia ).
ā€¢ Images may not be as sharp in some cases. MRI machines make buzzing and clicking noises that
you may find disturbing. Some centers provide earplugs to help block this noise out.
ā€¢ MRI scans are most often used to look for possible spread of lung cancer to the brain or spinal
cord.
ā€¢ For a PET scan, a form of low radioactivity sugar (fluorodeoxyglucose or FDG) is injected into
the blood. Cancer cells (growing rapidly in the body) absorb large amounts of FDG. After about
an hour, one would enter & lie on the table of a PET scanner for 30 minutes
ā€¢ A special camera creates a picture of areas of radioactivity in the body. The picture is not finely
detailed like a CT or MRI but could be very important test for early stage lung cancer.
ā€¢ PET scans are also useful if your doctor thinks the cancer may have spread but doesn't know
where. PET can reveal spread of cancer to the liver, bones, adrenal glands, or some other organs
(not as useful for looking at the brain, since all brain cells use a lot of glucose).
ā€¢ Special machines are able to perform both a PET and CT scan at the same time (PET/CT scan)
for comparison of areas of higher radioactivity on the PET with the more detailed appearance of
that area on the CT.
Positron emission tomography (PET)
scan
MRI
PET
Bone scan
ā€¢ A bone scan can help show if a cancer has metastasized (spread) to the
bones.
ā€¢ For this test, a small amount of low-level radioactive material is
injected into a vein (intravenously, or IV) which settles in areas of
bone changes throughout the entire skeleton over a couple of hours.
In ~30 min or so, a special camera detects the radioactivity and
creates a picture of the skeleton.
ā€¢ Areas of active bone changes show up as "hot spots" on the skeleton
ā€¢ May suggest the presence of metastatic cancer, but arthritis or other
bone diseases can give false +ve.
ā€¢ PET scans, which are often done in patients with NSCLC, can usually
show if cancer has spread to the bones, so bone scans aren't needed
very often.
ā€¢ Bone scans are done mainly when there is reason to think the cancer may
have spread to the bones (because of symptoms such as bone pain) and
other test results aren't clear.
Fifty-four-year old female presented with non-small-cell lung cancer and a false-negative PET/CT
scan for bone metastasis. (A) Coronal PET image from PET/CT scan demonstrates hypermetabolic
right lower lung mass, mediastinal lymph nodes and multiple lung nodules. However, no definite
bony metastases were identified. (B) Bone scan image demonstrates focal radiotracer uptake in
the left 8th rib (arrow).
Song et al. (2009), Lung Cancer, 65, 333ā€“338
ā€¢ The results of a CT scan or another imaging test may strongly suggest that lung cancer is present,
but to confirm the diagnosis a sample of the tumor cells needs to be looked at
under the microscope. To get this sample, one or more of the tests below may be used. Some
of these tests may also be used to see how far a lung cancer has spread.
ā€¢ Bronchoscopy
ā€¢ For this exam, a bronchoscope (lighted, flexible fiber-optic tube ) is passed through the mouth or
nose and down into the windpipe and bronchi (mouth and throat are sprayed first with an
anesthetic).
ā€¢ Bronchoscopy can find some tumors or blockages in the larger airways of the lungs. At the same
time, small instruments can be passed down the bronchoscope to take biopsies; cells can be
sampled from the lining of bronchi (bronchial brushing) or by rinsing the bronchi .
ā€¢ These tissue and cell samples are then looked at under a microscope.
ā€¢ Endobronchial ultrasound
ā€¢ Ultrasound waves create pictures of the inside of your body. Small, microphone-like instrument
(a transducer) emits sound waves and picks up the echoes as they bounce off body tissues, which a
computer turns into a black and white image.
ā€¢ For endobronchial ultrasound, a bronchoscope is fitted with an ultrasound transducer & pointed in
different directions (at lymph nodes and other structures in the mediastinum). If enlarged lymph
nodes are seen on the ultrasound, a biopsy is obtained. The samples are then sent to a lab to be
looked at under a microscope.
ā€¢ There are many other tests for confirmation of NSCLC.
Fine needle aspiration (FNA)
biopsy
ā€¢ A needle biopsy can often be used to get a small sample of cells from a
suspicious area (mass).
ā€¢ First, the skin on the chest wall is treated with local anesthesia; a thin, hollow
needle is then guided into the area while looking at the lungs with either
fluoroscopy or CT scans.
ā€¢ Unlike fluoroscopy, CT doesn't give a continuous picture, so the needle is
inserted toward the mass, a CT image is taken, and the direction of the needle
is guided based on the image and repeated a few times until the needle is
within the mass.
ā€¢ A small sample of the mass is then sucked into a syringe and sent to a lab,
where it is looked at under the microscope for cancer cells.
ā€¢ When the diagnosis isn't clear based on the FNA biopsy, a larger needle may
be used to remove a slightly bigger piece of lung tissue (core needle biopsy).
ā€¢ A needle biopsy may be useful for getting samples from tumors in the outer
portions of the lungs, where other tests such as bronchoscopy may not be as
helpful.
Lab tests for biopsy and other
samples
ā€¢ Immunohistochemistry: very thin slices of the sample are attached
to glass microscope slides and trated with antibodies designed to attach
only to certain cancer cell antigens. Chemicals are then added so that
antibodies attached to the cells change color. The pathologist can see
this color change under microscope.
ā€¢ Molecular tests: sometimes specific gene changes in the cancer cells
affect how they are best treated.
ā€¢ e.g., the epidermal growth factor receptor (EGFR) protein appears in high
amounts on the surface of adenocarcinoma cells and helps them grow. Some newer
anti-EGFR drugs work best against lung cancers with EGFR gene change.
ā€¢ these changes are more common in non-smokers, women, and Asians but not in
patients with the KRAS gene change. Tests are now done for changes in genes such
as EGFR and KRAS to determine if these newer treatments are likely to be helpful.
ā€¢ Newer lab tests for certain other genes or proteins may also help guide
the choice of treatment.
Blood tests
ā€¢ Blood tests are not used to diagnose lung cancer, but they are done to
get a sense of a person's overall health.
ā€¢ eg,, before surgery, blood tests can help tell if a person is healthy enough
to have an operation.
ā€¢ A CBC can determine whether the blood has normal counts of various
cell types.
ā€¢ it can show if one is anemic; low number of blood platelets or an increased
risk for infections (because of a low number of white blood cells); this test
will be repeated regularly if you are treated with chemotherapy (as chemo
drugs can affect blood-forming cells of the bone marrow).
ā€¢ Blood chemistry tests can help spot abnormalities in some of your
organs, such as the liver or kidneys.
ā€¢ if cancer has spread to the liver and bones, it may cause abnormal levels of
lactate dehydrogenase (LDH).
Pulmonary function tests
(PFTs)
ā€¢ PFTs are done after lung cancer is diagnosed to see how well your lungs are
working
ā€¢ e.g.,, how much emphysema or chronic obstructive lung disease is
present.
ā€¢ important if surgery is an option in treating the cancer (surgery to remove
cancer may mean removing part or all of a lung & how well the lungs are
working now).
ā€¢ patients with poor lung function (say from smoking) donā€™t have enough
lung reserve to tolerate removing even part of a lung.
ā€¢ There are different types of PFTs, but they all basically one has to breathe in
and out through a tube that is connected to a machine that measures airflow.
ā€¢ this can be coupled with arterial blood gas. In this test, blood is removed
from an artery to measure the amount of oxygen and carbon dioxide that
it contains.
NSCLC Survival
ā€¢ Below are the survival rates calculated from the NCI's Surveillance,
Epidemiology, and End Results (SEER) database, based on people who were
diagnosed with non-small cell lung cancer between 1998 and 2000.
ā€¢ Survival rate refers to the percentage of patients who live for a given period of
time after their cancer is diagnosed. For example, 5-year survival rate refers
to the percentage of patients who live at least 5 years after their cancer is
diagnosed. Of course, many of these people live much longer than 5 years.
Continued to ..
Non-small Cell Lung
Cancer II
(Treatments, Clinical Trials)

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Non small cell lung cancer I

  • 1. Dr. Bhaswat S. Chakraborty Non-small Cell Lung Cancer I (Basics, Diagnosis, Survival Rates)
  • 2. ļ‚— Lungs are 2 sponge-like organs found in your chest. The right lung has 3 lobes, while the left lung has 2 lobes only (because the heart takes up more room on the left). ļ‚— While breathing, air enters through mouth or nose into your lungs through the trachea which divides into bronchi, then into bronchioles. At the end of each bronchiole, there are tiny air sacs, alveoli. ļ‚— Tiny blood vessels in alveoli absorb O2 from the inhaled air into the bloodstream and pass CO2 from the body into the alveoli, which is then exhaled. ļ‚— Taking in oxygen and getting rid of carbon dioxide are the main functions of lungs. ā€¢ A thin lining layer called the pleura surrounds the lungs. The pleura protects the lungs and helps them slide back and forth against the chest wall as they expand and contract during breathing. ā€¢ Below the lungs, a dome-shaped muscle called the diaphragm separates the chest from the abdomen. When you breathe, the diaphragm moves up and down, forcing air in and out of the lungs. Source: American Cancer Soc.
  • 3. Start and Spread of Lung Cancer ā€¢ Lung cancers can start in the cells lining the bronchi and in bronchioles or alveoli. ā€¢ They start as areas of pre-cancerous changes in the lung. The first changes happen in the genes of the cells themselves and may cause them to grow faster. ā€¢ The cells may look a bit abnormal if seen under a microscope, but at this point they do not form a mass or tumor. ā€¢ Over time, these pre-cancerous changes in the cells progress to true cancer. As a cancer develops, the cancer cells may make chemicals that cause new blood vessels (angiogenesis) nourishing the cancer cells. ā€¢ At some point, cells from the cancer may break away from the original tumor and spread (metastasize) to other parts of the body. ā€¢ Lung cancer is often a life-threatening disease because it tends to spread in this way even before it can be detected on an imaging test e.g., chest x-ray.
  • 4. The Lymph (Lymphatic) System ā€¢ The lymph system is one of the ways in which lung cancers can spread. ā€¢ Lymph nodes are small, bean-shaped collections of immune system cells (cells that fight infections) that are connected by lymphatic vessels. ā€¢ Lymphatic vessels are like small veins, except that they carry a clear fluid called lymph (instead of blood) away from the lungs. ā€¢ Lymph contains excess fluid and waste products from body tissues, as well as immune system cells. ā€¢ Lung cancer cells can enter lymphatic vessels and begin to grow in lymph nodes around the bronchi and in the mediastinum. ā€¢ From lymph nodes, cancer cells spread to other organs of the body. ā€¢ The stage (extent) of the cancer and decisions about treatment are based on whether or not the cancer has spread to the nearby lymph nodes in the mediastinum.
  • 5. Types of Lung Cancer ā€¢ There are 2 major types of lung cancer: ā€¢ Small cell lung cancer (SCLC) ā€¢ Non-small cell lung cancer (NSCLC) ā€¢ (If a lung cancer has characteristics of both types it is called a mixed small cell/large cell cancer. This is uncommon.) ā€¢ These 2 types of lung cancer are treated very differently.
  • 6. Non-small Cell Lung Cancer (NSCLC) ļ‚—About 85% of all lung cancers are of the non-small cell type. There are 3 sub-types of NSCLC. The cells in these sub-types differ in size, shape, and chemical make-up. ļ‚—Squamous cell carcinoma: about 25% to 30% of all lung cancers are of this kind starting in early versions of squamous cells (flat cells that line the inside of lungs). They are linked to smoking and tend to be found near the bronchus. ļ‚—Adenocarcinoma: this type accounts for about 40% of lung cancers starting in cells that normally secrete substances such as mucus. It is usually found in the outer part of the lung ļ‚—Large-cell undifferentiated carcinoma: about 10% to 15% of lung cancers are this type. It can start in any part of the lung. It tends to grow and spread quickly.Ā  ļ‚—Other subtypes: There are also a few other subtypes of non-small cell lung cancer, such as adenosquamous carcinoma and sarcomatoid carcinoma. These are much less common.
  • 7. Adenocarcinoma (A), squamous cell carcinoma (B), and large cell carcinoma (C). Immunohistochemical analysis for Ki-67 in an adenocarcinoma (D).
  • 8.
  • 9. The TNM Staging System ā€¢ The system used to describe the growth and spread of non-small cell lung cancer (NSCLC) is the American Joint Committee on Cancer (AJCC) TNM staging system. The TNM system is based on 3 key pieces of information: ā€¢ T indicates the size of the main (primary) tumor and whether it has grown into nearby areas. ā€¢ N describes the spread of cancer to nearby (regional) lymph nodes. Lymph nodes are small bean-shaped collections of immune system cells that help fight infections. Cancers often spread to the lymph nodes before going to other parts of the body. ā€¢ M indicates whether the cancer has spread (metastasized) to other organs of the body (e.g., brain, bones, adrenal glands, liver, kidneys, and the other lung.) ā€¢ Numbers or letters appear after T, N, and M to provide more details about each of these factors. The numbers 0 through 4 indicate increasing severity. The letter X means "cannot be assessed because the information is not available.ā€
  • 10.
  • 11. Stage Grouping for Lung Cancer ā€¢ Once the T, N, and M categories have been assigned, this information is combined to assign an overall stage of 0, I, II, III, or IV. This process is called stage grouping. Some stages are subdivided into A and B. Patients with lower stage numbers tend to have a better prognosis. ā€¢ Occult cancer ā€¢ TX, N0, M0: Cancer cells are seen in a sample of sputum or other lung fluids, but the cancer isn't found with other tests, so its location can't be determined. ā€¢ Stage 0 ā€¢ Tis, N0, M0: The cancer is found only in the top layers of cells lining the air passages. It has not invaded deeper into other lung tissues and has not spread to lymph nodes or distant sites. ā€¢ Stage IA ā€¢ T1a/T1b, N0, M0: The cancer is no larger than 3 cm across, has not reached the membranes that surround the lungs, and does not affect the main branches of the bronchi. It has not spread to lymph nodes or distant sites. ā€¢ Stage IB ā€¢ T2a, N0, M0: The cancer has 1 or more of the following features: ā€¢ main tumor is between 3 and 5 cm across; tumor has grown into a main bronchus, but is not within 2 cm of the carina; grown into the visceral pleura; partially clogging the airways; in any case, not larger than 5 cm; cancer has not spread to lymph nodes or distant sites.
  • 12. Stage Grouping for Lung Cancer.. ā€¢ Stage IIA ā€¢ T1a/T1b, N1, M0: The cancer is no larger than 3 cm across, has not grown into the membranes that surround the lungs, and does not affect the main branches of the bronchi; spread to lymph nodes within the lung and/or hilar lymph nodes); not spread to distant sites. OR ā€¢ T2a, N1, M0: The main tumor is between 3 and 5 cm across; grown into a main bronchus, but is not within 2 cm of the carina; tumor has grown into the visceral pleura; it is partially clogging the airways; in any case, not larger than 5 cm; spread to lymph nodes within the lung and/or hilar lymph nodes; cancer has not spread to distant sites. OR ā€¢ T2b, N0, M0: main tumor is between 5 and 7 cm across; grown into a main bronchus, but is not within 2 cm of the carina; tumor has grown into the visceral pleura; it is partially clogging the airways; cancer has not spread to lymph nodes or distant sites. ā€¢ Stage IIB ā€¢ T2b, N1, M0: main tumor is between 5 and 7 cm across; grown into a main bronchus, but is not within 2 cm of the carina; tumor has grown into the visceral pleura; it is partially clogging the airways; The cancer has spread to lymph nodes within the lung and/or hilar lymph nodes and has not spread to distant sites. OR ā€¢ T3, N0, M0: The main tumor is larger than 7 cm across; has grown into diaphragm, mediastinal pleura, or parietal pericardium; invades a main bronchus and is closer than 2 cm (about Ā¾ inch) to the carina, but it does not involve the carina itself; has grown into the airways enough to cause an entire lung to collapse or to cause pneumonia in the entire lung; or more separate tumor nodules are present in the same lobe of a lung; cancer has not spread to lymph nodes or distant sites.
  • 13. Stage Grouping for Lung Cancerā€¦ ā€¢ Stage IIIA ļ‚— T1 to T3, N2, M0: The main tumor can be any size; not grown into mediastinum, the heart, the aorta, trachea, esophagus, the backbone, or the carina; not spread to different lobes of the same lung; cancer has spread to lymph nodes around the carina or in the mediastinum; cancer has not spread to distant sites. OR ļ‚— T3, N1, M0: The cancer is larger than 7 cm across; has grown into the diaphragm, mediastinal pleura, or parietal pericardium; invades a main bronchus and is closer than 2 cm to the carina, but it does not involve the carina itself; or more separate tumor nodules are present in the same lobe of a lung; has grown into the airways enough to cause an entire lung to collapse or to cause pneumonia in the entire lung; spread to lymph nodes within the lung and/or the hilar lymph nodes; has not spread to distant sites. OR ļ‚— T4, N0 or N1, M0: The tumor of any size has grown into the mediastinum, the heart, the aorta or any other large blood vessels, the trachea, esophagus, the backbone, or the carina; or more separate tumor nodules are present in different lobes of the same lung; may or may not have spread to lymph nodes within the lung and/or hilar lymph nodes; affected lymph nodes are on the same side as the cancer; not spread to distant sites.
  • 14. Stage Grouping for Lung Cancerā€¦ ā€¢ Stage IIIB ā€¢ Two combinations of categories make up this stage; any T, N3, M0: The cancer can be of any size; may or may not have grown into nearby structures or caused pneumonia or lung collapse; spread to lymph nodes near the collarbone on either side, and/or has spread to hilar or mediastinal lymph nodes on the side opposite the primary tumor; cancer has not spread to distant sites; OR ā€¢ T4, N2, M0: The tumor of any size has grown into the mediastinum; the heart, the aorta; the trachea; the esophagus, the backbone, or the carina; or more separate tumor nodules are present in different lobes of the same lung; cancer has also spread to lymph nodes around the carina or in the mediastinum; affected lymph nodes are on the same side as the main lung tumor; has not spread to distant sites. ā€¢ Stage IV ā€¢ Two combinations of categories make up this stage; any T, any N, M1a: The cancer can be any size and may or may not have grown into nearby structures or reached nearby lymph nodes; also cancer has spread to the other lung; malignant pleural effusion; malignant pericardial effusion. OR ā€¢ Any T, any N, M1b: The cancer can be any size and may or may not have grown into nearby structures or reached nearby lymph nodes. It has spread to distant lymph nodes or to other organs such as the liver, bones, or brain.
  • 15. Risk Factors for NSCLC ā€¢ A risk factor is anything that affects a person's chance of getting a disease such as cancer. ā€¢ Different cancers have different risk factors, e.g., unprotected exposure to strong sunlight is a risk factor for skin cancer. ā€¢ But risk factors don't tell us everything. Having a risk factor, or even several risk factors, does not mean that one will get the disease. ā€¢ And some people who get the disease may not have had any known risk factors. ā€¢ Even if a person with lung cancer has a risk factor, it is often very hard to know how much that risk factor may have contributed to the cancer. ā€¢ Several risk factors can make you more likely to develop lung cancer.
  • 16. Tobacco Smoke ā€¢ Smoking is by far the leading risk factor for lung cancer. About 80% of lung cancer deaths are thought to result from smoking. ā€¢ The risk for lung cancer among smokers is many times higher than among non- smokers. The longer one smokes and the more packs a day, the greater the risk. ā€¢ Secondhand smoke: If you don't smoke, breathing in the smoke of others (called secondhand smoke or environmental tobacco smoke) can increase your risk of developing lung cancer. ā€¢ A non-smoker who lives with a smoker has about a 20% to 30% greater risk of developing lung cancer. Radon ā€¢ Radon is a naturally occurring radioactive gas that results from the breakdown of uranium in soil and rocks. It cannot be seen, tasted, or smelled.. ā€¢ Outdoors, there is so little radon that it is not likely to be dangerous. But indoors, radon can be more concentrated. ā€¢ When it is breathed in, it enters the lungs, exposing them to small amounts of radiation. This may increase a person's risk of lung cancer.
  • 17. Asbestos ā€¢ Workplace exposure to asbestos fibers is an important risk factor for lung cancer. ā€¢ Studies have found that people who work with asbestos (in some mines, mills, textile plants, etc.) are several times more likely to die of lung cancer. ā€¢ Both smokers and non-smokers exposed to asbestos also have a greater risk of developing mesothelioma, a type of cancer that starts in the pleura. Other workplace cancer-causing agents ā€¢ Radioactive ores such as uranium ā€¢ Inhaled chemicals or minerals such as arsenic, beryllium, cadmium, silica, vinyl chloride, nickel compounds, chromium compounds, coal products, mustard gas, and chloromethyl ethers ā€¢ Diesel exhaust ā€¢ Also radiation therapy to the lungs ā€¢ People who have had radiation therapy to the chest for other cancers are at higher risk for lung cancer, particularly if they smoke.
  • 18. Arsenic ā€¢ High levels of arsenic in drinking water may increase the risk of lung cancer. This is even more pronounced in smokers. ā€¢ Brothers, sisters, and children of those who have had lung cancer may have a slightly higher risk of lung cancer themselves, ā€¢ It is not clear how much of this risk might be due to genetics and how much might be from shared household exposures. ā€¢ Researchers have found that genetics does seem to play a role in some families with a strong history of lung cancer. ā€¢ e.g., people who inherit certain DNA changes in a particular chromosome (chromosome 6) are more likely to develop lung cancer, even if they only smoke a little. Personal or family history of lung cancer Certain dietary supplements ā€¢ Possible role of antioxidant supplements in reducing lung cancer risk does not seem promising so far. In fact, 2 large studies found that smokers who took beta carotene supplements actually had an increased risk of lung cancer. ā€¢ Results of these studies suggest that smokers should avoid taking beta carotene supplements.
  • 19. Inherited gene changes ā€¢ Some people inherit DNA mutations (changes) from their parents that greatly increase their risk for developing certain cancers. ā€¢ However, inherited mutations are not thought to cause very many lung cancers. ā€¢ Genes, however, do seem to play a role in some families with a history of lung cancer. ā€¢ e.g., some people seem to inherit a reduced ability to break down or get rid of certain types of cancer-causing chemicals in the body, such as those found in tobacco smoke putting them at higher risk for lung cancer. ā€¢ Others may inherit faulty DNA repair mechanisms that make it more likely they will end up with DNA changes. ā€¢ e.g., patients with repair enzymes that don't work well might be especially vulnerable to cancer-causing chemicals and radiation. ā€¢ Researchers are developing reliable tests for identifying such people, but for now, physicians recommend that all people avoid tobacco smoke and other exposures that might increase their cancer risk.
  • 20. Acquired gene changes ā€¢ Gene changes related to lung cancer are usually acquired during life rather than inherited. ā€¢ Acquired mutations in lung cells often result from exposure to factors in the environment, such as cancer-causing chemicals in tobacco smoke. ā€¢ But some gene changes may just be random events that sometimes happen inside a cell, without having an external cause. ā€¢ Acquired changes in certain genes, such as the p53 or p16 tumor suppressor genes and the K-RAS oncogene, are thought to be important in the development of non-small cell lung cancer. ā€¢ Changes in these and other genes may also make some lung cancers likely to grow and spread more rapidly than others. ā€¢ Not all lung cancers share the same gene changes
  • 21. Diagnosis of NSCLCā€¢ Most lung cancers are not found until they start to cause symptoms. Symptoms can suggest that a person may have lung cancer, but the actual diagnosis is made by looking at lung cells under a microscope. ā€¢ Common signs and symptoms of lung cancer ā€¢ Most lung cancers do not cause any symptoms until they have spread too far to be cured, but symptoms do occur in some people with early lung cancer. The most common symptoms of lung cancer are: ā€¢ A cough that does not go away or gets worse ā€¢ Chest pain that is often worse with deep breathing, coughing, or laughing ā€¢ Hoarseness ā€¢ Weight loss and loss of appetite ā€¢ Coughing up blood or rust-colored sputum (spit or phlegm) ā€¢ Shortness of breath ā€¢ Feeling tired or weak ā€¢ Infections such as bronchitis and pneumonia that donā€™t go away or keep coming back ā€¢ New onset of wheezing ā€¢ When lung cancer spreads to distant organs, it may cause: ā€¢ Bone pain (like pain in the back or hips) Contd.. ā€¢ Neurologic changes (such as headache, weakness or numbness of an arm or leg, dizziness, balance problems, or seizures) ā€¢ Jaundice (yellowing of the skin and eyes) ā€¢ Lumps near the surface of the body, due to cancer spreading to the skin or to lymph nodes (collections of immune system cells) in the neck or above the collarbone ā€¢ Most of the symptoms listed above are more likely to be caused by conditions other than lung cancer. Still, if you have any of these problems, it's important to see your doctor right away so the cause can be found and treated, if needed. ā€¢ Some lung cancers can cause a group of very specific symptoms (syndromes).
  • 22. Horner syndrome ā€¢ Cancers of the top part of the lungs (called Pancoast tumors) may damage a nerve that passes from the upper chest to neck causing Horner syndrome: ā€¢ Severe shoulder pain. ā€¢ Drooping or weakness of one eyelid; having a smaller pupil in the same eye ā€¢ Reduced or absent sweating on the same side of the face ā€¢ Conditions other than lung cancer can also cause Horner syndrome. ā€¢ Tumors in upper part of the right lung and the lymph nodes may push on the SVC, which can cause the blood to back up in the veins. This can cause swelling in the face, neck, arms, and upper chest (sometimes with a bluish-red skin color). ā€¢ While SVC syndrome can develop gradually over time, in some cases it can become life- threatening, and needs to be treated right away. Superior vena cava (SVC) syndrome Paraneoplastic syndromes ā€¢ Some lung cancers may make hormone-like substances that enter the bloodstream and cause problems with distant tissues and organs, even though the cancer has not spread to those tissues or organs, viz., paraneoplastic syndromes. ā€¢ Common paraneoplastic syndromes include: hypercalcemia, constipation, nausea, vomiting, weakness, dizziness, confusion, and other nervous system problems; excess growth of certain bones, especially painful finger tip bones, gynecomastia
  • 23. Horner syndrome Superior vena cava syndrome Paraneoplastic syndromes
  • 24. Diagnosis.. ā€¢ Medical history and physical exam ā€¢ Any signs or symptoms of lung cancer must be checked by a qualified physician who will take a medical history to check for risk factors and signs of lung cancer and other health problems. ā€¢ If the results of the history and physical exam suggest lung cancer, more involved tests are done. These might include imaging tests and/or getting biopsies of lung tissue. ā€¢ Imaging tests use x-rays, magnetic fields, sound waves, or radioactive substances to create pictures of the inside of body: ā€¢ To help find a suspicious area that might be cancerous ā€¢ To learn how far cancer may have spread ā€¢ To help determine if treatment has been effective ā€¢ To look for possible signs of cancer recurrence after treatment ā€¢ Chest x-ray is often the first test your doctor will do to look for any masses or spots on the lungs. ā€¢ If the x-ray is normal, there is no lung cancer ā€¢ If something suspicious is seen, additional tests may be done
  • 25.
  • 26. Computed tomography (CT) scan ā€¢ The CT or CAT scan uses x-rays to produce detailed cross-sectional images of your body. Instead of taking one picture, like a regular x-ray, a CT scanner takes many pictures as it rotates around the patient on a table. ā€¢ A computer then combines these pictures into images of slices of the part of your body being studied. Unlike a regular x-ray, a CT scan creates detailed images of the soft tissues in the body. ā€¢ Before the CT scan, a drink or injection of a contrast solution can be given.The contrast may cause some flushing (a feeling of warmth, especially in the face). ā€¢ CT scans take longer than regular x-rays, and they expose one to a small amount of radiation. The test itself is painless, other than, perhaps, the insertion of the IV line. ā€¢ A CT scan can provide precise information about the size, shape, and position of any tumors and can help find enlarged lymph nodes that might contain cancer that has spread from the lung. CT scans are more sensitive than routine chest x-rays in finding early lung cancers. ā€¢ CT guided needle biopsy (see a later slide): In cases where a suspected area of cancer lies deep within the body, a CT scan can be used to guide a biopsy needle precisely into the suspected area.
  • 27.
  • 28. Magnetic resonance imaging (MRI) scan ā€¢ Like CT scans, MRI scans provide detailed images of soft tissues in the body. But MRI scans use radio waves and strong magnets instead of x-rays. A contrast material called gadolinium is often injected into a vein before the scan to better see details. ā€¢ MRI scans are a little more uncomfortable than CT scans. (a) they take longer ā€“ often up to an hour; (b) patient has to lie inside a narrow tube (difficult for people with claustrophobia ). ā€¢ Images may not be as sharp in some cases. MRI machines make buzzing and clicking noises that you may find disturbing. Some centers provide earplugs to help block this noise out. ā€¢ MRI scans are most often used to look for possible spread of lung cancer to the brain or spinal cord. ā€¢ For a PET scan, a form of low radioactivity sugar (fluorodeoxyglucose or FDG) is injected into the blood. Cancer cells (growing rapidly in the body) absorb large amounts of FDG. After about an hour, one would enter & lie on the table of a PET scanner for 30 minutes ā€¢ A special camera creates a picture of areas of radioactivity in the body. The picture is not finely detailed like a CT or MRI but could be very important test for early stage lung cancer. ā€¢ PET scans are also useful if your doctor thinks the cancer may have spread but doesn't know where. PET can reveal spread of cancer to the liver, bones, adrenal glands, or some other organs (not as useful for looking at the brain, since all brain cells use a lot of glucose). ā€¢ Special machines are able to perform both a PET and CT scan at the same time (PET/CT scan) for comparison of areas of higher radioactivity on the PET with the more detailed appearance of that area on the CT. Positron emission tomography (PET) scan
  • 30. Bone scan ā€¢ A bone scan can help show if a cancer has metastasized (spread) to the bones. ā€¢ For this test, a small amount of low-level radioactive material is injected into a vein (intravenously, or IV) which settles in areas of bone changes throughout the entire skeleton over a couple of hours. In ~30 min or so, a special camera detects the radioactivity and creates a picture of the skeleton. ā€¢ Areas of active bone changes show up as "hot spots" on the skeleton ā€¢ May suggest the presence of metastatic cancer, but arthritis or other bone diseases can give false +ve. ā€¢ PET scans, which are often done in patients with NSCLC, can usually show if cancer has spread to the bones, so bone scans aren't needed very often. ā€¢ Bone scans are done mainly when there is reason to think the cancer may have spread to the bones (because of symptoms such as bone pain) and other test results aren't clear.
  • 31. Fifty-four-year old female presented with non-small-cell lung cancer and a false-negative PET/CT scan for bone metastasis. (A) Coronal PET image from PET/CT scan demonstrates hypermetabolic right lower lung mass, mediastinal lymph nodes and multiple lung nodules. However, no definite bony metastases were identified. (B) Bone scan image demonstrates focal radiotracer uptake in the left 8th rib (arrow). Song et al. (2009), Lung Cancer, 65, 333ā€“338
  • 32. ā€¢ The results of a CT scan or another imaging test may strongly suggest that lung cancer is present, but to confirm the diagnosis a sample of the tumor cells needs to be looked at under the microscope. To get this sample, one or more of the tests below may be used. Some of these tests may also be used to see how far a lung cancer has spread. ā€¢ Bronchoscopy ā€¢ For this exam, a bronchoscope (lighted, flexible fiber-optic tube ) is passed through the mouth or nose and down into the windpipe and bronchi (mouth and throat are sprayed first with an anesthetic). ā€¢ Bronchoscopy can find some tumors or blockages in the larger airways of the lungs. At the same time, small instruments can be passed down the bronchoscope to take biopsies; cells can be sampled from the lining of bronchi (bronchial brushing) or by rinsing the bronchi . ā€¢ These tissue and cell samples are then looked at under a microscope. ā€¢ Endobronchial ultrasound ā€¢ Ultrasound waves create pictures of the inside of your body. Small, microphone-like instrument (a transducer) emits sound waves and picks up the echoes as they bounce off body tissues, which a computer turns into a black and white image. ā€¢ For endobronchial ultrasound, a bronchoscope is fitted with an ultrasound transducer & pointed in different directions (at lymph nodes and other structures in the mediastinum). If enlarged lymph nodes are seen on the ultrasound, a biopsy is obtained. The samples are then sent to a lab to be looked at under a microscope. ā€¢ There are many other tests for confirmation of NSCLC.
  • 33. Fine needle aspiration (FNA) biopsy ā€¢ A needle biopsy can often be used to get a small sample of cells from a suspicious area (mass). ā€¢ First, the skin on the chest wall is treated with local anesthesia; a thin, hollow needle is then guided into the area while looking at the lungs with either fluoroscopy or CT scans. ā€¢ Unlike fluoroscopy, CT doesn't give a continuous picture, so the needle is inserted toward the mass, a CT image is taken, and the direction of the needle is guided based on the image and repeated a few times until the needle is within the mass. ā€¢ A small sample of the mass is then sucked into a syringe and sent to a lab, where it is looked at under the microscope for cancer cells. ā€¢ When the diagnosis isn't clear based on the FNA biopsy, a larger needle may be used to remove a slightly bigger piece of lung tissue (core needle biopsy). ā€¢ A needle biopsy may be useful for getting samples from tumors in the outer portions of the lungs, where other tests such as bronchoscopy may not be as helpful.
  • 34.
  • 35. Lab tests for biopsy and other samples ā€¢ Immunohistochemistry: very thin slices of the sample are attached to glass microscope slides and trated with antibodies designed to attach only to certain cancer cell antigens. Chemicals are then added so that antibodies attached to the cells change color. The pathologist can see this color change under microscope. ā€¢ Molecular tests: sometimes specific gene changes in the cancer cells affect how they are best treated. ā€¢ e.g., the epidermal growth factor receptor (EGFR) protein appears in high amounts on the surface of adenocarcinoma cells and helps them grow. Some newer anti-EGFR drugs work best against lung cancers with EGFR gene change. ā€¢ these changes are more common in non-smokers, women, and Asians but not in patients with the KRAS gene change. Tests are now done for changes in genes such as EGFR and KRAS to determine if these newer treatments are likely to be helpful. ā€¢ Newer lab tests for certain other genes or proteins may also help guide the choice of treatment.
  • 36. Blood tests ā€¢ Blood tests are not used to diagnose lung cancer, but they are done to get a sense of a person's overall health. ā€¢ eg,, before surgery, blood tests can help tell if a person is healthy enough to have an operation. ā€¢ A CBC can determine whether the blood has normal counts of various cell types. ā€¢ it can show if one is anemic; low number of blood platelets or an increased risk for infections (because of a low number of white blood cells); this test will be repeated regularly if you are treated with chemotherapy (as chemo drugs can affect blood-forming cells of the bone marrow). ā€¢ Blood chemistry tests can help spot abnormalities in some of your organs, such as the liver or kidneys. ā€¢ if cancer has spread to the liver and bones, it may cause abnormal levels of lactate dehydrogenase (LDH).
  • 37. Pulmonary function tests (PFTs) ā€¢ PFTs are done after lung cancer is diagnosed to see how well your lungs are working ā€¢ e.g.,, how much emphysema or chronic obstructive lung disease is present. ā€¢ important if surgery is an option in treating the cancer (surgery to remove cancer may mean removing part or all of a lung & how well the lungs are working now). ā€¢ patients with poor lung function (say from smoking) donā€™t have enough lung reserve to tolerate removing even part of a lung. ā€¢ There are different types of PFTs, but they all basically one has to breathe in and out through a tube that is connected to a machine that measures airflow. ā€¢ this can be coupled with arterial blood gas. In this test, blood is removed from an artery to measure the amount of oxygen and carbon dioxide that it contains.
  • 38. NSCLC Survival ā€¢ Below are the survival rates calculated from the NCI's Surveillance, Epidemiology, and End Results (SEER) database, based on people who were diagnosed with non-small cell lung cancer between 1998 and 2000. ā€¢ Survival rate refers to the percentage of patients who live for a given period of time after their cancer is diagnosed. For example, 5-year survival rate refers to the percentage of patients who live at least 5 years after their cancer is diagnosed. Of course, many of these people live much longer than 5 years.
  • 39. Continued to .. Non-small Cell Lung Cancer II (Treatments, Clinical Trials)