Lung cancer is defined as an uncontrolled growth of abnormal cells in one or more of the lungs. It is the leading cause of cancer deaths worldwide. The two main types are small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), which accounts for approximately 75% of cases. NSCLC can be further classified into adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Staging helps determine appropriate treatment and prognosis, with earlier stages having higher survival rates. Treatment options include surgery, chemotherapy, and radiation therapy, either alone or in combination, depending on the cancer type and stage.

1. Lung Cancer
Disease, diagnosis and treatment
By: Jennifer Gutierrez, Nuclear Medicine Clinical Specialist
DEFINITION
ETIOLOGY
In the United States, over 165,000 people die of lung cancer every year, composing 28% of all cancer deaths. It is the
leading cause of cancer deaths in men and women worldwide.
The median age of patients receiving a lung cancer diagnosis is 70 years. Over 85% of lung cancers are attributed to
smoking, the chief risk factor in developing the disease. Female smokers are at a higher risk (approximately twice as likely
to develop lung cancer) than male smokers, although there are not yet any clinical indicators as to why.
Other risk factors for lung cancer include: second-hand smoke, family history of cancer, radiation exposure, asbestos
exposure (asbestos workers are seven times more likely to develop lung cancers than non-asbestos workers), air
pollution, and exposure to radon, uranium, arsenic, coal products, nickel chromates, gasoline and diesel exhaust.
TYPES OF LUNG CANCER
The two most common types of lung cancer are small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC).
Each type of lung cancer has different behaviors and clinical patterns, is composed of different types of cells and
responds to different types of treatments. Clinical staging also differs among different types of lung cancer.
Small cell lung cancer:
Small cell lung cancer, also called oat cell carcinoma and small cell undifferentiated carcinoma, accounts for
approximately 20% of all lung cancer cases. SCLC is characterized by an aggressive clinical pattern involving distinct
cells that grow and metastasize more rapidly than those involved in other types of lung cancer. In addition to rapid growth,
the cancer cells involved with SCLC are more sensitive to chemotherapy and radiation therapy. Surgery is rarely used in
this type of treatment due to the rapid onset of SCLC, its likelihood of spreading to organs outside of the lungs and its
sensitivity to other treatments. SCLC is highly associated with smoking.
Non-small cell lung cancer:
Non-small cell lung cancer composes approximately 75% of all lung cancers. Although surgery is the preferred treatment
for NSCLC, most patients are diagnosed too late for surgery to be effective.
As there are different types of lung cancer, there are also different types of NSCLC, depending on the type of tumor
existing in each case. Each carcinoma group arises in a distinct part of the lungs, varies in cell size/shape and/or varies in
treatment options. When localized, all groups have the potential of cure with surgical resection.
Adenocarcinoma: Adenocarcinoma is the most common type of lung cancer and composes approximately 40% of
all lung cancers. This type of lung cancer has no relationship with smoking. It originates on the outer boundaries of the
lungs.
Squamous cell carcinoma:
Squamous cell carcinoma, also called epidermoid cancer, is the second most common lung
cancer. It composes approximately 20-30% of all lung cancers. Squamous cell carcinoma usually originates in the
bronchial tubes and the bronchial epithelium. Squamous cell carcinoma spreads locally and later metastasizes throughout
the body.
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Lung cancer, a malignancy of the lungs, is defined as an uncontrolled growth of abnormal cells in one or
more of the lungs.

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Large cell carcinoma:
Large cell carcinoma composes approximately 10% of all lung cancers. This type of cancer is
composed of large, abnormal cells and begins along the outer edges of the lungs.
Secondary lung cancer:
Secondary lung cancer is a malignancy of the lung that has spread from other parts of the body (the lung is not the area of
primary cancer). Secondary lung cancer does not have the same characteristics or clinical patterns as primary lung
cancers and is not treated or staged as such.
CLINICAL MANIFESTATIONS
Symptoms:
Symptoms of lung cancer that may present while lung cancer is still localized to the lung area are: persistent cough, loss
of appetite, weight loss, shortness of breath, blood in phlegm and recurring respiratory infections. Symptoms that may
occur after metastases include: bone pain, jaundice, dizziness, swelling of the neck or face, headaches, neurological
changes and palpable masses near the skin. Unfortunately, when these symptoms present themselves cancer has
usually spread a substantial amount and prognosis is not good. The time of onset to manifestations varies and depends
on the type of cancer as well as the location.
Lung nodules can be detected on chest x-rays (routine physical examinations and pre-operative testing) before clinical
manifestations occur. Screening may occur after certain symptoms present themselves or as a routine screening due to
risk factors. Many nodules found on x-rays and during lung cancer screening are benign. Currently, it is difficult to assess
the possible malignancy of such nodules, as further assessment tends to be costly and/or invasive.
Most cancers of the lung, if not detected while they are still localized, will be fatal within 5 years.
Diagnosis, monitoring and staging procedures:
Physical exam:
A physical exam could detect certain symptoms that are sometimes present in lung cancer such as
breathing difficulties, infection in the lungs or obstruction of the airway.
Sputum cytology: Mucous cells (expectorant) are examined under a microscope to determine if cancerous cells are
present.
Biopsy: A sample of tissue or fluid is removed from the patient for examination under a microscope to determine if
cancerous cells are present.
Chest x-ray:
When respiratory symptoms present themselves, a chest x-ray is the most commonly performed test to
evaluate anatomy for abnormalities. Images in the anterior, posterior and lateral views are usually taken. Not all
abnormalities on a chest x-ray will indicate a malignancy and not all malignancies can be detected from a chest x-ray. If
an abnormality is detected on a chest x-ray, further means of lung cancer screening/assessment may be suggested.
Commonly used assessments of nodule malignancy can be costly (PET or PET/CT imaging) or invasive (biopsy).
Bronchoscopy:
An instrument called a bronchoscope is inserted into the mouth or nose of the patient and cells and
anatomy of the airways and lungs are visually examined. Tissue can also be collected for biopsy using the bronchoscope.
Some bronchoscopes have video recording devices incorporated into the instrument so the examination can be replayed
and analyzed.
Needle aspiration:
A needle is inserted through the chest and into the tumor to remove tumor cells for pathological
evaluation.
Thoracentesis:
A needle is inserted through the chest into the cavity surrounding the lungs and fluid is removed for
pathological evaluation.
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CT:
Computerized tomography may be indicated when no abnormalities are found on an x-ray or when it is necessary to
visualize an abnormality in more detail. CT scans take x-ray images from multiple angles and anatomy can be viewed in 3
planes. CT scans may also be indicated to assess other parts of the body for metastatic disease.
MRI:
Magnetic resonance imaging can be used to visualize detailed anatomy of the lungs and bordering structures and
may be indicated when an x-ray has not shown an abnormality or failed to show necessary detail. More detailed images
can be obtained using MRI than chest x-ray and images can be viewed in 3 planes. MRI shows superior contrast between
soft tissues than other imaging procedures such as CT and x-ray. Unlike CT and x-ray, MRI does not use ionizing
radiation.
Nuclear bone scan:
This imaging procedure is used to detect if lung cancer has spread to the bones or if metastases
remain in the bones after treatment. A radioisotope attached to a phosphate analogue is injected intravenously and whole-
body images are taken using a gamma camera. In areas of increased bone metabolism, the phosphate analogue will
accumulate, thereby emitting more radiation than normal bone. The gamma camera detectors will image the bones and
the radioactive activity indicating high levels of bone metabolism, often times an indicator of metastatic activity.
PET:
Positron emission tomography is used to stage disease and monitor disease progression and effectiveness of
treatment. A positron-emitting radioisotope is attached to a glucose molecule and injected into the patient’s blood stream.
The glucose molecule will localize in increased areas of metabolic activity such as tumors. A PET scanner detects the
radiation present throughout the body and creates images in 3 planes. Unlike X-ray, MRI and CT, PET images the
physiology of the body rather than the anatomy. When used in the detection of mediastinal metastasis, PET sensitivity
and specificity are found to be higher than that of CT.
PET/CT:
When PET and CT are used together, a hybrid camera can be used to image both physiology and anatomy. The
detail and high resolution provided by CT is fused with the metabolic information gathered by PET to detect not only the
size and exact location of abnormalities, but their metabolic activity as well.
Blood tests:
Blood tests can be helpful in staging previously diagnosed cancers or can be an indicator of a possible
malignancy. Certain enzymes may exist in the blood, such as alkaline phosphatase, that can indicate bone metastasis.
Elevated calcium levels could also be an indication of bone metastasis. Elevated levels of enzymes found in liver cells,
such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), could signal liver disease, and possible
malignancy of/metastasis to the liver.
Tumor markers, also called biomarkers, are substances that are sometimes found in a specific concentration in the blood
(as well as other body fluids or tissues) that may indicate a certain type of cancer is present in the body. Blood is drawn
from the patient and tested for biomarkers specific to lung cancer. Researchers have discovered over 400 biomarkers
associated with lung cancer to date. Assessment of biomarkers can be used for early detection, as well as treatment
selection and monitoring of disease. A recent study has found an abnormal structure of micro RNA (miRNA) to be present
in lung cancer patients. The study also found this biomarker to be present in patients before CT scans were able to detect
lung nodules in the patients.
DISEASE PROGRESSION
Lung cancer will always originate in the lung and can remain localized without any symptoms. The most common disease
progression is:
• local tumor(s) present in the lung
• invasion of airways and blood vessels by tumor(s)
• primary symptoms may appear
• malignancy spreads to the lymph nodes
• lung cancer metastasizes throughout the body (most often to the liver, adrenal glands, bones and brain)
• advanced symptoms may appear
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STAGING
Staging is an attempt to define the true extent of
cancer in each patient based on the extent of the
primary tumor and the presence or absence of
lymphatic involvement or distant metastases.
Treatment and prognosis rely on accurate staging for
effectiveness and accuracy.
Staging SCLC:
There are two classifications in the staging of SCLC:
limited and extensive. A staging classification of limited
stage (LS) signifies that disease is confined to the
chest with involvement of only one lung and one
nearby lymph node. Any further progression of disease
(the disease has spread to other organs) is classified
as extensive stage (ES).
Staging NSCLC:
NSCLC is staged using roman numerals I-IV, as well
as a Stage 0, each having a specific definition
indicating the progression of the disease and anatomy
involved. 0 indicates local cancer (cancer is in situ)
while IV indicates cancer outside of the chest. The
chart to the right outlines the different stages of NSCLC
and survival rates associated with each.
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Roman Numeral Staging
0
disease limited to air passage lining: has not
invaded lung tissue; can usually be treated and
eliminated when diagnosed in this stage
I
disease limited to lung tissue; has not invaded
lymph nodes or other organs; 60-80% chance
of survival at 5 years if treated at this stage
II
disease has invaded nearby lymph nodes or
has spread to the chest wall; 40-50% chance
of survival at 5 years if treated at this stage
IIIA
disease has invaded lymph nodes outside of
the lung area; surgery is usually ruled out as a
course of treatment; 15-30% chance of
survival at 5 years if treated at this stage
IIIB
disease has invaded organs and structures
surrounding the lungs such as the heart,
trachea and esophagus; disease still confined
to the chest area; surgery is not a treatment
option; 10-15% chance of survival if treated at
this stage
IV
disease has invaded structures and organs
throughout the body, such as liver, bones and
brain; less than 2% chance of survival at 5
years if treated at this stage
TREATMENT REGIMES
Which treatment or combination of treatments to use is
determined by the stage of the cancer and the patient’s
overall health. In earlier stages of lung cancer, surgery
may be successful in removal of the malignancy. When
lung cancer has metastasized to a more advanced stage, surgery may no longer be an option.
NSCLC stages 0 - I are usually treated with surgery, while stage II cancers are often treated with surgery followed by
chemotherapy or radiation therapy. NSCLC stages III and IV will usually use a combination of chemotherapy and
radiation therapy, as the disease is too widespread to surgically remove the malignancy with positive results.
SCLC in limited stage (LS) may be treatable with surgery, although it is extremely rare for SCLC to be diagnosed at
that stage. Chemotherapy is the main treatment for SCLC, while it can be combined with other treatments as well.
Surgery:
Surgery is used to remove malignancies that are confined to a defined area of the lung anatomy. In most cases,
surgery is performed to remove a malignancy before it can metastasize throughout the body. Lymph nodes
surrounding the area of the malignancy are often removed as a precautionary measure or if a biopsy has shown
lymph node involvement. Surgery may not be an option for certain patients who are not healthy enough to undergo
the physical demands of such an intensive mediastinal procedure.
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Segmentectemoy/wedge resection:
removal of small segments or wedges of the lung
Lobectomy:
removal of a lobe of the lung
Pneumonectomy:
removal of a lung
Lymph node removal:
removal of lymph nodes surrounding the malignancy
Chemotherapy:
Chemotherapy is the use of cytotoxic, or cell-killing, drugs to kill cancerous cells in the body or to decrease their
activity. Chemotherapy differs from surgery and radiation therapy in that it is a systemic treatment, targeting cancer
cells throughout the entire body. Chemotherapy is often used in conjunction with surgery and/or radiation therapy in
case malignancy has spread to undetectable locations in the body. Because chemotherapy is most commonly used in
addition to other treatments, it can be referred to as an adjuvant therapy. Chemotherapy may also be used to shrink
tumor size before surgery (neo-adjuvant therapy) or to shrink tumor size to decrease tumor effects (such as a large
tumor obstructing an airway). Chemotherapy may also be used in late-stage lung cancer to prolong life.
Lung cancer treatment with chemotherapy usually uses a combination of 2 or more drugs and is given in cycles of 3-4
weeks, usually 4-6 times. Chemotherapy agents can be given orally or intravenously. Cisplatin and carboplatin are two
commonly used chemotherapy drugs to treat lung cancer. These platinum-containing agents will bind to DNA and
trigger apoptosis (cell death). It is common for patients to develop a resistance to these agents over time.
Radiation therapy:
Radiation therapy, also called radiotherapy, uses high-energy radiation targeted to specific areas of malignancy to kill
or shrink tumors. The radiation damages cell DNA causing cell death. Radiation therapy is often combined with
chemotherapy and/or surgery to treat SCLC and NSCLC. Two types of commonly used radiation therapy are external
beam radiation therapy and internal radiation therapy (brachytherapy). Research into other brachytherapy protocols,
such as the implantation of radioactive seeds next to malignancies in the lung (which has been successful in prostate
cancer treatment), is currently underway.
External beam radiation therapy:
A linear accelerator emits high-energy radiation targeted towards the area of
treatment.
Internal radiation (brachytherapy) therapy: In lung cancer, brachytherapy can be administered by passing
radioactive material through a plastic tube inserted into the lung where the malignancy to be treated is (this is done via
bronchoscopy).
PROGNOSIS AND OUTCOMES
Of all diagnosed cases of lung cancer, 10% are ultimately cured. If a
patient cannot be cured by surgery at the time of diagnosis there exists a
50% chance of survival for one year. 85% of all lung cancers diagnosed
are in stage II or higher (NSCLC) or in extensive stage (SCLC). The 1-
year survival rate is 41% for lung cancers diagnosed in this stage (stage II
or higher or ES) and the 5-year survival rate is approximately 15%
(compared to approximately 65% for colon cancer and approximately 90%
for breast cancer). If lung cancer is diagnosed before it has spread to the
lymph nodes, the 5-year survival rate increases to about 42%, although
less than 20% of all lung cancers are diagnosed at this early of a stage.
Most symptoms of lung cancer do not present themselves until after
metastasis has occurred.
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FACTORS INFLUENCING PROGNOSIS
Stage
Location of tumor
Type of lung cancer
Response to certain treatments
Patient’s relative health
Patient’s age

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REFERENCES CONSULTED
Hansen, H. (Ed.). (2008). Textbook of Lung Cancer (2nd
Edition), London, Informa Healthcare.
American Cancer Society
U.S. National Library of Medicine (NIH), Medline Plus
World Health Organization, International Agency for Research on Cancer
Journal of the American Medical Association, Lung Cancer Facts
Proceedings of the National Academy of Sciences, MicroRNA signatures in tissues and plasma predict
development and prognosis of computed tomography detected lung cancer, Mattia Boeri, Carla Verri, Davide
Conte, Luca Roz, Piergiorgio Modena, Federica Facchinetti, Elisa Calabro, Carlo M. Croce, Ugo Pastorino, and
Gabriella Sozzi, 2011.
5. How is NSCLC in Stage 0 usually treated?
a. Brachytherapy
b. Surgery
c. Chemotherapy
d. Chemotherapy and Radiation Therapy
e. Radiation Therapy
6. Which of the following statements is true
regarding PET imaging?
a. It does not expose the patient to ionizing
radiation
b. It images physiology rather than anatomy
c. It has a higher sensitivity and specificity in
evaluating mediastinal masses than CT
d. A & C
e. B & C
7. What is the main factor influencing the
prognosis/survival rate of a patient diagnosed with
lung cancer?
a. Location of primary lung nodule in lung
b. Proximity of primary nodule to other organs
c. Stage of lung cancer at the time of diagnosis
d. Patient’s age
e. Patient’s family history
8. What piece of information collected in a recent
study on lung cancer biomarkers shows promise in
lung cancer screening?
a. An abnormal structure of miRNA is the first
biomarker that has been discovered to be linked
to lung cancer
LEARNING ASSESSMENT
1. What is the most common type of lung cancer?
a. Large cell carcinoma
b. Oat cell carcinoma
c. Adenocarcinoma
d. Small cell undifferentiated carcinoma
e. Squamous cell carcinoma
2. Which lung cancer is characterized by cells that
grow and metastasize more rapidly than cells
involved in other types of lung cancer?
a. Adenocarcinoma
b. NSCLC
c. SCLC
d. Secondary lung cancer
e. B & C
3. Which type of lung cancer is known to originate in
the bronchial tubes and the bronchial epithelium?
a. Adenocarcinoma
b. Large cell lung cancer
c. Secondary lung cancer
d. Squamous cell carcinoma
e. Small cell undifferentiated carcinoma
4. Which cancer has the lowest 5-year survival rate?
a. Breast Cancer
b. Lung Cancer
c. Colon Cancer
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7.
b. miRNA only exists in patients with lung cancer
c. An abnormal structure of miRNA was found in
lung cancer patients before nodules were
visualized in CT imaging
d. The presence of abnormal miRNA can indicate
lung cancer has metastasized into the bone
9. What element do chemotherapy agents ciplatin
and carboplatin contain that acts on cancer cells by
leading to apoptosis?
a. Zinc
b. Iron
c. Platinum
d. Aluminum
e. Phosphate
10. It is rare for SCLC to be diagnosed ___________.
a. before the age of 70
b. in limited stage
c. in extensive stage
d. in men
e. using chest x-ray
11. In which procedure is a radioisotope and
phosphate analogue used to assess the occurrence
of bone metastasis?
a. PET
b. PET/CT
c. CT
d. Nuclear bone scan
e. MRI
12. Elevated levels of __________ found in a blood
test could indicate bone metastasis.
a. Micro RNA
b. Alanine aminotransferase
c. Alkaline phosphatase
d. Calcium
e. B & C
f. C & D
13. What type of lung cancer is staged using LS and
ES classifications?
a. NSCLC
b. SCLC
c. Adenocarcinoma
d. NSCLC and SCLC
e. All of the above
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14. Which procedure involves the removal of a lung?
a. Lobectomy
b. Wedge resection
c. Pneumonectomy
d. Lymph node removal
e. Brachytherapy
15. In which NSCLC stage is the disease limited only
to the lung tissue and has no lymph node
involvement?
a. 0
b. I
c. II
d. III
e. IV
16. In which NSCLC stage has the disease
metastasized to distant organs and tissues, such as
the brain and bones?
a. 0
b. I
c. II
d. III
e. IV
17. What is most commonly the main treatment
regime for SCLC?
a. Internal radiation therapy
b. Chemotherapy
c. External beam radiation
d. Lobectomy
e. Pneumonectomy
18. In regards to treatment regimes, what does it
mean for a treatment to be systemic?
a. It targets malignancy in a specific part of the
body
b. It is used in addition to other treatments
c. The treatment is given over a duration of time in
specific cycles
d. The treatment targets malignancy throughout
the entire body
e. Patients can develop resistance to the treatment
over time

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19. Which of the following treatment regimes is
considered a systemic treatment?
a. Chemotherapy
b. External beam radiation therapy
c. Surgery
d. Internal beam radiation therapy
20. Most noticeable symptoms of lung cancer
a. Occur as respiratory symptoms
b. Are usually ignored by patients
c. Do not present themselves until after metastasis
occurs
d. Present themselves more often in SCLC than
NSCLC
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