BIOE 301

Lung CancerWarning: I have determined that cigarette smoke is dangerous to your health.

Lung Cancer: 2005

• 174,470 new cases in US, 2006– accounts for 13% of new cancer cases

• 162,460 deaths in US, 2006– and 29% of all cancer deaths each year in US

• Signs and Symptoms– symptoms of lung cancer can take many years to develop which

often leads to diagnosis at an advanced stage of this disease. • Increase in volume of sputum• Wheezing• Change in color of sputum• Blood in sputum• Repeated episodes of pneumonia or bronchitis

Lung Cancer• Risk Factors:

#1 Tobacco Use. -90% of lung cancer cases in men and 78% of lung cancer cases in women are caused by smoking tobacco.

-Smokers vs. Non-smokersA smokers risk for developing lung cancer is 20 to 30 times

greater than a non smoker Second Hand Smoke

-Second hand (passive) tobacco smoke is carcinogenic and may increase the lung cancer risk by 20%.

Radon Exposure-Radon is an invisible gas that occurs naturally in rock and soil. About 10% of lung cancer cases are due to excessive radon exposure.

Asbestos ExposureAsbestos is a fibrous mineral used in many industries. Exposure increases ones risk of developing lung cancer by 3-4 times.

www.who.intwww.cancer.gov

Tobacco Use in the US, 1900-2000

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*Age-adjusted to 2000 US standard population. Source: Death rates: US Mortality Public Use Tapes, 1960-2000, US Mortality Volumes, 1930-1959, National Center for Health Statistics, Centers for Disease Control and Prevention, 2002. Cigarette consumption: US Department of Agriculture, 1900-2000.

Per capita cigarette consumption

Male lung cancer death rate

Female lung cancer death rate

Male lung cancer death rate

Geographical Incidence of Lung Cancer: 2004

www.cdc.gov

Incidence & Mortality

Lung Cancer Around the World• Incidence:

– Lung cancer is the most common cancer worldwide, accounting for 1.2 million new cases annually

– Lung cancer accounts for 17.8% of all cancer deaths – Half of all cases (49.9%) occur in the developing world– The estimated numbers of lung cancer cases– worldwide has increased by 51% since 1985– Highest incidence in:

• North America• Europe (esp. Eastern Europe)

• Mortality:– Most common cause of death from cancer, with 1.18 million

deaths worldwide

Lung Cancer Around the World

American Cancer Society Cancer Atlas

Cancer Risks for Boyshttp://www.cancer.org/downloads/AA/CancerAtlas03.pdf

Cancer Risks for Girlshttp://www.cancer.org/downloads/AA/CancerAtlas04.pdf

Lung Cancer Around the Worldhttp://www.cancer.org/downloads/AA/CancerAtlas13.pdf

Incidence: Male v. FemaleWorld Wide Incidence of Lung Cancer: Men vs. Women

A little Background: The Lungs

Initiation of Cellular Changes

Normal Epithelium

Injurious inhalant

Squamous Metaplasia

Persistent Squamous Metaplasia

Carcinogen

Increasingly severe atypia

Cancer in situ

Invasive Carcinoma

Progression of tissue changes leading to cancer

Normal epithelium of the bronchi

Cellular Changes:

•Thickening of the epithelium =hyperplasia

•Loss of the ciliated columnar cells which are replaced by a squamous epithelium

•Proliferation of basal cells = dysplasia

•Development of abnormal cell structure and abnormal nuclei

Surface view: normal lung

Cross-section: cancerous

lung

Surface view: cancerous

lung

Cross-section: normal lung

Surface view: normal lung

Cross-section: normal lung

Your CONFIDENTIAL Test Resultshave arrived….

Lung Cancer Screening

Your CONFIDENTIAL Test Results

• You can open now, or you can wait and learn more…

Possible Outcome Cancer Diagnosis Automatic 100% on Exam 2 True Positive: You have cancer and the

test correctly identified your condition. You will receive treatment.

Lose 10 points on Exam 2 False Negative: You have cancer, but the test did not identify your condition. You will not receive treatment.

Lose 1 point on Exam 2 False Positive: You do not have cancer, but the test says you do. You will undergo unnecessary, painful tests.

No effect on Exam 2 score True Negative: You do not have cancer and the test correctly identified that you do not have cancer,

Who Should be Screened?

• According to the American Cancer Society, February 2006, no organization recommends screening for lung cancer in asymptomatic individuals.

• WHY?

Inadequate evidence to determine whether or not screening truly reduces mortality.

Potential Risks of Screening

• Knowing that you have cancer may not improve your health or help you live longer.

• False Negative Results

• False Positive Results

• Side effects of screening process (exposure to radiation)

Lung Cancer: Screening

2 Methods Available:

• Chest X-Ray

• Spiral CT

What are X-Rays???

http://imagine.gsfc.nasa.gov/docs/science/know_l1/emspectrum.html

X-Rays are a type of electromagnetic radiation

Shorter Wavelengths,

Higher Energy

Longer Wavelengths,

Lower Energy

Electromagnetic waves are made up of discrete particles called photons

How Are X-Rays Produced?

http://radiology.med.sc.edu/2prod&use.htm

CathodeAnode

X-Ray Tube

electrons

•Electrons produced at cathode accelerate towards anode.

•Electrons interact with Tungsten atoms producing X-rays via two modes of interaction:

-Bremsstrahlung

-Characteristic Radiation

http://www.colorado.edu/physics/2000/xray/making_xrays.html

How are X-Ray Images Produced?• X-Rays interact with the bone, tissues, and air in the

body.

• These interactions cause a decrease in X-Ray energy called “attenuation.” The amount of X-Ray attenuation is related to the density of the material.

• Mass Attenuation Coefficients (μ/ρ)

Dry Air 0.1541 cm2/g

Lung Tissue 0.1695 cm2/g

Bone 0.1855 cm2/gValues taken at X-Ray energy of 100keV: energy level typical of chest x-rays

Increasing attenuation

Source: http://physics.nist.gov/PhysRefData/XrayMassCoef/tab4.html

How are Chest X-Ray Images Produced?

tumorPatient

http://radiology.med.sc.edu/2prod&use.htm http://www.cancercouncil.com.au/editorial.asp?pageid=48

Image: Chest X-RayDiagram of X-Ray Imaging Setup

Setup of the Chest X-Ray

http://www.radiologyinfo.org/en/photocat/photos_pc.cfm?Image=philip21.jpg&pg=chestrad

Limitations of Chest X-Rays

• Details of soft tissues are hard to resolve

• Some structures (cancers) are too small to be detected.

• Subject to human interpretation (and error).

A New Kind of X-Ray: Low Dose CT (LDCT)

http://www.cqch.org/images/ct_lg.jpg

http://www.radiologyinfo.org/en/photocat/photos_pc.cfm?image=chest-ct-lungs.jpg&&pg=chestct

Limitations of LDCT Scans

• Motion can lessen the quality of the image

• Requires patient to hold their breath for 20 seconds.

• Improved soft tissue detail over conventional X-Ray, but still not great.

Is CT Screening Cost Effective?

• Some scenarios….

1) Annually screen 100,000, 60 yr. old smokers-1 QALY costs $116,300

2) Annually screen 100,000 60 yr. old smokers in the process of quitting.

-1 QALY costs $558,600

3) Annually screen 100,000, 60 yr. old former smokers (quit in last 5 years)

-1 QALY costs $2.3 million!

How does a chest X-ray compare to a LDCT?

• National Cancer Institute Randomized Controlled Trial: The Lung Screening Study

• 3318 Participants

• 30 pack-year history– 1 Pack a day for the last 30 years, 2 packs a day for last 15

years, 3 packs a day for last 7.5 years, etc...

• Participants randomized to receive either a LDCT scan or a Chest X-Ray.

Gohagan,J. Marcus,P. Fagerstrom,R. Pinsky,P. Kramer,B. and Prorok P. Baseline findings of a randomized feasability trial of lung cancer screening with spiral CT scan vs chest radiograph: the lung screening study of the National Cancer Institute. 2004. Chest.126:114-121.

Study Results: CXR vs. LDCT CXR LDCT

# of Participants 1550 1586

# of positive screens 152 (9.8%) 325 (20.5%)

# of people with positive screens that had an additional invasive procedure

15 (10%) 55 (17%)

# diagnosed with cancer

7 (0.45% of total)

30 (1.9% of total)

# of false positives 145 (9%) 295 (19%)

Ongoing Trials• National Cancer Institute: National Lung

Screening Trial• 50,000 participants (former and heavy smokers)• 8 years long (scheduled to end in 2009)• Compare risks and benefits of standard chest x-ray

to LDCT

• Should Produce more definitive screening recommendations

• Local Connection: MD Anderson is one of 30 hospitals participating in this trial.

Your CONFIDENTIAL Test Results

• Second Chance, do you want to choose to be screened?