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Lung Cancer.

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1 Lung Cancer

2 Summary: Content of Lung Cancer Tutorial
∙Statistics in the United States ∙Anatomy of the lungs and respiratory system ∙Lung cancer types ∙Lung cancer progression ∙Staging ∙Symptoms ∙Risk factors / risk reduction factors ∙Screening ∙Treatment ∙Clinical Trials ∙Current state of lung cancer research ∙References

3 Summary: Statistics ∙ Statistics in the United States
∙Incidence by race ∙Death by race ∙Incidence according to geographical location ∙ Death according to geographical location ∙ Comparison of incidence and death rates between men and women

4 Top Ten Cancers in the U.S. Lung Cancer Statistics
Lung cancer is the leading cause of cancer death among men and women ∙ 60% of all people diagnosed with lung cancer die within one year ∙ 1 in 12 men will be diagnosed with lung cancer, and a 1in 16 women ∙16% of people diagnosed with non-small call lung cancer survive to 5 years ∙Survival rate has remained steady 10 years ∙6.95% of people born today will be diagnosed with lung cancer ∙ 70% of lung cancers are diagnosed after the age of 60 89,575 68,431 108,355 87,897

5 Lung Cancer Incidence According to Race in the U.S.
∙ Currently the highest incidence rate among African Americans ∙ Caucasians> American Indian/Alaskan Natives Asians/ Pacific Islanders > Hispanics

6 Lung Cancer Death According to Race in the U.S.
∙ Death rate highest among African Americans. ∙ Caucasians> American Indians/Alaskan natives > Asians/Pacific Islanders > Hispanics

7 Lung Cancer Incidence- Geographical Location in the U.S.
∙ Lowest Incidence in UT, and NM ∙ Highest Incidence in WV, KY and TN ∙ Colorado is in the lowest bracket for incidence.

8 Lung Cancer Deaths- Geographical Location in the U.S.
∙ Death rate does not perfectly correlate with incidence rate ∙ Lowest death rates in UT and NM ∙ Highest death rates are in MO, AR, LA, WV, KY, TN and MS ∙ Colorado is in the lowest bracket for death rate

9 Lung Cancer Rates for Men
∙ Rates for both death and mortality is ↓ for men.

10 Lung Cancer Rates for Women
∙ From 1975 – 2000 both incidence and death rates ↑. ∙ Rates appear to be leveling off.

11 Summary: Content of Lung Cancer Tutorial
∙Statistics in the United States ∙Anatomy of the lungs and respiratory system ∙Lung cancer types ∙Lung cancer progression ∙Staging ∙Symptoms ∙Risk factors / risk reduction factors ∙Screening ∙Treatment ∙Clinical Trials ∙Current state of lung cancer research ∙References

12 Summary: Anatomy of the Lungs and Respiratory System
∙ Basic Respiratory Anatomy ∙ Detailed anatomy of the lungs ∙ Lung function

13 Basic Respiratory Anatomy
∙Food and air pass through the pharynx ∙ Air then passes through the larynx and down through the trachea into the lungs Lungdisease.about.com

14 Detailed Anatomy of the Lungs
∙ Trachea leads to the bronchi (carina is where the trachea splits into the right and left bronchi) (not shown) ∙ Bronchi go to secondary and tertiary bronchi ∙ Tertiary bronchi lead to the bronchioles ∙ Bronchioles end with alveoli

15 Lung Function ∙ Oxygen enters through mouth/nose ∙ Travels to the lungs ∙ Oxygen extracted and sent through body via the blood stream ∙ Carbon dioxide brought to lungs via blood stream and exhaled

16 Summary: Content of Lung Cancer Tutorial
∙Statistics in the United States ∙Anatomy of the lungs and respiratory system ∙Lung cancer types ∙Lung cancer progression ∙Staging ∙Symptoms ∙Risk factors / risk reduction factors ∙Screening ∙Treatment ∙Clinical Trials ∙Current state of lung cancer research ∙References

17 Summary: Lung Cancer Types
· How lung cancer is classified · Types of lung cancers · Non-Small Cell Lung Cancer (NSCLC) · Types of NSCLC · Small Cell Lung Cancer (SCLC) · Types of SCLC

18 Classification of lung cancer
· There are 2 major types of lung cancers : non-small cell (NSCLC) and small cell (SCLC) · These groups are further divided · Classification of the cancer is done by the types of cells it occurs in · Cell types are defined by the shape seen under a microscope ↑ cancerous tumor shown in x-ray

19 Lung Cancer (2 Major Types) ↙ ↘
↙ ↘ Non-small cell lung cancer (NSCLC) ↓ ↓ major types minor types ↓ ↓ Small-cell lung cancer (SCLC) 3 types Small-cell carcinoma Mixed small-cell / large-cell carcinoma Combined small-cell carcinoma Squamous cell carcinoma Adenocarcinoma Large-cell undifferentiated carcinoma Pleomorphoic Carcinoid tumor Salivary gland carcinoma Unclassified carcinoma SCLC cells   NSCLC cells

20 Non-Small Cell Lung Cancer (NSCLC)
∙ 80% of lung cancers are NSCLC ∙ 3 main subtypes of NSCLC ∙ At least 4 other less common types of NSCLC Non-small cell lung cancer (NSCLC) ↓ ↓ 3 major types minor types ↓ ↓ Squamous cell carcinoma pleomorphic Adenocarcinoma carcinoid tumor Large cell undifferentiated Salivary gland carcinoma carcinoma 4. unclassified carcinoma

21 Squamous Cell Carcinoma
∙ 25% - 30% of all lung cancers ∙ Also called epidermoid cancer ∙ Found in the middle of the lungs near the bronchi · Linked to smoking Non-small cell lung cancer (NSCLC) ↓ ↓ 3 major types minor types ↓ ↓ Squamous cell carcinoma pleomorphic Adenocarcinoma carcinoid tumor Large cell undifferentiated Salivary gland carcinoma carcinoma 4. unclassified carcinoma

22 Adenocarcinoma Non-small cell lung cancer (NSCLC) ↓ ↓ 3 major types minor types ↓ ↓ Squamous cell carcinoma pleomorphic Adenocarcinoma carcinoid tumor Large cell undifferentiated Salivary gland carcinoma carcinoma 4. unclassified carcinoma ∙ 40% of all lung cancers ∙ Also called bronchiolalveaoar adenocarcinoma ∙ Typically found in the outer parts of the lung · Begins in the cells that line the alveoli · Makes substances such as mucus · Have better prognosis than those with other lung cancer types

23 Large cell Undifferentiated Carcinoma
∙ 10% - 15% of all lung cancers ∙ May begin in several types of large cells · May appear in any part of the lung · Grows and spreads quickly · Poor prognosis Non-small cell lung cancer (NSCLC) ↓ ↓ 3 major types minor types ↓ ↓ Squamous cell carcinoma pleomorphic Adenocarcinoma carcinoid tumor Large cell undifferentiated Salivary gland carcinoma carcinoma 4. unclassified carcinoma

24 4 Minor Types Of Non-Small Cell Lung Cancer (NSCLC)
∙ All four types account for < 5% of all lung cancers Non-small cell lung cancer (NSCLC) ↓ ↓ 3 major types minor types ↓ ↓ Squamous cell carcinoma pleomorphic Adenocarcinoma carcinoid tumor Large cell undifferentiated Salivary gland carcinoma carcinoma 4. unclassified carcinoma

25 Small Cell Lung Cancer (SCLC)
3 Types Small cell carcinoma Mixed small cell / large cell carcinoma Combined small cell carcinoma · Accounts for 10-15% of all lung cancers · Almost always caused by smoking · Starts in the bronchi near the center of the chest · Grows and spreads rapidly · Surgery must be combined with other treatments · Rarely cured by current treatments · Patient usually dies within 1-2 years

26 Small cell Carcinoma SCLC ↓ 3 types Small cell carcinoma
Mixed small cell / large cell carcinoma Combined small cell carcinoma · Also called oat cell carcinoma or small cell undifferentiated carcinoma · 4-19% of small cell carcinomas · Less sensitive to chemo and radiation therapy than small cell carcinoma alone · Made of small cell and squamous cell lung cancer cells or small cell and adenocarcinoma cells

27 Lung Cancer (2 Major Types) ↙ ↘
↙ ↘ Most common Almost always caused by smoking Non-small cell lung cancer (NSCLC) ↓ ↓ major types minor types ↓ ↓ Small-cell lung cancer (SCLC) 3 types Small-cell carcinoma Mixed small-cell / large-cell carcinoma Combined small-cell carcinoma 80% all lung cancers <5% all lung cancers 10%-15% all lung cancers 1-2 year survival Squamous cell carcinoma (Smoking) Adenocarcinoma (Better prognosis) Large-cell undifferentiated carcinoma (Poor Prognosis) Pleomorphoic Carcinoid tumor Salivary gland carcinoma Unclassified carcinoma

28 Summary: Content of Lung Cancer Tutorial
∙Statistics in the United States ∙Anatomy of the lungs and respiratory system ∙Lung cancer types ∙Lung cancer progression ∙Staging ∙Symptoms ∙Risk factors / risk reduction factors ∙Screening ∙Treatment ∙Clinical Trials ∙Current state of lung cancer research ∙References

29 Summary: Lung Cancer Progression
· Cancer · Metastasis Begins at a primary site Spread to near by areas (lymph nodes) Metastasizes to distant areas in the body Academic.evergreen.edu

30 Cancer · Lung cancer occurs when lung cells begin to grow and divide without control ∙ Lung cancer is caused by mutations within the DNA in the lung, mutations are typically caused by carcinogens ∙ Carcinogens are chemicals that have been show to cause mutations in DNA that can result in damage to “cancer genes” Cancerous lung tumor

31 Metastasis lung cancer that has metastasized to the brain · Metastasis occurs when the cancer cells enter the blood stream or lymphatic system and replace normal cells in other tissues · Lung cancer that has spread to another organ is still lung cancer · Cancer that has spread to the lungs from another tissue is not lung cancer

32 Summary: Content of Lung Cancer Tutorial
∙Statistics in the United States ∙Anatomy of the lungs and respiratory system ∙Lung cancer types ∙Lung cancer progression ∙Staging ∙Symptoms ∙Risk factors / risk reduction factor ∙Screening ∙Treatment ∙Clinical Trials ∙Current state of lung cancer research ∙References

33 Summary: Staging of Lung Cancer
· Staging of NSCLC · T categories · N categories · M categories · Stage grouping · Staging of SCLC

34 Staging of NSCLC · Staging is a standardized way to describe the extent to which the cancer has spread · The lung cancer type as well as the stage determines treatment as well as prognosis · NSCLC is staged using the AJCC/TNM system · Category: T category, N category or M category

35 T, N, and M Categories; Stage Grouping
T- T stands for tumor; describes the size of the tumor and how far it has spread in the lung and to near by organs N- N stands for spread to Lymph Nodes (small bean like structures that produce white blood cells as well as filter bacteria and other particles, also called lymph glands) M- stands for Metastasis Stage Grouping T: Tis- T4 N: N1-N4 M: M0-M1

36 Stage Grouping · Lower stage / group = better prognosis Group
T,N,M categories 5 year survival % Tis (Carcinoma in situ), N0, M0 IA T1, N0, M0 62% IB T2, N0, M0 38% IIA T1, N1, M0 34% IIB T2, N1, M0 / T3, N0, M0 24% IIIA T1-2, N2, M0 / T3, N1-2, M0 13% IIIB T4, any N, M0 / any T, N3, M0 5% IV Any T, any N, M1 1%

37 Staging of SCLC · 2 stage system Limited stage- cancer is contained to 1 lung and the lymph nodes on the same side Extensive stage- cancer has spread to other lung, or lymph nodes on the other side of the chest, or to distant organs

38 Summary: Content of Lung Cancer Tutorial
∙Statistics in the United States ∙Anatomy of the lungs and respiratory system ∙Lung cancer types ∙Lung cancer progression ∙Staging ∙Symptoms ∙Risk factors / risk reduction factors ∙Screening ∙Treatment ∙Clinical Trials ∙Current state of lung cancer research ∙References

39 Summary: Symptoms · Symptoms · Early and late disease symptoms

40 Symptoms ∙ Most people do not experience symptoms until the cancer has spread to far to be cured ∙ Many of the symptoms are common to other diseases, only a doctor can determine if lung cancer is the cause ∙ Symptoms are the same for both NSCLC and SCLC

41 Possible Early and Late Disease Symptoms
Possible Early Symptoms Possible Late Symptoms (metastasis) · Cough that doesn’t go away · Chest pain; aggravated by deep breathing, coughing or laughter · Hoarseness · Weight loss / appetite loss · bloody / rust colored phlegm or spit · Reoccurring bronchitis / pneumonia ·Wheezing · Bone pain · Neurological changes: headache, weakness/numbness of limbs, dizziness, seizures · Jaundice · Visible masses from cancer spreading to skin or lymph nodes

42 Summary: Content of Lung Cancer Tutorial
∙Statistics in the United States ∙Anatomy of the lungs and respiratory system ∙Lung cancer types ∙Lung cancer progression ∙Staging ∙Symptoms ∙Risk factors / risk reduction factors ∙Screening ∙Treatment ∙Clinical Trials ∙Current state of lung cancer research ∙References

43 Summary: Risk Factors / Risk Reduction Factors
· Risk Factors · Smoking and Lung Cancer Statistics Healthguide.howstuffworks.com

44 Risk Factors Risk Factors
Radon Levels in the U.S. Risk Factors · Smoking · Asbestos · Radon gas (Test home for ↑ levels) · High levels of arsenic in drinking water · Carcinogens found in the workplace · Radiation treatment to the lungs/chest ·Personal / family history (usually related to smoking) ·Air pollution Pink= ↑Radon levels Yellow= ↓ Radon levels southmetro-ppi.com static.howstuffworks.com

45 Smoking and Lung Cancer Statistics
· People who smoke are X more likely to die from lung cancer · 90% of lung cancer deaths in men and 80% in women are caused from smoking · Cigarettes contain > 4000 chemicals, at least 43 of which are carcinogenic · Quitting smoking will ↓ risk for lung cancer ∙ The more cigarettes smoked and the longer a person smokes ↑ risk for lung cancer

46 Summary: Content of Lung Cancer Tutorial
∙Statistics in the United States ∙Anatomy of the lungs and respiratory system ∙Lung cancer types ∙Lung cancer progression ∙Staging ∙Symptoms ∙Risk factors / risk reduction factors ∙Screening ∙Treatment ∙Clinical Trials ∙Current state of lung cancer research ∙References

47 Summary: Screening ∙ Imaging Tests ∙ Chest x-ray, CT, MRI, and PET scan ∙ Bone scan ∙ Screening sampling tissues or cells ∙ Sputum cytology, Blood counts/ blood count chemistry ∙ Bronchoscopy, Mediastinoscopy, ∙ Needles Biopsy, Thoracentesis

48 Imaging tests ∙ Imaging tests are non-invasive procedures ∙ Chest X-ray is often the first test performed ∙ CT Scan takes many cross sectional x-ray images and combines them into a detailed image ∙ MRI uses radio waves and strong magnets to produce a detailed image ∙ PET uses a small amount radioactive glucose injected in a vein (Cancer cells absorb large amounts of sugar) ∙ Bone Scan Similar to PET but bone absorbs radioactive substance MRI PET MRI/PET

49 Screening Sampling Tissues or Cells
∙ Screening sampling tissues or cells require a sample from the area of the lung that the cancer is found in ∙ The sample is examined for cancer cells by a pathologist ∙ One or more of the tests will be used to confirm cancer found from an imaging test ∙ Used to determine the type of cancer, and if it may have spread ∙ Often more invasive Bronchoscopy ↑  Biopsy Farm1static.flickr.com

50 Sputum Cytology, Blood Counts/ Blood Count Chemistry (CBC)
∙ Sputum cytology is performed by sampling phlegm that is collected over a few days for cancer cells ∙ CBC is often used after treatment has begun ∙ CBC can detect high levels of LDH, an indicator that cancer has spread to the liver and bones (poor prognosis) Human lung tissues that are stained with florescent dye and placed under a microscope

51 Bronchoscopy, Mediastinoscopy, Needle Biopsy, Thoracentesis
∙ Bronchoscopy: Bronchoscope is inserted through the mouth into the bronchi to test for tumors and blockages, other tips are often placed ∙ Mediastinoscopy requires a small incision to be made in the neck, and a tube is then inserted behind the sternum ∙ Needle Biopsy: Needle is inserted into the lungs and a tissue sample is taken ∙In Thoracentesis and Thoracoscopy a needle is inserted between the ribs to test if fluid build up in the pleura is from cancer  Mediastinoscopy Needle Biopsy  drkawley.com  Thoracentesis

52 Summary: Content of Lung Cancer Tutorial
∙Statistics in the United States ∙Anatomy of the lungs and respiratory system ∙Lung cancer types ∙Lung cancer progression ∙Staging ∙Symptoms ∙Risk factors / risk reduction factors ∙Screening ∙Treatment ∙Clinical Trials ∙Current state of lung cancer research ∙References

53 Summary: Treatment ∙ Definition of treatment types ∙ Treatment side effects ∙ Treatment for cancer types Lung Cancer ↙ ↘ ↓ ↓ ↓ ↓ Non Small Cell Lung Cancer (NSCLC) Small Cell Lung Cancer (SCLC) 3 major types 4 minor types 3 types  NSCLC cells AJCC/TNM staging system Limited and extensive stage SCLC cells 

54 Definitions of Treatment Types
∙ Surgery- A lobe of the lung may be removed (lobectomy), the entire lung may be removed (pneumonectomy), or a potion of the lung may be removed (segmentectomy), lymph nodes may also be removed ∙ Radiation Therapy- High energy waves rays (X-rays) are targeted toward the cancer either externally (external beam radiation therapy) or internally through a bronchoscope (brachytherapy) ∙ Chemotherapy- Anticancer drugs are given intravenously or orally over day cycles for 6-8 cycles ∙ Targeted therapy- Newer drugs that specifically target cancer cells, are usually given after chemo has failed ∙ Antiangiogenesis- drugs that block growth of new blood vessels , cause bleeding and can not be used for squamous cell cancer, cancer metastasized to the brain , people coughing up blood, or blood thinners

55 Treatment Side Effects
∙ Surgery- can only be performed on relatively healthy patients, pain, ↑ risk pneumonia and bleeding (only used for NSCLC) ∙ Radiation- mild skin problems, nausea, vomiting, fatigue, and can increase side effects of chemotherapy; used to treat primary lung cancer ∙ Chemotherapy- kill normal cells as well as cancer cells, nausea, vomiting, loss of appetite, loss of hair, mouth sores, severe diarrhea, ↑ risk of infection,↑ risk of bleeding/bruising and ↑ risk for fatigue; not used in poor health. Platinum based drugs (cisplatin and carboplatin) are common treatments, as well as combination therapies. ∙ Targeted therapy- skin rash and diarrhea ∙ Antiangiogenesis- bleeding; combined with chemo in advanced lung cancer www-tc.pbs.org

56 Treatment for Cancer Types
Good health Poor health metastasis Side effects NSCLC SCLC Surgery X * Radiation Chemo (drugs) Targeted Antiangiogenesis *Surgery is rarely performed on patients with SCLC, only about 1 in 20 cases SCLC treatment may also include Adjuvant Treatment, treatment such as radiation to areas where cancer may not have been detected (brain) to prevent metastasis Each X indicates the treatment is an option

57 Summary: Content of Lung Cancer Tutorial
∙Statistics in the United States ∙Anatomy of the lungs and respiratory system ∙Lung cancer types ∙Lung cancer progression ∙Staging ∙Symptoms ∙Risk factors / risk reduction factors ∙Screening ∙Treatment ∙Clinical Trials ∙Current state of lung cancer research ∙References

58 Summary: Clinical Trials
Drug Developed Laboratory Testing Clinical Trials ( I, II, III,) Statistical Analysis Submission to FDA Acceptance ∙ Definitions Stage I, II, III, and IV clinical trials

59 Clinical Trials ∙ Purpose is to test if a new and promising treatment will be valuable to patients ∙ Treatments often have real benefits Trial Stage Purpose I How a new treatment is best administered and what is the highest dose before side effects appear II To analyze if the drug works at the dosage found from stage I; side effects are still being examined III Involves many people (>100), a control group (receiving only standard treatment); if side effects are to great or one group is doing much better the study will end IV After approval by the FDA, studies conducted to make sure the drug is safe and effective

60 Summary: Content of Lung Cancer Tutorial
∙Statistics in the United States ∙Anatomy of the lungs and respiratory system ∙Lung cancer types ∙Lung cancer progression ∙Staging ∙Symptoms ∙Risk factors / risk reduction factors ∙Screening ∙Treatment ∙Clinical Trials ∙Current state of lung cancer research ∙References

61 Summary: Current State of Lung Cancer Research
∙ Chemoprevention ∙ Biological Therapy ∙ New Combinations jnci.oxfordjournals.org

62 Lung Cancer Research Research type Chemoprevention
Drugs that ↓ risk for developing lung cancer, or ↓ risk for lung cancer reoccurring *Biological Therapy/ Immunotherapy Substances that ↑ the body’s own immune system to fight and destroy cancer cells New Combinations New combinations of drugs or therapy types that may be more effective in treating lung cancer *Gene Therapy Genes are inserted into the patient to give healthy copies of damaged cancer causing genes, help to target cancer cells for therapy, increase immune response, kill cancer cells, or to inhibit the cancer cell’s ability to form new blood vessels necessary for growth *These are not yet in clinical trails

63 Summary: Content of Lung Cancer Tutorial
∙Statistics in the United States ∙Anatomy of the lungs and respiratory system ∙Lung cancer types ∙Lung cancer progression ∙Staging ∙Symptoms ∙Risk factors / risk reduction factors ∙Screening ∙Treatment ∙Clinical Trials ∙Current state of lung cancer research ∙References

64 References genesdev.cshlp.org hmg.oxfordjournals.org Molecular Biology in Medicine; Timothy M. Cox, John Sinclair Quick Facts: Lung Cancer What You Need to Know Now; American Cancer Society; 2007 Holland-Frie Manual of Cancer Medicine; Brown, Rini, Connell, Posner; 2005


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