Cancer Overview

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Cancer Overview
Chapter 1
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Cancer

• Neoplasm-new growth
• Uncontrolled growth
• Proliferation unregulated
• Cancer cells usually do not achieve same level of
  differentiation as normal cells.
• They are autonomous, excessive and disorganized.
• Pg 71 pathology health professions Damjanov 3Ed
  2006

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Definitions

• 1. Cancer
• A large group of diseases characterized by
  uncontrolled growth and spread of abnormal cells.
• 2. Neoplasm or Tumor
• A mass of new tissue growth independent of its
  surrounding structures it has no function.

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Seven Warning Signs of CancerKnow These!

• 1. Change in bowel or bladder habits.
• 2. A sore that does not heal.
• 3. Unusual bleeding or discharge.
• 4. Thickening or lump in breast or elsewhere.
• 5. Ingestion or difficulty in swallowing.
• 6. Obvious change in wart or mole.
• 7. Nagging cough or hoarseness.

CAUTION
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Causes of Cancer

• Chemicals in the environment
• Tobacco smoking is associated with lung cancer
  and bladder cancer.
• Prolonged exposure to asbestos fibers is
  associated with mesothelioma.
• Hundreds of chemicals have been identified as
  carcinogens.

http//en.wikipedia.org/wiki/CancerCauses
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Causes of Cancer

• Ionizing Radiation
• Sources of ionizing radiation, such as radon gas,
  can cause cancer. Prolonged exposure to
  ultraviolet radiation from the sun can lead to
  melanoma and other skin malignancies.
• Infectious Diseases
• Virus - The main viruses associated with human
  cancers are human papillomavirus, hepatitis B and
  hepatitis C virus, Epstein-Barr virus, and human
  T-lymphotropic virus.

http//en.wikipedia.org/wiki/CancerCauses
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Causes of Cancer

• Heredity
• Most forms of cancer are "sporadic", and have no
  basis in heredity. There are, however, a number
  of recognized syndromes of cancer with a
  hereditary component, often a defective tumor
  suppressor allele. Famous examples are
• Breast
• Familial adenomatous polyposis
• (colon caner)
• Retinoblastoma

http//en.wikipedia.org/wiki/CancerCauses
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Changes on a Cellular Level

• Cells out of control
• Proliferating abnormally
• Abnormal daughter cell division
• Mature cells begin to divide
• Differentiation is abnormal
• Tumors are the result of abnormal cell
  proliferationabnormal cell differentiation.
• Cell Differentiation
• The degree to which a cell resembles its cell of
  origin in morphology and function. Cancer cells
  usually do not achieve same level of
  differentiation as normal cells- They are
  autonomous, excessive and disorganized
• Pg 71 pathology health professions Damjanov 3Ed
  2006

http//www.medscape.com/content/2002/00/43/65/4365
33/436533_fig.html
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Genes Involved in Cancer Process

• Protooncogenes
• growth and differentiation (precursors of
  oncogenes).
• Oncogenes
• Cancer genes, associated with abnormal cell
  proliferation.
• DNA MUTATIONS
• -point mutations
• -translocations
• -gene amplification
• Antioncogenes- cancer suppressor genes
• Inactivation of antioncogenes allows the
  malignant process to flourish.

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Tumor Classification

• Anatomical Site
• Cell of Origin
• Biological behavior
• There are a large variety of tumors because
  tumors can originate from any cell type.

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Types of Differentiation

• 1. Well differentiated
• closely resemble the cell of origin
• easily classified by histology
• 2. Undifferentiated
• do not resemble normal cells
• more difficult to classify
• also called anaplastic

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Two Tumor Categories

• Benign-
• usually well differentiated
• Does not metastasize
• Encapsulated
• Slow growing
• Benign tumors usually
• cause little harm
• End in suffixoma

http//db2.photoresearchers.com/search?functionqu
erykeybenign
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Category-cont.

• Malignant-
• Well differentiated to undifferentiated
• Can metastasize or spread to a site in the body
  distant from the primary site
• Often invade/destroy normal tissue
• If left untreated can cause death

http//db2.photoresearchers.com/search?functionqu
erykeymalignant
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General Characteristics
Know this chart!!!!!!!!!
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Cancer Names

• Sarcomas- tumors arise from mesenchymal cells
  cartilage, bone, muscle. From cells other than
  epithelial.
• Example Chondrosarcoma or sarcoma of cartilage
• Carcinomas- from epithelium cells. All tissues
  that cover a surface or line a cavity.
• Example Squamous cell carcinoma of the lung is a
  tumor originating from the lining of the lung.
• Adenocarcinoma- tumors arising from epithelial
  cells that are glandular.
• Example Lining of stomach is adenocarcinoma of
  the stomach.

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Classifications of Neoplasms
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Histologies

• Site most common histology
• Oral cavity.. squamous cell carcinoma
• Pharynx.. squamous cell carcinoma
• Lung squamous cell carcinoma
• Breast . infiltrating ductal carcinoma
• Colon/Rectal.. adenocarcinoma
• Anus squamous cell carcinoma
• Cervix. squamous cell carcinoma
• Endometrium. adenocarcinoma
• Prostate.. adenocarcinoma
• Brain astrocytoma

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Cancer Outlook

• See Handout American Cancer Society 2007
• Five leading Cancer sites for Male/Female
• Five Leading Causes of Death for Male/Female

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Cancer Death Rates, for Women, US,1930-2003
Rate Per 100,000
Lung bronchus
Uterus
Breast
Colon rectum
Stomach
Ovary
Pancreas
Age-adjusted to the 2000 US standard
population. Source US Mortality Public Use Data
Tapes 1960-2003, US Mortality Volumes
1930-1959, National Center for Health Statistics,
Centers for Disease Control and Prevention, 2006.
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Cancer Death Rates, for Men, US,1930-2003
Rate Per 100,000
Lung bronchus
Stomach
Prostate
Colon rectum
Pancreas
Liver
Leukemia
Age-adjusted to the 2000 US standard
population. Source US Mortality Public Use Data
Tapes 1960-2003, US Mortality Volumes
1930-1959, National Center for Health Statistics,
Centers for Disease Control and Prevention, 2006.
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2007 Estimated US Cancer Deaths
ONSOther nervous system. Source American Cancer
Society, 2007.
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Trends in the Number of Cancer Deaths Among Men
and Women, US, 1930-2004
Men
Men
Women
Women
Number of Cancer Deaths
Source US Mortality Public Use Data Tape, 2004,
National Center for Health Statistics, Centers
for Disease Control and Prevention, 2006.
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Etiology-study of cause of diseases

• What causes cancer?
• Not really known, but we do know many
  agents/factors that are more likely to cause
  cancer.
• If we know the etiology we can develop
  educational programs.
• Prevention stop smoking, sunscreen, asbestos
• Identify target populations.
• American Cancer Society -mammogram guidelines
  -early detection.
• HPV vaccine.

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Epidemiology

• The study of disease incidence.
• Statistical databases identifying patterns of
  cancer occurrence.
• Researchers use this information and determine
  incidence of cancer in a general population.
• Use factors such as age,gender, race,
  geographical location.

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Detection/Diagnosis

• Signs and symptoms
• Is early detection important? Why?
• How does it influence survival?
• Lung cancer
• Throat cancer
• Ovarian cancer

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Screening Work -ups

• Screening Workups
• Mammogram MRI
• Pelvic exam Bone Scan
• Rectal exam Nuclear Med
• Blood tests-PSA Biopsy
• HPV Pap smear

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Screening Tests for Cancer Detection

• What is the purpose of screening tests?
• Give some examples of screening tests
• Are there screening tests for all types of
  cancer?
• What do sensitivity/specificity mean?
• What does false-positive and false negative mean?
• What factors are considered for screening tests
  to be useful?
• 1. 2.
• 3. 4.

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The waiting begins

• Diagnostic exams begin once a tumor is suspected.
• The work up will
• Provide the general health status of the pt
• Type of tumor, location, size, amount of tissue
  involved, Lymph node involvement ,metastasis
• Workups vary depending on the type of tumor
  suspected
• Lung, breast, prostate, colon

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Types of Diagnostic Exams

• Chest x-ray
• CT
• Colonoscopy
• MRI
• US

Normal Chest X-ray
MRI of Glioblastoma Multiforme
http//db2.photoresearchers.com/search?keytumorp
g2
Lung Cancer
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Biopsy Methods

• What is a biopsy?
• How do we get the tissue sample?
• Fine need aspiration
• Core needle
• Endoscopic
• Incisional
• Excisional

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How Big Is It, Has it Spread and How Far ?

• What is cancer staging?Cancer staging describes
  how much and where the cancer is located. The
  more cancer there is in the body, the more likely
  it is to spread and less likely that treatments
  will work.
• The more advanced stages can affect long-term
  results and survival
• What are some examples of staging systems?
• FIGO, Dukes, AJCC, TNM
• See Figure 1-3, pg 9

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Staging- Defining Tumor Size and Extension at
Point of Diagnosis

• Reason its important
• -provides a means of communication about tumors
• -provides a basis for comparison between tumors
• -helps in determining best treatment
• -Aids in predicting prognosis
• -provides a means for continuing research
• As technologies advance staging systems change
• TNM- is the current staging system used by the
  International Union Against Cancer and American
  Joint Committee on Cancer

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Staging
www.vh.org/.../Staging/ Images/TNM008.jpg
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http//www.kjronline.org/abstract/journal_figure.a
sp?imgv6n1008table1.jpgno406descdesc1
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TNM StagingTTumor, NNode, MMetastasis

• T-size and extent of primary tumor is assigned a
  number 0-4
• T0( zero)-no evidence of disease
• T1-confined to organ of origin, not invading
  other tissue
• T2-Deep extension into nearby structures or
  tissues
• T3-Confined to region of origin, rather than
  organ.
• T4-massive lesion extending into other tissues
  and organs causing fistulas in hollow organs and
  making a sinus in solid organs.

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Nnode Designates the status of lymph nodes and
the extent of lymph node involvement

• 0-4 designates the status of lymph nodes and the
  extent of lymph node involvement.
• N0 (zero)- no positive nodes are present.
• N1-palpable movable nodes in first drainage
  station the same site of the tumor (1-2 cm).
• N2-larger nodes 3-5 cm invading into capsule.
• N3-Nodes are fixed to bone, muscle, skin, or
  blood vessels usually 6 cm in size.
• N4- Positive nodes at more distant nodal sites
  beyond first station.

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MMetastasis, the presence and/or extent of.

• M0(zero) no metastasis
• M1- One metastasis in one organ or site
• M2-multiple metastatic lesions in one organ
  system.
• M3- Multiple organs involved with little or no
  impairment of function.
• M4- Multiple organs with impairment of function.
• MX unable to access
• Large numbers are more advanced
• Many more staging systems, but TNM is widely used.

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Gradeprovides info about the tumors
aggressiveness

• Grade is based on the degree of differentiation
  (histology).
• Grading can also be described as the degree of
  malignancy.
• G1-Well differentiated
• G2-Moderately well differentiated
• G3- Poorly differentiated
• G4- Very poorly differentiated
• The degree of malignancy is determined by the
  proportion of poorly differentiated to well
  differentiated cells.
• The more undifferentiated a tumor is the more
  likely it is to metastasize.
• Differentiation may be different throughout the
  tumor.

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Grade

• What does a tumors grade tell us?
• How is a tumors grade determined?
• For some tumors, for example brain tumors, grade
  is the most important prognostic factor. GBM or a
  high-stage astrocytoma.

http//db2.photoresearchers.com/search?keytumor
pg2
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More Grading Information

• http//cis.nci.nih.gov/fact/5_9.htm

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Grading Staging

• Together, the stage and grade offer an accurate
  picture of the tumor and its behavior.
• This allows physicians to make better, more
  effective, treatment decisions

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Treatment Decisions

• What are tumor boards?

http//www.danhosp.org/cancer/cancer_boards.jpg
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Treatment Options

• Surgery
• Radiation Therapy
• Chemotherapy
• Biotherapy(Immunotherapy)
• All of these modalities can be used to cure the
  patient or, with the exception of biotherapy, can
  be used for palliation.

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Surgery

• Surgery
• Diagnosis
• Biopsy-breast
• Staging-ovarian
• Treatment
• Alone- It is limited by tumor accessibility,
  patients medical condition, tumors extent
• In combination with other modalities-RT and/or
  chemo
• Cure or palliative goals

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Radiation Therapy

• Can be used alone or in combination with other
  modalities 50 of all cancer patients receive
  RT
• Cure and palliation
• Can preserve organ function - larynx,
  prostate-less impotence and incontinence than
  surgery
• Better Cosmesis-skin cancers
• Limited by critical structures
• Patient must be able to endure treatment

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Chemotherapy

• Emerging field only used for 30 years
• Chemotherapeutic drugs are administered orally,
  injected, intraarterially (infusion pump),
  intracavitary, intraperitoneal, intrathecal
  (space containing CSF) Can be used alone or in
  combination with surgery and RT
• Combinations of drugs are usually used vs. single
  agents
• Combination of drugs kill cells in different
  phases of the cell cycle
• Limited by amount of normal cell death
• What do therapists have to be careful of with
  patients on chemo?

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Biotherapy (Immunotherapy)

• Uses the bodys own immune system
• B and T cells are natural killer cell lymphocytes
  
• B cells
• Produce protein molecules or antibodies that
  attack and destroy foreign substances such as
  cancer
• T cells
• Mature into killer cells once they make contact
  with the antigen on a foreign substance

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Biotherapy (Immunotherapy)

• Natural killer cells
• Spontaneously attack and kill foreign substances
• Monoclonal antibodies
• Produced to react to a specific antigen
• Cytotoxic agent can be attached-more cell kill
  action
• Interferons
• Naturally occurring proteins that can kill cancer
  cells
• Can help identify the antigen of cancer cells
• Interleuken-2 (IL-2)
• Stimulate more T cell production (killer cells)

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Prognosis

• an estimation of life expectancy based on all
  information about the tumor and from tumor trials
  
• Prognosis is only an estimate
• Plays a role in the treatment plan
• Since the goal of treatment is to cure or to
  relieve symptoms while preserving quality of
  life, the prognosis helps assure this.

Five Year Survival Rule-If a patient is disease
free for 5 years , he/she is considered cured.
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Spread Patterns

• Growth characteristics and spread patterns have
  important prognostic implications
• Tumors that stay localized are more easily
  treated and have a better prognosis than those
  that are diffuse or spread to distant sites.

Tonsil gland cancer
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How does Cancer travel?

• Blood-can travel to distant sites
• Lymphatics-travel to distant sites
• Seeding
• cells break off from the primary tumor and spread
  to new sites and grow

Lymph node, drawing
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Common Metastatic Sites of Primary Tumors (Table
1 -7)
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Prognostic Factors

• Tumor Related Factors
• Grade
• Tumor size
• Status of lymph nodes
• Depth of invasion
• Histology

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How will your patient do?

• What is the term to describe how a patient is
  expected to do (life expectancy)?
• Is it 100 accurate?
• How does the prognosis affect the treatment plan?
• What is the overall treatment goal?
• How does the pattern of spread affect the
  prognosis?
• What are the 3 ways that cancer spreads?
• How does grade, stage, tumor size, status of LN,
  depth of invasion affect prognosis?

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Prognostic Factors

• Patient related
• Age
• Gender
• Race
• Medical conditions
• Prognostic factors will have different levels of
  importance with different tumors.

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Clinical Trials

• Patients participate in cancer studies
• Can be done at a single institution or many
  institutions
• The more participants in the study the more
  meaningful the results
• Often multidisciplinary studies

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Types of Studies

• Retrospective - review of patients who were
  treated in the past. Advantage quick retrieval
  of information on a national basis.
  Disadvantage information may be incomplete.
• Prospective - the study is planned prior to
  admitting patients. Advantage more complete
  records. Disadvantage Takes along time to
  complete(5 yrs)
• Phase I-to determine max tolerated dose-acute or
  long term toxicity
• Phase II-is it effective at dose decided in phase
  I
• Phase III-used to compare against standard
  treatment in random trials
• Randomized studies-patients who have the same
  type of disease can randomly be selected to
  receive different treatment. Selection into the
  study is random.

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Survival Reporting

• Endpoint of a study must be decided
• Rates of survival at the endpoint is one data
  set collected in studies
• Methods of survival reporting
• Absolute
• Those who are alive are counted and those who
  died are counted. There is no account for those
  patients who do not follow-up or die from other
  causes.
• Adjusted survival reporting
• Includes patients who died from other causes
• Relative survival reporting
• Takes into account normal survival rate for age,
  gender and race

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Survival Reporting

• Also important are if the patient failed
• locally
• regionally
• distally
• if they died were they disease free (NED) ?
• alive or dead with/out disease

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Additional Facts

• http//cis.nci.nih.gov/fact/5_32.htm