Transcript Principles of Onc

Principles of Oncology
Jeffrey T. Reisert, DO
University of New England
Physician Assistant Program
25 FEB-4 MAR 2010
Case
• A 55 y/o male “new patient” comes in
for a routine physical.
• They ask you to order “all the cancer
blood tests so they will know if they
are going to get cancer”
• They tell you that many of their
aunts, uncles, and cousins have had
assorted different cancers.
Case questions
• What are they talking about? Cancer
blood test? PSA? Something else?
• What family history is significant?
• What do you advise them?
Objectives
• Understand general approach to
cancer evaluation and treatment
• Given a case in common cancers,
such as lung, breast, colon, prostate,
and skin, select a treatment plan for
diagnosis, work up and treatment
Overview
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Diagnosis
Staging
Further testing and work up
Treatment planning
Screening for cancers
Approach to lung, breast, prostate,
colon, and skin cancers
Cancer
• Single clone of cells
• Autonomous growth-Unregulated
– Apoptosis (pre-programmed cell death) lost
• Anaplastic-Abnormal differentiation
• Metastatic-Spread
Growth
• Growth is unregulated
• Cancer growth usually slows when
tumors become large
• Not a constant doubling time
• At least in part due to blood supply
Etiology of Cancer
• Not completely understood
• Involves a predisposition (Genetics)
• Environmental role
Genetic role
• Oncogenes
– Tumor growth stimulated by presence of gene
• Tumor suppresser genes
– These genes if present prevent malignant growth. Involved in
preprogrammed cell death (apoptosis)
– If absent, increased risk of malignancy as cells don’t die
– Example is mutant p53 gene
• P53 is a tumor suppressor protein controlling cancer and aging
• Mutant gene if present puts cells at risk for uncontrolled
growth
Genetics II
• Many family members may be at risk
– Familial polyposis syndromes in colon cancer
– Multiple endocrine neoplasia (MEN
syndromes)
• Can be transmitted via viruses
– HTLV-I causes T cell lymphoma transported
by retrovirus
Family history?
• You can pick your friends but you
can’t pick your relatives
• Primary relatives?
–P
–S
– O/C
Environmental
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Radiation
Carcinogens such as tobacco
Viruses
Diet
Obesity (next slide)
Previous chemotherapy
Obesity in cancer
• Associated in men
with 14% of cancer
deaths including:
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Liver
Pancreas
Stomach
Esophagus
Colon/Rectal
Gallbladder
• Associated in
women with 20% of
cancer deaths
including
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Uterus
Kidney
Cervix
Pancreas
Esophagus
Tobacco
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Oral
Pharynx/Larynx
Lung
Esophagus
Renal Cell
Breast
Ovary
Problems with cancer
• Direct effect-Invasion
• Indirect
– Cytokines, TNF, Hormonal, Metabolic
• Psychological
• Stigma
• Death
Spread patterns
• Direct
• Lymph/ nodes
• Hematogenous after spreading
through a vessel
• Through serous cavities after exiting
an organ
Diagnosis of cancer
• Kills 25% of Americans (#2 to
cardiovascular diseases when
totaled)
• Common patterns of disease
Common patterns of disease
• History
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Age
Sex
Family History
Social History
• Physical
Examples
• Klinefelter’s syndrome-Male breast
cancer
• Mother with breast cancer
• Daughters of DES mothers-Vaginal
cancer
• Asbestos-Mesothelioma
• Reflux with Barrett’s esophagus
Work up and testing
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Begin with H&P
Labs
X-rays, other diagnostics
Tissue diagnosis
Staging
Lab work up
• Complete blood count
• Other specific tests
– Chemistries
– Tumor markers
– Genetics
Genetics
• Philadelphia chromosome
– (9,22) translocation- CML
• BRCA-Breast and ovarian cancer
Tumor markers
• Use
• Misuse
• ***Not for screening***
Tumor markers-Examples
• hCG
– Pregnancy
– Testicular and ovarian cancer
• CEA
– Bowel, other
– Also seen in smokers, COPD
• AFP
– Non seminomatous testicular cancer
Staging
• TNM
• Pathologic
• Others
Why stage?
• Treatment planning
– Initial
– Subsequent
• Prognostication
• Research studies
TNM
• Tumor-Size, location, invasion
• Node-Regional spread
• Metastasis-Distant spread
Pathologic staging
• Tissue diagnosis
• Origin of tissue
• Grade or differentiation
– For example, prostate cancer Gleason’s stage
Stage groupings
• See overhead for lung example
• Don’t memorize
Introduction to treatment planning
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Surgery
Chemotherapy
Hormonal therapy
Radiation therapy
Treatment planning-Goal
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Cure
Prevent local recurrence
Palliation
Organize treatment plan
– i.e.: neoadjuvant
Surgery
• Diagnosis-Must have tissue to
diagnosis
• Staging
• Prevent complications
– Local invasion
– Prevent obstruction
– Reduce tumor burden
• We will discuss this more soon
Chemotherapy
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Vesicants-Need central access
Recognize side effects
Cancer killing drugs
Other disease modifiers
– Hormones
– Cytokines (i.e.: IFN)
Common chemo problems
• Bone marrow toxicity
• GI
• Skin
– Alopecia
Specific chemotherapy examples
• Doxorubicin (Adriamycin)-Cardiac
• Bleomycin-Pulmonary fibrosis
• Cisplatin-Renal dysfunction
• We will discuss this more soon
Radiation therapy
• Short term problems
– Skin
– GI toxicity
• Long term problems
– Scarring/Fibrosis
– Malignancy potential
• We will discuss this more soon
Screening for cancers
• American Cancer Society
recommendations
• Others also publish guidelines for
screening
• Are often changing
• See handout
Lung cancer approach
• #1 MC cancer killer, men and women
• Tobacco association (95%+)
• No benefit of “screening chest x-ray”
even in smokers
• Other associations
– Asbestos (pleural tumor…..mesothelioma)
Lung Cancer cont.
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Small cell or non-small cell
Local vs.. spread
Surgery vs.. no surgery
Central or peripheral
– Large cell and adenocarcinoma-peripheral
– Small cell (oat cell) and squamous cell-central
• Smoker vs. non-smoker
– MC cell type in non-smoker is adenocarcinoma
Breast cancer approach
• Screening/prevention
• Lump and greater than 30-->Mammogram
• Radical mastectomy vs..
lumpectomy/RT..
• CMF, FAC
• Tamoxifen (Prevents reoccurrence)
Risk factors-Breast cancer
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Age >40
Early menarche (before 11), Late menopause
Nulliparity or first child late (after 25)
Primary relative
Previous biopsy
Radiation exposure
ETOH, tobacco
(Fat in diet is not clearly a RF)
(Breast feeding may reduce risk)
Estrogen ???
– May increase risk
– Seems to come up in the literature commonly
Prognosis/Staging-Breast cancer
• Large tumor
• Positive lymph nodes
• Negative receptors
Spread- Breast Cancer
• 2 L’s, 3 B’s
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Lung
Liver
Bone
Brain
Breast
Prostate cancer approach
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Risk factors
Lump
Testing
Bone metastasis
Risk factors-Prostate cancer
• Age
• Race-African American
• Family history
Prostate specific antigen (PSA)
• NOT A PERFECT TEST
• Never been shown to decrease
mortality/morbidity
• Only effective as screening with
digital rectal exam
• Routine screening of men over 75
not recommended by some (2009
change)
Colon cancer approach
• Risk factors (Family history, colitis,
polyps)
• Colon vs.. rectal
• Surgery usually indicated
(obstruction)
• Chemo or adjuvant chemotherapy
Colon Cancer cont.
• One of screenable cancers
• Colonoscopy
– 50 and up
– Every 5-10 years
• Fecal Occult Blood testing
– Not great
– Can be useful, and with low risk
– Annual, over 50
Skin cancer approach
• 700,000 new cases per year
• Sun exposed areas
– SPF 30 or greater recommended
• Basal cell-Raised, umbilicated, nonpigmented pearly lesions
• Squamous cell-Often excoriated
• Melanoma (32,000 of the new cases)
• Others
Skin cancer-ABCD’s
• Asymmetry
– Mirror image if divided in half
• Border
– Scalloped?
• Color
– Variation, unusual
• Diameter
– 6mm (pencil eraser size)
Case wrap up
• There are no real cancer blood tests
recommended for healthy folks.
• Cousins and aunts/uncles don’t
really increase your risk
• Let there exam and symptoms guide
you.
• More to come……
Summary
• Look for common cancers and
prevent them if you can!
• Recognize spread patterns
• Multidisciplinary approach
• Realistic goals for patient
References
• Cecil’s or Harrison’s
• DeVida’s textbook of oncology
• American Cancer Society
– Cancer Manual and website (www.cancer.org)
– Textbook of Clinical Oncology (Murphy et al)
– CA-A Cancer Journal for Clinicians (For free
subscription Email [email protected])
• Clinical Oncology (Rubin)