principles of oncology jeffrey t. reisert, do university of new england physician assistant program...
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Principles of Oncology
Jeffrey T. Reisert, DO
University of New England
Physician Assistant Program
25 FEB-4 MAR 2010
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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.
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Case questions
• What are they talking about? Cancer blood test? PSA? Something else?
• What family history is significant?
• What do you advise them?
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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
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Overview
• Diagnosis
• Staging
• Further testing and work up
• Treatment planning
• Screening for cancers
• Approach to lung, breast, prostate, colon, and skin cancers
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Cancer
• Single clone of cells
• Autonomous growth-Unregulated– Apoptosis (pre-programmed cell death) lost
• Anaplastic-Abnormal differentiation
• Metastatic-Spread
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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
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Etiology of Cancer
• Not completely understood
• Involves a predisposition (Genetics)
• Environmental role
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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
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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
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Family history?
• You can pick your friends but you can’t pick your relatives
• Primary relatives?– P– S– O/C
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Environmental
• Radiation
• Carcinogens such as tobacco
• Viruses
• Diet
• Obesity (next slide)
• Previous chemotherapy
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Obesity in cancer
• Associated in men with 14% of cancer deaths including:– Liver
– Pancreas
– Stomach
– Esophagus
– Colon/Rectal
– Gallbladder
• Associated in women with 20% of cancer deaths including– Uterus
– Kidney
– Cervix
– Pancreas
– Esophagus
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Tobacco
• Oral
• Pharynx/Larynx
• Lung
• Esophagus
• Renal Cell
• Breast
• Ovary
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Problems with cancer
• Direct effect-Invasion
• Indirect– Cytokines, TNF, Hormonal, Metabolic
• Psychological
• Stigma
• Death
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Spread patterns
• Direct
• Lymph/ nodes
• Hematogenous after spreading through a vessel
• Through serous cavities after exiting an organ
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Diagnosis of cancer
• Kills 25% of Americans (#2 to cardiovascular diseases when totaled)
• Common patterns of disease
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Common patterns of disease
• History– Age– Sex– Family History– Social History
• Physical
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Examples
• Klinefelter’s syndrome-Male breast cancer
• Mother with breast cancer
• Daughters of DES mothers-Vaginal cancer
• Asbestos-Mesothelioma
• Reflux with Barrett’s esophagus
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Work up and testing
• Begin with H&P
• Labs
• X-rays, other diagnostics
• Tissue diagnosis
• Staging
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Lab work up
• Complete blood count
• Other specific tests– Chemistries– Tumor markers– Genetics
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Genetics
• Philadelphia chromosome– (9,22) translocation- CML
• BRCA-Breast and ovarian cancer
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Tumor markers
• Use
• Misuse
• ***Not for screening***
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Tumor markers-Examples
• hCG– Pregnancy– Testicular and ovarian cancer
• CEA– Bowel, other– Also seen in smokers, COPD
• AFP– Non seminomatous testicular cancer
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Staging
• TNM
• Pathologic
• Others
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Why stage?
• Treatment planning– Initial– Subsequent
• Prognostication
• Research studies
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TNM
• Tumor-Size, location, invasion
• Node-Regional spread
• Metastasis-Distant spread
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Pathologic staging
• Tissue diagnosis
• Origin of tissue
• Grade or differentiation– For example, prostate cancer Gleason’s stage
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Stage groupings
• See overhead for lung example
• Don’t memorize
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Introduction to treatment planning
• Surgery
• Chemotherapy
• Hormonal therapy
• Radiation therapy
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Treatment planning-Goal
• Cure
• Prevent local recurrence
• Palliation
• Organize treatment plan– i.e.: neoadjuvant
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Surgery
• Diagnosis-Must have tissue to diagnosis
• Staging• Prevent complications
– Local invasion– Prevent obstruction– Reduce tumor burden
• We will discuss this more soon
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Chemotherapy
• Vesicants-Need central access
• Recognize side effects
• Cancer killing drugs
• Other disease modifiers– Hormones– Cytokines (i.e.: IFN)
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Common chemo problems
• Bone marrow toxicity
• GI
• Skin– Alopecia
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Specific chemotherapy examples
• Doxorubicin (Adriamycin)-Cardiac
• Bleomycin-Pulmonary fibrosis
• Cisplatin-Renal dysfunction
• We will discuss this more soon
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Radiation therapy
• Short term problems– Skin– GI toxicity
• Long term problems– Scarring/Fibrosis– Malignancy potential
• We will discuss this more soon
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Screening for cancers
• American Cancer Society recommendations
• Others also publish guidelines for screening
• Are often changing
• See handout
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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)
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Lung Cancer cont.
• 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
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Breast cancer approach
• Screening/prevention
• Lump and greater than 30--->Mammogram
• Radical mastectomy vs.. lumpectomy/RT..
• CMF, FAC
• Tamoxifen (Prevents reoccurrence)
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Risk factors-Breast cancer
• 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
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Prognosis/Staging-Breast cancer
• Large tumor
• Positive lymph nodes
• Negative receptors
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Spread- Breast Cancer
• 2 L’s, 3 B’s– Lung– Liver– Bone– Brain– Breast
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Prostate cancer approach
• Risk factors
• Lump
• Testing
• Bone metastasis
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Risk factors-Prostate cancer
• Age
• Race-African American
• Family history
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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)
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Colon cancer approach
• Risk factors (Family history, colitis, polyps)
• Colon vs.. rectal
• Surgery usually indicated (obstruction)
• Chemo or adjuvant chemotherapy
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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
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Skin cancer approach
• 700,000 new cases per year• Sun exposed areas
– SPF 30 or greater recommended
• Basal cell-Raised, umbilicated, non-pigmented pearly lesions
• Squamous cell-Often excoriated• Melanoma (32,000 of the new cases)• Others
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Skin cancer-ABCD’s
• Asymmetry– Mirror image if divided in half
• Border– Scalloped?
• Color– Variation, unusual
• Diameter– 6mm (pencil eraser size)
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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……
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Summary
• Look for common cancers and prevent them if you can!
• Recognize spread patterns
• Multidisciplinary approach
• Realistic goals for patient
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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)