principles of oncology jeffrey t. reisert, do university of new england physician assistant program...
TRANSCRIPT
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
• 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
• Radiation
• Carcinogens such as tobacco
• Viruses
• Diet
• Obesity (next slide)
• Previous chemotherapy
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
Tobacco
• 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– 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
• 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
• Surgery
• Chemotherapy
• Hormonal therapy
• Radiation therapy
Treatment planning-Goal
• 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
• 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.
• 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
• 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– Lung– Liver– Bone– Brain– Breast
Prostate cancer approach
• 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, non-pigmented 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)