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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, 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)