Principles of Oncology

1. Principles of Oncology Jeffrey T. Reisert, DO University of New England Physician Assistant Program 25 FEB-4 MAR 2010

2. 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.

3. Case questions • What are they talking about? Cancer blood test? PSA? Something else? • What family history is significant? • What do you advise them?

4. 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

5. Overview • Diagnosis • Staging • Further testing and work up • Treatment planning • Screening for cancers • Approach to lung, breast, prostate, colon, and skin cancers

6. Cancer • Single clone of cells • Autonomous growth-Unregulated • Apoptosis (pre-programmed cell death) lost • Anaplastic-Abnormal differentiation • Metastatic-Spread

7. 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

8. Etiology of Cancer • Not completely understood • Involves a predisposition (Genetics) • Environmental role

9. 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

10. 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

11. Family history? • You can pick your friends but you can’t pick your relatives • Primary relatives? • P • S • O/C

12. Environmental • Radiation • Carcinogens such as tobacco • Viruses • Diet • Obesity (next slide) • Previous chemotherapy

13. 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 Obesity in cancer

14. Tobacco • Oral • Pharynx/Larynx • Lung • Esophagus • Renal Cell • Breast • Ovary

15. Problems with cancer • Direct effect-Invasion • Indirect • Cytokines, TNF, Hormonal, Metabolic • Psychological • Stigma • Death

16. Spread patterns • Direct • Lymph/ nodes • Hematogenous after spreading through a vessel • Through serous cavities after exiting an organ

17. Diagnosis of cancer • Kills 25% of Americans (#2 to cardiovascular diseases when totaled) • Common patterns of disease

18. Common patterns of disease • History • Age • Sex • Family History • Social History • Physical

19. Examples • Klinefelter’s syndrome-Male breast cancer • Mother with breast cancer • Daughters of DES mothers-Vaginal cancer • Asbestos-Mesothelioma • Reflux with Barrett’s esophagus

20. Work up and testing • Begin with H&P • Labs • X-rays, other diagnostics • Tissue diagnosis • Staging

21. Lab work up • Complete blood count • Other specific tests • Chemistries • Tumor markers • Genetics

22. Genetics • Philadelphia chromosome • (9,22) translocation- CML • BRCA-Breast and ovarian cancer

23. Tumor markers • Use • Misuse • ***Not for screening***

24. Tumor markers-Examples • hCG • Pregnancy • Testicular and ovarian cancer • CEA • Bowel, other • Also seen in smokers, COPD • AFP • Non seminomatous testicular cancer

25. Staging • TNM • Pathologic • Others

26. Why stage? • Treatment planning • Initial • Subsequent • Prognostication • Research studies

27. TNM • Tumor-Size, location, invasion • Node-Regional spread • Metastasis-Distant spread

28. Pathologic staging • Tissue diagnosis • Origin of tissue • Grade or differentiation • For example, prostate cancer Gleason’s stage

29. Stage groupings • See overhead for lung example • Don’t memorize

30. Introduction to treatment planning • Surgery • Chemotherapy • Hormonal therapy • Radiation therapy

31. Treatment planning-Goal • Cure • Prevent local recurrence • Palliation • Organize treatment plan • i.e.: neoadjuvant

32. Surgery • Diagnosis-Must have tissue to diagnosis • Staging • Prevent complications • Local invasion • Prevent obstruction • Reduce tumor burden • We will discuss this more soon

33. Chemotherapy • Vesicants-Need central access • Recognize side effects • Cancer killing drugs • Other disease modifiers • Hormones • Cytokines (i.e.: IFN)

34. Common chemo problems • Bone marrow toxicity • GI • Skin • Alopecia

35. Specific chemotherapy examples • Doxorubicin (Adriamycin)-Cardiac • Bleomycin-Pulmonary fibrosis • Cisplatin-Renal dysfunction • We will discuss this more soon

36. Radiation therapy • Short term problems • Skin • GI toxicity • Long term problems • Scarring/Fibrosis • Malignancy potential • We will discuss this more soon

37. Screening for cancers • American Cancer Society recommendations • Others also publish guidelines for screening • Are often changing • See handout

38. 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)

39. 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

40. Breast cancer approach • Screening/prevention • Lump and greater than 30--->Mammogram • Radical mastectomy vs.. lumpectomy/RT.. • CMF, FAC • Tamoxifen (Prevents reoccurrence)

41. 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

42. Prognosis/Staging-Breast cancer • Large tumor • Positive lymph nodes • Negative receptors

43. Spread- Breast Cancer • 2 L’s, 3 B’s • Lung • Liver • Bone • Brain • Breast

44. Prostate cancer approach • Risk factors • Lump • Testing • Bone metastasis

45. Risk factors-Prostate cancer • Age • Race-African American • Family history

46. 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)

47. Colon cancer approach • Risk factors (Family history, colitis, polyps) • Colon vs.. rectal • Surgery usually indicated (obstruction) • Chemo or adjuvant chemotherapy

48. 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

49. 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

50. Skin cancer-ABCD’s • Asymmetry • Mirror image if divided in half • Border • Scalloped? • Color • Variation, unusual • Diameter • 6mm (pencil eraser size)