Oncology LMCC Refresher Course

1. Oncology LMCC Refresher Course Dr. Garth Nicholas

2. Outline • How Big A Problem? • Cells and Molecules • Risk Factors and Screening • Diagnosis and Staging • Treatments • Specific Cancers

3. How Big A Problem? • 145 500 new cancers in Canada in 2004 • 68 300 cancer deaths in 2004 • Projected to be the commonest cause of death in Canadians by 2010.

4. How Big A Problem? • Lifetime risk of developing cancer for Canadians • Women 38% • Men 43% • 31% of PYLL due to cancer (954 000 years) • 65% of diagnoses and 80% of deaths are in people over the age of 60

5. Canadian New Cases and Deaths

6. Women Men

7. Women Men

8. Cells and Molecules • Cancer: • Characterized by growth and division of cells outside the control of normal regulatory mechanisms • Characterized as benign or malignant by their capacity for metastasis • Benign tumours designated by the suffix -oma • Malignant tumours are divided most broadly into carcinomas and sarcomas, and blastomas in children

9. Exceptions to the nomenclature rules: • Hepatoma • Melanoma • Leukemia • Glioblastoma

10. Carcinomas • Carcinomas • Arise from epithelium • Commonest are adenocarcinoma and squamous carcinoma • Many others, including germ cell tumours, transitional cell carcinomas, large cell carcinoma,neuroendocrine carcinoma

11. Carcinomas • Adenocarcinoma • Breast • Lung • Prostate • Most GI, including colon • Endocrine malignancies • Characterized by gland formation

13. Carcinomas • Squamous carcinoma • Head and neck cancers • Lung • Skin • Cervix • Esophagus • Anus

15. Carcinomas • Germ Cell Tumours • Most commonly testicular cancers • Ovarian • Primary mediastinal • Histologic subtypes include teratomas, embryonal carcinomas, yolk sac tumours

17. Sarcomas • Much rarer than carcinomas • Arise from parenchymal tissue • About 800 soft-tissue sarcomas per year in Canada, and fewer bone sarcomas • Named for the tissue they arise from, when known

18. Sarcomas • Known tissues of origin • Liposarcoma Fat • Rhabdomyosarcoma Striated muscle • Leiomyosarcoma Smooth muscle • Osteosarcoma Bone • Chondrosarcoma Cartilage • Unknown tissue of origin • Malignant fibrous histiocytoma, Ewing’s Sarcoma, alveolar soft parts tumour

21. Others • Hematologic malignancies • Do not fit well into the carcinoma/sarcoma spectrum • Technically, lymphomas are considered sarcomas (reticulosarcoma) while leukemias are considered carcinomas • Practically, no one makes this distinction

23. Blastomas Aggressive childhood tumours • Neuroblastoma, retinoblastoma, medulloblastoma • Named for their histologic resemblance to cells at the centre of blastocytes

25. Summary • Histologic characteristics of cancer • Excessive cellularity • Disrupted architecture • Frequent mitoses, sometimes bizarre • Unusual cell appearance • Large, hyperchromatic nuclei • Varying degrees of differentiation • Invasion into surrounding tissue

27. Genetic Changes • Cancers arise due to changes in a cell’s genetic machinery • These changes involve genes that are divided into two major groups • Oncogenes • Tumour suppressor genes

28. Genetic Changes • Oncogenes • Are altered forms of normal genes called proto-oncogenes • Genes have dominant transforming properties: one abnormal copy is sufficient • Proto-oncogenes tend to function in normal cell cycling and differentiation • Mutation or overexpression leads to unregulated cell division

29. Genetic Changes • Tumour Suppressor Genes • Genes which are normally involved in the negative regulation of cell cycling • Genes have recessive transforming properties: both copies must be abnormal • Classic example is retinoblastoma • Loss of these genes allows cells to proliferate unregulated, or with reduced restraints

30. Genetic Changes • CML is driven by the bcr-abl oncogene (Philadelphia chromosome)

31. Genetic Changes

32. Genetic Changes • In reality, single mutations are usually insufficient for malignant transformation, and cancer cells contain a number of genetic abnormalities, many of uncertain significance

35. Risk Factors • Risk factors for cancer are difficult to study • Long interval between exposure and disease • Many exposures to agents of unknown significance • Unclear correlation between carcinogenesis in laboratory and in real world • ?Threshold levels for carcinogenesis • IARC publishes a list of known causes of cancer, and estimates of their significance

36. Risk Factors

37. Risk Factors • Environmental Causes • Aflatoxin Hepatocellular carcinoma • Erionite Mesothelioma • Radon Lung (RR=2) • Solar Radiation Melanoma (RR=3)

38. Risk Factors • Lifestyle Causes • Tobacco Lung (RR=12) Larynx (12) Oral cavity (5), esophagus(4), kidney (3), bladder (3), pancreas (2) • Smokeless tobacco Oral Cavity (2) • Betel and tobacco Oral Cavity (9) • Alcohol Oral cavity (5), esophagus(4), larynx (3) liver (3) • Diet

39. Risk Factors • Occupational (35 factors listed) • Benzene Leukemia (RR=3) • Asbestos Mesothelioma (6), lung (3) • Pharmacologic (18 factors listed) • Alkylating agents (9) Leukemias • Immunosuppressants(2) Lymphomas • Hormones (5) Endometrium • Others (2)

40. Risk Factors • Biologic Causes • EBV Burkitt’s lymphoma (RR=30) • H. pylori Gastric (4) • HBV Liver (100) • HCV Liver (20) • HIV KS (1000), NHL (100) • HPV t16,18 Cervix (20) • HTLV-1 Adult T-cell lymphoma (4) • O. viverrini Cholangiocarcinoma (5) • S. haematobilium Bladder (5)

41. Screening • Screening is the routine testing of asymptomatic individuals for the presence of cancer • Underlying screening is the assumption that cancers detected at the asymptomatic stage are more amenable to therapy

42. Screening • Cancers commonly screened for in adults are: • Breast (mammography) • Cervix (Pap smears) • Colon (Barium enema/colonoscopy/FOBT) • Prostate (PSA) • Evidence behind screening is surprisingly contentious, in part because of the difficulty of designing studies to avoid bias

43. Screening • Lead-time Bias Cancer becomes incurable Symptoms Cancer starts Diagnosis and treatment Death Time Treatment Diagnosis by screening

44. Screening • Length Time Bias * * * * * * * * * 1 2 3 4

45. Screening • Breast • Recommendations are for annual breast exam and biannual mammography starting at age 50 (?ending at age 74) • Cervix • Recommend Pap smears annually for first three years after becoming sexually active, then every two years until age 70 • Frequency is different if any test is abnormal

46. Screening • Prostate • Ontario guidelines state that “Healthy men without symptoms may decide to have a PSA test after talking to their family doctor or if they are at high risk for prostate cancer ("first degree" relatives with the disease, men of African ancestry).” • Not covered by OHIP because no trial has ever shown a survival advantage to screening

47. Screening • Colon • Methods include fecal occult blood testing (FOBT), colonoscopy, Ba enema, sigmoidoscopy • Ontario is currently running a pilot program of FOBT in 12 areas to inform eventual development of a province-wide policy • Other modalities are inconsistently used, and probably too expensive for mass screening

48. Why Not Screen for All Cancers? • Cancer-related factors Cancer Starts Symptoms Death Incurable Preclinical interval too short Incurable Cancer Starts Death Symptoms Cancer incurable, even if screen detected

49. Why Not Screen for All Cancers? • Test-related factors • Test not sensitive/specific enough • Test can’t be applied to whole population • Too expensive • Insufficient infrastructure/personnel • Unacceptable to majority of population • Tumour not common enough

50. Diagnosis • Impossible to list all possible symptoms of cancer • Systematically think about symptoms in four categories: • Local symptoms of tumour • Symptoms from regional (nodal) spread • Symptoms from metastatic spread • Symptoms from paraneoplastic phenomena