1. Leicester Warwick Medical School Neoplasia IV Incidence, Prognosis, Treatment of Cancer Professor Rosemary A Walker raw14@le.ac.uk Department of Pathology

2. INCIDENCE OF CANCER MALEFEMALE Lung 21%Breast 27% Prostate 15%Lung 12% Colorectal 13%Colorectal 12% Bladder 8%Ovary 5% Lymphoma 4%Lymphoma 3%

3. AGE INCIDENCE Cancer Registrations per year. UK Age Range

4. AGE INCIDENCE <10-childhood neoplasms (Wilms, neuroblastoma, retinoblastoma), leukaemia, CNS tumours 10-10-leukaemia, osteosarcomas 20-29-leukaemia, teratomas, lymphoma 30-39-carcinoma, seminoma, lymphoma, sarcoma 40-49-carcinoma, lymphoma, glioma, sarcoma 50<-carcinoma, sarcoma, lymphoma, leukaemia

5. CANCER MORTALITY MALEFEMALE Lung 28%Breast 18% Prostate 12%Lung 17% Colorectal 11%Colorectal 12% Stomach 6%Ovary 6% Oesophagus 5%Pancreas 5%

6. 5 YEAR SURVIVAL RATES FROM CANCER Pancreas 3%Prostate60% Lung12%Breast65% Stomach19%Non-melanoma90% Ovary35%NH lymphoma37% Colon/rectum50%

7. PREDICTING TUMOUR BEHAVIOUR Size of tumour Node status Distant metastasis Staging Grade Receptors/Molecular alterations

10. STAGING Dukes staging for neoplasms of rectum A Not extending through muscularis propria >90% 5 yr survival B Extending through muscularis propria 70% 5 yr survival C Lymph nodes involved 30% 5 yr survival

11. STAGING TNM T = tumour N = node M = metastasis eg. breast, lung T1 = <2cm size T2 = 2 - 5 cm T3 = skin and/ or chest wall involved N0 = no axilliary nodes involved N1 = mobile nodes involved M0 = no metastases M1 = demonstrable metastases

12. STAGING Hodgkin’s Disease (Ann Arbor) Ione group of nodes involved IItwo separate groups, same side of diaphragm IIInodes involved both sides of diaphragm, plus spleen IVbone marrow, lung, other sites A no symptoms Bfever, itching

13. GRADING Degree of differentiation e.g. breast degree of tubule formation extent of nuclear variation number of mitoses

14. Grade 1 Grade 2 Grade 3

16. TREATMENT Surgery Radiotherapy Chemotherapy Hormone therapy Others – cancer specific, vaccines

17. TREATMENT Primary Depends on of nature of tumour Stage Adjuvant Recurrent/metastases

18. RADIOTHERAPY Factors Type of radiation Cumulative dose Rate of delivery Target tissues

19. RADIOTHERAPY Cells and tissues of the body and their tumours vary in their capacity to sustain injury Phase of cell cycle Repair mechanisms Oxygenation

20. RADIOTHERAPY SENSITIVITY NormalTumour HighLymphoidLymphoma Bone marrowLeukaemia SpermatogoniaSeminoma Fairly highEpidermisSquamous G I mucosa carcinomas

21. RADIOTHERAPY SENSITIVITY NORMALTUMOUR Mediumbreastcarcinomas of pancreasbreast, pancreas, bladderbladder, ovary, lung Lowbone, maturesarcomas cartilage,gliomas nerves

22. CHEMOTHERAPY Drugs used have effects at particular stages of the cell cycle Effects depend on tumour cells being in cell cycle Also have an effect on rapidly dividing cells eg. bone marrow

23. CHEMOTHERAPY Cyclophosphamide- can act on cells in G1, S phase and mitosis. Vincristine - can block cells entering cell cycle and act on mitosis Methotrexate - acts on cells in S phase

24. PREDICTING RESPONSE Hormone Therapy Detection of hormone (oestrogen) receptor Herceptin Detection of amplification/overexpression of HER-2

25. High oestrogen receptor (ER) Low ER Neg ER

26. c-erbB-2/neu/HER-2 antibodies made and modified for use in humans if HER-2 present as detected by Hercep- Test, then can use Herceptin ® for treatment

27. TUMOUR MARKERS Products liberated from tumour into blood stream May aid diagnosis and can be used to gauge response to therapy and for follow up.

28. TUMOUR MARKERS Alpha fetoprotein-Hepatocellular carcinoma Germ cell tumours Human chorionic-Trophoblastic tumours gonadotrophin

29. TUMOUR MARKERS Acid phosphatase-Prostatic carcinoma Prostate specific antigen Carcinoembryonic -GI tract antigen Hormone products-Endocrine tumours

30. SCREENING Aims to detect pre-malignant, non invasive and early invasive cancers to improve prognosis. Cervix Breast Large Intestine Prostate

31. SCREENING Cervical Relies on cytological examination of smears to detect “early” changes - dysplasia Factors include-age range screened -population at risk -adequate smear -cytological examination

32. SCREENING Breast Aims to identify invasive cancers before they can be felt (10-15 mm in size ) Relies on mammography 50-64 (69) years Factors - frequency of screening - age range - would all lesions progress?

33. HOW CAN WE IMPROVE PROGNOSIS? Identify “at risk” groups familial occupational Detect at an earlier stage cervix breast Prevention