1. Statistics and Medicine – Friends or Foes? Monika Krzyzanowska MD MPH Medical Oncologist, Princess Margaret Cancer Centre Associate Professor of Medicine, University of Toronto

2. Case 61 year old male tailor Presented with iron deficiency anemia Colonoscopy: tumour in colon Sent to general surgeon who removed the primary cancer from the colon The surgeon has referred the patient to you (medical oncologist) for an opinion regarding what to do next?

3. What do you need to know to advise the patient on next steps? How serious is the cancer? What are the “treatment” options? What are the benefits of treatment? What are the risks?

4. Evidence Pyramid

5. What do you need to know to advise the patient on next steps? How serious is the cancer? What are the “treatment” options? What are the benefits of treatment? What are the risks?

6. How serious is the cancer? PROGNOSIS

7. Colorectal Cancer Stages

8. TNM Staging System T: depth of invasion into bowel wall – T1Invasion of submucosa – T2Invasion into muscularis propria – T3Invasion through muscularis into serosa – T4Invasion of other organs +/- perforation N: regional nodes – N0No nodal mets – N1Mets to 1-3 lymph nodes – N2Mets in  4 nodes M: distant metastases

9. TNM Staging System TNM ClassificationDukes’Survival (no tx) Stage IT1N0M0 T2N0M0 A> 90% Stage IIIIA IIB T3N0M0 T4N0M0 B60-85% Stage IIIIIIA IIIB IIIC T1-2N1M0 T3-4N1M0 anyTN2M0 C25-65% Stage IVanyTanyNM1D5%

10. Case Revisited CT scans – no spread of disease Pathology – Adenocarcinoma – invading through the muscularis into serosa – 7/15 LN involved with tumour Stage: pT3N2M0 (Stage 3)

11. TNM Staging TNM ClassificationDukes’Survival (no tx) Stage IT1N0M0 T2N0M0 A> 90% Stage IIIIA IIB T3N0M0 T4N0M0 B60-85% Stage IIIIIIA IIIB IIIC T1-2N1M0 T3-4N1M0 anyTN2M0 C25-65% Stage IVanyTanyNM1D5%

12. Adjuvant! Online https://www.newadjuvant.com/default2.aspx

13. What do you need to know to advise the patient on next steps? How serious is the cancer? What are the “treatment” options? What are the benefits of treatment? What are the risks?

14. What are the treatment options? Do nothing Surveillance Chemotherapy http://www.psmag.com/health/evidence-of-a-need-for-change-4241/

15. Adjuvant Therapy Treatment given after the primary treatment to increase the chances of a cure; may include chemotherapy, radiation therapy, hormone therapy, or biological therapy.

16. What do you need to know to advise the patient on next steps? How serious is the cancer? What are the “treatment” options? What are the benefits of treatment? What are the risks?

17. Chemotherapy Options for St 3 Colon Cancer in 2013 Drug A -- 5-fluorouracil (5-FU) Drug B – capecitabine Combination therapy (Drug A or B plus other drugs)

18. Drug A vs No Treatment

21. MOSAIC Trial St II & III colon n = 2,246 RANDOMIZATIONRANDOMIZATION Combination Drug A – 5FU Andre NEJM 2004

24. Evidence Pyramid

25. Adjuvant! Online https://www.newadjuvant.com/default2.aspx

26. What do you need to know to advise the patient on next steps? How serious is the cancer? What are the “treatment” options? What are the benefits of treatment? What are the risks?

27. MOSAIC Trial: Serious Toxicity Toxicity 5FU FOLFOX Neuropathy0.212.4 Neutropenia4.741.1 Diarrhea6.610.7 Vomiting1.45.8 Febrile neutropenia0.21.8 Death0.5

28. MOSAIC Trial: Serious Toxicity Toxicity 5FU FOLFOX Neuropathy0.212.4 Neutropenia4.741.1 Diarrhea6.610.7 Vomiting1.45.8 Febrile neutropenia0.21.8 Death0.5

29. Back to the Case 61 year old male tailor Stage 3 colon cancer What would you recommend? a.Do nothing b.Surveillance c.Chemotherapy

30. Evidence Based Medicine

31. Guidelines https://www.cancercare.on.ca/common/pages/UserFile.aspx?fileId=14002

32. Guideline Concordance

33. Statistics & Medicine Explain & describe disease – Natural history – Risk factors – Causes Evaluate treatments – Benefit – Risk Communicate with patient Assess quality of care Friends or Foes?