1. Diet / Lifestyle and Colorectal CancerJeffrey Meyerhardt, MD, MPHDana-Farber Cancer Institute Boston, MA
2. American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention• Recommendations for Individuals – Achieve and maintain a healthy weight throughout life – Adopt a physically active lifestyle – Consume a healthy diet, with an emphasis on plant foods • Choose foods and beverages in amounts that help achieve and maintain a healthy weight. • Limit consumption of processed meats and red meats. • Eat at least 2.5 cups of vegetables and fruits each day. • Choose whole grains instead of refined grain products. – If you drink alcoholic beverages, limit consumption. Kushi et al Ca: Can J Clin 2012
3. American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention• Recommendations for Community Action – Increase access to affordable, healthy foods in communities, worksites, and schools, and decrease access to and marketing of foods and beverages of low nutritional value, particularly to youth. – Provide safe, enjoyable, and accessible environments for physical activity in schools and worksites, and for transportation and recreation in communities. Kushi et al Ca: Can J Clin 2012
4. American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention – CRC• Best advice to reduce the risk of colon cancer is to… – Increase intensity and duration of physical activity – Limit intake of red and processed meat – Consume recommended levels of calcium – Ensure sufficient vitamin D status – Eat more vegetables and fruits – Avoid obesity and central weight gain – Avoid excess alcohol consumption• In addition, it is very important to follow the ACS guidelines for regular colorectal screening, as identifying and removing precursor polyps in the colon can prevent colorectal cancer. Kushi et al Ca: Can J Clin 2012
5. Proportion of Colon CancerPreventable in Middle-Aged Men: HPFS• Body mass index 25 kg/m2• Physical activity 15 MET-hours/week• Daily folate containing multivitamin• Alcohol < 15 g/day• Non-smoker• Red meat 2 servings/week 3.1% of all men Eliminate 71% of all colorectal cancer (95% CI, 33-92%) Platz Cancer Cause Contr 2000
6. What about CancerPatients/Survivors?
7. In 2001, an expert panel convened by the American Cancer Society concluded “…Properly conducted studies of the effect of nutrition and physical activity on the prognosis of cancer survivors are urgently needed, and should be a high priority for all academic and research funding agencies.”
8. Doc, what should I eat? Should I exercise? What else can I do?
9. Colorectal Cancer: Diet and Lifestyle Impact on Cancer Patients• Many studies on diet / lifestyle and risk of DEVELOPING colorectal cancer• Few studies show whether these factors affect patients with colorectal cancer – Disease recurrence – Survival – Tolerance to chemotherapy
10. Quick Epidemiology LesionRelative risks / Hazard Ratios• Probability of an event (eg disease) in people exposed to something compared to those not exposed• Relative risk of 2 means that there is double the risk of a disease due to some exposure compared to no exposure• Relative risk of 0.5 means that there is ½ the risk of a disease due to some exposures compared to no exposure
11. Quick Epidemiology Lesion• HOWEVER, the baseline risk is important – If baseline risk is 1/1000, then a relative risk of 2 is double but still ~1/500 only (0.2%) – If baseline risk is 1/10, then a relative risk of 2 is ~ 1/5 (20%)
12. Cautions on Relative Risk• Relative Risks are relative to another group• Hazard ratios are like relative risk but also account for time• Marathon running vegetarians get colorectal cancer• Not all obese, meat and potato only couch potatoes get colorectal cancer
13. Disclaimer / Audience Promise• Everything from today’s talk relates to data from large groups of individuals• None should be translated as direct recommendations to individual people• Any changes that you are considering MUST be discussed with your own doctor
14. Physical Activity andColorectal Cancer Outcomes
15. Colorectal Cancer: CALGB 89803• NCI-sponsored adjuvant therapy trial for stage III colon cancer• Patients randomized to 2 different chemotherapy regimens• 1264 patients enrolled between 1999 and 2001 Complete Complete questionnaire questionnaire Patients enroll on 0 2 4 6 8 10 12 14 16 adjuvant therapy chemotherapy every 3 month f/u trial Saltz, L. B. et al. J Clin Oncol; 25:3456-3461 2007
16. Sample Question: Physical Activity
17. Colorectal Cancer: CALGB 89803
18. 89803 and Exercise: Disease-Free Survival in Stage III Colon Cancer Survivors 1.2Hazard Ratio Recurrence or Death 1 1 0.8 0.87 0.9 0.6 0.4 0.51 0.55 0.2 0 <3 3-8.9 9-17.9 18.26.9 >27 Regular Physical Activity (met-hours per week) Meyerhardt, J. A. et al. J Clin Oncol; 24:3535-3541 2006
19. How do you get these METs? Leisure-Time Activity MET-HoursNormal pace walking (2 to 2.9 mph) 3Brisk pace walking (3 to 3.9 mph) 4Very brisk pace walking (4+ mph) 4.5Jogging (slower than 10 min/mile) 7Running (faster than 10 min/mile) 12Bicycling 7Tennis, squash, racquetball 7Lap swimming 7Calisthenic, ski/stair machine, other aerobic exercise 6Yoga, stretching, toning, lower intensity exercise 4Other vigorous activities (lawn mowing) 6
20. Physical Activity Consistent Across Groups Meyerhardt, J. A. et al. J Clin Oncol; 24:3535-3541 2006
21. NHS and Post-diagnosis Physical Activity Meyerhardt, J. A. et al. J Clin Oncol; 24:3527-3534 2006
22. NHS and Post-diagnosis Physical Activity Meyerhardt, J. A. et al. J Clin Oncol; 24:3527-3534 2006
23. NHS and Pre-diagnosis Physical Activity Meyerhardt, J. A. et al. J Clin Oncol; 24:3527-3534 2006
24. CHALLENGE: Colon Health and Life-Long Exercise Change trialHigh risk Stage II or stage III colon cancer - completed adjuvant chemotherapy within 2-6 months REGISTRATION Baseline Testing STRATIFICATION Disease stage high risk III; centre; BMI ≤ 27.5 vs. > 27.5; ECOG PS 0 vs. 1 RANDOMIZATION ARM 1 ARM 2 Physical Activity Program + General Good Health General Health Education Materials Education Material (Intervention Arm) (Control Arm) Assessment of disease-free survival every 6 months for first 3 years and annually from years 4-10 Courneya Curr Oncol.2008 Dec;15(6):271-8.
25. CHALLENGE: Colon Health and Life-Long Exercise Change trial – Intervention Arm Content Baseline to 6 mo. 6-12mo. 12-36 mo.Behavior support 12 mandatory face-to-face sessions 12 Mandatory sessions held Mandatory monthlysessions held biweekly biweekly, with option for face- sessions, with option for to-face or telephone delivery face-to-face or telephone deliverySupervised physical 12 Mandatory sessions combined 12 sessions recommended; Monthly sessionsactivity sessions with the mandatory behavior can be combined with the recommended; can be support sessions biweekly behavior support combined with the monthly sessions for those who behavior support sessions 12 Additional supervised physical choose face-to-face sessions for those who choose face- activity sessions on alternate to-face sessions weeks strongly recommendedPhysical activity Gradually increase recreational Individualized (based on Individualized (based ongoal physical activity by 10 metabolic phase I results) to a phase II results) to a equivalent tast (MET)- hours maximum increase of 20 maximum total of 27 MET- weekly over baseline (to 10-19 MET-hours weekly (to a total hours weekly MET-hours weekly) of 20-27 MET-hours weekly) Courneya Curr Oncol. 2008 Dec;15(6):271-8.
26. Diet and ColorectalCancer Outcomes
27. Dietary Patterns• Western and prudent pattern diets predictive of heart disease, diabetes, colorectal cancer• Prudent pattern: high intakes of vegetables, fruit, legumes, whole grains, fish, and poultry• Western pattern: high intakes of red meat, processed meat, refined grains, sweets and dessert, French fries, and high-fat dairy products
28. Dietary Patterns in Colon Cancer PatientsHazard Ratio for Cancer Recurrence or Death 4 3.9 3.5 P, trend < 0.001 3 2.5 Western diet 2 2.2 2 1.5 1.2 1.3 1 1 1.1 1 0.5 Prudent diet 0.7 0 1 2 3 4 5 Quintiles of Dietary Pattern Meyerhardt, J. et al. JAMA 2007298(7):754-764.
29. CALGB 89803: Dietary Pattern Meyerhardt, J. et al. JAMA 2007;298:2263-a.
30. Weight and Colorectal Cancer Outcomes
31. Body Mass Index in Colon Cancer Dignam, J. J. et al. J. Natl. Cancer Inst. 2006 98:1647-1654
32. Author Years N Outcome Hazard Ratio (95% CI) or P value (compared to normal weight)Tartter 1976-1979 279 Recur Rate P = 0.003 for above median weightMeyerhardt 1988-1992 3759 DFS 1.11 (0.94-1.30) BMI > 30 kg/m2 OS 1.11 (0.96-1.29) BMI > 30 kg/mMeyerhardt 1990-1992 1792 DFS 1.10 (0.91-1.32) BMI > 30 kg/m2 rectal OS 1.09 (0.90-1.33) BMI > 30 kg/m2 Local Recur 1.31 (0.91-1.88) BMI > 30 kg/m2Dignam 1989-1994 4288 DFS 1.06 (0.93-1.21) BMI 30-34.9 kg/m2 1.27 (1.05-1.53) BMI > 35 kg/m2Meyerhardt 1999-2001 1053 DFS 1.00 (0.72-1.40) BMI 30-34.9 kg/m2 1.24 (0.84-1.83) BMI > 35 kg/m2 OS 0.90 (0.61-1.34) BMI 30-34.9 kg/m2 0.87 (0.54-1.42) BMI > 35 kg/m2Hines 1981-2001 496 OS 0.77 (0.61-0.97) BMI > 25 all stages 0.92 (0.65-1.30) stage I-II 0.92 (0.59-1.45) stage III 0.58 (0.37-0.90) stage IV
33. Body Mass Index in Colon Cancer Patients over Past Decade < 21 21-24.9 25-29.9 30-34.9 > 35INT-0089 14 % 34 % 34 % 13 % 5%(1988-92)89803 8% 26 % 36 % 20 % 10 %(1999-2001)% change in a - 43% - 24% + 6% + 54% + 100%decade
34. Other Factors and Colorectal Cancer Outcomes
35. Aspirin Use in Colon Cancer Patients Chan, A. T. et al. JAMA 2009;302:649-658.
36. Aspirin Use and Cancer Recurrence in Stage III Colon Cancer: Findings from CALGB 89803 Hazard Ratio for Cancer Recurrence (95% CI) Consistent aspirin use 0.45 (0.21-0.97) Celecoxib or Rofecoxib use 0.56 (0.21-1.54) Fuchs ASCO 2005
37. CALGB/SWOG 80702 for Stage III Colon Cancer Celecoxib versus Placebo N = 2,500 Arm A Arm B 12 FOLFOX 12 FOLFOX + + Placebo daily Celecoxib 6 versus 12 400 mg daily treatments FOLFOX Arm C Arm D 6 FOLFOX 6 FOLFOX + + Placebo daily Celecoxib 400 mg daily Celecoxib starts concurrently with FOLFOX and continue for 3 years
38. Plasma Vitamin D and Survival in Colorectal Cancer Patients 1 1 0.9 0.89 0.83Hazard Ratio for Death 0.8 0.7 0.6 0.5 0.49 0.4 P, trend = 0.01 0.3 0.2 0.1 0 <22.8 22.8-27.1 27.2-33.1 >33.1 Quintiles of plasma Vitamin D ng/mL Ng et al J Clin Oncol. 2008 Jun 20;26(18):2984-91
39. Predicted Vitamin D Level* & Survival inColorectal Cancer Patients: NHS/HPFS (N=1017) CRC Specific Mortality Overall Mortality* Based on race, geography, exercise, BMI,dietary vitamin D, supplement vitamin D Ng et al Br J Cancer. 2009 101: 916-23.
40. Conclusions• Colorectal cancer is a common disease• Ways to prevent colorectal cancer – Diet and lifestyle – Get screening• Colorectal cancer patients – Need to do standard therapies – surgery, chemo if recommended, radiation for certain rectal cancers – Discuss with oncologist other things to complement standard therapy – However, changing behavior is not easy
41. Where Do We Go From Here?• Are observational data enough?• Survivorship raises issues of addressing other diseases down the road• Better biomarkers to study effects – decrease sample size?• Single exposure v multiple exposure intervention
42. Where Do We Go From Here?• All of these studies required collaborative efforts and funding – Cooperative group system – Large prospective cohort studies• Intervention trials – Expensive – Need participation from providers and patients