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Exercise and cancer Professor Robert Thomas Consultant Oncologist

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1 Exercise and cancer Professor Robert Thomas Consultant Oncologist
Addenbrooke’s, Bedford Cambridge University NHS Trusts Cranfield University

2 The cancer problem 1 in 3 population will get cancer 1 in 4 die
Most common cause of death in young women UK Ca breast 41,700 new women annually

3 Outcomes improving 2 million cancer survivors in the UK

4 Common symptoms and risk amoung cancer survivors
Fatigue and tiredness Mood, anxiety Depression Brain power and intellect Poor appetite Constipation Blood clots (thrombosis) Quality of life Hot flushes Bone density Poor sleep pattern Secondary cancers Bowel adhesions Weight gain Indigestion Sore hands

5 Self help and lifestyle after Cancer
“Teachable moment”

6 What is the evidence? Lifestyle and cancer news -

7 Exercise after Cancer Reduce risks and side effects of treatment
Slow the growth of an established cancer Prevent relapse after initial therapy Improve overall chance of cure

8 Reduce side effects and risks of treatments

9 Cancer Related Fatigue
28 RCT and 2 meta analysis reduces the severity of fatigue Supervised aerobic exercise programmes more effective. Adverse events during exercise were extremely low Cramp and Daniel, 2008), Velthuis et al., 2009

10 Prostate Cancer Patients on hormones
Progressive resistance and aerobic training 20 wk Improved muscle strength, Functional performance Balance in older men Mood, depression Metabolic syndrome (Adult Treatment Panel III criteria) Abdominal obesity, High triglyceride, Hyperglycaemia Daniel et al. Medicine & Science in Sports: Vol 38; 12 - pp Segal et al JCO, Vol 27, No 3 , 2009: pp .;

11 Prostate Radiotherapy Late Toxicity and Lifestyle Study
Robert Thomas Bedford, Addenbrookes, Cranfield Mea Holme Oxford University Madeleine Williams Bedford Hospital Patricia Bellamy Cranfield University Christine Steel MacMillan Cancer Relief Jervoise Andreyev Royal Marsden Hospital

12 Purpose Do self help lifestyle factors correlate with late toxicity after radiotherapy? Exercise Smoking BMI Age

13 Methods Lifestyle Toxicity Vaizey rectal toxicity score
470 live men sourced on the Lantis RXT data base Referred from Bedford Hospital over 10 years 440 completed the study questionnaire (94%) Approached in Clinic or via post +/- telephone calls Toxicity Vaizey rectal toxicity score NCI common toxicity score Rectal bleeding Erectile function Urinary incontinence  Lifestyle Smoking habits BMI, age General practice physical activity questionnaire

14 Results 8% (35) smokers 1% were underweight (BMI <18.5) 36% normal weight ( ), 38% over weight ( ) 25% obese (>25%).

15 Results 58% inactive, 27% moderately inactive/active, 11% active
4% exercising more than 3 hrs a week

16 Results  Rectal toxicity Incontinence Erectile function GPPAQ
Smoker (during Rxt) Smoker (now) Age (time of survey) BMI class Rectal toxicity NS Incontinence Erectile function

17 Slow the growth of an established cancer

18 Lifestyle and cancer-mechanisms
Initial DNA damage Continuing DNA damage, Hormonal environment Immunity Proliferation, de-differentiation, adhesion, apoptosis, angiogenesis, invasion, metastasis

19 Lifestyle & tumour progression
93 men with indolent prostate cancer Exercise (>20 mins brisk walking 6 days a week) Yoga, Vegan diet High soy and antioxidant rich intake Ornish, 2005 #92

20 PSA at 1 year PSA Exercise (>20 mins brisk walking 6 days a wk)
Yoga, Vegan diet High soy intake Control - increase by 6% PSA 10% difference significant at P>0.01 Intervention - decrease by 4% Trial entry At one year Ornish D, et al The Journal of Urology, : p

21 Cellular growth Intervention - 70% growth reduction
Prostate cell lines Intervention - 70% growth reduction Control group – 6% growth reduction 64% difference highly significant at P>0.001 Those with largest PSA reduction had highest reduction Ornish D, et al The Journal of Urology, : p

22 Lifestyle / salicylate study
A randomised double blind phase II study of lifestyle counselling and salicylate +/- dietary supplements in patients with progressive prostate cancer. Robert Thomas, Roger Oakes, Dr Simon Russell, Ms Madeleine Williams. Thomas, et al. NCRN Conference proceeding 2008 Journal of Food and Science March 2009

23 3. Lifestyle / salicylate study

24 Improve overall chance of cure
Prevent relapse after initial therapy Improve overall chance of cure

25 Nurse’s Health Study (Breast cancer)
5204 registered nurses, Breast cancer 860 deaths (553 breast cancer) BMI at diagnosis = Overall survival = Breast cancer relapse (nonsmokers) Weight gain more than 0.5kg/m2 at 1yr (greatest if >2kg/m2) = Overall survival = Breast cancer specific survival Kroenke CH, et al JCO (7): p

26 Fat intake after breast cancer Lifestyle intervention study
2,437 postmenopausal women with early breast cancer Randomised to nutritional and lifestyle counselling, or not. Eight bi-weekly individual exercise and lifestyle counselling sessions for median 60 months. Results; In the Intervention group: - Dietary fat intake reduction was significantly greater. - Weight was lower - Relapse rate was significantly lower (p=0.03) - Overall survival greater. Chlebowski RT, et al., JCO 2005(10): p. 3s

27 Exercise & Bowel cancer relapse
Australian cohort study, 526 patients, colorectal cancer ,. Exercisers def: recreational sport 1-2 week sweat and breathless Results at 5 yrs - 57% alive (non-exercisers) - 71% alive (exercisers) - statistically significant 14% (p<0.05) - greatest benefit in stage III USA cohort study, 816, colon cancer, stage III. Exercise questionnaire, 18 or more MET-hours of activity a week (6 hours walking at a mod pace) - 35% difference in relapse rate between in the those in the upper to lower quartiles of activity - overall survival significantly different Giles GG, IARC Sci Publ, : p Meyerhardt JA, et al., Proc Am Soc Clin Oncol, : 3534

28 Mechanisms - Exercise Lower IGF-1 and higher IGFBP-3 levels
Serum from exercisers encourage P53 activity Prostaglandin and COX-2 inhibition Reduce weight – and help hormonal mileau Increases the bowel transit time Reduce cholesterol and lipids

29 Exercise and breast cancer relapse
933 BC survivors PE> 2.5 hrs/week 67% reduction in RR (Irwin M et al 2007 JCO) 4482 BC survivors PE > 2.8 hrs/wk 35-49% reduction in RR (Holick C et al Cancer Epidemiological Biomarkers Prev 2008) Nurses Health study 2987 BC survivors 3-5 hrs/wk better survival and RR (Holmes et al JAMA 2005) 1490 BC survivors 30 mins 6 days a wk (+ >5 fruit/veg a day) greater survival (Pierce JP Clin Onc)

30 Exercise and prostate cancer relapse rates
2,686 men in the Health Professionals follow up study diagnosed with localised prostate cancer 554 died 122 (22%) of prostate cancer. 3 or more MET-hours per week reduced the risk of death by 35% (overall survival) >90mins brisk walking had a 51% reduction in the risk of death 6 or more MET- hours (5 or more hours of vigorous exercise / week e.g. Jogging) had a 56% reduction in the specifical prostate cancer risk of dying. (Kenfield et al 2010)

31 Cancer Survivorship Exercise Expert Advisory Group
Chair: Robert Thomas Manager: Jo Foster

32 Aims?

33 Motivate Educate Research Convince Cost effectiveness Lobby

34 Local exercise programmes Practical solutions
Hospital based programme Hospital based programme Lifestyle counselling & information Community based programme Community based programme Discharge

35 Activity for Health Referral Scheme
2001 DoH white paper Run by PCT who pay for training of instructors Referral to one of 5,700 municipal leisure centres

36 80 referrals Pilot evaluation No adverse events
44% contacted gyms after initial referral 38% contacted gyms only after prompting 10% changed their minds 82% proceeded to exercise sessions 100% who started the programme finished (12wks) R Thomas, Pei Ding, M Williams. Is the National activity for health referral scheme the practical solution for exercise rehabilitation after cancer.

37 Cancer rehabilitation National accreditation Level 4
Skills active (DoH) Minimal standards - personal trainers July 2010 agreed Course designed April 2011

38 Evaluation of the cancer exercise rehabilitation programme
400 Patients post initial therapies (Breast, colorectal, prostate) Lifestyle and exercise advice Lifestyle and exercise advice & referral Primary clinical end points: Average weekly exercise - The General Practice Physical Activity Questionnaire Secondary clinical end points: Qol questionnaire - Psychological Flourishing Scale Utilisation of health services (laxatives, BP, cholesterol) Laboratory end points: Serum IGF levels correlated against exercise levels Ability of serum from participant to inhibit cancer cell line growth Cost benefit analysis

39 More information Lifestyle and cancer – the facts
Evidence review for the national survivorship programme Lifestyle and cancer evidence news summary Sign up:

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