Fighting cancer with exercise and nutrition

Cancer is a complex disease associated with multiple modifiable risk factors – such as diet, physical activity (PA), tobacco and alcohol – and non-modifiable risk factors, including family history, number of years of potential fertility and nulliparity. The incidence of cancer is increasing worldwide with an estimated 19.5 million new cases expected to be diagnosed annually by 2025. 

Furthermore, due to improved early detection and medical treatment, cancer survivorship rates are increasing. Therefore, cancer represents a major source of premature morbidity and mortality worldwide. Identifying and targeting strategies to help reduce cancer incidence and severity is of utmost importance.

MedEx programmes

MedEx is a large-scale community-based exercise rehabilitation programme at Dublin City University (DCU). The MedEx programme addresses two modifiable factors – diet and PA  – and currently runs three programmes for people with cancer:

• The Cancer Prepare programme is for people with newly diagnosed cancer awaiting surgery and incorporates intense exercise training aimed at improving fitness, fatigue and health-related quality of life (HRQoL)

• Move On is a 12-week programme for people with cancer following completion of surgery/adjuvant cancer treatment and incorporates twice-weekly exercise classes aimed at improving fitness, fatigue and HRQoL

• The Living Life programme offers gentle supervised exercise classes for people with metastatic cancer aimed at improving HRQoL and fitness. 

The individuals who are referred for ‘Move On’ are typically at very low risk of malnutrition. Therefore in the following sections on nutrition, we will briefly outline some of the evidence for nutrition in cancer survivors.

International recommendations

In 2007 the World Cancer Research Fund (WCRF) and the American Institute of Cancer Research (AICR) issued eight recommendations for cancer prevention plus two special recommendations (see Table 1).

Since these recommendations were published, several studies have noted adherence was inversely associated with decreased risk of several cancers in multiple populations.^{1,2,3,4,5,6,7} Evidence from large observational studies demonstrates that adhering to the WCRF recommendations results in significant reductions in cancer incidence and mortality, as well as cardiovascular/respiratory mortality and all-cause mortality.^8,9

Additionally, greater prediagnostic adherence to the WCRF recommendations was associated with 30% decreased risk of colorectal cancer mortality and all-cause mortality.¹⁰

It is well known that certain modifiable lifestyle factors can influence cancer prognosis, recurrence and even mortality while non-cancer outcomes can also be heavily influenced. Interestingly, the second special recommendation is for cancer survivors to follow the recommendations for cancer prevention.

A recent large prospective cohort study was published in the American Journal of Clinical Nutrition. There was an 18% decreased risk of all-cause mortality and a 31% decrease in cancer-specific mortality in those with the highest adherence to the WCRF recommendations compared to those with the lowest adherence.¹¹

In another large cohort, cancer mortality was 61% lower in individuals who met ≥5 recommendations compared to those who met none.¹²

Adherence to the WCRF guidelines has also been independently associated with a 49% decreased odds of progression from Barrett’s oesophagus to oesophageal adenocarcinoma.¹³ Also, in men diagnosed with prostate cancer, adherence to the WCRF recommendations has been associated with decreased disease aggressiveness.¹⁴

Importantly, adherence to the WCRF recommendations also improves HRQoL among cancer survivors.^15,16 Some evidence suggests that dietary and more complex, multi-modal lifestyle interventions are not only feasible, but also effective in cancer survivors.¹⁷

Physical activity is a core WCRF guideline, and fitness is also an important component in cancer care. Lower levels of physical fitness are associated with an increased adverse outcome following surgery, including major complications and mortality.^18,19

In addition, changes in nutritional status are linked to treatment-related side effects, eg. nausea, vomiting, mycosis and impaired taste and smell.²⁰

The effects of cancer treatment on nutritional status and physical fitness appear to be related to the type of treatment, being worse in those receiving combination therapy than in those who receive monotherapy.^21,22

These data highlight the high risk of adverse outcome following major cancer surgery, not least due to the impact of neoadjuvant cancer treatments. 

Exercise aids treatment

Exercise training at cancer diagnosis may have important implications: exercise training can stimulate skeletal muscle adaptations such as increased mitochondrial content and improved oxygen uptake capacity,²³ both contributors to physical fitness, which possibly could reduce the adverse effects of cancer treatment and improve surgical outcome. 

Furthermore, increasing physical activity levels may reduce breast and colorectal cancer mortality^24,25 and all-cause mortality in individuals with non-metastatic colorectal cancer.²⁵ Higher levels of exercise may be associated with improved prognosis in those with solid tumours.²⁶

Together, aerobic exercise and chemotherapy have a beneficial effect on tumour progression and chemotherapy efficacy on solid tumours.²⁷

Exercise training at different time points in the cancer journey is beneficial. In people with newly diagnosed cancer, exercise training programmes incorporating moderate to severe intensities improve fitness. However, the effect on post-operative outcome remains unknown due to lack of adequately powered trials.²⁸ For people undergoing adjuvant cancer treatment following surgery, a continuous exercise programme improves fitness, HRQoL and fatigue.²⁹

End-of-life HRQoL boost

People with metastatic cancer can experience several episodes of palliative treatment before entering the terminal phase of their illness. The symptoms related to disease and treatment significantly diminish physical fitness leading to loss of mobility and independence, which can be very distressing and negatively impact HRQo.³⁰

The evidence indicates that far from being detrimental in this group, exercise can improve fitness and HRQoL.^31,32 Exercise incorporating resistance training increases strength for people with metastatic disease, but further research is required to determine additional benefits when carried out in combination with aerobic exercise.³³

Potential mechanisms

Metabolic syndrome (MetSyn) is a cluster of factors that is related to future cardiovascular morbidity and mortality, but also non-CVD outcomes. Among those with cancer, non-adherence to the WCRF recommendations was associated with an approximate 120% greater risk of MetSyn.^34,35

In addition, higher compared to lower adherence to the WCRF recommendations has been associated with lower inflammation (CRP, TNFα), insulin response (C-peptide) oxidative stress (F2-isoprostan) and serum sex hormones, estrone, estradiol, but higher adiponectin and antioxidant status (γ-tocopherol).^36,37 

However, despite the evidence, several large cohort studies have reported that adherence to the WCRF recommendations is low in several populations.^{38,39,40,41,42} Further studies have even reported that adherence was higher in individuals with no cancer history compared with cancer survivors.⁴³

Lifestyle 

Cancer survivors can be predisposed to developing chronic, non-cancer health conditions,^40,44 which has been suggested to be related to modifiable lifestyle choices.⁴⁵ Anecdotal evidence from Move On participants suggest that many received no dietary or exercise advice. Perhaps of concern, many well-nourished participants received potentially inappropriate dietary and exercise advice from various well-meaning healthcare professionals to ‘eat what you like’ and avoid physical activity. 

Finally, many Move On individuals reported frustration and disbelief with such advice and sought information from elsewhere, eg. internet, alternative therapists.

Nutrition and exercise are major modifiable factors that can potentially improve HRQoL, cancer prognosis and overall longevity. However, a recent report concluded that ‘there is ample room for improvement of lifestyle recommendations in virtually all cancer survivors’.⁴⁶ Additionally, there have been suggestions that nutritional counselling is ‘an essential component of survivorship care’.⁴⁵

When it comes to well-nourished cancer survivors, perhaps it’s time to ‘Move On’ from ‘eat what you like and bed rest’.

Conor Kerley is chairperson of the Scientific and Research Steering Group at the Irish Nutrition and Dietetic Institute and director of Nutrition and Dietetics at MedEx and Move On at the MedEx Research Cluster, School of Health and Human Performance, Dublin City University (DCU) and Lisa Loughney is a MedEx exercise physiologist at the MedEx Research Cluster, School of Health and Human Performance, DCU

Contact Conor at conorkerleynutrition@gmail.com

References

1. Hastert TA, Beresford SA, Patterson RE, Kristal AR, et al. Adherence to WCRF/AICR cancer prevention recommendations and risk of postmenopausal breast cancer. Cancer Epidemiol Biomarkers Prev 2013; 22(9): 1498-508
2. Catsburg C, Miller AB, Rohan TE. Adherence to cancer prevention guidelines and risk of breast cancer. Int J Cancer 2014; 135(10): 2444-52
3. Harris HR, Bergkvist L, Wolk A. Adherence to the World Cancer Research Fund/American Institute for Cancer Research recommendations and breast cancer risk. Int J Cancer 2016; 138(11): 2657-64
4. Jankovic N, Geelen A, Winkels RM, et al. Adherence to the WCRF/AICR Dietary Recommendations for Cancer Prevention and Risk of Cancer in Elderly from Europe and the United States: A Meta-Analysis within the CHANCES Project. Cancer Epidemiol Biomarkers Prev 2017; 26(1); 136-144
5. Lucas AL, Bravi F, Boffetta P, et al. Adherence to World Cancer Research Fund/American Institute for Cancer Researchrecommendations and pancreatic cancer risk. Cancer Epidemiol 2016; 40: 15-21
6. Nomura SJ, Inoue-Choi M, Lazovich D, et al. WCRF/AICR recommendation adherence and breast cancer incidence among postmenopausal women with and without non-modifiable risk factors. Int J Cancer 2016; 138(11): 2602-15
7. Romaguera D, Vergnaud AC, Peeters PH, et al. Is concordance with World Cancer Research Fund/American Institute for Cancer Research guidelines for cancer prevention related to subsequent risk of cancer? Results from the EPIC study. Am J Clin Nutr 2012; 96(1): 150-63
8. Vergnaud AC, Romaguera D, Peeters PH, et al. Adherence to the World Cancer Research Fund/American Institute for Cancer Researchguidelines and risk of death in Europe: results from the European Prospective Investigation into Nutrition and Cancer cohort study. Am J Clin Nutr 2013; 97(5): 1107-20
9. Maresso KC, Hawk E.Cancer Prevention Recommendations: Impact of Adherence. Semin Oncol Nurs 2016; 32(3): 306-13
10. Romaguera D, Ward H, Wark PA, et al. Pre-diagnostic concordance with the WCRF/AICR guidelines and survival in European colorectal cancer patients: a cohort study. BMC Med 2015; 13: 107
11. Lohse T, Faeh D, Bopp M, Rohrmann S; Swiss National Cohort Study Group. Adherence to the cancer prevention recommendations of the World Cancer ResearchFund/American Institute for Cancer Research and mortality: a census-linked cohort. Am J Clin Nutr 2016; 104(3): 678-85
12. Hastert TA, Beresford SA, Sheppard L, et al. Adherence to the WCRF/AICR cancer prevention recommendations and cancer-specific mortality: results from the Vitamins and Lifestyle (VITAL) Study. Cancer Causes Control 2014; 25(5): 541-52
13. Realdon S, Antonello A, Arcidiacono D, et al. Adherence to WCRF/AICR lifestyle recommendations for cancer prevention and the risk of Barrett’s esophagus onset and evolution to esophageal adenocarcinoma: results from a pilot study in a high-risk population. Eur J Nutr 2016; 55(4): 1563-71
14. Arab L, Su J, Steck SE, et al. Adherence to World Cancer Research Fund/American Institute for Cancer Research lifestyle recommendations reduces prostate cancer aggressiveness among African and Caucasian Americans. Nutr Cancer 2013; 65(5): 633-43
15. Inoue-Choi M, Lazovich D, Prizment AE, et al. Adherence to the World Cancer Research Fund/American Institute for Cancer Research recommendations for cancer prevention is associated with better health-related quality of life among elderly female cancer survivors. J Clin Oncol 2013; 31(14): 1758-66
16. Song S, Hwang E, Moon HG, et al. Adherence to guidelines for cancer survivors and health-related quality of life among Korean breast cancer survivors. Nutrients 2015; 7(12): 10307-19
17. Finocchiaro C, Ossola M, Monge T, et al. Effect of specific educational program on dietary change and weight loss in breast-cancer survivors. Clin Nutr 2016; 35(4): 864-70
18. Older P, Hall A, Hader R. Cardiopulmonary exercise testing as a screening test for perioperative management of major surgery in the elderly. Chest 1999; 116(2): 355
19. Snowden CP, Prentis J, Jacques B, et al. Cardiorespiratory fitness predicts mortality and hospital length of stay after major elective surgery in older people. Annals of Surgery 2013; 257(6 ): 999–1004
20. Comeau TB, Epstein JB, Migas C. Taste and smell dysfunction in patients receiving chemotherapy: a review of current knowledge. Support Care Cancer 2001; 9(8): 575-80
21. Moros MT, Ruidiaz M, Caballero A, et al. Effects of an exercise training program on the quality of life of women with breast cancer on chemotherapy. Rev Med Chil 2010; 138(6): 715-22
22. Hebuterne X, Lemarie E, Michallet M, et al. Prevalence of malnutrition and current use of nutrition support in patients with cancer. JPEN J Parenter Enteral Nutr 2014; 38(2): 196-204
23. Holloszy JO, Coyle EF. Adaptations of skeletal muscle to endurance exercise and their metabolic consequences. Journal of Applied Physiology 1984; 56(4): 831-38
24. Holmes MD, Chen WY, Feskanich D, et al. Physical activity and survival after breast cancer diagnosis. JAMA 2005; 11(5): 106
25. Meyerhardt JA, Giovannucci EL, Holmes MD, et al. Physical activity and survival after colorectal cancer diagnosis. Journal of Clinical Oncology 2006; 24(22): 3527-34
26. Jones LW, Alfano CM. Exercise-oncology research: past, present, and future. Acta Oncol 2013; 52(2): 195-215
27. Betof AS, Lascola CD, Weitzel D, et al. Modulation of murine breast tumor vascularity, hypoxia and chemotherapeutic response by exercise. Journal of National Cancer Institute 2015; 107(5): djv040
28. Loughney L, West MA, Kemp GJ, et al. Exercise intervention in people with cancer undergoing neoadjuvant cancer treatment and surgery: A systematic review. European Journal of Surgical Oncology 2016; 42(1): 28-38
29. Loughney L, West MA, Kemp GJ, et al. Exercise intervention in people with cancer undergoing adjuvant cancer treatment following surgery: A systematic review. European Journal of Surgical Oncology 2015; 41(12): 1590-602
30. Brown P, Clark MM, Atherton P, et al. Will improvement in quality of life (QoL) impact fatigue in patients receiving radiation therapy for advanced cancer? American Journal of Clinical Oncology 2006; 29: 52-58
31. Beaton R, Pagdin-Friesen W, Robertson C, et al. Effects of exercise intervention on persons with metastatic cancer: a systematic review. Physiotherapy Canada 2009; 61: 141-153
32. Lowe S, Watanabe S, Courneya K. Physical activity as a supportive care intervention in palliative cancer patients: a systematic review. Supportive Oncology 2009; 7(1): 27-33
33. Cramp F, James A, Lambert J. The effects of resistance training on quality of life in cancer: a systematic literature review and meta-analysis. Supportive Care in Cancer 2010; 18: 1367-1376
34. Smith WA, Li C, Nottage KA, et al. Lifestyle and metabolic syndrome in adult survivors of childhood cancer: a report from the St Jude Lifetime Cohort Study. Cancer 2014; 120(17): 2742-50
35. Bruno E, Gargano G, Villarini A, Mercandino A, et al. Adherence to WCRF/AICR cancer prevention recommendations and metabolic syndrome in breast cancer patients. Int J Cancer 2016; 138(1): 237-44
36. Tabung FK, Fung TT, Chavarro JE, et al. Associations between adherence to the World Cancer Research Fund/American Institute for Cancer Research cancer prevention recommendations and biomarkers of inflammation, hormonal and insulin response. Int J Cancer 2017; 140(4): 764-77637
37. Morimoto Y, Beckford F, Cooney RV, et al. Adherence to cancer prevention recommendations and antioxidant and inflammatory status in premenopausal women. Br J Nutr 2015; 114(1): 134-43
38. Nomura SJ, Dash , Rosenburg L, et al. Adherence to diet, physical activity and body weight recommendations and breast cancer incidence in the Black Women’s Health Study. Int J Cancer 2016; 139(12): 2738-2752
39. Vossenaar M, Mayorga E, Soto-Méndez MJ, et al. The positive deviance approach can be used to create culturally appropriate eating guides compatible with reduced cancer risk. J Nutr 2009; 139(4): 755-62
40. Zhang FF, Saltzman E, Must A, et al. Do childhood cancer survivors meet the diet and physical activity guidelines? A review of guidelines and literature. Int J Child Health Nutr 2012; 1(1): 44-58
41. Robien K, Ness KK, Klesges LM, et al. Poor adherence to dietary guidelines among adult survivors of childhood acute lymphoblastic leukemia. J Pediatr Hematol Oncol 2008; 30(11): 815-22
42. Valdes-Ramos R, Cervantes I, Mendoza-Perdomo I, et al. Concordance of diets and eating practices in a rural Guatemalan setting with the cancer prevention recommendations of the World Cancer Research Fund: estimates from existing dietary intake. Asia Pac J Clin Nutr 2006; 15(2): 259-66
43. Ollberding NJ, Maskarinec G, Wilkens LR, et al. Comparison of modifiable health behaviours between persons with and without cancer: the Multi-ethnic Cohort. Public Health Nutr 2011; 14(10): 1796-804
44. Smith SA, Claridy MD, Whitehead MS, et al. Lifestyle modification experiences of African American breast cancer survivors: A needs assessment. JMIR Cancer 2015; 1(2): e9
45. Ladas EJ. Nutritional counseling in survivors of childhood cancer: An essential component of survivorship care. Children (Basel) 2014; 1(2): 107-18
46. Winkels RM, van Lee L, Beijer S, et al. Adherence to the World Cancer Research Fund/American Institute for Cancer Research lifestyle recommendations in colorectal cancer survivors: results of the PROFILES registry. Cancer Med 2016; 5(9): 2587-95