1. Physical Activity in Palliative Care Max Watson Medical Director Northern Ireland Hospice Visiting Professor University of Ulster Honorary Senior Lecturer Queens University Belfast Honorary Consultant in Palliative Medicine Princess Alice Hospice

2. Physical Activity in Palliative Care Declaration Personal Interest Thank you

3. Exercise in Cancer Anorexia Syndrome Exercise in Cancer Rehabilitation Exercise and Palliative Care professionals Physical Activity in Palliative Care

4. Importance Overview - Cancer Cachexia and exercise Definitions Medical Assessment Symptom management Re-Framing Exercise in Cancer Anorexia Syndrome

5. Impact of CACS Weight loss/fatigue/anorexia Occurs in up to 20% at dx; up to 80% in advanced cancer Attributed as main cause of death in ~20% patients Loss of >10% of premorbid weight = poor prognostic indicator & associated with decreased survival Strasser & Bruera, Hematol Oncol Clin N Am 2002

6. Asthenia/Fatigue has been ranked as the longest-lasting, most disruptive sx with the greatest impact on QOL 95% cancer patients endorse this as chief symptom: most common symptom Assessment difficult; multiple contributing factors Cancer, treatment, complications of tx or ca, meds, other physical & psychological conditions Barnes & Bruera, Intl J Gynecol Cancer 2002

7. Additional impact in Palliative Setting Profound sense of loss associated with drastic changes in body image & ability to be active Often a cause in people’s withdrawal from social life Leads to increases stress around food/feeding by patient, family, friends Loss of functional status Decreased performance status = decreased treatment candidate All 3 symptoms very common in other life- limiting illnesses: AIDS, COPD, CHF, CKD, RA Withdrawl

8. Manifest in number of diseases – Cancer – HIV/Aids – Chronic Heart Disease – Chronic Renal Disease – Chronic Respiratory disease – Acute and Chronic infections can also produce some similar effects K E Y Q U E S T I O N O N E I s C A C S p a t h o l o g i c a l o r p h y s i o l o g i c a l ? Impact Anorexia/ Cachexia/Fatigue Syndrome

9. Overview Many routes to the same end

10. CAUSES OF CACS Deconditioning

11. PRIMARY ANOREXIA CACHEXIA SYNDROME

14. “We treat the wrong patients at the wrong time with the wrong treatments”

16. Definitions

17. Cancer Cachexia definition 2010, 2 international acceptance 3 Cancer cachexia is a multifactorial syndrome defined by an ongoing loss of skeletal muscle mass ( with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment. Its pathophysiology is characterised by negative protein and negative energy balance driven by a variable combination of reduced food intake and abnormal metabolism. 1: Blum D et al. (EPCRC) Support Care Cancer 2010;18(3):273-9 2: Fearon K & Strasser F, et al., (EPCRC) 2010 3: Argilés JM et al. J Am Med Dir Assoc 2010;11:229-30

18. CACS Cachexia: involuntary profound loss of lean body mass and adipose tissue. Anorexia: Loss of appetite Asthenia/Fatigue: listlessness, decreased energy, decreased motivation; physical + cognitive components

19. Cancer cachexia is a multifactorial syndrome defined by a ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment. Its pathophysiology is characterized by negative protein and negative energy balance driven by a variable combination of reduced food intake and abnormal metabolism. IMPROVEMENT: To assess, treat, and evaluate patients with CACS, now recognised need for objective assessments of physical function. 1 1: Helbostad JL et al. Supp care Cancer 2010

20. Consensual Cancer Cachexia Classification Definition and Diagnosis Phases (early, cachexia, refractory) Phenotypes (inflamm, anorexia, muscle)

21. Classification of cachexia: cachexia represents a spectrum. Not all patients will progress down the spectrum. There are no robust biomarkers to identify those in the pre-cachectic phase who are likely to complete the journey or the rate at which they will do so. Phases

22. Pre-clinical cachexia (or early cachexia) In patients with cancer, early clinical (e.g., loss of appetite, decreased nutritional intake) and metabolic (e.g. insulin resistance, inflammation), signs of cachexia can be present, without the presence of significant involuntary weight loss (i.e. ≤ 5%) Muscle mass is always money in the bank

23. Cachexia Weight loss more than 5% over 6 months and continuing Presence of inflammatory markers (CRP) Reduced food intake Goals of intervention Dietary assessment and encouragement Exercise and muscle mass protection Good symptom control Reduce inflammatory process

24. Cachexia Weight loss more than 5% over 6 months and continuing Presence of inflammatory markers (CRP) Reduced food intake Goals of intervention Dietary assessment and encouragement Exercise and muscle mass protection Good symptom control Reduce inflammatory process Muscle mass is always money in the bank

25. Refractory (late) cancer cachexia Advanced muscle wasting (with or without loss of fat) due to progressive cancer, no longer responding to anticancer treatment. Patients have a low performance status and short life expectancy (<3months) At this stage the burden of artificial nutritional support usually outweighs any potential benefit. Therapeutic Goals focus on alleviating the consequences/complications of cachexia, e.g. symptom control (appetite stimulation, nausea), eating-related distress of patients and families. Exercise about using the muscle you have to best advantage

26. Improvements for daily clinical care? Muscle building/maintaining intervention at a time when intervention effective Functional goal intervention at a time when supportive care is appropriate Scientific support to differentiate between the two You cannot not exercise, even if the goals of exercise change

27. Sarcopenia The loss of skeletal muscle mass and strength Fatigue

28. Volume and quality of muscle now key Visser M, Kritchevsky SB, Goodpaster BH, et al. Leg muscle mass and composition in relation to lower extremity performance in men and women aged 70 to 79: the health, aging and body composition study. J Am Geriatr Soc 2002; 50: 897–904.

29. Invest New Drugs. 2013 Dec 17. Low skeletal muscle is associated with toxicity in patients included in phase I trials. Cousin SCousin S1, Hollebecque A, Koscielny S, Mir O, Varga A, Baracos VE, Soria JC, Antoun S.que A, Kosciearga A, Bara JC, S.

30. Loss of Muscle Mass Loss of Muscle Quality Ativity levels matter

31. Assessment

32. Assessment Confirm diagnosis and stage of CACS Identify Secondary causes of CACS Treat reversible causes of CACS Slow down irreversible causes of CACS Assess potential multimodal interventions

33. Which Zeta Jones has ACS?

34. Reversible Causes? General Medical Assessment Specific Medical Assessment

35. Attention to detail Lothian Guidelines

36. Investigations CRP - Inflammation present acute phase proteins Other disease markers?, Anaemia/ LFT/ U&E/ Albumin/Infections Hormonal Status? Testosterone, Thyroid, Insulin? Muscle Mass? Functional assessments Psychological Investigations (BDI) Sleep assessment Medicine Review

37. Symptom Management

38. Treatment Issues Non selective application of treatments Anti-cachexia drugs: Progestins, C-steroids NSAIDS- high price for short-term better appetite 1 Anti-cancer treatment - variable cachexia improvement & deterioration 2 Nutritional supplement - enteral, parenteral very variable results from nutrition studies 3 Physical function interventions- responses seem to vary, not explained: age, sex 5 Psychosocial interventions - uncertainty when and how to counsel 6 1: Oxford Textbook of Palliative Medicine, 4 th Edition; 2: Oberholzer R et. al., EAPC 2010, Poster #281; 3: Ravasco P et al., Clin Nutr 2007;26:7-15; 4: Bozzetti F et al. Clinical Nutrition 28 (2009) 445– 454; 5: Oldervoll L et al. EAPC 2010, oral comm. #30; 6: Hopkinson J et al., EAPC 2010, oral comm.

39. When we dont know we risk bluffing

40. Cancer Related Fatigue (CRF)  Correlation between fatigue and inflammatory markers  Toxicities and musculoskeletal alterations following Rx  Co-morbidities: anaemia, cachexia, sleep disorders and depression  Exercise has the strongest evidence base for the management of CRF

41. High intensity exercise is safe (Adamsen et al, 2009) Resistance exercises as beneficial as aerobic exercise (Courneya et al, 2007) Programme type and timing need careful consideration (Thorsen et al, 2005) Advanced cancer studies (Lowe et al, 2009) Physical activity interventions significantly reduced fatigue post treatment (Speck et al, 2010). 14 studies, 93% positive, 50% statistically significant Strength of the effect size varies largely between studies Cancer Related Fatigue and exercise

42. Current common treatments Most single therapies not very efficacious No magic bullet Apart from........ Exercise +

44. Multimodal Management cancer cachexia.

46. Management Montreal High index of suspicion good relations with oncologists Early assessment by dietician, OT, Physio and Doctor CRP, WCC, Testosterone level, exercise tolerance Early intervention –Exclude and treat secondary causes –Promote regular exercise (Use it or loose it) –Nutritional advice (CNR website) –Social support

47. Early Intervention Montreal Cancer Nutrition Rehabilitation Programme Doctor, 2 physios, Dietician, Gym, Complementary Therapies All patients with Lung Cancer and raised CRP Assessment Management

48. Don’t touch my bone…. CACS care is multiprofessional

49. Re-Framing

50. Patient and family need clear diet and exercise goals

51. “Appropriate nourishment and exercise across the life span” REFRAMING CRUCIAL FOR FAMILIES

54. Current novel research Targeted therapies Proteasome inhibitors TNF inhibitors Monoclonal antibodies to IL-6 Anabolic cytokines (IL-15) Specific cannabinoid-receptor antagonists Role of Grehlin (‘gut-brain’ hormone), leptin Alpha-melanocyte-stimulating hormone Growth Hormone/IGF/IGF-I treatments Immunonutrition (omega 3 EFA, L-arginine, L-carnitine glutamine, nucleotides) Anti-cytokine approaches Anti-sense NFkappa-B Soluble TNF-alpha receptors Cytokine antagonists (pentoxifylline, bradykinin antagonists)

55. What would I want? Early intervention, team approach, multimodal interventions Exercise Support Nutritional support (whey protein) /anti- inflammatory/anaemia therapy/testosterone check Megestrol acetate??/ibuprofen Metoclopramide Oral nutritional supplements/eicosapentaenoic acid(EPA)

56. Exercise in Cancer Rehabilitation

57. Back On Track

59. Barriers: Illness/Other health problems (37.3%) Joint Stiffness (36.9%) Fatigue (35.7%) Pain (30.1%) Lack of motivation (26.5%) Facilitators: Fun (88.0%) Variety of exercises (81.8%) Gradually progressed ((78.9%) Flexible (75.5%) Personal goal setting (73.9%)

60. Cancer Rehabilitation Exercise in Cancer and Palliative Rehabilitation

61. Intervention A holistic baseline assessment Multiprofessional clinic involving a 20min consultation with each professional Exercise/information package Personal Diary Pedometer Weekly contact over 8 weeks Personalised plan

62. This consisted of the option to partake in:  Group based exercise programme, conducted at the research gymn with home based walking and exercise (strengthening)  Home based walking programme and exercise (strengthening) with weekly phone call  Exit - (community based) onward referral to appropriate exercise programmes in the community Personalised 8 week exercise plan

63. CharacteristicWithin the pilot overallWithin the focus groups Gender 2 males and 16 females2 males and 11 females Age Aged 40 to 60 8 Aged 61to 85 10 Aged 40 to 60 5 Aged 61 to 85 8 Type of Cancer [1] 15 breast 1 colon 1 bone I myeloma 1 prostate 11 breast 1 bone I myeloma 1 prostate County of Residence Antrim 7 Down 6 Tyrone 2 Fermanagh 2 Derry/Londonderry 1 Antrim 6 Down 4 Tyrone 2 Fermanagh 0 Derry/Londonderry 1 Home based programme or gym based Home based 12 Gym 6 Home based 7 Gym 6 [1] Note: Numbers exceed 18 because one participant had multiple cancers. Results

65. For a cost of 200 pounds per patient there is an economic saving to the NHS of 1500 pounds (Mutrie et al, BMJ, 2007) Results Statistically significant improvements were seen in; the primary outcome of fatigue the secondary outcomes of six minute walk test timed sit to stand depression reduction in triceps skin fold thickness. If exercise was second line chemotherapy....

66. Overall Assessment “[It] did what it said… really helped fatigue…”, “more energy” “gave you skills [to self manage fatigue]” “completely transformed my life… energy, sleeping pattern… feel I’ve got my life back”, “I feel I have got my life back… a few weeks ago, I wouldn’t have sat here [in the focus group] and spoken... joined in… didn’t have the confidence… I’m even back to playing badminton!” “[has been] life saving”. If exercise was second line chemotherapy....

67. Exercise and Palliative Care Professionals

68. 68 The Problem To identify best venous thrombus prophylaxis practice for hospice we need to know; The prevalence of VTE in hospice patients The Impact of VTE on hospice patients The impact of of using venous thrombous prophylaxis on hospice patients

70. What others have done Pilates at lunch times twice a week Cycle to work scheme support Use of Physiotherapy department for staff Staff contract with local gymn Standing meetings “We are good at looking after our patients but lousy at looking after ourselves” How can we build that 15 minutes a day into our lives?

71. Exercise in Cancer Anorexia Syndrome Exercise in Cancer Rehabilitation Exercise and Palliative Care professionals Physical Activity in Palliative Care

72. It doesn’t need to be “hightech” to be transformational