ESMO PRECEPTORSHIP PROGRAMME SUPPORTIVE AND PALLIATIVE CARE

SESSION 6 MULTIMODAL AND MULTIPROFESSIONALMANAGEMENT

NUTRITION IN THE CANCER PATIENT: HOW TO MAKE DECISIONS (NUTRITION, ANTICANCER DRUGS), WHEN TO MOVE TO INVASIVE NUTRITION, VALUE OF PHYSICAL TRAINING

Florian Strasser, MD

Assoc. Professor (PD, Dr. med., ABHPM)

Oncological Palliative Medicine,

Clinic Medical Oncology and Hematology, Dept. Internal

Medicine, Cantonal Hospital, St.Gallen

ESMO Designated Centers Working Group, past Chair

Tuesay 17. April 2018 / 09:00-09:25

Lugano

DISCLOSURE SLIDE

Unrestricted Grant to Institution for

Cachexia research from Helsinn

Advisory Boards, Expert Opinion

reimbursed to Institution last two

years from Danone-Nutricia,

Grünenthal, Helsinn, Mundipharma,

Novartis, Ono, PrIME, Vifor

Nutrition in the cancer patient- Malnutrition versus cachexia

- Principles of nuritional therapies incl needs

- Mgmt of secondary nutrition impact symptoms

Decisional processes – invasive treatments- Chemotherapy in palliative intention

- Invasive Nutrition - parenteral

Muldimodal management- nutrition & anticancer treatment & empowerment

- Physical training

- Cancer rehabilitation

Mr K, 72-j, Pancreas-adeno-ca, liver-mets, 2nd line

gemcitabine/nab-paclitaxel, Fatigue, Anorexia, PS2, BMI 21, Weight loss 14%/6mts,

CRP 45

45y teacher, metastatic colo-rectal cancer, 1st line

anticancer treatment„Fatigue bothering“, PS 1BMI 22.2, weight stable,

CRP 8

Cancer patients living with cancer having nutritional issues

61y, metast. cervical cancer, no anticancer

treatment. Fatigue, anorexia, distress,

PS3, BMI 17, CRP 36, Weight loss 21%/6mts

62y man, SCC-H&N, refused controls, PS4 Fatigue anorexia, weight loss 18% / 6 mts, BMI 22, referred(GP) for terminal care

Nutritional needs: 25-30 kcal/ kg body weight

1.0-1.5 g Protein / kg body weight

Vitamins & minerals: as healthy people (if no deficiency)

Pre-cachexia CachexiarefractoryCachexia

Malnutrition noCachexia

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In clinical practice, several mechanism and cofactors happen at the same time in my patient(s)���� structured thinking helpful

1: Fearon K & Strasser F, et al. Lancet Oncol 2011;12:489-95

2: Argilés JM et al. J Am Med Dir Assoc 2010;11:229-30

Gut-brain-

axis

Inflammation,

active tumorMuscle & Fat

loss

Sarcopenia caused by:

Hypogonadism

Physical inactivity

Corticosteroids

Thyroid dysfunction

Age-related*

- Less muscle stem cell response to acute resistance exercise- Same Type I, less Type II fibres- myogenic program reduced- impaired induction of MyoD in Pax7 cells

Malnutrition and Cachexia

* McKay B etz al. FASEB J 2012;(26):2509–2521

Joseph AM et al. Aging Cell 2012; 11: 801–809

Malnutrition (Starvation) caused by:

●●●● Diet mistakes / misconceptions: too healthy, ..

●●●● neglect for maintenance of nutritional intake

- “no eating” due to procedures, hospitalization1

- helping patients to eat (edentulousness1)

●●●● Secondary Nutrition-Impact symptoms2

- Pain, breathlessness, constipation, dysgeusia, …- Periods of nausea/vomiting, stomatitis, dysphagia, gastric acid- (partial) bowel obstruction, diarrhea,

malabsorption, prolonged constipation, ..

●●●● Cachexia

1: van der Pols-Vijlbrief R et al. Ageing Res Rev 2014;18:112-31

2: Omlin A et al. J Cach Sarcop Muscle 2013;55-61

Inflammation caused by:

Infections- If steep increase of C-Reactive Protein (x 2-5 /3-5 days)- may consider empirical antibiotic therapy (after cultures)- may1 measure Pro-CalciTonin (neg & pos predictive value)2

- may use PCT/CRP ratio3

Corticosteroids

Chronic inflammatoric diseases

Pro-inflammatoric drugs & herbal therapies

Aktive tumor disease (Cachexia)

1: Naito T et al. Intern Med 2015;54:1989-94; Chaftari AM et al. PLoS ONE 2015;10:e0130999

2: Sbrana A et al. New Microbiol 2016;39(3); Wu CW et al. Support Care Cancer 2015;23:2863-72

3: Hangai S et al. Leuk Lymphoma 2015;56:910-4; Markova M et al. Support Care Cancer 2014;21:2733-42

Cachexia requires assessment-based multidimensional interventionsdelivered by multiprofessional teams

● Depletion of reserves:

muscle mass and fat mass

● Nutritional intake and „gut-

brain axis“ symptoms

● Inflammation and tumor

dynamics

● Neuro-muscular and

emotional-cognitive function

How to assess in daily care?

First screen all patients for anorexia,

decrease nutritional intake, and weight loss

Then perform a cachexia assessment

Reserves Weight loss history (%; 1, 2, 6 mts), BMI(muscles) check for edema (thigh), (if fluid retention consider CT L3/4 or DEXA)

Intake 2 day diet diary, % kcal/protein / needs (Harris Benedikt)(gut-brain) Appetite, hunger, satiety, taste/smell

Search nutrition impact symptoms (S-NIS checklist, PG-SGA), treat(smell, taste, teeth, mouth, dysphagia, gastric acid, constipation, anal, diet, …)

Catabolism Estimate cancer disease dynamics & responsiveness to TxCRP >10mg/l (no clinical infection, consider PCT/CRP)Albumin

Function Physical function (KPS), muscle strength (stairs – floors)Estimate Patients Motivation/Participation

���� Decide on cachexia phase* and goals of intervention

Patient-centred care: adequate assessment of cachexia domains

* Blum D et al. Ann Oncol 2014;25:1635-42

Cachexia requires assessment-based multidimensional interventionsdelivered by multiprofessional teams

● Depletion of reserves:

muscle mass and fat mass

● Nutritional intake and „gut-

brain axis“ symptoms

● Inflammation and tumor

dynamics

● Neuro-muscular and

emotional-cognitive function

«Best Supportive Care1»

«Early Integrated Cancer Palliative Care2»

1: Cherny JCO 2009; Zafar Lancet Oncol 20122: Temel NEJM 2011; Zimmermann C Lancet 2014; Bakitas M JCO 2015; Temel JCO 2016

(Lung & non-CRC GI); Maltoni EJC 2016; Ferrell ASCO JCO 2017

1: Baldwin C J Natl Cancer Inst 2012 // 2: Oberholzer R JPSM 2013., Reid J J Adv Nurs. 2013, Amano K, JSCM 2016 // 3: Stene GB Crit Rev Oncol Hematol. 2013 // 4: Quill TE & Abernethy A.

NEJM 2013. Smith TJ et al. JCO 2012 // 5: Köberle D JCO 2008; Au H-J JCO 2009 // 6: Fearon K

Nat Rev Clin Oncol 2013; Bruggemann AR JOP 2016;12:1163-71.

► needs-adjusted adequate nutritional intake1,2

► adequate physical function (resistancetraining & aerobic activity)3

► multidimensional symptom control, patienteducation

► anticachexia drugs6

► tolerable anticancer therapy to control tumoractivity5

► Illness & prognosis understanding, coping, relieve eating-related distress participation4

► continuity of care: patient & family members

► needs-adjusted adequate nutritional intake1,2

► adequate physical function (resistancetraining & aerobic activity)3

► multidimensional symptom control, patienteducation

► anticachexia drugs6

► tolerable anticancer therapy to control tumoractivity5

► Illness & prognosis understanding, coping, relieve eating-related distress participation4

► continuity of care: patient & family members

„physical activity: any bodily movement produced

by the skeletal muscles resulting in a substantial

increase in energy expenditure over resting levels“.

� individualized, maybe a program

Therapeutic Physical Activity in cancer cachexia

„Prescribe“: 3-4 x week both muscles & walk- Muscle: 2 x 10 Repetitions of arms & legs- Walk 10-15 Minutes Borg 4 (0-10): mild sweating

Evidence in advanced cancer patients*: some to many patients do profit, mixed populations contaminate effects

* Stene GB et al. Crit Rev Oncol Hematol. 2013 Aug 8

What do physiotherapists?

Resistance-Training

(Muscles) � Strenght

Physical Activity Training

(Bike etc.) � Endurance

Support daily activity ���� QoL

Balance � gait, no falls

Massage ���� Pain, QoL

Both aerobic & resistance training are important

combined

aerobic and

resistance

aerobic

exercise

resistance

exercise

Effect of physical activity on muscle strenghtin incurable cancer patients

Stene GB et al. Crit Rev Oncol Hematol. 2013;88:573-93

Systematic review: physical activity in cachexia Misconceptions on physical activity of

patients having cancer cachexia

●

●●

● „Resting and sleeping will help muscles to recover“

●

●●

● „Physical activity will absorbe too much energy“

●

●●

● Standard Rehabilitation programs are for all patients

●

●●

● Walking is sufficient for muscle training

●

●●

● ...

Nutritional counselling and patient education

1: Shragge JE, et al. Palliat Med 2007;21: 227-33.2: Halfdanarson T et al. J Support Oncol 2008;6:234–237; 3: Ravasco P et al. J Clin Oncol 2005.

Prado CM et al. Can J Diet Pract Res. 2012 ;73(4):e298-303; Baldwin C et al. J Natl Cancer Inst 104, 371–385 4: Balstad TR et al. Crit Rev Onc Hem 2014 // 5 Oberholzer R, Hopkinson J, et al., JPSM 2013; 46:77-95

6: van der Pols-Vijlbrief R et al. Ageing Res Rev 2014;18:112-31; Omlin A et al. J Cach Sarcop Muscle 2013;55-61

Concious control of eating1

Eat, even if you are not feeling hungry, moderate pressure

Nutritional counselling2,3,4

● Assess and improve intake of calories and protein

(Harris-Benedict, disease factor, mobility factor)

● Assess patients‘ individual eating habits

● Check and increase frequencies of daily meals1

● Empower patients to change their daily habits

● Help patients and family members to understand (early satiety, no hunger, taste

changes, etc

● In refractory cachexia Patients: alleviate eating-related distress, fabric talk5

Manage secondary nutrition impact symptoms6

Weight loss. Normal 85. 6 mts ago: 77 kg. 1 mts ago: 74 kg. actual: 68 kg

Nutritional intake:Not enough calories, Proteins with 2 drinks ok

Counselling. Small (low volume) meals, many. Proteins (Fat). Minimize water, but enough fluids

Patients overestimate nutritional intake

���� requires formal nutritional assessment

Nutritional advice: Living with cancer ESPEN Guidelines 2016; Arends J et al Clin Nutr 2017;36:11-48

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FStrasser TV: https://www.srf.ch/sendungen/puls/krebs-diaeten-ueberlange-grippesaison-hallo-puls

Cognitive control of eating: good education of patient and proxies important- my body gives me not any more the same signals [hunger, taste, satiety] as before

- need to change daily habits: frequency, types of food, expected pleasure from food

Frequency increase! 7 x / day (every 1 ½-2 hours: clock!)

Protein- and fat-rich Nutrition: Energy density increased

Nuts, eggs, butter, (double) cream, sour cream, condensed milk, olive-oil,

other oils, milk powder, hemp powder, crumbled cheese, mayonnaise

Honey, sugar, concentrated pear juice, maple sirup

„healthy Diet“ (few Fat, many fibres, 5 x fruits/vegetables per day) are not

appropriate for advanced cancer patients. BUT: Biological Food Yes.

Drinking fluids: inbetween meals, NOT before

Consider bitters (vermouth, yarrow, centaury), alcohol (!)

Nutritional supplements: cold, «creative» flavor, between meals, non-chemo days

ESMO CPG Cachexia, submitted

Manage secondarynutrition impact

symptoms: THE BIG 5

. Drug-related- CINV: KJ S4

. Stomatitis-Esophagitis- Mucositis: FS S4

. Gastric acid related- PPIs, Al-oxide et al

. Constipation- combination laxatives

. Bowel obstruction- if irreversible: PEN

* Drugs: Opioids, amiodarone, anticonvulsants, etc

Good management of gastro-intestinal function can conserve – improve appetite

Constipation: identify, treat, prevent- Medical history: frequence, amount, colour, quality- stepwise approach: osmotic & stimulating laxatives- lots and lots of patient education

Procinetic therapy: Metoclopramide, Domperidon1,2

Consider pragmatical protone-blockade for 1 week

1: Bruera E et al. J Pain Symptom Manage 2000; 19:427.

2: Yavuzsen T et al. J Clin Oncol 2005;23:8500-8511.

���� If irreversible misfunction of GI-tract: consider ParEnteral Nutrition

1: Good P et al. Medically assisted nutrition for adult palliative care patients. Cochrane 20142: Dev R et al. Curr Opin Support Palliat Care 2012:365-7

Evidence for PEN (defined population, defined intervention, control, if patient-reported outcomes then mandatory placebo, defined time to endpoints,

endpoints covering all important domains) is poor1,2

* Richter E Anticancer Res 2012;32:2111-8; Pelzer BMC Cancer 2010;10:86; 2: Orrevall Y Nutrients 2013; Bozzetti Ann Oncol 2014; Culine S Supp Care C 2014; Senesse P JPSM 2015; Chen Eur J Cancer Care 2013

More prospective phase II studies or case series from 17-414 pts*

Bozzetti F et al. Ann Oncol 2014

KPS ≤/>50 mGPS*Metastatic

� If «mild» Cachexia(and decreased intake

due to intestinal dys-

function) PEN may help

* CRP >10mg/dlAlbumin <35g/l

Laird BJ et al. Clin Cancer Res 2013;19:5456-64

Outcomes are drivennot by nutritional

needs alone, but byinflammation

Conceptual Framework: Fearon K & Strasser F, et al. Definition and classification of cancercachexia, an international consensus. Lancet Oncol 2011;12(5):489-95

Cancer Anorexia Cachexia Syndrome can develop from Precachexia to Cachexia to Refractory Cachexia

Performance Status low ([2],3,4)

Close to End of life

BUT

In modern oncology

increasingly

challenging concept

of refractory cachexia

ESMO CPG Cachexia, submitted

Anticancer treatment���� causing Secondary Nutrition Impact Symptoms and muscle toxicity

Systematic review (Medline 2005-16: n=24)

Chemotherapy-related digestive symptoms

likely to impair nutritional status:

dry mouth, nausea/vomiting, stomach pain,

diarrhea and constipation

Caillet P Clin Nutr 2016 Dec 18

Köberle D JCO

2008;26:3702-8

Cholangio-Ca

Patient-derived

clinical benefit

response

PR: 7/10

SD: 16/24

PD: 2/5

Anticancer treatment���� explicit goals to improve cancer-related symptoms

Clinical trials with primary endpoint cancer-

related symptoms & syndromes are still rare

Anticancer treatments can cause a lot of

secondary nutrition impact symptoms, these

data are not well reported, but clinical reality

- Stomatitis, Xerostomia, Taste alterations

- Nausea/vomiting, stomach pain

- GI mucositis, Diarrhea, Constipation

- Endocrine abnormalities, etc,

Muscle toxicity �

Anticancer treatment ���� Impact on Muscle

Folfox/Folfiri causes. mitochondrial depletion

Barreto R

Oncotarget

2016;

43442-60

MEK-1

Inhibitor

Soluble

Activinin

Rec 2B

. activation of ERK1/2 & p38 MAPKs-dependendpathways

Chen JA J Cach

Sarcop Musc

2015;6:132-143

Cisplatin (& tumor) causes muscle atrophy. downregulate Akt, myoD, myogenin. upregulate proteolysis (UbP), Myostatin

. Ghrelin may partially reverse effects

Chemo � inflammation, oxidative stressSultani M Chemother Res Pract 2012;490804

Chen JA J Cach Sarcop Musc 2015;6:132-143

How to make decisions forinvasive interventions?

Strasser F, et al Cancer J 2010;16:483-7

Priority in the context of all issuesmultidimensional: values, needs, symptoms

Price of intervention: QoL, AEs, time, cashConsider real impact on patient

Probability: desired, concrete outcomeLikelihood of and expected time to reach

Prognosis time to experience outcomeConsider cancer dieases & comorbidities

Progression: illness expected to be stableDynamics of cancer disease

Prevention of (expected) sufferingLikelihood of complications / deterioration

Preference of patient (after education)Ensure real understanding, accept choice

Concrete clinical management (in my practice) of parenteral nutrition

● Find and manage reversible secondary causes

● Decide if refractory Cachexia

- CRP > 30g/dl without Infection ?

- cancer-specific treatment likely effective?

● Decisional approach with patient (7 P’s)*(Priority, Prognosis, Progression, Probability, Price, Prevention,

Preference)

Sideeffects: Infections, iv-line, time invest, dependence

● First 4 days updosing (refeeding)

monitor: Na, K, Phosp, Gluc, TG, AST, ALT

● Effect defined: KPS, Fatigue, Symptoms, prealbumin

● After 1 week, then weekly, decide multiprofessional (nurse

(!), nutritionist, oncologist, physiotherapist, ..) to continue

Key message:A therapeutic trial

may help in uncertainty

balancing starvationvs cachexia

Conclusions

Decisions regarding nutritional treatment in advanced cancer patient

depend on multidimensional assessment based definition of the

cachexia phase (or «simple» malnutrition), which requires close

communication of different professionals

Decisional proceses require a structured assessment of patients

understanding of the disease, of the possible interventions and the

expected outcomes

Outcomes shall be concrete, measurable and with a likelihood tag and

a time until outcome tag

A structured thinking approach may guide decisional practice