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Recognizing anorexia cachexia early how to intervene · 19.11.2015 5 SIOG 13. Nov 2015 Anorexia Cachexia / F. Strasser Malnutrition causes in cancer patients Diet mistakes / misconceptions:

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Text of Recognizing anorexia cachexia early how to intervene · 19.11.2015 5 SIOG 13. Nov 2015 Anorexia...

  • 19.11.2015

    1

    SIOG 13. Nov 2015 Anorexia Cachexia / F. Strasser

    Disclosure Slide (last 5 years)

    Unrestricted industry-grants for clinical research- Celgene (Lenalidomide Cachexia trial)- Fresenius (Survey parenteral nutrition malignant bowel obstruction)- Helsinn (for Palliative Research Center, MENAC trial & other)

    Participation in company-lead clinical cachexia trials- Novartis (BYM338 cachexia trial)

    Punctual Advisorship (Boards, Expert meetings)Acacia, ACRAF, Amgen, Baxter, Celgene, Danone, Fresenius, GSK, Grünenthal, Helsinn, ISIS Global, Millennium/Takeda, Mundipharma,

    Novartis, Novelpharm, Nycomed, Obexia, Otsuka, Ono, Pharm-Olam, Pfizer, Psioxus, PrIME, Santhera, Sunstone, Teva, Vifor

    No: Mono-sponsored industry-controlled Sattelite meetings No: Personal financial interest (stocks, private use of honoraria, ...)

    SIOG 13. Nov 2015 Anorexia Cachexia / F. Strasser

    Florian Strasser, MD ABHPMOncological Palliative Medicine,

    Clinic Oncology/Hematology, Dept Internal Medicine & Palliative Centre

    Cantonal Hospital St.Gallen, Switzerland

    Special SIOG & MASCC partnership session 13. Nov 2015 Multinational Association of Supportive Care in Cancer

    Nutrition issues and challenges in older patients with cancer

    Recognizing anorexia cachexia early how to intervene

    ESMO Palliative Supportive Care Working Group, ChairMASCC Working Group Nutrition and Cachexia, Co-Chair

    Society Cachexia Wasting Sarcopenia, Board

  • 19.11.2015

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    SIOG 13. Nov 2015 Anorexia Cachexia / F. Strasser

    Mr K, 72-j, Pancreas-adenocarcinoma liver-metsGemcitabine weekly second-line, since 3 weeks

    „How are you“: swollen legs, people do nothing about it.

    Am tired and weak, poor appetite, I want living at my home.

    „It is difficult

    seeing him

    getting thinner

    he does not

    eat enough

    SIOG 13. Nov 2015 Anorexia Cachexia / F. Strasser

    clinical «nutritional» challenges in care of theolder patient with cancer

    ● how to screen for and assess nutritional issues?

    ● how to set goals to motivate patients forpalliative rehabilitation?

    ● who is the patient who profits from nutritional interventions or drugs for anorexia/cachexia?

  • 19.11.2015

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    SIOG 13. Nov 2015 Anorexia Cachexia / F. Strasser

    Age-related Sarcopenia- Aging of the neuromuscular junctions, loss of motoneurons,

    of the myogenic capacity and muscle mass

    - Loss of muscle strenght and physical function

    Secondary Sarcopenia- Hypogonadism, Corticosteroids, Thyroid, physical inactivity

    Malnutrition („Starvation“)- Many causes for decreased oral intake in elderly patients

    Cancer cachexia- hypercatabolic, hypoanabolic, inflammatory changes,

    decreased intake, loss of muscle & function

    Cachexia caused by Comorbidities- chronic heart failure, COPD, etc.

    Nutritional issues in the older patient with cancer

    SIOG 13. Nov 2015 Anorexia Cachexia / F. Strasser

    Slid

    e c

    ourt

    esy

    ofV

    ickie

    Bara

    cos

    9.2

    014

    Co-Occurrence in cancer patients

  • 19.11.2015

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    SIOG 13. Nov 2015 Anorexia Cachexia / F. Strasser

    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

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

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

    SIOG 13. Nov 2015 Anorexia Cachexia / F. Strasser

    Malnutrition

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

    Systematic Literature review for cofactors: 28 studies,

    122 unique potential & 37 sufficiently used determinants

    Association of determinant with protein-energy

    malnutrition

    Strong evidence poor appetite

    Moderate evidence for edentulousness, having no diabetes,

    hospitalization and poor self-reported health.

    Strong evidence for no association: anxiety, chewing difficulty,

    few friends, living alone, feeling lonely, death of spouse, high

    number of diseases, heart failure and coronary failure, stroke,

    anti-inflammatory medications.

    Frequency in older people 5-35%,

    depending on population

  • 19.11.2015

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    SIOG 13. Nov 2015 Anorexia Cachexia / F. Strasser

    Malnutrition causes in cancer patients

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

    ●●●● neglect for maintenance of nutritional intake- Periods of “no eating” due to procedures

    - helping patients to eat (dentures)

    ●●●● Secondary Nutrition-Impact symptoms1

    (pain, breathlessness, constipation, dysgeusia, …)

    - Periods of nausea/vomiting, stomatitis, dysphagia, gastric acid

    - (partial) bowel obstruction, diarrhea, malabsorption, prolonged constipation, ..

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

    SIOG 13. Nov 2015 Anorexia Cachexia / F. Strasser

    Hyper-catabolism(Inflammation, cancer dynamics)

    Hypo-anabolismAnorexiaNutritional Intake ▼Autonomic Dysfunction

    European Association Palliative Care - Research Network 2012 // 1: Tan BH et al.

    EMBO Mol Med 2012;4(6):462-71; 2: Solheim TS et al. Br J Cancer. 2011;105(8):1244-51.

    Cancer anorexia cachexia

    Pa

    tien

    t X

    Pa

    tien

    t Y

    Loss of mass and quality

    of skeletal muscle

    Decline of “neuro”- &

    muscular function

    Pa

    tien

    t Z

    Fearon K & Strasser F, et al. Lancet Oncol 2011 ;12:489-95Argilés JM et al. J Am Med Dir Assoc 2010;11:229-30

  • 19.11.2015

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    SIOG 13. Nov 2015 Anorexia Cachexia / F. Strasser

    How to screen for nutritional issues in our patients?

    When should we start in the course ofcancer disease?

    Measure what mattersto patients QoL and anticancer Tx

    SIOG 13. Nov 2015 Anorexia Cachexia / F. Strasser

    Anorexia & cachexia related symptoms are frequent ….

    Seow H, et al. J Clin Oncol 2011:1151-8

    Tired & Appetite: top 2 / 10 (ESAS)� Many patients have cachexia

  • 19.11.2015

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    SIOG 13. Nov 2015 Anorexia Cachexia / F. Strasser

    Chochinov H et al. JPSM 2009;38:641-9

    N=253 adult pts (545 eligible)

    Life expectancy < 6 mts

    In palliative care program

    Age mean 69, SD 13.5

    Patient Dignity Inventory

    (Scale 1-5; Problem ≥ 3)

    � Several distressing

    factors (directly)

    related to Sarcopenia -

    Starvation

    Distress in advancedincurable patients

    SIOG 13. Nov 2015 Anorexia Cachexia / F. Strasser

    “nutritional issues” (malnutrition & cachexia) ���� survival

    ● Performance Status (abundant data from various tumors)

    ●BMI●Weight loss abundant data1 (mixed with starvation)●Weight loss & BMI2 (BMI: available reserves)

    ● Muscle mass (Sarcopenia)3

    ● Muscle attenuation3 (pro-catabolism, hypo-anabolism)

    ● Inflammation (CRP) & Albumin4 / Lymphocytes5

    1: Bozzetti F Crit Rev HemOnc 2013;173; 2: Martin L JCO 2015;90; 3: Martin L JCO

    2013;1539; 4 Laird BJ Clin Cancer Res 2013;5456; 5:Jafri BMC Cancer 2013;158

    modified Glasgow Prognostic Score4

    mGP

    S

  • 19.11.2015

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    SIOG 13. Nov 2015 Anorexia Cachexia / F. Strasser

    Renfro

    L e

    t al. J

    Clin

    Oncol2015;3

    3Associationof BMI and

    Survival

    Renfro L et al.

    J Clin Oncol

    2015;33

    SIOG 13. Nov 2015 Anorexia Cachexia / F. StrasserMartin L JCO 2015;90

    Grade

    0

    Grade

    1

    Grade

    2

    Grade

    3

    Grade

    4

    22.1 13.6 14.1 9.8 5.3

    Survival in months

    Weight loss and BMI

    CRP ≥ 10 mg/L

    Grade

    0

    Grade

    1

    Grade

    2

    Grade

    3

    Grade

    4

    38.3 30.6 27.8 18.1 8.1

    Grade

    0

    Grade

    1

    Grade

    2

    Grade

    3

    Grade

    4

    10.7 7.7 7.0 6.0 4.8

    CRP < 10 mg/L

    Survival in months

    Weight loss and BMI

    CRP

  • 19.11.2015

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    SIOG 13. Nov 2015 Anorexia Cachexia / F. StrasserSlide courtesy of Vickie Baracos 9.2014

    Surgical complicationspost-operative

    infections, reha-

    bilitation effect

    Lieffers JR Br J Cancer 2012

    But other (not

    North America)

    data seem less

    dramatic ..?

    Gu W et al. JCSM 2015:222

    SIOG 13. Nov 2015 Anorexia Cachexia / F. Strasser

    How to screen for nutritional issues in ourpatients?

    Fatigue, Anorexia: just ask, VAS (ESAS)BMI, weight loss

    Anticancer treatment toxicities

    When should we start in the course ofcancer disease?

    Early ! Means together with anticancer tx

  • 19.11.2015

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    SIOG 13. Nov 2015 Anorexia Cachexia / F. Strasser

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

    Secondary sarcopenia (C-steroids, bed rest,.)

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

    Second. nutrition impact (S-NIS, PG-SGA)

    Catabolism Cancer dynamics & responsivenessCRP >10mg/l (no clinical infection)Albumin

    Function Physical function (KPS), muscle strenghtMotivation/Participation

    Impact on TxPrior anticancer treatment toxicities

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

    Assess sarcopenia, malnutrition, cancer cachexia

    SIOG 13. Nov 2015 Anorexia Cachexia / F. Strasser

    Timon CM et al. British Journal of Nutrition 2015;113, 654–664

    Novel Assessment of Nutrition and AgeingSelf assessed on a computer screen

  • 19.11.2015

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    SIOG 13. Nov 2015 Anorexia Cachexia / F. Strasser

    Timon CM et al. British Journal of Nutrition 2015;113, 654–664

    Novel Assessment of Nutrition and Ageing

    not bad compared to four day assessment

    SIOG 13. Nov 2015 Anorexia Cachexia / F. Strasser

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

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

    Close to End of life

    What can I (meaningful, worthwhile) do? Setting fair goals «managing» Sarcopenia-Starvation

  • 19.11.2015

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    SIOG 13. Nov 2015 Anorexia Cachexia / F. Strasser

    Normal Precachexia Cachexia Refractory

    CachexiaDeath

    cachexia therapy goals, influencing interventions

    Reserves prevent loss stablilize - improve unavoidable loss

    Nutritional Intake prevent decrease stablilize - improve alleviate distress

    Inflam / Cancer Act. control cancer control cancer not controllable

    Function maintain maintain - improve unavoidable loss

    Cancer Supportive

    & Palliative Care

    Cancer Therapy

    ToxicitiesImportant effects Short-term alle-

    viation, EOL

    Anticancer therapy early lines ≥ 2nd lines no standards

    Goals Pre-emptive Stabilize Alleviate

    Influencing factors & interventions

    SIOG 13. Nov 2015 Anorexia Cachexia / F. Strasser

    If not refractory: Multidimensional Cachexiainterventions delivered 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

    ►needs-adjusted adequate nutritional intake

    ►adequate physical function(resistance training & activity)

    ►multidimensional symptom control, patient education

    ►anticachexia drugs (coming soon)

    ► tolerable anticancer therapy tocontrol tumor activity

    ► Illness & prognosis under-standing, disease coping

    ►continuity of care for patient & family members

    ►needs-adjusted adequate nutritional intake

    ►adequate physical function(resistance training & activity)

    ►multidimensional symptom control, patient education

    ►anticachexia drugs (coming soon)

    ► tolerable anticancer therapy tocontrol tumor activity

    ► Illness & prognosis under-standing, disease coping

    ►continuity of care for patient & family members

    These interventions areoverlapping with

    interventions of cancerpalliative care, and

    cancer rehabilitation

  • 19.11.2015

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    SIOG 13. Nov 2015 Anorexia Cachexia / F. Strasser

    To define goals of intervention, assess before (the need

    for) each Key Intervention Palliative Care

    llness & prognosis understanding

    Multidimensonal Symptom Control: Appetite, Fatigue

    Decision processes structured, guided, value-based process

    End of life preparation legacy, premortal grief/role, finish business

    Continuity of care Network multiprofessional workforce, family

    Care of family members burden of caregiving, distress

    Spirituality meaning of life, transcendence, religion, connectedness

    Adapted (Magaya N, Strasser F et al 2015) from Temel J et al,

    NEJM 2010; Jacobsen J, et al. J Pall Med 2011

    Possible form: Interactive checklist-based needs-assessment

    SIOG 13. Nov 2015 Anorexia Cachexia / F. Strasser

    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.

    Concious control of eating1

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

    Nutritional counselling2,3

    ● 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.)

  • 19.11.2015

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    SIOG 13. Nov 2015 Anorexia Cachexia / F. Strasser

    Baldwin C et al. J Natl Cancer Inst 104, 371–385

    Effectiveness of oral nutritional interventions in the management of weight loss in patients with cancer

    Metaanalysis: Dietary advice or ONS or both, 13 RCTs, 1414 pts

    Evans WK JCO 1987; Macia E Nutrition 1990; Nayel H Nutrition 1991; Ravasco P JCO 2005; Ravasco P Head Neck 2005

    Significant benefit on nutritional status, but heterogenity high (I2=76%)

    SIOG 13. Nov 2015 Anorexia Cachexia / F. Strasser

    Protein supplementation improves physical performance in frail elderly people: a randomized, double-blind, placebo-controlled trial

    65 frail elderly subjects: either daily protein or placebo supple-

    mentation (15 g protein at breakfast and lunch) x 24 wks

    Skeletal muscle mass: no change protein- (45.8 ± 1.7 to 45.8 ±

    1.7 kg) vs placebo (46.7 ± 1.7 to 46.6 ± 1.7 kg)

    Muscle strength (leg extension) increased in both groups

    (P < .01): protein (57±5 to 68±5 kg), placebo (57±5 to 63±5 kg)

    Physical performance improved (8.9±0.6 to 10.0±0.6) protein

    group, not change placebo (from 7.8±0.6 to 7.9 ±0.6)

    Tieland M et al. J Am Med Dir Assoc 2012;13(8):720-6

  • 19.11.2015

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    SIOG 13. Nov 2015 Anorexia Cachexia / F. Strasser

    „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

    Effect on muscle strength in cancer

    Both aerobic & resistance training are importantThe less inflammation, cachexia – the better it works

    combined aerobic

    and resistance

    aerobic exercise resistance exercise

    Effect of physical activity on muscle strenght in incurable cancer patients

  • 19.11.2015

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    SIOG 13. Nov 2015 Anorexia Cachexia / F. Strasser

    Misconceptions of physical activity in 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

    ● ...

    ���� Educate !

    SIOG 13. Nov 2015 Anorexia Cachexia / F. Strasser

    Cortico-steroids: effect only on appetite, only 1-2 weeks

    placebo-ctrl RCTs: 4 mg Dexamethasone 2 wks or 16mg

    methylprednisolone bid 7 days improve fatigue, anorexia1,2

    SE: proximal myopathy, candidiasis, depression, anxiety

    �C-Steroids are only drugs to relieve short term distress

    1: Yennu S et al. J Clin Oncol 2013;31:3076; 2: Paulsen O et al., J Clin Oncol 2014;32:3221

    3: Ruiz Garcia V et al. Cochrane Database Syst Rev 2013;3:CD004310

    4: Dev R et al. Cancer 2007;110:1173; 5:

    Current drugs used for cachectic patients

    Progestins: effect appetite (NNT 4), weight (NNT 12)but only fluid or fat mass, no better QoL, anti-anabolic effect 3,4

    SE: Dyspnea, edema, impotence, thromboembolism, mortality

    Procinetics: effect only on satiety, clinically important5

    (Metoclopramide 4 x 10mg, Domperidon 4 x 10mg)

  • 19.11.2015

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    SIOG 13. Nov 2015 Anorexia Cachexia / F. Strasser

    CannabinoidsFull plant contains many cannabinoids & 9-d-THC (dronabinol)

    Two negative big RCTs (vs placebo, vs megestat)

    Recent RCT: Dronabinol improves taste & protein consumption

    in dysgesuia pts1

    Drugs with in-sufficient evidence to improve cachexia

    1: Brisbois TD Ann Oncol 2011; 2: Ries A Palliat Med 2012; 3: Murphy RA Cancer 2011; 4: van der

    Meij BS Eur J Clin Nutr 2012; 5: Maccio A Gynecol Oncol 2012; 6: Solheim TS Acta Oncol 2012

    Fish oil or eicosapentanoic acidFish oil contains EPA (omega-3-fatty acids)

    Insufficient evidence (3 systematic literature reviews)2

    Recent (small) RCTs: may improve muscle mass NSCLC3,4

    NSARInsufficient evidence from small trials or only in combinations5

    SIOG 13. Nov 2015 Anorexia Cachexia / F. Strasser

    ● Melanocortin Receptor 4-antagonists

    ● Ghrelin & its analogues (natural Ghrelin, Anamorelin, etc.)

    � Anamorelin two finished global phase III trials (Romana)

    ● Androgen (SARMs, ...), β2-mimetics,...� Enobosarm two finished phase III trials (Power) 1

    Increase muscle mass, associated with stair climb power, fat ↓

    ● Muscle pathways (anti-myostatin, Act-RIIB,.)

    ● Anti-inflammatory (anti-IL-12, anti-IL-6, anti-TNF, Lenalidomide, Thalidomide, EPA)

    ● many other promises

    Anti-cachexia emerging drugs

    1: Dobs AS et al. Lancet Oncol 2013;14:335;

    Phase III: Crawford J et al oral presentation MASCC 2014;0546;

    2: Hong DS Phase I Lancet Oncol 2014

  • 19.11.2015

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    SIOG 13. Nov 2015 Anorexia Cachexia / F. Strasser

    Stores:Muscle increase

    Fat increase

    Muscle strenght:Handgrip no change

    Legs & physical activity not measured

    Symptoms:Cachexia-related

    Symptoms improved

    (FAACT)

    Fatigue (FACIT)

    improved

    Anamorelin

    Anticancer treatment toxicity not measured

    SIOG 13. Nov 2015 Anorexia Cachexia / F. Strasser

    Multimodal Intervention: pre-MENAC randomized Phase II 12 weeks

    Exercise Physiotherapist – initial instruction and assessmentAerobic – >= 2 x 30 minute sessions per week (Borg scale 12-14)Resistance – tailored 0.5-5kg weights. 3x20 minute sessions / week

    NutritionNutritionist – instruction & assessment, dietary advice & ONS

    Anti-inflammatory MedicationNSAID (celecoxib 200mg BID), EPA 2g/day (ONS)

    Patientsadvanced lung or pancreatic cancer start palliative chemotherapy

    Primary outcome: feasibility (compliance, enrolment).Secondary outcomes: weight, physical activity (using ActivPAL)

    CT based muscle mass.

    PreMENAC - Kaasa S et al. ASCO 2015 Poster

  • 19.11.2015

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    SIOG 13. Nov 2015 Anorexia Cachexia / F. Strasser

    Compliance with the multimodal intervention: adequate

    Week 0-6 80% compliance

    n % n % n %

    Celecoxib 6 24 2 8 17 68

    ONS 13 52 2 8 10 40

    Exercise

    -Strength 10 40 3 12 12 48

    -Aerobic 10 40 3 12 12 48

    PreMENAC - Kaasa S et al. ASCO 2015 Poster

    Multimodal Intervention: pre-MENAC

    Encouraging weight increase

    in the treatment arm

    � Phase III started 6.2015

    SIOG 13. Nov 2015 Anorexia Cachexia / F. Strasser

    Conclusion

    Nutritional issues in older patients having cancer include often

    co-occuring malnutrition, age-related sarcopenia and thecancer anorexia-cachexia syndrome

    Screening shall focus on physical fatigue, BMI, weight loss,

    decreased appetite and intake: not the tool, the do matters

    A rational therapeutic strategy for the older patient with nutritional issues is based on the and the defined phase of

    cancer cachexia andcause its target domains

    Care for these multidimensional problems are mechanism-based interventions focused on patients‘ quality of life,

    including both rehabilitation and alleviating suffering.

    A close interplay of oncology and all providers of key interventions palliative care is required to achieve goals.

    New drugs are needed, promising in pipeline

  • 19.11.2015

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    SIOG 13. Nov 2015 Anorexia Cachexia / F. Strasser

    [email protected]

    Thank you

    MANY SESSIONS ON CANCER CACHEXIA

    www.cachexia.org