Click here to load reader

Predicve/prognosc value of anorexia-cachexia...Definion of Cancer Cachexia • BMI, body mass index. Fearon K, et al. Lancet Oncol. 2011;12:489-495 . – Mul%-factorial syndrome •

  • View
    2

  • Download
    0

Embed Size (px)

Text of Predicve/prognosc value of anorexia-cachexia...Definion of Cancer Cachexia • BMI, body mass...

  • Predic've/prognos'cvalueofanorexia-cachexia

  • Prognos'cvalueofAnorexia-Cachexia

    Rela%onshipbetweenPrognosis•  Weight•  Appe%te•  Nutri%onalImpactSymptoms•  BodyComposi%on•  Mul%pleDomainsofcachexia

  • uncertainty

    •  Widevaria%oninguidelines1anduseofweightlosscriteria•  Systema%creviewofcachexiadomainsandweightlosscriteria25%loss[n=12]10%[n=20]specific%[n=29]kglost[n=10]%meperiod6months[n=18],3months[n=4],unspecified[n=16]•  Oncologistsunclearwhichcut-offsareclinicallysignificant3,4

    1.MauriBMJSuppPall20142.BlumCritRevOncHem20112.SpiroBJC20063.DelFabbroJSO2015

  • Defini'onofCancerCachexia

    •  BMI,bodymassindex.FearonK,etal.LancetOncol.2011;12:489-495.

    –  Mul%-factorialsyndrome• Characterizedbyongoinglossofskeletalmusclemass±lossoffatmass• Cannotbereversedfullybyconven%onalnutri%onalsupport•  Leadstoprogressivefunc%onalimpairment

    5

    Weight loss >5% over 6 mo that cannot be attributed to simple starvation

    or BMI 2%

    or Appendicular skeletal muscle mass index consistent

    with sarcopenia + weight loss >2%

  • StagesofCancerCachexia

    •  FearonK,etal.LancetOncol.2011;12:489-495.

    6

    Refractory cachexia

    Death Normal

    Low performance score Immunocompromise,

    5%

    Reduced food intake/ systemic inflammation

  • Weight-RelatedOutcomesinPa'entswithCancer

    1.DeWysWB,etal.AmJMed.1980;69:491-497;2.RossPJ,etal.BrJCancer.2004;90:1905-1911;3.Kazemi-BajestaniSM.SemincellDev2016;4.ParmarMP,etal.SupportCareCancer.2013;21:2049-2057;5.MarianiL,etal.SupportCareCancer.2012;20:301-309;6AndreyevEurJCancer1998;7Chlebowski,8.ThoresenEurJCancerCare2012

    •  Increasedriskforcomplica%ons,death1• Decreasedtreatmentresponse2• Greaterfailuretocompletecyclesoftherapy2,6•  Increasedtoxicity3•  Increasedfa%gue4•  LowerQoL5,8• DecreasedPerformancestatus•  Lowtestsoterone

  • Weightlossandprognosis

    •  Obesityincreasingworldwide•  Classifica%onofWeightlossbasedoncontemporarydata•  EuropeanandCanadianstudyof8160pa%ents•  Prognos%csignificanceofWeightlossinpa%entswhoini%allyhavealow,intermediate,orhighBMI

    •  Published in: Lisa Martin; Pierre Senesse; Ioannis Gioulbasanis; Sami Antoun; Federico Bozzetti; Chris Deans; Florian Strasser; Lene Thoresen; R. Thomas Jagoe; Martin Chasen; Kent Lundholm; Ingvar Bosaeus; Kenneth H. Fearon; Vickie E. Baracos; JCO 2015, 33, 90-99.

  • Fig 1. Line graphs representing the relationships between deciles of (A) body mass index (BMI) and (B) percent weight loss (%WL) to overall survival. Decile 1 represents (A) the lowest BMI and (B) the highest %WL. Decile 10 represents (A) the highest BMI and (B) the lowest %WL. Blue lines represent unadjusted estimated hazard ratios (HRs) associated with reduced overall survival. Reference categories are BMI decile 10 (BMI > 30.9 kg/m2; HR, 1.0) and weight stable (WS; ± 2.4%; HR, 1.0). Risk of reduced survival increases with decreasing BMI and increasing %WL. Gold lines represent the estimated median overall survival in months. Median survival decreases with decreasing BMI and increasing %WL. Different shades of blue in the figures indicate significant differences (P < .05) in median survival between deciles. (*) WS is ± 2.4%.

    Published in: Lisa Martin; Pierre Senesse; Ioannis Gioulbasanis; Sami Antoun; Federico Bozzetti; Chris Deans; Florian Strasser; Lene Thoresen; R. Thomas Jagoe; Martin Chasen; Kent Lundholm; Ingvar Bosaeus; Kenneth H. Fearon; Vickie E. Baracos; JCO 2015, 33, 90-99.

    Weightloss,BMI,prognosis

  • Panels A to C represent a 5 × 5 matrix analysis of the five categories of BMI and five categories of %WL for a total of 25 possible combinations. The (A) sample size, (B) median overall survival (months), and (C) unadjusted estimated hazard ratios (HRs; HR, 1.0) are presented for each cell. (*) Reference categories are BMI ≥ 28.0 kg/m2 and weight stable ± 2.4%. Different colors represent significant differences (P < .05) in median overall survival and HRs within and between cells of the matrix. Panel D represents the BMI-adjusted WL grading system (grades 0 to 4) Lisa Martin; Pierre Senesse; Ioannis Gioulbasanis; Sami Antoun; Federico Bozzetti; Chris Deans; Florian Strasser; Lene Thoresen; R. Thomas Jagoe; Martin Chasen; Kent Lundholm; Ingvar Bosaeus; Kenneth H. Fearon; Vickie E. Baracos; JCO 2015, 33, 90-99.

    Mediansurvivalbygrade0=20.9months1=14.62=10.83=7.64=4.3

    Reducedsurvival=afunc'onofbodymassindex&percentweightloss

  • Survivalcurvesfromthesubgroupanalysisfor(A)gastroesophagealand(B)headandneckcancersbygrade

    Published in: Lisa Martin; Pierre Senesse; Ioannis Gioulbasanis; Sami Antoun; Federico Bozzetti; Chris Deans; Florian Strasser; Lene Thoresen; R. Thomas Jagoe; Martin Chasen; Kent Lundholm; Ingvar Bosaeus; Kenneth H. Fearon; Vickie E. Baracos; JCO 2015, 33, 90-99. DOI: 10.1200/JCO.2014.56.1894 Copyright © 2014

  • Gradingsystemforweightlossincancer

    •  Func%onof%weightlossandBMI•  PrognosisIndependentofcancersite,stageorperformancestatus

    •  Implica%onsforclinicaltrialenrollment•  Limita%ons%meframeofweightlossperformancestatusmeasurestypeofchemo

  • Applicabilityofaweightlossgradingsystemincancercachexia:alongitudinalanalysis

    JournalofCachexia,SarcopeniaandMuscleVolume8,Issue5,pages789-797,18JUN2017

    Confirm the system‘s prognostic validity Relationship to cachexia domains Ability to predict cachexia progression

  • Theapplicabilityofaweightlossgradingsystemincancercachexia:alongitudinalanalysis

    JournalofCachexia,SarcopeniaandMuscleVolume8,Issue5,pages789-797,18JUN2017

  • Iden'fyingprogressionorreversibility

  • Panels A to C represent a 5 × 5 matrix analysis of the five categories of BMI and five categories of %WL for a total of 25 possible combinations. The (A) sample size, (B) median overall survival (months), and (C) unadjusted estimated hazard ratios (HRs; HR, 1.0) are presented for each cell. (*) Reference categories are BMI ≥ 28.0 kg/m2 and weight stable ± 2.4%. Different colors represent significant differences (P < .05) in median overall survival and HRs within and between cells of the matrix. Panel D represents the BMI-adjusted WL grading system (grades 0 to 4) Lisa Martin; Pierre Senesse; Ioannis Gioulbasanis; Sami Antoun; Federico Bozzetti; Chris Deans; Florian Strasser; Lene Thoresen; R. Thomas Jagoe; Martin Chasen; Kent Lundholm; Ingvar Bosaeus; Kenneth H. Fearon; Vickie E. Baracos; JCO 2015, 33, 90-99.

    Mediansurvivalbygrade0=20.9months1=14.62=10.83=7.64=4.3

    Reducedsurvival=Func'onofbodymassindex&percentweightloss

  • Addi'onaldomains

    •  1.Prado.ProcnutrSoc2016QuintenLancetOncology2011.2.Farhangfar2010OralOnc.3.ZhouJPSM20174.DelFabbroJPM20106.NasrahClinNutr.20169.BurneyJCEM2012

    •  Bodycomposi%on1•  Pa%entreportedoutcomesAppe%te2Nutri%onImpactsymptoms3,4Fa%gueandfunc%on5•  Dietaryintake6•  PhysicalFunc%on7•  Chronicinflamma%on8•  Other-chemo&endocrinedysfunc%on9

  • Extensivemusclewas%ngcanbeobscuredbylargefatmass

    Fearon,K.etal.(2012)Understandingthemechanismsandtreatmentop%onsincancercachexiaNat.Rev.Clin.Oncol.

    Bodycomposi'onandprognosis

  • Varia'onbetweenskeletalmuscleindex(SMI)andbodymassindex(BMI)

    forfemales(n=645)

    Martin L et al. JCO 2013;31:1539-1547 ©2013 by American Society of Clinical Oncology

    Pa%entswithcancercachexiabytheconven%onalcriterion(involuntaryweightloss)andbytwoaddi%onalcriteria(muscledeple%onandlowmuscleaoenua%on)shareapoorprognosis,regardlessofoverallbodyweight

  • DelFabbroOncologist2012

    •  Sarcopeniaoddsforresponse29%lowerforeachunithigherBMI•  Normalweight(26pCRsof44total)responsebeoerinsarcopenia•  Howfarupordownstreamshouldbodycomposi%onbeevaluated?•  Dosingofchemotherapybeoerdeterminedbybodycomposi%on?•  Othermethodsforevalua%ngbodycomposi%onUltrasound,Bioimpedance,DEXA,MRI

  • Bodycomposi'onandprognosisin3262early-stage(I-III)colorectalcancer

    Bette J. Caan et al. Cancer Epidemiol Biomarkers

  • Pa'entReportedOutcomesHRQOL,symptomsandprognosisincancer

    •  HRQOLhasindependentprognos%cvalueforsurvival

    •  104studiesshowglobalqualityoflife,func%ondomainsandsymptomscoressuchasappe%te,fa%gueandpainwerethemostimportantindicators,individuallyorincombina%on,forsurvivalMontezariHealthQualLifeout2009

  • Overallsurvivalcurvesstra%fiedbyQLQ-C30appe%telossscoreQLQ-C30=theEuropeanOrganisa%onforResearchandTreatmentofCancerquality-of-lifecoreques%onnaire

    Chantal Quinten, Corneel Coens, Murielle Mauer, Sylvie Comte, Mirjam AG Sprangers, Charles Cleeland, David Osoba, Kristin Bjordal, Andrew Bottomley

    Baselinequalityoflifeasprognos%cindicatorofsurvivalMeta-analysisofindividualpa%entdataEORTCclinicaltrials

    Lancet Oncol Volume 10, Issue 9, 2009, 865–871

  • BaselineQoL:aprognos'cindicatorofsurvivalMeta-analysis:pa'entdatafromEORTCclinicaltrialsQuinten2009LancetOncol

    •  HRQOLparametersofphysicalfunc%oning,painandappe%telossp

  • Nutri%onalImpactSymptomsandtreatment

    InaCancerCachexiaClinic

    •  DelFabbro,Hui,Dalal,Dev,Brueraetal.JPallMed.2011;14:1004-1008.

    Nutri'onImpactSymptoms

    NumberAffected(%)

    CorrespondingInterven'on

    NumberTreatedAmongAffected(%)

    Earlysa'ety 94(62) Metoclopramide 74(79)

    Cons'pa'on 78(52) Laxa've 68(87)

    Nausea/vomi'ng 67(44) An'eme'c(metoclopramide) 54(81)

    Depressedmood 63(42) An'depressant(mirtazapine) 51(81)

    Dysgeusia 42(28) Zincsupplement 20(48)

    Dysphagia 21(14) GI/speechtherapy 5(24)

    Drymouth 14(9) Ar'ficialsaliva 2(14)

    Mucosi'spain 11(7) Opioid,topicalmouthwash 3(27)

    Dentalissues 8(5) Dentalreferral 2(25)

  • FindingsandClinicaloutcomes

    •  ThemediannumberofNIS=366%=2-4NIS20%=5-8NIS•  HighernumberofNISassociatedwithpoorappe%tep=0.008weightlossp=0.036•  Appe%tescoreimprovedfrom7to5p=0.001•  34%ofpa%entsgainedweight

  • Cumulative hazard plots of survival (days) for total symptom score quintiles. Arazm Farhangfar, Marcin Makarewicz, Sunita Ghosh, Naresh Jha, Rufus Scrimger, Leah Gramlich, Vickie Baracos

    Nutrition impact symptoms in a population cohort of head & neck cancer patients: Multivariate regression analysis of symptoms on oral intake, weight loss and survival

    Oral Oncology, Volume 50, Issue 9, 2014, 877–883

  • UsingMul'pleDomainsWeightloss,BMI,appe'te,imaging,labdataforCancerCachexiastages

    •  1.ViganoA,etal.CritRevOncog.2012;17:293-303;2..BlumD,etal.AnnOncol.2014;25:1635-16423.Argiles,CASCOJCSM2011

    –  N=207 –  Metastases, 66%1

    29 ■  N=861 ■  Metastases, 85%2

    Time, d 0 200 400 600

    0

    1.0

    0.8

    0.6

    0.4

    0.2 Su

    rviva

    l

    P

  • Development and validation of a clinically applicable score to classify cachexia stages in advanced cancer patients

    Zhou T.J Cachexia Sarcopenia Muscle. 2018

  • Othermarkersordomainsincachexia

  • Survival analyses (Kaplan-Meier) with comparisons of curves . Survival of male patients with testosterone levels ≤185 ng/dL (blue) was decreased

    Egidio Del Fabbro, David Hui, Zohra I. Nooruddin, Shalini Dalal, Rony Dev, Gina Freer, Lynn Roberts, J. Lynn Palmer, Eduardo Bruera

    Associations Among Hypogonadism, C-Reactive Protein, and Survival in Male Cancer Patients with Cachexia

    Journal of Pain and Symptom Management, Volume 39, Issue 6, 2010, 1016–1024

  • Summary

    •  ConsensusCancerCachexiadefini%onupdated•  Corecriterion=weightlossWeightlosscriteriamodifiedbyini%alBMI•  Validatedbylargestudyresul%ngingradingsystem0-4•  Addi%onaldomainsmayenhancethesystem•  Importanceofappe%teandNIS•  Bodycomposi%onthroughouttrajectory•  Iden%fypa%entsinclinicalprac%ce,prognos%cate,designandinclusionofsubjectsinclinicaltrials