predicve/prognosc value of anorexia-cachexia...definion of cancer cachexia • bmi, body mass...
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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 <20 + weight loss >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,
<3-mo expected survival
Pre-cachexia
Weight loss ≤5%
Metabolic/endocrine change
“Inthebeginningofthemaladyitiseasytocurebutdifficulttodetect,butinthecourseof%me,nothavingbeeneitherdetectedortreatedinthebeginning,itbecomeseasytodetectbutdifficulttocure.”
—NiccoloMachiavelli
Cachexia
Weight loss >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<0·0001providedsignificantprognos%cinforma%oninaddi%onto
• age• sex• distantmetastasesp<0·0001
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<0.001 for cachexia or refractory cachexia vs no cachexia
Log-rank test P<0.001
Cum
ulat
ive S
urviv
al
Time, wk 0 50 100 150
0
1.0
0.8
0.6
0.4
0.2
150
No cachexia
Pre-cachexia
Cachexia
Refractory cachexia
No cachexia
Pre-cachexia
Cachexia
Refractory cachexia
ConsensuscriteriaforweightandBMImul'plecancertypes
ConsensuscriteriaforweightandBMI,plusbiochemicalmarkersandpa'entcharacteris'cs:LungandGIcancer
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