Ondersteunde therapie bij kanker - Deel 1: Oefentherapie

2012 KCE REPORT 1

ONDE

DEEL 1: O

85A

RSTEU

OEFENTH

NENDE

ERAPIE

E THERA

APIE BIJ KANKER

Het Federa

Raad van B

aal Kennisce

Bestuur

entrum voo

Het progr Minis beleid Voorz Leide Voorz Voorz (vice-Admin Verteg Verteg Verteg Interm Beroe Beroe Zieke Socia Kame

r de Gezond

Federaal Kenn rammawet (1) va ster van Volksg dsondersteunen

zitter

nd ambtenaar RIZ zitter FOD Volksge zitter FOD Sociale

voorzitter) nistrateur-generaa genwoordigers M genwoordigers M genwoordigers M mutualistisch Agen epsverenigingen v epsverenigingen v nhuisfederaties ale partners er van Volksverteg

dheidszorg

iscentrum voor an 24 december gezondheid en de studies binne ZIV (vice-voorzitte ezondheid (vice-v e Zekerheid al FAGG

inister van Volksg inister van Sociale inisterraad ntschap van de artsen van de verpleegku genwoordigers r de Gezondhe r 2002 (artikelen Sociale Zaken. en de sector van Eff Pie er) Jo voorzitter) Dir Fra Xa gezondheid Be Ma e Zaken Oli Ri Jea Da Mic Pa Xa Ma Jea undigen Mic My Joh Jea Rit Pa Lie eidszorg is ee 259 tot 281) die . Het Centrum de gezondheids fectieve Leden erre Gillet De Cock rk Cuypers ank Van Massenh avier De Cuyper ernard Lange arco Schetgen vier de Stexhe De Ridder an-Noël Godin aniel Devos chiel Callens atrick Verertbrugge avier Brenez arc Moens an-Pierre Baeyen chel Foulon yriam Hubinon han Pauwels an-Claude Praet ta Thys aul Palsterman eve Wierinck n parastatale, e onder de bevo is belast met szorg en de ziekt Plaats Benoît Chris D hove Jan Be Greet M Franço Annick Karel V Lambe Frédér Bart Oo Frank D en Yoland Geert M Roland s Rita Cu Ludo M Olivier Katrien Pierre Leo Ne Celien opgericht doo oegdheid valt va het realiseren teverzekering. vervangende Le Collin Decoster ertels Musch ois Perl k Poncé Vermeyen ert Stamatakis ric Lernoux oghe De Smet de Husden Messiaen d Lemye uypers Meyers Thonon n Kesteloot Smiets eels Van Moerkerke r de an de van den

Controle

Directie

Contact

Rege Algem Adjun Progr Fede Doorb Kruid B-100 Belgi T +32 F +32 info@ http:// ringscommissaris meen Directeur nct Algemeen Dire rammadirectie raal Kenniscentru building (10e verd dtuinlaan 55 00 Brussel um 2 [0]2 287 33 88 2 [0]2 287 33 85 @kce.fgov.be /www.kce.fgov.be s ecteur um voor de Gezon ieping) e Yv Ra Jea Ch Kri ndheidszorg (KCE es Roger af Mertens an-Pierre Closon hristian Léonard stel De Gauquier E)

2012 KCE REPORT 1 GOOD CLINICA

ONDE

DEEL 1: O

KIRSTEN HOL 85A AL PRACTICE

RSTEU

OEFENTH

DT HENNINGSEN

NENDE

ERAPIE

N, ANJA DESOM

E THERA

ER, SOPHIE HAN

APIE B

NSSENS, JOAN V

IJ KAN

VLAYEN

KER

www.kce.fgoov.be

COLOFON

Titel: Auteurs: Externe experte Externe Validat Belangenconflic Layout: Disclaimer: Publicatiedatum Domein: MeSH: NLM classificat Taal: Formaat: Wettelijk depot:

N

en: toren: ct: m: tie: : Onde Kirste Ahm Anne Leuv Didie Jeroe Jean Kree uitvo Ine V • D ra w • V u w • To • A al 9 okt Good Neop QZ 2 Nede Adob D/20 ersteunende thera en Holdt Henning ad Awada (Institu emarie Coolbrand ven), Robert Parid er Vander Steiche

en Mebis (Limbur n-Pierre van den B

g een beurs, hon eren van onderzo Verhulst

De externe expert apport. Hun opm wetenschappelijk

ervolgens werd it een consensu wetenschappelijk

ot slot werd dit r Alleen het KCE is

lsook voor de aa tober 2012 d Clinical Practice plasms; Chemothe 266 erlands, Engels be® PDF™ (A4) 12/10.273/59

apie bij kanker – D sen (KCE), Anja D ut Bordet), Sabien dt (UZ Leuven), Ju daens (UZ Leuve l (Fondation Cont gs Oncologisch C Berg (Meander Me noraria of fondsen oek: Annemarie C

rten werden gera merkingen werde e rapport en ging een (finale) vers us of een meerd e rapport en ging rapport unaniem s verantwoordel anbevelingen aan e (GCP) erapy, Adjuvant; R Deel 1: Oefenther Desomer (KCE), S n Bauwens (UZ B

ulie Degée (Institu en), Marc Peeters tre le Cancer) Centrum), Emman

edisch Centrum, N n voor een perso Coolbrandt

aadpleegd over e en tijdens vergad gen niet noodza sie aan de valida derheidsstem tus

gen niet noodza goedgekeurd do lijk voor de eve n de overheid.

Radiotherapy; Exe rapie

Sophie Hanssens Brussel), Tom Bote

ut Bordet), Frédér s (UZA), Ward R nuel Simons (Rugs

Nederland) oneelslid of een a een (preliminaire deringen bespro kelijk akkoord m atoren voorgeleg ssen de validato kelijk alle drie ak oor de Raad van ntuele resterend

ercise Therapy

s (UZ Brussel), Jo erberg (UGent), J ric Duprez (UGen Rommel (Vlaamse school - Ecole du andere vorm van

e) versie van he oken. Zij zijn gee met de inhoud erv d. De validatie v oren. Zij zijn gee kkoord met de in

Bestuur. de vergissingen

an Vlayen (KCE) Jan Bourgois (UG nt), Johan Menten e Liga tegen Kan dos CHU Brugma compensatie voo

t wetenschappe en coauteur van van.

van het rapport v en coauteur van nhoud ervan. of onvolledighe Gent), n (UZ nker), ann), or het lijke n het volgt het eden

Copyright

Hoe refereren nnaar dit document

De K http:/ t? Holdt Deel Gezo Dit Gezo KCE-rapporten w //kce.fgov.be/nl/co t Henningsen K, 1: Oefentherapie ondheidszorg (KC document is be ondheidszorg. worden gepublice ontent/de-copyrigh Desomer A, Ha e. Good Clinical CE). 2012. KCE Re eschikbaar op eerd onder de L hts-van-de-kce-ra nssens S, Vlaye Practice (GCP). eport 185A. D/201 de website van Licentie Creative apporten. n J. Ondersteune Brussel: Federa 12/10.273/59. n het Federaal e Commons « b

ende therapie bij aal Kenniscentrum Kenniscentrum by/nc/nd » j kanker – m voor de voor de

KCE Report 185

„ VOOR

5A

RWOORD

Het KCE haanbeveling

chemothera worden om Andere, me belang te z geen enke beantwoord Het huidige van onders Deze vier behandelin voor alle pr Jean-Pierre Adjunct Alg Oefentherap

eeft reeds heel w gen beperken zic apie, radiotherapi de kanker te stop eer ondersteunen zijn voor het welz le reden, en wel den welke van dez e rapport over oe

teunende behand rapporten gaan n gen op een trans rofessionals die ka

e CLOSON gemeen Directeur

pie voor volwasse

wat rapporten gep ch echter meesta ie en chirurgie. U ppen of uit te roeie nde interventies w zijn van de patiën

l in tegendeel, o ze interventies ee fentherapie luidt deling bestuderen

niet over één spe sversale manier v

anker bestrijden o

n kankerpatiënten

publiceerd met kli al tot diagnostisch Uiteraard zijn dit

en.

worden in de prak t tijdens de zeer m ons niet te in en bewezen nut he

een serie in van bij patiënten die e ecifiek kankertype voor alle kankerty op de meest mens n inische aanbeveli he procedures en ook de interventi ktijk nochtans oo belastende beha teresseren voor ebben, wanneer e vier rapporten di een curatieve beh e. Ze onderzoek pes. Wij hopen d selijke en draaglijk

ingen met betrekk n tot therapeutisc

ies die voor alle k vaak toegepast andeling van hun deze interventies en voor welk kank ie opeenvolgend handeling onderga

en het nut van d dat ze een nuttig

ke manier voor hu

king tot kanker. D he interventies, z kankertypes geb t en blijken van g kanker. Er is daa s en om de vraa kertype. verschillende vor aan voor hun kan deze ondersteune hulpmiddel zullen un patiënt. Raf MERTENS Algemeen Direc i Deze zoals bruikt groot arom ag te rmen ker. ende n zijn cteur

ii

„ SAME

TOEL

ENVATT

LICHTING

TING EN

GEN

Oefentherappie voor volwasse

I

E m Z v d o a o b 2 w o p b e A o k re p v • • • • D a v c s b v n kankerpatiënten

NLEIDING

Er bestaat een gr maatschappelijke Zo zal iedereen oo verdienen, onderm de moeilijke pe ondergaan. Maar, aanbevelingen toe onbelangrijk, gez belangrijkste actie 2008-2010 en één werkt samen met ondersteuning b praktijkrichtlijnen. borstkanker, color en maagkanker en Aangezien veel ri ondersteunende z kanker, werd bes

eeks van vier rap patiënten die een volgende aspecten Oefentherapie Behandeling en/of radiothe Psychosociale Behandeling v Dit rapport wil, aanbevelingen fo volwassen patiën chemo- en/of radio symptomen gerela borstkankerpatiënt vallen buiten het b n

G

rote hoeveelheid consensus dat b ok beamen dat ka meer voor hun nie eriode wanneer , kunnen we hie evoegen aan on zien de ontwikk epunten is van n van de taken va het College voor bij de gezame

Tot op heden rectale kanker, tee n baarmoederhals

ichtlijnen nu al v zorg, die vaak nie

loten om dieper pporten uit te wer n actieve behand n worden behand e tijdens chemoth van nevenwerki erapie; e ondersteuning; van kankergerelat op basis va ormuleren met nten die een cu

otherapie. Oefent ateerd aan een b ten of urinaire inc bestek van dit rapp

wetenschappelijk beweging goed is ankerpatiënten ee et-medische node ze chemothera erover meer prec ze kankerrichtlijn keling van rich het Belgische N an het College voo

r Oncologie en bi enlijke ontwikke n werden richtlij elbalkanker, panc skanker (www.kce erschillende aspe et specifiek zijn v op de vraag in te rken over de onde eling voor hun k eld:

erapie en/of radio ngen gerelateerd teerde pijn. an wetenschapp betrekking tot uratieve behande therapie of fysioth bepaald kankertyp continentie bij pro port.

KCE Report 1

k bewijs en een b s voor de gezond

n brede onderste en, en dit vooral tij apie of radiothe cies zijn en spec nen? De vraag is htlijnen één van Nationaal Kanker or Oncologie. Het iedt wetenschapp eling van klin jnen uitgewerkt creaskanker, slokd e.fgov.be).

ecten behandelen voor een bepaald

e gaan en een a ersteunende zorg kanker ondergaan otherapie; d aan chemothe pelijk bewijsmate oefentherapie eling ondergaan herapie voor spec pe, bv. lymfoedee ostaatkankerpatië 185A brede dheid. uning jdens erapie cifieke s niet n de Plan t KCE pelijke nische voor darm- n van d type aparte g voor n. De erapie eriaal, voor met cifieke em bij ënten,

KCE Report 185

METHOD

De volgende on

Wat is het effec actieve curatiev De volgende uit 1. Levenskwa zoals de EORTC-C3 2. Cardiopulm VO2max, h minuten wa 3. Vermoeidh zoals de P FACT ‘ver Inventory); 4. Veiligheid effecten). Tekstkader 1: FACT WHOQOL-BRE EQ-5D SF-36 EORTC-C30 FACIT 5A

DEN

nderzoeksvraag w ct van oefentherap ve behandeling? tkomsten werden aliteit (gemeten m FACT schalen, 30. Zie tekstkader monaire functie ( hartritme, Metabo andeltest); heid (gemeten me Piper Fatigue Sc rmoeidheid’ subsc van oefentherapie Schalen voor he Function EF WHO qu EuroQol Short Fo Europea Treatme Function werd behandeld in

pie voor volwasse

in overweging ge met gevalideerde WHOQOL-BREF r); (gemeten met d olic Equivalence o et gevalideerde s cale, Brief Fatigu chaal, FACIT-F,

e (i.e. frequentie

et meten van de l nal Assessment of uality of life assess

-5D instrument

orm Health Survey an Organisation nt of Cancer- Qua nal Assessment of Oefentherap n dit overzicht: en kankerpatiënten enomen: schalen of instru F, QOL EQ-5D, de absolute of r of Task, of de 6 schalen of instru ue Inventory, FA Multidimensional en type van ong

evenskwaliteit f Cancer Therapy sment instrument y n for Researc ality of Life-C30 f Chronic Illness T

pie voor volwasse

n tijdens umenten, SF-36, relatieve 6- of 12-umenten, ACT-F of Fatigue ewenste ch and Therapy A b n g in 3 o m H m g a • • S d o ( w D V g g v n n kankerpatiënten

Als actieve beha beschouwd. Horm niet opgenomen gedefinieerd als d

ngreep, tot een w 3 weken na oefentherapie mo maar kon nog doo Het literatuuronde meta-analyses. Na geen enkele rece als die ontwikkeld RCT's te sel reviews, en Een volledig

van alle releva Systematische rev databanken: OVID of Systematic Re DARE) en Hea werden gezocht in De zoektocht gebe Voor de kritische gemaakt van he geïncludeerde RC van de Cochrane C niveaus van bewijs

n ndeling werden monale behandelin in de definitie. e periode vanaf d week na de laatste de laatste che est starten binne orlopen na deze pe erzoek richtte zich a een evaluatie v ente systematisch voor dit rapport. B lecteren uit de r literatuuronderzoe ante studies te ga views en meta-an D Medline en PreM eviews, Database lth Technology n: OVID Medline eurde tussen dece

beoordeling van et AMSTAR-instr CT's werd bepaald Collaboration. He skracht en graad enkel radiotherap ng (voor borst- en De "actieve be diagnose tot 3 wek e radiotherapeutis emotherapeutisch en de hierboven g eriode. h initieel op syst van de reviews we he review dezelfd Bijgevolg werd be referentielijsten v ek te doen naar aranderen. nalyses werden g Medline, EMBASE e of Abstracts o Assessment (HT , PreMedline, EM ember 2011 en fe n systematische r rument. Het risic d door middel van et GRADE-systeem van aanbeveling t pie en chemothe n prostaatkanker) ehandelperiode" ken na de chirurg sche behandeling he behandeling. gedefinieerde per tematische review erd echter duidelij de definities hante esloten om van de systemat RCT's om de inc ezocht in de volg E, Cochrane Data of Reviews of E TA) databank. R MBASE en CENT ebruari 2012. reviews werd ge co op bias voo

het 'Risk of Bias m werd gebruikt o toe te wijzen. iii erapie werd werd gische of tot De riode, ws en jk dat eerde tische clusie gende abase ffects RCT's TRAL. bruikt or de Tool’ om de

iv

RESULTA

Effectiviteit

In totaal werde borstkanker het het dus mogelij thuisgebaseerd met krachttrain was niet moge aantal studies. worden per kan

Veiligheid

In ongeveer de veiligheid van concluderen w behandeling on

ATEN

n 33 RCT’s geïde t meest frequent jk om ziekenhuisg de interventies en ing (bvb. spierve elijk voor de ande

. De conclusies nkertype weergege

e helft van de geï oefentherapie b we dat oefenther ndergaan voor kan

entificeerd (zie ta waren (12 studie gebaseerde interv n aërobe training ersterkende oefen ere kankertypes o over de effecti even in onderstaa ïncludeerde studie eschikbaar. Op apie veilig lijkt t nker.

Oefentherap

bel), waarbij stud s). Voor borstkan venties te vergelij (bvb. wandelen, ningen). Deze ver

omwille van het b iviteit van oefen ande tabel.

es zijn gegevens basis van deze te zijn bij patiën

pie voor volwasse

dies over nker was ken met fietsen) rgelijking beperkte ntherapie over de studies nten die

KCE Report 185 Kankertype Borstkanker Prostaatkanke Longkanker Colorectale ka Hematologisch Hematopoëtisch stamceltranspla Lymfoom Acute myeloïde Gemengde kankerpopulat 5A N 1 er 4 1 anker 2 he kankers he antatie 4 1 e leukemie 1 ties 8 N studies Con 2 • • • • 4 • • 2 • • 4 • • • • • 8 • Oefentherap nclusies Tegenstrijdig bew rapporteren) over of thuis gebeurt, o Tegenstrijdig bew niveau van bewijs Het bewijsmater verbeteren van d Tegenstrijdig bew bewijskracht) Tegenstrijdig bew functie en vermoe Een combinatie v geen effect te he Het bewijsmateri cardiopulmonaire Er zijn aanwijzing Oefentherapie lijk Tegenstrijdig be vermoeidheid (er Het is aannemel verdwijnt 6 maan Het is aanneme vermoeidheid (ma Oefentherapie lijk Tegenstrijdig bew functie en vermoe

pie voor volwasse

wijsmateriaal (nl. r het effect van oe of aërobe en/of kr wijsmateriaal ove skracht)

riaal lijkt erop te e cardiopulmonai wijsmateriaal ove

wijsmateriaal ove eidheid (erg laag van preoperatieve bben op de leven iaal lijkt erop te e functie (erg laag gen dat oefenthera

kt geen significant ewijsmateriaal ov

rg laag niveau van ijk dat oefenthera den na het stoppe elijk dat oefenthe atig niveau van be kt een tijdelijk effe wijsmateriaal ove eidheid (erg laag

n kankerpatiënten

een mix van stu

efentherapie op d rachttraining is (er r het effect van o e wijzen dat aër

re functie (laag ni r het effect van o

er het effect van niveau van bewijs e ziekenhuisgeba skwaliteit en de c wijzen dat oefen niveau van bewij apie geen effect h

t effect te hebben er het effect va n bewijskracht)

apie een significa en van de oefenth erapie een signif ewijskracht) ect te hebben op v er het effect van

niveau van bewijs n

udies die een po

de levenskwaliteit, rg laag niveau van oefentherapie op robe training sup

iveau van bewijsk oefentherapie op oefentherapie o skracht) aseerde en posto cardiopulmonaire f ntherapie geen ef jskracht) heeft op vermoeid op de levenskwa an oefentherapie

ant effect heeft o herapie(matig nive

fcant effect heef

vermoeidheid (erg oefentherapie o skracht) ositief effect en s , ongeacht of dez n bewijskracht) de cardiopulmon perieur is aan k kracht) de vermoeidheid p de levenskwal operatieve thuisge functie (laag nivea ffect heeft op de dheid (laag niveau

aliteit (erg laag niv e op de cardiop

op de levenskwali eau van bewijskra ft op de cardiop

g laag niveau van p de levenskwal

tudies die geen

e binnen een inst naire functie (erg rachttraining voo d (erg laag niveau

iteit, cardiopulmo

ebaseerde trainin au van bewijskrac e levenskwaliteit u van bewijskracht

veau van bewijskra pulmonaire functi

iteit, hoewel het acht) pulmonaire functi bewijskracht) iteit, cardiopulmo v effect telling g laag or het u van onaire g lijkt cht) of de t) acht) e en effect ie en onaire

vi

CONCLU

In deze studie a nadelen van behandeling me Slechts een kle kankertypes, b methodologisch zeer heterogee verschillende b de verschillen gerapporteerd: • Voor de m de effect cardiopulm van studie rapporteerd kwaliteit) u positieve re • Noch von levenskwa vermoeidhe oefenthera hoewel ni oefenthera Het lijkt niet z omwille van d geïncludeerde aanbevelingen trainingsinterve dat oefentherap

SIES

analyseerden we oefentherapie et chemotherapie ein aantal RCT’s behalve voor bo he beperkingen. B en wat betreft d ehandelschema’s nde schalen h meeste kankertype tiviteit van oef monaire functie en es die een pos den. Een uitzonde uitgevoerd op lym esultaten rapporte nden we cons liteit of cardiop eid doet toenem apie veilig is tijden

iet alle studies apie rapporteerden

zinvol om de re de bovenvermel studies. Het b

te formuleren entie. Het goede n

pie schadelijk is tij

de gepubliceerde bij volwassen

en/of radiotherap kon worden geïn orstkanker. De Bovendien waren de populatie (ver s) en wat betreft d heen werden t es vonden we gee fentherapie, waa vermoeidheid: d sitief effect en s ering was de enig mfoompatiënten, eerde voor alle op sistent bewijs pulmonaire func men. Bovendien s adjuvante thera ongewenste ef n. sultaten en conc de verschillen i bewijsmateriaal n ten gunste nieuws is dat er ge jdens de behande Oefentherap e RCT's over de v kankerpatiënten pie. cludeerd voor de meeste studies de geïncludeerde rschillende kanke de uitkomstschale tegenstrijdige re en consistent bew aronder levensk d.w.z. dat er een studies die gee ge studie (van be die statistisch si pgenomen uitkoms dat oefenthera ctie vermindert was er enig be apie voor kankerpa

ffecten gerelatee clusies te veralg in populatie tus liet ook niet t van een sp een reden is om te eling van kanker.

pie voor volwasse

voor- en tijdens e meeste hadden e studies erstadia, en. Over esultaten wijs voor kwaliteit, mix was n effect hoorlijke gnificant sten. pie de of de wijs dat atiënten, erd aan gemenen ssen de toe om pecifieke e vrezen

KCE Report 185

„ AANB

a Alleen het 5A

BEVELIN

t KCE is verantwoor

NGEN

a

rdelijk voor deze aa

Oefentherap Voor de cl • Door termijn kanke aanbe algem aanbe contex • Gezien kanke beweg Agenda vo • Aange effecti over d onderg • Voor gestan gemee de res • Voor t en de signifi anbevelingen.

pie voor volwasse

linici het ontbreken v n van oefenthera rpatiënten onde velingen formule een aanvaarde veling; erg laag xt en voorkeuren n er geen con rpatiënten die c ging af te raden ( oor onderzoek ezien er een ge iviteit (in termen de veiligheid va

gaan, zijn grote k uitkomsten z ndaardiseerde, enschap overeen sultaten vergelijk toekomstige stud sterkte van he cantie. n kankerpatiënten van consistent b apie op levenskw er chemotherapie eren ten voordel

principe dat niveau van bew n van de patiënt m nsistent bewijsm chemo- of radio (zwakke aanbeve ebrek is aan co n van levenskwa n oefentherapie kwaliteitsvolle R zoals levenskw gevalideerde u nkomen om een kbaar worden.

dies is het crucia et effect voor u

n

bewijsmateriaal waliteit, cardiopu

e of radiotherap le van een speci

beweging goed wijskracht). Het i mee in overwegi materiaal is dat therapie onderg eling; erg laag ni

onsistent en kw aliteit, cardiopulm voor kankerpat RCT's noodzakelij waliteit en ver uitkomstschalen generieke en zie aal om vooraf de itkomstmaten te over de gunstig ulmonaire functie pie, kunnen we ifiek type oefenth d is voor de g is daarom aange ing te nemen. t oefentherapie gaan, is er ook

veau van bewijs

waliteitsvol bew monaire functie tiënten die een jk. rmoeidheid mo n gebruiken, e ektespecifieke to e belangrijkste u e definiëren op ge effecten op e en vermoeidhe geen meer pre herapie, boveno gezondheid (zw ewezen om de lo schadelijk is geen reden om kracht). ijsmateriaal ove en vermoeidheid actieve behand oeten onderzoe en moeten ze ool te gebruiken z itkomsten te bep basis van klini

vii korte eid bij cieze p het wakke okale voor m hen er de d) en deling ekers als zodat palen ische

KCE Report 185

„ TABL

5

LE OF CO

ONTENT

LIST LIST „ 1 2 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 3 3.1 3.2 4 4.1 4.2 Exercise t

TS

OF TABLES ... OF ABBREVIAT SCIENTIFIC INTRODUCT METHODS ... SCOPING .... 2.1.1 Meth 2.1.2 Rese DEFINITIONS LITERATURE SELECTION SELECTION QUALITY AP GRADING OF FORMULATIO SEARCH RE SYSTEMATIC RANDOMIZE EVIDENCE R BREAST CAN 4.1.1 Qua 4.1.2 Card 4.1.3 Fatig 4.1.4 Safe PROSTATE C 4.2.1 Qua

treatment for adult

... TIONS ... REPORT ... ION ... ... ... hodology ... earch questions a S ... E SEARCH ... CRITERIA ... PROCESS ... PRAISAL ... F EVIDENCE ... ON OF RECOMM SULTS ... C REVIEWS ... ED CONTROLLED REPORT ... NCER ... lity of Life ... diopulmonary func gue ... ety ... CANCER ... lity of Life ... t cancer patients ... ... ... ... ... ... ... and outcomes ... ... ... ... ... ... ... MENDATIONS ... ... ... D TRIALS ... ... ... ... ction ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... 1 ... 1 ... 1 ... 1 ... 1 ... 1 ... 1 ... 1 ... 1 ... 1 ... 2 ... 2 ... 3 ... 3 ... 3 1 . 4 . 5 . 7 . 7 . 8 . 8 . 8 . 8 . 8 . 9 . 9 10 10 10 12 13 13 14 15 15 15 25 28 30 30 30

2 4.3 4.4 4.5 4.6 5 6 6.1 6.2 7 7.1 Exercise t 4.2.2 Card 4.2.3 Fatig 4.2.4 Safe LUNG CANC 4.3.1 Qua 4.3.2 Card 4.3.3 Fatig 4.3.4 Safe COLORECTA 4.4.1 Qua 4.4.2 Card 4.4.3 Fatig 4.4.4 Safe HAEMATOLO 4.5.1 Qua 4.5.2 Card 4.5.3 Fatig 4.5.4 Safe MIXED CANC 4.6.1 Qua 4.6.2 Card 4.6.3 Fatig 4.6.4 Safe DISCUSSION RECOMMEN CLINICAL RE RESEARCH A APPENDICES APPENDIX 1

treatment for adult

diopulmonary func gue ... ety ... ER ... lity of life ... diopulmonary func gue ... ety ... AL CANCER ... lity of Life ... diopulmonary func gue ... ety ... OGICAL CANCER lity of life ... diopulmonary func gue ... ety ... CER POPULATIO lity of life ... diopulmonary func gue ... ety ... N... DATIONS ... ECOMMENDATIO AGENDA ... S... : QUALITY APPR t cancer patients ction ... ... ... ... ... ction ... ... ... ... ... ction ... ... ... RS ... ... ction ... ... ... ONS... ... ction ... ... ... ... ... ONS ... ... ... RAISAL INSTRUM ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... MENTS ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... KCE Report ... 3 ... 3 ... 3 ... 3 ... 3 ... 3 ... 3 ... 3 ... 3 ... 3 ... 3 ... 3 ... 3 ... 3 ... 3 ... 4 ... 4 ... 4 ... 4 ... 4 ... 4 ... 5 ... 5 ... 5 ... 5 ... 5 ... 5 ... 5 ... 5 t 185 32 33 35 35 35 35 35 36 36 36 36 36 38 38 38 40 42 44 45 45 47 51 55 55 57 57 57 58 58

KCE Report 1855 7.2 7.3 7.4 „ Exercise t 7.1.1 AMS 7.1.2 Coch APPENDIX 2 7.2.1 Syst 7.2.2 Rand APPENDIX 3 APPENDIX 4 7.4.1 Brea 7.4.2 Pros 7.4.3 Lung 7.4.4 Colo 7.4.5 Haem 7.4.6 Mixe REFERENCE

treatment for adult

STAR ... hrane Collaboratio : SEARCH SYNT tematic reviews .... domized controlle : GRADE PROFIL : EVIDENCE TAB ast cancer ... state cancer ... g cancer ... orectal cancer ... matological cance ed cancers ... ES ... t cancer patients ... on’s tool for asses TAX BY DATABAS ... ed trials ... LES BY INTERVE BLES ... ... ... ... ... ers ... ... ... ... ssing risk of bias . SE ... ... ... ENTION AND OU ... ... ... ... ... ... ... ... ... ... ... ... ... TCOME ... ... ... ... ... ... ... ... ... ... 5 ... 6 ... 6 ... 6 ... 6 ... 7 ... 7 ... 7 ... 8 ... 9 ... 9 ... 9 ... 10 ... 11 3 58 60 62 62 65 70 74 74 88 93 94 96 06 17

4

LIST OF T

TABLES

Table_Table

Table Table Table Table in pat Table in pat Table in pat Table in pat Table and p Table Table Table Table Table Table Table haem Table haem Table cell tr Table Table Table Exercise t

e 1 – In- and exclu e 2 – Levels of evi e 3 – Down- or up e 4 – Strength of r e 5 – Factors that e 6 – Effect of inst tients with breast e 7 – Effect of hom

tients with breast e 8 – Effect of aer tients with breast e 9 – Effect of resi tients with breast e 10 – Effect of co physical subscales e 11 – Effect of ex e 12 – Effect of ex e 13 – Effect of ex e 14 – Effect of ex e 15 – Effect of ex e 16 – Effect of ex e 17 – Effect of ex matopoietic stem c e 18 – Effect of ex matopoietic stem c e 19 – Effect of ex ransplantation ... e 20 – Effect of ex e 21 – Effect of ex e 22 – Effect of ex

treatment for adult

usion criteria ... idence according grading the evide recommendations influence the stre titution-based exe cancer... me-based exercise cancer... obic interventions cancer... istance interventio cancer... ombined aerobic a s of QOL in patien xercise treatment xercise treatment xercise treatment xercise treatment xercise treatment xercise treatment xercise treatment cell transplantation xercise treatment cell transplantation xercise treatment ... xercise treatment xercise treatment xercise treatment t cancer patients ... to the GRADE sy ence according to s according to the ength of a recomm ercise on quality of ... e on quality of life ... s on quality of life ... ons on quality of l ... and resistance inte

nts with breast ca on cardiopulmona on fatigue in patie on quality of life in on cardiopulmona on fatigue in pros on fatigue in patie on quality of life in n ... on cardiopulmona n ... on fatigue in patie ... on quality of life in on cardiopulmona on fatigue in mixe ... ystem ... the GRADE syste GRADE system .. mendation... f life (QOL) and p ... e (QOL) and physi ... (QOL) and physic ... ife (QOL) and phy ... erventions on qua ncer ... ary function in pat ents with breast ca n prostate cancer ary function in pro state cancer patien

ents with colorecta n patients undergo ... ary function in pat ... ents undergoing h ... n mixed cancer po ary function in mix ed cancer populat ... ... em ... ... ... physical subscales ... ical subscales of Q ... cal subscales of Q ... ysical subscales o ... ality of life (QOL) ... tients with breast c ancer ...

patients... ostate cancer patie

nts ... al cancer ... oing ... tients undergoing ... haematopoietic ste ... opulations ... xed cancer popula

ions ... KCE Report ... ... 1 ... 1 ... 1 ... 1 s of QOL ... 1 QOL ... 1 QOL ... 2 of QOL ... 2 ... 2 cancer ... 2 ... 2 ... 3 ents ... 3 ... 3 ... 3 ... 3 ... 4 em ... 4 ... 4 ations ... 4 ... 5 t 185 . 9 11 11 12 12 16 18 21 23 24 26 29 31 32 34 37 39 41 43 46 49 52

KCE Report 185

LIST OF A

5

ABBREVIA

ATIONS

Exercise t ABBREVIATION 95%CI ADL ADT AMSTAR BFI bpm CG EORTC-QLQ-C3 EQ-5D FACIT FACIT-F FACT FACT-AN FACT-B FACT-C FACT-F FACT-G FACT-GP FACT-P GRADE HR HSCT HTA IG ITT KCE LASA

treatment for adult

N DEFINITI 95% conf Activities Androgen Quality a Brief Fati Beats pe Control g 30 European EuroQol-Functiona Functiona Functiona Functiona Functiona Functiona Functiona Functiona Functiona Functiona Grading o Heart rate Haemato Health te Interventi Intention Belgian H Linear An t cancer patients ION fidence interval of daily living n depression thera ppraisal tool to as gue Inventory r minute group n Organisation for -5D instrument al Assessment of al Assessment of al Assessment of al Assessment of al Assessment of al Assessment of al Assessment of al Assessment of al Assessment of al Assessment of of Recommendati e

opoietic stem cell t chnology assessm ion group to treat Healthcare Knowle nalogue Scales of apy ssess systematic r r Research and T Chronic Illness T Chronic Illness T Cancer Therapy Cancer Therapy Cancer Therapy Cancer Therapy Cancer Therapy Cancer Therapy Cancer Therapy Cancer Therapy ions Assessment, transplantation ment edge Centre f Assessment reviews reatment of Canc herapy herapy-Fatigue - Anemia scale - Breast Cancer - Colorectal Canc - Fatigue - General - General Populat - Prostate Cancer , Development an

er- Quality of Life

cer tion r d Evaluation 5 -C30

6 Exercise t MD MET min MOS NSCLC POMS QOL RCT SD SDS SF-36 SR STAI TOI-AN VAS VO2max WHOQOL-BREF

treatment for adult

Mean diff Metabolic Minutes Medical O Non-sma Profile of Quality of Randomi Standard Symptom Short For Systemat Spielberg Trial Outc Visual an Maximal F WHO qua t cancer patients ference c Equivalent of Ta Outcome Study all cell lung cancer

f Mood States f life

zed controlled tria d deviation m distress scale rm Health Survey tic review ger’s state-trait an come Index-Anem nalogue scale Oxygen Consump ality of life assess

ask r al nxiety inventory mia ption sment instrument KCE Reportt 185

KCE Report 185

„ SCIE

5

NTIFIC R

REPORT

Exercise t

T

treatment for adult

1

T B C p g c g S c to c a to s T re re c s in p T th t cancer patients

1 INTROD

The development Belgian National College of Oncolo provides scientifi guidelines. Up to cancer, colorecta gastrointestinal ca Since many canc care, which are of o develop a sepa cancer patients re aspects will be co

o chemotherapy support, and treatm The present repor

ecommendations eceiving active c cancer. Exercise symptoms, e.g. ncontinence in p present report. This report is inten

he supportive car

DUCTION

of care pathway Cancer Plan 20 ogy. KCE collabor

c support in t this date guidel l cancer, testicu ancer and cervical cer-specific guide ften not specific t rate series of fou eceiving active tre

vered by this seri and/or radiother ment of cancer-re rt aims to formula relative to exerc urative treatment treatment or phy lymphoedema in prostate cancer p nded to be used b e of cancer patien ys is one of the 08-2010 and one rates with the Co he development ines were jointly ular cancer, panc cancer (www.kce lines also cover to a certain cance r reports on the s eatment for their ies: treatment of a rapy, exercise tre elated pain.

ate, on the basis cise treatment for t (chemo- and/or ysiotherapy for s n breast cancer patients, are out

by health care pro nts during active t

main items withi e of the tasks o ollege of Oncology t of clinical pra developed on b creatic cancer, u e.fgov.be). aspects of supp er type, it was de supportive care of

cancer. The follo adverse events re eatment, psychos of scientific evid r adult cancer pa radiotherapy) for specific cancer-re r patients or ur of the scope o ofessionals involv reatment. 7 n the of the y and actice breast upper ortive cided adult owing elated social ence, tients r their elated rinary of the ved in

8

2 METH

2.1 Scopin

2.1.1 Metho On 8 Novembe the basis of a w research ques presented to a clinical practice by the KCE in validated by the 2.1.2 Resea For exercise tr being of primary • Which evid during activ The reason for guidelines deve Additionally, th during the peri referred to as t this period was of these RCTs collaboration w focus on cance Exercise treatm psychosocial multidisciplinary psychosocial su

ODS

g

odology er 2011, a stakeh web-survey condu tions and outco an expert group i e. A final selection collaboration with e experts via ema

arch questions a

reatment the follo y interest:

dence exists on e ve curative treatm

focusing on the a eloped by the KCE e experts expres od immediately f the “rehabilitation found1. This revie s measured outco ith the content ex r patients during a ment as part of a support was c y programs will upport. holder meeting to ucted prior to the m

mes related to in order to discu n and prioritization h a content exper il. and outcomes owing research q xercise programs ment? active treatment p E focus on this pe ssed an interest following treatmen n” period. One sy ew included four omes within the xpert, it was conse active treatment. a multidisciplinary onsidered to b be discussed in Exercise t ok place at the K meeting, a list of p exercise treatme uss themes of int

n of outcomes wa rt (Sophie Hansse

question was def s for adult cancer period is that mos eriod.

in the effect of nt – a period som ystematic review c

RCTs. However, scope of our pro equently decided y program also i be out-of-scope.

n a separate re

treatment for adult

KCE. On potential ent was terest to as made ens) and fined as patients st cancer exercise metimes covering only two oject. In to solely nvolving These eport on T w • • • •

2

D fr c a d u w c ( w th w p E s T m c t cancer patients

The list of outcom with the content ex Quality of Lif EQ-5D, SF-36 Cardiopulmon heart rate, ME Fatigue (Pipe FACT fatigue or similar instr Safety (expre intervention o

2.2 Definition

Definitions for the rom the literature close collaboration aligned with the cu defined as being f until one week aft weeks after the cancer type or t including breast c were not consider he definitions de within the period d period.

Exercise treatmen setting and measu The results in cha mixed cancer pop cancer types.

mes to be studied xpert and ranked fe (measured by 6, EORTC-C30, F nary function (mea ET or 6 or 12 minu er Fatigue Scale subscales, FACIT rument); essed as adver r relapse).

ns

“active treatment e, including a re n with the conten urrent Belgian con rom diagnosis un ter the last radiat

last chemotherap treatment form. cancer patients an red to be on activ

scribed above. T defined and descr

nt included all ex ured by the define

apter 4 are desc pulations contains

d was similarly d according to impo

FACT scales, W FACIT scale or sim asured by absolu ute walk tests); e, Brief Fatigue

T-F, Multidimensi rse events relat

” phase were dev cent Dutch syste nt expert to ensur

ntext. The “active til 3 weeks post-s tion treatment or py treatment. Th Patients being nd patients on AD ve treatment unle The exercise inte ibed above, but co xercise interventio

d outcomes. cribed per cancer

s the RCTs with KCE Report efined in collabor ortance: WHOQOL-BREF, milar instrument); ute or relative VO2 Inventory, FACT onal Fatigue Inve ted to the exe

veloped with inspir ematic review2 a re our definitions

treatment” period surgery, from diag

from diagnosis u his was regardle

on hormone the DT for prostate ca

ss they also fell w ervention had to

ould continue afte ons performed in r type. The sectio at least two diff

t 185 ration QOL 2max, -F or entory rcise-ration nd in were d was gnosis until 3 ss of erapy ancer) within begin er this n any on on ferent

KCE Report 185

2.3 Literatu

For all research meta-analyses. systematic revi systematic revie • OVID Med • EMBASE ( • Cochrane D • DARE (Wil • HTA datab • National G Depending on additional searc following source • OVID Med • EMBASE ( • CENTRAL Medline and EM were run on 13 run on 27 Feb searched on 2 was run in 16 January 201 5

ure search

h topics, the searc If guidelines we iew of the literatu ew. The following line and PreMedli (Embase.com)

Database of Syste ey)

base (Wiley) uideline Clearingh

the quality and ch for randomize es were used: line and PreMedli (Embase.com) (Wiley) MBASE searches 3 December 2011 bruary 2012. The 9 February 2012 Medline on 12 2. Detailed searc ch first focused o re identified that ure, they were in sources were us ne ematic Reviews (W house. d currency of th ed controlled trials ne for systematic re . The search in t e National Guide 2. The search for

January 2012 ch strategies can b

Exercise t

n systematic revie were clearly bas ncluded and treat

ed:

Wiley)

e identified revie s (RCTs) was do

views and meta-a he Cochrane Libr eline Clearinghou r primary studies

and in EMBA be found in appen

treatment for adult

ews and sed on a ted as a ews, an one. The analyses rary was use was (RCTs) ASE on ndix 2.

2

T T S c P In O D L t cancer patients

2.4 Selection

The selection crite Table 1 – In- and Selection criteria In Population A tr w tr r c ntervention E Outcome Q s Design M g Language E

criteria

eria are summariz exclusion criteri nclusion criteria

Adult cancer patie reatment is define weeks post-surger reatment) or from adiation treatmen chemotherapy trea Exercise-programs Quality of life, card safety Meta-analysis, sys guideline, HTA, RC English, Dutch, Fr ed in Table 1. ia a nts during active ed as being from d ry (regardless of c diagnosis until on nt or from diagnos atment s performed in an diopulmonary func stematic review, e CT ench treatment. Active diagnosis until 3 cancer type and ne week of last

is until 3 weeks o ny setting

ction, fatigue and evidence-based

9

10

2.5 Selecti

For the select Henningsen) p Doubtful cases and consensus first selection, t Before assessin appraisal was appraisal were: • Searched i • Data of sea • Quality ap looking at t Reviews not me After a review o no recent syste was completel Consequently, primary studies perform an add inclusion of all r to that of syste abstract (AD), abstracts (AD), Doubtful cases

on process

tion of systemat performed a first s were discussed was achieved wit he full-text of the ng the methodolo performed of e n Medline and at arch mentioned ppraisal of includ

the quality of appr eeting these criter of the finally selec ematic review had

ly comparable t it was decided t s from the refere ditional literature relevant studies. T ematic reviews. T

a second selectio which was also d were discussed w ic reviews, one t selection based with a second r th a third reviewe selected abstracts gical quality of ea each full-text. Th

least one other d ded primary stud raisal and the use ria were excluded cted systematic re

defined the study to the definition to select relevant nce lists of the s search for RCT The selection pro The first selection

on was based on discussed with the with the third revie

Exercise t reviewer (Kirste d on title and a reviewer (Anja D r (Joan Vlayen). A s was retrieved. ach review, a quic

e criteria of the atabase

dies performed ed tool)

d from further revie eviews it was evid y population in a w

used for this t and potentially systematic review s in order to ens cess of RCTs wa n was based on n the full-text of s e second reviewe ewer (JV).

treatment for adult

en Holdt abstract. esomer) After this ck critical e critical (not yet ew. dent that way that review. relevant w and to sure the s similar title and selected r (KHH).

2

F w k • • • F a it ‘u C re o w a in a

2

D te F in c w t cancer patients

2.6 Quality

ap

For the quality ap was used (see ap key for labelling a Item 3: Was a Item 7: Was t documented? Item 9: Were appropriate? For the quality ap assessing risk of tem includes thre unclear risk of bia Cochrane Handbo egarding detectio outcomes (e.g. su was labelled as lo according to the c ndividual study, t appendix 4).

2.7 Grading

o

Data extraction w emplate for evide For each clinical

ndividual treatme conclusion using t was down- or upgr

ppraisal

ppraisal of system ppendix 1). Three review as high qu a comprehensive l he scientific quali ? e the methods us ppraisal of RCTs

bias3 _{was used}

ee categories: ‘low as’. For each crite ook3 were used. on bias and attri bjective and obje ow risk of bias, u criteria described the risk of bias is

of evidence

was done by on nce tables (see a

question, conclu nt outcomes. A le the GRADE syste raded based on p

matic reviews, the items of this che uality: literature search p ty of the included sed to combine t , the Cochrane C (see appendix 1 w risk of bias’, ‘h erion the definitio

If applicable, risk tion bias were a ctive outcomes). A unclear risk of bia

in the Cochrane s reported in the

ne reviewer usin ppendix 4). usions were form

evel of evidence em4 _{(Table 2). T}

predefined criteria

KCE Report

e AMSTAR instru ecklist were consid

performed? studies assessed the findings of st Collaboration’s to ). Judgement of high risk of bias’ ns as described i k of bias for the assessed per cla At the end, each as or high risk of Handbook3. For evidence tables

ng the standard mulated at the lev was assigned to he quality of evid (Table 3). t 185 ument dered d and tudies ol for each , and in the items ass of study f bias each (see KCE vel of each dence

KCE Report 185 Table 2 – Leve Quality level High Moderate Low Very low Table 3 – Dow Study design RCT Observational 5 els of evidence ac Definition We are very con estimate of the We are modera likely to be clos that it is substan Our confidence substantially dif We have very li likely to be subs n- or upgrading Quality High Modera study Low Very lo ccording to the G

nfident that the tru effect

ately confident in t e to the estimate ntially different

in the effect estim fferent from the es

ttle confidence in stantially different the evidence acc y of evidence

ate

ow

Exercise t

GRADE system

ue effect lies close he effect estimate of the effect, but t mate is limited: the

stimate of the effe the effect estimat from the estimate cording to the G Lower if Risk of bias: -1 Serious -2 Very serious Inconsistency: -1 Serious -2 Very serious Indirectness: -1 Serious -2 Very serious Imprecision: -1 Serious -2 Very serious Publication bias: -1 Likely -2 Very likely

treatment for adult

e to that of the e: the true effect is

there is a possibil e true effect may b ect

te: the true effect e of the effect RADE system Higher if Large effect: +1 Large +2 Very large Dose respons +1 Evidence o All plausible co +1 Would redu +1 Would sugg t cancer patients Methodolog RCTs withou observationa s

ity RCTs with imflaws, indirec observationa be RCTs with ve series is e: of a gradient onfounding: uce a demonstrate gest a spurious ef gical quality of su ut important limita al studies mportant limitation ct, or imprecise) o al studies

ery important limit

ed effect

ffect when results

upporting eviden tions or overwhel ns (inconsistent re or exceptionally st tations or observa s show no effect nce

ming evidence fro esults, methodolog trong evidence fro

ational studies or c 11 om gical om case

12

2.8 Formul

Based on the re was prepared b together with th 2 weeks prior t occasion (22 M changed if im discussion mee grade of recom the GRADE sy more circulated Table 4 – Str system Grade Defin Strong The d unde Weak The d unde

lation of recom

etrieved evidence by a small workin he evidence table to the face-to-fac May 2012) to discu portant evidence etings a second d mmendation was ystem (Table 4 a d to the guideline d rength of recom nition desirable effects o esirable effects, or desirable effects o esirable effects, or

mmendations

e, a first draft of u ng group (KH, AD s was circulated t ce meeting. The e

uss the first draft. e supported this draft of recommen assigned to eac nd Table 5). The development grou mmendations acc of an intervention r clearly do not of an intervention r probably do not Exercise t pdated recommen D, SH, JV). This f

to the expert grou expert group met . Recommendatio change. Based ndations was prep h recommendatio e second draft w up for final approv cording to the

clearly outweigh probably outweig

treatment for adult

ndations first draft up about t on one ons were on the pared. A on using was once val. GRADE the gh the T F B d u e Q e V p C a t cancer patients Table 5 – Factors Factor Balance between desirable and undesirable effects Quality of evidence Values and preferences Costs (resource allocation) s that influence t Comment n The larger the

undesirable e strong recomm the gradient, t recommendat The higher the likelihood that The more valu greater the un the higher the recommendat The higher the greater the re likelihood that

he strength of a

e difference betwe ffects, the higher mendation is warr the higher the like tion is warranted e quality of eviden t a strong recomm ues and preferenc ncertainty in value e likelihood that a tion is warranted e costs of an inter sources consume t a strong recomm KCE Report recommendatio

een the desirable the likelihood tha ranted. The narrow elihood that a wea

nce, the higher the mendation is warra

ces vary, or the es and preference

weak

rvention – that is, ed – the lower the mendation is warra t 185 n and t a wer ak e anted es, the e anted

KCE Report 185

3 SEARC

3.1 System

The searches y Database Cochrane Data Medline PreMedline EMBASE DARE HTA database National Guide After a review o full-text review. papers fulfilled systematic revie comprised a c Consequently i reference lists search on prim inclusion of all r 5

CH RESUL

matic reviews

yielded the followin

abase of System

eline Clearingho of title and abstra Based on the fu

the inclusion cri ews it became ev comparably defin

t was decided to of the systemat mary studies duri relevant studies.

LTS

ng number of hits matic Reviews use ct (2 931 hits) 68 ull-text (and the q teria1,2,5-25_{. After}

vident that no rece ned study popul o select relevant tic reviews and t ng the full period

Exercise t per database: Number of hits 89 1 685 23 1 066 61 6 1 papers were sele uick critical appra a review of the ent systematic rev ation for this g primary studies f to perform an ad d in order to ens

treatment for adult

9 5 3 6 6 ected for aisal) 24 selected view fully uideline. from the dditional sure the t cancer patients 13

14

3.2 Rando

The search for 44 primary stud The additional fulfilled the inc selected for the Database CENTRAL Medline PreMedline EMBASE

mized controlle

primary studies t dies of which 25 fu

search for prima clusion criteria. e report26-59_.

ed trials

hrough the refere ulfilled inclusion cr ry studies reveale Thus, in total 3

Exercise t

ence lists initially r riteria. ed 67 studies of 33 primary studie Number of hits 132 191 2 2 088

treatment for adult

revealed which 8 es were 2 2 8

KCE Report 185

4 EVIDE

4.1 Breast

A total of 12 st our predefined 242, with a me intensity seated exercise progra 4.1.1 Qualit 4.1.1.1 Inst Five RCTs rep interventions44,4 remaining had measurement s WHOQOL-BRE Estimates of the physical subsca Two small stud overall QOL. O and the other found no signifi One small stud (p<0.001, WHO effect on phys subscale45. 5

ENCE REPO

cancer

tudies on breast c outcomes were ean of 92 wome d exercise progra ams at targeted he ty of Life titution-based in ported quality of 45,49,53,56_{. One stu} an either modera scales varied an EF and SF-36 with e effect of instituti ales of QOL differ dies reported a One study found t study at 12 wee cant effect on ove dy found a positi OQOL-BREF subs ical subscales44,5

ORT

cancer patients a included. Sample n. Interventions am48 to progress eart rate or maxim

terventions

life (QOL) measu udy had a low ate44,45,49,53,56 _{or h}

d included FACT h some studies us

ion-based exercis red widely across positive effect of the effect at 5 we eks (FACT-G)44_.

erall QOL at any m ve effect on a p scale “physical”)49

53,56_{. One study d}

Exercise t

assessing one or e size ranged fro ranged from a m ive aerobic or re mal repetitions45_.

ures for institutio risk of bias53_{, w}

high risk of bias44

T-G, FACT-B, FA sing more than on se on quality of life

the studies (Table f supervised exer eeks

(WHOQOL-The three larger measure point45,53

hysical subscale

9_{. Three studies f}

did not report a

treatment for adult

more of om 22 to moderate sistance on-based while the ,49_{. QOL} ACT-AN, e scale. e and on e 6). rcise on BREF)49 r studies 3,56_. of QOL found no physical C • • t cancer patients Conclusions Conflicting e exercise trea patients (ver 2007, Mutrie Conflicting e exercise trea breast cance 2005, Hwang evidence is availa atment on over ry low level of e 2007, Hwang 200 evidence is availa atment on phys er patients (ver g 2008, Mutrie 200

able on the effec rall quality of li evidence; Camp 08, Segal 2001). able on the effec sical subscales ry low level of 07, Segal 2001). ct of institution-b ife in breast ca pbell 2005, Cour ct of institution-b of quality of li evidence; Cam 15 based ancer rneya based fe in mpbell

16 Table 6 – Effec Study N Courneya 200745 N= Mutrie 200753 N= Segal 200156 N= Hwang 200849 N= Campbell 200544 N= * Data on the 83 ct of institution-b Overall =242 No effec (measur for any o interven test (me and at 6 =203 No effec any mea Effect fo weeks ( months =123* No effec FACT-B =40 Positive WHOQO =22 Positive (p=0.46) No effec women receiving ch based exercise o QOL ct on overall QOL red by FACT-AN) of the two

ntion arms at post-edian 17 weeks) 6-months follow-up ct for FAGT-G at asure point or FACT-B at 12 p=0.0007) and 6 (p=0.039) ct for FACT-G and B effect for OL-BREF (p<0.00 effect FACT-G ) ct for FACT-B hemotherapy are re Exercise t on quality of life ( Physical su -p No physical reporting No effect for “Physical” (F measure poi d No effect for functioning” institution-ba for patients r chemotherap outcome)

01) Positive effe(WHOQOL-B “physical”)

No effect for being” subsc

eported.

treatment for adult

(QOL) and physi bscale subscale subscale FACT-G) at any nt “physical (SF-36) in ased study arm receiving py (primary ct, p<0.001 BREF subscale “physical well-cale (FACT-B) t cancer patients cal subscales of Measure point Baseline Post-test (med 17 weeks) 6-months follow up Baseline 12 weeks 6 months (follo up) Baseline 26 weeks Baseline 5 weeks Baseline 12 weeks f QOL in patients t(s) Interventio ian w-RET (resist repetitions a maximum AET (aerob ergometer, VO2max Control gro asked not to w-45 min of m weekly + an Control gro Supervised exercise at 2 other wee Two contro directed exe care i.e. ge Exercise 3 x aerobic exe adjusted ma Control gro could contin Supervised adjusted he Control gro

s with breast can on characteristics

tance arm): 3 x we at 60-70% of one bic arm): 3 x week treadmill or ellipti up received usua o initiate exercise moderate level gro n additional exerc up received usua

arm: exercise 3 x prescribed pace) ekdays

l groups, one grou ercise and one gr neral advice x weekly for 50 m ercise). Heart rate

aximum

up performed sho nue their normal a exercise 2 x wee eart rate maximum

up received usua KCE Report ncer s eekly 2 sets of repetition kly on cycle cal at 60% of l care and were e program oup exercise 2 x cise session at hom

l care

x weekly (walking + exercise at hom up performed self roup received usu min (stretching and

: 50-70% of age oulder exercises a activities ekly at 60-75% ag m l care t 185 me me f-al d and e

KCE Report 185 4.1.1.2 Hom Six RCTs (incl home-based in limitations. Fou studies had a h 5D, EORTC C studies using m Estimates of th subscales of QO One study foun linear growth r quadratic growt One 3-arm stu supervised inte (FACT-B, FACT home-based int One study foun at 3 months (p months (p=0.02 Three studies measures for Q measured as le

48 _{and one stud}

study it was no on the SF-36 su 5 me-based interv uding a total of 4 nterventions43,47,48 ur studies had a high risk of bias48,5 C30, FACT-G, FA more than one sca

he effect of home OL differed across nd a positive effec rate difference b th rate difference udy compared a ervention or usual T-G), but an effe tervention arm an nd a positive effec p=0.006) and on 2). Neither of thes had an unclear QOL43,48,51. One of ess decline in ove dy suggested no e ot possible to asse ubscale “Physical ventions 453 patients) rep 8,51,56,58_{. All stud} a moderate risk 58_{. QOL measurem} ACT-B, SF-36 a ale. e-based exercise s the studies (Tab ct on overall QOL between groups

between groups ( home-based exe l care and found ect on SF-36 “ph nd not in the supe ct on generic hea EORTC C30 “ph se effects remaine or limited reporti f these studies su erall QOL (p=0.02 effect for exercise ess whether there Functioning“ or n

Exercise t

ported QOL meas dies had method of bias43,47,51,56 a ment scales includ and FACIT-F wit

on QOL and on ble 7). L (FACT-G), meas (t70=3.76, p<0.0 (t70=2.64, p=0.01 ercise intervention no effect on over hysical functioning ervised interventio alth-related QOL hysical functionin ed after 6-months4 ing of group com uggested a positiv 254) in the exercis e on overall QOL43 e was a suggeste not51.

treatment for adult

sures for dological and two ded EQ-th some physical sured as 01) and 1)58. n with a rall QOL g” in the on arm56_. (EQ-5D) ng” at 3-47_. mparison ve effect se group 3_{. In one} ed effect C • • t cancer patients Conclusions Conflicting e exercise trea patients (ver Headley 2004 Conflicting e exercise trea breast cance Haines 2010, evidence is ava atment on over ry low level of ev 4, Segal 2001, Wa evidence is ava atment on phys er patients (very Headley 2004, M ailable on the ef rall quality of li vidence; Cadmu ang 2011). ailable on the ef sical subscales low level of evid Mock 2005, Sega ffect of home-b ife of breast ca us 2009, Haines 2 ffect of home-b of quality of li dence; Cadmus 2 l 2001). 17 based ancer 2010, based fe of 2009,

18 Table 7 – Effec Study N Segal 200156 N= Mock 200551 N= Haines 201047 N= ct of home-based Overall Q =123* No effect FACT-B =119 No repor =89 Positive e health-re 5D) at 3 No effect (EQ-5D) d exercise on qu QOL

t for FACT-G and

rting of overall QO

effect on generic elated QOL

(EQ-months (p=0.006) t on generic QOL

at 6 months

Exercise t

uality of life (QOL Physical sub Effect on SF-functioning” ( patient receiv chemotherap outcome) OL Unclear repo comparison m 36 “Physical subscale) ) Positive effec C30 physical subscale (p= months No effect on physical func at 6-months

treatment for adult

L) and physical s bscale -36 “Physical (p=0.03) for ving py (primary orting of group measures (SF-Functioning” ct on EORTC l functioning =0.02) at 3-EORTC C30 ctioning subscale t cancer patients subscales of QOL Measure point Baseline 26 weeks Baseline After interventio Intervention len dependent on le adjuvant therap weeks of radiot 3-6 months of chemotherapy) Baseline, 3, 6 a months follow-u L in patients with t Inte Self wee prog Two sup rece on ngth was ength of py (either 6 therapy or Pre 50-7 with 30 m Con mai Pos 39% 28% and 12-up Hommob prog exe Con and Par 3 m h breast cancer ervention charac f-directed arm: Ex ekly performing a gram o control groups: o pervised exercise

eived usual care i escription to exerc 70% of maximum h 15 minutes walk min as training pro ntrol group was en intain usual activit ssible dilution of tr % of usual care gr % of the exercise g

me-based strengt bility and cardiova gram; recommend ercises harder eve

ntrol group particip d flexibility activitie

rticipant adherenc months than in the

KCE Report

cteristics xercise at home 5

progressive walk one group perform and one group .e. general advice ise 5-6 x weekly a heart rate, startin k that increased to ogressed ncouraged to ty level reatment effect as roup exercised an

group did not h, balance, should ascular endurance ded to make ery 2-4 weeks pated in relaxation es

ce higher in the firs second 3 months t 185 x ing med e at ng o s nd der e n st s

KCE Report 185 Wang 201158 N= Cadmus 200943 N= Headley 200448 N= * Data on the 83 **Results provide *** Only data from **** The mean de bin/discuss/msg.c 5 =72 FACT-G the 2 gro different rate (t70= and quad (t70 = 2.6 =50*** Unclear r (FACT-B group co measure Authors s significan =32 Statistics endpoint Overall Q declined Exercise slower ra group (p= graphica results) women receiving ch ed in text and graph m IMPACT study ar ecrease of -1.5 poin cgi?msg=1592). change between oups significantly at linear growth =3.76, p <0.001) dratic growth rate 64, p=0.011)** reporting of QOL B and FACT-G) mparison s suggest no nce s between s not provided QOL (FACIT-F)

for both groups group declining a ate than control

=0.0254, only l presentation of hemotherapy are re hs only. re retrieved. nts in the exercise g Exercise t No reporting subscales Unclear repo comparison m SF-36 subsc Authors sugg (p<0.05) favo group**** at Insufficient d Statistics bet not provided Physical well subscale): ex declining at a than control, graphical pre results) eported.

roup did not reach c

treatment for adult

of physical

orting of group measures on

ale “physical” gest significance ouring usual care

ata reporting tween endpoints l-being (FACIT-F xercise group a slower rate (p=0.0252, only esentation of clinical significance t cancer patients 4 measure poin surgery baselin 24 hours prior t of chemotherap day of expected which is 7-10 d chemotherapy and end of 6-we intervention (tim Baseline 6 months Baseline At the beginnin course of chem for 12 weeks (a four measurem (information retriev nts; Pre-ne (time 1), to first day py (time 2), d nadir, ays after (time 3) eeks me 4) 6-w 3 to Low hea 60% Con 30 m Inst of p part Con but to th 64% exe g of each motherapy a total of ments) 30 m usin Pro inte Con exe any ved from http://www weeks, home-base o 5 sessions per w w to moderate inte art rate maximum %

ntrol group receive

min of activity 5 d tructed to maintain predicted maximum

ticipant received w ntrol group could e the study program hese patients % of participants m ercising 150 min p

min of seated exe ng a commercially ogram consisted o ensity repetitive m ntrol group receive ercises but were p y usual physical ac

w.sf-36.org/cgi-ed, walking progra week ensity measured b (HR max) from 40 ed usual care ays weekly. n activity at 60-80 m heart rate. Eac weekly phone call exercise if they ch m was not availab met the goal of per week ercise 3 x weekly y available video of 20 min moderate otion exercise ed no specific permitted to contin ctivity 19 am, by a 0 to 0% h ls hose ble e-nue

20 4.1.1.3 Aer Nine RCTs r interventions43-4 remaining had a QOL measure WHOQOL-BRE one scale. Estimates of the subscales of QO Overall quality Two studies fo One of these st as linear growt growth rate d (N=40) found a BREF (p<0.001 One small stud overall QOL me larger study (N (p=0.0007) and Two studies fou by FACT-AN an Two other stud measures for Q measured as le suggested no e robic intervention reported quality 45,48,49,51,53,56,58_{. On} an either moderat ement scales in EF, FACIT-F and

e effect of aerobic OL differed widely y of life ound a positive e tudies (N=72) fou th rate difference ifference betwee a positive effect 1)49. dy (N=22) found easured by FACT N=203) found a d 6 months (p=0.0 und no effect of a nd (FACT-G + FA ies had an unclea QOL43,48_{. One of}

ess decline in QO effect for exercise

ns of life (QOL) ne study had a lo te43,45,51,56 or high ncluded FACT-G SF-36 with some c exercise on qua y across the studi

ffect of aerobic e nd a positive effe between groups en groups (p=0.0 on overall QOL a positive effec T-G (p=0.46), but positive effect fo 39) and no effect aerobic exercise o ACT-B), respective ar or limited repor these studies su OL in the exercis on overall QOL43 Exercise t measures for w risk of bias53_{, w} risk of bias44,48,49, G, FACT-B, FA e studies using mo lity of life and on p es (Table 8). exercise on overa ct for FACT-G, m (p<0.001) and q 011)58_{. The othe} measured by WH t of aerobic exe no effect for FAC or FACT-B at 12

for FACT-G53_.

on overall QOL m ely45,56.

rting of group com ggested a positiv se group48 _{and on}

.

treatment for adult

aerobic while the 58_. ACT-AN, ore than physical all QOL. measured quadratic er study HOQOL-rcise on CT-B44. A 2 weeks measured mparison ve effect ne study P O m O ( b T b T m p o S w O m t cancer patients Physical subscal One small study (N measured by WHO One study found

SF-36) for patien but not for patients Two studies did n by “physical” (FAC Two studies had measures for phys positive effect on other study sugge SF-36 subscale “p whether there was One study did n measure45_. le of quality of lif N=40) found a po OQOL-BREF subs an effect of aero nts in a self-direc s in a supervised not find an effect CT-GP)53 _{and by “}

an unclear or l sical QOL subsca

physical well-bei ested an effect (p< physical”. In anoth s a suggested effe ot include a phy fe ositive effect of ae scale physical (p< obic exercise on cted (home-based (institution-based for physical QOL physical well-bein limited reporting ales. One of thes

ng (FACIT-F sub <0.05) in favour o her study it was n ect or not51_.

ysical QOL subs

KCE Report robic exercise on <0.001)49_. “physical functio d) study arm (p=0 ) study arm56_. L subscales, meas ng” (FACT-B)44_. of group compa e studies sugges bscale; p=0.0252) of the control grou

not possible to as scale as an out t 185 QOL oning” 0.03), sured arison sted a . The up on ssess come

KCE Report 185 Table 8 – Effec Study N Courneya 200745 N= Mutrie 200753 N= Mock 200551 N= Segal 200156 N= Wang 201158 N= 5 ct of aerobic inte Overall =242 No effec measure =203 No effec measure Effect fo (p=0.000 (p=0.039 =119 No repor =123* No effec FACT-B =72 FACT-G 2 groups at linear erventions on qu QOL ct (FACT-AN) at a e point ct for FAGT-G at a e point r FACT-B at 12 w 07) and 6 months 9) rting of overall QO

ct for FACT-G and

change between s significantly diffe

growth rate (t70=

Exercise t

ality of life (QOL Physical ny No physic any weeks No effect G) at any OL Unclear r 36 “Physi subscale measures d No effect functionin institution patients r chemothe Positive e “Physical for patien receiving the erent =3.76, No report subscales

treatment for adult

L) and physical s subscale cal subscale repo

for Physical (FAC y measure point reporting of MOS S ical Functioning” group compariso s for “physical ng” (SF-36) in n-based study arm

receiving erapy effect on SF-36 functioning” (p=0 nt in self-directed a chemotherapy ting of physical s t cancer patients ubscales of QOL Measure p rting Baseline Post-test ( weeks) 6-months CT- Baseline 12 weeks 6 months SF-n Baseline After interv Interventio dependen adjuvant th 6 weeks o or 3-6 mon chemothe m for 0.03) arm Baseline a 4 measure surgery ba 1), 24 hou L in patients with point (median 17 follow-up A (follow-up) vention on length was t on length of herapy (either of radiotherapy nths of rapy) and 26 weeks e points; Pre-aseline (time rs prior to first h breast cancer Intervention cha AET (aerobic arm cycle ergometer, beginning at 60% See Table 6 See Table 7 Supervised arm: e (walking exercise + expected to exe other weekdays Self-directed arm 5 x weekly. Partic progressive walki 60% of maximal o Control group rec general advice See Table 7 aracteristics m): 3 x weekly on treadmill or elliptic % of VO2max exercise 3 x week e at prescribed pac ercise at home 2 : Exercise at hom cipants performed ng program at 50 oxygen uptake ceived usual care

21 cal kly ce) me a 0-i.e.