Radiotherapy in bone metastasis : the Dutch bone metastasis study Linden, Y.M. van der
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Hele tekst
(2) #OST UTILITY ANALYSIS OF SINGLE VERSUS MULTIPLE FRACTION RADIOTHERAPY IN PATIENTS WITH PAINFUL BONE METASTASES 8JMCFSU#WBOEFO)PVU :WFUUF.WBOEFS-JOEFO &MTCFUI4UFFOMBOE 3VVE(+8JHHFOSBBE +PC,JFWJU )BOOFLFEF)BFT +BO8JMMFN)-FFSGPS UIF%VUDI#POF.FUBTUBTJT(SPVQ +PVSOBMPGUIF/BUJPOBM$BODFS*OTUJUVUF .
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¾DBOUEJGGFSFODFTXFSFGPVOEJOQBJO SFTQPOTF USFBUNFOUTJEFFGGFDUT BOEEFTDSJQUJWFRVBMJUZPGMJGF"MJNJUFE BOBMZTJTPGUIFDPTUTPGSBEJPUIFSBQZTVHHFTUFEUIBUUIFDPTUEJGGFSFODFXBT TNBMM5IFNFEJDBMDPTUTGPSUIFTJOHMFGSBDUJPOTDIFEVMFXFSFPOMZMPXFS CFDBVTFBMBSHFQSPQPSUJPOPGUIFDPTUTEJEOPUDIBOHFXJUIUIFOVNCFSPG GSBDUJPOT.PSFPWFS UIFDPTUEJGGFSFODFXBTEFDSFBTFECZUIFOVNCFSPGSF USFBUNFOUT XIJDIXBTBGUFSUIFTJOHMFGSBDUJPOTDIFEVMFDPNQBSFEXJUI POMZBGUFSUIFNVMUJQMFGSBDUJPOTDIFEVMF 5PEFUFSNJOFGSPNBTPDJFUBMQFSTQFDUJWFXIJDISBEJPUIFSBQZTDIFEVMFQSP WJEFTCFUUFSWBMVFGPSUIFNPOFZ XFQFSGPSNFEBGVMMDPTUVUJMJUZBOBMZTJTPG UIF%VUDI#POF.FUBTUBTJT4UVEZ*OUIFDPTUVUJMJUZBOBMZTJT FGGFDUJWFOFTTJT NFBTVSFECZRVBMJUZBEKVTUFEMJGFFYQFDUBODZ JF UIFPWFSBMMWBMVBUJPOPGUIF IFBMUIPGUIFQBUJFOUTJOUIFTUVEZ5IFEJGGFSFODFJOUIJTRVBMJUZBEKVTUFEMJGF FYQFDUBODZXBTDPNQBSFEXJUIUIFEJGGFSFODFJOUIFUPUBMDPTUTUPTPDJFUZ JODMVEJOHUIFNFEJDBMDPTUTPGSBEJPUIFSBQZ PUIFSDPTUTPGIFBMUIDBSFVUJMJ [BUJPO BOEDPTUTJODVSSFECZUIFQBUJFOUT. -ATERIAL AND -ETHODS 3TUDY POPULATION %FUBJMPGUIFQBUJFOUQPQVMBUJPOBOETUVEZEFTJHOGPSUIF%VUDI#POF.FUBT UBTJT4UVEZIBWFCFFOQVCMJTIFEFMTFXIFSF *OCSJFG GSPN.BSDIUISPVHI 4FQUFNCFS QBUJFOUTXJUIQBJOGVMCPOFNFUBTUBTFTGSPNTPMJEUVNPST XFSFSBOEPNMZBTTJHOFEUPSFDFJWFFJUIFSBTJOHMFGSBDUJPOPG(Z O PS GSBDUJPOTPG(Z O 5IFQBUJFOUTXFSFFOSPMMFEJOUIFTUVEZGSPN GSPN%VUDISBEJPUIFSBQZJOTUJUVUJPOT0GUIFQBUJFOUT IBECPOF.
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(8) 2ESULTS. ,% #(!2!#4%2)34)#3 !4 "!3%,).% /& 4(% %.4)2% 3!-0,% /& 0!4)%.43 %.2/,,%$ ). 4(% $54#( "/.% -%4!34!3)3 345$9 !.$ 2!.$/-,9 !33)'.%$ 4/ 2%#%)6% %)4(%2 3).',% /2 -5,4)0,% &2!#4)/. 2!$)/4(%2!09 !.$ /& 4(% 35"3!-0,% /& 0!4)%.43 7(/ &),,%$ /54 #/34 15%34)/..!)2%3. 3UBSAMPLE OF PATIENTS WHO l LLED OUT THE COST QUESTIONNAIRES. 'Y X N . 'Y X N . 'Y X N . 'Y X N .
(9) Y AGE GE. . . . . DER
(10) N E ALE. . . . . IAL PAIN SCORE o AGE GE NOFSKY SCORE p AGE GE. . . . . . . . . MARY TUMOR
(11) N MMA G TATE ER. . . . . 5IFQVSQPTFPGUIFTUVEZXBTUPEFUFSNJOFGSPNBTPDJFUBMQFSTQFDUJWFXIJDI SBEJPUIFSBQZTDIFEVMFQSPWJEFECFUUFSWBMVFGPSUIFNPOFZ5IFCBTFMJOF DIBSBDUFSJTUJDTPGUIFFOUJSFTBNQMFPGQBUJFOUTFOSPMMFEJOUIFTUVEZBSF TIPXOJO5BCMF UPHFUIFSXJUIUIFTVCTBNQMFPGQBUJFOUTXIP¾MMFEPVU UIFBEEJUJPOBMDPTURVFTUJPOOBJSFT5IFQBUJFOUTJOUIFTVCTBNQMFIBEXPSTF JOJUJBMQBJOTDPSFTUIBOUIFQBUJFOUTJOUIFFOUJSFTBNQMF WFSTVT 1 8JUIJOUIFTVCTBNQMF UIFHSPVQPGQBUJFOUTSBOEPNMZBTTJHOFEUP SFDFJWFUIFTJOHMFGSBDUJPOUSFBUNFOUTDIFEVMFJODMVEFENPSFXPNFO 1 "MMPUIFSEJGGFSFODFTXFSFOPUTUBUJTUJDBMMZTJHOJ¾DBOU 1 1UALITY ADJUSTED LIFE YEARS %VSJOHUIFTUVEZQFSJPE PGBMMQBUJFOUTEJFE&TUJNBUFEDVNVMBUJWFNPS UBMJUZGPSUIF¾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l LLED OUT COST QUESTIONNAIRES WAS SELECTED FROM CONSECUTIVELY ENROLLED PATIENTS IN THREE INSTITUTIONS )NITIAL PAIN SCORE MAXIMUM PAIN SCORE DURING THE WEEK PRECEDING RANDOMIZATION
(12) ON AN POINT SCALE FROM NO PAIN TO WORST IMAGINABLE PAIN +ARNOFSKY SCORE +ARNNOFSKY 0ERFORMANCE 3TATUS 3CALE
(13) RANGING FROM NORMAL NO COMPLAINTS NO EVIDENCE OF DISEASE THROUGH ARES FOR SELF UNABLE TO CARRY ON NORMAL ACTIVITY OR DO ACTIVE WORK TO DEATH. 3TATISTICAL ANALYSIS "MMBOBMZTFTXFSFQFSGPSNFEPOBOJOUFOUUPUSFBUCBTJT(SPVQTXFSFDPNQBSFE CZVTFPGTUBOEBSEUXPTJEFEVOFRVBMWBSJBODF UUFTUTBUBTJHOJ¾DBODF MFWFM XJUIUIFDPSSFTQPOEJOHDPO¾EFODFJOUFSWBMT $*T GPSUIFEJGGFSFODF JONFBOT3FQPSUFE$*TGPSNFBOTXJUIJOHSPVQTBSFTUBOEBSE$*T BWFSBHF <U O YO >YTUBOEBSEEFWJBUJPO "TUBOEBSENVMUJWBSJBUFSFHSFTTJPOBOBMZ TJTBEKVTUFEGPSUIFSBOEPNJ[BUJPOTDIFEVMFXBTVTFEUPJEFOUJGZTUBUJTUJDBMMZ TJHOJ¾DBOUQSFEJDUPSTPGDPTUTBNPOHUIFWBSJBCMFTUIBUEJGGFSFECFUXFFO TBNQMFTPSSBOEPNJ[BUJPOHSPVQT"MMTUBUJTUJDBMBOBMZTFTXFSFQFSGPSNFEXJUI 4144TPGUXBSF WFSTJPO 4144*OD $IJDBHP *- . &)'52% . &)'52% . 0ROPORTION SURVIVING AND AVERAGE %URO1OL CLASSIl CATION SYSTEM %1 $ UTILITY FOR THE SINGLE AND MULTIPLE FRACTION RADIOTHERAPY GROUPS #ENSURED SURVIVAL TIMES AND MISSING %1 $ UTILITY MEASUREMENTS WERE EXTRAPOLATED FROM THE LAST AVAILABLE %1 $ UTILITY MEASUREMENT %1 $ UTILITY REPRESENTS THE VALUATION OF HEALTH ON A SCALE FROM EQUIVALENT TO DEATH TO OPTIMAL HEALTH 3INGLE FRACTION THERAPY REFERS TO A SINGLE FRACTION OF 'Y -ULTIPLE FRACTION THERAPY REFERS TO SIX FRACTIONS OF 'Y 7EEKS SINCE RANDOMIZATION REFERS TO THE TIME THE PATIENTS WERE ENROLLED IN THE $UTCH "ONE -ETASTASIS 3TUDY. !VERAGE %URO1OL CLASSIl CATION SYSTEM %1 $ UTILITY FOR SINGLE AND MULTIPLE FRACTION RADIOTHERAPY GROUPS
(14) AS A FUN OF REMAINING LIFETIME !VERAGES ARE OVER ALL MEASUREMENTS PARTICULAR MONTHS
(15) WITHOUT EXTRAPOLATION OF MISSING MEASUREMENTS %1 $ UTILITY REPRESENTS THE VALUATION OF H ON A SCALE FROM EQUIVALENT TO DEATH TO OPTIM HEALTH 3INGLE FRACTION THERAPY REFERS TO A SINGLE FRACTION -ULTIPLE FRACTION THERAPY REFERS TO SIX FRACTIONS OF 'Y UNTIL END OF LIFE REFERS TO THE TIME UNTIL DEATH FOR PATIEN ENROLLED IN THE $UTCH "ONE -ETASTASIS 3TUDY. 0ROPORTION SURVIVING AND AVERAGE %1 $ UTILITY. PCUBJOFEGSPNUIFQBUJFOUTXIP¾MMFEPVUUIFDPTURVFTUJPOOBJSFT O 5IF CBTFMJOFDPTU°VUJMJUZBOBMZTJTVTFEUIFTPDJFUBMQFSTQFDUJWF JODMVEJOHBMMDPTUT JODVSSFEEVSJOHUIF¾STUXFFLTBGUFSSBOEPNJ[BUJPO*OBEEJUJPO XFQFS GPSNFETFOTJUJWJUZBOBMZTFTGSPNUIFNFEJDBMQFSTQFDUJWF JODMVEJOHPOMZ NFEJDBMDPTUTPGSBEJPUIFSBQZBOEPGPUIFSIFBMUIDBSFEVSJOHUIF¾STUXFFLT BGUFSSBOEPNJ[BUJPO BOEUIFMPOHUFSNSBEJPUIFSBQZQFSTQFDUJWF JODMVEJOH POMZNFEJDBMBOEOPONFEJDBMDPTUTPGSBEJPUIFSBQZEVSJOHUIF¾STUZFBST BGUFSSBOEPNJ[BUJPO . . 3URVIVAL. 3INGLE FRACTION -ULTIPLE FRACTION. . %1 $ . 7EEKS SINCE RANDOMIZATION. !VERAGE %1 $ UTILITY. %NTIRE SAMPLE. 3INGLE FRACTION -ULTIPLE FRACTION . . 7EEKS UNTIL END OF LIFE. .
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¾DBOU 5BCMF 5IFPWFSBMMBWFSBHF MJGFFYQFDUBODZXBTBQQSPYJNBUFMZNPOUIT EJGGFSFODF °XFFLT $* °UPXFFLT %VSJOHUIF¾STUXFFLTBGUFSSBOEPNJ[BUJPO IFBMUI XBTWBMVFEBUBQQSPYJNBUFMZPOFUIJSEUIFWBMVFPGPQUJNBMIFBMUI EJGGFSFODF JO2"-:TEVSJOHUIF¾STUXFFLT °XFFLT $* °UPXFFLT 5IFPWFSBMMBWFSBHFRVBMJUZBEKVTUFEMJGFFYQFDUBODZXBTBQQSPYJNBUFMZ NPOUIT EJGGFSFODF °XFFLT $* °UPXFFLT . 4!",% ,)&% %80%#4!.#9 !.$ 15!,)49 !$*534%$ ,)&% %80%#4!.#9 /& 4(% 0!4)%.43 %.2/,,%$ ). 4(% $54#( "/.% -%4!34!3)3 345$9 !.$ 2!.$/-,9 !33)'.%$ 4/ 2%#%)6% %)4(%2 3).',% /2 -5,4)0,% &2!#4)/. 2!$)/4(%2!09. -ULTIPLE FRACTION 'Y X N .O OF WEEKS #). 3INGLE FRACTION 'Y X N .O OF WEEKSo #) TO TO TO . ,IFE EXPECTANCY 1!,9 ) WEEKSp 1!,9S. TO TO TO . P VALUE . . 'Y GRAY 1!,9S QUALITY ADJUSTED LIFE YEARS #) CONl DENCE INTERVAL AVERAGE ¢ T N
(17) X N X STANDARD DEVIATION 0 VALUES DERIVED FROM STANDARD TWO SIDED UNEQUAL VARIANCE T TESTS o !VERAGE NUMBER OF WEEKS p $URATION TRUNCATED AT WEEKS AFTER RANDOMIZATION TO QUANTIFY THE VALUATION OF SHORT TERM QUALITY OF LIFE. 4!",% %34)-!4%$ -%$)#!, #/343 /& 2!$)/4(%2!09 &/2 4(% #/.3425#4%$ 490)#!, 2!$)/4(%2!09 $%0!24-%.4 #OSTS PER ALLOCATION BASE IN K. 4OTAL COSTS IN K. 4REATMENTS. &RACTIONS. 'RAY. 0ERSONNEL %QUIPMENT -ATERIAL (OUSING /VERHEAD. . . . . !NNUAL COSTS IN K !NNUAL NUMBER o 5NIT COSTS IN p 'Y X SCHEDULE 'Y X SCHEDULE. . . . . X X. X X. X X. . /NE K EQUALS 3EPARATE COST ITEMS ARE ALLOCATED TO TREATMENTS IF THEY ARE INDEPENDENT OF THE TREATMENT SCHEDULE
(18) TO SESSIONS IF THEY ARE PROPORTIONAL TO THE NUMBER OF FRACTIONS IN A TREATMENT SCHEDULE
(19) AND TO GRAY IF THEY ARE PROPORTIONAL TO THE RADIATION DOSE DELIVERED o /BTAINED BY DIVIDING THE ANNUAL COSTS BY THE ANNUAL NUMBER
(20) FOR EACH ALLOCATION BASE p /BTAINED BY MULTIPLYING THE UNIT COSTS WITH THE NUMBER OF UNITS OF THE SCHEDULE . #OSTS OF RADIOTHERAPY 8FFTUJNBUFEUIFNFEJDBMDPTUTPGSBEJPUIFSBQZGPSUIFDPOTUSVDUFEUZQJDBM SBEJPUIFSBQZEFQBSUNFOU 5BCMF 5IFUPUBMBOOVBMDPTUTGPSUIJTUZQJDBM EFQBSUNFOUXFSFNJMMJPOEPMMBST*UVTFEBUPUBMPGGVMMUJNFFRVJWBMFOU QFSTPOOFM JODMVEJOHGVMMUJNFFRVJWBMFOUSBEJBUJPOPODPMPHJTUT"QQSPYJ NBUFMZUXPUIJSETPGUIFDPTUTPGQFSTPOOFMXFSFBUUSJCVUFEUPUIFUSFBUNFOUT NBJOMZSBEJBUJPOPODPMPHJTUTBOEQMBOOJOH BOEBQQSPYJNBUFMZPOFUIJSEUP UIFTFTTJPOT SBEJBUJPOUIFSBQJTUTBOEUFDIOPMPHJTUT 5IFUZQJDBMEFQBSUNFOU IBEMJOFBSBDDFMFSBUPST5IFDPTUTPGFRVJQNFOUXFSFBQQSPYJNBUFMZFRVBMMZ EJTUSJCVUFEPWFSUIFUISFFBMMPDBUJPOCBTFTUSFBUNFOUT TJNVMBUJPO QMBOOJOH BOENBJOUFOBODF TFTTJPOT CFDBVTFMJOFBSBDDFMFSBUPSTXFBSPVUCZUVSOJOH UIFNPOBOEPGG BOEHSBZ CFDBVTFMJOFBSBDDFMFSBUPSTXFBSPVUBDDPSEJOHUP UIFEVSBUJPOPGUIFPOQFSJPE $PTUTPGIPVTJOHXFSFQSJNBSJMZBTTJHOFEUPUIF TFTTJPOT JF GPSQBUJFOUXBJUJOHSPPNTBOEUIFMJOFBSBDDFMFSBUPST CVUBMTPUP UIFUSFBUNFOUT JF GPSTUBGG $PTUTPGPWFSIFBEXFSFQSJNBSJMZBTTJHOFEUP UIFUSFBUNFOUTBOE UIFSFGPSF EPOPUDPOUSJCVUFUPUIFEJGGFSFODFJODPTUT CFUXFFOCPUITDIFEVMFT5IFFTUJNBUFENFEJDBMDPTUTQFSBMMPDBUJPOCBTFXFSF QFSUSFBUNFOU QFSTFTTJPO BOEQFSHSBZ"GUFSNVMUJ QMZJOHCZUIFBQQSPQSJBUFOVNCFSTGPSFBDISBEJPUIFSBQZTDIFEVMF UIFFTUJ NBUFENFEJDBMDPTUTXFSFGPSUIFTJOHMFGSBDUJPOTDIFEVMFBOE GPSUIFNVMUJQMFGSBDUJPOTDIFEVMF5IFFTUJNBUFEEJGGFSFODFJONFEJDBMDPTUT GPSUIFJOJUJBMSBEJBUJPOUSFBUNFOUXBTUIFSFGPSF 8FOFYUFTUJNBUFEUIFUPUBMSBEJPUIFSBQZDPTUT 'JHBOE5BCMF JODMVEJOH SFUSFBUNFOUBOEOPONFEJDBMDPTUTEVSJOHUIF¾STUXFFLTBGUFSSBOEPNJ [BUJPO5IFMBSHFTUDPTUEJGGFSFODFXBTPCTFSWFEJOUIFTFDPOEXFFLQFSJPE "UUIBUUJNF NPTUTJOHMFGSBDUJPOUSFBUNFOUTDIFEVMFTIBEFOEFE XIFSFBTUIF NVMUJQMFGSBDUJPOTDIFEVMFTUJMMHFOFSBUFEDPTUTCFDBVTFPGUIFMPOHFSXBJUJOH UJNFSFRVJSFEUPTDIFEVMFUIFUSFBUNFOUBOEUIFMPOHFSUSFBUNFOUUJNF"GUFS XFFLT UIFDPTUEJGGFSFODFCFUXFFOUIFTJOHMFBOENVMUJQMFGSBDUJPOHSPVQT XBTSFWFSTFECFDBVTFUIFOVNCFSPGSFUSFBUNFOUTJOUIFTJOHMFGSBDUJPOHSPVQ XBTMBSHFSUIBOJOUIFNVMUJQMFGSBDUJPOHSPVQ WFSTVT EVSJOHUIF¾STU XFFLTBGUFSSBOEPNJ[BUJPO 5IJTEJGGFSFODFJOUIFOVNCFSPGSFUSFBUNFOUT SFEVDFEUIFJOJUJBMDPTUEJGGFSFODFCZ0GUIFOPONFEJDBMDPTUT XFSF BTTPDJBUFEXJUIUSBWFMFYQFOTFT XFSFBTTPDJBUFEXJUIUJNFDPTUT BOE XFSFBTTPDJBUFEXJUIPVUPGQPDLFUFYQFOTFT TVDIBTNFBMT#FDBVTFPGUIF EJGGFSFODFJOUIFOVNCFSPGSBEJPUIFSBQZGSBDUJPOTJOUIFUSFBUNFOUTDIFEVMFT UIFOPONFEJDBMDPTUTGPSUIFTJOHMFGSBDUJPOHSPVQXFSFMFTTUIBOUIPTF GPSUIFNVMUJQMFGSBDUJPOHSPVQ5IFFTUJNBUFETPDJFUBMDPTUTPGSBEJPUIFSBQZ EVSJOHUIF¾STUXFFLTBGUFSSBOEPNJ[BUJPOXFSFGPSUIFTJOHMFGSBD UJPOTDIFEVMFBOEGPSUIFNVMUJQMFGSBDUJPOTDIFEVMF BOFTUJNBUFE EJGGFSFODFPG $* UP .
(21) "MUIPVHIUIFCBTFMJOFBOBMZTJTPOMZJODMVEFEDPTUTEVSJOHUIFJOJUJBMXFFLT BGUFSSBOEPNJ[BUJPO XFBMTPFTUJNBUFEUIFDPTUTPGMPOHUFSNSFUSFBUNFOUT "NPOHUIFQBUJFOUTXIPSFUVSOFEUIFDPTURVFTUJPOOBJSFT ¾WFQBUJFOUT XFSFSFUSFBUFEBGUFSNPSFUIBOXFFLTJOCPUISBOEPNJ[BUJPOHSPVQT*O DMVEJOHUJNFBOEUSBWFM UIFDPTUTPGUIFTFMPOHUFSNSFUSFBUNFOUTXFSF JOUIFTJOHMFGSBDUJPOHSPVQBOEJOUIFNVMUJQMFGSBDUJPOHSPVQ XIJDI XBTOPUBTUBUJTUJDBMMZTJHOJ¾DBOUEJGGFSFODF 1 5IFDPNCJOFETIPSUBOE MPOHUFSNSFUSFBUNFOUSBUFTJOUIFTVCTFUPGQBUJFOUTXIPSFUVSOFEUIFDPTU RVFTUJPOOBJSFT GPSUIFTJOHMFGSBDUJPOHSPVQBOEGPSUIFNVMUJQMF GSBDUJPOHSPVQ XFSFOPUTUBUJTUJDBMMZTJHOJ¾DBOUMZEJGGFSFOU 1 GSPNUIPTF JOUIFFOUJSFTBNQMF BOE SFTQFDUJWFMZ 3OCIETAL COSTS 0GBMMQPTTJCMFMJGFUJNFDPTURVFTUJPOOBJSFT XFSFPCUBJOFEBOEVTFEUP FTUJNBUFIFBMUIDBSFVUJMJ[BUJPOBOEDPTUT 5BCMF 5IFNFEJDBMDPTUT FYDMVEJOH SBEJPUIFSBQZUSFBUNFOUDPTUT DPOTJTUFENBJOMZPGUIFDPTUTBTTPDJBUFEXJUI IPTQJUBMJ[BUJPOT5IFZXFSFFRVJWBMFOUJOTJ[FUPSBEJPUIFSBQZUSFBUNFOUDPTUT CVUUIFEJGGFSFODFCFUXFFOUIFSBOEPNJ[BUJPOHSPVQTXBTOPUTUBUJTUJDBMMZ TJHOJ¾DBOU 1 5IFUPUBMOPONFEJDBMDPTUTPUIFSUIBOGPSSBEJPUIFSBQZ XFSFTNBMMCFDBVTFUIFBEEJUJPOBMDPTUTXFSFDPNQFOTBUFECZUIFWBMVFPGUIF QSPWJEFEMBCPS"MUIPVHITPNFPGUIFEJGGFSFODFTJOUIFTFOPOSBEJPUIFSBQZ DPTUJUFNTXFSFDPOTJEFSBCMF UIFZXFSFBMMOPUTUBUJTUJDBMMZTJHOJ¾DBOU 1 5IFPWFSBMMNFEJDBMDPTUT JODMVEJOHUIFNFEJDBMDPTUTPGSBEJPUIFSBQZBOE. &)'52% !VERAGE SOCIETAL COSTS FOR THE SINGLE AND MULTIPLE FRACTION RADIOTHERAPY GROUPS 2ADIOTHERAPY COSTS REFER TO THE MEDICAL AND NONMEDICAL COSTS OF RADIOTHERAPY .ONRADIOTHERAPY COSTS REFER TO ALL OTHER SOCIETAL COSTS MEDICAL AND NONMEDICAL NONRADIOTHERAPY COSTS 3INGLE FRACTION THERAPY REFERS TO A SINGLE FRACTION OF 'Y -ULTIPLE FRACTION THERAPY REFERS TO SIX FRACTIONS OF 'Y 7EEKS SINCE RANDOMIZATION REFERS TO THE TIME THE PATIENTS WERE ENROLLED IN THE $UTCH "ONE -ETASTASIS 3TUDY
(22) . 2ADIOTHERAPY COSTS
(23) SINGLE FRACTION 2ADIOTHERAPY COSTS
(24) MULTIPLE FRACTION .ON RADIOTHERAPY COSTS
(25) SINGLE FRACTION .ON RADIOTHERAPY COSTS
(26) MULTIPLE FRACTION. !VERAGE SOCIETAL COSTS IN .
(27)
(28)
(29) . . 7EEKS SINCE RANDOMIZATION. . 4!",% %34)-!4%$ (%!,4( #!2% 54),):!4)/. !.$ #/343 0%2 0!4)%.4 $52).' 4(% &)234 7%%+3 !&4%2 2!.$/-):!4)/. &/2 4(% 3).',% !.$ -5,4)0,% &2!#4)/. 2!$)/4(%2!09 '2/503. -ULTIPLE FRACTIONS 'Y X N . 3INGLE FRACTION 'Y X N 5TILIZATION o #OSTS OF RADIOTHERAPY )NITIAL TREATMENT 2ETREATMENTS a WEEKS 4IME
(30) TRAVEL
(31) OUT OF POCKET /THER MEDICAL COSTS (OSPITALIZATION 3YSTEMIC THERAPY #ONSULTATIONS 0AIN MEDICATION /THER MEDICATION (OME NURSING CARE /THER NON MEDICAL COSTS 4IME
(32) TRAVEL /UT OF POCKET $OMESTIC HELP 5N PAID LABOR -EDICAL COSTS 3OCIETAL COSTS. H H H H H. p #OSTS #) TO TO TO TO TO TO TO TO TO TO TO TO TO TO TO TO TO TO . 5TILIZATION e. H H H H. 0 VALU. p #OSTS #) TO TO TO TO . . TO TO TO TO TO TO TO . . TO TO TO TO TO TO TO . . . 'Y GRAY #) CONl DENCE INTERVAL AVERAGE T N
(33) X N X STANDARD DEVIATION 0 VALUES DERIVED FROM STANDARD TWO SIDED UNEQUAL VARIANCE T TESTS o 0ERCENTAGE OF PATIENTS RECEIVING PARTICULAR CARE
(34) TOTAL NUMBER OF CONSULTATIONS
(35) OR HOURS OF CARE
(36) p !VERAGE COSTS IN #OSTS WERE DERIVED FROM $UTCH STANDARD PRICES e .EGATIVE COSTS REPRESENT PROl TS. BMMPUIFSNFEJDBMDPTUT XFSFFTUJNBUFEUPCFMPXFSGPSQBUJFOUTJOUIF TJOHMFGSBDUJPOHSPVQUIBOGPSQBUJFOUTJOUIFNVMUJQMFGSBDUJPOHSPVQ $* °UP 4JNJMBSMZ UIFPWFSBMMTPDJFUBMDPTUT JODMVEJOHBMMNFEJDBMBOE BMMOPONFEJDBMDPTUT XFSFFTUJNBUFEUPCFMPXFSGPSQBUJFOUTJOUIF TJOHMFGSBDUJPOHSPVQ $* °UP )PXFWFS CPUIPWFSBMMEJGGFS FODFTXFSFOPUTUBUJTUJDBMMZTJHOJ¾DBOU 1 BOE1 SFTQFDUJWFMZ #FDBVTFUIFEJGGFSFODFTJOJOJUJBMQBJOTDPSFBOETFY 5BCMF DPVMEIBWF JO¿VFODFEUIFDPNQBSJTPO XFQFSGPSNFEBNVMUJWBSJBUFSFHSFTTJPOBOBMZTJTPG UIFFTUJNBUFESBEJPUIFSBQZDPTUT UIFNFEJDBMDPTUT BOEUIFTPDJFUBMDPTUT "GUFSBEKVTUJOHGPSUIFSBOEPNJ[BUJPOTDIFEVMF DPTUTXFSFOPUTUBUJTUJDBMMZ TJHOJ¾DBOUMZQSFEJDUFECZUIFJOJUJBMQBJOTDPSF 1 1 BOE1 SFTQFDUJWFMZ PSCZTFY 1 1 BOE1 SFTQFDUJWFMZ "MTP UIF FTUJNBUFE2"-:TPGUIFQBUJFOUTXIP¾MMFEPVUUIFDPTURVFTUJPOOBJSFTEJEOPU EJGGFSGSPNUIFFTUJNBUFE2"-:TJOUIFFOUJSFTBNQMF 1 GPSUIFTJOHMF GSBDUJPOHSPVQBOE1 GPSUIFNVMUJQMFGSBDUJPOHSPVQ #OST UTILITY ANALYSIS 5IFFTUJNBUFE2"-:TBOETPDJFUBMDPTUTCPUIGBWPSFEUIFTJOHMFGSBDUJPOUSFBU NFOUTDIFEVMF QSPWJEJOHBOBEEJUJPOBMRVBMJUZBEKVTUFEXFFLTBOETBWJOH SFMBUJWFUPUIFNVMUJQMFGSBDUJPOTDIFEVMF BMUIPVHIJOOFJUIFSDBTFXBT.
(37) &)'52% . 0 VALUE OF EQUAL NET BENEl T IN BOTH RANDOMIZATION GROUPS. 0 VALUES DERIVED FROM TESTING THE HYPOTHESIS OF EQUAL NET BENEl T WILLINGNESS TO PAY X QUALITY ADJUSTED LIFE YEARS ;1!,9S= n COSTS IN BOTH RANDOMIZATION GROUPS
(38) PLOTTED IN ACCEPTABILITY CURVES USING STANDARD TWO SIDED UNEQUAL VARIANCE T TESTS 3TATISTICALLY SIGNIl CANTLY BETTER COST EFFECTIVENESS OF THE SINGLE FRACTION TREATMENT SCHEDULE IS DEMONSTRATED IF THE CURVE IS BELOW 4HE SOCIETAL PERSPECTIVE INCLUDES ALL COSTS INCURRED DURING THE l RST WEEKS AFTER RANDOMIZATION 4HE MEDICAL PERSPECTIVE INCLUDES ALL MEDICAL COSTS OF RADIOTHERAPY AND OF OTHER HEALTH CARE DURING THE l RST WEEKS AFTER RANDOMIZATION 4HE LONG TERM RADIOTHERAPY PERSPECTIVE INCLUDES ALL MEDICAL AND NONMEDICAL COSTS OF RADIOTHERAPY DURING THE l RST YEARS AFTER RANDOMIZATION . 8FBMTPQFSGPSNFEBTFOTJUJWJUZBOBMZTJT DPOTJEFSJOHEJGGFSFOUDPTUQFS TQFDUJWFT'SPNBNFEJDBMDPTUQFSTQFDUJWF UIF1WBMVFTXFSFTPNFXIBUMFTT GBWPSBCMFUIBOGSPNUIFTPDJFUBMDPTUQFSTQFDUJWFBOESFNBJOFEBCPWFUIF TUBUJTUJDBMTJHOJ¾DBODFMFWFM 'JH 3FTUSJDUJOHDPTUTUPUIFTIPSUBOEMPOH UFSNDPTUTPGSBEJPUIFSBQZ UIFCFUUFSDPTUFGGFDUJWFOFTTPGUIFTJOHMFGSBDUJPO TDIFEVMFXBTTUBUJTUJDBMMZTJHOJ¾DBOUGPSBMMXJMMJOHOFTTUPQBZWBMVFTMFTT UIBO5IJTSBOHFXBTDPNQBSBCMFUPUIBUPCUBJOFEGSPNUIFTPDJFUBM QFSTQFDUJWF . $ISCUSSION. . 3OCIETAL PERSECTIVE -EDICAL PERSECTIVE ,ONG TERMS RADIOTHERAPY PERSECTIVE. . . . . . 7EEKS SINCE RANDOMIZATION . UIFEJGGFSFODFTUBUJTUJDBMMZTJHOJ¾DBOU$POTFRVFOUMZ UIFTJOHMFGSBDUJPO TDIFEVMFJTMJLFMZUPCFNPSFDPTUFGGFDUJWFUIBOUIFNVMUJQMFGSBDUJPOTDIFEVMF 5IFTUBUJTUJDBMDFSUBJOUZPGUIJTTUBUFNFOUEFQFOET IPXFWFS POUIFSFMBUJWF WBMVFPG2"-:TDPNQBSFEXJUIUIFSFMBUJWFWBMVFPGNPOFZ UIBUJT POIPX NVDIPOFJTXJMMJOHUPQBZQFS2"-:*G POUIFPOFIBOE 2"-:TBSFJO¾OJUFMZ NPSFWBMVBCMFUIBONPOFZ UIFODPNQBSJOHDPTU°VUJMJUZSFEVDFTUPDPNQBSJOH 2"-:T 5BCMF 1 *G POUIFPUIFSIBOE NPOFZJTJO¾OJUFMZNPSFWBMVBCMF UIBO2"-:T UIFODPNQBSJOHDPTU°VUJMJUZSFEVDFTUPDPNQBSJOHTPDJFUBMDPTUT 5BCMF 1 *UJTEJG¾DVMUUPTBZIPXNVDITPDJFUZJTXJMMJOHUPQBZGPSB2"-:"SVMF PGUIVNCUIBUJTPGUFORVPUFEJOUIFJOUFSOBUJPOBMMJUFSBUVSFJTUIBU QFS2"-:JTBDDFQUBCMF XIFSFBTQFS2"-:NJHIUOPUCFBDDFQUBCMF 8FUFTUFEDPTUFGGFDUJWFOFTTCZDPNQBSJOHUIFOFUCFOF¾UJOCPUISBOEP NJ[BUJPOHSPVQTUIFCFUUFSDPTUFGGFDUJWFOFTTPGUIFTJOHMFGSBDUJPOUSFBUNFOU TDIFEVMFJTEFNPOTUSBUFEJGUIFOFUCFOF¾UJOUIFTJOHMFGSBDUJPOHSPVQJT TUBUJTUJDBMMZTJHOJ¾DBOUMZCFUUFSUIBOUIBUJOUIFNVMUJQMFGSBDUJPOHSPVQ5IF EFSJWFE1WBMVFTGPSEJGGFSFOUMFWFMTPGUIFXJMMJOHOFTTUPQBZXFSFUIFOQMPUUFE JOBDDFQUBCJMJUZDVSWFT 'JH 'SPNBTPDJFUBMQFSTQFDUJWF UIFCFUUFSDPTU FGGFDUJWFOFTTPGUIFTJOHMFGSBDUJPOSBEJPUIFSBQZXBTTUBUJTUJDBMMZTJHOJ¾DBOUJG POFWBMVFTB2"-:CFUXFFOBOE8IFOB2"-:JTWBMVFEBUMFTT UIBOPSNPSFUIBO UIFOCFUUFSDPTUFGGFDUJWFOFTTPGUIFTJOHMF GSBDUJPOTDIFEVMFXBTTUJMMMJLFMZCVUOPMPOHFSTUBUJTUJDBMMZTJHOJ¾DBOU'PS FYBNQMF BUBOEQFS2"-: UIFTUBUJTUJDBMTJHOJ¾DBODFXBT 1 BOE1 SFTQFDUJWFMZ. 5IF%VUDI#POF.FUBTUBTJT4UVEZTIPXFEUIBUTJOHMFGSBDUJPOSBEJPUIFSBQZ FWFOUIPVHIJUIBEBIJHIFSSFUSFBUNFOUSBUF XBTJONBOZSFTQFDUTDPNQB SBCMFUPNVMUJQMFGSBDUJPOSBEJPUIFSBQZ XJUIOPTUBUJTUJDBMMZTJHOJ¾DBOU EJGGFSFODFTJEFOUJ¾FEJOQBJOSFTQPOTF BOBMHFTJDDPOTVNQUJPO USFBUNFOUTJEF FGGFDUT PSRVBMJUZPGMJGF 5IFTFSFTVMUTIBWFHPPEFYUFSOBMWBMJEJUZSFTVMUJOH GSPNUIFMBSHFOVNCFSPGQBSUJDJQBUJOHJOTUJUVUJPOTBOEUIFEJWFSTFQBUJFOU QPQVMBUJPO *OUIFDPTU°VUJMJUZBOBMZTJTQSFTFOUFEIFSF FGGFDUJWFOFTTXBTNFBTVSFECZ RVBMJUZBEKVTUFEMJGFFYQFDUBODZ UIBUJT UIFPWFSBMMWBMVBUJPOPGIFBMUI"HBJO XFGPVOEOPTUBUJTUJDBMMZTJHOJ¾DBOUEJGGFSFODFCFUXFFOTJOHMFBOENVMUJQMF GSBDUJPOSBEJPUIFSBQZ5IFBWFSBHFOPOBEKVTUFEMJGFFYQFDUBODJFTXFSF XFFLTGPSUIFTJOHMFGSBDUJPOTDIFEVMFBOEXFFLTGPSUIFNVMUJQMFGSBDUJPO TDIFEVMF XIJDIXBTOPUBTUBUJTUJDBMMZTJHOJ¾DBOUEJGGFSFODF5IFTPDJFUBMWBMVF PGUIFTFMJGFFYQFDUBODJFTXBTBTTFTTFEVTJOHUIF&2%RVFTUJPOOBJSF UBLJOH JOUPBDDPVOUNPCJMJUZ TFMGDBSF VTVBMBDUJWJUJFT QBJOEJTDPNGPSU BOEBOYJFUZ EFQSFTTJPO#FTJEFTUIFTFHFOFSBMBUUSJCVUFT UIFSFBSFPUIFSJTTVFTUIBUBSF BMTPTQFDJ¾DBMMZSFMFWBOUJOUIFWBMVBUJPOPGFOEPGMJGFDBSF 'PSFYBNQMF QTZDIPTPDJBMPVUDPNFTTVDIBTSFMJFWJOHUIFCVSEFOPGDBSFBOETUSFOHUIFOJOH SFMBUJPOTIJQTXJUIMPWFEPOFTBSFOPUJODMVEFEJOUIF&2%6OGPSUVOBUFMZ IPXFWFS OPWBMVBUJPOJOTUSVNFOUFYJTUTUIBUJODPSQPSBUFTUIFTFTQFDJ¾DFOE PGMJGFJTTVFT.PSFPWFS XFOPUFEBEJTUJODUEFDSFBTFPGUIF&2%VUJMJUZPWFS UJNF FTQFDJBMMZUPXBSEUIFFOEPGMJGF TVHHFTUJOHUIBUUIFJOTUSVNFOUJT SFTQPOTJWFUPUIFDIBOHJOHIFBMUITUBUVTPGUIFTFQBUJFOUT0OUIFCBTJTPGUIF &2%NFBTVSFNFOUT UIFBWFSBHFRVBMJUZBEKVTUFEMJGFFYQFDUBODJFTXFSF XFFLTJOUIFTJOHMFGSBDUJPOHSPVQBOEXFFLTJOUIFNVMUJQMFGSBDUJPO HSPVQ XIJDIXBTOPUBTUBUJTUJDBMMZTJHOJ¾DBOUEJGGFSFODF 'SPNUIFQBUJFOUQFSTQFDUJWF JUJTPCWJPVTUIBUBTJOHMFGSBDUJPOTDIFEVMFJT MFTTCVSEFOTPNFUIBOBNVMUJQMFGSBDUJPOTDIFEVMF5IFPOFPVUDPNFNFBTVSF JOPVSTUVEZUIBUDPVMENBLFQBUJFOUTGBWPSUIFNVMUJQMFGSBDUJPOPWFSBTJOHMF.
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(40) 0OWERS 7%
(41) -OSS 74
(42) 0EREZ #! "ONE METASTASIS REVIEW AND CRITICAL ANALYSIS OF RANDOM ALLOCATION TRIALS OF LOCAL lELD TREATMENT ;SEE COMMENTS= )NT * 2ADIAT /NCOL "IOL 0HYS 'Y SINGLE FRACTION RADIOTHERAPY FOR THE TREATMENT OF METASTATIC SKELETAL PAIN RANDOMISED COMPARISON WITH A MULTIFRACTION SCHEDULE OVER MONTHS OF PATIENT FOLLOW UP "ONE 0AIN 4RIAL 7ORKING 0ARTY 2ADIOTHER /NCOL #OLE $* ! RANDOMIZED TRIAL OF A SINGLE TREATMENT VERSUS CONVENTIONAL FRACTIONATION IN THE PALLIATIVE RADIOTHERAPY OF PAINFUL BONE METASTASES #LIN /NCOL 2 #OLL 2ADIOL 'AZE -.
(43) +ELLY #'
(44) +ERR '2
(45) #ULL !
(46) #OWIE 6*
(47) 'REGOR ! ET AL 0AIN RELIEF AND QUALITY OF LIFE FOLLOWING RADIOTHERAPY FOR BONE METASTASES A RANDOMISED TRIAL OF TWO FRACTIONATION SCHEDULES 2ADIOTHER /NCOL .IELSEN /3
(48) "ENTZEN 3-
(49) 3ANDBERG %
(50) 'ADEBERG ##
(51) 4IMOTHY !2 2ANDOMIZED TRIAL OF SINGLE DOSE VERSUS FRACTIONATED PALLIATIVE RADIOTHERAPY OF BONE METASTASES 2ADIOTHER /NCOL 0RICE 0
(52) (OSKIN 0*
(53) %ASTON $
(54) !USTIN $
(55) 0ALMER 3'
(56) 9ARNOLD *2 0ROSPECTIVE RANDOMISED TRIAL OF SINGLE AND MULTIFRACTION RADIOTHERAPY SCHEDULES IN THE TREATMENT OF PAINFUL BONY METASTASES 2ADIOTHER /NCOL 2OOS $% #ONTINUING RELUCTANCE TO USE SINGLE FRACTIONS OF RADIOTHERAPY FOR METASTATIC BONE PAIN AN AUSTRALIAN AND NEW ZEALAND PRACTICE SURVEY AND LITERATURE REVIEW 2ADIOTHER /NCOL 3TEENLAND %
(57) ,EER *7
(58) VAN (OUWELINGEN (
(59) 0OST 7*
(60) VAN DEN (OUT 7"
(61) +IEVIT * ET AL 4HE EFFECT OF A SINGLE FRACTION COMPARED TO MULTIPLE FRACTIONS ON PAINFUL BONE METASTASES A GLOBAL ANALYSIS OF $UTCH "ONE -ETASTASIS 3TUDY 2ADIOTHER /NCOL .IEWALD -
(62) 4KOCZ (*
(63) !BEL 5
(64) 3CHEIB 4
(65) 7ALTER +
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(68) *ENSEN !"
(69) !NDERSSON -
(70) "ANNING !-
(71) (OFFMANN 4 ET AL )RRADIATION OF BONE METASTASES IN BREAST CANCER PATIENTS A RANDOMIZED STUDY WITH YEAR FOLLOW UP 2ADIOTHER /NCOL 4ONG $
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(74) +AROLY 0
(75) "RAVER 3 4HE MEASUREMENT OF CLINICAL PAIN INTENSITY A COMPARISON OF SIX METHODS 0AIN .
(76) %URO1OL A NEW FACILITY FOR THE MEASUREMENT OF HEALTH RELATED QUALITY OF LIFE 4HE %URO1OL 'ROUP (EALTH 0OLICY $OLAN 0 -ODELING VALUATIONS FOR %URO1OL (EALTH STATES -ED #ARE 'OLD -2
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(81) +OOPMANSCHAP -!
(82) 2UTTEN && -ANUAL FOR COST ANALYSES
(83) METHODS AND STANDARD PRICES FOR ECONOMIC EVALUATIONS IN HEALTH CARE IN $UTCH $UTCH (EALTH )NSURANCE %XECUTIVE "OARD
(84) EDITOR !MSTELVEEN 4HE .ETHERLANDS $UTCH (EALTH )NSURANCE %XECUTIVE "OARD 0HARMACOTHERAPEUTIC #OMPASS IN $UTCH $UTCH (EALTH )NSURANCE %XECUTIVE "OARD
(85) EDITOR !MSTELVEEN 4HE .ETHERLANDS VAN (OUT "!
(86) !L -*
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(88) 2UTTEN && #OSTS
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(90) /"RIEN "*
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(92) "ARBER *! (OW SHOULD COST DATA IN PRAGMATIC RANDOMISED TRIALS BE ANALYSED "-* %ARLE ##
(93) #HAPMAN 2(
(94) "AKER #3
(95) "ELL #-
(96) 3ONE 07
(97) 3ANDBERG %! 3YSTEMATIC OVERVIEW OF COST UTILITY ASSESSMENTS IN ONCOLOGY * #LIN /NCOL 3INGER 0!
(98) -ARTIN $+
(99) +ELNER - 1UALITY END OF LIFE CARE PATIENTS PERSEPCTIVES *!-! 4UBIANA -
(100) %SCHWEGE & #ONFORMAL RADIOTHERAPY AND INTENSITY MODULATED RADIOTHERAPY CLINICAL DATA !CTA /NCOL 3UIT ( 4HE 'RAY ,ECTURE COMING TECHNICAL ADVANCES IN RADIATION ONCOLOGY )NT * 2ADIAT /NCOL "IOL 0HYS "EN *OSEF %
(101) 3HAMSA &
(102) 7ILLIAMS !/
(103) 0ORTER !4 2ADIOTHERAPEUTIC MANAGEMENT OF OSSEOUS METASTASES A SURVEY OF CURRENT PATTERNS OF CARE )NT * 2ADIAT /NCOL "IOL 0HYS ,IEVENS 9
(104) 6AN DEN "7
(105) 2IJNDERS !
(106) +UTCHER '
(107) +ESTELOOT + 0ALLIATIVE RADIOTHERAPY PRACTICE WITHIN WESTERN EUROPEAN COUNTRIES IMPACT OF THE RADIOTHERAPY lNANCING SYSTEM 2ADIOTHER /NCOL $UTCH 3OCIETY FOR 2ADIOTHERAPY AND /NCOLOGY -ASTERPLAN ON RADIOTHERAPY CAPACITY SHORTAGE
(108) A SHARED CONCERN !MERSFOORT 4HE .ETHERLANDS
(109) $UTCH 3OCIETY FOR 2ADIOTHERAPY AND /NCOLOGY . $ISCUSSION AND FUTURE PERSPECTIVES.
(110)
GERELATEERDE DOCUMENTEN
License: Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden Downloaded from: https://hdl.handle.net/1887/4330.
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