Radiotherapy in bone metastasis : the Dutch bone metastasis study Linden, Y.M. van der
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Hele tekst
(2) 0ATIENTS WITH A FAVORABLE PROGNOSIS ARE EQUALLY PALLIATED WITH SINGLE AND MULTIPLE FRACTION RADIOTHERAPY RESULTS ON SURVIVAL IN THE $UTCH "ONE -ETASTASIS 3TUDY :WFUUF.WBOEFS-JOEFO &MTCFUI4UFFOMBOE )BOT+$WBO)PVXFMJOHFO 8FOEZ+1PTU #JOH4#0FJ $PSSJF"..BSJKOFO +BO8JMMFN)-FFS GPSUIF%VUDI#POF.FUBTUBTJT4UVEZ(SPVQ 4VCNJUUFEGPSQVCMJDBUJPO.
(3) )NTRODUCTION. !BSTRACT )NTRODUCTION *OUIFQSPTQFDUJWFMZSBOEPNJ[FE%VUDI#POF.FUBTUBTJT4UVEZPOUIFFGGFDUPG BTJOHMFGSBDUJPOPG(ZWFSTVT(ZJOTJYGSBDUJPOTPOQBJOGVMCPOFNFUBTUBTFT PGUIF QBUJFOUTTVSWJWFEGPSNPSFUIBOPOFZFBS1VSQPTFPGUIFQSFTFOUTUVEZXBTUPBOBMZ[FUIF QBMMJBUJWFFGGFDUPGSBEJPUIFSBQZJOMPOHUFSNTVSWJWJOHQBUJFOUT BOEUPJEFOUJGZQSPHOPTUJD GBDUPSTGPSTVSWJWBM -ATERIAL AND -ETHODS 3FTQPOTFSBUFTXFSFDPNQBSFEJOBMMQBUJFOUTTVSWJWJOH XFFLT 5IF$PYQSPQPSUJPOBMIB[BSETNPEFMTUSBUJGJFECZQSJNBSZUVNPSXBTVTFEGPSNVMUJWBSJBUF .7 BOBMZTFTPGQSPHOPTUJDGBDUPSTGPSTVSWJWBM 2ESULTS *OQBUJFOUTTVSWJWJOH XFFLT SFTQPOTFTXFSFBGUFS(ZBOEBGUFS (Z 1 %VSBUJPOPGSFTQPOTFBOEQSPHSFTTJPOSBUFTXFSFTJNJMBS'PSBMMQSJNBSZUVNPST QSPHOPTUJDGBDUPSTGPSTVSWJWBMXFSFBHPPE,BSOPGTLZ1FSGPSNBODF4DPSF BTPMJUBSZCPOF NFUBTUBTJT OPWJTDFSBMNFUBTUBTFT BOEOPOPQPJEBOBMHFTJDTJOUBLF BMMGBDUPST .71 #ONCLUSIONS 4JOHMFGSBDUJPOSBEJPUIFSBQZTIPVMECFUIFTUBOEBSEEPTFTDIFEVMFGPSQBUJFOUT XJUIQBJOGVMCPOFNFUBTUBTFTJODMVEJOHQBUJFOUTXJUIBOFYQFDUFEGBWPSBCMFTVSWJWBM(FOFSBM QSPHOPTUJDBUPSTBTUIF,BSOPGTLZ1FSGPSNBODF4DPSFBOENFUBTUBUJDUVNPSMPBEBSFVTFGVMJO QSFEJDUJOHTVSWJWBM. 5IFUSFBUNFOUPGQBUJFOUTXJUIQBJOGVMCPOFNFUBTUBTFTDPNQSJTFTBTVCTUBO UJBMQBSUPGUIFEBJMZXPSLMPBEPGUIFBWFSBHFSBEJPUIFSBQZEFQBSUNFOU4JODFB MBSHFOVNCFSPGSFUSPTQFDUJWFBOEQSPTQFDUJWFMZSBOEPNJ[FETUVEJFTSFQPSUFE UIBUTJOHMFGSBDUJPOSBEJPUIFSBQZQSPWJEFTFRVBMQBMMJBUJPOXIFODPNQBSFEUP NVMUJQMFGSBDUJPOSFHJNFOT UIJTUSFBUNFOUIBTNPSFBOENPSFCFDPNFUIF TUBOEBSEUIFSBQZ8IJMFJOUIFQBTUUIFWBMVFPGBTJOHMFGSBDUJPOIBTCFFO DSJUJDJ[FE SFDFOUSFWJFXT BOEBNFUBBOBMZTJT SFQPSUFEFRVBMPWFSBMM SFTQPOTFQFSDFOUBHFTPGUPJOFWBMVBCMFQBUJFOUT0GDPVSTF GPSUIFQB UJFOU UIFBEWBOUBHFPGBTJOHMFGSBDUJPOJOTUFBEPGNVMUJQMFGSBDUJPOTJTFWJEFOU GFXFSUJSJOHBOEQBJOGVMWJTJUTUPUIFIPTQJUBM'PSUIFSBEJPUIFSBQZEFQBSUNFOU UIFVTFPGBTJOHMFGSBDUJPONFBOTBNPSFFDPOPNJDVTFPGMJNJUFESFTPVSDFT "MUIPVHINPTUQBUJFOUTXJUIQBJOGVMCPOFNFUBTUBTFTIBWFBMJNJUFENFEJBO PWFSBMMTVSWJWBMPGUPNPOUIT TPNFQBUJFOUTMJWFMPOHFS5IFSFJTDPO DFSOBNPOHSBEJBUJPOPODPMPHJTUTUIBUJOUIFTFQBUJFOUTBTJOHMFGSBDUJPONJHIU OPUCFCFOF¾DJBM1BJONBZXFMMCFDPOUSPMMFENPSFBEFRVBUFMZJGUIFZSFDFJWF NVMUJQMFGSBDUJPOTXJUIBIJHIFSUPUBMEPTF MFBEJOHUPBSFEVDFEUVNPSMPBEBU UIFTJUFPGUIFNFUBTUBTJT 5PBOTXFSUIJTRVFTUJPO UIFQSPTQFDUJWFMZSBOEPNJ[FE%VUDI#POF.FUBT UBTJT4UVEZ %#.4 POUIFQBMMJBUJWFFGGFDUPGBTJOHMFGSBDUJPOPG(ZWFSTVT (ZJOGSBDUJPOTTUSBUJ¾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
(4) 1VSQPTFPGUIFTUVEZXBTUPQSPWFUIFFRVBMFGGFDUJWFOFTTPG4'WFSTVT.' FOEQPJOUPGUIFTUVEZXBTSFTQPOTFUPQBJO5IFDSJUFSJBGPSSBOEPNJ[BUJPOBSF MJTUFEJO5BCMF*OFJHIUQBSUJDJQBUJOHJOTUJUVUFT QBUJFOUTXFSFTUSBUJ¾FEBDDPS EJOHUPFYQFDUFEGBWPSBCMFPSMFTTGBWPSBCMFQSPHOPTJT1BUJFOUTXFSFFMJHJCMFGPS UIFGBWPSBCMFQSPHOPTJTTVCHSPVQJGUIFZIBECSFBTUDBODFSXJUIPVUWJTDFSBM NFUBTUBTFTXJUIBMPOHUFSNSFNJTTJPO NPSFUIBOZFBS EVFUP¾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¿BNNBUPSZESVHT PSQIBTF OPOPQPJE BOBMHFTJDDPNCJOBUJPOTXJUIXFBLPQPJET UPQIBTF TUSPOHPQPJETMJLF NPSQIJOF PSQIBTF OPOPSBMBENJOJTUSBUJPOPGPQPJET XBTOPUFEBTBO BOBMHFTJDJODSFBTF*GUIFQBUJFOUTUPQQFEVTJOHQIBTFPSBOBMHFTJDT UIJT XBTOPUFEBTBOBOBMHFTJDEFDSFBTF 3FTQPOTFXBTEF¾OFEBTB BEFDSFBTFJOUIFJOJUJBMQBJOTDPSFCZBUMFBTU UXPQPJOUTPOUIFQBJOTDBMF XJUIPVUBOBMHFTJDJODSFBTF PSC BDIBOHFJO BOBMHFTJDTGSPNQIBTFPSUPBMPXFSQIBTFXJUIPVUBOJODSFBTFJOQBJO$PN QMFUFSFTQPOTF $3 XBTEF¾OFEBTBEFDSFBTFJOUIFJOJUJBMQBJOTDPSFUP[FSP POUIFQBJOTDBMF XJUIPVUDPODPNJUBOUBOBMHFTJDJODSFBTF1SPHSFTTJPOBGUFS SFTQPOTFXBTEF¾OFEBTB BOJODSFBTFJOQBJOXJUISFUVSOUPUIFJOJUJBMQBJO TDPSFPSIJHIFS XJUIPVUBOBMHFTJDJODSFBTF PSC BOJODSFBTFJOBOBMHFTJDT GSPNBMPXFSQIBTFUPQIBTFPSJSSFTQFDUJWFPGUIFQBJOTDPSF 'PSUIFDBMDVMBUJPOPGSFTQPOTF OP¾YFEUJNFJOUFSWBMGSPNUIFEBUFPG SBOEPNJ[BUJPOXBTBQQMJFE3FTQPOTFUPUSFBUNFOUXBTDBMDVMBUFEJGBUMFBTU UXPTVDDFTTJWFGPMMPXVQQBJOTDPSFTXFSFBWBJMBCMF5JNFUPSFTQPOTFBOEUJNF UPQSPHSFTTJPOXFSFDBMDVMBUFEGSPNUIFEBUFPGSBOEPNJ[BUJPO%VSBUJPOPG SFNJTTJPOXBTDBMDVMBUFETVCUSBDUJOHUJNFUPSFTQPOTFGSPNUJNFUPQSPHSFT TJPO3FTQPOTFUPJOJUJBMUSFBUNFOUXBTDBMDVMBUFEJODMVEJOHBOEFYDMVEJOH UIFFGGFDUPGBQPTTJCMFSFUSFBUNFOUEVSJOHGPMMPXVQ 8IFOBQBUJFOUXBT SFUSFBUFEEVSJOHGPMMPXVQ UIFSFTQPOTFTUBUVT FJUIFSOPSFTQPOTF JOSFT QPOTF PSXJUIQSPHSFTTJPO UIFXFFLCFGPSFSFUSFBUNFOUXBTMBCFMFEUPJEFOUJGZ SFBTPOTGPSSFUSFBUNFOU*OBEEJUJPO UIFEJSFDUFGGFDUPGSFUSFBUNFOU JF DIBOHFTJOQBJOTDPSFDPNQBSFEUPUIFQBJOTDPSFUIFXFFLCFGPSFSFUSFBUNFOU XBTTUVEJFE. 4!",% ).#,53)/. !.$ %8#,53)/. #2)4%2)! /& 4(% $54#( "/.% -%4!34!3)3 345$9 2ANDOMIZATION CRITERIA )NCLUSION. %XCLUSION. )NFORMED CONSENT -ETASTASES OF SOLID TUMORS 0AIN SCORE MINIMUM ON POINT SCALE NO PAIN TO WORST IMAGINABLE PAIN -ETASTASES TREATABLE IN ONE RADIOTHERAPY TARGET VOLUME .O PREVIOUS RADIOTHERAPY TO SAME METASTASES. .O INFORMED CONSENT 0ATHOLOGICAL FRACTURE OR IMPENDING FRACTURE NEEDING SURGICAL l XATION 3PINAL CORD COMPRESSION -ETASTASES OF RENAL CELL CARCINOMA OR MELANOMA. -ETASTASES IN CERVICAL SPINEo &OR SOME INSTITUTIONS PATIENTS WITH AN EXPECTED FAVORABLE PROGNOSISp. -ETASTASES OF RENAL CELL CARCINOMA OR MELANOMA WERE EXCLUDED BECAUSE OF EXPECTED DIFFERENT BIOLOGICAL BEHAVIOR o -ETASTASES IN THE CERVICAL SPINE WERE EXCLUDED BECAUSE IT WAS BELIEVED THAT LARGE FRACTIONS MIGHT LEAD TO A RADIATION INDUCED MYELOPATHY p 0ATIENTS WITH BREAST CANCER WITHOUT VISCERAL METASTASES WITH A LONG TERM REMISSION MORE THAN YEAR DUE TO l RST LINE SYSTEMIC TREATMENT
(5) AND PATIENTS WITH PROSTATE CANCER
(6) A +ARNOFSKY 0ERFORMANCE 3CORE OF OR MORE
(7) WHO HAD NOT BEEN TREATED WITH HORMONE THERAPY YET. "ASELINE CHARACTERISTICS AND RESPONSE TO TREATMENT IN PATIENTS WITH AN OBSERVED FAVORABLE PROGNOSIS . *OPSEFSUPQFSGPSNTVCHSPVQBOBMZTFT XFBOBMZ[FEQFSUSFBUNFOUTDIFEVMF UIFCBTFMJOFDIBSBDUFSJTUJDTPGBMMQBUJFOUTXIPTVSWJWFEGPSNPSFUIBOZFBS BGUFSSBOEPNJ[BUJPOBHF TFY ,14 QSJNBSZUVNPS USFBUNFOUTJUF QSFTFODF PGPUIFSCPOFNFUBTUBTFT QSFTFODFPGWJTDFSBMNFUBTUBTFT BOBMHFTJDTJOUBLF DPODPNJUBOUTZTUFNJDUSFBUNFOU BOEQBJOTDPSFBUSBOEPNJ[BUJPO 3FTQPOTFUPJOJUJBMUSFBUNFOU UJNFUPSFTQPOTF EVSBUJPOPGSFTQPOTF OVN CFSPGSFUSFBUNFOUT BOESFTQPOTFUPSFUSFBUNFOUXFSFTUVEJFEVQUPXFFLT BGUFSSBOEPNJ[BUJPO"GUFSXFFLT GFXQBUJFOUTSFUVSOFERVFTUJPOOBJSFT NBLJOHDPNQBSJTPOPGQBJOTDPSFTCFZPOEXFFLTVOSFMJBCMF"OBMZTJTPG.
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¿VFODFECZUIFQSJNBSZUVNPSTJUF B$PYQSPQPSUJPOBMIB[BSET NPEFMTUSBUJGZJOHGPSUIFQSJNBSZUVNPSXBTVTFEGPSVOJWBSJBUFBOENVMUJ WBSJBUF .7 BOBMZTFTPGQSPHOPTUJDGBDUPSTGPSTVSWJWBM*OUFSBDUJPOTXFSF TUVEJFEXJUIJOUIF$PYQSPQPSUJPOBMIB[BSETNPEFM$IJ4RVBSFBOE'JTIFSµT &YBDUUFTUTXFSFVTFEUPDPNQBSFQSPQPSUJPOTGPSCBTFMJOFDIBSBDUFSJTUJDT .BOO8IJUOFZUFTUTXFSFVTFEUPDPNQBSFRVBOUJUBUJWFBOEPSEFSFEWBSJBCMFT GPSCBTFMJOFDIBSBDUFSJTUJDT"MMSFQPSUFE1WBMVFTBSFCBTFEPOUXPTJEFEUFTUT XJUI1 UBLFOUPCFTJHOJ¾DBOU. 4!",% "!3%,).% #(!2!#4%2)34)#3 0%2 42%!4-%.4 3#(%$5,% ). 0!4)%.43 3526)6).' 7%%+3 &2/- 2!.$/-):!4)/. 42%!4%$ 7)4(). 4(% $54#( "/.% -%4!34!3)3 345$9 3).',% &2!#4)/. 6%2353 -5,4)0,% &2!#4)/.3 X 'Y . . . 3$. X 'Y . . 3$. 0 VALUE. !GE -EAN RANGE . YRS . YRS . . 3EX MALE FEMALE. . . . +03o -EAN RANGE . . . 0RIMARY TUMOR "REAST 0ROSTATE ,UNG /THER. . . 4REATMENT SITE 3PINE 0ELVIS &EMUR 2IBS (UMERUS /THER. . . .UMBER OF BONE METASTASES 3OLITARY -ULTIPLE . . . 6ISCERAL METASTASES !BSENT 0RESENT. . . . p 0AIN MEDICATION PHASE .O 9ES . . . . . . . . . . . 3YSTEMIC TREATMENT .O 9ES 0AIN SCOREe -EAN RANGE . . . . . 3$ STANDARD DEVIATION o +03 +ARNOFSKY 0ERFORMANCE 3CORE
(9) A CONDITIONAL SCORE RANGING FROM DEATH TO NORMAL SITUATION
(10) NO COMPLAINTS p 0AIN MEDICATION PHASE STRONG OPOIDS LIKE MORPHINE
(11) PHASE NON ORAL ADMINISTRATION OF OPOIDS e 0AIN SCORE AT RANDOMIZATION POINT PAIN SCORE RANGING FROM NO PAIN TO WORST IMAGINABLE PAIN . 2ESULTS %XPECTED FAVORABLE PROGNOSIS . VERSUS EXPECTED LESS FAVORABLE PROGNOSIS . 5ISFFIVOESFEBOEUXFOUZQBUJFOUTTVSWJWFEGPS XFFLTBGUFSSBOEPNJ[B UJPO0GUIFTFQBSBUFMZSBOEPNJ[FEQBUJFOUTXJUIBOFYQFDUFEGBWPSBCMF QSPHOPTJT POMZTVSWJWFEGPSNPSFUIBOZFBS5IFTFXFSFQBUJFOUT XJUICSFBTUDBODFSBOEQBUJFOUTXJUIQSPTUBUFDBODFS0GUIFSFNBJOJOH QBUJFOUTXIPEJEOPUNFFUUIFSBOEPNJ[BUJPODSJUFSJBGPSGBWPSBCMFQSPHOPTJT OPOFUIFMFTTTVSWJWFEGPSNPSFUIBOPOFZFBS8FDPODMVEFUIBUUIF %#.4DSJUFSJBGPSTFQBSBUFSBOEPNJ[BUJPOPGQBUJFOUTJOUPUIFFYQFDUFE GBWPSBCMFQSPHOPTJTHSPVQXFSFOPUBEFRVBUF. 4!",% 2%30/.3% 4/ 2!$)/4(%2!09 0%2 42%!4-%.4 3#(%$5,% ). 0!4)%.43 3526)6).' 7%%+3 &2/- 2!.$/-):!4)/. 42%!4%$ 7)4(). 4(% $54#( "/.% -%4!34!3)3 345$9 X 'Y . 2ESPONSE. X 'Y 0 VALUE (2 #) . 2ESPONSE. "REAST CANCER. . . . . . . 0ROSTATE CANCER. . . . . . . ,UNG CANCER. . . . . . . /THER TYPES. . . . . . . 0 VALUE UNIVARIATE ANALYSIS
(12) (2 HAZARD RATIO CALCULATED WITH #OX PROPORTIONAL HAZARDS MODEL #) CONl DENCE INTERVALS.
(13) &)'52% . &)'52% . 0AIN SCORES DURING THE l RST YEAR AFTER RANDOMIZATION FOR PATIENTS SURVIVING WEEKS WITHIN THE $UTCH "ONE -ETASTASIS 3TUDY PER TREATMENT SCHEDULE. 3URVIVAL IN PATIENTS TREATED WITHIN THE $UTCH "ONE -ETASTASIS 3TUDY PER PRIMARY TUMOR. . . . 3URVIVAL . . X 'Y. "REAST. . . /THER 0ROSTATE ,UNG. X 'Y. . 2ESPONSE TO TREATMENT IN PATIENTS WITH AN OBSERVED FAVORABLE PROGNOSIS . 0GBMMQBUJFOUTXJUIBTVSWJWBM XFFLT SFTQPOEFEUP4'BOEUP.' 1 )3 $* 'JWFQFSDFOUPGBMMSFTQPOTFTXFSFDBVTFECZB EFDSFBTFJOBOBMHFTJDJOUBLF$PNQMFUFSFTQPOTFXBTOPUFEJOBGUFS4'BOE BGUFS.' 1 )3 $* .FBOUJNFUPSFTQPOTFXBT XFFLTJOCPUIUSFBUNFOUHSPVQT.FBOEVSBUJPOPGSFTQPOTFXBTXFFLTBGUFS B4' NFEJBOEVSBUJPOXFFLT BOEXFFLTBGUFS.' NFEJBOEVSBUJPO XFFLT 1SPHSFTTJWFQBJOXBTSFQPSUFEJOPG4'SFTQPOEFSTBOEJOPG.' SFTQPOEFST'PSQBUJFOUTXIPFYQFSJFODFEQSPHSFTTJWFQBJO NFBOUJNFUP QSPHSFTTJPOBGUFSSFTQPOTFXBTSFBDIFEXBTXFFLTGPS4'QBUJFOUTBOE XFFLTGPS.'QBUJFOUT 'PSUIFQSJNBSZUVNPSHSPVQTSFTQPOTFUPUSFBUNFOUJTMJTUFEJOUBCMF BHBJO OPEJGGFSFODFTCFUXFFOUIFTJOHMFGSBDUJPOBOENVMUJQMFGSBDUJPOSFHJ NFOXFSFTFFO1BUJFOUTXJUICSFBTUDBODFSPSQSPTUBUFDBODFSIBEUP SFTQPOTFBGUFSCPUISFHJNFOT 1 BOE1 SFTQFDUJWFMZ "MUIPVHI QBUJFOUTXJUIMVOHDBODFSSFBDIFESFTQPOTFUP4' DPNQBSFEUPPOMZ UP.' EVFUPTNBMMOVNCFSTUIFTFPVUDPNFTXFSFOPUTUBUJTUJDBMMZTJHOJ¾DBOUMZ EJGGFSFOU 1 )3 $* 'JHVSFTIPXTUIF¾STUZFBSQBJOTDPSFTPGUIF4'BOE.'QBUJFOUT "HBJO NFBOQBJOTDPSFTPWFSMBQDPOTJTUFOUMZUISPVHIPVUUIFZFBSTIPXJOHUIF FRVBMJUZPGSFTQPOTFUPCPUIUSFBUNFOUTDIFEVMFT *OUPUBM PGUIFQBUJFOUTSFDFJWFEBTFDPOESBEJPUIFSBQZUSFBUNFOU QBUJFOUTXJUIJOUIF¾STUZFBS BOEQBUJFOUTXJUIJOUIFGPMMPXJOHZFBS .PSF4'QBUJFOUTUIBO.'QBUJFOUTXFSFSFUSFBUFE4'QBUJFOUT WFSTVT .'QBUJFOUT 5IFIJHIFSSFUSFBUNFOUQFSDFOUBHFBGUFSJOJUJBM4'EJE OPUTJHOJ¾DBOUMZBMUFSUIFSFTQPOTFQFSDFOUBHFTGPSUIFUXPUSFBUNFOUTDIF EVMFTXIFOFYDMVEJOHUIFFGGFDUPGSFUSFBUNFOUGSPNUIFSFTQPOTFQFSDFOUBHFT UPJOJUJBMUSFBUNFOU SFTQPOEFEUP4'BOEUP.' 1 )3 . . . 0AIN SCORE. "ASELINE CHARACTERISTICS IN PATIENTS WITH AN OBSERVED FAVORABLE PROGNOSIS . 0GUIFPCTFSWFEMPOHUFSNTVSWJWPST UIFQSJNBSZUVNPSXBTJOUIFCSFBTU JO JOUIFQSPTUBUFJO JOUIFMVOHJO BOEBUPUIFSTJUFTJO 'JGUZPOFQFSDFOUXBTSBOEPNJ[FEJOUPUIF4'HSPVQBOEJOUPUIF.'HSPVQ #FUXFFO4'BOE.'MPOHUFSNTVSWJWJOHQBUJFOUTOPNBKPSEJGGFSFODFTJOBHF TFY ,14 QSJNBSZUVNPSTJUF QSFTFODFPGPUIFSCPOFNFUBTUBTFT QSFTFODF PGWJTDFSBMNFUBTUBTFT BOBMHFTJDTJOUBLF DPODPNJUBOUTZTUFNJDUSFBUNFOU PS QBJOTDPSFBUSBOEPNJ[BUJPOXFSFGPVOE 5BCMF 0OMZUSFBUNFOUTJUFEJGGFSFE CFUXFFOUIFUXPSFHJNFOT 1 CVUUIFDMJOJDBMJNQMJDBUJPOPGUIJTPVU DPNFJTDPOTJEFSFENJOPS. . . 4IME FROM RANDOMIZATION MONTHS . . . 4IME FROM RANDOMIZATION WEEKS 0AIN WAS SCORED ON AN POINT PAIN SCALE RANGING FROM NO PAIN TO WORST IMAGINABLE PAIN 0AIN SCORES OF PATIENTS WITH A SURVIVAL WEEKS TREATED WITH X 'Y GREY LINES WITH CONl DENCE INTERVALS
(14) . VERSUS X 'Y BLACK LINES WITH CONl DENCE INTERVALS
(15) . ARE PRESENTED bb 4IME FROM RANDOMIZATION IN WEEKS AFTER WEEKLY QUESTIONNAIRES FOLLOW UP WAS ALTERED INTO MONTHLY QUESTIONNAIRES TO A MAXIMUM OF TWO YEARS OR UNTIL DEATH. .UMBER OF PATIENTS @AT RISK "REAST 0ROSTATE ,UNG /THER PRIMARIES . $* .FBOUJNFUPSFUSFBUNFOUXBTXFFLTJO4'QBUJFOUT SBOHF XFFLT BOEXFFLTJO.'QBUJFOUT SBOHFXFFLT "USFUSFBUNFOU PGUIFQBUJFOUTXFSFSFTQPOEFSTUPJOJUJBMUSFBUNFOU0GUIFTFSFTQPOEFST IBEQSPHSFTTJWFQBJOCFGPSFSFUSFBUNFOU5IJSUZ¾WFQBUJFOUTXFSFOPO SFTQPOEFS8IFOUIFBEEJUJPOBMFGGFDUPGSFUSFBUNFOUPOUIFQBJOTDPSFSFQPSUFE BUSBOEPNJ[BUJPOXBTTUVEJFE PGJOJUJBMOPOSFTQPOEFSTSFTQPOEFEZFU BOBEEJUJPOBMJODSFBTFPGSFTQPOTFUP 8IFODBMDVMBUJOHUIFEJSFDUFGGFDUPGSFUSFBUNFOU JFDIBOHFTJOQBJOTDPSF DPNQBSFEUPUIFQBJOTDPSFUIFXFFLCFGPSFSFUSFBUNFOU PG4'QBUJFOUT SFTQPOEFE BOEPG.'QBUJFOUT 1 )3 $* 3URVIVAL . 'SPNSBOEPNJ[BUJPO QBUJFOUTXJUICSFBTUDBODFSIBEUIFCFTUNFEJBOPWFSBMM TVSWJWBM NPOUIT $*°NPOUIT GPMMPXFECZQSPTUBUFDBODFS NFEJBO04NPOUIT $*° BOEPUIFSUZQFTPGDBODFS NFEJBO 04NPOUIT $*° 1 'JHVSF 1BUJFOUTXJUIMVOHDBODFS TVGGFSFEUIFXPSTUNFEJBOPWFSBMMTVSWJWBMNPOUITPOMZ $*° NPOUIT .
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(17) (2 HAZARD RATIO CALCULATED WITH #OX PROPORTIONAL HAZARDS MODEL
(18) #) CONl DENCE INTERVALS
(19) -6 MULTIVARIATE ANALYSIS WITH STRATIl CATION BY PRIMARY TUMOR +03 +ARNOFSKY 0ERFORMANCE 3CORE
(20) A CONDITIONAL SCORE RANGING FROM DEATH TO NORMAL SITUATION
(21) NO COMPLAINTS 0AIN MEDICATION PHASE STRONG OPOIDS LIKE MORPHINE
(22) PHASE NON ORAL ADMINISTRATION OF OPOIDS AIN SCORE AT RANDOMIZATION POINT PAIN SCORE RANGING FROM NO PAIN TO WORST IMAGINABLE PAIN 3& SINGLE FRACTION
(23) X 'Y
(24) -& MULTIPLE FRACTIONS
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
(28) "ENTZEN 3-
(29) 3ANDBERG %
(30) 'ADEBERG ##
(31) 4IMOTHY !2 2ANDOMIZED TRIAL OF SINGLE DOSE VERSUS FRACTIONATED PALLIATIVE RADIOTHERAPY OF BONE METASTASES 2ADIOTHER /NCOL 'AZE -.
(32) +ELLY #'
(33) +ERR '2
(34) #ULL !
(35) #OWIE 6*
(36) 'REGOR ! ET AL 0AIN RELIEF AND QUALITY OF LIFE FOLLOWING RADIOTHERAPY FOR BONE METASTASES A RANDOMISED TRIAL OF TWO FRACTIONATION SCHEDULES 2ADIOTHER /NCOL 0RICE 0
(37) (OSKIN 0*
(38) %ASTON $
(39) !USTIN $
(40) 0ALMER 3'
(41) 9ARNOLD *2 0ROSPECTIVE RANDOMISED TRIAL OF SINGLE AND MULTIFRACTION RADIOTHERAPY SCHEDULES IN THE TREATMENT OF PAINFUL BONY METASTASES 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 3TEENLAND %
(42) ,EER *7
(43) VAN (OUWELINGEN (
(44) 0OST 7*
(45) VAN DEN (OUT 7"
(46) +IEVIT * ET AL 4HE EFFECT OF A SINGLE FRACTION COMPARED TO MULTIPLE FRACTIONS ON PAINFUL BONE METASTASES A GLOBAL ANALYSIS OF THE $UTCH "ONE -ETASTASIS 3TUDY 2ADIOTHER /NCOL VAN DER ,INDEN 9-
(47) ,OK **
(48) 3TEENLAND %
(49) -ARTIJN (
(50) (OUWELINGEN *#
(51) ,EER *7( ET AL 3INGLE FRACTION RADIOTHERAPY IS EFlCACIOUS A FURTHER ANALYSIS OF THE $UTCH "ONE -ETASTASIS 3TUDY CONTROLLING FOR THE INmUENCE OF RETREATMENT )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 +OSWIG 3
(52) "UDACH 6 ;2EMINERALIZATION AND PAIN RELIEF IN BONE METASTASES AFTER AFTER DIFFERENT RADIOTHERAPY FRACTIONS TIMES 'Y VS TIME 'Y ! PROSPECTIVE STUDY= 3TRAHLENTHER /NKOL .IEWALD -
(53) 4KOCZ (*
(54) !BEL 5
(55) 3CHEIB 4
(56) 7ALTER +
(57) .IEDER # ET AL 2APID COURSE RADIATION THERAPY VS MORE STANDARD TREATMENT A RANDOMIZED TRIAL FOR BONE METASTASES )NT * 2ADIAT /NCOL "IOL 0HYS 2ASMUSSON "
(58) 6EJBORG )
(59) *ENSEN !"
(60) !NDERSSON -
(61) "ANNING !-
(62) (OFFMANN 4 ET AL )RRADIATION OF BONE METASTASES IN BREAST CANCER PATIENTS A RANDOMIZED STUDY WITH YEAR FOLLOW UP 2ADIOTHER /NCOL -ADSEN %, 0AINFUL BONE METASTASIS EFlCACY OF RADIOTHERAPY ASSESSED BY THE PATIENTS A RANDOMIZED TRIAL COMPARING 'Y 8 VERSUS 'Y 8 )NT * 2ADIAT /NCOL "IOL 0HYS *EREMIC "
(63) 3HIBAMOTO 9
(64) !CIMOVIC ,
(65) -ILICIC "
(66) -ILISAVLJEVIC 3
(67) .IKOLIC . ET AL ! RANDOMIZED TRIAL OF THREE SINGLE DOSE RADIATION THERAPY REGIMENS IN THE TREATMENT OF METASTATIC BONE PAIN )NT * 2ADIAT /NCOL "IOL 0HYS . (OSKIN 0*
(68) 0RICE 0
(69) %ASTON $
(70) 2EGAN *
(71) !USTIN $
(72) 0ALMER 3 ET AL ! PROSPECTIVE RANDOMISED TRIAL OF 'Y OR 'Y SINGLE DOSES IN THE TREATMENT OF METASTATIC BONE PAIN 2ADIOTHER /NCOL 0RICE 0
(73) (OSKIN 0*
(74) %ASTON $
(75) !USTIN $
(76) 0ALMER 3
(77) 9ARNOLD *2 ,OW DOSE SINGLE FRACTION RADIOTHERAPY IN THE TREATMENT OF METASTATIC BONE PAIN A PILOT STUDY 2ADIOTHER /NCOL 5PPELSCHOTEN *-
(78) 7ANDERS 3,
(79) DE *ONG *- 3INGLE DOSE RADIOTHERAPY 'Y PALLIATION IN PAINFUL BONE METASTASES 2ADIOTHER /NCOL /KAWA 4
(80) +ITA -
(81) 'OTO -
(82) .ISHIJIMA (
(83) -IYAJI . 2ANDOMIZED PROSPECTIVE CLINICAL STUDY OF SMALL
(84) LARGE AND TWICE A DAY FRACTION RADIOTHERAPY FOR PAINFUL BONE METASTASES 2ADIOTHER /NCOL (ARTSELL 7&
(85) 3COTT #
(86) "RUNER $7
(87) 3CARANTINO #7
(88) )VKER 2
(89) 2OACH - ET AL 0HASE ))) RANDOMIZED TRIA OF 'Y IN FRACTION VS 'Y IN FRACTIONS FOR PALLIATION OF PAINFUL BONEMETASTASES PRELIMINARY RESULTS OF 24/' )NT * 2ADIAT /NCOL "IOL 0HYS 3UPPL 3 4ONG $
(90) 'ILLICK ,
(91) (ENDRICKSON &2 4HE PALLIATION OF SYMPTOMATIC OSSEOUS METASTASES lNAL RESULTS OF THE 3TUDY BY THE 2ADIATION 4HERAPY /NCOLOGY 'ROUP #ANCER "LITZER 0( 2EANALYSIS OF THE 24/' STUDY OF THE PALLIATION OF SYMPTOMATIC OSSEOUS METASTASIS #ANCER 2ATANATHARATHORN 6
(92) 0OWERS 7%
(93) -OSS 74
(94) 0EREZ #! "ONE METASTASIS REVIEW AND CRITICAL ANALYSIS OF RANDOM ALLOCATION TRIALS OF LOCAL lELD TREATMENT )NT * 2ADIAT /NCOL "IOL 0HYS 2OOS $% #ONTINUING RELUCTANCE TO USE SINGLE FRACTIONS OF RADIOTHERAPY FOR METASTATIC BONE PAIN AN AUSTRALIAN AND NEW ZEALAND PRACTICE SURVEY AND LITERATURE REVIEW 2ADIOTHER /NCOL *EREMIC " 3INGLE FRACTION EXTERNAL BEAM RADIATION THERAPY IN THE TREATMENT OF LOCALIZED METASTATIC BONE PAIN ! REVIEW * 0AIN 3YMPTOM -ANAGE 3ZE 7-
(95) 3HELLEY -$
(96) (ELD )
(97) 7ILT 4*
(98) -ASON -$ 0ALLIATION OF METASTATIC BONE PAIN SINGLE FRACTION VERSUS MULIFRACTION RADIOTHERAPY ! SYSTEMATIC REVIEW OF RANDOMISED TRIALS #LIN /NCOL 2 #OLL 2ADIOL -C1UAY (*
(99) #OLLINS 3,
(100) #ARROLL $ 2ADIOTHERAPY FOR THE PALLIATION OF PAINFUL BONE METASTASES #OCHRANE REVIEW 4HE #OCHRANE ,IBRARY )SSUE 7U *3
(101) 7ONG 2
(102) *OHNSTON -
(103) "EZJAK !
(104) 7HELAN 4 -ETA ANALYSIS OF DOSE FRACTIONATION RADIOTHERAPY TRIALS FOR THE PALLIATION OF PAINFUL BONE METASTASES )NT * 2ADIAT /NCOL "IOL 0HYS +ARNOFSKY $!
(105) !BELMANN 7(
(106) +RAVER ,& 4HE USE OF NOTROGEN MUSTARDS IN THE PALLIATIVE TREATMENT OF CARCINOMA WITH PARTICULAR REFERENCE TO BRONCHOGENIC CARCINOMA #ANCER #HOW %
(107) 7U *
(108) (OSKIN 0
(109) #OIA ,
(110) "ENTZEN 3
(111) "LITZER 0 )NTERNATIONAL CONSENSUS ON PALLIATIVE RADIOTHERAPY ENDPOINTS FOR FUTURE CLINICAL TRIALS IN BONE METASTASES 2ADIOTHER /NCOL #HOW %
(112) (ARTH 4
(113) (RUBY '
(114) &INKELSTEIN *
(115) 7U *
(116) $ANJOUX # (OW ACCURATE ARE PHYSICIANS CLINICAL PREDICTIONS OF SURVIVAL AND THE AVAILABLE PROGNOSTIC TOOLS IN ESTIMATING SURVIVAL TIMES IN TERMINA ILL CANCER PATIENTS ! SYSTEMATIC REVIEW #LIN /NCOL 2 #OLL 2ADIOL #HOW %
(117) &UNG +
(118) 0ANZARELLA 4
(119) "EZJAK !
(120) $ANJOUX #
(121) 4ANNOCK ) ! PREDICTIVE MODEL FOR SURVIVAL IN METASTATIC CANCER PATIENTS ATTENDING AN OUTPATIENT PALLIATIVE RADIOTHERAPY CLINIC )NT * 2ADIAT /NCOL "IOL 0HYS *EREMIC "
(122) 3HIBAMOTO 9
(123) )GRUTINOVIC ) 3INGLE 'Y RE IRRADIATION FOR PAINFUL BONE METASTASIS FOLLOWING SINGLE FRACTION RADIOTHERAPY 2ADIOTHER /NCOL *EREMIC "
(124) 3HIBAMOTO 9
(125) )GRUTINOVIC ) 3ECOND SINGLE 'Y REIRRADIATION FOR PAINFUL BONE METASTASIS * 0AIN 3YMPTOM -ANAGE -ITHAL .0
(126) .EEDHAM 02
(127) (OSKIN 0* 2ETREATMENT WITH RADIOTHERAPY FOR PAINFUL BONE METASTASES )NT * 2ADIAT /NCOL "IOL 0HYS .
(128)
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