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  • Bone M

    etastasis

  • iii

    7080 40

    QOL

    RANKL

    QOL

    QOL

    2015 3

  • v

    evidence-based medicineEBM

    European Society of Medical OncologyESMO

    ESMO

    face-to-face

    2015 3

  • vii

    10

    1

    2

    IVR IVR KKR

  • viii

    3Clinical Question Clinical QuestionCQCQ

    Minds 2014 PICOPatientInterventionComparisonOutcomea

    2003 2013 PubMedCochrane LibraryCINAHLb

    c

    Minds 2014ABCD 4 11, 2d

    CQ

  • ix

    2 701 3

    4 Clinical Question

    5

    63

    7

    8

    1 A B C

    D

    2

  • x

    1. 100 2. 3. 10 4. 50 5. 50 6. 200 7. 200 8. 200 9. 200 10. 100 11.NPO

    1 2 3 4 5 67 8 9 10 11

    KKR

  • xi

    MSD

    JONIE

    OxOnc

    MSD

    2

  • xiii

    1 22 53 8

    Clinical Question

    CQ 1 12CQ 2 13CQ 3 14CQ 4 16CQ 5 Cancer Board 17CQ 6 18CQ 7 20CQ 8 22CQ 9 24CQ 10 26CQ 11 28CQ 12 BMA 29CQ 13 BMA 31CQ 14 33CQ 15 35CQ 16 37CQ 17 39CQ 18 BMA 41CQ 19 BMA 43CQ 20 44CQ 21 45CQ 22 47CQ 23 48CQ 24 89 50CQ 25 52CQ 26 54

    55

    BMACancer BoardONJRANKLPROSELFRFASRE

    61

  • xiv

    123IMIBG 123Imetaiodobenzylguanidine1CTP carboxyterminaltelopeptideoftypecollagen C 99mTcMDP technetiummethylenediphosphonate99mTcHMDP technetiumhydroxymethylenediphosphonateADC apparentdiffusioncoefficientADL activitiesofdailyliving BAP bonespecificalkalinephosphatase BKP balloonkyphoplasty BMA bonemodifyingagent BMP bonemorphogeneticprotein BPI briefpaininventoryBSI bonescanindexCAB combinedandrogenblockadeCI confidenceinterval CRPC castrationresistantprostatecancer CT computedtomographyCTx typecollagencrosslinkedCterminaltelopeptide C DIC disseminatedintravascularcoagulation DKK1 Dickkopfrelatedprotein1DPD deoxypyridinoline EGF epidermalgrowthfactor eGFR estimatedglomerularfiltrationrate FACTG functionalassessmentofcancertherapygeneralfastFE fastfieldechoFDGPET fluorodeoxyglucosepositronemissiontomographyFIM functionalindependencemeasure HR hazardratio IGF insulinlikegrowthfactor IL interleukin IVR interventionalradiology LHRH luteinizinghormonereleasinghormoneMIP1 macrophageinflammatoryprotein1 1MRI magneticresonanceimagingMRONJ medicationrelatedosteonecrosisofthejawMST mediansurvivaltime NCCN TheNationalComprehensiveCancerNetworkNICE NationalInstituteforHealthandCareExcellenceNRS numericratingscaleNTx typecollagencrosslinkedNtelopeptide N ONJ osteonecrosisofthejaw OS overallsurvival PD progressivediseasePFS progressionfreesurvival PICP procollagentypeCterminalpropeptide C PID painintensitydifferencePINP procollagentypeNterminalpropeptide N PMMA polymethylmethacrylate PRO patientreportedoutcomesPS performancestatus PSA prostatespecificantigen PTHrP parathyroidhormonerelatedproteinC C PVP percutaneousvertebroplasty PYD pyridinoline QOL qualityoflife RANKL receptoractivatorofnuclearfactorkappaBligand

  • xv

    RCT randomizedcontrolledtrial RECIST ResponseEvaluationCriteriaInSolidTumorsRFA radiofrequencyablation RR relativerisk SEERprogram Surveillance,Epidemiology,andEndResultsprogramSPECT singlephotonemissioncomputedtomographySRE skeletalrelatedevent STIR shortTIinversionrecoveryTES totalen blocspondylectomy TGF transforminggrowthfactor TNF tumornecrosisfactor TRACP5b tartrateresistantacidphosphatase5b VAS visualanalogscale

  • xvi

    CQ 2. CQ 3. CQ 4.

    CQ 1. CQ 5.

    CQ 26. +

    CQ 67. CQ 1218. BMA/

    CQ 9. CQ 10. CQ 11. CQ 1218. BMA/ CQ 19. BMA

    CQ 20. CQ 21. CQ 25.

    Follow Up/

    CQ 10. CQ 11. CQ 1218. BMA/ CQ 24.

    CQ 1218. BMA/ CQ 22. CQ 23. CQ 25.

    CQ 1218. BMA/

    CQ. 8

    Ca

    +

    CQ 67. CQ 1218. BMA/ CQ 19. BMA

    Follow Up /

    Ca

  • 2

    1

    1

    1 37550 20

    2

    4

    5 4 63 64 6

    7

    8

    1

    19591997

    19591997

    75.275.054.350.031.330.727.824.6

    22.922.722.521.317.416.813.0

    3

  • 1

    3

    9disseminated intravascular coagulationDIC

    3

    10 11

    receptor activator of nuclear factor kappa-B ligandRANKL 1RANKL RANKRANKLdecoy receptorosteoprotegerinOPG

    RANKL RANKL parathyroid hormonerelated proteinPTHrPinterleukinIL1IL6IL11tumor necrosis factorTNFmacrophage inflammatory protein 1MIP1insulinlike growth factorIGFtransforming growth factorTGFepidermal growth factorEGFbone morphogenetic proteinBMP 2

    12 13

    1CFUMGEMegLcolonyforming unitmacrophagegranulocyteerythroidmegakaryocyte lymphocyteMCSFmacrophage colonystimulating factor

    multipotential stem cells

    CFUM MCSF

    RANKLRANKL

    premonocyte

    preosteoclast

    monocyte

    mononuclearosteoclast

    macrophage

    osteoclast

    granulocyte

    erythorocyte

    platelet

    lymphocyte

    RANKL,TNF

    CFUG

    CFUE

    CFUMeg

    CFUL

  • 4

    RANKL bone modifying agentsBMA

    RANKL

    OPG

    EGFTGFFGFsBMPsIGFs

    RANKLPTHrPPGsIL6IL1

    2PGprostaglandin

  • 2

    5

    2

    1

    skeletal related eventSRE 6575 6575 4060 3040 40 2035 1445 5 1416

    2760 17, 18CQ 267

    2a

    CQ 2 b

    bone specific alkaline phosphataseBAP N procollagen type Nterminal propeptidePINP C procollagen type Cterminal propeptidePICP N type collagen crosslinked NtelopeptideNTx C type collagen cross-linked Cterminal telopeptideCTx C carboxyterminal telopeptide of type collagen1CTPdeoxypyridinolineDPDpyridinolinePYDtartrate-resistant acid phosphatase5bTRAPC5b RANKL BMA CQ 20

    3 X computed tomographyCTmagnetic resonance imagingMRI

    fluorodeoxyglucosepositron emission tomographyFDGPETCT 19CQ 3 a

    X CT

  • 6

    31

    Paget osteopathia striata 4

    MRI X CT MRI 1 MRI T1 shortTI inversion

    1

    X CT MRI

    FDG-PET/CT

    NaF-PET/CTT1 T2 T1

    160 MRI T1 abCTc

    a

    c

    b

    MRI T1

    CT

    MRI

  • 2

    7

    recoverySTIR fast field echoFET1 STIR b 6001,000secmm2 DWIBS diffusion weighted whole body imaging with background body signal suppressionb

    technetium-hydroxymethylene diphosphonate99mTcHMDP technetium-methylene diphosphonate99mTcMDPCa10PO46OH2

    18FFDGPETCT 218FFDGPETCT

    18FNaFsodium 18FfluoridePETCT PETCT 2 20, 2118FNaFPET 18FNaFPETCT

    PETMRI

    270 18FFDGPETCT a18FNaFPETCT b

    a b

    FDGPET MIP NaFPET MIP

  • 8

    3

    1

    a

    BMA

    48 CQ 67

    22

    45 8 23

    CQ 8CQ 25CQ 9interventional radiologyIVRCQ 1011CQ 24CQ 2223Cancer BoardCQ 5b

    1 1769 05100 819CQ 7 48

    2

    WHO

    48 48

    BMA BMA 34

  • 3

    9

    3

    BMA CQ 121824 a

    859 2428 1348 2933 performance statusPSbBMA

    BMA RANKL 2 BMA SRE

    POP PCP 34 35 RasRhoRab G 35, 36

    RANKL RANKL 6080 14 11.5 35

    osteonecrosis of the jawONJCQ 18 .c

    89153223

    4

    CQ 2223

  • 10

    CQ 825 quality of lifeQOL

    5

    BMA SRE activities of daily livingADLQOL ADL QOL CQ 25

    6 QOL

    37CQ 26 a

    b

    CQ 2 38

    c

    BMA ONJ D ONJ 39d

    40

  • Clinical Question

  • Clinical Question

    12

    Clinical Question 1

    PS

    Danish National Patient Registry 1997200723,0875693 1 5 87 56 47 3 41skeletal related eventSRE 5 1 65 Surveillance, Epidemiology, and End ResultsSEERprogram 1999 2005 126,978 1.75.9 3.3 hazard ratioHR SRE 6.6 SRE 10.2 42Danish National Patient Registry 35,912 431,4944575.8 8.3 4446

    47, 48

    4953

    808 performance statusPS 6 1 54

    1

    6 122403 98.1 91.4 77.846 74.0 49.3 27.6710 26.9 6.0 2.1 54

  • CQ 2

    13

    Clinical Question 2

    skeletal related eventSRE

    13 3 55 1 8 56 4 4 57a

    58 1

    2 59b60

    2030 12 mgdL

    Payne mgdLmgdLgdL4

    16

    2

  • Clinical Question

    14

    Clinical Question 3

    18FFDGPETPETCT MRI 75.9 C

    randomized controlled trialRCT18Ffluorodeoxyglucosepositron emission tomography18FFDGPETpositron emission tomographycomputed tomographyPETCTmagnetic resonance imagingMRI 92The Oxford Centre for EvidenceBased MedicineOCEBM2011 2 13 6 6166 5 61651 MRI 664 6265

    single photon emission computed tomographySPECT 8 40 86 81SPECT 61 SPECT

    18FFDGPETPETCT 18FFDGPET 19 PETCT 7 9097 61 18FFDGPETCT The National Comprehensive Cancer NetworkNCCN 18FFDGPETCT 6718FFDGPET CT 68

    MRI MRI MRI 6618FFDGPETCT MRI 61MRI 15 91 95 66 MRI 11 90 92 96 66 MRI MRI

    131ISPECT 18FFDGPETCT 69 123I metaiodobenzylguanidine123IMIBGSPECT18FFDGPETPETCT 70, 71

  • CQ 3

    15

    18FNaFsodium 18FfluoridePETCT SPECT 21

    X CT CT 72

    RCT

    No

    Yes

    Yes

    No X CT 18FFDGPETCT

  • Clinical Question

    16

    Clinical Question 4

    7375 7578 75, 79

    computed tomographyCT 75, 80, 81 82

    7094 75, 80, 81, 83, 84 71 79 80, 81 80

    125 28 22.4 78 78 73 76, 79

  • CQ 5

    17

    Clinical Question 5

    Cancer Board

    Cancer Board

    quality of lifeQOLbone modifying agentsBMA 85 86

    Cancer Board Cancer Board 87 Cancer Board 8891 91Cancer Board skeletal related eventSRE 92

  • Clinical Question

    18

    Clinical Question 6

    86.2 B

    quality of lifeQOL 93

    Patchell 101 50 51 2 94 9497 48 6 94, 96 94, 95Rades 108 Match Pair Analysis randomized controlled trialRCT 98

    Tomita Tokuhashi 96, 97bone modifying agentsBMA 2014 Katagiri 54, 99, 100Cancer Board

    93total en bloc spondylectomyTES 96

  • CQ 6

    19

    RCT

    No

    Yes

    No

    No

  • Clinical Question

    20

    Clinical Question 7

    96.6 C

    101103quality of lifeQOL 3 104106 106111QOL

    112, 113 23

    MirelsLinden 114, 115Mirels 116118Linden 3 cm 50Mirels 115bone modifying agentsBMA

    12 819 23, 101, 104, 106112

    119, 120 121

  • CQ 7

    21

    interventional radiologyIVRCQ 24

    Cancer BoardCQ 5

    3 104, 105, 116

    No

    Yes

    No

    Yes

  • Clinical Question

    22

    Clinical Question 8

    89.7 C

    quality of lifeQOL

    QOL

    QOL 122randomized controlled trialRCT 123125 125127Stadhouder 503 RCT Oswestry Disability Index 128

    12 performance statusPS

    RCT RCT

  • CQ 8

    23

    No

    Yes

    Yes

    Yes

  • Clinical Question

    24

    Clinical Question 9

    100 A

    59732334 12913153612627 132

    30 Gy10 20 Gy5 8 Gy1 6073 5973 2334 2432 129131 1 3 8randomized controlled trialRCT 133RCT 53 61 26 27 2.4 3.7 132RCT 1 87 85 29 30 134

    78 2022 129131 58 135 3366 5770 136 6670 3357 136

    RCT 30 Gy 81 137 RCT 130, 138 3.3 3.0 131

    30 mm 138RCT 2.83.0 1.61.9 130, 131

    10 1720 RCT 139, 140 131 131

  • CQ 9

    25

    Yes

    Yes

    Yes

    Yes

  • Clinical Question

    26

    Clinical Question 10

    75.9 C

    www.jsivr.jpguidelineguideline.html

    percutaneous vertebroplastyPVPPVP 1984 1997 141, 142

    143 144 13 145quality of lifeQOL 146

    X computed tomographyCT magnetic resonance imagingMRI T1 T2 147 X CT 148 1114 G polymethyl metacrylate

    PMMAPMMA balloon kyphoplastyBKP 149

    PVP randomized controlled trialRCT 61 12 7395confidence intervalCI5685 150 1,000 7080 151, 152

  • CQ 10

    27

    NoRCT

    Yes

    Yes

    Yes

  • Clinical Question

    28

    Clinical Question 11

    96.6 C

    radiofrequency ablationRFAK6973 153

    RFA 1998 2 randomized controlled trialRCT 154, 155 156160 161

    K7734RFA 162

    2RCT

    No

    No

    No

    No

  • CQ 12

    29

    Clinical Question 12

    BMA

    SRE 100 A

    3040 163, 164 fluorodeoxyglucosepositron emission tomographyFDGPET 48 40 165skeletal related eventSRE SRE 2030 164166SRE SRESRE 166SRE performance statusPS 167

    PS SRE SRE

    50 8 4 mg randomized controlled trialRCT87 SRE 4 mg 38.9 48.0p0.039 168, 169 40 RCT SRE 16.3 20.6 p0.06 170 171overall survivalOS 172 SRE SRE

    RCT

  • Clinical Question

    30

    Yes

    Yes

    Yes

    Yes

  • CQ 13

    31

    Clinical Question 13

    BMA

    SRE 100 A

    skeletal related eventSRESRE 173 382 90 mg

    randomized controlled trialRCTSRE 4.0 2.5quality of lifeQOLprogressionfree survivalPFSoverall survivalOS 55, 173

    90 mg 4 mg 8 mg 1,648 8 mg 4 mg SRE 1,130 SRE 20QOL PFSOS 174 4 mg SRE 41QOLPFSOS 175 SRE 176ibandronate 50 mg 6 mg 4 SRE QOL 177180

    136 2,046 RCT SRE 18 SRE 23FACTGfunctional assessment of cancer therapygeneral QOL 25 QOL 37.1 31.4PFSOS osteonecrosis of the jawONJ 2.0 1.4 181, 182Cochrane review2012 clodronate 10 8 SRE relative riskRR0.8595

    confidence intervalCI0.770.94 SRE

  • Clinical Question

    32

    RR0.80 SRE RR0.78QOL 2 OS 1 183

    bone modifying agentsBMA 184National Institute for Health and Care ExcellenceNICE Guidance 185The American Society of Clinical OncologyASCO SRE 186

    187

    SRE QOLOSPFS

    No

    Yes

    YesSRE

    YesBMA SRE

  • CQ 14

    33

    Clinical Question 14

    SRE 96.6 A

    188, 189lutenizing hormone releasing hormoneLHRH combined andorogen blockadeCAB 190, 191 LHRH 192 2 castrationresistant prostate cancerCRPC 193, 194

    Dearnaley 1 clodronate 195 clodronate

    hazard ratioHR0.7795confidence intervalCI0.600.98p0.032 3

    randomized controlled trialRCTskeletal related eventSREprogressionfree survivalPFSoverall survivalOS 196Ueno SRE RCT 197

    CRPC 2 SRE quality of lifeQOL 198 SRE CRPC 643 RCT SRE 56, 19915 SRE 4 mg 33.2 44.2p0.021 13.122.1p0.015SRE 420 321 p0.011 4 mg 546 464 p0.094

  • Clinical Question

    34

    CRPC 1,901 RCT SRE 200SRE 20.7 17.1 p0.0085 SRE 18HR0.82p0.00813 vs. 6p0.0001osteonecrosis of the jawONJ2 vs. 1p0.09 SRE ONJ

    RCT

    Yes

    YesSRE ONJ

    Yes 1

    Yes

  • CQ 15

    35

    Clinical Question 15

    SRE 100 A

    90 mgskeletal related eventSRE9 24 vs. 41p0.001 201performance statusPSquality of lifeQOL30 mg90 mg 202300 mg SRE 203 clodronate 2,400 mg 24 12 vs. 24p0.026 204randomized controlled trialRCT SRE 205 clodronate RCT SRE 27 vs. 35hazard ratioHR0.7495confidence intervalCI0.620.87p0.0004 206, 20735 vs. 43p0.003810 vs. 17p0.0068 RCT relative riskRR0.7495 CI 0.620.89 SRERR0.8095 CI0.720.89RR0.7595 CI0.600.95 208

    clodronate overall survivalOSHR0.8495 CI0.740.96p0.0118progressionfree survivalPFSHR0.8895 CI0.800.98p0.0179206, 207 OS HR0.9695 CI0.821.13p0.64OS HR0.6195 CI0.280.98 208

    RCT SRE 19.0 vs. 14.4 , HR0.8395 CI0.710.97p0.022 209, 210 OS HR2.2695CI1.134.50 10

    MP MP VMP 35HR

  • Clinical Question

    36

    0.653p0.001 211 212 ALP Dickkopfrelated protein 1DKK1

    Yes

    Yes

    Yes 1 ,

    Yes

  • CQ 16

    37

    Clinical Question 16

    SREBMA 96.6 C

    1520 210bone modifying agentsBMA

    10 4 mg skeletal related eventSRErandomized controlled trialRCT SRE 168 SRE

    3 SRE 211

    264 SRE 212 15 3 visual analog scaleVAS 213 SRE

    SRE BMA

    BMA 2

    RCT

  • Clinical Question

    38

    No

    Yes BMA

    Yes

    Yes4 1 BMA

  • CQ 17

    39

    Clinical Question 17

    BMA 75.9 D

    diffusely infiltrative carcinoma 1936 Jarcho 21440 1979 215Etoh disseminated intravascular coagulationDIC 23 DIC 15 median survival timeMST 11 2 216

    DIC 10 MF 8 DIC 217Hironaka 18 9 DIC 8 MF DIC 2 1 MST 113 218Takahashi DIC 22 18 MF 17 DIC 219Rhee DIC 21 18 14 MST 99 best sup-portive care 7 MST 16 p0.001 220 221225

    bone modifying agentsBMA BMA 223, 226229BMA prostate specific antigenPSA 1 230

    BMA

    DIC BMA

  • Clinical Question

    40

    No

    No

    No

    No

  • CQ 18

    41

    Clinical Question 18

    BMA

    ONJ

    1ONJosteonecrosis of the jawONJbone modifying agentsBMA

    BMA ONJ BMA 8

    ONJ110 231 232ONJ RANKLreceptor activator of nuclear factor kappaB ligand 181 ONJ 412 1.52748 7.7 231

    BMA ONJ 233, 234 BMA 186 BMA ONJ 235ONJ 236238 BMA BMA 1421 239

    2014RANKLRANKL MRONJmedicationrelated osteonecrosis of the jaw

    2 1

    estimated glomerular filtration rateeGFR4.944.5 57, 169, 170, 181, 200, 24024312 3 0.46.1 57, 169, 181, 244 243

    65 2 2434.75.4 244, 245

    60 mL 170, 181

  • Clinical Question

    42

    245 50 mL 5 100 mL 15 57, 168, 169

    3.314.7 3 0.4 170, 181, 200

    33.39.0 170, 181, 200, 211, 242, 244

    3 1.04.7 170, 200, 211, 244 1.710.8 170, 181, 200, 211, 246 3 1.35.1 170, 181, 2002 4 170, 181, 200, 211 D BMA D 56 170, 181, 200 D 400 IU500 mg D D 247, 248 10

    BMA 2 BMA

    4 3

    17.722.0 8.410.4 181, 200, 242

    1 2.3

    relative riskRR1.5095confidence intervalCI0.259.00 249 250

    1

    1 2

    mg100mL152

    11234

    1 12mg/dL2mL605060404930394.0 mg,3.5 mg,3.3 mg,3.0 mg

    120 mg 4 13

    3500 mg 400 IU

  • CQ 19

    43

    Clinical Question 19

    BMA

    93.1 C

    Cochrane Library 19 PubMed 128 96 bone modifying agentsBMA

    251255

    186, 256osteonecrosis of the jawONJ 257

    randomized controlled trialRCT

    BMA

    No

    Yes

    Yes

    NoBMA

  • Clinical Question

    44

    Clinical Question 20

    bone modifying agentsBMArandomized controlled trialRCT 56, 57, 168, 199, 258skeletal related eventSRESRE Brown N type collagen cross-linked NtelopeptideNTx

    bone specific alkaline phosphataseBAP 259Coleman 3 NTx BAP NTx 46 24 SRE 260

    Lipton NTx SRE 261 NTx relative riskRR0.5295confidence intervalCI0.220.83p0.0116 26290 SRE 5.6 5.9 263 C carboxyterminal telopeptide of type collagen1CTP N procollagen type Nterminal propeptidePINPBAP C type collagen cross-linked C terminal telopeptideCTx 264267

    BMA The American Society of Clinical OncologyASCO BMA BMA 186

  • CQ 21

    45

    Clinical Question 21

    CT MRI

    1970 X 268270RECISTResponse Evaluation Criteria in Solid Tumors 1.1 2009 X fluorodeoxyglucosepositron emission tomographyFDGPET computed tomographyCT magnetic resonance imagingMRI 271

    2Prostate Cancer Working Group 2 progressive diseasePD flareup 12 2 PD 6 PD 272 273bone scan indexBSI88BSIprostate specific antigenPSA BSI PSA 274

    CTconventional CT RECIST 1.1 271perfusion CT 275

    MRIconventional MRI RECIST 1.1 271 MRI apparent diffusion coefficientADC

    ADC ADC ADC 276ADC 277 ADC 278

  • Clinical Question

    46

    MRIdynamic contrastenhanced MRIDCEMRI DCEMRI 279

    FDGPET FDG RECIST 1.1 FDGPET FDGPET 280FDGPET

    patientreported outcomesPROPRO 281 PRO 282 McGillMelzack present pain intensityPPIscale brief pain inventoryBPIscale 283 PRO 198, 284286 287

  • CQ 22

    47

    Clinical Question 22

    100 C

    WHO

    randomized controlled trialRCT 288, 289Joishy 290 8

    ketorolac20 mg 67ketorolac 120 mg 291 292 293 8 6

    294nonsteroidal antiinflammatory drugsNSAIDs 288, 289 NSAIDs 295NSAIDspain flareChow 2968 Gy 33 8 mg 2 pain flare 3 Hird 297 10 pain flare 41 9 22 15 7 610 2

    CQ NSAIDs

    No

    Yes

    Yes

    Yes

  • Clinical Question

    48

    Clinical Question 23

    96.6 C

    10 1995 CQ 2 randomized controlled trialRCT 460 RCT 298

    25g120 mg brief pain inventoryBPI 422 numeric rating scoreNRS4246 RCT 299pain intensity differ-encePID0.3 1.5 WHO 300, 301

    302 25 NRS 4 303

    98 17 304

  • CQ 23

    49

    No RCT

    Yes

    Yes

    Yes

  • Clinical Question

    50

    Clinical Question 24

    89

    100 B

    89Sr8916 305 23 2030 306, 307Sr89 quality of lifeQOL 305 Sr89 153Sm153186Re186 305307 305307 Sr89 306 308

    Sr89 306 Sr89 Sr89 Sr89 305, 306

    Sr89 bone modifying agentsBMA Sr89 309randomized controlled trialRCTSr89 skeletal related eventSREoverall survivalOS 310 RCT

    Sr89 1 OS 311 RCT Sr89 312Sr89 313315

    Sr89

    prostate specific antigenPSA 316Sr89 3 315 1550 2 305307disseminated intravascular coagulationDIC Sr89

    2013 5 223Ra223

  • CQ 24

    51

    Sr89 Ra223 RCT OSSRE 317

    RCT Sr89 Sr89

    No

    Yes

    Yes1

    Yes

  • Clinical Question

    52

    Clinical Question 25

    ADL QOL 96.6 C

    bone modifying agentsBMAactivities of daily livingADLquality of lifeQOLJane 318Ruff n42randomized controlled trialRCTp0.001p0.001Beck depression inventory satisfaction with life scale p0.001 319Tang functional independence measureFIMFIM p0.02 320

    196 321

    3 RCTACTRN12611001158954 Medical Outcomes Study ShortForm 36SF36 45 3222013 20 83 323

    skeletal related eventSRE ADL QOL SRE ADL QOL

    Physiotherapy Evidence DatabasePEDro

  • CQ 25

    53

    No

    NoSRE

    No

    No

  • Clinical Question

    54

    Clinical Question 26

    PROSELF 1 6 1 1 3 6 2 4 5 PROSELF randomized controlled trialRCT 324, 325 326 327, 328quality of lifeQOL 329

    QOL 330332osteonecrosis of the jawONJ QOL ONJ 333335

    4 336 RCT 1618 337

  • 56

    BMABMAbone modifying agentsBMA

    RANKLreceptor activator of nuclear factor kappaB ligand

    RANKL BMA skeletal related eventSRE

    osteonecrosis of the jawONJ

    Cancer Board

    Tumor BoardCancer Board

    ONJONJosteonecrosis of the jaw

    ONJ BMA ONJ 2 BMA ONJBRONJbisphosphonaterelated ONJ RANKL ONJ 2014

    MRONJmedicationrelated ONJ

    PROSELFMiaskowski 2004

    1

    245 36

    RANKL

    RANKLRANK

    RANKLreceptor activator of nuclear factor kappa-B ligandparathyroid hormone-related proteinCPTHrP interleukinIL11 RANKL RANK RANKL RANK RANKLRANKL RANK

    RFARFA radiofrequency ablation

    heat ablation

    10 kHz100 GHz 300 kHz6 MHz

    RFA 450480 kHz

    2004 RFA

  • 57

    computed tomographyCT

    interventional radiologyIVR

    SRE

    4

    skeletal related eventsSRESRE SRE activities of daily livingADLquality of lifeQOL SRE

    RFA

    10.2 mgdL

    mgdL4gdL 12 mgdL

    C parathyroid hormonerelated proteinCPTHrP

    15 mgdL

    1CTP

    C carboxyterminal telopeptide of type collagen1CTP C 1CTP PINP

    N procollagen type Nterminal propeptidePINPPINP PINP BAP

    bone specific alkaline phosphataseBAPBAP BAPCTx

    C type collagen crosslinked Cterminal telopeptideCTx C CTx NTx

    N type collagen crosslinked NtelopeptideNTxN NTx

  • 58

    13performance statusPSPS Mirels 4 5BMA

    QOL

    metastatic spinal cord compressionMSCC10MSCC QOL Frankel 2Frankel Agolden time 48

    impending fracture 50Mirels4 5 5060 3540angulation sign

    pedicle signCT

    RANKL IgG2

    RANKL RANK RANKL 120 mg 4 1 SRE D

    instrument total en bloc spondylectomyTESTES

  • 59

    1 8922389

    Paget

    15 70 1 30

    ruffled border

    PCP

    23 tumor necrosis factor TNF ONJ

    1

    0 1 1 2

    012345

    slowmoderaterapid

    124

    0 1 2

    012

    treatableuntreatable

    024

    >3 2

    0 1 2

    3 02112

    01 2

    solitarymultiple

    12

    PS 34PS 2PS 01

    0 1 2

    PS 34PS 2PS 01

    0 1 2

    0 2

    Frankel AB Frankel CD Frankel E

    012

    >3 12 0

    012

    6103502

    121591108

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    2

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    5Recommended Treatment due to Total Scoring PointsMirels 1989 7 8 9

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    114

    4Scoring System for Predicting Impending Pathological FracturesMirels 1989 1 2 3

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    114

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    Bballoon kyphoplastyBKP26bisphosphonaterelated ONJBRONJ56bone modifying agentsBMA4, 9, 29, 31, 37, 41, 43, 44,

    56bone morphogenetic proteinBMP3bone specific alkaline phosphataseBAP5, 44, 57

    CCancer Board16, 56carboxyterminal telopeptide of type collagen1CTP5,

    44, 57castrationresistant prostate cancerCRPC33

    DEdeoxypyridinolineDPD5disseminated intravascular coagulationDIC3, 39dynamic contrastenhanced MRIDCEMRI46epidermal growth factorEGF3

    F18Ffluorodeoxyglucosepositron emission tomogrphy18FFDGPET14

    Frankel 60functional independence measureFIM52

    Iinsulinlike growth factorIGF3interleukinIL3

    MOmacrophage inflammatory protein 1MIP13magnetic resonance imagingMRI14medicationrelated osteonecrosis of the jawMRONJ

    41, 56metastatic spinal cord compressionMSCC58osteonecrosis of the jawONJ41, 56

    Pparathyroid hormonerelated proteinPTHrP3Payne 13percutaneous vertebroplastyPVP26polymethyl metacrylatePMMA26positron emission tomogrphycomputed tomographyPETCT14

    PROSELF54, 56procollagen type Cterminal propeptidePICP5procollagen type N terminal propeptidePINP

    5, 44, 57pyridinolinePYD5

    Rradiofrequency ablationRFA28, 56receptor activator of nuclear factor kappa-B ligandRANKL3, 56

    Ssingle photon emission computed tomographySPECT14skeletal related eventSRE5, 12, 13, 29, 31, 57

    Ttartrate-resistant acid phosphatase5bTRAPC5b5total en bloc spondylectomyTES18, 58transforming growth factorTGF3tumor necrosis factorTNF3type collagen cross-linked Cterminal telopeptideCTx

    5, 44, 57type collagen cross-linked NtelopeptideNTx5, 44, 57

    C 5 C 5, 44, 57 N 5, 44, 57 C 5, 44, 57 N 5, 57

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    548

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  • 2015 3 30

    113841042 6 03381172360338117239http://www.nankodo.co.jp/

    Printed and Bound in JapanISBN9784524265343

    Practical Guideline of Bone Metastasis Japanese Society of Medical Oncology, 2015

    0335136969FAX 0335136979e-mail: [email protected]

    00_100_100_201_p001_02_p002-010_02p011_03-CQ_p012-054_03-CQp055_04_p056-071_0402_p072-074_p075_4