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Author contact info: Todd J. Scarbrough, M.D. 1130-A South Hickory St., Melbourne, FL 32901 321.409.1956 (ASTRO contact #: 321.431.9650) email: [email protected]
Seed Marker-based IGRT for Prostate Cancer: Excellent Preliminary Toxicity Outcomes
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Todd J. Scarbrough, M.D.*†; Joseph Y. Ting, Ph.D.*†; Laura Feja*; Nanialei M. Golden, M.D.*; Brian Oliveira*; Chad A. Levitt, M.D.**MIMA Cancer Center, Melbourne, Florida; †Oregon Health & Science University, Department of Radiation Medicine, Portland, Oregon
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AbstractINTRODUCTION
In2004,wecompletedextensiveprostateimage-guidedradiationtherapy(IGRT)comparisonanalyses.Ourpublishedresultsindicateahightargetingaccuracyisachievablewithseedmarker-basedIGRT(Scarbroughetal., Int J Rad Oncol Biol Phys2006;65:378-87).Post-repositioninganalysesindicatedasubstantialreductionofplanningtargetvolumemargins(inthe3mmrange)waspossible(Tingetal.,Hematol Oncol Clin North Am,2006;20:63-86).Bettertargetingandreducedmarginscouldleadtoimprovedoutcomes.Thisisaprelimi-naryanalysisofourclinicalresults.
METHODS & RESULTSThesamplecomprisesacontinuouscohortof267patientsfollowedaminimumof6months(medianf/u:1.5years).Allpatientsweretreatedusingimage-guided,intensity-modulatedradiationtherapy(IMRT).Mostpatients (76%)werecontouredusingMRI/CTfusion.Minimumprostatedosewas81Gy/45.Allpatientsweretreatedus-ingIMRT(slidingwindow),kVX-rayIGRT,and6MVphotonbeams.Nopatienthasbeenlosttofollowup.Rectaltoxicitywasassessedac-cordingtoCommonTerminologyCriteriaforAdverseEvents(CTCAE)v3.0andGUtoxicitybyInternationalProstateSymptomScore(IPSS).Patientsalsocompletedsexualsatisfactionquestionnaires.Only5/267patientshadrectalcomplaintsaftertreatment.Therewasnosignifi-cantdifferenceinpre-andpost-treatmentIPSS;1/267patientsde-velopedurinaryincontinenceaftertreatment.Some(34%)patientshadimprovedGUprofilesafterhigh-doseIMRT.Amonginitiallypo-tent,non-hormonallytreatedpatients,77%maintainedatleastsomepotencypost-treatment.Biochemicaldisease-freesurvivalis97%(bythreesuccessiverisesornadirplustwocriteria;4/267patientshavehadPSAfailure,2ofthese4withmetastaticprogression).
CONCLUSIONSModern high-dose, image-guided, intensity-modulated externalbeamradiationtherapyisalow-morbiditytreatment.Longerfollow-uptimesarenecessary,butinitialresultsarepromising.
IGR
T +
IMR
T
1.8 cm
Spheroprobability plot (all kV X-ray patient positions)N = 1,019
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0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30Vector of kV Xray data with IGRT technique, mm
1.8 cm
Spheroprobability plot (kV X-ray post-positioning)N = 97
IGRT technique achieves ~95%of all shifts/errors within 3 mm
of iso in 3D space
measured non-IGRT versus... measured IGRT
isocenterisocenter
(setup to skin marks, no repositioning) (setup to skin marks, patients repositioned using seeds)
95% PTVcoverage margin=
1.5 cm
95% PTVcoverage margin=
0.3 cm
Figure A.Seedmarker-basedIGRTforprostatecancersignificantlyincreasesaccuracy.Figure B. CT/MRI marker visualiza-tion.Figures C&D. HighlyconformalIMRT,withexcellentrectalsparing,requiresIGRTforproperdelivery.Figure E.Viewatthetreatmentcon-solealigningpre-plannedmarkerpo-sitions with measured marker posi-tions. A B C D E
Grade 0Grade 1
Grade 2Grade 3+
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PER
CEN
T o
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TIEN
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MIMA 81 Gy IMRT + IGRT (N = 267)
Memorial Sloan-Kettering CancerCenter 81 Gy IMRT (N = 171)Zelefsky et al., Radiother Oncol 55:241-9, 2000.
Memorial Sloan-Kettering CancerCenter 81 Gy 3DCRT (N = 61)Zelefsky et al., Radiother Oncol 55:241-9, 2000.
M.D. Anderson 78 Gy (N = 151)50 Gy 4-field + 28 Gy 3DCRT boostPollack et al., Int J Rad Oncol Biol Phys 53:1097-1105,2002.
LATE RECTAL TOXICITY
0 .5 1 1.5 2 2.5 3 3.5 4
Time (years)
No hormone tx (N = 117)Short-course hormone tx (N=150)Mean duration: 5 ± 3 months
0%
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100%
PSA
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trol
(nad
ir +
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roba
bilit
y
P = 0.520
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14
PSA
(n
g/m
L)
pre-tx PSA(N=267)
post-tx PSAno hormone tx
(N=117)
post-tx PSAshort-course hormone
(N=150)
Time (years)
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
PSA
con
trol
(nad
ir +
2) p
roba
bilit
y
PSA 10<20 (N = 59)PSA 20+ (N = 11)
0 .5 1 1.5 2 2.5 3 3.5 4
PSA 0<10 (N = 197)
P = 0.047
By“oldASTRO”(threesuccessivePSAelevations)ornadir+2criteria,biochemicaldisease-freesurvivalis97%forallN=267.Theonlytrend(P=0.046)inbiochemicalfailurewasnotedforpatientswithincreasedPSA(notrendforGleason’sorstage).
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Ch
ang
e in
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st-
vers
us
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-tre
atm
ent
0 5 10 15 20 25 30 35
Pre-treatment IPSS for all patients (N = 267)
Change in IPSS = 5.2 - 0.6*Pre-IPSS, R2 = 0.328
IMPR
OV
EM
EN
TW
OR
SEN
ING
P < 0.001
-30
-20
-10
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Ch
ang
e in
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atm
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Pre-treatment IPSS for hormonally treated patients (N = 150)
IMPR
OV
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ang
e in
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atm
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0 5 10 15 20 25 30 35
Pre-treatment IPSS for non-hormone patients (N = 117)
IMPR
OV
EM
EN
TW
OR
SEN
ING
P < 0.001
Mean pre-tx IPSS: 7/35Mean post-tx IPSS: 8/35Pre- vs post-tx IPSS: P = 0.28IPSS increased post-tx: 176 ptsIPSS decreased post-tx: 91 pts
267patients
137 impotentpre-tx
130 potentpre-tx
61/130 received hormones
22/61 impotentpost-tx
39/61
64%potency
preservation
69/130 no hormone tx
16/69 impotentpost-tx
53/69
77%potency
preservation
71% overall potencypreservation rate
92/130potent post-tx
Rectaltoxicityratesareverylow,evenatthishighdose.Potencypreservationratesarehigh,withslightlymorenon-hormonallyexposedmenmaintainingsomepotencyaf-tertreatment.AnalysisofGUtoxicityrevealsnosignificantdifferenceinpre-andpost-txIPSS(P=0.28).Asubstantialportion,esp.thehigh-IPSSpatients,hadimprovement.
Patient Outcomes
Ch
aracteristics
MEAN AGE & RANGE: 74 years (46-90)
MEDIAN F/U for all N = 267: 1.5 years
STAGE DISTRIBUTION:cT1a/b: 4 (1.5%) cT2c: 54 (20.2%)cT1c: 95 (35.6%) cT3a: 10 (3.7%)cT2a: 74 (27.7%) cT3b: 3 (1.1%)cT2b: 27 (10.1%)
GLEASON SUM DISTRIBUTION:4: 1 (0.4%) 7: 80 (30.0%)5: 4 (1.5%) 8: 21 (7.9%)6: 152 (56.9%) 9: 9 (3.4%)
PRESENTING PSA (ng/mL):0-4: 43 (16.1%) 10-20: 59 (22.1%)4-10: 154 (57.7%) 20+: 11 (4.1%)
CORE POSITIVITY RATIO:0-33%: 151 (56.6%) 34-50%: 78 (29.2%)50+%: 38 (14.2%)
PERINEURAL INVASION:93 (34.8%)
PROSTATE VOLUME: 49 cc (7-184)
HORMONE (N =150) DURATION:4-6 months: 112 (41.9%) 8 months: 29 (10.9%)12 months: 8 (3.0%) 24 months: 1 (0.3%)
PTV MARGIN SPECIFICATIONS:Intermediate to high risk:45 Gy/25 fx:Elective nodal irradiation (24/267 patients) w/ 7-9 mmplus SVs+prostate w/ 10 mm (5 mm rectum)27 Gy/15 fx:Prostate w/ 4 mm9 Gy/5 fx:Prostate w/ 4 mm (0 mm rectum)
Low risk:72 Gy/40 fx:Prostate w/ 4 mm9 Gy/5 fx:Prostate w/ 4 mm (0 mm rectum)
