nieuwe toepassingen van prostaat brachytherapie · randomized phase 3 study on the assessment of...
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Nieuwe Toepassingen van Prostaat Brachytherapie
Bradley PietersAcademisch Medisch Centrum /
Universiteit van Amsterdam
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Young 1926
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Retropubic Prostate Implant Technique
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Perineal prostate implantation
• Perineal technique• Ultrasound guided• Ultrasound probe on
immobilizer• Template
Holm, J Urol 1983
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Brachytherapy Boost
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EBRT vs. Brachy
Hoskin, Radiother Oncol 2012
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Late Toxicity
Hoskin, Radiother Oncol 2012
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NCCN Intermediate- and High-riskPSA ≤ 40 ng/ml
< T3bProstate volume ≤ 75 cm3
R
3D-CRT46 Gy pelvis32 Gy boost
3D-CRT + Brachy46 Gy pelvis
115 Gy I-125 boost
Ascende-RT
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biochemical Progression Free Survival Overall Survival
Morris et al. Int J Radiat Oncol Biol Phys. doi: 10.1016/j.ijrobp.2016.11.026.
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Increased Toxicity with LDR Brachytherapy?
Rodda et al. Int J Radiat Oncol Biol Phys 2017; 98:286-295
Incidence Prevalence
GU GU
GI GI
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Urethral Stricture
Less risk urethra stricture
• Periapical V150 < 0.8 ml
• Apical urethra dose < 174 Gy
• Distance 100% isodose line < 1.1 cm from apex
Earley et al, Radiother Oncol 2012
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Urethral Stricture
Merrick et al, J Urol 2006
Most predictive•Bulbomembranous dose•Supplementary EBRT
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PROBACH
Randomized Phase 3 Study On The Assessment Of Late Toxicity By Comparing IMRT High Dose External
Beam Radiotherapy Only With External Beam Radiotherapy Combined With HDR Or PDR
Brachytherapy In Patients With Intermediate/high Risk Prostate Cancer
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Intermediate / High Risk Prostate Cancer
R
IMRT 35 x 2.2 Gy IMRT 20 x 2.2 Gy+
1 x 13 Gy HDR
Toxicity Assessment
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JAMA. 2018;319(9):896-905. doi:10.1001/jama.2018.0587
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1809 patients:EBRT + BT is associated with lower PCA specific Mortality
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HDR Monotherapy
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HDR brachytherapy monotherapy: Planning aim
34 Gy in 4 fractions36-38 Gy in 4 fractions31.5 Gy in 3 fractions26 Gy in 2 fractions
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Published HDR monotherapy studies
From Zamboglu et al IJROB 2013
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718 patients: 38Gy/4f/48hrs38Gy/4f/15days34.5Gy/3f/6weeks
Zamboglou et al. Int J Radiat Oncol Biol Phys 2013;85:672-678
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Acute toxicity
Late toxicity
Zamboglou et al. Int J Radiat Oncol Biol Phys 2013;85:672-678
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Multifractionated schedules
Biochemical control 85%-99%
GU grade 2 1.5%-25%
GU grade 3 0%-9.2%
GI grade 2 0%-13%
GI grade 3 0%-2%
Most common4-9 fractions
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SBRT?
Spratt et al. Brachytherapy 2013;12:428-433
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BRAG-Peak
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BRACH-Peak
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Single Dose HDR Brachytherapy
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Toxicity Single Dose
Morton et al. Radiother Oncol 2017:122;87-92
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QOL of Single Dose
Morton et al. Radiother Oncol 2017:122;87-921
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QOL and Single Dose
UrinaryIncontinence
UrinaryIrritative
Bowel Sexual Hormonal
Gomez-Iturriaga et al. Radiother Oncol 2017;126:278-2822
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Single Dose Equivalent to 2-3 Fractions
1 x 19-20 Gy 2 x 13 Gy 3 x 10.5 Gy
Hoskin et al. Radiother Oncol 2017:124:56-60
FFBR
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T1-2 92% Gleason 6 84% PSA≤ 10 ng/ml
No grade 3-4 late toxicity
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Single dose1 x 19-20 Gy
High biochemical control and low toxicityHoskin et al. Radiother Oncol 2017:124:56-60Morton et al. Radiother Oncol 2017:122;87-92Gomez-Iturriaga et al. Radiother Oncol 2017;126:278-282
Caution for biochemical failurePrada et al. Radiother Oncol 2016;119:411-416
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Primary Focal Brachytherapy for Prostate Cancer
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Donovan JL et al. N Engl J Med 2016;375:1425-1437.
Outcomes for Urinary Function and Effect on Quality of Life.
Outcomes for Sexual Function and Effect on Quality of Life.
Use of padsErectile firmnessSexual quality of life
Active monitoring Superior for:
PROTECT trial
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Keyes et al. Brachytherapy 2015;14:334-341
Erectile Dysfunction after Brachytherapy
100% full potency 100% partial potency
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Erectile Dysfunction
Author Erectile function(%)
Stone I125 61 Urology 2007;69:338-342
Bottomley I125 42 Radiother Oncol 2007;82:46-49
Cesaretti I125, Pd103 32-68 BJUI Int 2007;100:362-67
Sanchez-Ortiz I125, Pd103 49 Int J Impot Res 2000;12:S18-S24
Merrick I125, Pd103 39 Int J Radiat Oncol Biol Phys2002;52:893-902
Mabjeesh I125 80 Int J Impot Res 2005;17:96-101
Merrick I125, Pd103 59 Int J Cancer 2001;96:313-319
Taira I125, Pd103 56 Int J Radiat Oncol Biol Phys2009;75:639-648
Budäus et al. Eur Urol 2012;61:112-127
Functional Outcomes and Complications Following Radiation Therapy for Prostate Cancer: A Critical Analysis of the Literature
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Focal therapy for localised unifocal and multifocal prostate cancer: a prospective development study
Ahmed et al. Lancet Oncol 2012;13:622–632
Pad-freeLeak-freeErections sufficient for penetration
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Dosimetric analysis
Hemigland Target Hemigland contralateral Whole gland
D90 153.8 Gy 47.5 Gy
V100 93.1% 24.6%
D0.1cm3 NV 219.8 Gy 62.9 Gy
D30 urethra 150.4 Gy 175.6 Gy
D2cm3 rectum 75.5 Gy 94.9 Gy
Laing et al. Radiother Oncol 2016:121:310-315
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Erectile Function After partial Treatment
Yap et al. Eur Urol 2016;69:844-851
IIEF development from 3 prospective studies with HIFU• Hemi trial• Focal trial• Lesion-Control trial
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POWERPartial Or Whole gland for ERections
Randomized trial for the evaluation of erectile dysfunction after whole or partial gland prostate
brachytherapy
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Randomization
Whole gland Hemigland
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Hypothesis Primary Endpoint• 50% ED @ 5 years (Control arm)• 30% ED @ 5 years (Experimental arm)
• ∆20%, Type I error 5% (1-sided), Power 90%
• 127 patients in each arm (254 total)
• Statistics: Cox-regression analysis and Kaplan-Meier curves
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Conclusions
• Brachytherapy as boost result in superior biochemical control– GU side effects can be a concern
• HDR Monotherapy results are comparable to LDR for low- and intermediate-risk PCA
• Further investigations necessary to evaluate safety of single dose HDR brachytherapy
• Partial prostate brachytherapy is investigational in studies to follow