Brachytherapy for Prostate Cancer 2017

WELCOME TO ESTRO PROSTATE BRACHYTHERAPY IN BRUSSELS

ESTRO, Brussels Elena Giusti

Your teachers ……………..

• Peter Hoskin:

Mount Vernon, UK

• Bashar AlQaisieh:

Leeds

• Stefan Machtens:

Bergisch Gladbach,DE

• Carl Salembier:

Brussels, BE

• Frank Andre Siebert:

Kiel, DE

Our exhibitors

• Eckert and Ziegler • Nucletron • Varian

Age specific incidence rates UK 2009/11

Age-Standardised Incidence Rates, , UK, 1993-2011

Cancer incidence and mortality, males, Europe: 2010

IARC

http://www.cancerresearchuk.org/cancer-info/cancerstats/world/incidence/#By

Age standardised incidence and mortality rates Europe 1975-2011

Incidence

Mortality

Worldwide Age standardised incidence and mortality rates 2010

IAR

182,123 men in SEER database

• Peer review evidence based trees estimate:

RP: 24% (15-30) EBRT: 58% (54-64%) BT: 9.6% (6-17.9%)

• Actual utilisations rates:

RP: 13-44% EBRT: 43-56% BT: 1.8-10.9%

Lo w

Intermediate

High

Prostate Brachytherapy: Anatomy

S. Machtens

Director of the

Department of Urology and Paediatric Urology

Academic Teaching Hospital

Marien-Hospital Bergisch Gladbach

With Courtesy from Geert Villeirs UZ Gent

ESTRO Teaching Course on Brachytherapy for Prostate Cancer Brussels, June 29th-July 1st 2017

The Prostate

The prostate surrounds the urethra and is situated below the bladder.

The prostate produces fluid that is needed by sperms to move.

Ultrasound Normal Anatomy

CG

PZ

PZ

Isoechoic PZ Hypo/hyperechoic CG

Corpora Amylacea

Ultrasound Normal Anatomy

Urethra

Urethra Sagittal

Ultrasound Normal Anatomy

Seminal Vesicles Convoluted Hypoechoic Cystic Structures

Ultrasound Sagittal: urethral measurements

ULTRASOUND – Dorsal vein plexus

Zonal Anatomy Central Gland

Periurethral Glands (paracoronal view)

Periurethral Glands

Zonal Anatomy Central Gland

Transition Zone (transverse view)

Transition Zone

Zonal Anatomy Central Gland

Central Zone (paracoronal view)

Central Zone

Zonal Anatomy Overview

Peripheral Zone (paracoronal view)

Peripheral Zone

Zonal Anatomy Overview

Anterior Fibromuscular Stroma

AFS (paracoronal view)

Zonal anatomy in MRI and Ultrasound

Anatomy Prostate

CG

CG

PZ PZ

PZ

PZ

PZ

PZ

Prostatic Apex Midprostate Prostatic Base

Imaging of Prostate Cancer Body coil versus Endorectal coil

Normal Prostate with Body Coil

Normal Prostate with Endorectal Coil

1.5 Tesla MRI

MRI: • Resolution: good • Contrast: good, especially soft tissue contrast

Zentrale Zone

Periphere Zone

Tumor

1.5 T

T2-weigthed

T1-weighted

3.0 Tesla MRI

T1 weighted

T2 -weighted

3.0 Tesla MRI + Endorectal coil

Anatomy Hyperplasia

CG

CG

CG

PZ

PZ

Benign Prostatic Hyperplasia

Variation of bladder neck according to BPH

Anatomy Urethra

External Sphincter

Urethra

Sagittal

Coronal

Transverse

Platinum Slide Series

Transversal section of the prostatic apex. A considerable part of the urethral sphincter is located intraprostatically between the prostatic apex and the colliculus seminalis.SMS = smooth muscle sphincter; SS = striated sphincter (rhabdosphincter); CS = colliculus seminalis; PA = prostatic apex.

Thorsten Schlomm et al. Eur Urol 2011;2:320-329

1/11

Platinum Slide Series

Anatomic variability of the prostatic apex. Depending on the individual apex shape, between 10% and 40% of the functional urethra is covered by parenchymal apex tissue. Otherwise, the prostatic apex is covered by some muscular tissue on the ventral and rectal aspects as rudiments of embryonic and adolescent prostatic development.

Thorsten Schlomm et al. Eur Urol 2011;2:320-329

10/11

Platinum Slide Series

Surgical anatomy of the urethral sphincter complex. (A) Fixation of the urethral sphincter (modified from Luschka [16]). (B) Lateral aspect of the urethral sphincter after nerve sparing.PPL = puboprostatic ligament; PVL = pubovesicalis ligament; PP = puboperinealis muscle; DA = detrusor apron; B = bladder; FSS = fascia of the striated sphincter; ML = Mueller's ligaments (ischioprostatic ligaments); NVB = neurovascular bundle; R = rectum; MDR = medial dorsal raphe; RU = rectourethralis muscle; OI = Os ischiadicum; SS = striated sphincter (rhabdosphincter); PB = pubis bone.

Thorsten Schlomm et al. Eur Urol 2011;2:320-329

8/11

Anatomy Seminal Vesicles

Transverse

Coronal

Anatomy Periprostatic Structures

S

IO

IO

P

L

L

P

IO

IO

ugd

i

i

c c B

i

i

R

L

L

Transverse

Coronal

Variation in Genitourinary diaphragm

Apex: Anatomische Variabilität

31 Akademie Expertenkurs

Walz et al, Eur Urol, 2010

Parasympathic nerves

Course of neurovascular bundle

Abb.: 5

Stolzenburg et al, Eur Urol, 2007

34 Akademie Expertenkurs

Standardtechnik

intrafasziale Technik

Abb.: 6

Stolzenburg et al, Eur Urol, 2007

35 Akademie Expertenkurs 35

Walz et al, Eur Urol, 2010

36 Akademie Expertenkurs

Prostate Brachytherapy Course

“Selection of patients for prostate cancer permanent implant brachytherapy”

C. Salembier

Department of Radiotherapy-Oncology Europe Hospitals – Brussels - Belgium

Patient selection: • do we have recommendations ? • if yes, what do they learn us ?

ABS 1999

ESTRO 2000

Actually only minor differences with the ABS paper ...

a lot of literature

but

no new recommendations

until …. 2012

199 9

200 0

201

Patient selection for prostate LDR brachytherapy …. Do we have all the answers reading these recommendations ?

… no … after reading the literature some questions remain …

High dose rate brachytherapy for prostate cancer: PATIENT SELECTION

Peter Hoskin Mount Vernon Cancer Centre Northwood UK

HDR prostate brachytherapy

• Practical ➢ Existing source, afterloading

• Physical ➢ Greater implant volume ➢ including seminal vesicles

• Biological ➢ Low  /  tumour; greater biological dose with high dose per fraction

Advantages of temporary HDR prostate brachytherapy

Radioprotection

– no free live sources – no risk of source loss – no radioprotection issues after discharge

Cheap: utilises existing HDR source and equipment

Day case procedure

Disadvantages of temporary HDR prostate brachytherapy

High dose rate radiation requires fractionation – no longer!?

– logistics:

• Quality assurance

Selection for HDR prostate brachytherapy

• Boost with external beam

• Monotherapy

Pre treatment investigations

• General medical assessment • Prostate biopsy

• PSA • IPSS • IEFS • Flow rate • Pelvic MRI • Staging investigations ➢ PSA ➢ Bone scan ➢ (Whole body MRI) ➢ (Choline PET) ➢ (PSMA PET)

Indications for HDR prostate brachytherapy BOOST

Where there is a significant predictive risk of extracapsular or seminal vesical involvement:

External beam

Brachytherapy

Indications for HDR prostate brachytherapy BOOST

Where there is a significant predictive risk of extracapsular or seminal vesical involvement:

T3a T3b ?T2c

Gleason 8 – 10 ?Gleason 4+3

Probability of organ confined disease

[Partin 2001]

PSA 6.1-10.0

Gleason T1c

T2a

T2b

T2c

3+4

54% (49-59)

35% (30-40)

26% (22-31)

24% (17-32)

4+3

43% (35-51)

25% (19-32)

19% (14-25)

16% (10-24 )

8-10

37% (28-48)

21% (15-28)

15% (10-21)

13% (8-20 )

Probability of organ confined disease

[Partin 2001]

PSA >10.0

Gleason T1c

T2a

T2b

T2c

3+4

37% (32-42)

20% (17-24)

14% (11-17)

11% (7-17)

4+3

27% (21-34)

14% (10-18)

9% (8-13)

7% (4-12 )

8-10

22% (16-30)

11% (7-15)

7% (4-10)

6% (3-10 )

Ext beam/HDR boost for prostate

?The low risk patient – PSA<10ng/ml

……….what is the risk of ECE or seminal vesicle invasion??...............

– Gleason 6 or below (?3+4) – T2a or less

Probability of organ confined disease

[Partin 2001]

PSA 4.1-6.0

Gleason T1c

T2a

T2b

T2c

2-4

90% (78-98)

81% (63-95)

75% (55-93)

73% (52-93 )

5-6

80% (78-83)

66% (62-70)

57% (52-63)

55% (44-64 )

3+4

63% (58-68)

44% (39-50)

35% (29-40)

31% (23-41)

54 patients Gland size median 57ml; range 50-97.3ml

All dosimetric goals achieved

164 patients HDR monotherapy; median CTV volume 60mls (range 14-2

Toxicity

bRFS

Pubic arch interference

• Patient position: ➢

Hyperextended vs standard Plane of prostate vs pubic arch

➢

➢

Table / stand positions

• Needle insertion ➢

Bend the needle?

➢

Enter via adjacent co-ordinate

HDR PROSTATE BRACHYTHERAPY INDICATIONS

• Boost with external beam therapy ➢ Intermediate/high risk disease ➢ ?Low risk disease

• Monotherapy

➢ Phase II studies….. ➢ Low/Intermediate/high risk disease

HDR monotherapy for prostate

? low risk patient

Intermediate risk patient

High risk patient

HDR monotherapy; published series and risk groups

LOW INT HIGH

Yoshioka et al MSKCC

X X

X

Hoskin et al MVCC

X X

Rogers et al

X

Mark et al Texas

X X

X

Prada et al Spain

X X

Martinez et al Michigan

X X

Demanes et al CET

X X

Zamboglu et al Offenbach X X

X

HDR monotherapy: what the guidelines say…………

GEC ESTRO

ABS

HDR for salvage? GEC ESTRO guidelines 2013

HDR for salvage? ABS guidelines 2013

Selection for HDR prostate brachytherapy

Boost with external beam

Monotherapy

Salvage

Selection for HDR prostate brachytherapy …………whole gland or focal…….

Indications for consideration of focal HDR BT

– HDR BT indicated – Focal lesion identified by:

• mpMRI ‘dominant’ lesion • Template biopsy mapping

Prostate Brachytherapy: Imaging for prostate brachytherapy

S. Machtens

Director of the

Department of Urology and Paediatric Urology

Academic Teaching Hospital

Marien-Hospital Bergisch Gladbach

Teaching Course Brussels 2017

Ultrasound Prostate Carcinoma

Hypoechoic nodule compared to normal PZ Low specificity (atrophy, prostatitis, ...)

Ultrasound Diagnostic Performance

• Performance in tumour localization

➢ Sensitivity : 32-85% : false negatives! ➢ Specificity : 41-79% : false positives!

• Inappropriate for screening of general population

Ultrasound Staging Performance

• Performance in tumour staging

➢

Extracapsular extension ▪ sensitivity : 50-90% ▪ specificity : 50-90% Seminal vesicle invasion ▪ sensitivity : 20-60% ▪ specificity : 50-90%

➢

• Inappropriate for staging

Ultrasound Value

• Initial evaluation of patients with elevated PSA and/or abnormal digital rectal examination

• Biopsy guidance

• Determination of prostate seize

• Guidance in brachytherapy

Elastography

Elastography

Sensitivität: 69-80% Spezifität: 78-90%

Elastography plus conventional TRUS-Bx Salomon et al., BJUInt. 2014; 113(4):548-53

1024 men (10+4 cores) Detektionsrates: 10fach TRUS 39,1%, RTE 29%, Combination 46,2%

Prostate HistoScanning™

Tissue Differentiation and Visualization

▪ Computer-based information of 3D data. ▪ Visualization based on different acustic signals. ▪ HistoScanning™ signals appear as red pixels.

Imaging of Prostate Cancer Body Coil Imaging

Imaging of Prostate Cancer Tumour Detection (Body Coil)

Decreased signal intensity relative to normal peripheral zone tissue (70% in peripheral zone)

Imaging of Prostate Cancer Diagnostic Accuracy (Body Coil) (Sensitivity)

Carter 48% Tempany Radiology 1994;192:47 54% Hricak Radiology 1994;193:703 68% Rifkin N Engl J Med 1990;323:621 69% Jager Radiology 1997;203:645 72% Huch Boni Clin Radiol 1995;50:593 76% Kier AJR 1993;161:601 87% Radiology 1991;178:523

Imaging of Prostate Cancer Endorectal Coil Imaging

Endorectal Coil

60 cc

Imaging of Prostate Cancer Body coil versus Endorectal coil

Normal Prostate with Body Coil

Normal Prostate with Endorectal Coil

Imaging of Prostate Cancer Tumour Presence (Endorectal Coil)

Peripheral Zone Tumour with Body Coil

Peripheral Zone Tumour with Endorectal Coil

Imaging of Prostate Cancer Diagnostic Accuracy (Endorectal Coil) (Sensitivity

Tempany Radiology 1994;192:47 61% Presti AJR 1996;166:103 63% Beyersdorff Radiology 2002;224:701 68% Perrotti J Urol 1999;162:1314 70% Vilanova Eur Radiol 2001;11:229 71% Ogura Urology 2001;57:721 72% Ikonen Acta Radiol 2001;42:348 74% Cornud Br J Urol 1996;77:843 74% Bates Clin Radiol 1996;51:550 77% Bartolozzi Eur Radiol 1996;6:339 82% Huch Boni JCAT 1995;19:232 82% Huch Boni Clin Radiol 1995;50:593 88%

Imaging of Prostate Cancer Tumour detection @ 3 Tesla

Courtesy: Fütterer JJ, Nijmegen

Kim, J Comput Assist Tomogr 2006;30:7-11 (70%) Heijmink, Radiology 2007;244:184 (ERC > BC)

1.5 Tesla MRI

MRI: • Resolution: good • Contrast: good, especially soft tissue contrast

Zentrale Zone

Periphere Zone

Tumor

1.5 T

T2-weigthed

T1-weighted

3.0 Tesla MRI

T1 weighted

T2 -weighted

3.0 Tesla MRI + Endorectal coil

MRT-Ultrasound-Fusion

Hradaschik, J Urol 2012

MR-guided Biopsy

Transrectal approach: roboter-guided biopsy

Transgluteal approach in open MR

Functional Imaging

Functional Imaging

• Magnetic Resonance Spectroscopy

• Dynamic Contrast-Enhanced MRI

• Diffusion Weighted Imaging

• Cholin PET

Magnetic Resonance Spectroscopy

MR-Spectroscopy

• acquisition of spectra from small volumes (voxels) throughout the prostate gland

• detection of cellular metabolites

➢

citrate in normal tissue and BPH

➢

choline in tumour lesions

MR-Spectroscopy Normal Prostate

1 H-spectra: dominant citrate peak no elevated choline

Normal prostate volume

MR-Spectroscopy Prostate Cancer

1 H-spectra: reduced citrate elevated choline

Prostate Cancer

MR-Spectroscopy Spectral Maps

MR-Spectroscopy Choline/Citrate Ratio Images

Choline

Citrate

Spectrum

Index

MR-Spectroscopy Choline/Citrate Ratio Images

MR-Spectroscopy Diagnostic accuracy (Sensitivity)

Dynamic Contrast-Enhanced MRI

Dynamic Contrast-Enhanced MRI Assessment of Angiogenesis

Enhancement

Lesion Morphology

Angiogenic Factors

Increased in- en efflux Expanded extracellular space Increased extravasation

Growth of existing vessels De novo angiogenesis

Abnormal configuration: AV-shunts and defective endothelium

Earlier onset of enhancement Increased slope

Dynamic Contrast-Enhanced MRI Assessment of Angiogenesis

Early

Fast

*G. Jager, J. Barentsz, Nijmegen Group

Dynamic Contrast-Enhanced MRI Assessment of Angiogenesis

Late

Slow

*G. Jager, J. Barentsz, Nijmegen Group

Dynamic Contrast-Enhanced MRI Assessment of Angiogenesis

63-year old man Suspicious lesion in left peripheral zone

Imaging of Prostate Cancer Diagnostic accuracy (dCE MRI)(Sensitivity)

Diffusion Weighted Imaging

Diffusion Weighted Imaging

• visualize the amount of random (‘Brownian’) movements of water molecules (diffusion)

• surrogate for “cellular density”

Diffusion Weighted Imaging

T2W

b1000

ADC

T2W

b1000

ADC

Dickinson L et al.; Eur Urol 59(2011):477-494

Dickinson L et al.; Eur Urol 59(2011):477-494

T2w: PI-RADS

Röthke M, Fortschr Röntgenstr 2013; 185: 253–261

DWI MRI: PI-RADS

Röthke M, Fortschr Röntgenstr 2013; 185: 253–261

DCE MRI: PI-RADS

Röthke M, Fortschr Röntgenstr 2013; 185: 253–261

Can clinically significant prostate cancer be detected with multipara- metric magnetic resonance imaging? A systematic review of the literature. Fütterer JJ et al., Eur Urol 2015; Epub ahead of print been shown that multiparametric magnetic resonance imaging (mpMRI) facilitates tion of PCa and can help in targeting prostate biopsy. Objective: To systematically review the literature to determine the diagnostic accuracy

localisa-

of

mpMRI

in

the detection

of

clinically

significant

PCa.

Evidenceacquisition:

ThePubmed,Embase,andCochraneCentral Register of ControlledTrials

(CENTRAL) databases were searched the search criteria‘‘prostateORPcaORPSAORprostaticORprostatecancer’’ AND‘‘MRORNMROR NMRI ORMRI ORmagnetic resonance ORADCORDWI ORDCEORdiffusion weighted OR dynamiccontrast ORmultiparametricORMRSI ORMRspectroscopy’’. Two reviewersindepen- dently assessed 1729 records. Two independent reviewersassessed themethodologic quality using theQuality Assessment of Diagnostic Accuracy Studies (QUADAS-2) 2 tool. Evidence synthesis: Twelve articles were eventually selected. Patients had a median age of 62–65 yr (range 39–83 yr), amedian prostate-specific antigen (PSA) level of 5.1–13.4 ng/ml (range1.2–228 ng/ml), and Gleason scoreof 6–10. Variousdefini tions of clinical significance were used, mainly based on maximum cancer core length and grade at biopsy, number of positive cores, and PSA. Detection of clinically significant PCausingmpMRI ranged from 44% to 87%in biopsy-naı¨vemales and men with prior negative biopsies using prostate biopsy or definitive pathology of a radical prostatectomy specimen as the reference standard. The negative predictive value for exclusion of significant disease ranged from 63%to 98%. Conclusions: mpMRI isabletodetect significant PCain biopsy-naı¨vemalesandmenwith prior negativebiopsies. Thenegativepredictivevalueof mpMRI is important to theclinician because mpMRI couldbeused toruleout significant disease.Thismay result in fewer or nosystematicor targeted biopsies in patientswith PSAsuspicious for prostate cancer. Patient summary: We reviewed the diagnostic accuracy of multiparametric magnetic reso- from January 1, 2000 to September 30, 2014, using

ith

atic

illeirs c ,

earch IRCCS of Urology, University artment of Radiology, r, New York, NY, USA; rology, LilleUniversity Institute,

jor

challenge.

It

has

)

facilitates

localisa-

gnostic accuracy

of

r of Controlled Trials 30, 2014, using the ND‘‘MRORNMROR fusion weighted OR reviewersindepen- ethodologic quality ) 2 tool. ad a median age of el of 5.1–13.4 ng/ml clinical significance t biopsy, number of RI ranged from 44% g prostate biopsy or

Hospital admissions after transrectal ultrasound- guided biopsy of the prostate in men diagnmosed with prostate cancer: a database analysis from England. Anastasiadis E et al., Int J Urol 2015; 22: 181 - 186

• n = 198.361 men between 2000 – 2008

• 30-days complicationrate: 3.7% • 1.1% Urinary infection / Sepsis • 1.4% Hematuria • 1.3% Urinary retention

• Increase 1998 => 2008 • HR = 1.20, 95% confidence interval 1.08-1.34 • HR = 1.72, 95% confidence interval 1.41-2.10 for infectin/sepsis

Seite 60

Biopsy: transrectal vs transperineal

Transrectal 1

Transperineal 2

Complication

43,6%

0%

Pain

17,5%

0%

Urinary infection

4.5%

0.4%

Prostatitis

0.7%

0%

Urosepsis

65,8%

41,8%

Hematuria

92,6%

N/A

Hematospermia

36,8%

0%

Hematochezie

n.k.

13,4%

Urinray retention

1 DJ. Rosario et al.BMJ 2012;344 2 Porres D et al., DGU 2014

Seite 61

Biopsy PCA-Detectionrates – Comparison Literature

PCA-Detectionrates

Transrectal Saturation (TRUS) 1

30% – 43%

Transperineal (TRUS) 2

62.5%

MRT-supported (biopsynaiv) 3

66%

1 EAU Guidelines on PCA 2 Porres D et al., DGU 2014 3 CM. Moore et al. Eur Urol 63 (2013), 125-140

Neue Tracer und ihre Anknüpfungspunkte beim PET

11 C Cholin PET

Simultaneous 68 Ga-PSMA HBED-CC PET/MRI improves the Localization of Primary Prostate Cancer Eiber et al; Eur Urol (16), 2016

ith

atic

N=66 Patienten

illeirs c ,

12/30 mit Lymphknotenmetastasen

earch IRCCS of Urology, University artment of Radiology, r, New York, NY, USA; rology, LilleUniversity Institute,

Sensitivität PET: 66% Sensitivität mpMRI: 92% Sensitivität PET/MRI: 98%

jor

challenge.

It

has

)

facilitates

localisa-

gnostic accuracy

of

Schlußfolgerung: Höchste diagnostische Genauigkeit bei PET/MRI im Vergleich zu PET und mpMRI

r of Controlled Trials 30, 2014, using the ND‘‘MRORNMROR fusion weighted OR reviewersindepen- ethodologic quality ) 2 tool. ad a median age of el of 5.1–13.4 ng/ml clinical significance t biopsy, number of RI ranged from 44% g prostate biopsy or

Initial Experience of 68Ga-PSMA PET/CT imaging in High-risk Prostate Cancer Patients prior to Radical Prostatectomy. Budäus et al; Eur Urol (15), 2015

ith

atic

N=30 Patienten

illeirs c ,

12/30 mit Lymphknotenmetastasen

earch IRCCS of Urology, University artment of Radiology, r, New York, NY, USA; rology, LilleUniversity Institute,

4 Patienten (33%) richtig positiv 8 Patienten (66,7%) als falsch negativ

jor

challenge.

It

has

)

facilitates

localisa-

Sensitivität: 33% Spezifität: 100%

gnostic accuracy

of

r of Controlled Trials 30, 2014, using the ND‘‘MRORNMROR fusion weighted OR reviewersindepen- ethodologic quality ) 2 tool. ad a median age of el of 5.1–13.4 ng/ml clinical significance t biopsy, number of RI ranged from 44% g prostate biopsy or

Positiv prädiktiver Wert: 100% Negativ prädiktiver Wert: 69,2%

Conclusions

• Ultrasound

➢ initial assessment of patients with increased PSA and/or abnormal DRE, but low diagnostic yield

➢

excellent for biopsy guidance

➢

no screening

➢

no staging

Conclusions

• CT

➢

no value for local tumor detection

➢

lymph node staging

➢

targeted imaging after bone scan

➢

(detection of visceral metastases)

Conclusions

• MRI

➢

optimally depicts prostatic anatomy

➢ primarily detects peripheral zone carcinoma

Conclusions

• Tumour detection

➢

T2-weighted imaging ▪

baseline examination!

➢

MR-spectroscopy ▪ primarily detects higher grade tumours

➢

dynamic contrast enhanced MRI ▪ imaging of tumor neovascularisation

➢

diffusion weighted imaging Minimal requirement in MRI imaging

Conclusions

• MRI

➢ Still not recommended before primary biopsy

➢ Recommendation before secondary biopsy

➢ Rising importance in follow-up under active surveillance

Conclusions

• PET

➢ Indication in primary tumour detection unclear.

➢

Unclear indication during staging.

➢ No indication in case of recurrence with PSA<1ng/ml

➢ Unclear indication and evidence in case of recurrence with PSA>1ng/ml

Bashar Al-Qaisieh

Planning modality

Description

Creation of a plan on the OR just before the implant procedure, with immediate execution of the plan

Intra-operative planning

Stepwise refinement of the treatment plan using computerised dose calculations derived from image-based needle position feedback Constant updating of calculations of dose distribution, using continuous deposited seed position feedback

Interactive planning

Dynamic dose distribution

From Polo et al. Review of intraoperative imaging and planning techniques in permanent seed prostate brachytherapy. RO 94(2010) 12-23.