Mangili [Sola lettura] - AIFM - Mangili... · LDR interstitial brachytherapy can delivery an...

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Associazione Italiana di Fisica In MedicinaCentro di Cultura Scientifica “A. Volta”

Scuola Superiore di Fisica in Medicina “P. Caldirola”(Direttore della Scuola: A. Torresin)

Coordinatore del Corso: C. Marchetti

Impiego di semi radioattivi nel trattamento del carcinoma della prostataP. Mangili, , IRCCS S. Raffaele Milano

Impiego di semi radioattivi nel

trattamento del carcinoma della prostata

P. Mangili, B. Longobardi & R. CalandrinoIRCCS S. Raffaele - Milano

Innovazioni in BrachiterapiaScuola Superiore di Fisica in Medicina “P.Caldirola”

12-14 novembre, 2001 - Villa Olmo - Como

PSA era

Europe: ≈30 / 100.000Incidence of Prostate Cancer

USA: 178 / 100.000

(Wilkinson & Handy, 2001)

↑organ-confined and curable detected cancer

↓patients’ age (diagnosis 6-7 yrs in advance)

Therapeutic efficacy Quality of life

Therapeutic Options

Radical ProstatectomyEBRT

Radiation TherapyBrachytherapy

Androgen BlockageCrioablationHIFURITA

Watchful Waiting

LDR interstitial brachytherapy can delivery anarbitrary prescribed dose to the prostate and to an

additional margin of approximately 5 mm

MonotherapyLocalized prostate cancer

Combined therapy

Brachytherapy limiting factors

Radioactive souces

Predominant isotopes used:

Iodine-125 Palladium-103

Low energyLow half life

Low dose rate

I-125 Pd-103

Energy 28 keV 21 keV

T1/2 59.4 d 16.97 d

Dose-rate 8 cGy/h 24 cGy/h

HVL (tissue) 20 mm 16 mm

HVL (Pb) 0,025 mm 0,008 mm

Physical properties

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125I seed mod 6711Nycomed Amersham

Welded titanium tube containing a silver wire with activematerial, silver iodide (AgI), adsorbed on its surface

Silver wire also provides radiographic identification

103Pd seed - mod 200 Theragenics Corp.

Laser-welded titanium tube containing two graphite pallets plated with 103Pd

Lead marker in between the pallets provides radiographic identification

Point source approximation

Sk = air kerma strength (U = cGy cm2 h-1)

Λ = dose rate constant (cGy h-1 U-1)

1/r2 = geometry factorg(r) = radial dose functionφan (r) = anisotropy factor

( ) ( ) ( )rrgr

SrD ank φ2

1Λ=&

Dose rate calculationAAPM TG 43

The isodose curves are produced by sources with air kerma strength of 100U

Monotherapy Combined(45-50 Gy EBRT+BT)

I-125 145 Gy(ex 160)

110 Gy(ex 120)

Pd-103 125-135 Gy(ex 115)

100-105 Gy(ex 90)

Dose values follow the recommendations in AAPM TG43 & report 69

Clinical properties

RadiobiologyBiologically Effective Dose (BED)

Dose rate effectrepair of sublethal damage (recovery)

repopulation (potential doubling time)

Implant vs EBRT

Clinical properties

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G Steel

I-125:slowly proliferating tumors (Tpot > 15 days)

Pd-103:rapidly proliferating tumors (Tpot < 15 days)

combined with EBRT

(Ling, 1994; Dale, 1998; Peschel 1999 stydy with clinical correlations)

Clinical properties

I-125:edema 50% & T 1/2 = 10 days pre-implant overestimation error: 5%

Pd-103:edema 50% & T 1/2 = 10 days pre-implant overestimation error: 15%

(Chen, 2000; Waterman, 1998)

Clinical properties TIPPB: Procedure Overview

Volume StudyActivity Quality ControlPre-Implant Dose PlanNeedle LoadingImplantSafety ControlPost-Implant Dosimetry

Volume Study

Patient is in dorsal lithotomy position

Uretral catheter (Foley) is insertedSerial transversal images of the prostate at 5mm arerecorded (from the base to the apex)Each image is overlaid electronically with 5mm gridpattern to determine needle and source positions

These slices provide the basis for the treatment plan performed by a dedicated TPS

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Volume Study

The prostate must be centered, within the templategrid layout, on the ultrasound screen “D” column(mid-line sagittal plane)

By convention, the grid is labeled as follows: Vertical column coordinate (letter) Horizontal row coordinate (number)

Volume Study

The posterior-most row of the coordinate grid patternmust lay at least 1-2 mm below the posterior prostateborder in all slices

The posterior prostate border should be flat on the rows

Pubic arch study must be performed (TRUS, CT)

No pubic arch interference

Pubic arch interference

3 mm

4 mm

(Wallner, 1999)

Volume definition:

CTV = Prostate UrethraPTV = CTV + margin Anterior Rectal Wall

A sagittal image serves as a cross-check to thevolume study

Volume Study

GTVthe gross palpable or visible/demonstrable extent and

location of the malignant growthCTV = Prostate

a tissue volume that contains a GTV and/or subclinicalmicroscopic malignant disease, which has to be eliminated

PTVa geometrical concept, it’s defined to ensure that the

prescribed dose is actually absorbed in the CTV

Volume Study

PTV = An enlargement of the CTV (prostate):

2 to 3 mm in the lateral and anterior dimension

No margin at prostate-anterior rectal wall interface

Additional margin at the posterior base (seminalvesicles) and at the apex

Additional margin in cases of large variation betweenadjacent slices

Volume Study

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Activity Quality Control

At least 10% of patient sources (AAPM recommendation)

Rapid strandSingle source Cartridge

Activity Quality Control Quality Control

Pre-Implant Dose Plan

Goals

Minimize areas receiving less than the prescribed dose

Minimize the dose to the urethra

Minimize the dose to the anterior rectum wall

Minimize number of needles

Pre-Implant Dose Plandosimetric constraints

PTV: dose ≥ prescribed dose (98%)

Urethra: dose ≤ 150% prescribed dose

Anterior rectal wall: dose ≤ prescribed dose

Positive biopsy hot spots

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Seeds placed in a regular array at 1 cm spacing

Seeds on adjacent planes offset by 0.5 cm in X and Y

low activity per seed

high dose to the urethra

Pre-Implant Dose Plan uniform scheme loading algorithm Uniform Scheme

Seeds placed mostly near the target perifery

Seeds on adjacent planes offset by 0.5 cm in X and Y

high activity per seed

low dose to the urethra

Pre-Implant Dose Plan peripheral scheme loading algorithm Peripheral Scheme

Modified peripheral scheme

Seeds placed 1 cm apart in most casesSeeds on adjacent planes offset by 0.5 cm in X and Y in most casesSpecial needles can be useLoose seeds can be placed close to the urethra

low dose to the urethradense seed pattern

Pre-Implant Dose PlanModified Peripheral Scheme

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Pre-planned OR-planned

Resolved the problem of pre-planning

and position reproduction

Increased operating time by 15 min

Pre-Implant Dose Plan

TRUS volume study to calculate needed seed

number (NO preplan)

Place approximately 75% of seeds on periphery

and approximately 25% in the central portion

Pre-Implant Dose PlanProseed Method

Assured a dose coverage ≥ 90%

(reference dose:160 Gy)

Many seeds placed outside the prostate

Pre-Implant Dose PlanProseed Method

Needles placement instructions

Source loadings required per needleSpecial needles loading scheme

Summary of sources to be orderedNumber of extra seeds

Isodose distribution - DVH

Pre-Implant Dose Plan Implant Data-Sheets

SeedsPd-103 loose seeds

I-125 loose seedsI-125 suture mounted - 1 cm spacing

4.5 mm long

SpacersAbsorbable catgut suture

5.5 mm long

Needle loading

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Disposable Needles

18 gauge, 20 cm

Echogenic tip - visualize on ultrasound

cm marks on stylet - # seeds in needle

cm marks on needle - manipulation

sealed in sterile package

Stabilization needles – Hawkin’s needle

Needle loading

Remove stylet & plug end with bone waxLoad seed first (tip) followed by spacerAlternate seed/spacer for 1 cm spacingAlways end with a spacer - insert styletPlaced loaded needle in sorting container

Grouped by #seed/needle or template layout

Care must be taken of special needlesNeedles with arbitrary sequence of seeds and spacers

Needle loading Pre-Loaded Needles: Loose Seeds

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Advantages:Load seeds in needles prior to surgeryEasy to alter seed spacing in needles

Disadvantages:Tedious to setup-seed handling & loadingLess flexibility for adding seeds at time of surgery

Needle loading Pre-Loaded Needles: Loose Seeds

I-125 seeds mounted in vicryl suture

Seed spacing 1 cm

Suture thermally stiffened & sterilized

Shipped in plastic spacing inside stainless steelshielding tube

Needle loading Pre-Loaded Needles: Suture Mounted Seeds

Remove stylet and plug end with bone wax ordip needle vertically into molten Anusol-HC

Remove needle and cool for ~ 10 min

Open pre-sterilized packageSharp scalpel-cut along perpendicular groovebetween seeds

Cut excess suture material from the end


Tweezers-grasp suture between seedsGently insert suture strand into needleGently insert stylet into needlePlace needle in sorting box - room temp

Load horizontal so weight of stylet does not push out


Advantages:Decreases needle loading time if bone wax is usedVisual seed count, spacing - no spacersMinimizes seed migrationMinimizes radiation exposure


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Disadvantages:Tendency to stick in needleTime consuming procedure if Anusol-HC usedSuture swells & softens when exposed to bodyfluidsMust load loose seeds in needles if need to alterseed spacing


Seeds fed from a cartridgeLoad seeds in cartridgeAutoclave loaded cartridge

Needle retractor mechanism

Needle loading Mick Applicator

Advantages:Maximum flexibility - ad hocChange source spacingAdd extra sources easilyEliminates pre-loading needles

Needle loading Mick Applicator

Disadvantages:Occasionally jamsRequires more experience than pre-loaded needles

Ultrasound guidance

CT guidance

MR guidance

Implant

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ImplantUS guidance

ImplantUS guidance

ImplantUS guidance

ImplantUS guidance

ImplantUS guidance

ImplantCT guidance

Wallner, 1994

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ImplantCT guidance

Koutrouvelis, 2001

ImplantMR guidance

Cormack, 2000

Plane 0.0

2 mm Seed4.5 mm

Implant Needle release

= 2.5 mm

Implant Needle release

Implant Mick applicator

Safety Control

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Safety Control Safety Control

Actual delivered dose control:

seed placement errors

seed migration

seed loss

change in the prostate volume and shape

post-procedure edema

Post-Implant Dosimetry:rationale

Source placement errors(Roberson, 1997; AAPM TG64)

Prostate motion (rotation and placement)

uncertainties in needle placement or loading

Post-Implant Dosimetry

Prostate motion

Spacing errors: sources are not spaced asplanned(Roberson, 1997)

Splaying errors-tenting: sources are not parallelto the planned needle axis

(mean 300 - Roy, 1993)

Release errors-rotation: sources are releasedalong a curve trajectory(mean 50-100- Nath 2000)


Uncertainties in needle placement

Needle placement errors: all sources from a needleare displaced relative to the planned positionSources loading errors in a needle: distancebetween two seeds is different from the plannedone


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Seed migration:

The fixity likelihood of seeds implanted inthe prostate and in the periprostatic regionis high(>98% - Merrick, 2000)


Seed loss:

In the bladder and/or urethra(urethrocistoscopy )

In other sites(lung embolization:11% loose seeds vs 0.7% rapid strand - Tapen, 1999;10% Merrick, 2000)


Postoperative edema:Increases prostate volume:

cranial-caudal: 11.5% -13.5%anterior-posterior: 8%lateral: 2.5%(Merrick, 1998-2000)

Has variable half life(mean = 10 days - Waterman, 1998-2000;Yue, 1999)


Chen,2000

I-125:

optimum time: 6 ± 1 weeks

post-implant dosimetry ± 8%

Pd-103:

optimum time: 16 ± 8 days

post-implant dosimetry ± 10%

Post-Implant Dosimetry:timing

0-1 day after the implant(Willins & Wallner, 1997; Merrick, 1998-2000, Wilkinson, 2000)

1 month after the implant(Prestidge, 1998;Lee, 2000; Stock & Stone, 2000)

depending on the isotope:I-125: 4-6 weeksPd-103: 2-3 weeks

(AAPM TG64, 1999; Yue, 1999; Roach III, 2000)

Volumes definition + Seeds localization

AP x-raysCross-sectional images:

CTMRITRUSImage fusion

Post-Implant Dosimetry:imaging

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Post-Implant Dosimetry Post-Implant Dosimetry

Post-Implant Dosimetry:procedure optimization

CT/MRI fusion

MRI(different sequences,endorectal coil)

TRUS(echoseed, FDA-4/6/2001)

A. Polo et al. - EIO, Milano ReferenceIsodose


Prostate DVH

D90; D100

V100; V150

Critical structures DVHsIsodose contours + cold-area definition

(sector-analysis)

ABS 1999; ESTRO/EAU/EORTC, 2000

Post-Implant Dosimetry:data sheet

When an implant can be defined adequate?

Post-Implant Dosimetry:evaluation

Post-implant 0-1day after the implant:D80 ≥ prescribed dose

(Willins & Wallner, 1997)

Post-implant at the optimum time:D90 ≥ prescribed dose

(AAPM TG 64, 1999; Stock & Stone, 1998)

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In case of inadequate implant,the clinician has four possibilities:

watchful waitingre-implantandrogen blockadeexternal radiotherapy

Post-Implant Dosimetry:evaluation

Re-implant

94 vs 109 seeds

D90 = 82.3%

123 seeds

D90 = 152.8%

Procedure Optimization

MRSI (magnetic resonance spectroscopy imaging)

Intraoperative plan

Intraoperative post-plan

Radiobiological models (dose escalation)

Post-implant dosimetry for all Pts.

Exhaustive dosimetric data report

Guidelines:patient managementpost-implant dosimetry protocol

Post-Implant Dosimetry:take-home messages

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