International Symposium “Standards, Applications …...INV015, “New brachytherapy standards paradigm shift”, Maria Pia Toni, ENEA-INMRI IAEA International Symposium "Standards,

INV015, “New brachytherapy standards paradigm shift”, Maria Pia Toni, ENEA-INMRIIAEA International Symposium "Standards, Applications and QA in Medical Radiation Dosimetry (IDOS)“, Vienna, 9-12 November 2010

Maria Pia Toni

Istituto Nazionale di Metrologia delle Radiazioni Ionizzanti

Agenzia Nazionale per le Nuove Tecnologie, l’Energia e lo Sviluppo Economico sostenibile Italy

International Symposium “Standards, Applications and QA in Medical Radiation Dosimetry ”

November 9−12 2010, Vienna, Austria

New brachytherapy standards paradigm shiftNew brachytherapy standards paradigm shift


inci

den

ce o

f dam

age

(%)

tum

or

contr

ol (%

)

Dw dose delivered (a.u.)

A lower dose delivered to the target volume could result in lack of tumor

control

Increasing damage

to healthy tissue could result from

exceeding the tolerance levels

uclinic

< 5% (k = 1)

Dw , is the quantity of interest for dosimetry in radiotherapy, this includes either the dosimetry of external radiation beams or the dosimetry of brachytherapy (BT) sources.

The IAEA TRS 398 (2000) recommends a direct traceability chain starting on Dw primary standards:

Rationale for a paradigma shift in BT dosimetry

to avoid additional uncertainties in the measurement of Dw and to optimize the dose delivery in radiation therapy;

to achieve the goal of 5% (k = 1) for the uncertainty of the dose delivered to the target volume at reference conditions, in the clinic.


In external beam dosimetry, Dw primary standards are currently operating for dosimetry of external radiation beams used in radiotherapy and the uncertainty on Dw,1 cm is about 2% (k = 1).

In BT dosimetry, no Dw primary standards have been so far made available for dosimetry of the gamma sources used in current BT treatments and the uncertainty on Dw,1 cm is typically from 5% to 8% (k = 1).



(a) Brachytherapy sources and (b) transfer standards

calibrated in terms of Reference Air Kerma Rate.

(a) Air Kerma primary standards and secondary standards calibrated in terms of air kerma for the energy

spectrum of brachytherapy sources or (b) Reference Air Kerma Rate

primary standards.

STATE OF ART(a)

(b)

( ) ( )( ) ( ) ( )θ

θθθ ,

,,,

00

rFrgrGrGSrD KW ⋅⋅⎥

⎦

⎤⎢⎣

⎡⋅Λ⋅=&

dose rate constant

Conversion from Reference Air Kerma Rate to Absorbed Dose Rate to water (AAPM TG 43)

(a)

(b)

A significant part of the uncertainty in current BT dosimetry is due to this lack of metrology, because the conversion procedure needed for BT dosimetry is a relevant additional component of uncertainty on the final value of the absorbed dose imparted to the patient.



National medical associations and scientific internationa l organizations ─ESTRO, AAPM-BTSC, IAEA, ICRU,

BIPM and

EURAMET─

have ongoing research programs in the field of Brachytherapy and encouraged the metrological community to develop

absorbed dose standards to assure direct traceability

of brachytherapy sources.

The European project “Brachytherapy”

is establishing absorbed

dose primary standards for brachytherapy.

8%

7%

5%3%

9%

68%

gynaecologyprostatebreastbronchushead & neckothers

Main sitesof tumor

treated with Brachytherapy(ESTRO, 2007)

This new approach is expected to improve the accuracy of brachytherapy dosimetry towards a level comparable to that typical of dosimetry in radiotherapy with external beams.



The project “Increasing cancer treatment efficacy using 3D Brachytherapy” is one of the 21 European Joint Research Projects in metrology selected for funding in 2008 within the action iMERA plus under the Seventh Framework Programme

for research

and technological development of the European Commission.

The European Commission

co-fund the project according to the

Grant Agreement No. 217257

signed with the European

Association of National Metrology Institutes (EURAMET e.V.).

The project was launched on July 2008

for a period of 36

months

(ending in June 2011), with code T2.J06

and short name

“Brachytherapy”.



This collaborative research project refers to research in ionizing radiation metrology focused on the program “TP2:

Health” in the European

Metrology Research Programme.

It responds to the necessity that:

the dose measurements for brachytherapy treatments be traceable to absorbed-

dose-to-water primary standards;

the uncertainty

on the dose delivered to

the target volume be within international accepted tolerance levels.

Target programmeTP2: HEALTHIn our centre

the Human as theMeasurement Object



PARTICIPANTS

The project puts together the research and measurement capabilities of ten European National Metrology Laboratories

in the field of ionizing

radiation:BEV

(Austria); CMI

(Czech Republic);

ENEA-INMRI

(Italy); ITN

(Portugal);

LNE-LNHB

(France); VSL

(The

Netherlands); NPL

(United Kingdom);

PTB

(Germany); SSM

(Sweden); STUK

(Finland).

Project coordination has been entrusted to the ENEA-INRI, Italy (Dr. Maria Pia Toni).



Collaborations for research activities were formalized with:

the company PTW-Freiburg GmbH, Germany

the company IBA Dosimetry

GmbH, Germany

the Linköping

University, Sweden

A scientific collaboration has started with the BRAPHYQS (BRAchytherapy PHYsics Quality assurances System ) group of GEC-

ESTRO as representative of the project end users.

The chair of the BRAPHYQS group, dr. Frank-Andrè

Siebert, gives his contribute to “Brachytherapy”

project meetings.



Absorbed dose to water primary standards for brachytherapy sources based on calorimetry (a) or ionometry (b) and Monte Carlo based conversi on procedures

Brachytherapy sources (a) and transfer standards (b) directly calibrated in terms of Dw, 1 cm

(a)

(b)

(a)

(b)

The joint research project “Brachytherapy” developed absorbed dose primary standards for brachytherapy for a more sound metrology and with a target uncertainty on the absorbed dose imparted to the patient in the future brachytherapy practice:

u (Dw

, 1 cm) less than 5% (k=1)


OBJECTIVES


Dw

STANDARDSFOR LOW DOSE RATE BRACHYTHERAPY SOURCES

(prescription dose rate from 5 to 20 mGy/min)

Development and commissioning of a set of three independent primary standards

to allow the determination of the DW

at the reference distance of 1 cm from the source, with an uncertainty u(Dw

) ≈2%, k=1.

Standards are based on ionometric methods

(the more

appropriate due the low intensity of the sources): wide-angle and/or variable volume ionisation chambers.

A preliminary comparison exercise has started to assess the standards agreement and identify possible errors (results should be available by February 2011).

New brachytherapy standards for LDR BT sources


Dw

STANDARDSFOR LOW DOSE RATE

BRACHYTHERAPY SOURCES

(prescription dose rate from 5 to 20 mGy/min)

1 cm

S

Air

Water

S,wK&

LNE-LNHB standard based on a free-in-

air ring-shaped ionisation chamber

and a water equivalent spherical

source phantom assembly.

PTB standard based on a large

extrapolation ionisation chamber

with water equivalent front and back walls.

ENEA standard based on a

large angle and variable volume

ionisation chamber that allows measurements in

graphite phantom.

New brachytherapy standards for LDR BT sources


The LNE-LNHB is establishing a two-step procedure to overcome practical difficulties encountered when measuring Dw .

K&

The LNE-LNHB primary standard development in terms of Dw

for 125I brachytherapy seedsI. Aubineau-Lanièce, P. Aviles-Lucas , J.-M. Bordy, B. Chauvenet, D. Cutarella, J. Gouriou, J. Plagnard

1 cm

Water

?wD&

Air

wcolK ,&

1 cm

What we want to assessTheoretical configuration really considered -> a correction factor will be applied to compensate for the lack of backscattering photons because the water sphere is surrounded by air instead of water.

Liquid water is replaced by PMMA -> a correction factor will be applied for the non perfect equivalence of PMMA with liquid water

1. Determine the water at the surface of a 1 cm radius water equivalent spherical phantom placed in air and containing the LDR seed in its centre.

1 cm

Air PMMA

PMMAcolK ,&

The LNE-LNHB Dw

primary standard for 125I BT seeds


The LNE-LNHB is establishing a two-step procedure to overcome practical difficulties encountered when measuring Dw .

2. Use a free-in-air circular ring-shaped ionization chamber to measure and apply appropriate MC correction factors to go from to

aircolK ,&

aircolK ,& PMMAcolK ,

&

=wD& .1.)1(

1.1..ge

w

airair −⎟⎠⎞

⎜⎝⎛

ρI.

V ∏i

ikglobalF

The LNE-LNHB Dw



The PTB Dw



This factor converts the difference of air kerma at chamber deptThis factor converts the difference of air kerma at chamber depths xhs xii a a and and xi+1xi+1 directly into the water kerma at chamber depth x=0 .directly into the water kerma at chamber depth x=0 .

As in phantom extrapolation measurements are having a nonlinear As in phantom extrapolation measurements are having a nonlinear dependence of dependence of Q(x)Q(x) due to attenuation and scatter, a Montedue to attenuation and scatter, a Monte--Carlo Carlo based conversion factor was introducedbased conversion factor was introduced

New extrapolation concept for the GROVEX IINew extrapolation concept for the GROVEX II

If the thickness of the chamber front wall is equivalent to 1 cm of water, then: )1()0( cmDK W

PhW

&& ≅

The PTB Dw



Measurements with the Grovex II in the PTB reference fields for X-radiation

The PTB Dw



graphitepolystyrene air lead

dxxdQ

meWxD

aa

)(1)( =

)(1)()(1)()()( νρ

ννρ

ννν eaeaa divKdivBKD Ψ−≅Ψ−−= Ephotons

< 40 keV

[ ] eiia

aa xQxQme

WdKdKii

ΔΨ+−=− +∫∫+

)()(1)()( 1

1

νννννν

∫ ∫+

+

−

=

1

1

)()(

)0(),(

x x

ii

V Vaa

gMCxx

dKdK

KC

νννν

effective measuring volume

Δx

P

x

variable measuring volume

x0

P

r = 30 cm

source P

P0r

source

P

1

2 3

The ENEA-INMRI Dw


Potential rings (V/2)

Set-up A

( )[ ] eMC

xxiiMC

xxgiiii

CxQxQCAe

WPK ΔΨ+−=++

+ ),(1),(11

)(1)(

)()()( , PKCPKPD gMC

wgww =≅ )()(0

,0 PDCPD wMC

PPw ⋅=


Preliminary results by Monte Carlo calculation EGS code (set-up A)

The measurement method applied to the ENEA-INMRI standard was developed by PTB as described in:

T Schneider, B Lange and H-J Selbach, Towards a determination of the absorbed dose to water in water for low-energy photon-emitting brachytherapy seeds, Metrologia 44 (2007) 407–414

T Schneider, A method to determine the water kerma in a phantom for x-rays with energies up to 40 keV, Metrologia 46 (2009) 95–100

ongoing

The ENEA-INMRI Dw


N.B.Minimum chamber depth x0 and distances between the

effective measuring volume and the lateral chamber wall are greater than the CSDA range for secondary particles generated in air by photons with E < 40 keV


graphitepolystyrene air lead

dxxdQ

meWxD

aa

)(1)( =

)(1)()(1)()()( νρ

ννρ

ννν eaeaa divKdivBKD Ψ−≅Ψ−−=

[ ] eiia

aa xQxQme

WdKdKii

ΔΨ+−=− +∫∫+

)()(1)()( 1

1

νννννν

effective measuring volume

ΔxP

x

variable measuring volume

x0

P

source

source

The ENEA-INMRI Dw


Potential rings (0 ÷ V)

P0

P0

)(')()( ,00 ogMC

wgww PKCPKPD ⋅=≅

( )[ ] eMC

xxiiMC

xxgiiii

CxQxQCAe

WPK ΔΨ+−=++

+'

),(1'

),(011

)(1)(

( )( ) ( )∫ ∫

+

+ −=

1

1

0'),(

x x

ii

V Vaa

gMCxx KK

PKC

νν

Ephotons

< 40 keV

1

2

Set-up B


Dw

STANDARDSFOR HIGH DOSE RATE


(prescription dose rate of 200 mGy/min or higher)

Development and commissioning of a set of four independent primary standards

to allow the determination of the Dw at the

reference distance of 1 cm from the source, with an uncertainty u(Dw

) ≈2%, k=1.

The standards are based on calorimetry: water calorimeters and graphite calorimeters.

A preliminary comparison exercise has started to assess the standards agreement and identify possible errors (results should be available by February 2011).

New brachytherapy standards for HDR BT sources


Dw

STANDARDSFOR HIGH DOSE RATE


(prescription dose rate of 200 mGy/min or higher)

Thermistor (4x)

Heat sink (Al) Glass cell wall

NPL standard based on a ring-shaped graphite

calorimeter

ENEA-INMRI standard based on a ring-shaped graphite

calorimeter

VSL standard based on water calorimeter

PTB standard based on a water calorimeter

New brachytherapy standards for HDR BT sources


Detector arrangement changed for use with HDR BT sources

possible meassurement positions: +60 mm, +48 mm, +24 mm, -24 mm

stainless steel needle for 1.1 mm source

The PTB Dw

primary standard for 192Ir HDR BT sources


The PTB Dw


Detector arrangement changed for use with HDR BT sources


PEEK

cell wall

Thermistor (4x)

Source

entranceconnected to after‐loader

Glass cell wall

Aluminum

heat sink

The VSL Dw



Validation heat transport model

The VSL Dw



Wednesday, 17 November 2010

27

Complete

system of NPL’s new brachytherapy calorimeter

Measurement electronics:

Nanovoltmeters

Power supplies for heaters

Wheatstone bridges for sensors

Vacuum pump

Vacuum housing for HDR brachytherapy graphite calorimeter

Electrical connections of heating and sensing thermistors

The NPL Dw



Wednesday, 17 November 2010

Ring shaped graphite core (2 mm x 5 mm, radius = 2.5 cm)

Sectional view

Vacuum gaps between core, inner graphite tubes and central aluminium tube to control source self-heating

Cylindrical graphite phantom (radius = 10 cm, height = 14 cm) enclosed in vacuum can (not shown)

HDR brachytherapy source will be inserted through aluminium tube

Objective: Direct measurement of absorbed dose to graphite at 2.5 cm due to HDR 192Ir brachytherapy source conversion to quantity of interest: absorbed dose to water at 1 cm

The NPL Dw



Schematic section of the ENEA-INMRI calorimeter (left) with the core in black and the calorimeter assembled (right) in the PMMA housing, (13 cm ext dia, 10 cm int dia ).

medium

top graphite disc with source holder

sou

rce h

old

er

heate

r h

old

er

Bottom graphite disc

j-co

re b

ase

PM

MA

ho

usi

ng

j-co

re b

ase

mediumh

eate

r h

old

er

PM

MA

ho

usi

ng

The ENEA-INMRI Dw



Left: the core and the jacket base fixed to the jacket-core base after embedding the thermistors in the core and in the jacket base. The core is suspended on the jacket base by 3 polystyrene 1 mm dia pins.

The ENEA-INMRI Dw


Right: detail of the core and the 0.3 mm dia NTC thermistor, used in the core and in the jacket.


20 c

m

20 cm13 cm

11 c

mThe calorimeter is inserted in a larger graphite phantom (left) to ensure at the core position the full backscattering conditions for 192Ir .

On the right, detail of the 3D heat transfer calculations: irradiation

The ENEA-INMRI Dw



MethodologyStar-shaped comparisons

Indirect comparisons by circulating two transfer standard instruments from one NMI to another, for each comparison

Two ionisation well-type chambers of different types have been selected to act as transfer standard instruments: the same chamber models, but different samples, for LDR and HDR comparisons

Each partner will have to determine:

the calibration coefficient of the transfer instruments based on the value determined with its novel primary standard for its own source .

the calibration coefficient of the transfer instruments in terms of to allow an experimental determination of the conversion gamma constant Λ

with an improved uncertainty.

WD&

RK&

Novel LDR&HDR standards comparison exercises


Transfer standard instruments

PTW 33004

Outer Height 19.05 cm

Outer base diameter 17.8 cm

Outer well diameter 9.3 cm

Inner well diameter 3.2 cm

Weight 2.4 kg

Volume 200 cm3

Potential of HV electrode with respect to collecting electrode

300 V

SI HDR 1000+(ref 90008)

Height 15.6 cm

Diameter 10.2 cm

Weight 2.7 kg

Volume 245 cm3

Potential of HV electrode with respect to collecting electrode

300 V



SOURCES USED FOR THE LDR COMPARISON

BEBIG IsoSeeds® I-125 sources (reference I25.S16)

The IsoSeeds® I-125 sources contain a cylindrical-shaped ceramic saturated with an iodine-125 compound, which is enclosed in a laser- welded titanium tube.

Range Air kerma strength(µGy m²/h)

Apparent activity (mCi)

Apparent activity (MBq)

A25 26.10 – 31.75 20.6 – 25.0 761 - 925




35

Nucletron microSelectron-v1 classic HDR 192Ir source (PTB and NPL)

Nucletron microSelectron-v2 HDR 192Ir source (ENEA-INMRI and VSL)

SOURCES USED FOR THE LDR COMPARISON


LDR comparison schedulePTB provided the transfer chambers and carry out the stability checks

The participants will have two weeks to realize the calibration of both transfer chambers.

The instruments will circulate according to the schedule given below.

All the results would be exchanged between participants at the end of January

Measurements at NMI

PTB: from 13 to 26 September 2010 (done)

LNE-LNHB: from 04 to 17 October 2010 (done)

ENEA-INMRI: from 15 to 28 November 2010

PTB

LNE- LNHB

ENEA - INMRI

Stability checks



NPL provided the transfer chambers and carry out the stability checks

Calibration at PTB:7-18 Jun 10 (done)

Calibration at VSL:6-16 Jul 10 (done)

Calibration at ENEA-INMRI:25 Oct - 7 Nov 10 (done)

All the results would be exchanged between participants at the end of January

ENEA- INMRI

(I)

NPL

Stability check

PTB(DE)

NPL(UK)

VSL(NL)

1 2

3

4

56

7

8


HDR comparison schedule


Dissemination of the novel BT standards

Dw

BASED METROLOGICAL CHAIN

The final objective of the “Brachytherapy” project is to implementat a metrological chain to assure the traceability

of brachytherapy dosimetry to the new absorbed dose to water standards.

Transfer standard:

well-type ionization chamber;

small volume ionization chambers associated with water phantom

plastic scintillator dosemeters (PSDs) associated with water phantom


System with six 0,0System with six 0,088

cmcm33

ionizing chambers for ionizing chambers for measurements in water phantom


Well type chambers acting Well type chambers acting as transfer standard as transfer standard (dose (dose calibrators) calibrators)


Development of the secondary standard based on well-type ionization chamber

(PTW TM33004):

BEV secondary standard for absorbed dose to water quantity for brachytherapy sources was calibrated at the PTB.

Calibration sheet was issued also for NDw quantity with source relevant Λ conversion factor experimentally determined according to the new standard.



What does it change in treatment plans?

( ) ( )( ) ( ) ( )θ

θθθ ,

,,,

00

rFrgrGrGSrD KW ⋅⋅⎥

⎦

⎤⎢⎣

⎡⋅Λ⋅=&

The updating of the tretment plans for the shift from Air kerma to Absorbed dose to water as reference quantity for calibration of BT source just need to substitute the product (Sk L) with Dw , in the formalism of the AAPM TG 43 protocol:

Dw


A three-day scientific Symposium is organized to present the results obtained to the interested Medical Physics community and promote a updated brachytherapy dosimetry protocol based on direct calibrations in terms of Dw .

The symposium is organized together with the project “EBCT” that deals with external beam cancer therapy using ionising radiation and high-intensity ultrasound

Title: "Symposium on developments in physical measurement for cancer therapy".Period: 29.11.2011 to 01.12.2011. Place: PTB, Braunsweigh, Germany

Representative of the association and task group relevant on these topics are expected to contribute to the symposium



A set of Dw primary standards have been developed within the project “Brachytherapy”.

The dissemination of project results is of direct interest to the international community of radiotherapy centres performing BT clinical treatments.

The possibility given by the present project of basing BT dosimetry on Dw primary standards will potentially increase the accuracy and safety of BT to a level comparable to that typical of radiotherapy with external accelerator beams.

Conclusion


Conclusion

Based on the current developments, a progress is encouraged for a more direct and accurate traceability chain of BT sources according to the demand for a more sound metrology and an optimization of dose delivery in BT treatments.

No efforts are required at SSDL or clinic level: the same reference chamber (well type ionization chambers) could be still used and to update the software for treatment plan results easy.


Organization, late next year, of a key comparison to validate the new Dw BT standards.

Implementation of a Dw based metrological chain to disseminate the new standards througt the SSDL laboratories

Availability of calibrations in terms of DW to brachytherapy centres.

Availability of updated protocols in terms of DW for more accurate dosimetry to brachytherapy centres.

Future work


The research within the EURAMET joint research project “Brachytherapy” receives funding from the European Community’s Seventh Framework Programme, ERA-NET Plus, under the iMERA-Plus Project - Grant Agreement No. 217257.

The author would like to thank the partners of the “Brachytherapy” project for their support to this contribute.

In particular:Isabelle Aubineau-Lanièce

(CEA, LIST, Laboratoire National Henri Becquerel, France),Thorsten Sander

(National Physical Laboratory, United Kingdom),Hans-Joachim Selbach

(Physikalisch-Technische Bundesanstalt, Germany), Jacco de Pooter

(Van Swinden Laboratorium B.V., The Netherlands).

Acknowledgements


Documents

International Symposium “Standards, Applications …...INV015, “New brachytherapy standards paradigm shift”, Maria Pia Toni, ENEA-INMRI IAEA International Symposium "Standards,