Zhang - Intrabeam.pdf

Physics and Dosimetry of the INTRABEAM System: y y yan Intraoperative Brachytherapy Platform

Susha Pillai and Junan ZhangSusha Pillai and Junan Zhang

Scheme

Intrabeam System Physicsy Dosimetry/Radiobiology Clinical Study Clinical Study QA/Workflow

Carl Zeiss INTRABEAM System

Designed for mobile electronic brachytherapy.

Perform IORT treatment in OR, with no special radiation shielding requirements.

M f t d b C l Z i S i lManufactured by Carl Zeiss Surgical , Germany, which acquired Intrabeam as the asset of Photoelectron Corp, USA (bankrupted.)

Received FDA approval for intraoperative treatment in1999.

R i d l i 2005 t t t h l Received approval in 2005 to treat whole body use.- skin, gynecological applications

Operates at 50kVp (breast)/40kVp (brain) d 40 Aand 40A.

Surgical removal of the tumor

Applicator with X-ray probe positioned in the lumpectomy site. Treatment last for about 20 to 50minute to deliver 20Gy in single fraction to the applicator surface

Surgical removal of the tumor

Intrabeam Radiotherapy system components

X-ray probe (XRS unit) Miniature X-ray source 10cm long 3.2mm diameter probe Gold target

INTRABEAM X-ray Source (XRS 4)Energy (max.): 50 kV, 40 AWeight: approximately 1.6 kgDimensions (L x W x H in cm): 17.5 x 11 x 7

Gold target Operates under 50kVp/40 A or 40kVp/40 A. Low energy X-rays emitted isotropic pattern Internal Radiation Monitor (IRM)

Continuously monitor the treatment deliveryIt is a measure of the radiation re-eneters the probe

Beam Deflector

Probe

Internal Radiation Monitor

Probe tip

Spherical Applicators A set of spherical applicators to adapt for varying tumor sizep pp p y g Made of polyetherimide (C37H24O6N2) Size ranging from 1.5cm to 5.0cm with 5mm increment Reusable up to 100 sterilization cycles, biocompatible and radiation resistant can be steam sterilized

Intrabeam Surgical Carrier System 6 degrees of freedom Weight compensation Magnetic brakes Magnetic brakes Easy, flexible and precise probe placement in the treatment area.

Intrabeam cartIntrabeam cartTo store all treatment and QA compoenentsEasy transportation to/from OR roomQA check can be performed on the cart

To avoid schedule OR room for the QA.

Scheme


X-ray probe and dose distribution

Cutaway view of the intrabeam probe

1. Probe tip (made of beryllium, 3. No high voltage p ( y ,allowing x-ray to pass through).

Coated with a film of nickel and titanium nitride.

4. Internal radiation monitor

g goutside of the tube housing to ensure patient and personnel safetysafety

2. Made of Mu-metal. Shield the Earths magnetic field (0.5 G). Sensitivity (0.06mm/G)

Cutaway view of the intrabeam probe

Beam hardening and depth dose curve

Beam attenuated by approximately r-3

The first HVL is 0.11 mm Al for breast treatment (50kVp) and 1.11 mmAl (23.5keV) at 10 mm depth in Solid Water.

The first HVL is 0.10 mm Al for brain treatment (40kVp) and 0.71 mmAl (19.9keV) at 10 mm depth in Solid water.p

50kVp, 40A

Scheme


Prescription Dose

20 G t th li t f d 20 Gy at the applicator surface and 5-6 Gy at 1cm tissue depth.

Radiobiological view:Radiobiological view: Relative biological effectiveness (RBE) Is the dose tolerable?

I th d ffi i t?

Figure adapted from JS. Vaidya 2005

Is the dose sufficient?

Relative Biological Effectiveness (RBE)

RBE i d fi d D /D h D /D RBE is defined as Dref/Dtx, where Dref/Dtx, are respectively the doses of reference radiation and treatment radiation required for equal biological effectbiological effect.

Typically, reference radiation is 250-kV X-ray or Co-60 X-ray. We choose Co-60 in this discussiondiscussion.

As a example, to achieve 0.01 survival level, Dneutron =7Gy, Dref = 10.5Gy. =>RBE=10 5/7=1 5=>RBE=10.5/7=1.5

Biologically weighted DoseFigure adapted from Halls book

=dose XRBE=7Gyx1.5=10.5Sv(Gy). Higher RBE=> Higher Biological Dose


RBE(I t b )?RBE(Intrabeam)? depends on Linear Energy Transfer (LET)

depends on cell surviving level depends on cell surviving level depends on treatment time

Photon Interactions

Photon interaction generates Photon interaction generates secondary electrons though photoelectric effect or Compton scattering.

In PE,bk EhE

In CS

cos11

cos1

hEk

where =hv/moc2

Electron Range

Thumb rule: electron range in Thumb rule: electron range in water is about E(MeV)/2 cm

In other words, all megavoltage electron beams lose kineticelectron beams lose kinetic energy in a similar rate, linear stopping power dE/dx = 2 MeV/cmdE/dx = 2 MeV/cm

=2,000 keV/ 10,000 m =0.2 keV/m

Wh t i dE/d f kil lt What is dE/dx for kilovoltage electrons?

Bremsstrahlung

Radiation energy loss through bremsstrahlung production. The lost energy is converted intoThe lost energy is converted into X-ray.

In water/tissue, radiation energy loss is relatively small.

Collisional Energy Loss

Electrons lose kinetic energy through l t bit l l t lli i ielectron-orbital electron collision, causing

ionizations.This energy loss rate is called linear energy t f (LET) dEtransfer (LET)

Slow electrons get more scattering than fast dx

dELET ion

electrons per track length2

electronvcLET

222 vFtpE

electronv

LET for Secondary Electrons

LET(>1MeV)=2 MeV/cm=0.2 kev/m

LET(10keV)= 20 MeV/cm= 2.0 keV/m

Kilovoltage x-ray has higher LET (of secondary electrons) than Megavoltage x rayMegavoltage x-ray.

RBE varies with LET


RBE(Intrabeam)? depends on Linear Energy Transfer (LET)

d d ll i i l l depends on cell surviving level depends on treatment time


RBE l d d ll i l l l RBE also depends on cell survival level, and corresponding radiation dose.

As a example, at 0.01 survival level, RBE(neutron)=1050/700=1.5

At 0.7 level, RBE(neutron)=300/100=3.0

Figure adapted from Halls book

RBE varies with LET and cell survival level

Linear Quadratic Model

C ll i l 2DD Cell survival Find Dref to achieve the same cell

survival level caused by DIORT . To achieve the same cell survival level

2DDeS

To achieve the same cell survival level.

Solving the equation

22refrefrefrefIORTIORTIORTIORT DDDD

fD

IORTIORTIORTref

IORT

ref

DDD

DD

reftrwIORTRBE

1412

)...(

2

refrefIORT

refrefrefIORT

D

Da

D

0

2

IORTrefIORT D

Chapmens experiment(1977)

Chinese hamster cells.

The value increases with LET untilThe value increases with LET until reaches a maximal around 100-150 keV/m

Th l d t h t hThe value does not change too much and can be considered as a constant.

RBE for intrabeam treatment

For low dose regime , RBE d ithBeam

hardeningRBE decreases with depth due to beam hardening

60

)0(

Co

IORT

IORTDRBE

RBE for intrabeam treatment

For high dose regime , RBE i ith d th d tincreases with depth due to dose attenuation


RBE?RBE? depends on Linear Energy Transfer (LET)

depends on cell surviving level depends on cell surviving level depends on treatment time

After considering cell repairing during tx time.

RBE from radiobiology experiment

RBE and Equivalent Dose of Intrabeam

Depth Physical Dose

RBE Equivalent Dose

Surface 20 Gy 1~1.2 20-25 Gy10mm 5-6 Gy 1.5 ~8 Gy25 mm ~2 Gy 2 ~4 Gy

Biological dose decreases slower than physical dose as the depth increases.

Fractionation effect

))2()2(( 22 GyGyanDaD IORTIORT

respondinglateGa

respondingearlyGa

aGyGyaGyGyn

355

1030

]/21[2/22122

It is estimated that an external-beam dose of 60 Gy given in 30 fractions at 2 Gy per fraction is equivalent to a single intraoperative radiotherapy fraction of 2022 Gy (with an / ratio at 10 Gy considered typical for tumours and acutely reacting tissues).

With this same regimen, but when the tolerance of late-responding tissues (/ ratio at 3 Gy) is taken in to consideration, the equivalent value is at least 110 Gyvalue is at least 110 Gy.

However, the linear-quadratic model is reliable only for single doses up to 68 Gy, and therefore might not be appropriate for modeling the effects of higher single doses (2025 Gy) used in intraoperative radiotherapy orof higher single doses (20 25 Gy) used in intraoperative radiotherapy or radiosurgery.

Scheme

Intrabeam System Physics y Dosimetry/Radiobiology Clinical Study Clinical Study QA/Workflow

TARGIT-A trial

Ph III t d ff ti f I t b th f Phase III study: effectiveness of Intrabeam therapy for prevention of local breast ca recurrence

Rationale: 90% of local recurrence occur near the original gtumor location (index quadrant).

Randomized study conducted in 28 centers in 9 countries. 2232 breast cancer patients; 1113 was scheduled for 2232 breast cancer patients; 1113 was scheduled for

intrabeam therapy Rest was scheduled for conventional whole breast therapy. age over 45 or older with uni-focal invasive ductal carcinoma. Breast conserving surgery before therapy. Four years follow up Four years follow up

Local Recurrence

T o trail arms sho ed no significant Two trail arms showed no significant difference in local recurrence:

1.2% for TARGIT arm vs 0.9% for control arm (6 v s 5 cases at 4 years)control arm. (6 v.s. 5 cases at 4 years)

Clinically significant complications

Incidence rate of major toxicity was similar between two arms Targeted IORT patients have a higher risk of seroma and delayed wound healing . EBRT whole breast patients have a higher risk of RT related complication EBRT whole breast patients have a higher risk of RT-related complication.

Scheme

Intrabeam System Physics/QAy Dosimetry/Radiobiology Clinical Study Clinical Study QA/Workflow

Intrabeam Quality Assurance Tools

Manufacturer provided full set of radiation shielded QA instruments.

PDA(Photodiode Array)PDA(Photodiode Array) Contains five photodiodes at orthogonal

positions Isotropy check

PIACH (Probe adjuster/ionization

Mount for ion chamber

PIACH (Probe adjuster/ionization chamber holder) Measures and adjusts the straightness of the

probe manually Inbuilt thermometer for temperature/pressure

PAICHPDA Inbuilt thermometer for temperature/pressure

correction Mount for ionchamber

High precision water phantom (optional/send back to factory to QA)

Water phantom

(optional/send back to factory to QA) To perform independent verification of the

depth dose and Dose distribution Radiation shielded with lead glass.

M h i l iti i f +/ Mechanical positioning accuracy of +/-0.1mm

Probe straightness

X (XRS) b t X-ray source (XRS) probe can not be bended. Handle it with care.

Always use V-block guide to insertAlways use V block guide to insert XRS into QA devices.

XRS probe straightening (PAICH)

PAICH

Manually straighten the probe using a plunger if needed

Rotate PAICH 360deg aroundPlunger

Rotate PAICH 360deg around the XRS probe

LED/photo detector unit tracks the probe position Cross sectional viewthe probe position

Runout value less than 0.1mm ( ~0.07mm)

XRS probe

Dynamic offset (PDA)

Electronic alignment of the XRS probe Align the electron beam direction with the

mechanical center of the probe

PDA

Steering of electron beam based on the five Photodiode readings

Mechanical alignment of the probe should g pfollowed by Dynamic Offset check. XRS

PDA source check

Verify the isotropy of the X-ray beam emits from the probe tip Compare the voltage measured by the five photodiodes

located inside the PDA

f Measurement of count rate with the Internal Radiation Monitor (IRM) IRM is located inside the XRS probe

PAICH output check

PAICHIon chamber

Soft X-ray chamber & PTW electrometer In-air measurement of the current

Corrected for Temperature and pressure XRS b

PAICH

Corrected for Temperature and pressure (10% tolerance)

PAITCH output (Gy/min) DTreat= IT P (A) * Nk (Gy/C) * kQ *(60s/min)

XRS probe

IT.P (A) Nk (Gy/C) kQ (60s/min)

IT.P is the measured current after temp pressure correctionpressure correction.

Nk is the dose calibration factor of the parallel plate IC.

k i th ti f tPTW Unidos Electrometer

kQ is the energy correction factor.

PAICH does not pro ide absol te doserateWater phantom

PAICH does not provide absolute doseratein any water depth.

However since all PAICH units andionization chambers features an identicalionization chambers features an identicaldesign, it is possible to compare in-airmeasurement at custom side to in-wartermeasurement at factory and custom side

d th t d t i th b l t d tand thus to determine the absolute dose rateof XRS prior to treatment.

D(Paich) in air Corrected dose in water(XRS probe) apply transfer function for applicator apply PDD for the XRS source= gives you the dose at treatment depth= gives you the dose at treatment depth

Intrabeam Treatment Workflow

1) Applicators sterilized and kept in the OR1) Applicators sterilized and kept in the OR2) QA procedure must be performed within

36hrs of each treatment.3) Lumpectomy procedure4) A th it i d l t th4) Assess the cavity size and select the

proper applicator5) XRS probe and the Intrabeam stand are

covered in a sterile polyethylene bag6) S th li t t th XRS b6) Secure the applicator to the XRS probe7) Position the applicator in the

lumpectomy cavity (Surgeon/RadiationOncologist)

8) If necessary, the chest wall and skin can be protected (95% shielding) by radio-opaque tungsten-filled polyurethane caps. (avoid significant skin doses that occur with distances of

Intrabeam Treatment Workflow

9) Place tungsten-filled drape for shielding10) Treatment plan

Entry of treatment parametersD t i i i Does not require imaging

Some centers use ultrasound to document the distance from the skin

11) Treatment parameter verification Applicator size Prescription dose Treatment depth

12) Treatment delivery time is about 20 to12) Treatment delivery time is about 20 to 55mins

13) Radiation survey14) Evaluation and documentation of Treatment

recordsrecords

Shielding and Radiation Survey

Electronic brachytherapy

Currently, there are two electronic brachytherapy (EBT) devices available for partial breast irradiationpartial breast irradiation.

The End

Thank you!

Documents

Zhang - Intrabeam.pdf