Delivery and Verification

Lutters, SRO 2011 PSI, 24.10.2011

Our goal today?

How do you define DELIVERY?

How do you define VERIFICATION?

Good DELIVERY

..

..

Good VERIFICATION

….….

Our goal today?

DELIVERY and VERIFICATION depend on

1. Mechanical properties

2. Particles physical properties

3. Mathematical models

4. Work flow/System integration

5. Patient anatomy and biology

6. Staff training and education

7. User/Patient acceptance

8. Resources, Cost, Reimbursement

9. Error free and safe to use!

Figure 2.5 (a) The Seed-Selectron with the (b) double cassette for the 125I sources

and the spacers. (Courtesy Nucletron)

Brachy seed therapy

Figure 2.10 (a) The Guidant Galileo (TM) Afterloader is using a 32P-wire source with

stepping source technology. A touch screen allows to enter the treatment parameters.

This image illustrates a possible calibration procedure with the delivery catheter inserted

into a well type chamber. (b) The 90Sr source train of the Novoste BetaCath(TM) device

is moved into the delivery catheter by using a hydraulic mechanism. During storage and

transportation the device is located in a lead storage box.

Brachy afterloader therapy

intravascular

Fig. 6. (a) Digital subtraction angiography (DSA)

of stenotic (50% luminal reduction) lesions of

left femoro-popliteal artery with normal

segment in between.

(b) DSA of proximal PTA balloon position (4 cm

length/5 mm diameter) indicating a 45 mm IL.

(c) DSA of distal PTA balloon position (4 cm

length/5 mm diameter). This second balloon

position is overlapping the proximal PTA

position expanding the IL to 75 mm.

(d) X-Ray veri®cation of 7F PARIS delivery

catheter showing the 105 mm ASL resulting in

a 100 mm RIL. Provided in co-operation with

Professor Erich Minar, MD, Division of

Angiology, Department of Internal Medicine II,

University Hospital Vienna, Vienna, Austria.

Brachytherapy

Fig. 3. (a) Cross-sectional

image of a coronary artery

from IVUS. Source,

IVUS probe and EEL are

shown. The RLDi, the isodose

lines indicating the

RLDo and the RDD, the RLDP

and the RDDP as determined

based on

angiographic ® findings are

superimposed onto the IVUS

image.

Brachytherapy

Figure 2.4 (a) The Nucletron Selectron LDR

afterloader for 137Cs pellet sources in clinical

operation

(afterloader inside the room, control unit

outside the room), and (b) the mechanism of

the source and

dummy-source selection of the device.

(Courtesy Nucletron)

Brachytherapy

Figure 2.7 Modern afterloading machines for

HDR techniques: (a) the MicroSelectron HDR

(Courtesy Nucletron), and (b) the curietronmultisource HDR (Courtesy BEBIG),

Brachytherapy

Figure 2.9 The guiding system for the check cable and the source cable of the

Nucletron MicroSelectron HDR device. In the off-position, the source is located in the

center of the tungsten safe. From there, the source can be transported through the

indexer ring to the source transfer tubes (not shown). (Courtesy Nucletron)

Brachytherapy

Figure 2.11 (a) A double C-arm fluoroscopic system integrated into the operating

theatre equipment, making the direct transfer of images to a treatment planning

system possible. (b) Images of a head-and neck implant. Due to the relatively high

cost of such integrated brachytherapy units, these systems have not found wide

distribution in the departments. (Courtesy Nucletron).

Brachytherapy

Fig. 7. Position of a library applicator (in the middle) in the transversal (left) and

sagittal (right) plane.

Brachytherapy

Figure 3.4 A Standard Imaging well type

ionisation chamber. Dedicated inserts can be

used for calibration of specified source types

at well-defined source positions. (Photograph

provided with courtesy by Varian)

The “Krieger” phantom (DGMP 1999a)

connected to a Varian afterloading unit. For

each phantom design (distance between

sources and ion chamber, size and material of

the phantom) and source type the correction

factor for lack of full scatter needs to be

determined separately.

Brachytherapy

Figure 6.2 Check ruler and marker wire to

determine the programmed position of the

source in a stepping HDR or PDR source

afterloader. (Courtesy Varian), (b) Set of

orthogonal images taken on a C-arm X-ray unit

of a uterine tube and two shielded ovoids

showing the position of the shields inside the

ovoids. (Courtesy Varian)

Brachytherapy

Figure 6.3 (a) Autoradiograph of the source positions programmed with an HDR

afterloader with 6 catheters placed directly on the surface of a verification film

(Kodak XV film). (b) The “Baltas” phantom, designed for geometry checks in

brachytherapy.

Brachytherapy

IORT (Novac7)

Novac7 and MOBETRON: The first scope of

application was in breast cancer, at that time the

big innovation was the boost radiation or in a

single dose and at the same time as the

resection in the operating room (ELIOT).

Intraoperative radiotherapy (IORT) using PeC (Carl-Zeiss) system is a method of

delivering conformal radiotherapy to the tumor region. The small tumors (2-4 cm

diameter) of the brain and breast cancer are precisely excised and irradiated using

special IORT applicators and verified by onsite pathologists providing frozen

section pathology input.

IORT (IntraBeam)

IORT (IntraBeam)

MammoSiteMammoSite-catheter is placed in the cavity after surgery and filled with saline solution.

Two times a day for five days a HDR unit moves the source into the balloon.

MammoSite

Also MammoSite-treatment can be planned with modern TPS. The optimization of dose distribution, adaption to target volume is limited.

IORT Comparison

IORTProblems: Dosimetry (6 and 18MeV electrons, angled and straight)Either Linac in surgery theatre (shielding!) ordesinfection of Linac bunker

X-Ray EBRT

1. Energy 20-80kV (superficial) or 80-300kV (ortovoltage)

2. Dose distribution fixed by applicator shape and size (Individual cut-outs)

3. Depth dose depends on tube length

1. Difficult targeting and dosimetry

2. Low cost and complexity

3. Used for benign tumors, inflammatory diseases

EBRT devices with radioactive sources

Gammaknife

An Elekta Leksell gamma knife used in radiosurgery of the head

Single day treatment, stereotactic ring fixed in scull, precise

Boron Neutron Capture

Boron Neutron Capture

Accelerator based systems

Depth dose comparison (focus to superficial tumors i.e. breast cancer)

What is the best modality?

C-Arm Linac head

C-Arm Linac add-ons

EPID

Treatment Table

External coordinate system (laser, camera)

Fluoroscopy & cone-beam CT system (kV, MV)

Record and verify

Linac

Construction of the head of Elekta Precise®

accelerator

[1].

Figure

Accelerating structure of Elekta Precise® [2].

C-Arm Linac

MLC design

MLC design

Flattened beam vs. IMRT

Reasons?

Optimal Plan? Optimal delivery?

Who does better?

•Linac mechanics

•Beam production

•Record and Verify

•Imaging

Or is TPS or R&V insufficient?

Movement of Linac and Table

HD250 (SIEMENS) tries to simulate an 250 leaf MLC by moving collimator head, MLC and table (not supported by TPS!)

Tomotherapy

Complete system: CT, TPS, rotational IMRT with moving table and CBCT in one device.

What are the limitations?

Tomotherapy

Delivering techniques

Flattened vs. unflattened Beams.

IMRTsMLCdMLCVMATRotational IMRT flattening filter free

Differences?……

Imaging

What is the goal, what do we need to see?

…

CT on rails

Pro: real diagnostic image quality

Con: no absolute coordinate origin

Cyberknife

Robotic system (Linac arm and table)

Integrated verification and motion management system

Field size fixed by cone diameter

Dose is build up by many spots

Electron IMRT (MERT)

Radiotherapy and Oncology Volume 100, Issue 2, August 2011, Pages 253-258 Comparison of modulated electron radiotherapy to conventional electron boost irradiation and volumetric modulated photon arc therapy for treatment of tumour bed boost in breast cancerAndrew Alexander a, et al. McGill University, Montreal, Quebec, CanadaAbstract

Background and purposeTo compare few leaf electron collimator (FLEC)-based modulated electron radiotherapy (MERT) to conventional direct electron (DE) and volumetric modulated photon arc therapy (VMAT) for the treatment of tumour bed boost in breast cancer.Materials and methodsFourteen patients with breast cancer treated by lumpectomy and requiring post-operative whole breast radiotherapy with tumour bed boost were planned retrospectively using conventional DE, VMAT and FLEC-based MERT. The planning goal was to deliver 10 Gy to at least 95% of the tumourbed volume. Dosimetry parameters for all techniques were compared.ResultsDose evaluation volume (DEV) coverage and homogeneity were best for MERT (D98 = 9.77 Gy, D2 = 11.03 Gy) followed by VMAT (D98 = 9.56 Gy, D2 = 11.07 Gy) and DE (D98 = 9.81 Gy, D2 = 11.52 Gy). Relative to the DE plans, the MERT plans predicted a reduction of 35% in mean breast dose (p< 0.05), 54% in mean lung dose (p < 0.05) and 46% in mean body dose (p < 0.05). Relative to the VMAT plans, the MERT plans predicted a reduction of 24%, 36% and 39% in mean breast dose, heart dose and body dose, respectively (p < 0.05).ConclusionsMERT plans were a considerable improvement in dosim etry over DE boost plans. There was a dosimetric advantage in using MERT over VMAT for inc reased DEV conformity and low-dose sparing of healthy tissue including the integral do se; however, the cost is often an increase in the ipsilateral lung high-dose volume.

EMLC

The EMLC consists of 30 brass leaf pairs with the bottom edge located 16 cm above the isocenter. The resulting maximum field size at 100 cm isocenter is 21.4 cm x 21.4 cm. All leaves can be moved up to a fourth of the maximum field size beyond the central field axis (leaf overtravel).

In comparison with the standard applicator from 6 to 14 MeV, the only differences in dose distribution are the greater beam penumbra of 0.7 to 0.3 cm and the larger build-up effect in the depth-dose curves quantified by the lower surface dose of 3 to 4%. Radiation leakage of the EMLC at 14 MeV amounts to 1.5 to 2.5% relative dose, which could be effectively reduced up to the dose contribution from photon contamination of the electron beam due to our tongue-and-groove leaf design. The total weight of the EMLC is 23 kg. “Elekta Research Prize” for the development. The ESTRO honoured this

development with the “Jack Fowler-University of Wisconsin Award”. Images T.Gauer Diss. Uni Hamburg

Heavy Particle Therapy

J Radiat Res (Tokyo). 2010;51(4):365-83. Recent advances in the biology of heavy-ion cancer therapy. Hamada N, et al Radiation Safety Research Center,, Komae, Tokyo, Japan. t

Superb biological effectiveness and dose conformity represent a rationale for heavy-ion therapy,

which has thus far achieved good cancer controllability while sparing critical normal organs.

Immediately after irradiation, heavy ions produce dense ionization along their trajectories, cause

irreparable clustered DNA damage, and alter cellular ultrastructure. These ions, as a consequence,

inactivate cells more effectively with less cell-cy cle and oxygen dependence than

conventional photons. The modes of heavy ion-induced cell death/inactivation include apoptosis,

necrosis, autophagy, premature senescence, accelerated differentiation, delayed reproductive death

of progeny cells, and bystander cell death. This paper briefly reviews the current knowledge of the

biological aspects of heavy-ion therapy, with emphasis on the authors' recent findings. The topics

include (i) repair mechanisms of heavy ion-induced DNA damage, (ii) superior effects of heavy ions

on radioresistant tumor cells (intratumor quiescent cell population, TP53-mutated and BCL2-

overexpressing tumors), (iii) novel capacity of heavy ions in suppressing cancer metastasis and

neoangiogenesis, and (iv) potential of heavy ions to induce secondary (especially breast) cancer.

Pion Therapy

Pions belong to a group of short-lived subatomic particles called mesons. They

are the lightest of the mesons, having about one seventh the mass of protons

or neutrons. Some are electrically neutral, while others carry a single positive or

negative charge . Pions are not normally found in the free state in nature: when

a nucleus is struck by a proton having a certain energy, pions are ejected from

the nucleus. Beams of charged pions can be guided, bent or focused by

magnetic fields, just as light beams are controlled by prisms or lenses

Applikation Protonen

Proton

Proton Gantry

Photon Gantry

Proton facility

Heavy Ion

One room proton facilities

BIG ROOMS! Cheaper? Acceleration WIP. No Gantry?.

Tomotherapy Proton facility

Conventional protons are delivered with only a few fields. Photon Tomography has greater high dose conformity but there is less integral dose with protons.

Dielectric wall accelerator• DWA is a multistage inductive accelerator underdevelopment at Lawrence Livermore National Lab.• Acceleration gradient of 100 MV/m possible.• 200 MeV protons in 2 meters.• Beam energy, intensity and spot size variable pulse-topulse.• IMPT can be achieved with spot scanning or distal edge tracking through limited arcs.

The method has been implemented clinically at GSI Darmstadt. The picture shows the

treatment of a patient with a skull base tumour at the heavy ion treatment facility at GSI

Darmstadt. For a precise positioning the head of the patient is fixed by means of an

individual mask. The gamma quanta generated by the positron annihilation are marked

in red. Above and below the patient the detectors of the positron emission tomograph

are mounted.

Heavy Ion

Proton delivery technique

Scanning

Scatter

Passive Scattering

• Range Shifter Wheel

um Bragg-Peakauszuziehen (entlang der Tiefenachse)

• Scatterer um Strahl aufzustreuen (seitlich zur Tiefenachse)

• Filter

• Kompensatoren um der Geometrie des Tumors gerecht zu werden

Active Scanning

Lomax, Pedroni, PSI Villigen

Eye tumors

Bilder Hug E, PSI Villingen

Comparison Photons Protons

Tumor sizeMotion inter- and intra-fractionSpecific uncertaintiesDose rate (treatment time)Verification....

Biology enhanced treatments

Always in addition radio therapy !

Temperatures 39-43 degree Celsius in target region

Microwave Hyperthermia Nano particles as carriers Nano particles as heat generatorsHigh Focused Ultrasound

Advantage: NO extra long term side effects

Superficial hyperthermia● Range ~ 1 – 3 cm

water bolus

0

3

6

9

12

151 4 7 10 13

Z [°C]

X [cm]

Y [cm]

Spiral-Applikator-8

42-42.5

41.5-42

41-41.5

40.5-41

40-40.5

39.5-40

39-39.5

38.5-39

38-38.5

37.5-38

37-37.5

36.5-37

36-36.5

35.5-36

35-35.5

Superficial-HT: Spiral applicators

dimensions (5-24cm)water-bolus-system8/24 channelindividually controllableadaption to the heat distribution

Deep Hyperthermia

8 antennas

•software for a 2D-field control

THT planning

QA–tool: Lamp phantom

Effect of operating frequencySigma-60

0

10

20

30

40

50

70 80 90 100 110 120 130

frequency MHz

% re

flect

ion

76 MHz 92 MHz 125 MHz

THT

Diversity of

nanoparticles used in

drug delivery strategies.

Nanoparticulate

formulations can be

tailored based on the

required drug to be

encapsulated/carried.

While hydrophobic

molecules can be

incorporated inside the

core of the nanoparticles,

hydrophilic molecules

can be carried more

readily within an aqueous

core protected by a

polymeric or lipidic shell.

Nano particles

Nano particles (MagForce)

NanoTherm® therapy is a new approach for the local treatment of solid tumors. The principle

of the method is the direct introduction of magnetic nanoparticles into a tumor and their

subsequent heating in an alternating magnetic field. The water soluble nanoparticles are

extremely small (approximately 15 nanometers in diameter), and contain an iron oxide core

with an aminosaline coating. The particles are activated by a magnetic field that changes its

polarity 100,000 times per second, and heat is produced.

Depending on the duration of treatment and the achieved intratumoral temperatures, the

tumor cells are either directly destroyed (thermal ablation) or sensitized for concomitant

chemo or radiotherapy (hyperthermia).

With this new procedure, it is possible to combat the tumor from the inside out, thereby

sparing surrounding health tissue. The nanoparticles remain in place at the treatment area,

allowing for repeated treatments and the integration of multimodal therapy concepts.

HIFU

The in the MRT integrated ultrasound unit

sends focussed impulses to the myomas.

Verification Imaging

What is the goal?

Treatment chain verification !

• http://www.astro.org/Meetings/ConferencesAndSymposia/IGRTSymposium/ScientificProg

ram/documents/Amies.pdf

Fig. 5. Dose calculation on patient treated for recurrent naso-pharyngeal carcinoma with intensity-modulated radiotherapy. No weight loss or anatomy deformation observed between CT and megavoltage cone-beam CT (MVCBCT).(Above) Isodose lines at treatment isocenter planes on conventional CT and MVCBCT.(Below) Good qualitative agree-ment observed with dose–volume histograms obtained from dose calculations performed using CT (solid lines) and MVCBCT (dashed lines).

I. J. Radiation Oncology ● Biology ● Physics Volume 67, Number 4, 2007

Adaptive RT

Conventional CT reconstruction 2 mm (IMRT pelvis, H&N,)

CT with Gating to determine the security margindepending on the movement of the tumour.IMRT breast, 3D conformal lung>

in the future IMRT lung

security margin depending on the movement of the tumour

Bildaufnahme

Verification fluence with FPP + 3D Delta 4 detector

With original Gantry angle

FPP Fluenze Verifikation

Multi point 3D absolute dose check

With original Gantry angleTable effect

+

=?

TPS Dose

Delta 4 Dose (measured)

=?

Dose verification with FPP + MU–Future

With original Gantry angle

Multi point MU checkData transfer check

MU CALCULATOR DIAMOND

+

=?

FPP Fluenze Verifikation

Patient-specific QASetup Verification

• Standard

� Orthogonal portal vs. DRR

- (FPP, film, CR)

� Verification Isocenter

� Field shape/perture (port during)

� preferred

� MVCB

� Isocenter verification

� Tumor (markers), OAR, outline change monitoring

Dosisaspekt bei MVCB CT

We can calculate the applied dose. In the IMRT optimization we can even consider the dose from the MVCB-CT (Pinnacle 7.6 c, KonRad 2.2.)

KonRad 2.2 Plannung Karin Markl, Siemens

Pinnacle7.6 c Planung Shaka Khan, KSA

DOSE CALCULATION

DOSE COMPENSATION

Lutters IMRT clinical implementation at KSA, Heidelberg IMRT IGRT School ,2007

Pre-Treatment 3D Dose verification In-vivo 3D Dose verification Nijsten et al. MAASTRO Physics Abstract

Pre -tretment

In vivo 3D dose reconstruction in MVCB CT

IMRT chain control

Positioning and immobilization

Image acquisition

Structure segmentation

Treatment planning and evaluation

File transfer and management

Plan validation

Setup verification

IMRT treatment delivery and verification Ezzell et al, 2002

Patient specific QASetup verification

• Standard� Orthogonal portal vs. DRR - (FPP, film, CR)� Isocenter verification� Field shape/aperture (port

during)

� Preferable� MVCB/kV CBCT/CT on rails � vs. CT� Isocenter verification� Tumor (markers), OAR, outline

change monitoring

Consider protocols for setup correction e. g. NAL

Pre-Treatment 3D Dose verification In-vivo 3D Dose verification Nijsten et al. MAASTRO Physics Abstract

Pre -tretment

In vivo 3D dose reconstruction in MVCB CT

Exit dosimetry, EPID in vivo

Differences between predicted and measured portal dose during breast treatment ∆D =3% , Δr=5 mm

W. J. C. van Elmpt et al., Medical Physics, Volume 32, Issue 9, pp. 2805-2818, September 2005.

Non-ionising verification

Calypso: Tumor GPS

Vision RT: Surface detection

Tracks the 3D surface of a patient in real time without the need to apply external markers or any other physical device to the patient.

MOSAIC xxx: Accessory registration

New design for motion and verification adaption

Adaptive RT and Dose summation

Most common evaluation parameters:

� Gamma index (Law et al. 1998), see Figure� DTA (Distance To Agreement)the distance between a measured data point and the nearest point in the calculated dose distribution that exhibits the same dose.

� Dose difference� Isodose overlay

Other : NAT =Normalized Agreement Test(Childress et al.2004) , Gradient analysis (Moran et al., 2005)

Patient specific QAEvaluation

Figure Gamma concept. Depuydt, 2002

Common gamma criteria: ∆D = 3 - 4% ; ∆d =2 - 3 mm Gamma passed when ≤ 1other criteria % points <1 , < 1.5, <2

Statistical analysis of the results helps to set up protocols with criteria of acceptability

DGRT: it’s the dose that matters

Volumetric-modulated arc therapy (VMAT) entails rap id execution of a sequence of control points each defi ning multileaf collimator (MLC) shape, MLC segment dose, and a gantry-angle window across which each shape sweeps dynamically.

Adaptive radiotherapy ART

Dose-guided radiotherapy

MVCBCT and DGRT

Every new machine enables us to do a better treatment !

Consider a prostate, breast and lung treatment

Which machine do you choose?• Tomotherapy• Linac• Cyberknife• Protons

• Which technique do you choose?• IMRT/IMPT, IMAT, etc.• Gating• Stereotaxy

Machines deliver planned dose distributions !

Which TPS (algorithm) do you choose?• Stereotaxy calculation • Pencil beam• Convolution/collapsed cone• Monte Carlo

Which verification system do you choose?• Film/CR• EPID• Cone beam (kV or MV) or InRoom CT• Soft Tissue or Markers or Bony Landmark

Congratulations: You chose the best system

Accuracy of • modality• dose distribution• dose calculation• verification image qualityis simply the best

BUT: Did you think about • the patient and• his physician ?Do they fit into the precision of delivery and veri fication?

How precise is the patient?

Setup errors consist out of• Systematic errors• Random errors• Motion errors

Systematic errors are…..

Random errors are …

Motion errors are ……

Geometric Uncertainties in Radiotherapy; Defining the Planning Target Volume, British Institute of Radiology (Januar

2003) ISBN-10: 0905749537 ISBN-13: 978-0905749532

How precise is the patient?

Difficult to determine in advance for an individual patient.

ICRU52 and 60 define the target and organ at risk v olumes. They introduce a margin concept for unpredictable e rrors.

Solution: population based margin recipes (Marcel v . Herk)http://www.aapm.org/meetings/amos2/pdf/35-9817-23186-884.pdf

How precise is the physician

• Inter-observer variability• Intra-observer variability• Use of multimodality imaging• Understanding MRI/PET• Management of motion (artifacts)• Tumor staging • Tumor delineation

What is the QA for the physicians work?

Solution: Get a colleague to review every contour, dose plan, verification image every time.

http://www.rcr.ac.uk/docs/oncology/pdf/BFCO(08)5_On_target.pdf

Total uncertainty

• Dosimetry• Calculation • Delivery• Verification• Delineation• Set up • Motion

What is the biggest error, where is it easiest to i mprove?

->Intra- and inter-observer variability in tumor del ineation!CF Njeh, Tumor delineation: The weakest link in the search f or accuracy in radiotherapy ; Journal of Medical

Physics; Review article, 2008, Volume : 33, Issue : 4, Page : 136--140

Greetings to PSI neutron imaging