THE NEXT GENERATION OF RADIOBIOLOGY EXPERIMENTS …accelconf.web.cern.ch/AccelConf/pac2013/talks/weocb2_talk.pdf · THE NEXT GENERATION OF RADIOBIOLOGY EXPERIMENTS P. A. Posocco Imperial

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THE NEXT GENERATION OF RADIOBIOLOGY EXPERIMENTS

P. A. Posocco Imperial College London The Cockcroft Institute Gunnar Nilssons Cancerstiftelse

+Content

1  Why we (still) need Radiobiological experiments

2  What we have learned from previous experiments

3  Rationale for new experiments

4  Radiobiological experiments: the next generation

02/10/2013 P.A. Posocco - Imperial College London

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+The concept of RBE… (Relative Biological Effectiveness)

Definition of RBE

RBE =D

Dprotonseffect

0.001

0.01

0.1

1

0 1 2 3 4 5 6 7 8 Dose [Gy]

Cel

l Sur

viva

l

protons

Introduction n  Based on the clonogenic assay:

n  Growing cells in the incubator;

n  Counting them (density);

n  Plating them;

n  Irradiating them;

n  Re-plating them;

n  Leaving them in the incubator (for approx. 2 weeks) to grow further;

n  Counting the number of cells which have generated colonies (visually);

n  Repeating the process for different dose levels

In-vitro radiobiology


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Linear Quadratic (LQ) function

N.A.P. Franken, H.M. Rodermond, J. S, J. Haveman and C. van Bree, Clonogenic assay of cells in vitro, Nature Protocols, Vol.1, No.5 2006, pp. 2315-19.

+… and its implications for treatments…

RBE as a function of particle energy / LET

An increasing RBE with depth cause anextended biologically effective range (1-2 mm)

119-1126

100

120biological dose

2000:27,11

tons

60

80

physical dose

Med.Phys.

Pro

20

40

2 G tti,Goitein:

depth in water [cm]

1.5 2.0 2.5 3.0 3.5

0

2 Gy

Paganetdepth in water [cm]

RBE (depth) for Carbon beamsRBE as a function of particle energy / LET

son

Ion

Car

boC

RBE effect for protons Example of flat SOBP for C-12

Spread Out Bragg Peak (SOBP)


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+… with some exceptions

n  2 opposite fields:

n  RBE effect is practically cancelled due to field compensation!

n  Unfortunately not every case is as simple as this one…

Ideal Proton Therapy Patient in the US Treatment Modality

Prostate cancer

tum

or

dos

e depth

tum

or

dos

e

depth

w/o RBE

with RBE


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+The PIDE* (Particle Irradiation Data Ensemble) n  It’s a database containing results

of more than 800 cell survival experiments from different laboratories all over the world, using different cell types and different ions at various energies.

n  It only includes publications for which the LQ parameters of the response to photons as reference radiation were available or derivable

What is it? Overview of the results…


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* T. Friedrich, U. Scholz, T. Elsässer, M. Durante and M. Scholz, Systematic analysis of RBE and related quantities using a database of cell survival experiments with ion beam irradiation, Journal of Radiation Research, 2012, pp 1–21

Early responding Late responding

+Statistics about source of radiation in PIDE…

Photons Ions


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Photons of different energy have different RBE

+… and region and year

Region

Year


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Dominated by the experiments at HIMAC / RIKEN

ICRU, 2007, Report 78

Number of Particle facilities around the world

38

56

ICRU, 2007, Report 78

+Challenges (1/2): Heterogeneities

n  80 different cell lines investigated. The same cell line may behave differently depending on experimental factors or age of the cell line.

n  44% human, 56% rodent

n  21% cancer, 79% normal

Cell cycle Types of cells


9

ESTRO Conference – W. Dörr

+Challenges (2/2): Dosimetry and Statistics

n  Experimental data must be fitted with the LQ function

n  Data show big error bars: n  Hor.: dosimetry. The dose can

be measured directly using RadioChromic Films previously calibrated for a specific LET or counting the number of particles and estimating the LET;

n  Ver.: statistics. The number of cells per sample which can be easily counted is approx. 50, the number of samples is limited to maintain the same experimental conditions throughout the whole curve.


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J.C.G. Jeynes, et al., High throughput hadron irradiation of mammalian cells using a vertical facility, Radiation and Environmental Biophysics, 0301-634X, 2013.

+What have we learned from those experiments? The RBE value depends:

n  On the dose level (survival fraction);

n  On the cell type;

n  On the mass and energy of the particles (LET value).


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W. Weyrather et al. ,IJRB 1999; 75:1357–64.

B. Jones, Preliminary analysis on PIDE data

proton

He

C

Ne

Nor

mal

ised

RBE

RBE turnover point

+New generation of Radiobiological Experiments

n  Experiments set up to prove a specific aspect of the RBE model, maintaining most of the parameters fixed

n  Large database of response upon variation of all parameters

n  Optimisation of experimental conditions

This can lead to only one solution:

n  Accelerator totally dedicated to these experiments, and

n  Located close or in the radiobiology departments, same as the photon irradiators

n  A table-top (around 10 m2) multi-TW Ti : Sapphire laser system: n  Femtoseconds pulse length n  Power density of ~1019 W/cm2 n  Spot size of a few microns n  Solid targets ~10 um thick

n  Why? Because: n  “Standard” equipment for the plasma

groups working on laser-plasma particle acceleration

n  Strong interest from the community in developing such systems for various applications

n  Starting with a “medical” application could facilitate its development towards a proper particle therapy facility

n  10 MeV protons are already available


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Must have Possible solution

+Radiobiological experiments with laser accelerated protons

D. Doria et al., Belfast (2012) S.D. Kraft et al., Dresden (2010)


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J. Bin et al., Munich (2012)

+Proposal of Imperial College


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2 Gabor lenses

Permanent magnets 90 deg FFAG bend

cells

Come to see our posters: THPSM10 THPSM11 THPSM12 THPSM13

Ti-Sapphire laser

+Thank you!

n  Henry Tsang and Hugo Larose (UG students at Imperial College) for their hard work during a very hot summer

n  Prof B. Jones (Oxford) for the fruitful discussions and material

n  The CRUK centre in Hammersmith for their financial support

Patients who benefit most from hadron therapy Acknowledgments


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Documents

THE NEXT GENERATION OF RADIOBIOLOGY EXPERIMENTS …accelconf.web.cern.ch/AccelConf/pac2013/talks/weocb2_talk.pdf · THE NEXT GENERATION OF RADIOBIOLOGY EXPERIMENTS P. A. Posocco Imperial