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Introduction. What is radiation therapy (RT)?. Cancer treatment Tumor versus normal tissues External photon beam RT. Intensity-modulated RT (IMRT). Brahme et al. 1982 Fluence-modulated beams Homogeneous, concave dose distributions

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What is radiation therapy rt
What is radiation therapy (RT)?

  • Cancer treatment

  • Tumor versus normal tissues

  • External photon beam RT


Intensity modulated rt imrt
Intensity-modulated RT (IMRT)

  • Brahme et al. 1982

    • Fluence-modulated beams

    • Homogeneous, concave dose distributions

  • Better target dose conformity and/or better sparing of organs at risk (OARs)




Biological imaging
Biological imaging

  • PET

  • SPECT

  • fMRI

  • MRSI

Brain

Tumor


Tumor biology characterization
Tumor biology characterization

Apisarnthanarax and Chao 2005


Biological imaging for rt
Biological imaging for RT

  • Improvement of diagnostic and staging accuracy

  • Guidance of target volume definition and dose prescription

  • Evaluation of therapeutic response


Target volume definition
Target volume definition

  • Gross tumor volume (GTV)

  • Clinical target volume (CTV)

  • Planning target volume (PTV)






Dose painting by numbers1
Dose painting by numbers

Biologically Conformal Radiation Therapy


Dose calculation algorithms
Dose calculation algorithms

  • Speed versus accuracy:

    • Broad beam

    • Pencil beam (PB)

    • Convolution/superposition (CS)

    • Monte Carlo (MC)

  • Monte Carlo dose engine MCDE Reynaert et al. 2004

Accuracy ↑

Speed ↓


Mc dose calculation accuracy
MC dose calculation accuracy

  • Cross section data

  • Treatment beam modeling

  • Patient modeling

    • CT conversion

    • Electron disequilibrium

    • Conversion of dose to medium to dose to water

  • Statistical uncertainties



Implementation of bcrt relationship between signal intensity and radiation dose

Dose

Dhigh

Dlow

Signal intensity

Ilow

Ihigh

Implementation of BCRT:Relationship between signal intensity and radiation dose


Implementation of bcrt treatment planning strategy
Implementation of BCRT: Treatment planning strategy


Implementation of bcrt biology based segmentation tool
Implementation of BCRT:Biology-based segmentation tool

  • 2D segmentation grid in template beam’s eye view

    • Projection of targets (+)

    • Integration of signal intensities along rayline (+)

    • Projection of organs at risk (-)

    • Distance

  • Segment contours from iso-value lines of segmentation grid


Implementation of bcrt objective function
Implementation of BCRT:Objective function

  • Optimization of segment weights and shapes (leaf positions)

  • Expression of planning goals

  • Biological:

    • Tumor control probability (TCP)

    • Normal tissue complication probability (NTCP)

  • Physical:

    • Dose prescription


Implementation of bcrt treatment plan evaluation
Implementation of BCRT:Treatment plan evaluation

QVH


Implementation of bcrt example
Implementation of BCRT:Example

  • [18F]FDG-PET guided BCRT for oropharyngeal cancer

  • PTV dose prescription:




Implementation of bcrt conclusions
Implementation of BCRT:Conclusions

  • Technical solution

    • Biology-based segmentation tool

    • Objective function

  • Feasibility

    • Planning constraints OK

    • Best biological conformity for the lowest level of dose escalation


Bcrt planning study set up
BCRT planning study:Set-up

  • BCRT or dose painting-by-numbers (“voxel intensity-based IMRT”) versus dose painting (“contour-based IMRT”)

  • 15 head and neck cancer patients

  • Comparison of clinically relevant dose-volume characteristics

    • Between “cb250” and “vib216-250”

    • Between “vib216-250” and “vib216-300”


Bcrt planning study target dose prescription
BCRT planning study:Target dose prescription


Bcrt planning study cb 250 blue versus vib 216 250 green
BCRT planning study:“cb250” (blue) versus “vib216-250” (green)


Bcrt planning study vib 216 250 green versus vib 216 300 orange
BCRT planning study:“vib216-250” (green) versus “vib216-300” (orange)




Bcrt planning study conclusions
BCRT planning study:Conclusions

  • BCRT did not compromise the planning constraints for the OARs

  • Best biological conformity was obtained for the lowest level of dose escalation

  • Compared to dose painting by contours, improved target dose coverage was achieved using BCRT


Mc dose calculations in the clinic
MC dose calculations in the clinic

  • Comparison of PB, CS and MCDE for lung IMRT

  • Comparison of 6 MV and 18 MV photons for lung IMRT

  • Conversion of CT numbers into tissue parameters: a multi-centre study

  • Evaluation of uncertainty-based stopping criteria

  • Feasibility of MC-based IMRT optimization


Ct conversion multi centre study
CT conversion: multi-centre study

  • Stoichiometric calibration

  • Dosimetrically equivalent tissue subsets

  • Gammex RMI 465 tissue calibration phantom

  • Patient dose calculations

  • Conversion of dose to medium to dose to water



Ct conversion conclusions
CT conversion: conclusions

  • Accuracy of MC patient dose calculations

  • Proposed CT conversion scheme:

    Air, lung, adipose, muscle, 10 bone bins

  • Validated on phantoms

  • Patient study:

    Multiple bone bins necessary if dose is converted to dose to water



Biologically conformal rt
Biologically conformal RT

  • Technical solution

    • Bound-constrained linear model

    • Treatment plan optimization

      • Biology-based segmentation tool

      • Objective function

    • Treatment plan evaluation

  • Feasibility of FDG-PET guided BCRT for head and neck cancer


Mc dose calculations
MC dose calculations

  • Individual patients may benefit from highly accurate MC dose calculations

  • Improvement of MCDE

    • CT conversion

    • Uncertainty-based stopping criteria

  • Feasibility of MC-based IMRT optimization

  • MCDE is unsuitable for routine clinical use, but represents an excellent benchmarking tool



Adaptive rt inter fraction tumor tracking
Adaptive RT:Inter-fraction tumor tracking

  • Anatomical & biological changes during RT

  • Re-imaging and re-planning

  • Ghent University Hospital: phase I trial on adaptive FDG-PET guided BCRT in head and neck cancer


Summation of dvhs
Summation of DVHs

Dose 1

CT 2

Dose 2

CT 1

Registration

Structure 1

Structure 2

Points

TPoints

P Doses

TP Doses

Total

DVH

Total doses


Summation of qvhs
Summation of QVHs

PET 1

Dose 1

PET 2

CT 2

Dose 2

CT 1

Registration

Registration

Registration

Structure 1

Structure 2

Points

TPoints

Disregard TPoints

outside structure 2

P Q-values

TP Q-values

Total

QVH

Total Q-values


Fundamental research in vitro, animal studies

Radiobiology

  • Biological imaging

  • Tracers

  • Acquisition, reconstruction, quantification

  • Treatment planning and delivery

  • Biological optimisation

  • Adaptive RT

Treatment outcome

Nuclear medicine

Radiotherapy physics

Radiotherapy

Clinical investigations


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