1. Giulio Magrin, TERA Foundation, Manjit Dosanjh, ENLIGHT++, CERN
Quality concept: The multidisciplinary approach of the European Network for LIGht ion Therapy, ENLIGHT
Giulio Magrin, TERA Foundation, Manjit Dosanjh, ENLIGHT++, CERN
Quality in HadronTherapy - Oct '06 - G Magrin, M Dosanjh

2. What is ENLIGHT
ENLIGHT, : an international-multidisciplinary arena open to discussion
ENLIGHT was composed of:
Centres in Heidelberg, Lyon, and Pavia, CERN, EORTC, ESTRO, GSI, Karolinska, MedAustron, TERA
Main achievements:
The creation of a European Hadrontherapy Community
ENLIGHT spurred leap from basic science institutes to clinical environment
Source of inspiration for meetings and articles
Serve as platform for education and dissemination
Quality in HadronTherapy - Oct '06 - G Magrin, M Dosanjh

3. What ENLIGHT is not
The network is NOT responsible for adopting Codes of Practice.
Recommendations: The deliverable represent the result of the common effort of the group of ENLIGHT Institutions and are NOT unique answer.
Info and documents: AND
Quality in HadronTherapy - Oct '06 - G Magrin, M Dosanjh

4. From ENLIGHT… to ENLIGHT++
In 2006 ENLIGHT++:
+ one “plus” for more hadrons (specifically protons),
++ the second “plus” refers to more Countries (15 countries, with 60 Institutions)
ENLIGHT++ goes beyond being a network:
Main Objective: Being more INCLUSIVE and becoming a RESEARCH network
Quality in HadronTherapy - Oct '06 - G Magrin, M Dosanjh

5. What is ENLIGHT++
The new network will focus on specific research topics:
Clinical Studies
Radiobiology
Treatment Planning for Intensity Modulated Particle Therapy
Adaptive ion therapy and treating of moving organs
Novel in-beam PET systems
Feasibility study for innovative gantry designs
Information and Communication Technologies for Hadron therapy
…and Networking.
Quality in HadronTherapy - Oct '06 - G Magrin, M Dosanjh

6. Hadron therapy numbers…
1954 the first patient treated with protons in Berkeley, California.
1954
Berkeley
Today: 51,000 patients since ‘54 (44,000 protons, 2,900 carbon ions).
Ten years ago: 22,000 patients since ’54 (18,300 protons)
Quality in HadronTherapy - Oct '06 - G Magrin, M Dosanjh

7. Where to find hadron therapy
Europe is moving coherently towards the realization of a network of Hadron therapy Centers with CARBON ION beams:
PAVIA
Surface buildings
HEIDELBERG
2006:
Completed
building
The synchrotron bunker is ready
Quality in HadronTherapy - Oct '06 - G Magrin, M Dosanjh

8. Where to find hadron therapy
Heidelberg and Pavia are foreseen to start operation in 2007
France, Austria and Germany (Marburg) approved,
Sweden, Belgium, Netherlands, Spain, UK…
Japan has 2 carbon facilities and 4 proton facilities
New PROTONS centers: USA (3 …), Korea, China, Germany, Italy, UK, Russia
Quality in HadronTherapy - Oct '06 - G Magrin, M Dosanjh

9. Numbers of potential patients
From studies in Austria, France, Germany and Italy
X-ray therapy
every 10 million inhabitants………….……20'000 pts/year
Proton therapy
12% of X-ray patients ………………………2'400 pts/year
Carbon ions
3% of X-ray patients…………………………. 600 pts/year
Elective therapy: About 3'000 pts/year of hadron therapy every 10 M (130,000 in big Europe)
Boost therapy: Much larger… difficult to say
Quality in HadronTherapy - Oct '06 - G Magrin, M Dosanjh

10. Quality concepts in hadron therapy
Quality in HadronTherapy - Oct '06 - G Magrin, M Dosanjh

11. Beam quality & RBE
RBE is defined as the ratio of the absorbed dose delivered by a reference radiation (60Co), with the absorbed dose delivered by a radiation of different quality, that results in the same effect in a given biological system under identical conditions.
RBE varies with:
effect
biological system
(iii) dose
Quality in HadronTherapy - Oct '06 - G Magrin, M Dosanjh

12. Treatment fractionation
Treatment timing and biological effects:
Dose per fraction (constant or variable)
Interval between fractions
Number of fractions
Rest period
Dose rate and treatment time of each dose fraction
Overall treatment time
Quality in HadronTherapy - Oct '06 - G Magrin, M Dosanjh

13. RBE in the facilities 1. In vitro data
In 1975, a first attempt in Berkeley, California, RBE directly transferred from in vitro experiments (no tissue nor fractionation effects)
2. CHIBA
1994 in Chiba, Japan, the approach assumed, that carbon ions should have the same clinical RBE as known from a large body of clinical neutron experience.
3. Local effect model
Starting 1997 at GSI Darmstadt the Local Effect Model (LEM) was used to describe the RBE of carbon. In the inactivation of cells is calculated on the basis of the track structure of the ions and the measured x-ray sensitivity of the same tissue.
Quality in HadronTherapy - Oct '06 - G Magrin, M Dosanjh

14. RBE in vitro and in vivo The implication of repopulation
… A potential problem of implementing model calculations into routine treatment planning is the fact that it is very difficult, if not impossible, to transfer radiosensitivity data from in vitro measurements to in vivo situations…
H. Paganetti, MGH
The implication of repopulation
The effect of hypoxia
Intracellular contact
V79 cells (or human skin fibroblasts or…) different RBE than tumor cells
Quality in HadronTherapy - Oct '06 - G Magrin, M Dosanjh

15. CHIBA dose delivery system
Added for “layer stacking”
Quality in HadronTherapy - Oct '06 - G Magrin, M Dosanjh

16. CHIBA dose delivery system
Issues related to RBE
- Ridge filters (containes the info on RBE for TP)
Absorbers (fragmentation)
Passive Dose delivery (transversal physical isodose)
- Conformity: 2 (2 ½)
Quality in HadronTherapy - Oct '06 - G Magrin, M Dosanjh

17. CHIBA models
… Although the RBE values may differ for different tissue types and dose-time fractioning employed, a single value of 3 was used …
H. Tsukii, Himac
… We use fixed RBE values independent of dose levels, although this apparently contradicts radiobiologic observations. Our RBE system depends only on LET of the heavy-ion radiation fields …
T. Kanai, Himac
Quality in HadronTherapy - Oct '06 - G Magrin, M Dosanjh

18. CHIBA models
… Although the RBE values may differ for different tissue types and dose-time fractioning employed a single value of 3 was used …
H. Tsukii
… We use fixed RBE values independent of dose levels, although this apparently contradicts radiobiologic observations. Our RBE system depends only on LET of the heavy-ion radiation fields …
T. Kanai, Himac
Quality in HadronTherapy - Oct '06 - G Magrin, M Dosanjh

19. GSI raster scanning 3D control of the BP
Accelerator controlled energy modulation accelerator controlled
3D Conformity
Active dose delivery: an individual RBE assigned to each voxel
Quality in HadronTherapy - Oct '06 - G Magrin, M Dosanjh

20. Local effect models 1. Average size oft the cell nucleus +
2. Radial dose distribution +
3. Dose-response cure for x-ray for specific tumor =
Probability of induction of a lethal lesion
G. Kraft · M. Scholz · U. Bechthold
Quality in HadronTherapy - Oct '06 - G Magrin, M Dosanjh

21. …microdosimetric approach
Beam quality and RBE characterized from the microdosimetric spectrum and waiting function of the biological response.
Microdosimetry
Physical absorbed dose and biological dose (Nice therapeutic proton beam)
8Gy Loncol’s
radiobiological data: human melanoma, human tongue cell carcinoma
Weighting functions
Quality in HadronTherapy - Oct '06 - G Magrin, M Dosanjh

22. Quality and ion species
Protons: presently assumed constant radiobiological effects in the SOBP; lower morbidity and better conformation compare to X-ray; long experience; pediatric tumor.
Light ions: Helium, Lithium, Beryllium, Carbon, Nitrogen, Oxygen, Flour. Increased radiobiological efficiency at the end. Reduced lateral and distal fall-off. Carbon “selected” compromise (high LET- low fragmentation).
Heavier ions: high LET at the entrance, high fragmentation, high rigidity.
Quality in HadronTherapy - Oct '06 - G Magrin, M Dosanjh

23. Quality and ion species
J. Kempe, I. Gudowska, A. Brahme, Karolinska Institutet
Quality in HadronTherapy - Oct '06 - G Magrin, M Dosanjh

24. Quality and ion species
… Heavy ions combine the advantage of better physical selectivity of protons with the radiobiological advantages of fast neutrons for some tumour types. …
A. Wambersie, UCL
Quality in HadronTherapy - Oct '06 - G Magrin, M Dosanjh

25. Biological dosimetry
TECHNICAL REPORTS SERIES No. 398, INTERNATIONAL ATOMIC ENERGY AGENCY, VIENNA, 2000
(a) Biological dose distributions of therapeutic carbon beams of energy 290 MeV/u.
(b) physical dose distributions of the beam shown in (a) .
SOBPs of 20 to 120 mm width are designed to yield uniform biological effect in the peaks;
Quality in HadronTherapy - Oct '06 - G Magrin, M Dosanjh

26. Common effort of ICRU IAEA
In the IAEA decides not to suggest any code of practice in the case of biological effective dosimetry. Biological studies can be made on the basis of uniform dosimetry procedures in a “robust common framework”
IAEA, 398 TRS
Joint effort of ICRU and IAEA initiated in 2004.
Inter-facilities uniformity and comparison.
Exchange of information.
Harmonization of data.
Quality in HadronTherapy - Oct '06 - G Magrin, M Dosanjh

27. M. Krämer, J F Wang, and W Weyrather
Biological dosimetry
Biological dosimetry of complex ion radiation fields. Phys. Med. Biol. 48 (2003) 2063–2070
Chinese hamster ovary cells (CHO-K1)
M. Krämer, J F Wang, and W Weyrather .
Quality in HadronTherapy - Oct '06 - G Magrin, M Dosanjh

28. Biological dosimetry for light ions
Measured (left) and calculated (right) two-dimensional survival distribution.
The black ‘H’ marks the intended target.
Beam directions are indicated by the two arrows.
Quality in HadronTherapy - Oct '06 - G Magrin, M Dosanjh

29. Physical dosimetry of hadrons
Dw,h = Mh  ND,w,Qo kh,Qo
ph : other perturbation factor
Absorbed dose to water or air kerma calibration
Quality in HadronTherapy - Oct '06 - G Magrin, M Dosanjh

30. Physical dosimetry of hadrons
Dw,h = Mh  ND,w,Qo kh,Qo
Taken to be constant for all ion beams
Taken unity for all ion beams
Uncertainties for PROTON BEAMS: 2.0 % Uncertainties for LIGHT ION BEAMS: 3.5 %
Quality in HadronTherapy - Oct '06 - G Magrin, M Dosanjh

31. Physical dosimetry: Uncertainties
Dose usually required 5% accuracy of dose determination
Clinically established dose-response relation for advanced head and neck tumors.
PB , benefit probability
PI , injury probability
P+, probability that patients are cured without severe complications in normal tissue
[Brahme et al.]
Photons
Quality in HadronTherapy - Oct '06 - G Magrin, M Dosanjh

32. …ENLIGHT++ after all Conclusions
Creation of common interdisciplinary environment
Creation of maximum possible uniformity
Inter-facilities uniformity and comparison
Ease exchange of information.
Harmonization of data
…ENLIGHT++ after all
Quality in HadronTherapy - Oct '06 - G Magrin, M Dosanjh

33. Thank you for the attention…
The end
Thank you for the attention…
Quality in HadronTherapy - Oct '06 - G Magrin, M Dosanjh