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Low Energy Gamma and X-ray therapy

Final Report Summary - LOGX (Low Energy Gamma and X-ray therapy)

• In phase I the basic knowledge necessary for this project is established for dosimetry as well as for microdosimetry. The level of detail required for the accurate dosimetry for low energy photons is assessed from Monte Carlo calculations and measurements. Milestones: obtain accurate dosimetry and microdosimetry around low energy photon sources for full patient geometry.
• In phase II a faster calculation algorithm is developed including eventual approximations that have been shown to be acceptable in phase I. An optimization procedure is obtained taking into account all the relevant parameters determined in phase I and the possibility to modulate the energy for EBS. Milestone: the knowledge from phase I is translated into a tool suitable for clinical use.
• In phase III the fast algorithm is combined with the radiobiology knowledge obtained in phase I and the optimization procedure is extended to take into account the radiobiological effectiveness given by the microdosimetric calculations and measurements. Milestone: availability of a tool allowing assessing the effect of brachytherapy procedure with low energy photons from both a dosimetric and a radiobiological point of view for the full patient geometry.

• Phase I: obtain accurate dosimetry and microdosimetry around low energy photon sources for full patient geometry.

In phase I the effect of tissue heterogeneity for low energy photons was assessed. Although the water approximation is acceptable for isotope with the highest energies such as Ir-192, for low energies below 100 keV, it compromises the accuracy of the calculations for the planning of patients in a very variable way from one patient to another. One of the main issues for dosimetry around low energy photon sources is that the dose deposition is very tissue-dependent due to the fact that low energy photons interact primarily through photoelectric effect. It is consequently of utmost importance to identify those tissues properly. Since the beginning of the project, we have first worked on quantifying the effect of the tissues for low energy photons using the Monte Carlo calculations codes Geant4 and EGSnrc 1,2,3,4,5. The difference in the dose distribution between different tissue types of relevance for low energy brachytherapy such as breast and prostate has been calculated. The effect of the variability of the tissue composition from one patient to another was also investigated using published data about tissue composition 6,7,8,9,10. Since the effect of the tissue has been shown to be significant, it is also important to be able to assign them correctly for each patient. The use of CT images and Dual energy CT to extract tissue composition from imaging for patient was investigated 11,12,13. We also showed that due to the photoelectric effect, the content of trace elements in the tissue is also important 14.
Regarding the RBE, our team has been working on further calculations of RBE using Monte Carlo simulations for the transport of the photons and a damage estimator code to assess the biological damage to cells in term of strand breaks 15.
phase II: the knowledge from phase I is translated into a tool suitable for clinical use.
We focused in the second part on the project on the idea to integrate our knowledge in treatment planning softwares (TPS) to be used for patients. We collaborate with a group in Brazil that has developed a Monte Carlo based TPS that is an ideal platform to translate our research into a real clinical tool 16.
High Dose Rate (HDR) treatment for gyneacology is administered in 3 or 4 fractions and is often combined with external beam to the whole pelvis. The standard at this point to obtain the dose for the whole treatment is to add the dose-volume histogram parameters like the dose to 90% of the volume (D90) or the volume receiving 100% of the dose (V100) for the target and the dose to small volume for the OAR, typically 2cm3 (D2cc). This scheme ignores the deformation of the tissue, making the safe assumption for the OAR that the volume receiving the highest dose is always at the same position. This method only gives the worse case scenario as even if the same plan is used for the different fractions, the probability that the same cells of the bladder or of the rectum wall receive the highest dose is very low. Our group tried to use deformation algorithms to model the deformation. The deformed dose distributions can be projected on the same set of images and be cumulated. This kind of procedure is used for external beam but is very difficult to apply for brachytherapy in view of the very high dose gradients involved 17. This issue is also important to increase the accuracy of TPS.

Phase III: availability of a tool allowing assessing the effect of brachytherapy procedure with low energy photons from both a dosimetric and a radiobiological point of view for the full patient geometry.
Our group recently started a retrospective study in collaboration with the Karolinska Institute in Stockholm about the recalculation using MC of some of their patients treated with brachytherapy for base of tong tumor.
One of the questions raised in the report of the TG186 18 was to assess the effect of the artifact generated by the metal used for brachytherapy applicators or eventual shielding in the CT images. Those situations where metal is used are those for which taking care of the heterogeneities is the most important yet the presence of image artifact introduces errors in the reconstructed density and tissue misassigment. Our group is currently working on evaluating these effects.
We also assessed the effect of tissue composition on RBE for low energy photons. Works has also been performed by our collaborators in Canada to assess the consequences of dose heterogeneity on biological efficiency of Pd-103 permanent breast seed implants in terms of biological effective dose (BED) or equivalent uniform BED (EUBED) 19.

During this project, the American Association for Physics in Medicine (AAPM) has published a report concerning the dose calculation algorithms around brachytherapy sources (Task Group 186). These reports are of great importance in the medical physics community and are very much followed worldwide. The results published by our group have been used in this report and so contribute to the spreading of improved dose calculation for brachytherapy patients.

1 G. Landry, B. Reniers, L. Murrer, L. Lutgens, E. B. Gurp, J. P. Pignol, B. Keller, L. Beaulieu and F. Verhaegen, "Sensitivity of low energy brachytherapy Monte Carlo dose calculations to uncertainties in human tissue composition," Medical physics 37, 5188-5198 (2010).
2 G. Landry, B. Reniers, J. P. Pignol, L. Beaulieu and F. Verhaegen, "The difference of scoring dose to water or tissues in Monte Carlo dose calculations for low energy brachytherapy photon sources," Medical physics 38, 1526-1533 (2011).
3 H. Afsharpour, J. P. Pignol, B. Keller, J. F. Carrier, B. Reniers, F. Verhaegen and L. Beaulieu, "Influence of breast composition and interseed attenuation in dose calculations for post-implant assessment of permanent breast 103Pd seed implant," Physics in medicine and biology 55, 4547-4561 (2010).
4 A. S. White, G. Landry, F. van Gils, F. Verhaegen and B. Reniers, "Influence of trace elements in human tissue in low energy photon brachytherapy dosimetry," Phys Med Biol 2012 Jun 7;57(11):3585-96.
5 A. S. White, G. Landry, G. Paiva Fonseca, R. Holt, T. Rusch, L. Beaulieu, F. Verhaegen, B. Reniers Comparison of TG-43 and TG-186 in breast irradiation using a low energy electronic brachytherapy source, Med Phys, 41, 061701 (2014)
6 ICRU, "Photon, Electron, Proton and Neutron Interaction Data for Body Tissues," ICRU Report No. 46 (Bethesda, MD, 1992) (1992).
7 ICRU, "Tissue substitutes in radiation dosimetry and measurement," ICRU Report No. 44 (Bethesda, MD, 1989). (1989).
8 H. Q. Woodard and D. R. White, "The composition of body tissues," The British journal of radiology 59, 1209-1218 (1986).
9 ICRP, "Basic anatomical and physiological data for use in radiological protection: Reference values," ICRP Report No. 89 (Pergamon, Oxford,2002) (2002).
10 R. L. Maughan, P. J. Chuba, A. T. Porter, E. Ben-Josef and D. R. Lucas, "The elemental composition of tumors: kerma data for neutrons," Medical physics 24, 1241-1244 (1997).
11 H. Afsharpour, G. Landry, B. Reniers, J. P. Pignol, L. Beaulieu and F. Verhaegen, "Tissue modeling schemes in low energy breast brachytherapy," Physics in medicine and biology 56, 7045-7060 (2011).
12 G. Landry, P. V. Granton, B. Reniers, M. C. Ollers, L. Beaulieu, J. E. Wildberger and F. Verhaegen, "Simulation study on potential accuracy gains from dual energy CT tissue segmentation for low-energy brachytherapy Monte Carlo dose calculations," physics in medicine and biology 56, 6257-6278 (2011).
13 G. Landry, B. Reniers, P. V. Granton, B. van Rooijen, L. Beaulieu, J. E. Wildberger and F. Verhaegen, "Extracting atomic numbers and electron densities from a dual source dual energy CT scanner: experiments and a simulation model," Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 100, 375-379 (2011).
14 White SA, Landry G, van Gils F, Verhaegen F, Reniers B. Influence of trace elements in human tissue in low-energy photon brachytherapy dosimetry. Phys. Med. Biol. 2012 May 16;57(11):3585–3596.
15 B. Reniers, T. Rusch and F. Verhaegen, "estimation of relative biological effectiveness for a novel electronic brachytherapy x-ray source," Radiother. and Oncol. 90 (suppl 3), S106 (2009).
16 G. Paiva Fonseca, B. Reniers, G. Landry, M. Bellezzo, P C G Antunes, C. P. de Sales, E. Wellteman, H. Yoriyaz, F. Verhaegen, AMIGOBrachy: Algorithm for Medical Image-based Generating Object - Brachytherapy module - Features, Applications and Relevance for Brachytherapy, submitted to Brachytherapy
17 B. Reniers, G. Janssens, J Orban de Xivry, G. Landry, F Verhaegen. Dose distribution for gynaecological brachytherapy with dose accumulation between insertions: feasibility study. ESTRO, Geneva, April 2013
18 Beaulieu L, Carlsson Tedgren A, Carrier J-F, Davis SD, Mourtada F, Rivard MJ, et al. Report of the Task Group 186 on model-based dose calculation methods in brachytherapy beyond the TG-43 formalism: Current status and recommendations for clinical implementation. Med. Phys. 2012;39(10):6208.
19 Afsharpour H., Reniers B., Landry G*., Pignol J.P. Keller B.M. Verhaegen F. Consequences of dose heterogeneity on biological efficiency of 103Pd permanent breast seed implants, Phys. Med. Biol, 2012, 57, pp 3273