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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - u-PBeam (Microdosimetry study of a new radiation therapy method based on proton minibeams)

Teaser

Summary

Radiotherapy (RT) is the medical use of ionising radiation to treat cancer. The main challenge is to deposit a high enough (curative) dose in the tumor while risk organs near the tumour remain at tolerable doses. About 52% of cancer patients receive RT at least once during treatment. The RT has achieved great success in the cure or palliation of various cancers, but for improving this statistic, new treatment modalities as proton radiotherapy (PT) are rapidly expanding. PT achieves very high dose conformity around the target, allowing a better protection of the organs at risk (decreasing radiation side effect). However, using PT the dose delivered to a tumour is still conditioned by the dose that can be tolerated by the surrounding normal tissues. This is particularly critical for certain types of radioresistant tumours, such as hypoxic tumors, for those localized near organs at risk or sensitive structures (e.g. the spinal cord), and paediatrics cancers. For these types of cancers with poor prognosis it is imperative to find new RT approaches that reduce the normal tissue complication probability (NTCP). A recent novel therapy aim to increase the effective dose therapies by using a distinct dose delivery method based on proton minibeams (pMBRT). To implement this promising technique at clinical centers, microdosimetric data are required on the radiation quality aspects of proton minibeams to take advantage of their enhanced relative biological effectiveness versus conventional radiotherapy sources. Currently there are only one array of microdosimeters, as the proposed herein, capable of measuring these parameters in proton therapy.

This project has an important social impact since it addressed the first pre-clinical studies for the implementation in a proton therapy center (ICPO, France). It will be the first place where it is expected that it will be implemented in patients worldwide.

The main objectives have been focused on performing a multidisciplinar study by (i) optimizing the generation method of p-MBRT in a clinical center with Monte Carlo simulations, (ii) performing new 3D-microdetectors able to be used at clinical fluence rates, and (iii) developing radiobiology studies with that new modality.

Work performed

I was involved in the a pionner research group performing proton minibeam radiotherapy (p-MBRT) studies. To implement this promising technique at clinical centers, microdosimetric data are required on the radiation quality aspects to take advantage of their enhanced relative biological effectiveness versus conventional radiotherapy sources. Along with my collaborators, I proposed the optimization of 3D-microdosimeters that are capable of measuring those data in proton therapy. We have demonstrated the feasibility of these sensors at the level of therapeutic fluence rates. Likewise, I performed the first dose calculation engine in proton minibeam radiotherapy based on Monte Carlo GATE (Geant4) simulations. It allowed us to study the dosimetry behind the pre-clinical implementation. To this end, I used Computed Tomography (CT) images taken in the Inst. Curie of one representative animal (7-week-old male Fischer rats) as those that would be irradiated in the pre-clinical trials in the Protontherapy Center of Orsay (ICPO). Additionally, I carried out the first in vitro study in a X-ray Small Animal Radiation Research Platform modified for minibeam irradiations.

Final results

First, a Monte Carlo dose calculation engine for pMBRT implementation with mechanical collimation has been developed. This tool can be used to guide and interpret the results of in vivo trials. The dose calculation engine was benchmarked against experimental data and was then used to assess dose distributions in computed tomography images of a rat, resulting from different irradiation configurations used in several experiments. It reduced in an order of magnitude the computational time. This allows us to speed up simulations for in vivo trials for pMBRT targeting the tumour and crossing the animal head.

Secondly, we peformed experimental tests in hadron beam lines with a new generation of 3D-microdetectors. Results showed a good agreement between experimental and simulated microdosimetric distributions even at the high fluence rates associated with clinical beams.

Third,we report on the first in vitro study performed in an X-ray Small Animal Radiation Research Platform (SARRP) modified for minibeam irradiations. F98 rat and U87 human glioma cells were irradiated with either an array of minibeams or with conventional homogeneous beams. We conclude that MBRT has the potential to improve the therapeutic index for gliomas