A Phase I-II Synchrotron Radiation Application to the Treatment of Intracranial Tumors

Synchrotron radiation (SR) is used to produce monochromatic X-ray photons of very high intensity with tunable energy in the range of medium energies (0-150 keV). Thus freed of low energies, the penetration is still important and the types of possible interactions are, in addition to the Compton Effect in water, the photoelectric effect with any atom much heavier than those of the living mater represented by the carbon, oxygen, hydrogen, nitrogen and phosphorus. Photoelectric interactions cause energy deposits much larger than the Compton Effect, but they require the presence of foreign atoms in living tissue to occur. It may be, for example iodine, platinum or gadolinium, all these atoms are commonly introduced into the human body in medical practice as contrast media in radiology, or as anti-neoplastic chemotherapy.

The use of SR for radiotherapy, if you want to take advantage of its original properties, needs the use of a combined treatment: radiation plus medication bringing the heavy atoms suitable for photo electric effect. Such a concept of combined therapy is widely used in radiotherapy for decades and was the source of many advances in treatment, some are presently routine practices (chemo-radiotherapy, photodynamic therapy) other are still under study as translational research (boron neutron capture therapy). The SR photons at these "photoelectric" energy band can cause highly cytotoxic damages in tumors especially when treated with platinum (cisplatin or carboplatin). Indeed, they provide a photoelectric activation of platinum atoms leading to a massive energy deposition in the DNA of tumors. This therapeutic principle has been called platinum photoactivation therapy (PAT-plat). It is particularly suitable for tumors of small to medium volumes, localized small to medium-depth and suitable for a multi-beam ballistics. Also if there is a possibility of loading the tumor tissue with high doses of heavy compounds to achieve the combined treatment in favorable conditions, one would expect a greater therapeutic effect than conventional treatments. Brain tumors represent a model with these features, thanks to recent techniques of convection enhanced delivery (CED), which allow a direct infusion of medication in the tumor.

This work is not conceptually particularly complex although technically sensitive and very original since ESRF and the Grenoble University Hospital are the only institution which have made the effort to date to develop in close cooperation a SR line entirely devoted to biomedical research. There is no other site in the world is this situation, most of the other centers have either lower energies, or do not have the immediate vicinity of an academic medical center that can set up the collaboration needed or are too new to have already reached this experimental level. On the other hand, the technical and material investments are rather important and as information flow is very free, it was not considered appropriate at this time to start such research simultaneously in several sites. The ESRF and the RSRM team ("Rayonnement Synchrotron et Recherche Médicale") are therefore pioneers in this field and their work is well known worldwide. The 2010 Equipex call for tender agreed to fund the first table top synchrotron prototype to be designed and assembled in Orsay : ThomX project at the LAL, laboratoire de l'accélérateur linéaire, our team is associated to this development. Our technique might spread outside the domain of the great instruments [http://sera.lal.in2p3.fr/thomx/\]..

To carry out the treatment with a satisfactory distribution of the dose of SR, it is necessary to increase the stopping power of the target tumor by the use of an injection of iodinated contrast medium at the time of irradiation. This treatment can be applied to any tumor having good contrast uptake at CTscan and incidentally which may be treated with platinum. For these reasons, the anatomical location of intracranial human tumors has been chosen for the study of the application of this treatment with SR monochromatic 80 keV.

The experimental treatment will be a part of standard treatment for brain metastases under conformal radiotherapy or stereotactic. This irradiation will complement a pan-encephalic standard irradiation that will be made later, thus providing additional security in terms of dosimetry.