For better use of radiotherapy in children

To be able to offer children with cancer access to all available treatments is the purpose of this new programme, in which biologists, radiotherapists and paediatricians are collaborating. “To date, doctors have three weapons at their disposal with which to fight against cancer: surgery, radiotherapy and chemotherapy”, explained Celio Pouponnot, head of a research team at Orsay (CNRS/Inserm/Institut Curie) and the coordinator of this programme.

In children with brain tumours, radiotherapy remains a key treatment. “Unfortunately, in young children whose brain is still developing, it can have major consequences”, deplored paediatrician-oncologist François Doz. Because of its toxicity, all the more marked if the child is young at the time of treatment, it is therefore ruled out for infants and rarely prescribed for children aged under 3 years. Furthermore, some very aggressive paediatric brain tumours recur after radiotherapy treatment. This applies in particular to one of the most common malignant childhood brain tumours, medulloblastoma, in which the teams of biologists of Celio Pouponot and Olivier Ayrault specialise, and atypical teratoid rhabdoid tumours (ATRT), now being studied by the research team of the paediatrician-researcher Franck Bourdeaut.

”It is urgent to find new ways of improving the effectiveness of radiotherapy in young children with these two kinds of brain tumours”, said Celio Pouponnot. “Our aim is to explore the feasibility of two approaches currently being developed by teams from Institut Curie to reduce side effects, and to increase the efficacy of radiotherapy”.

Strong, fast treatment seems to be a good means of limiting the side effects of radiotherapy. “On experimental models, “flash” irradiation protects healthy tissues from the onset of side effects very selectively whilst anti-tumour efficacy remains the same ”, explained radiobiologist Vincent Favaudon, Inserm Research Director Emeritus at Institut Curie.

The other avenue involves the Dbait molecules, discovered by Marie Dutreix and her team at Institut Curie. These molecules “trick” the tumour cells, thereby preventing the repair of lesions created by the radiotherapy and thus increase its effectiveness. A clinical trial based on this approach in adult patients showed good tolerance and effectiveness of the Dbait/radiotherapy combination.

These are all avenues which the research teams of Celio Pouponnot, Olivier Ayrault and Franck Bourdeaut have decided to evaluate in medulloblastomas and ATRTs. “Initially, we will compare the toxicity induced by classic radiotherapy, “Flash” mode-administered radiotherapy and the radiotherapy/Dbait combination in developing tissues”, announced Olivier Ayrault. The status of some genes, in particular the famous P53 gene which apparently plays a role in tumour radioresistance, will be studied by the researchers. This medical and scientific project is fully in line with the Institut Curie’s strategy of developing a key area dedicated to radiation biology at the Orsay site. It should also benefit technological developments, namely the “Pencil Beam Scanning” treatment system, currently being installed at the Proton Therapy Centre of Institut Curie at Orsay for the delivery of Flash irradiation.

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Radioresistance and toxicity of radiotherapy in pediatric brain tumors

Coordinator :

• Celio Pouponnot, co-group leader Raf and Maf signaling in oncogenesis and development

Partners :

• Olivier Ayrault, group leader Signaling in development and brain tumors,
• Marie Dutreix, group leader Recombination, repair, and cancer: from molecule to patient, Vincent Favaudon, researcher, Franck Bourdeaut, pediatrician et co-leader of the SIRIC pediatric oncology team,
• François Doz, pediatrician, Claire Alapetite, pediatrician,
• Pierre Verrelle, radiotherapist,
• François Boussin of the CEA (iRCM, CEA).