New clues for brain cancer treatment at the ESRF

02-04-2004

A team of researchers from the University Hospital of Grenoble (CHU Inserm U647) and the ESRF has found a new treatment that improves the survival of rats with high-grade gliomas. This research was carried out at the ESRF Medical Beamline. It showed that after a year of this treatment, three rats out of 10 were considered cured, whereas without treatment, all would be dead. The results have just been published in the scientific journal Cancer Research. A glioma is one of the most frequent brain tumours in human adults, and it is not curable.

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Today, the median survival for patients with glioma is less than a year. Around 5 to 10 adults out of 100.000 suffer from this brain tumour. Traditional radiotherapy using hospital X-rays only has a palliative effect because gliomas are some of the most radio-resistant human tumours. Chemotherapy is ineffective most of the time. Several therapeutic techniques have been developed over the last years using animal models, but none has had such successful results as this new treatment with cis-platinum combined with monochromatic synchrotron X-rays. This new technique combines chemotherapy with radiotherapy in such a way that both techniques are effective when associated.

In this study, a drug called Cis-platinum was injected into the brain of rats bearing F98 glioma. The substance entered the DNAs of the tumour and limited the tumoral proliferation. A day later, at the Medical Beamline of the ESRF, the tumour was irradiated with X-rays of a very precise energy (monochromatic). The difference between these X-rays and the conventional X-ray sources used in hospitals is the brilliance: the beam produced by the ESRF synchrotron is a hundred thousand times brighter than the beam produced by a hospital X-ray machine, allowing the beam to be tuned at a convenient wavelength.

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The team (from left to right): François Estève, Hélène Elleaume, Jean-François Adam, Jean-François Le Bas, Wendy Renier, Aurélie Joubert, Nicolas Foray, Caroline Boudou, Marie Claude Biston, Anne Marie Charvet. Absent in the picture: Sylvain Bohic and Jacques Balosso.

This in vivo experiment was preceded by in vitro experiments on cells using the same tumoral model (F98). This tumour is extremely radioresistant and it spreads very quickly. The mean survival time of untreated rats was 28 days. If cis-platinum was injected, they survived up to 39 days. If the rats were irradiated with X-rays at a certain wavelength, it could result in a maximum of 48 days of survival. The combination of both treatments, with a specific radiation dose and a specific X-ray wavelength appeared to be the most efficient treatment tested and offered a mean survival time of around 200 days. This means a 6-fold increase in the life span of treated rats compared to those which didn’t receive any treatment.

The success of the trials has led CHU and ESRF researchers to envisage the elaboration of a protocol in order to use these techniques on humans. “There is a lot of technological development to be carried out, but it is feasible”, explains Doctor François Estève, one of the authors of the paper. “The ESRF Medical Beamline is a unique place in the world where pre-clinical and clinical research in radiotherapy with synchrotron radiation is possible nowadays” says Doctor Alberto Bravin, responsible for the Medical Beamline. Rats and humans don’t have so much physical resemblance, so doctors and physicists still cannot say whether they would have the same outstanding results if humans were treated. But François Estève is convinced that “taking into account the impossibility nowadays of healing this brain tumour, it is really a must to try this method”.

Reference: Biston et al., Cure of Fisher Rats Bearing Radioresistant F98 Glioma Treated with cis-Platinum and Irradiated with Monochromatic Synchrotron X-Rays, Cancer Res. 2004 64: 2317-2323.