Primary results of in-vivo photon activation therapy by synchrotron x-rays associated with intra-tumor cisplatinum in Fisher rats bearing orthotopic F98 glioma

Conventional radiotherapy of high-grade glioma is unsuccessful since less than 50 % of patients survive at 6 months. We propose a new radiotherapy procedure, the photon activation therapy (PAT), associating synchrotron radiation with a chemotherapy agent, cisdiamminedichloroplatinum (II) (CDDP). PAT aims at using the monochromaticity of the synchrotron source for selective excitation of a high-Z compound introduced in tumor cell DNA to maximize the photoelectric effect probability, thus increasing local toxicity, possibly by the contribution of Auger effect. We report the results obtained with 46 male Fisher 344 rats inoculated with 103 F98 glioma cells. The F98 model is known to be refractory to radiotherapy and very weakly immunogenic . On day 13 after stereotactic inoculation, 3 μg of CDDP in 5 μl were injected intra-cerebrally (ic) into the tumor. The rats were then irradiated on day 14, with 78 keV photons, and 15 Gy. All F98 cell implantations resulted in tumor development. Median Survival Time (MeST) of untreated rats was 26 days (n = 9). No significant difference (p 0.0754) as assessed by the log-rank (Mantel-Cox) test was seen between animals treated with CDDP alone (MeST = 39 days) (n = 10) versus radiation alone (MeST = 48 days) (n = 9). However, a very large difference (p < 0.0001) was found between irradiated alone versus rats treated with CDDP and radiation (MeST 206.5 days). After 260 days, 6 out of 18 rats treated with CDDP and radiation, are still alive. Previously, Barth et al reported an increased in life span relative to MeST of 188 % using Boron Neutron Capture Therapy. This dramatic increase in life span (694 %) is to our knowledge, the largest obtained up to now with the F98 glioma model