Irradiation of intracerebral 9L gliosarcoma by a single array of microplanar x-ray beams from a synchrotron: balance between curing and sparing

Abstract

The purpose of this work was the understanding of microbeam radiation therapy at the ESRF in order to find the best compromise between curing of tumors and sparing of normal tissues, to obtain a better understanding of survival curves and to report its efficiency. This method uses synchrotron-generated x-ray microbeams. Rats were implanted with 9L gliosarcomas and the tumors were diagnosed by MRI. They were irradiated 14 days after implantation by arrays of 25 microm wide microbeams in unidirectional mode, with a skin entrance dose of 625 Gy. The effect of using 200 or 100 microm center-to-center spacing between the microbeams was compared. The median survival time (post-implantation) was 40 and 67 days at 200 and 100 microm spacing, respectively. However, 72% of rats irradiated at 100 microm spacing showed abnormal clinical signs and weight patterns, whereas only 12% of rats were affected at 200 microm spacing. In parallel, histological lesions of the normal brain were found in the 100 microm series only. Although the increase in lifespan was equal to 273% and 102% for the 100 and 200 microm series, respectively, the 200 microm spacing protocol provides a better sparing of healthy tissue and may prove useful in combination with other radiation modalities or additional drugs.

Monte Carlo dose enhancement studies in microbeam radiation therapy

“…[11][12][13][14][15] Moreover, MRT protocols have been shown to be able to ablate highly aggressive animal tumor models. 10,[15][16][17][18][19][20][21] MRT, therefore, yields a higher therapeutic index than nonsegmented beams of a similar energy spectrum. 10,20 The outcome of MRT can be further improved by combining MRT irradiation with dose enhancers such as high-Z-labeled compounds.…”

Emerging neurosurgical applications of synchrotron-generated microbeams

“…Most of the experimental activity performed until now has been focused on the study of the effects of arrays of parallel microbeams [4,5,[9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][28][29][30]. MRT has been applied to several tumor models including intracerebral gliosarcoma (9LGS) in rats [11,13,30], murine mammary carcinoma (EMT-6) [19] and human squamous-cell carcinoma (SCCVII) in mouse and rat [9,20]. Rats bearing the intracranial 9L gliosarcoma irradiated anteroposteriorly with arrays composed of 27 gm thick microbeams spaced 100 gm on-center showed a clear survival advantage after MRT: 4 out of 14 rats irradiated at 625 Gy incident doses were longterm survivors with little brain damage revealed in histopathology [11].…”

Synchrotron Radiation Therapy from a Medical Physics point of view

“…It gives a measurement of the maximum peak dose in relation to the valley dose between two peaks and it is likely to be an important parameter in tissue sparing [14,17]. The PVDR should be low in the tumor in order to inhibit any possible repair mechanisms and high in the healthy tissues, always keeping the valley dose below the tolerances for the healthy tissues [17].…”

“…At the ESRF the center-to-center distances between beams range from 100 to 400 µm in MRT and it is 1200 µm in MBRT. The preclinical studies in MRT indicate a remarkable healthy tissue sparing capability [10,11,12,13,14,15] and the ablation of highly aggressive tumours in several animal models [16,17,18,19,20,21,22]. In MBRT, the first preclinical studies indicate that minibeams still keep (part) of the healthy tissue sparing capability observed in MRT [9,23].…”