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Fig. 54: Quantitative analysis of immuno-labelled sections showed an increased γH2AX-positive cell fraction after MRT, corresponding to increased cell death (a), whereas the fraction of dividing Ki67-positive cells decreased after multiport MRT (b). c) MRT5 induced a reduction in blood volume fraction, in particular at two weeks post irradiation, compared with the other irradiation configurations. d) Invasion of CD68-positive cells increased steadily after MRT2 and MRT5. e) A similar pattern was observed for microglia invasion (CD11b-positive cell fraction). Data are plotted as mean ± SEM. Significance was determined using multiple t-tests for p<0.05, and noted as *Ctrl vs. MRT5, ^Ctrl vs. MRT2, §Ctrl vs. BB, #BB vs. MRT5, ¶BB vs. MRT2, +MRT5 vs. MRT5, °MRT2 vs. MRT2, £BB vs. BB, xMRT5 vs. MRT2.
at the intersection of the beams targeting the tumour but spares normal tissue damage along non-targeted, unidirectionally irradiated areas, avoiding behavioural deficits in rats. A valley dose of 10 Gy (i.e., the dose deposited between microbeams), delivered by a single MRT port, improved tumour control and the median survival time of 9L tumour-bearing rats compared with an isodose of BB exposure. Overall benefits were significantly enhanced by increasing the number of ports, while maintaining the accumulated valley dose at 10 Gy. At identical valley isodoses, each additional MRT port extended survival: an exponential correlation between the number of ports and lifespan was found (r2=0.9925, Figure 53).
It was found that a 10 Gy valley dose in MRT mode, delivered through five ports, achieved the same survival as a 25 Gy BB irradiation. This effect was due to an accumulation
of microbeams creating dose hot spots at microbeam intersections. Effects on tumour growth delay and survival were improved, while the histopathological features of cell death, vascular damage and inflammatory response in the tumours increased (Figure 54).
The data confirm that an increasing number of MRT ports provides a non-linear improvement in tumour control, while sparing normal brain tissues. Indeed, multiport MRT reached biological equivalent doses of ~2.5 fold, a result never achieved by any other radiotherapeutic approach using geometrical effects. The remarkable normal tissue sparing and the outstanding therapeutic index make multiport MRT a promising and innovative irradiation method that is primed for clinical translation, possibly increasing survival and improving long-term outcomes in neuro-oncology patients.
PRINCIPAL PUBLICATION AND AUTHORS
Unexpected Benefits of Multiport Synchrotron Microbeam Radiation Therapy for Brain Tumors, L. Eling (a), A. Bouchet (a), A. Ocadiz (a), J.-F. Adam (a), S. Kershmiri (a), H. Elleaume (a), M. Krisch (b), C. Verry (c), J.A. Laissue (d), J. Balosso (c,e), R. Serduc (a), Cancers 13, 936 (2021); https:/doi.org/10.3390/cancers13050936 (a) INSERM UA7 STROBE, Grenoble (France) (b) ESRF (c) Radiotherapy Department, CHU, Grenoble (France) (d) Institute of Anatomy, University of Bern (Switzerland) (e) CLCC Francois Baclesse, Caen (France)
REFERENCES
[1] Q.T. Ostrom et al., Neuro. Oncol. 21, 1-100 (2019). [2] D.N. Louis et al., Acta Neuropathol. 131(6), 803-820 (2016). [3] J.A. Laissue et al., Int. J. Cancer 78, 654-660 (1998).
