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Gy BB over 5 days plus 2 x 8 Gy (valley dose) MRT over 3 days, with a peak dose of 181 Gy (50mm wide microbeams / 200mm on-center distance). Tumor growth was evaluated in vivo by MRI follow up at T-1 , T 7 , T 12 T 15 , T 20 , and T25 after radiation therapy, completed by cell cycle analysis by FACS, and by histologic studies (proliferative index and vascular response) at T 7 , T 12 , and T15 T 20. Results: FACS results showed that MRT induced significant and more prolonged G1 tumor cell arrest than did BB exposures (+12% at T 15 , P<0.001). On histological brain slices, MRT-irradiated tumors displayed a lower cell density and cell proliferation index than BB-irradiated tumors. MRI follow up revealed that MRT boosts completely stopped tumor growth during w4 weeks while BB-tumors recurred within few days after the last radiation fraction. At T25, tumor volumes for BB groups were 3 times greater than those of the MRT boosted group (P<0.001). This was associated with a significant increase in median survival time of animals boosted with MRT compared with that of animals irradiated with BB alone (33 (MRT) versus 26 (BB) days after treatment, P Z 0.0144). Conclusion: The data presented here are the first evidence that MRT, delivered as a boost to a conventional fractionated irradiation by broad Xray beams, is feasible, safe, and more efficient than a similar dose regimen delivered in a conventional radiation therapy mode. These results are a new step towards clinical application of MRT that could be applied as a therapeutic boost, e.g. as part of a hypofractionated radiation schedule for human metastasis management trial (3x11 Gy).

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