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Response of rat intracranial 9L gliosarcoma to microbeam radiation therapy

Brookhaven National Laboratory, Upton, NY 11973 (F.A.D., G.L.D., N.Z., L.A.P., T.B., J.T., B.R., P.L.M., M.M.N., J.A.N., F.P.R.); State University of New York, Stony Brook, NY 11794 (T.M.B., S.R.M.); Long Island Jewish Medical Center, New Hyde Park, NY 11040 (P.M.F., A.F., E.M.R); University of Ioannina, 45110 Ioannina, Greece (J.K.-E.); and Pharmacyclics, Inc., Sunnyvale, CA 94086 (J.A.L.S.)

² Address correspondence and reprint requests to F. Avraham Dilmanian, Medical Department, Bldg. 490, Brookhaven National Laboratory, Upton, NY 11973-5000.

Radiotherapeutic doses for malignant gliomas are generally palliative because greater, supposedly curative doses would impart clinically unacceptable damage to nearby vital CNS tissues. To improve radiation treatment for human gliomas, we evaluated microbeam radiation therapy, which utilizes an array of parallel, microscopically thin (<100 µm) planar beams (microbeams) of synchrotron-generated X rays. Rats with i.c. 9L gliosarcoma tumors were exposed laterally to a single microbeam, 27 µm wide and 3.8 mm high, stepwise, to produce irradiation arrays with 50, 75, or 100 µm of on-center beam spacings and 150, 250, 300, or 500 Gy of in-slice, skin-entrance, single-exposure doses. The resulting array size was 9 mm wide and 10.4 mm high (using three 3.8-mm vertical tiers); the beam's median energy was 70 keV. When all data were collated, the median survival was 70 days; no depletion of nerve cells was observed. However, when data from the highest skin-entrance dose and/or the smallest microbeam spacings were excluded, the median survival time of the subset of rats was 170 days, and no white matter necrosis was observed. Others have reported unilateral single-exposure broad-beam irradiation of i.c. 9L gliosarcomas at 22.5 Gy with a median survival of only 34 days and with severe depletion of neurons. These results suggest that the therapeutic index of unidirectional microbeams is larger than that of the broad beams and that an application for microbeam radiation therapy in treating certain malignant brain tumors may be found in the future.

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