Experimental Therapeutics: Normal Tissue Response

Sunday, October 16, 2005 1:30 PM-3:00 PM Room No. 610/612
Chair(s): Rehemtulla, Alnawaz; Williams, Jackie

(MS015) Radiation-induced myelitis in the spinal cord of rats after single and split doses of photons and carbon ions.

Peschke, Peter*,1, Karger, Christian 1, Scholz, Michael2, Sanchez-Brandelik, Rita1, Huber, Peter1, 3, Debus, Jürgen1, 3, 1 Dept. of Radiotherapy, 69120-Heidelberg, Germany, Germany2 Dept. of Biophysics, Darmstadt, Germany, Germany3 Dept. of Clinical Radiology, Heidelberg, Germany, Germany

ABSTRACT- Objective: Clinical studies at the GSI in Darmstad are accompanied by a biological program to assess the relative biological effectiveness (RBE) of carbon ion irradiations (12-C) related to photons with special emphasis on late complications of the central nervous system (CNS). Methods: The cranial part of the cervical spinal cords of 180 rats were irradiated with 1 and 2 fractions of 12-C or photons. The target volume (field size: 10x15mm) was positioned either in the plateau-region of a 270 MeV/u 12-C-beam or in the middle of an extended Bragg-peak of a 140 MeV/u 12-C-beam. Photons were was delivered by a linear accelerator (Siemens MPX, 15 MeV). Treatment fields were defined by a multileaf collimator with an aperture of 10x15mm. Thirty rats subdivided into 5 groups (n = 6) per treatment arm were irradiated with different doses (range: 12 Gy - 61 Gy). Two groups with 6 animals each served as controls. Animals were kept under daily observation with a special focus on radiation-induced acute reactions, latency and incidence of neurological disorders. Dose-response curves for the endpoint symptomatic myelopathy (paresis II) were established and the resulting values for ED50 (dose at 50% complication probability) for radiation myelopathy were used to determine RBE-values. Results: The overall median latency of myelitis was 167 days (range, 121-288 days). 80% of all symptomatic animals developed symptoms within 136 to 212 days after irradiation. The median latency after carbon ion irradiation was shorter in animals irradiated in the Bragg peak (T50 = 157 days) than in those irradiated with plateau ions (T50 = 178 days). The ED50-values for irradiation within the plateau-region were 17.1 Gy for single dose and 24.9 Gy for split dose experiments. Irradiation of spinal cords in the Bragg peak yielded ED50-values of 13.9, and 15.8 Gy for 1 and 2 fractions, respectively. The corresponding RBE-values were 1.43, 1.37 (for 1 and 2 fractions, plateau) and 1.76, 2.16 (for 1 and 2 fractions, peak), respectively. Conclusion: In the split dose experiments, a clear fractionation effect was observed in the plateau phase, which allows more sparing of normal tissues. In contrast, no clinically relevant effect of fractionation was obtained for spinal cords when carbon ion irradiation was performed in the Bragg maximum.

Key words: Carbon Ions, Spinal Cord, Late Effects, Normal Tissues

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2005 RRS