Radioresponse of human astrocytic tumors across grade as a function of acute and chronic irradiation.

Abstract

Astrocytomas make up the largest group of primary brain tumors of glial origin. Long term survival is rare with high grade tumors (grades 3 and 4), which recur despite subtotal resection, chemotherapy, and aggressive postoperative radiation therapy. In contrast, the 5-year survival for low grade astrocytomas (grades 1 and 2) following subtotal resection and postoperative radiotherapy approaches 50%. Variable sensitivity across grade may contribute to the difference in the behavior of these tumors. To investigate this possibility, the radioresponse of human glial tumors across grade as a function of the dose rate of irradiation was studied. Cell lines derived from a low grade astrocytoma (grade 1) and two high grade astrocytomas (grades 3 and 4) were established in culture. Clonal survival was determined following irradiation of the three cell lines with Cesium 137 gamma rays at high dose rate, 78 Gy/hr, and at low dose rate, range 14 cGy to 79 cGy/hr. The low grade astrocytoma was found to be more radiosensitive than either of the high grade tumors. The alpha/beta (Gy-1/Gy-2) values (linear quadratic model) were 0.35/0.082 for the grade 1 line and 0.20/0.036 and 0.30/0.045 for the grade 3 and 4, respectively. D0 (cGy) values (single-hit multi-target model) were 99, 144, and 117 for grades 1, 3, and 4, respectively. A dose rate effect was present for all three tumor lines irradiated from 14 cGy/hr to 78 Gy/hr. An inverse dose rate effect was also noted at 37 cGy/hr for each of the astrocytic lines. These findings may be useful in the development of strategies to treat astrocytic brain tumors which use high and/or low dose rate irradiation.