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Various attempts have been made to improve the effectiveness of radiation in the treatment of cerebral malignant astrocytomas. A trend favoring multiple daily fractionated (MDF) radiation therapy over conventional single daily fractionated (CF) radiation therapy was identified in our previous study. In order to assess the effect of MDF with and without misonidazole, a province-wide prospective randomized trial was initiated in January 1981. By March 1984, 124 patients with histologically verified grade III and IV astrocytomas were randomized to CF (5800 cGy/6 weeks/30 fractions), MDF (6141 cGy/4.5 weeks/69 fractions at 89 cGy every 3-4 hours, three times a day) and MDF in combination with misonidazole (1.25 g/m2 three times weekly for the first 3 weeks). Thirty-eight patients were randomized to CF, 43 patients to MDF, and 43 patients to MDF and misonidazole. At the preliminary assessment in July 1984, the median survival time was 27 weeks for the CF group, 39 weeks for the MDF group and 49 weeks for MDF and misonidazole group. The 1-year actuarial survival rate from surgery was 20% for CF group, 41% for MDF group, and 45% for MDF and misonidazole group. There is a statistically significant difference (P less than 0.001) between the CF and MDF group. However, the addition of misonidazole does not significantly alter survival.

In the first third of this century, the prevailing concept was that malignant cells had a brief period of sensitivity and radiation treatments were ideally given in overall times of 2 weeks or less. Following the Second World War, routine treatment times were extended to 5 to 8 weeks to avoid severe acute normal tissue reactions and achieve higher tumor doses. In reaction to these prolonged overall times, a series of large-fraction, shortened-overall-time clinical experiments were attempted, with disastrous normal tissue effects and poor tumor control. More recently, attempts to accelerate treatment have been accomplished by utilizing multiple fractions per day or semicontinuous irradiation. Unfortunately, the majority of these attempts have been forced by the occurrence of unacceptable normal tissue reactions to significantly reduce total dose or introduce lengthy splits in treatment. These results suggest that in our current state of knowledge accelerated schedules be reserved for use in the treatment of rapidly proliferating neoplasms or for palliation.Cuncer 5 5 2 1 12-21 17. 1985.

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