Comparison of postoperative radiotherapy and combined postoperative radiotherapy and chemotherapy in the multidisciplinary management of malignant gliomas. A joint radiation therapy oncology group and eastern cooperative oncology group study

Abstract

Recently, the RTOG and ECOG concluded a joint randomized study on malignant gliomas that was in progress for the past five years. A total of 626 patients entered this protocol. Sixty‐seven percent of the 535 evaluable patients have died and thus this represents a preliminary report of a major joint clinical trial. The objective of this study was to evaluate the efficacy after neurosurgery of three new treatment options as compared with control treatment of radiotherapy alone. The four options were: (1) control radiation; 6000 rad/6–7 weeks to whole brain; (2) a higher radiation dose; Control dose plus a booster dose of 1000 rad/1–2 weeks to the tumor; (3) control radiation dose plus BCNU (80 mg/m²/day IV X 3 and repeat BCNU every 8 weeks); (4) Control radiation dose plus combination methyl‐CCNU (125 mg/m²/day orally X 1 and repeat methyl‐CCNU every 8 weeks), and DTIC (150 mg/m²/day IV X 5 and repeat DTIC every 4 weeks). All pertinent patient characteristics were studied and several important prognostic factors have been identified. Notably, age, histologic type (Astrocytoma with anaplastic foci, versus glioblastoma multiforme), initial performance status, time since first symptoms and presence or absence of seizure. At this time, it appeared that there was no treatment option which was significantly better than the control. The study identified that age was the most important prognostic factor. Patients who were younger than age 40 years had an 18‐month survival of 64%, patients who were age 40–60 years had an 18‐month survival of 20%, and patients who were older than age 60 had an 18‐month survival of 8%. The study also demonstrated that a modified histologic classification of anaplastic astrocytoma versus glioblastoma provided better prognostic information than the astrocytoma grading system of Kernohan. Patients with anaplastic astrocytoma had a median survival of 27 months as compared to 8 months for patients with glioblastoma. In further evaluation of any beneficial effect of chemotherapy, it was identified that only among the 40–60‐year‐old groups, BCNU treated patients appeared to have significantly increased survival than patients in the control groups (P = 0.01, one‐sided). Similarly, methyl‐CCNU + DTIC was suggestively better than the control (P = 0.08, one‐sided). The higher radiation dose, 7000 rad/8–9 weeks appeared to give no significantly better survival over the control dose option. Both BCNU and methyl‐CCNU + DTIC produced some toxicity. The combination of methyl‐CCNU + DTIC was more toxic than BCNU, producing severe or worse thrombocytopenia in 23% of the patients as compared to 6% on BCNU.