QUALITY-ADJUSTED SURVIVAL ANALYSIS OF MALIGNANT GLIOMA, PATIENTS TREATED WITH TWICE-DAILY RADIATION (RT) AND CARMUSTINE - A REPORT OF RADIATION-THERAPY ONCOLOGY GROUP (RTOG)-83-02

Purpose: To quantify the quality of life of malignant glioma patients treated on a randomized Phase I/II trial of twice-daily radiation ther apy (RT) and carmustine, using a modified quality adjusted survival (Q AS) model, and to compare the QAS among assigned treatment arms. Mater ials and Methods: The Radiation Therapy Oncology Group (RTOG) accrued 786 malignant glioma patients to a Phase I/II randomized dose escalati on trial of twice-daily RT with carmustine from 1983 to 1989. Patients were randomized to one of four arms of hyperfractionated RT in 1.2 Gy twice daily (BID) fractions (64.8 Gy, 72.0 Gy, 76.8 Gy, or 81.6 Gy) o r to either of two accelerated hyperfractionated RT arms in 1.6 Gy BID fractions (48.0 or 54.4 Gy). Although preliminary toxicity and surviv al data have been published, little information is available regarding the quality of these patients' lives during and following such therap y. QAS is a refinement of the methodology for assessing survival quali ty among breast cancer patients receiving adjuvant chemotherapy. The Q AS method allows for inclusion of both improvement and decline in neur ologic functional status. Patients were scored by the presence or abse nce of 15 neurologic signs and symptoms at on-study and at every follo w-up. Within each category were gradations of severity, with the quali ty survival time (Q-TIME) adjusted according to any changes in these n eurologic findings. The summation of all changes in signs and symptoms were weighted by 1/15th and incorporated into the QAS model as QAS = Q-TIME - TOX - RRX. TOX was the time spent with treatment-related toxi cities, and RRX was the time spent in recovery from subsequent therapy . Results: Of 747 evaluable patients, the average QAS time was 18.5 mo nths. The average QAS for the hyperfractionated arms of 64.8 Gy, 72.0 Gy, 76.8 Gy, and 81.6 Gy were 15.6, 20.8, 10.0, and 13.7 months, respe ctively. For the accelerated hyperfractionated RT arms of 48.0 and 54. 4 Gy, the average QAS times were 13.1 and 13.4 months. The QAS time of the 72.0 Gy arm was significantly longer than that of all other group s, except the 64.8 Gy arm. As expected, the QAS times were strongly di scriminated by both age and Karnofsky Performance Scores (KPS) (p < 0. 001). Younger patients and patients with high KPS benefited most from assignment to the 72.0 Gy arm; QAS time was not significantly longer i n any treatment arm among patients over age 50 or with KPS scores of 8 0 or less. Conclusions: This quality-adjusted survival methodology can be successfully applied to malignant glioma patients and permits a qu antitative assessment of the influence of investigational therapies on patient quality of life. This analysis confirms the potential benefit of intermediate dose (72.0 Gy) hyperfractionated RT for selected mali gnant glioma patients.