Health related quality of life and cognitive status in patients with glioblastoma multiforme receiving escalating doses of conformal three dimensional radiation on RTOG 98-03

Abstract

The Radiation Therapy Oncology Group (RTOG) embarked on a phase I/II study of patients suffering from glioblastoma multiforme (protocol 98-03) to assess the impact of dose escalation with 3-D conformal techniques. The primary endpoints were feasibility and survival. This report describes the outcome of secondary endpoints (quality of life and neurocognitive function). Patients with supratentorial GBM were treated with a combination of carmustine (BCNU) and conformal irradiation (dose levels: 66, 72, 78, 84 Gy, respectively). Quality of Life was assessed with the Spitzer Quality of Life Index. Neurocognitive function was determined by the Mini Mental Status Examination. The latter tests were administered at the start of irradiation, at the end of irradiation and then at 4 month intervals. Relatively high compliance was achieved with both of the tools (SQLI; MMSE). Overall rates of survival between baseline SQLI scores <7 and 7-10 were statistically significantly different [HR = 1.72, 95% CI (1.22, 2.4), P = 0.0015]. The significant impact of high SQLI score on survival was preserved in multivariate analysis. The component of this index which made the greatest contribution was the patient's independence. There was continual deterioration of neurocognitive function within the populations studied. No correlation was seen between dose escalation and the secondary endpoints studied. Radiation dose escalation and assessment of its impact on life quality and neurocognition can be carried out in a large international trial. Baseline SQLI is a statistically significant determinant of survival. Those who maintain independence have superior survival to those who are reliant on others.

Fig. 1

Schema of RTOG 9803. a Radiation therapy to be administered in 2 Gy/day fractions. All patients will have a field reduction after 46 Gy. b BCNU (80 mg/m²) on days 1, 2, and 3 of the first week of radiotherapy repeated on days 56, 57 and 58. Then every 8 weeks for four cycles for a total of six cycles (maximum BCNU dose 1,440 mg/m²). c PTV₁ = CTV₁ + 3 mm (CTV₁ = gross tumor + 15 mm margin); PTV₂ = gross tumor + 3 mm margin

Fig. 2

Overall survival by SQLI scores (baseline and subdomains). a Overall survival by baseline SQLI score. b Overall survival by baseline SQLI daily living. c Overall survival by baseline SQLI outlook

Fig. 3

Time to clinical neurocognitive failure with scoring according to absolute MMSE breakpoint or with adjustments for age and educational levels. a Time to clinical deterioration (MMSE < 23) by group for baseline non-failures (MMSE ≥ 23 at baseline). b Time to clinical deterioration (MMSE < age/education cutoff) by group for baseline non-failures (MMSE ≥ age/education cutoff at baseline)