M. Taphoorn

Minimal clinically meaningful differences for the EORTC QLQ-C30 and EORTC QLQ-BN20 scales in brain cancer patients

BACKGROUND We aimed to determine the smallest changes in health-related quality of life (HRQoL) scores in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire core 30 and the Brain Cancer Module (QLQ-BN20), which could be considered as clinically meaningful in brain cancer patients. MATERIALS AND METHODS World Health Organisation performance status (PS) and mini-mental state examination (MMSE) were used as clinical anchors appropriate to related subscales to determine the minimal clinically important differences (MCIDs) in HRQoL change scores (range 0-100) in the QLQ-C30 and QLQ-BN20. A threshold of 0.2 standard deviation (SD) (small effect) was used to exclude anchor-based MCID estimates considered too small to inform interpretation. RESULTS Based on PS, our findings support the following integer estimates of the MCID for improvement and deterioration, respectively: physical (6, 9), role (14, 12), and cognitive functioning (8, 8); global health status (7, 4*), fatigue (12, 9), and motor dysfunction (4*, 5). Anchoring with MMSE, cognitive functioning MCID estimates for improvement and deterioration were (11, 2*) and for communication deficit were (9, 7). Estimates with asterisks were <0.2 SD and were excluded from our MCID range of 5-14. CONCLUSION These estimates can help clinicians evaluate changes in HRQoL over time, assess the value of a health care intervention and can be useful in determining sample sizes in designing future clinical trials.

Concomitant and adjuvant temozolomide (TMZ) and radiotherapy (RT) for newly diagnosed glioblastoma multiforme (GBM). Conclusive results of a randomized phase III trial by the EORTC Brain & RT Groups and NCIC Clinical Trials Group

2 Background: Standard therapy of GBM after biopsy or resection is RT. TMZ, a novel methylating agent demonstrated some activity against recurrent glioma. In a phase II trial we observed a potential survival advantage by adding TMZ concomitantly and adjuvant to RT (Stupp et al. JCO 2002). In this randomized trial we tested this novel regimen against RT. METHODS Patients (pts) age 18-70 years with histologically proven newly diagnosed GBM (WHO grade IV) were eligible. Pts were randomized between standard RT (60 Gy in 30 daily fractions of 2 Gy) versus the same RT and concomitant (TMZ 75 mg/m2/d, daily up to 42 days) followed by up to 6 cycles of adjuvant TMZ (150-200 mg/m2, daily x 5d, q28 d). Survival (intent to treat) was the primary endpoint aiming at a 30% improvement (log-rank). Pathology was centrally reviewed. RESULTS Five hundred and seventy-three pts from 85 centers were randomized. Median follow-up is 2 years, 436 patients have died. Median time between histological diagnosis and treatment start was 5 weeks. RT was delivered as prescribed in 93% of pts. Concomitant TMZ was administered without interruption in 76%, temporarily interrupted in 11% and prematurely discontinued in 12%. Adjuvant TMZ was given to 76% of pts, 36% completed all 6 cycles for a total of 924 cycles. The increase in median survival is 3 months. The log-rank test is significant with a p-value of < .0001. The hazard ratio is 0.62 (95% c.i. 0.51-0.75). Grade 3/4 hematotoxicity was observed in 7% of pts during concomitant TMZ/RT treatment, and in 16% (5.2% of cycles) of the adjuvant TMZ. Patients continue to be followed to evaluate long term effects of treatment. CONCLUSIONS Concomitant and adjuvant TMZ chemotherapy significantly improves PFS and overall survival in GBM pts. This treatment is safe and well tolerated. [Figure: see text] [Table: see text].