Clinical utility of neurocognitive function (NCF), quality of life (QOL), and symptom assessment as prognostic factors for survival and measures of treatment effects on RTOG 0525.

2016 Background: RTOG 0525, a randomized phase III study compared dose-dense (dd) versus standard dose (sd) temozolomide in patients with newly diagnosed glioblastoma. NCF tests, and Symptom and QOL questionnaires examined the Net Clinical Benefit (NCB) of therapy. The prognostic value of NCB measures for survival outcomes and the differential impact of therapy are reported here. Methods: NCF (Hopkins Verbal Learning Test-Revised, Trail Making Test, Controlled Oral Word Association), and Symptom (M. D. Anderson Symptom Inventory-Brain Tumor Module [MDASI-BT]) and QOL questionnaires (EORTC QLQ-C30/BN20) were completed in a subset of patients at baseline (B) and longitudinally while on study. Univariate (UV) and multivariate (MV) Cox proportional hazard regression modeling determined the prognostic value of a priori selected assessments at baseline (B) and early change from B to cycle 1 (C1Δ) for overall (OS) and progression free survival (PFS). Two-sample proportional test statistic was used to evaluate differences between treatments (dd vs sd) in symptomatic worsening from B to cycle 4 (C4Δ) in patients without progression. Results: Of 182 randomized patients (246 consented) > 85% completed assessment at B. NCF tests and the physical functioning QOL scale were associated with OS and PFS at B. C1Δ in all NCB components were associated with OS and PFS. The MDASI-BT and global QOL detected symptomatic differences between arms (dd > sd) at C4Δ. Conclusions: Longitudinal collection of NCB measures is feasible and complementary (Table) in cooperative group studies providing an added dimension to standard outcome measures. NCF and QOL at baseline were prognostic for OS and PFS and may impact stratification; NCB early changes were associated with OS and PFS and may help to assess response or progression; and MDASI-BT and QOL changes demonstrated sensitivity to adverse treatment effects (dd>sd) arm and may help in risk/benefit analyses. Support: NCI U10CA 21661, U10CA37422, ABC2, and Merck Pharmaceuticals. P<0.05 OS PFS Toxicity dd vs sd + = 1, ++ > 1 module UV MV UV MV B NCF ++ ++ ++ + MDASI QOL + + + + B→C1Δ NCF ++ ++ ++ + MDASI ++ + + + QOL + + B→C4Δ NCF MDASI ++ QOL +