Hypofractionated Dose-Escalation for Elderly Patients With a Newly Diagnosed Glioblastoma Improves Survival

Abstract

The standard of care for elderly glioblastoma patients (GBM) is 40 Gy in 15 fractions with temozolomide (TMZ). However, this regimen has a lower biologic equivalent dose (BED) compared to the Stupp regimen of 60 Gy in 30 fractions. We hypothesize that dose escalated hypofractionated radiation of 52.5 Gy in 15 fractions (BED equivalent to Stupp) will have superior survival compared to 40 Gy in 15 fractions.Elderly patients (> 60 yo) who received hypofractionated radiation with TMZ were included in this analysis. Overall survival (OS) and progression free survival (PFS) were defined as the time elapsed between surgery/biopsy and death from any cause or progression. Baseline characteristics were compared with pairwise tests. Univariate and multivariate analyses were performed.66 newly-diagnosed patients were eligible for this analysis. 39 patients were treated with 40 Gy in 15 fractions, and 27 patients were treated with 52.5 Gy in 15 fractions. The median follow up for this cohort was 8.8 months. Patients were well balanced with no significant differences in age, sex, MGMT, extent of resection, or KPS. The median OS was 7.9 months in the 40 Gy arm and 13.1 months in the 52.5 Gy arm (P = 0.035). For unmethylated patients, the median OS was 6.7 months in the 40 Gy arm and 11.3 months in the 52.5 Gy arm (P = 0.012). Increasing planning treatment volume (P = 0.007) was associated with decreased OS. On multivariate analysis, MGMT methylation (HR 0.45 [0.23-0.87] P = 0.018) and dose escalation (HR 0.45 [0.21-0.96] 0.04) remained independent prognostic factors for OS. In a multivariate model for PFS, only dose-escalation was significant (HR 0.49 [0.25-0.98] P = 0.045). No significant differences in toxicity were observed between treatment groups.Dose-escalation to 52.5 Gy in 15 fractions was associated with superior OS and PFS compared to standard of care 40 Gy in 15 fractions. This treatment regimen gives the elderly population an alternative to Stupp that is not de-escalating therapy. These hypothesis generating data support dose-escalated hypofractionation in future prospective trials.H.K. Perlow: None. M. Yang: None. B. Klamer: None. R. Raval: None. D.M. Blakaj: None. A.L. Arnett: None. S. Beyer: None. J.C. Grecula: None. M. Ammirati: None. J.B. Elder: None. R.R. Lonser: None. D. Hardesty: None. S.S. Ong: None. P. Giglio: None. C. Pillainayagam: None. J. Goranovich: None. A. Chakravarti: None. V. Gondi: Partner; Radiation Oncology Consultants, Ltd. Honoraria; UpToDate, RaySearch. Partnership; Radiation Oncology Consultants, Ltd. Co-Principal Investigator; NRG Oncology. P.D. Brown: None. J.D. Palmer: Research Grant; Varian Medical Systems, The Kroger Company. Consultant; Huron Consulting. Speaker's Bureau; Varian Medical Systems, Depuy Synthes. Advisory Board; Novocure. Member of panel; NCCN.