Discrepancies in Inter-Rater Agreement on Resectability of Recurrent Glioblastoma: Complementary Post-hoc Analysis of the Prospective, Randomized DIRECTOR Trial.

Karschnia, Philipp; Vik-Mo, Einar O; Broekman, Marike L D; Le Rhun, Emilie; Esquenazi, Yoshua; Young, Jacob S; Tabatabai, Ghazaleh; Wirsching, Hans-Georg; Steinbach, Joachim P; Roder, Constantin; Suchorska, Bogdana; Bello, Lorenzo; Teske, Nico; Berger, Mitchel S; Tonn, Joerg-Christian; Jakola, Asgeir S; Schnell, Oliver; Cahill, Daniel P; Vogelbaum, Michael A; Weller, Michael; Wick, Wolfgang; Drummond, Katharine J

doi:10.1093/neuonc/noag103

Journal Article

DKFZ-2026-01125

Discrepancies in Inter-Rater Agreement on Resectability of Recurrent Glioblastoma: Complementary Post-hoc Analysis of the Prospective, Randomized DIRECTOR Trial.

Karschnia, P.DKFZ* ; Teske, N. ; Le Rhun, E. ; Wirsching, H.-G. ; Jakola, A. S. ; Roder, C. ; Cahill, D. P. ; Vik-Mo, E. O. ; Berger, M. S. ; Young, J. S. ; Wick, W.DKFZ* ; Tabatabai, G.DKFZ* ; Steinbach, J. P. ; Suchorska, B. ; Drummond, K. J. ; Bello, L. ; Broekman, M. L. D. ; Vogelbaum, M. A. ; Esquenazi, Y. ; Schnell, O. ; Weller, M. ; Tonn, J.-C.DKFZ*

2026
Oxford Univ. Press Oxford

Neuro-Oncology nn, nn (2026) [10.1093/neuonc/noag103]

Abstract: Tumor resection is a prerequisite in many studies of new glioblastoma therapeutics; however, no clear parameters for 'resectability' exist. We evaluated inter-rater variability in assessing tumor resectability and potential associations between resectability and survival in a trial cohort of glioblastoma recurrence.DIRECTOR (NCT00941460; 9/2009-6/2012) evaluated two dose-dense temozolomide regimens for first recurrent glioblastoma, yielding similar outcomes between arms. Re-resection was allowed before initiation of systemic therapy by institutional decision. Eleven surgical neuro-oncologists (blinded to final outcomes) rated whether a 'meaningful resection' was achievable for each recurrent IDH-wildtype glioblastoma based on imaging and clinical data.MRI scans from 69 patients were available (median age:58.2 ± 1.1 years, median survival:10.0 months). 40 patients underwent re-resection (median age:56.4 ± 1.7 years, median survival:10.8 months). Surgical decision-making markedly varied between raters, ranging from 30-58 of 69 cases being classified as 'resectable' (κ = 0.405). In patients who received re-resection, a 'meaningful resection' was deemed feasible by > 80% of raters in 30/40 cases (75.0%). For patients without re-resection, unanimous agreement on non-resectability occurred in only 3/29 cases (10.4%); and 5/29 tumors (17.2%) were considered resectable by > 80% of raters. Knowledge of additional clinical factors virtually never changed MRI-based judgments. While patients who had a complete resection of contrast-enhancing tumor had favorable outcomes, a consensus on resectability by > 80% of raters was not associated with prolonged overall survival.Feasibility assessment for re-resection is heterogenous among neurosurgeons, challenging single-surgeon evaluation of 'resectability'. Those findings are limited by the number of surgical raters and the size of the DIRECTOR cohort.

Keyword(s): extent of resection ; glioblastoma ; heterogeneity ; resectability ; surgery