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Discrepancies in inter-rater agreement on resectability of recurrent glioblastoma: Complementary post-hoc analysis of the prospective, randomized DIRECTOR trial

Karschnia P, Teske N, Le Rhun E, Wirsching HG, Jakola AS, Roder C, Cahill DP, Vik-Mo EO, Berger MS, Young JS, Wick W, Tabatabai G, Steinbach JP, Suchorska B, Drummond KJ, Bello L, Broekman ML, Vogelbaum MA, Esquenazi Y, Schnell O, Weller M, Tonn JC (2026)

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Publication Type: Journal article

Publication year: 2026

Journal

Book Volume: 28

Pages Range: 2197-2210

Journal Issue: 9

DOI: 10.1093/neuonc/noag103

Abstract

Background: 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. Methods: 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. Results: MRI scans from 69 patients were available (median age: 58.2 ± 1.1 years, median survival: 10.0 months). Forty 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 to 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. Discussion: Feasibility assessment for re-resection is heterogeneous 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.

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APA:

Karschnia, P., Teske, N., Le Rhun, E., Wirsching, H.G., Jakola, A.S., Roder, C.,... Tonn, J.C. (2026). Discrepancies in inter-rater agreement on resectability of recurrent glioblastoma: Complementary post-hoc analysis of the prospective, randomized DIRECTOR trial. Neuro-Oncology, 28(9), 2197-2210. https://doi.org/10.1093/neuonc/noag103

MLA:

Karschnia, Philipp, et al. "Discrepancies in inter-rater agreement on resectability of recurrent glioblastoma: Complementary post-hoc analysis of the prospective, randomized DIRECTOR trial." Neuro-Oncology 28.9 (2026): 2197-2210.

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