SURG-83. Inter-rater agreement from an international expert panel on resectability of recurrent glioblastoma: a complementary post-hoc analysis of the prospective, randomized DIRECTOR trial

BACKGROUND Associations between higher extents of re-resection for glioblastoma and prolonged survival may reflect that tumors in less functional (surgically more accessible) brain areas identify with an inherently better prognosis. This post-hoc analysis of the DIRECTOR trial aimed to (I) evaluate inter-rater variability in assessing tumor resectability and (II) investigate associations between resectability, extent of resection, and survival. METHODS DIRECTOR (NCT00941460) evaluated two different temozolomide regimens for first glioblastoma relapse. Patients were eligible for re-resection per institutional decision. The two study arms were pooled due to similar outcomes; and eleven surgical neuro-oncologists rated tumor resectability for each IDH-wildtype glioblastoma with baseline MRI available. RESULTS We studied 69 patients with first IDH-wildtype glioblastoma recurrence, including 40 individuals who underwent re-resection prior to temozolomide re-challenge. In patients receiving a re-resection, a ‘meaningful resection’ was deemed feasible by 0-50% of the raters in 4/40 cases (10.0%), by 51-80% in 6/40 cases (15.0%), and by 81-100% in 30/40 cases (75.0%). Only among patients without post-operative contrast-enhancing tumor, pre-operative agreement on resectability was high. For patients without re-resection, in only 3/29 patients (10.4%) all raters agreed that tumors were not resectable; while 1-50% of the raters judged tumors as resectable in 14/29 patients (48.3%), 51-80% in 7/29 patients (24.1%), and 81-100% in 5/29 patients (17.2%). Additional knowledge of clinical factors virtually never changed the judgment based on MRI alone. Surgical decision-making markedly varied between raters, ranging from 29 to 59/69 cases being classified as ‘resectable’ (kappa-index: 0.405). Overall, consensus on resectability by >80% of the raters was not associated with favourable OS (10.4±1.8 vs 10.0±3.0 months, p=0.924) or PFS (2.0±0.5 vs 1.9±0.2 months, p=0.757). Compared to submaximal resection or patients without re-resection, patients with complete contrast-enhancement resection had longer survival, particularly in MGMT-unmethylated tumors. DISCUSSION Assessment of feasibility for re-resections in recurrent glioblastoma varies. An objective consensus would come with implications for trials and practice. We gratefully acknowledge the DIRECTOR investigators.