Tumor recurrence or treatment-related changes following chemoradiation in patients with glioblastoma: does pathology predict outcomes?

Background: Despite surgical resection and chemoradiation, all patients with GBM invariably recur. Radiological imaging is limited in differentiating tumor recurrence (TR) from treatment-related changes (TRC); therefore, re-resection is often needed. Few studies have assessed the relationship between re-resection histopathology and overall survival (OS). We performed a large retrospective study to analyze the clinical significance of histopathology following re-resection and its influence on genomic sequencing results. Methods: Clinical, radiographic, and histological information was compiled from 675 patients with GBM (2005–2017). 137-patients met the inclusion criteria. IDH1 p.R132H immunohistochemistry was performed in all patients. Next-generation sequencing interrogating 205 tumor-related genes was performed in 68-patients. Molecular alterations from initial and subsequent resections were compared in a subset of cases. Results: There were no differences in OS (17.3-months TRC vs. 21-months TR, p = 0.881) and survival from progression (9.0 vs. 11.7-months, p = 0.778) between patients with TR and TRC on re-resection. TR patients were more likely to receive salvage radiotherapy (26% vs. 0%) and tumor-treating fields (25% vs. 5%,) after the 2nd surgery than the TRC group (p = < 0.045). There was no correlation between mutations and TRC. IDH status was not predictive of TRC. Fifteen-patients had sequencing results from multiple surgeries without evident differences in genomic alterations. Conclusions: Histopathologic findings following chemoradiation do not correlate with clinical outcomes. Such findings should be considered during patient management and clinical trial enrollment. Standardization of tissue sampling and interpretation following reoperation is urgently needed. Future work is required to understand the relationship between the mutation profile following TRC and outcomes.