Abstract

Abstract BACKGROUND Radiotherapy remains a cornerstone in glioblastoma (GBM) management. A continued and unmet need in neuro-oncology is efficient non-invasive methods to differentiate post-radiation magnetic resonance imaging (MRI) changes from progressive disease (PD) in GBM patients. The clinical challenge is two-sided; avoid termination of effective therapy in case of pseudoprogression (PsP) and continuation of ineffective therapy in case of PD. We retrospectively assessed incidence, management, prognostic impact, and associated factors with PsP in a real-world GBM patient cohort. MATERIAL AND METHODS Adult (≥18 years) GBM patients diagnosed in the South-Eastern Health Region of Norway from 2015 to 2018, had received radiotherapy, and follow-up MRIs were included. Patient, tumor, and treatment characteristics were analyzed in relationship to re-evaluated MRI examinations at three and six months post-radiation using response assessment in neuro-oncology criteria. RESULTS PsP incidences at three and six months post-radiation were 20% and 8%, respectively. In adjusted analyses, methylated O6-methylguanine-DNA methyltransferase (MGMT) promoter and absence of neurological deterioration were associated with PsP at both three (p<0.001 and p=0.04, respectively) and six months (p=0.003 and p=0.04, respectively) post-radiation. Patients with PsP at MRI three months post-radiation had a median OS of 24.8 months compared to 11.4 months for patients with PD and 18.7 months in patients with stable disease (SD); the difference was significant only when comparing patients with PsP and PD (p<0.001). There was no survival benefit of treatment change for patients retrospectively evaluated as PD three months post-radiation (p=0.8). Median OS for patients in the PsP group was 31.8 months and thus longer than in the PD group (13.1 months) and the SD group (24.1 months). The difference was only significant when comparing patients with PsP and PD (p<0.001). CONCLUSION PsP incidence in this retrospective material was similar to previous reports. In addition to the previously described correlation of methylated MGMT promoter with PsP, we also found that the absence of neurological deterioration significantly correlated to PsP. Continuation of temozolomide courses did not compromise survival for patients with PD at three months post-radiation; therefore, we recommend continuing adjuvant temozolomide courses in case of inconclusive MRI findings. Funding: European Union's Horizon 2020 Programme European Research Council Grant 758657-ImPRESS.

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