Incidence and outcome of pseudoprogression after radiation therapy in glioblastoma patients: A cohort study

Hanne Blakstad; Eduardo Erasmo Mendoza Mireles; Liv Cathrine Heggebø; Henriette Magelssen; Mette Sprauten; Tom Børge Johannesen; Einar Osland Vik-Mo; Henning Leske; Pitt Niehusmann; Karoline Skogen; Eirik Helseth; Kyrre Eeg Emblem; Petter Brandal

doi:10.1093/nop/npad063

Incidence and outcome of pseudoprogression after radiation therapy in glioblastoma patients: A cohort study

Neurooncol Pract. 2023 Oct 3;11(1):36-45. doi: 10.1093/nop/npad063. eCollection 2024 Feb.

Authors

Hanne Blakstad^{1

2}, Eduardo Erasmo Mendoza Mireles^{3

4}, Liv Cathrine Heggebø^{1

2}, Henriette Magelssen¹, Mette Sprauten¹, Tom Børge Johannesen^{1

5}, Einar Osland Vik-Mo^{3

4}, Henning Leske^{6

7}, Pitt Niehusmann^{6

8}, Karoline Skogen⁹, Eirik Helseth^{2

3}, Kyrre Eeg Emblem¹⁰, Petter Brandal^{1

11}

Affiliations

¹ Department of Oncology, Oslo University Hospital, Oslo, Norway.
² Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
³ Department of Neurosurgery, Oslo University Hospital, Oslo, Norway.
⁴ Vilhelm Magnus Laboratory, Institute for Surgical Research, Oslo University Hospital, Oslo, Norway.
⁵ Cancer Registry of Norway, Oslo, Norway.
⁶ Department of Pathology, Oslo University Hospital, Oslo.
⁷ University of Oslo, Oslo, Norway.
⁸ Division of Cancer Medicine, Oslo University Hospital, Oslo.
⁹ Department of Radiology, Oslo University Hospital, Oslo, Norway.
¹⁰ Department of Physics and Computational Radiology, Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.
¹¹ Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway.

Abstract

Background: Differentiating post-radiation MRI changes from progressive disease (PD) in glioblastoma (GBM) patients represents a major challenge. The clinical problem 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 the incidence, management, and prognostic impact of PsP and analyzed factors associated with PsP in a GBM patient cohort.

Methods: Consecutive GBM patients diagnosed in the South-Eastern Norway Health Region from 2015 to 2018 who had received RT and follow-up MRI were included. Tumor, patient, and treatment characteristics were analyzed in relationship to re-evaluated MRI examinations at 3 and 6 months post-radiation using Response Assessment in Neuro-Oncology criteria.

Results: A total of 284 patients were included in the study. PsP incidence 3 and 6 months post-radiation was 19.4% and 7.0%, respectively. In adjusted analyses, methylated O⁶-methylguanine-DNA methyltransferase (MGMT) promoter and the absence of neurological deterioration were associated with PsP at both 3 (p < .001 and p = .029, respectively) and 6 months (p = .045 and p = .034, respectively) post-radiation. For patients retrospectively assessed as PD 3 months post-radiation, there was no survival benefit of treatment change (p = .838).

Conclusions: PsP incidence was similar to previous reports. In addition to the previously described correlation of methylated MGMT promoter with PsP, we also found that absence of neurological deterioration significantly correlated with PsP. Continuation of temozolomide courses did not seem to compromise survival for patients with PD at 3 months post-radiation; therefore, we recommend continuing adjuvant temozolomide courses in case of inconclusive MRI findings.

Keywords: associated factors; chemoradiotherapy; glioblastoma; prognostic factors pseudoprogression.