Isocitrate dehydrogenase 1 mutant glioblastomas demonstrate a decreased rate of pseudoprogression: A multi-institutional experience

Homan Mohammadi, Kevin Shiue, G. Daniel Grass, Vivek Verma, Kay Engellandt, Dirk Daubner, Gabriele Schackert, Mercia J. Gondim, Dibson Gondim, Alexander O. Vortmeyer, Aaron P. Kamer, William Jin, Timothy J. Robinson, Gordon Watson, Hsiang Hsuan M. Yu, Tim Lautenschlaeger

Research output: Contribution to journalArticle

Abstract

Background: Pseudoprogression (psPD) represents false radiologic evidence of tumor progression and is observed in some glioblastoma (GBM) patients after postoperative chemoradiation (CRT) with temozolomide (TMZ). The ambiguity of the psPD diagnosis confounds identification of true progression and may lead to unnecessary interventions. The association between psPD and isocitrate dehydrogenase 1 (IDH1) mutational (mut) status is understudied, and its incidence may alter clinical decision making. Methods: We retrospectively evaluated 120 patients with IDH1-mut (n = 60) and IDH1-wild-type (IDH-WT; [n = 60]) GBMs who received postoperative CRT with TMZ at 4 academic institutions. Response Assessment in Neuro-Oncology criteria were used to identify psPD rates in routine brain MRIs performed up to 90 days after CRT completion. Results: Within 90 days of completing CRT, 9 GBM patients (1 [1.7%] IDH1-mut and 8 [13.3%] IDH1-WTs) demonstrated true progression, whereas 17 patients (3 [5%] IDH1-muts and 14 [23.3%] IDH1-WTs) demonstrated psPD (P =. 004). IDH1-mut GBMs had a lower probability of psPD (hazard ratio: 0.173, 95% CI, 0.047-0.638, P =. 008). Among the patients with radiologic signs suggestive of progression (n = 26), psPD was found to be the cause in 3 of 4 (75.0%) of the IDH1-mut GBMs and 14 of 22 (63.6%) of the IDH1-WT GBMs (P =. 496). Median overall survival for IDH1-mut and IDH1-WT GBM patients was 40.3 and 23.0 months, respectively (P <. 001). Conclusions: IDH1-mut GBM patients demonstrate lower absolute rates of psPD expression. Irrespective of GBM subtype, psPD expression was more likely than true progression within 90 days of completing CRT. Continuing adjuvant treatment for IDH1-mut GBMs is suggested if radiologic progression is suspected during this time interval.

Original languageEnglish (US)
Pages (from-to)185-195
Number of pages11
JournalNeuro-Oncology Practice
Volume7
Issue number2
DOIs
StatePublished - Mar 19 2020

Keywords

  • glioblastoma
  • isocitrate dehydrogenase 1
  • pseudoprogression
  • radiation therapy
  • temozolomide

ASJC Scopus subject areas

  • Medicine (miscellaneous)

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    Mohammadi, H., Shiue, K., Grass, G. D., Verma, V., Engellandt, K., Daubner, D., Schackert, G., Gondim, M. J., Gondim, D., Vortmeyer, A. O., Kamer, A. P., Jin, W., Robinson, T. J., Watson, G., Yu, H. H. M., & Lautenschlaeger, T. (2020). Isocitrate dehydrogenase 1 mutant glioblastomas demonstrate a decreased rate of pseudoprogression: A multi-institutional experience. Neuro-Oncology Practice, 7(2), 185-195. https://doi.org/10.1093/nop/npz050