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. 2023 Mar 18;5(1):vdad028.
doi: 10.1093/noajnl/vdad028. eCollection 2023 Jan-Dec.

Retrospective examination of pseudoprogression in IDH mutant gliomas

Ethan A Wetzel  1 , Matthew J Farrell  2 , Blaine S C Eldred  1 , Vicki Liu  1 , Ishan Saha  1 , Serendipity Zapanta Rinonos  1 , Terry Prins  1 , Tie Li  1 , Minsong Cao  2 , John Hegde  2 , Tania Kaprealian  2 , Negar Khanlou  3 , Linda M Liau  4 , Phioanh Leia Nghiemphu  1 , Timothy Francis Cloughesy  1 , Robert A Chong  1 , Benjamin M Ellingson  4   5 , Albert Lai  1
Affiliations

Retrospective examination of pseudoprogression in IDH mutant gliomas

Ethan A Wetzel et al. Neurooncol Adv. .

Abstract

Background: Tumor surveillance of isocitrate dehydrogenase (IDH) mutant gliomas is accomplished via serial contrast MRI. When new contrast enhancement (CEnew) is detected during postsurgical surveillance, clinicians must assess whether CEnew indicates pseudoprogression (PsP) or tumor progression (TP). PsP has been better studied in IDH wild-type glioblastoma but has not been well characterized in IDH mutant gliomas. We conducted a retrospective study evaluating the incidence, predictors, natural history, and survival of PsP patients in a large cohort of IDH mutant glioma patients treated at a single institution.

Methods: We identified 587 IDH mutant glioma patients treated at UCLA. We directly inspected MRI images and radiology reports to identify CEnew and categorized CEnew into TP or PsP using MRI or histopathology.

Results: Fifty-six percent of patients developed CEnew (326/587); of these, 92/326 patients (28% of CEnew; 16% of all) developed PsP and 179/326 (55%) developed TP. All PsP patients had prior radiation, chemotherapy, or chemoradiotherapy. PsP was associated with longer overall survival (OS) versus TP patients and similar OS versus no CEnew. PsP differs from TP based on earlier time of onset (median 5.8 vs 17.4 months from treatment, P < .0001) and MRI features that include punctate enhancement and enhancement location.

Conclusion: PsP patients represented 28% of CEnew patients and 16% of all patients; PsP patients demonstrated superior outcomes to TP patients, and equivalent survival to patients without CEnew. PsP persists for <1 year, occurs after treatment, and differs from TP based on time of onset and radiographic features. Poor outcomes after CEnew are driven by TP.

Keywords: IDH1/2; contrast enhancement; glioma; pseudoprogression; radiation necrosis.

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Figures

Figure 1.
Figure 1.
Prognostic impact of CEnew and preoperative enhancement. Kaplan–Meier analysis of UCLA IDH mutant glioma patients evaluating the prognostic impact of CEnew (A–F). (A–F) show OS for patients with CEnew and patients with No CEnew. Log-rank P values comparing median OS between No CEnew and CEnew for All (A), LO (B), AO (C), LA (D), AA (E), and G4 Astro (F) were <.0001, .003, .002, .0001, <.0001, and .005, respectively. AA, anaplastic astrocytomas; AO, anaplastic oligodendrogliomas; CEnew, new contrast enhancement; G4 Astro, grade 4 astrocytomas; IDH, isocitrate dehydrogenase; LA, low-grade astrocytomas; LO, low-grade oligodendrogliomas; OS, overall survival.
Figure 2.
Figure 2.
Time from definitive therapy to PsP or TP. Kaplan–Meier analysis of the time from definitive therapy (chemotherapy or radiation) initiation to the appearance of PsP or TP in All (A), LO (B), AO (C), LA (D), AA (E), and G4 Astro (F). Log-rank P values comparing the time to PsP versus TP in All, LO, AO, LA, AA, and G4 Astro were <.0001, .008, .02, .007, <.0001, and .6, respectively. AA, anaplastic astrocytomas; AO, anaplastic oligodendrogliomas; G4 Astro, grade 4 astrocytomas; LA, low-grade astrocytomas; LO, low-grade oligodendrogliomas; PsP, pseudoprogression.
Figure 3.
Figure 3.
Prognostic impact of PsP on OS, Progression Free Survival (PFS), and resOS. Kaplan–Meier analysis examining the survival effects of PsP, TP, and No CEnew. (A) and (D) show OS and resOS, respectively, for patients with PsP and TP (log-rank P < .0001 and <.0001, respectively). (B) and (C) show OS for patients with PsP and no CEnew, where (C) has patients with both PsP and TP removed (log-rank P value = .01 and .9, respectively). CEnew, new contrast enhancement; OS, overall survival; PsP, pseudoprogression; resOS, residual overall survival.
Figure 4.
Figure 4.
Survival implications and predictors of CEnew, PsP, and TP. Flowchart depicting summary of findings and the change in PsP/TP risk and survival outcomes at various points in the clinical course of an IDH mutant glioma patient. Other results not shown here include, PsP duration = 8 months, 11% of PsP does not resolve, and repeat RT did not increase PsP risk. All OS values are in years and percentages are of all patients (n = 587, 10% are censored CEnew). CEnew, new contrast enhancement; IDH, isocitrate dehydrogenase; OS, overall survival; PsP, pseudoprogression; RT, radiation therapy.
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