Immune Checkpoint Inhibitor-Induced Cerebral Pseudoprogression: Patterns and Categorization.

Hans Urban,Joachim P Steinbach,Martin Sebastian,Markus Meissner,Peter Baumgarten,Agnes Koch,Adam Strzelczyk,Elke Hattingen,Katharina Filipski,Marie-Thérèse Forster,Martin Voss,Eike Steidl,Michael W Ronellenfitsch

doi:10.3389/fimmu.2021.798811

Abstract

BackgroundThe inclusion of immune checkpoint inhibitors (ICIs) in therapeutic algorithms has led to significant survival benefits in patients with various metastatic cancers. Concurrently, an increasing number of neurological immune related adverse events (IRAE) has been observed. In this retrospective analysis, we examine the ICI-induced incidence of cerebral pseudoprogression and propose a classification system.MethodsWe screened our hospital information system to identify patients with any in-house ICI treatment for any tumor disease during the years 2007-2019. All patients with cerebral MR imaging (cMRI) of sufficient diagnostic quality were included. cMRIs were retrospectively analyzed according to immunotherapy response assessment for neuro-oncology (iRANO) criteria.ResultsWe identified 12 cases of cerebral pseudoprogression in 123 patients treated with ICIs and sufficient MRI. These patients were receiving ICI therapy for lung cancer (n=5), malignant melanoma (n=4), glioblastoma (n=1), hepatocellular carcinoma (n=1) or lymphoma (n=1) when cerebral pseudoprogression was detected. Median time from the start of ICI treatment to pseudoprogression was 5 months. All but one patient developed neurological symptoms. Three different patterns of cerebral pseudoprogression could be distinguished: new or increasing contrast-enhancing lesions, new or increasing T2 predominant lesions and cerebral vasculitis type pattern.ConclusionCerebral pseudoprogression followed three distinct patterns and was detectable in 3.2% of all patients during ICI treatment and in 9.75% of the patients with sufficient brain imaging follow up. The fact that all but one of the affected patients developed neurological symptoms, which would be classified as progressive disease according to iRANO criteria, mandates vigilance in the diagnosis and treatment of ICI-induced cerebral lesions.

Highlights

Cancer cells can suppress immune system activation by hijacking inhibitory pathways of T cell activation
We identified 12 patients with cerebral pseudoprogression in a cohort of 372 patients with Immune-checkpoint inhibitors (ICIs) treatment (123 with sufficient brain imaging; 9.8% rate of cerebral pseudoprogression of the patients with sufficient imaging during the treatment) (Figure 1: Consort diagram)
At the time of diagnosis of pseudoprogression, patients had already been diagnosed with brain metastases or, in the one case of glioblastoma, primary cancer of the brain. of patients showed abnormal findings in the neurological examination upon diagnosis of pseudoprogression

Summary

Introduction

Cancer cells can suppress immune system activation by hijacking inhibitory pathways of T cell activation. The efficacy of ICIs has been demonstrated for treating cerebral metastases as well, both as monotherapy and in combination with radiation therapy [6, 7]. In these patients, it is of major importance to detect immune-related adverse events (IRAE), which can only be differentiated from progressive disease by specific additional examinations [8]. An increasing number of neurological immune related adverse events (IRAE) has been observed In this retrospective analysis, we examine the ICIinduced incidence of cerebral pseudoprogression and propose a classification system

Methods

Results

Discussion

Conclusion