Abstract
Simple SummaryPseudoprogression detection in glioblastoma patients remains a challenging task. Although pseudoprogression has only a moderate prevalence of 10–30% following first-line treatment of glioblastoma patients, it bears critical implications for affected patients. Non-invasive techniques, such as amino acid PET imaging using the tracer O-(2-[18F]-fluoroethyl)-L-tyrosine (FET), expose features that have been shown to provide useful information to distinguish tumor progression from pseudoprogression. The usefulness of FET-PET in IDH-wildtype glioblastoma exclusively, however, has not been investigated so far. Recently, machine learning (ML) algorithms have been shown to offer great potential particularly when multiparametric data is available. In this preliminary study, a Linear Discriminant Analysis-based ML algorithm was deployed in a cohort of newly diagnosed IDH-wildtype glioblastoma patients (n = 44) and demonstrated a significantly better diagnostic performance than conventional ROC analysis. This preliminary study is the first to assess the performance of ML in FET-PET for diagnosing pseudoprogression exclusively in IDH-wildtype glioblastoma and demonstrates its potential.Pseudoprogression (PSP) detection in glioblastoma remains challenging and has important clinical implications. We investigated the potential of machine learning (ML) in improving the performance of PET using O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) for differentiation of tumor progression from PSP in IDH-wildtype glioblastoma. We retrospectively evaluated the PET data of patients with newly diagnosed IDH-wildtype glioblastoma following chemoradiation. Contrast-enhanced MRI suspected PSP/TP and all patients underwent subsequently an additional dynamic FET-PET scan. The modified Response Assessment in Neuro-Oncology (RANO) criteria served to diagnose PSP. We trained a Linear Discriminant Analysis (LDA)-based classifier using FET-PET derived features on a hold-out validation set. The results of the ML model were compared with a conventional FET-PET analysis using the receiver-operating-characteristic (ROC) curve. Of the 44 patients included in this preliminary study, 14 patients were diagnosed with PSP. The mean (TBRmean) and maximum tumor-to-brain ratios (TBRmax) were significantly higher in the TP group as compared to the PSP group (p = 0.014 and p = 0.033, respectively). The area under the ROC curve (AUC) for TBRmax and TBRmean was 0.68 and 0.74, respectively. Using the LDA-based algorithm, the AUC (0.93) was significantly higher than the AUC for TBRmax. This preliminary study shows that in IDH-wildtype glioblastoma, ML-based PSP detection leads to better diagnostic performance.
Highlights
Despite therapeutic options consisting of maximal safe surgical resection, radiotherapy, and chemotherapy, glioblastoma has a poor prognosis with a median overall survival, depending upon age and O6-methylguanine-Deoxyribonucleic acid (DNA) methyltransferase (MGMT) promoter methylation status, ranging between 8.3 and 48.1 months [1,2,3,4]
In patients who did not undergo surgery to confirm PSP/true progression (TP) (77.3%), a follow-up magnetic resonance imaging (MRI) was obtained after a mean of 91.3 days and evaluated according to Response Assessment in Neuro-Oncology (RANO) criteria
The distribution of typical features in the study cohort in terms of age, Karnofsky Performance Status (KPS), the extent of resection, methylguanine-DNA methyltransferase (MGMT) promoter methylation, and IDH1 mutation status was balanced between the TP (n = 30) and PSP (n = 14) group (Table 1)
Summary
Despite therapeutic options consisting of maximal safe surgical resection, radiotherapy, and chemotherapy, glioblastoma has a poor prognosis with a median overall survival, depending upon age and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status, ranging between 8.3 and 48.1 months [1,2,3,4]. PSP is defined as a treatment-related tissue reaction that manifests itself as a progressive enhancing lesion on MRI ( referred to as index MRI) within the radiation field that remains stable or regresses during a further follow-up MRI without further treatment or any change of treatment [6]. The diagnosis of PSP, as per the modified Response Assessment in Neuro-Oncology (RANO) criteria [12,13], is based on either pathohistological confirmation through repeat surgery or a follow-up MRI (confirmatory MRI) obtained at least 4–6 weeks after the index MRI after chemoradiation completion [12,13]. On the confirmatory MRI, retrospective diagnosis of PSP is made when the progressive enhancing lesions regress or remain stable in size without any change in treatment
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