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Distinguishing Pseudoprogression From True Early Progression in Isocitrate Dehydrogenase Wild-Type Glioblastoma by Interrogating Clinical, Radiological, and Molecular Features.

ABSTRACT: Background: Pseudoprogression (PsP) mimics true early progression (TeP) in conventional imaging, which poses a diagnostic challenge in glioblastoma (GBM) patients who undergo standard concurrent chemoradiation (CCRT). This study aimed to investigate whether perioperative markers could distinguish and predict PsP from TeP in de novo isocitrate dehydrogenase (IDH) wild-type GBM patients. Methods: New or progressive gadolinium-enhancing lesions that emerged within 12 weeks after CCRT were defined as early progression. Lesions that remained stable or spontaneously regressed were classified as PsP, otherwise persistently enlarged as TeP. Clinical, radiological, and molecular information were collected for further analysis. Patients in the early progression subgroup were divided into derivation and validation sets (7:3, according to operation date). Results: Among 234 consecutive cases enrolled in this retrospective study, the incidences of PsP, TeP, and neither patterns of progression (nP) were 26.1% (61/234), 37.6% (88/234), and 36.3% (85/234), respectively. In the early progression subgroup, univariate analysis demonstrated female (OR: 2.161, P = 0.026), gross total removal (GTR) of the tumor (OR: 6.571, P < 001), located in the frontal lobe (OR: 2.561, P = 0.008), non-subventricular zone (SVZ) infringement (OR: 10.937, P < 0.001), and methylated O-6-methylguanine-DNA methyltransferase (MGMT) promoter (mMGMTp) (OR: 9.737, P < 0.001) were correlated with PsP, while GTR, non-SVZ infringement, and mMGMTp were further validated in multivariate analysis. Integrating quantitative MGMTp methylation levels from pyrosequencing, GTR, and non-SVZ infringement showed the best discriminative ability in the random forest model for derivation and validation set (AUC: 0.937, 0.911, respectively). Furthermore, a nomogram could effectively evaluate the importance of those markers in developing PsP (C-index: 0.916) and had a well-fitted calibration curve. Conclusion: Integrating those clinical, radiological, and molecular features provided a novel and robust method to distinguish PsP from TeP, which was crucial for subsequent clinical decision making, clinical trial enrollment, and prognostic assessment. By in-depth interrogation of perioperative markers, clinicians could distinguish PsP from TeP independent from advanced imaging.

SUBMITTER: Li M

PROVIDER: S-EPMC8093388 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background and purposeIsocitrate dehydrogenase (IDH) wild-type lower-grade gliomas (histologic grades II and III) with epidermal growth factor receptor (EGFR) amplification or telomerase reverse transcriptase (TERT) promoter mutation are reported to behave similar to glioblastoma. We aimed to evaluate whether MR imaging features could identify a subset of IDH wild-type lower-grade gliomas that carry molecular features of glioblastoma.Materials and methodsIn this multi-institutional retrospective study, pathologically confirmed IDH wild-type lower-grade gliomas from 2 tertiary institutions and The Cancer Genome Atlas constituted the training set (institution 1 and The Cancer Genome Atlas, 64 patients) and the independent test set (institution 2, 57 patients). Preoperative MRIs were analyzed using the Visually AcceSAble Rembrandt Images and radiomics. The molecular glioblastoma status was determined on the basis of the presence of EGFR amplification and TERT promoter mutation. Molecular glioblastoma was present in 73.4% and 56.1% in the training and test sets, respectively. Models using clinical, Visually AcceSAble Rembrandt Images, and radiomic features were built to predict the molecular glioblastoma status in the training set; then they were validated in the test set.ResultsIn the test set, a model using both Visually AcceSAble Rembrandt Images and radiomic features showed superior predictive performance (area under the curve = 0.854) than that with only clinical features or Visually AcceSAble Rembrandt Images (areas under the curve = 0.514 and 0.648, respectively; P < . 001, both). When both Visually AcceSAble Rembrandt Images and radiomics were added to clinical features, the predictive performance significantly increased (areas under the curve = 0.514 versus 0.863, P < .001).ConclusionsMR imaging features integrated with machine learning classifiers may predict a subset of IDH wild-type lower-grade gliomas that carry molecular features of glioblastoma.

Project description:PurposeGlioblastomas (GBM) are the most common malignant primary brain tumors in adults and have a dismal prognosis. Patients frequently suffer from local tumor recurrences, with limited therapeutic options. Re-irradiation represents a possible intervention, but given the recent 5th edition of the World Health Organization classification of central nervous system tumors, studies in isocitrate dehydrogenase wild type (IDH-wt) cohorts undergoing a second course of radiotherapy remain limited. Herein, we sought to describe our institutional experience and outcomes after GBM IDH-wt re-irradiation.Materials and methodsGBM patients with confirmed IDH-wt status undergoing re-irradiation were included in this single-center, retrospective analysis.ResultsA total of 88 patients were analyzed. The median clinical and radiographic follow-up periods were 4.6 months and 4.4 months, respectively. Most patients had a Karnofsky performance status of at least 80% (n = 57). The median biologically effective dose and 2 Gy equivalent dose (EQD2) for re-irradiations, assuming an α/β ratio of 10 Gy for GBM, were 51.4 and 42.8 Gy, respectively. In total, 71 deaths were recorded. The median overall survival (OS) was 8.0 months. Multivariable Cox regression of OS revealed a positive influence of gross total resection vs. biopsy or no resection (hazard ratio: 0.43, p = 0.02). The median progression-free survival (PFS) was 5.9 months. The multivariable Cox regression for PFS did not detect any significant factors. No clear evidence of radiation necrosis was recorded during the available follow-up. However, only a minority (n = 4) of patients underwent surgery after re-irradiation, none showing histopathological proof of radiation necrosis.ConclusionThe prognosis for recurrent IDH-wt GBM after re-irradiation is poor. Patients who are amenable and able to undergo re-resection may have a favorable OS. A second course of radiotherapy with a moderate cumulative EQD2 and small- to medium-sized planning target volumes appeared safe regarding the occurrence of radiation necrosis.

Project description:PurposeThis study aimed to develop a radiomics signature for the preoperative prognosis prediction of isocitrate dehydrogenase (IDH)-wild-type glioblastoma (GBM) patients and to provide personalized assistance in the clinical decision-making for different patients.Materials and methodsA total of 142 IDH-wild-type GBM patients classified using the new classification criteria of WHO 2021 from two centers were included in the study and randomly divided into a training set and a test set. Firstly, their clinical characteristics were screened using univariate Cox regression. Then, the radiomics features were extracted from the tumor and peritumoral edema areas on their contrast-enhanced T1-weighted image (CE-T1WI), T2-weighted image (T2WI), and T2-weighted fluid-attenuated inversion recovery (T2-FLAIR) magnetic resonance imaging (MRI) images. Subsequently, inter- and intra-class correlation coefficient (ICC) analysis, Spearman's correlation analysis, univariate Cox, and the least absolute shrinkage and selection operator (LASSO) Cox regression were used step by step for feature selection and the construction of a radiomics signature. The combined model was established by integrating the selected clinical factors. Kaplan-Meier analysis was performed for the validation of the discrimination ability of the model, and the C-index was used to evaluate consistency in the prediction. Finally, a Radiomics + Clinical nomogram was generated for personalized prognosis analysis and then validated using the calibration curve.ResultsAnalysis of the clinical characteristics resulted in the screening of four risk factors. The combination of ICC, Spearman's correlation, and univariate and LASSO Cox resulted in the selection of eight radiomics features, which made up the radiomics signature. Both the radiomics and combined models can significantly stratify high- and low-risk patients (p < 0.001 and p < 0.05 for the training and test sets, respectively) and obtained good prediction consistency (C-index = 0.74-0.86). The calibration plots exhibited good agreement in both 1- and 2-year survival between the prediction of the model and the actual observation.ConclusionRadiomics is an independent preoperative non-invasive prognostic tool for patients who were newly classified as having IDH-wild-type GBM. The constructed nomogram, which combined radiomics features with clinical factors, can predict the overall survival (OS) of IDH-wild-type GBM patients and could be a new supplement to treatment guidelines.

Project description:BackgroundConflicting data exist regarding the prognostic impact of the isocitrate dehydrogenase (IDH) mutation in intrahepatic cholangiocarcinoma (ICC), and limited data exist in patients with advanced-stage disease. Similarly, the clinical phenotype of patients with advanced IDH mutant (IDHm) ICC has not been characterized. In this study, we report the correlation of IDH mutation status with prognosis and clinicopathologic features in patients with advanced ICC.MethodsPatients with histologically confirmed advanced ICC who underwent tumor mutational profiling as a routine part of their care between 2009 and 2014 were evaluated. Clinical and pathological data were collected by retrospective chart review for patients with IDHm versus IDH wild-type (IDHwt) ICC. Pretreatment tumor volume was calculated on computed tomography or magnetic resonance imaging.ResultsOf the 104 patients with ICC who were evaluated, 30 (28.8%) had an IDH mutation (25.0% IDH1, 3.8% IDH2). The median overall survival did not differ significantly between IDHm and IDHwt patients (15.0 vs. 20.1 months, respectively; p = .17). The pretreatment serum carbohydrate antigen 19-9 (CA19-9) level in IDHm and IDHwt patients was 34.5 and 118.0 U/mL, respectively (p = .04). Age at diagnosis, sex, histologic grade, and pattern of metastasis did not differ significantly by IDH mutation status.ConclusionThe IDH mutation was not associated with prognosis in patients with advanced ICC. The clinical phenotypes of advanced IDHm and IDHwt ICC were similar, but patients with IDHm ICC had a lower median serum CA19-9 level at presentation.Implications for practicePrevious studies assessing the prognostic impact of the isocitrate dehydrogenase (IDH) gene mutation in intrahepatic cholangiocarcinoma (ICC) mainly focused on patients with early-stage disease who have undergone resection. These studies offer conflicting results. The target population for clinical trials of IDH inhibitors is patients with unresectable or metastatic disease, and the current study is the first to focus on the prognosis and clinical phenotype of this population and reports on the largest cohort of patients with advanced IDH mutant ICC to date. The finding that the IDH mutation lacks prognostic significance in advanced ICC is preliminary and needs to be confirmed prospectively in a larger study.

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Distinguishing Pseudoprogression From True Early Progression in Isocitrate Dehydrogenase Wild-Type Glioblastoma by Interrogating Clinical, Radiological, and Molecular Features.

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