Enhancing predictability of IDH mutation status in glioma patients at initial diagnosis: a comparative analysis of radiomics from MRI, [18F]FET PET, and TSPO PET.

PURPOSE: According to the World Health Organization classification for tumors of the central nervous system, mutation status of the isocitrate dehydrogenase (IDH) genes has become a major diagnostic discriminator for gliomas. Therefore, imaging-based prediction of IDH mutation status is of high interest for individual patient management. We compared and evaluated the diagnostic value of radiomics derived from dual positron emission tomography (PET) and magnetic resonance imaging (MRI) data to predict the IDH mutation status non-invasively. METHODS: Eighty-seven glioma patients at initial diagnosis who underwent PET targeting the translocator protein (TSPO) using [18F]GE-180, dynamic amino acid PET using [18F]FET, and T1-/T2-weighted MRI scans were examined. In addition to calculating tumor-to-background ratio (TBR) images for all modalities, parametric images quantifying dynamic [18F]FET PET information were generated. Radiomic features were extracted from TBR and parametric images. The area under the receiver operating characteristic curve (AUC) was employed to assess the performance of logistic regression (LR) classifiers. To report robust estimates, nested cross-validation with five folds and 50 repeats was applied. RESULTS: TBRGE-180 features extracted from TSPO-positive volumes had the highest predictive power among TBR images (AUC 0.88, with age as co-factor 0.94). Dynamic [18F]FET PET reached a similarly high performance (0.94, with age 0.96). The highest LR coefficients in multimodal analyses included TBRGE-180 features, parameters from kinetic and early static [18F]FET PET images, age, and the features from TBRT2 images such as the kurtosis (0.97). CONCLUSION: The findings suggest that incorporating TBRGE-180 features along with kinetic information from dynamic [18F]FET PET, kurtosis from TBRT2, and age can yield very high predictability of IDH mutation status, thus potentially improving early patient management.

MRI-based contrast clearance analysis shows high differentiation accuracy between radiation-induced reactions and progressive disease after cranial radiotherapy.

BACKGROUND: Pseudoprogression (PsP) or radiation necrosis (RN) may frequently occur after cranial radiotherapy and show a similar imaging pattern compared with progressive disease (PD). We aimed to evaluate the diagnostic accuracy of magnetic resonance imaging-based contrast clearance analysis (CCA) in this clinical setting. PATIENTS AND METHODS: Patients with equivocal imaging findings after cranial radiotherapy were consecutively included into this monocentric prospective study. CCA was carried out by software-based automated subtraction of imaging features in late versus early T1-weighted sequences after contrast agent application. Two experienced neuroradiologists evaluated CCA with respect to PsP/RN and PD being blinded for histological findings. The radiological assessment was compared with the histopathological results, and its accuracy was calculated statistically. RESULTS: A total of 33 patients were included; 16 (48.5%) were treated because of a primary brain tumor (BT), and 17 (51.1%) because of a secondary BT. In one patient, CCA was technically infeasible. The accuracy of CCA in predicting the histological result was 0.84 [95% confidence interval (CI) 0.67-0.95; one-sided P = 0.051; n = 32]. Sensitivity and specificity of CCA were 0.93 (95% CI 0.66-1.00) and 0.78 (95% CI 0.52-0.94), respectively. The accuracy in patients with secondary BTs was 0.94 (95% CI 0.71-1.00) and nonsignificantly higher compared with patients with primary BT with an accuracy of 0.73 (95% CI 0.45-0.92), P = 0.16. CONCLUSIONS: In this study, CCA was a highly accurate, easy, and helpful method for distinguishing PsP or RN from PD after cranial radiotherapy, especially in patients with secondary tumors after radiosurgical treatment.

18F-PSMA-1007 PET/CT for response assessment in patients with metastatic renal cell carcinoma undergoing tyrosine kinase or checkpoint inhibitor therapy: preliminary results.

INTRODUCTION: Tyrosine kinase (TKI) and checkpoint inhibitors (CI) prolonged overall survival in metastatic renal cell carcinoma (mRCC). Early prediction of treatment response is highly desirable for the individualization of patient management and improvement of therapeutic outcome; however, serum biochemistry is unable to predict therapeutic efficacy. Therefore, we compared 18F-PSMA-1007 PET imaging for response assessment in mRCC patients undergoing TKI or CI therapy compared to CT-based response assessment as the current imaging reference standard. METHODS: 18F-PSMA-1007 PET/CT was performed in mRCC patients prior to initiation of systemic treatment and 8 weeks after therapy initiation. Treatment response was evaluated separately on 18F-PSMA-PET and CT. Changes on PSMA-PET (SUVmean) were assessed on a per patient basis using a modified PERCIST scoring system. Complete response (CRPET) was defined as absence of any uptake in all target lesions on posttreatment PET. Partial response (PRPET) was defined as decrease in summed SUVmean of > 30%. The appearance of new, PET-positive lesions or an increase in summed SUVmean of > 30% was defined as progressive disease (PDPET). A change in summed SUVmean of ± 30% defined stable disease (SDPET). RECIST 1.1 criteria were used for response assessment on CT. Results of radiographic response assessment on PSMA-PET and CT were compared. RESULTS: Overall, 11 mRCC patients undergoing systemic treatment were included. At baseline PSMA-PET1, all mRCC patients showed at least one PSMA-avid lesion. On follow-up PET2, 3 patients showed CRPET, 3 PRPET, 4 SDPET, and 1 PDPET. According to RECIST 1.1, 1 patient showed PRCT, 9 SDCT, and 1 PDCT. Overall, concordant classifications were found in only 2 cases (2 SDCT + PET). Patients with CRPET on PET were classified as 3 SDCT on CT using RECIST 1.1. By contrast, the patient classified as PRCT on CT showed PSMA uptake without major changes during therapy (SDPET). However, among 9 patients with SDCT on CT, 3 were classified as CRPET, 3 as PRPET, 1 as PDPET, and only 2 as SDPET on PSMA-PET. CONCLUSION: On PSMA-PET, heterogeneous courses were observed during systemic treatment in mRCC patients with highly diverging results compared to RECIST 1.1. In the light of missing biomarkers for early response assessment, PSMA-PET might allow more precise response assessment to systemic treatment, especially in patients classified as SD on CT.

Recent advances of PET imaging in clinical radiation oncology.

Radiotherapy and radiation oncology play a key role in the clinical management of patients suffering from oncological diseases. In clinical routine, anatomic imaging such as contrast-enhanced CT and MRI are widely available and are usually used to improve the target volume delineation for subsequent radiotherapy. Moreover, these modalities are also used for treatment monitoring after radiotherapy. However, some diagnostic questions cannot be sufficiently addressed by the mere use standard morphological imaging. Therefore, positron emission tomography (PET) imaging gains increasing clinical significance in the management of oncological patients undergoing radiotherapy, as PET allows the visualization and quantification of tumoral features on a molecular level beyond the mere morphological extent shown by conventional imaging, such as tumor metabolism or receptor expression. The tumor metabolism or receptor expression information derived from PET can be used as tool for visualization of tumor extent, for assessing response during and after therapy, for prediction of patterns of failure and for definition of the volume in need of dose-escalation. This review focuses on recent and current advances of PET imaging within the field of clinical radiotherapy / radiation oncology in several oncological entities (neuro-oncology, head & neck cancer, lung cancer, gastrointestinal tumors and prostate cancer) with particular emphasis on radiotherapy planning, response assessment after radiotherapy and prognostication.

TSPO PET, tumour grading and molecular genetics in histologically verified glioma: a correlative 18F-GE-180 PET study.

BACKGROUND: The 18-kDa translocator protein (TSPO) is overexpressed in brain tumours and represents an interesting target for glioma imaging. 18F-GE-180, a novel TSPO ligand, has shown improved binding affinity and a high target-to-background contrast in patients with glioblastoma. However, the association of uptake characteristics on TSPO PET using 18F-GE-180 with the histological WHO grade and molecular genetic features so far remains unknown and was evaluated in the current study. METHODS: Fifty-eight patients with histologically validated glioma at initial diagnosis or recurrence were included. All patients underwent 18F-GE-180 PET, and the maximal and mean tumour-to-background ratios (TBRmax, TBRmean) as well as the PET volume were assessed. On MRI, presence/absence of contrast enhancement was evaluated. Imaging characteristics were correlated with neuropathological parameters (i.e. WHO grade, isocitrate dehydrogenase (IDH) mutation, O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and telomerase reverse transcriptase (TERT) promoter mutation). RESULTS: Six of 58 patients presented with WHO grade II, 16/58 grade III and 36/58 grade IV gliomas. An (IDH) mutation was found in 19/58 cases, and 39/58 were classified as IDH-wild type. High 18F-GE-180-uptake was observed in all but 4 cases (being WHO grade II glioma, IDH-mutant). A high association of 18F-GE-180-uptake and WHO grades was seen: WHO grade IV gliomas showed the highest uptake intensity compared with grades III and II gliomas (median TBRmax 5.15 (2.59-8.95) vs. 3.63 (1.85-7.64) vs. 1.63 (1.50-3.43), p < 0.001); this association with WHO grades persisted within the IDH-wild-type and IDH-mutant subgroup analyses (p < 0.05). Uptake intensity was also associated with the IDH mutational status with a trend towards higher 18F-GE-180-uptake in IDH-wild-type gliomas in the overall group (median TBRmax 4.67 (1.56-8.95) vs. 3.60 (1.50-7.64), p = 0.083); however, within each WHO grade, no differences were found (e.g. median TBRmax in WHO grade III glioma 4.05 (1.85-5.39) vs. 3.36 (2.32-7.64), p = 1.000). No association was found between uptake intensity and MGMT or TERT (p > 0.05 each). CONCLUSION: Uptake characteristics on 18F-GE-180 PET are highly associated with the histological WHO grades, with the highest 18F-GE-180 uptake in WHO grade IV glioblastomas and a PET-positive rate of 100% among the investigated high-grade gliomas. Conversely, all TSPO-negative cases were WHO grade II gliomas. The observed association of 18F-GE-180 uptake and the IDH mutational status seems to be related to the high inter-correlation of the IDH mutational status and the WHO grades.

Correction to: Biological tumour volumes of gliomas in early and standard 20-40 min 18F-FET PET images differ according to IDH mutation status.

The name of M. Unterrainer was inadvertently presented as M. Unterrrainer in the original article.

Biological tumour volumes of gliomas in early and standard 20-40 min 18F-FET PET images differ according to IDH mutation status.

PURPOSE: For the clinical evaluation of O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) PET images, the use of standard summation images obtained 20-40 min after injection is recommended. However, early summation images obtained 5-15 min after injection have been reported to allow better differentiation between low-grade glioma (LGG) and high-grade glioma (HGG) by capturing the early 18F-FET uptake peak specific for HGG. We compared early and standard summation images with regard to delineation of the PET-derived biological tumour volume (BTV) in correlation with the molecular genetic profile according the updated 2016 WHO classification. METHODS: The analysis included 245 patients with newly diagnosed, histologically verified glioma and a positive 18F-FET PET scan prior to any further treatment. BTVs were delineated during the early 5-15 min and standard 20-40 min time frames using a threshold of 1.6 × background activity and were compared intraindividually. Volume differences between early and late summation images of >20% were considered significant and were correlated with WHO grade and the molecular genetic profile (IDH mutation and 1p/19q codeletion status). RESULTS: In 52.2% of the patients (128/245), a significant difference in BTV of >20% between early and standard summation images was found. While 44.3% of WHO grade II gliomas (31 of 70) showed a significantly smaller BTV in the early summation images, 35.0% of WHO grade III gliomas (28/80) and 37.9% of WHO grade IV gliomas (36/95) had a significantly larger BTVs. Among IDH-wildtype gliomas, an even higher portion (44.4%, 67/151) showed significantly larger BTVs in the early summation images, which was observed in 5.3% (5/94) of IDH-mutant gliomas only: most of the latter had significantly smaller BTVs in the early summation images, i.e. 51.2% of IDH-mutant gliomas without 1p/19q codeletion (21/41) and 39.6% with 1p/19q codeletion (21/53). CONCLUSION: BTVs delineated in early and standard summation images differed significantly in more than half of gliomas. While the standard summation images seem appropriate for delineation of LGG as well as IDH-mutant gliomas, a remarkably high percentage of HGG and, particularly, IDH-wildtype gliomas were depicted with significantly larger volumes in early summation images. This finding might be of interest for optimization of treatment planning (e.g. radiotherapy) in accordance with the individual IDH mutation status.