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Background Glioblastomas all eventually relapse after initial treatment, and an option to treat these recurrences is fractionated stereotactic reirradiation (fSRT). The location of recurrences following reirradiation has not been studied for fSRT delivered by a dedicated stereotactic device. We aimed to analyze these locations to better elucidate safety margins, dose and fractionation regimens. Methods We retrospectively analyzed the data of patients with glioblastoma recurrence that had been reirradiated by fSRT in October 2010-December 2020, in 25 Gy in 5 fractions delivered by a CyberKnife ® at Institut de Cancérologie de Lorraine. We matched the images of the post-fSRT relapse with the stereotactic radiation treatment planning scan to determine the relapse location. Results The location of recurrences after fSRT was “out-field” in 43.5%, “marginal” in 40.3%, and “in-field” in 16.1% of patients ( N  = 62). A GTV-PTV margin of 1 mm (versus 2–3 mm, HR = 0.38 [0.15–0.95], p  = 0.037) and a PTV volume of ≥ 36 cc (HR = 5.18 [1.06–25.3], p  = 0.042) were significantly associated with the “marginal” recurrences. Being ≥ 60 years old at initial treatment (HR = 3.06 [1.17–8.01], p  = 0.023) and having one or more previous recurrences (HR = 5.29 [1.70–16.5], p  = 0.004) were significantly associated with “out-field” recurrences. The median PFS from fSRT was 3.4 months, and OS from diagnosis and from fSRT were 25.7 and 10.8 months respectively. Conclusion Reirradiation of glioblastoma recurrence by fSRT with 25 Gy in 5 fractions provides good local control.

Diffuse WHO grade II gliomas are diffusively infiltrative brain tumors characterized by an unavoidable anaplastic transformation. Their management is strongly dependent on their location in the brain due to interactions with functional regions and potential differences in molecular biology. In this paper, we present the construction of a probabilistic atlas mapping the preferential locations of diffuse WHO grade II gliomas in the brain. This is carried out through a sparse graph whose nodes correspond to clusters of tumors clustered together based on their spatial proximity. The interest of such an atlas is illustrated via two applications. The first one correlates tumor location with the patient's age via a statistical analysis, highlighting the interest of the atlas for studying the origins and behavior of the tumors. The second exploits the fact that the tumors have preferential locations for automatic segmentation. Through a coupled decomposed Markov Random Field model, the atlas guides the segmentation process, and characterizes which preferential location the tumor belongs to and consequently which behavior it could be associated to. Leave-one-out cross validation experiments on a large database highlight the robustness of the graph, and yield promising segmentation results.

BackgroundStatic [18F]-F-DOPA PET images are currently used for identifying patients with glioma recurrence/progression after treatment, although the additional diagnostic value of dynamic parameters remains unknown in this setting. The aim of this study was to evaluate the performances of static and dynamic [18F]-F-DOPA PET parameters for detecting patients with glioma recurrence/progression as well as assess further relationships with patient outcome.MethodsFifty-one consecutive patients who underwent an [18F]-F-DOPA PET for a suspected glioma recurrence/progression at post-resection MRI, were retrospectively included. Static parameters, including mean and maximum tumor-to-normal-brain (TBR) ratios, tumor-to-striatum (TSR) ratios, and metabolic tumor volume (MTV), as well as dynamic parameters with time-to-peak (TTP) values and curve slope, were tested for predicting the following: (1) glioma recurrence/progression at 6 months after the PET exam and (2) survival on longer follow-up.ResultsAll static parameters were significant predictors of glioma recurrence/progression (accuracy ≥ 94%) with all parameters also associated with mean progression-free survival (PFS) in the overall population (all p < 0.001, 29.7 vs. 0.4 months for TBRmax, TSRmax, and MTV). The curve slope was the sole dynamic PET predictor of glioma recurrence/progression (accuracy = 76.5%) and was also associated with mean PFS (p < 0.001, 18.0 vs. 0.4 months). However, no additional information was provided relative to static parameters in multivariate analysis.ConclusionAlthough patients with glioma recurrence/progression can be detected by both static and dynamic [18F]-F-DOPA PET parameters, most of this diagnostic information can be achieved by conventional static parameters.

Background The Response Assessment in Neuro-Oncology (RANO) group recently reported PET-based response assessment criteria for diffuse gliomas (PET RANO 1.0). The objective of this study was to evaluate the methodological application of these criteria for the amino acid [ 18 F]-FDOPA radiotracer. Patients with confirmed glioma who underwent at least one baseline [ 18 F]-FDOPA PET scan were retrospectively included. The PET RANO 1.0 criteria were evaluated regarding their methodological application. Patients with at least one follow-up PET scan were evaluated with the PET RANO 1.0 criteria as compared to the routine interpretation of two experts not using the PET RANO 1.0 criteria, defined as the reference. The different PET parameters included in the PET RANO 1.0 criteria were evaluated separately regarding their contribution. Results Ninety patients (52.0 ± 15.3 years old, 56% women) were included in this study regards to the methodology of application of the PET RANO 1.0 criteria, with 86% of patients presenting measurable diseases. Among these patients, 65 patients were evaluated for the comparison between the PET RANO 1.0 criteria and the expert interpretation: a concordance of 80%, equivalent for newly diagnosed and recurrent gliomas, as well as IDH-mutant vs. IDH-wildtype gliomas was found. The metabolic tumor volume represented the most contributive parameter (71% of cases) to the definition of response according to the PET RANO 1.0 criteria. Striatum infiltration, post-treatment related effects, measurable diseases criteria and thresholds for PET RANO 1.0 criteria were related to the cases discordances. Conclusion The PET RANO 1.0 criteria can be applied with [ 18 F]-FDOPA imaging, with a reasonable concordance with results of an expert interpretation. Description of discordant cases should help to improve future PET RANO 1.0 criteria updating.

Diffuse WHO grade II (GIIG) may be unresectable when involving critical structures. To assess the feasibility and functional tolerance (cognition and quality of life) of an original therapeutic strategy combining neoadjuvant chemotherapy followed by surgical resection for initially inoperable GIIG. Ten patients underwent Temozolomide for unresectable GIIG, as initial treatment or at recurrence after previous partial resection, due to invasion of eloquent areas or bi-hemispheric diffusion preventing a total/subtotal removal. Functional outcome after both treatments was assessed, with evaluation of seven cognitive domains. Chemotherapy induced tumor shrinkage (median volume decrease 38.9%) in ipsilateral functional areas in six patients and in the contralateral hemisphere in four. Only four patients had a 1p19q codeletion. The tumor shrinkage made possible the resection (mean extent of resection 93.3%, 9 total or subtotal removals) of initially inoperable tumors. Postoperatively, three patients had no deficits, while verbal episodic memory and executive functions were slightly impaired in seven patients. However, global quality of life was roughly preserved on the EORTC QLQ C30 + BN 20 (median score: 66.7%). Role functioning score was relatively reduced (median score: 66.7%) whereas KPS was preserved (median score: 90, range 80–100). Seven patients became seizure-free while three improved. This combined treatment is feasible, efficient (surgery made possible by neoadjuvant chemotherapy) and well-tolerated (preservation of quality of life, no serious cognitive disturbances). Cognitive deficits seem mostly related to tumor location. Because KPS is not reliable enough, a detailed neuropsychological assessment should be systematically performed in GIIG.

Purpose18F-FDopa PET imaging of gliomas is routinely interpreted with standardized uptake value (SUV)-derived indices. This study aimed to determine the added value of dynamic 18F-FDopa PET parameters for predicting the molecular features of newly diagnosed gliomas.MethodsWe retrospectively included 58 patients having undergone an 18F-FDopa PET for establishing the initial diagnosis of gliomas, whose molecular features were additionally characterized according to the WHO 2016 classification. Dynamic parameters, involving time-to-peak (TTP) values and curve slopes, were tested for the prediction of glioma types in addition to current static parameters, i.e., tumor-to-normal brain or tumor-to-striatum SUV ratios and metabolic tumor volume (MTV).ResultsThere were 21 IDH mutant without 1p/19q co-deletion (IDH+/1p19q−) gliomas, 16 IDH mutants with 1p/19q co-deletion (IDH+/1p19q+) gliomas, and 21 IDH wildtype (IDH−) gliomas. Dynamic parameters enabled differentiating the gliomas according to these molecular features, whereas static parameters did not. In particular, a longer TTP was the single best independent predictor for identifying (1) IDH mutation status (area under the curve (AUC) of 0.789, global accuracy of 74% for the criterion of a TTP ≥ 5.4 min) and (2) 1p/19q co-deletion status (AUC of 0.679, global accuracy of 69% for the criterion of a TTP ≥ 6.9 min). Moreover, the TTP from IDH− gliomas was significantly shorter than those from both IDH+/1p19q− and IDH+/1p19q+ (p ≤ 0.007).ConclusionPrediction of the molecular features of newly diagnosed gliomas with 18F-FDopa PET and especially of the presence or not of an IDH mutation, may be obtained with dynamic but not with current static uptake parameters.

Background. Idiopathic intracranial hypertension (IIH) mostly affects young obese women and can lead to permanent visual impairment. However, prognostic factors and therapeutic strategy remain unclear. Methods. We retrospectively collected data from all patients diagnosed and managed for IIH in our university center from January 2001 to December 2016. Results. Seventy-nine patients were diagnosed with IIH. Bilateral transverse sinus stenosis (TSS) was found in 74% of the population. Visual outcome at 6 months was poor for 46% of patients, including all patients presenting weight gain of at least 5% since diagnosis (p<0.001), whereas mean body mass index at diagnosis was not different between patients with poor versus good outcome (32.9±7.7 versus 34.6 ± 9.4 kg·m−2). Other significant factors of poor prognosis were bilateral TSS (OR = 5.2; 95 CI: 1.24–24.9; p=0.024). Thirteen patients with poor outcome after 6-month assessment underwent unilateral TSS stenting leading to visual improvement in 11 cases. Conclusion. Weight gain, rather than initial weight, emerged as the leading factor of poor visual outcome in patients with IIH, followed by presence of bilateral TSS. Consequently, first-line treatment must include dietary measures to control weight. Unilateral stenting appears to be a safe second-line treatment option for patients with bilateral TSS.

The involvement of eloquent brain areas may preclude the total/subtotal surgical resection of diffuse low-grade gliomas (DLGGs). The feasibility and functional tolerance of neoadjuvant chemotherapy have been demonstrated in such cases. The present study assesses the clinical and radiological impact of neoadjuvant chemotherapy on the natural course of DLGG. Seventeen patients without feasible surgical resection (infiltration of functional areas and/or large contralateral extension) were retrospectively selected. Temozolomide based neoadjuvant chemotherapy was initiated, inducing a tumor volume decrease and allowing a functional based maximal surgical resection. The median follow-up since initial radiological diagnosis was 5.9 years (range, 1.4–11). The median time to malignant transformation was 5.9 years. Six patients (35 %) had 1p19q codeletion, 12 patients (70 %) with IDH mutation and MGMT promoter methylation, and eight patients (47 %) had p53 overexpression. Chemotherapy reduced tumor volume (median −35.6 %, range −61.6 to −5.1 %) in contralateral hemisphere through the corpus callosum in seven cases (41 %) and in ipsi-lesional functional areas in ten cases (59 %). Chemotherapy significantly decreased the imaging tumor growth (measured by the velocity of diametric expansion VDE) with a median of −3.2 mm/year (range, −29.8 to −0.9 mm/year) ( p  < 0.001). A tumor volume decrease of more than 20 % was correlated with a lower postoperative residual tumor (median 2 cc, p  = 0.04), a greater extent of resection (93.1 vs. 89.5 %), a higher probability of total/subtotal removal. Neoadjuvant chemotherapy with Temozolomide could optimize the surgical resection of DLGGs and could impact their natural history. Further large prospective studies with long-term follow-up are needed.

Management of diffuse low-grade glioma (DLGG) relies extensively on tumour volume estimation from MRI datasets. Two methods are currently clinically used to define this volume: the commonly used three-diameters solution and the more rarely used software-based volume reconstruction from the manual segmentations approach. The authors conducted an initial study of inter-practitioners’ variability of software-based manual segmentations on DLGGs MRI datasets. A panel of 13 experts from various specialties and years of experience delineated 12 DLGGs’ MRI scans. A statistical analysis on the segmented tumour volumes and pixels indicated that the individual practitioner, the years of experience and the specialty seem to have no significant impact on the segmentation of DLGGs. This is an interesting result as it had not yet been demonstrated and as it encourages cross-disciplinary collaboration. Their second study was with the three-diameters method, investigating its impact and that of the software-based volume reconstruction from manual segmentations method on tumour volume. They relied on the same dataset and on a participant from the first study. They compared the average of tumour volumes acquired by software reconstruction from manual segmentations method with tumour volumes obtained with the three-diameters method. The authors found that there is no statistically significant difference between the volumes estimated with the two approaches. These results correspond to non-operated and easily delineable DLGGs and are particularly interesting for time-consuming CUBE MRIs. Nonetheless, the three-diameters method has limitations in estimating tumour volumes for resected DLGGs, for which case the software-based manual segmentation method becomes more appropriate.

Amino acid PET is recommended for the initial diagnosis of brain lesions, but its value for identifying aggressive lesions remains to be established. The current study therefore evaluates the added-value of dynamic [18 F]FDOPA PET as an adjunct to conventional MRI for determining the aggressiveness of presumed glial lesions at diagnosis.BACKGROUNDAmino acid PET is recommended for the initial diagnosis of brain lesions, but its value for identifying aggressive lesions remains to be established. The current study therefore evaluates the added-value of dynamic [18 F]FDOPA PET as an adjunct to conventional MRI for determining the aggressiveness of presumed glial lesions at diagnosis.Consecutive patients, with a minimal 1 year-follow-up, underwent contrast-enhanced MRI (CE MRI) and dynamic [18 F]FDOPA PET to characterize their suspected glial lesion. Lesions were classified semi-automatically by their CE MRI (MRI-/+), and PET parameters (static tumor-to-background ratio, TBR; dynamic time-to-peak ratio, TTPratio). Diagnostic accuracies of MRI and PET parameters for the differentiation of tumor aggressiveness were evaluated by chi-square test or receiver operating characteristic analyses. Aggressive lesions were either defined as lesions with dismal molecular characteristics based on the WHO 2021 classification of brain tumors or with compatible clinico-radiological profiles. Time-to-treatment failure (TTF) and overall survival (OS) were evaluated.METHODSConsecutive patients, with a minimal 1 year-follow-up, underwent contrast-enhanced MRI (CE MRI) and dynamic [18 F]FDOPA PET to characterize their suspected glial lesion. Lesions were classified semi-automatically by their CE MRI (MRI-/+), and PET parameters (static tumor-to-background ratio, TBR; dynamic time-to-peak ratio, TTPratio). Diagnostic accuracies of MRI and PET parameters for the differentiation of tumor aggressiveness were evaluated by chi-square test or receiver operating characteristic analyses. Aggressive lesions were either defined as lesions with dismal molecular characteristics based on the WHO 2021 classification of brain tumors or with compatible clinico-radiological profiles. Time-to-treatment failure (TTF) and overall survival (OS) were evaluated.Of the 109 patients included, 46 had aggressive lesions (45 confirmed by histo-molecular analyses). CE MRI identified aggressive lesions with an accuracy of 73%. TBRmax (threshold of 3.2), and TTPratio (threshold of 5.4 min) respectively identified aggressive lesions with an accuracy of 83% and 76% and were independent of CE MRI and clinical factors in the multivariate analysis. Among the MRI-lesions, 11/56 (20%) were aggressive and respectively 55% and 50% of these aggressive lesions showed high TBRmax and short TTPratio in PET. High TBRmax and short TTPratio in PET were significantly associated to poorer survivals (p ≤ 0.009).RESULTSOf the 109 patients included, 46 had aggressive lesions (45 confirmed by histo-molecular analyses). CE MRI identified aggressive lesions with an accuracy of 73%. TBRmax (threshold of 3.2), and TTPratio (threshold of 5.4 min) respectively identified aggressive lesions with an accuracy of 83% and 76% and were independent of CE MRI and clinical factors in the multivariate analysis. Among the MRI-lesions, 11/56 (20%) were aggressive and respectively 55% and 50% of these aggressive lesions showed high TBRmax and short TTPratio in PET. High TBRmax and short TTPratio in PET were significantly associated to poorer survivals (p ≤ 0.009).Dynamic [18 F]FDOPA PET provides a similar diagnostic accuracy as contrast enhancement in MRI to identify the aggressiveness of suspected glial lesions at diagnosis. Both methods, however, are complementary and [18 F]FDOPA PET may be a useful additional tool in equivocal cases.CONCLUSIONDynamic [18 F]FDOPA PET provides a similar diagnostic accuracy as contrast enhancement in MRI to identify the aggressiveness of suspected glial lesions at diagnosis. Both methods, however, are complementary and [18 F]FDOPA PET may be a useful additional tool in equivocal cases.