Purpose: This study aimed to determine the impact of carbidopa premedication on static, dynamic and radiomics parameters of ¹⁸F-FDOPA PET in brain tumors. Methods: The study included 54 patients, 18 of whom received carbidopa, who underwent ¹⁸F-FDOPA PET for newly diagnosed gliomas. SUV-derived, 105 radiomics features and TTP dynamic parameters were extracted from volumes of interest in healthy brains and tumors. Simulation of the effects of carbidopa on time-activity curves were generated. Results: All static and TTP dynamic parameters were significantly higher in healthy brain regions of premedicated patients (ΔSUV_mean = +53%, ΔTTP = +48%, p < 0.001). Furthermore, carbidopa impacted 81% of radiomics features, of which 92% correlated with SUV_mean (absolute correlation coefficient ≥ 0.4). In tumors, premedication with carbidopa was an independent predictor of SUV_mean (ΔSUV_mean = +52%, p < 0.001) and TTP (ΔTTP = +24%, p = 0.025). All parameters were no longer significantly modified by carbidopa premedication when using ratios to healthy brain. Simulated data confirmed that carbidopa leads to higher tumor TTP values, corrected by the ratios. Conclusion: In ¹⁸F-FDOPA PET, carbidopa induces similarly higher SUV and TTP dynamic parameters and similarly impacts SUV-dependent radiomics in healthy brain and tumor regions, which is compensated for by correcting for the tumor-to-healthy-brain ratio. This is a significant advantage for multicentric study harmonization.

Improving the onco-functional balance has always been a challenge in glioma surgery, especially regarding motor function. Given the importance of conation (i.e., the willingness which leads to action) in patient’s quality of life, we propose here to review the evolution of its intraoperative assessment through a reminder of the increasing knowledge of its neural foundations—based upon a meta-networking organization at three levels. Historical preservation of the primary motor cortex and pyramidal pathway (first level), which was mostly dedicated to avoid hemiplegia, has nonetheless shown its limits to prevent the occurrence of long-term deficits regarding complex movement. Then, preservation of the movement control network (second level) has permitted to prevent such more subtle (but possibly disabling) deficits thanks to intraoperative mapping with direct electrostimulations in awake conditions. Finally, integrating movement control in a multitasking evaluation during awake surgery (third level) enabled to preserve movement volition in its highest and finest level according to patients’ specific demands (e.g., to play instrument or to perform sports). Understanding these three levels of conation and its underlying cortico-subcortical neural basis is therefore critical to propose an individualized surgical strategy centered on patient’s choice: this implies an increasingly use of awake mapping and cognitive monitoring regardless of the involved hemisphere. Moreover, this also pleads for a finer and systematic assessment of conation before, during and after glioma surgery as well as for a stronger integration of fundamental neurosciences into clinical practice.

Background: The prognosis of recurrent glioblastoma (GBM) is poor, with limited options of palliative localized or systemic treatments. Survival can be improved by a second localized treatment; however, it is not currently possible to identify which patients would benefit from this approach. This study aims to evaluate which factors lead to a lower Karnofsky performance status (KPS) score after fractionated stereotactic RT (fSRT).Methods: We retrospectively collected data from patients treated with fSRT for recurrent GBM at the Institut de Cancérologie de Lorraine between October 2010 and November 2017 and analyzed which factors were associated with a lower KPS score.Results: 59 patients received a dose of 25 Gy in 5 sessions spread over 5–7 days (80% isodose). The median time from the end of primary radiotherapy to the initiation of fSRT was 10.7 months. The median follow-up after fSRT initiation was 8.8 months. The incidence of KPS and ADL impairment in all patients were 51.9% and 37.8% respectively with an adverse impact of PTV size on KPS (HR = 1.57 [95% CI 1.19–2.08],p = 0.028). Only two patients showed early grade 3 toxicity and none showed grade 4 or late toxicity. The median overall survival time, median overall survival time after fSRT, median progression-free survival and institutionalization-free survival times were 25.8, 8.8, 3.9 and 7.7 months, respectively. Initial surgery was associated with better progression-free survival (Hazard ratio (HR) = 0.48 [95% CI 0.27–0.86],p = 0.013).Conclusions: A larger PTV should predicts lower KPS in the treatment of recurrent GBM using fSRT.

The aim of this study was to evaluate the prognostic value of MCM6, in comparison with Ki-67, in two series of grade 1 and 2 meningiomas, and to evaluate its correlation with methylation classes. The first cohort included 100 benign (grade 1, World Health Organization 2021) meningiomas, and the second 69 atypical meningiomas (grade 2). Immunohistochemical Ki-67 and MCM6 labeling indices (LI) were evaluated independently by two observers. Among the atypical meningiomas, 33 cases were also studied by genome-wide DNA methylation. In grade 2 meningiomas, but not grade 1, both Ki-67 and MCM6 LIs were correlated with PFS (p = 0.004 and p = 0.005, respectively; Cox univariate analyses). Additionally, MCM6 was correlated with overall survival only in univariate analysis. In a multivariate model, including mitotic index, Ki-67, MCM6, age, sex, and the quality of surgical resection, only MCM6 was correlated with PFS (p = 0.046). Additionally, we found a significant correlation between PTEN loss and high MCM6 or Ki-67 LIs. Although no correlation was found with the methylation classes and subtypes returned by the meningioma algorithm MNGv2.4., MCM6 LI was significantly correlated with the methylation of 2 MCM6 gene body loci. In conclusion, MCM6 is a relevant prognostic marker in atypical meningiomas. This reproducible and easy-to-use marker allows the identification of a highly aggressive subtype of proliferative meningiomas, characterized notably by frequent PTEN losses, which was previously reported to be sensitive to histone deacetylase inhibitors.