An MRI Radiomics Approach to Predict the Hypercoagulable Status of Gliomas.

Venous thromboembolic events are frequent complications of Glioblastoma Multiforme (GBM) and low-grade gliomas (LGGs). The overexpression of tissue factor (TF) plays an essential role in the local hypercoagulable phenotype that underlies these complications. Our aim was to build an MRI radiomics model for the non-invasive exploration of the hypercoagulable status of LGG/GBM. Radiogenomics data from The Cancer Genome Atlas (TCGA) and REMBRANDT (Repository for molecular BRAin Neoplasia DaTa) cohorts were used. A logistic regression model (Radscore) was built in order to identify the top 20% TF-expressing tumors, considered to be at high thromboembolic risk. The most contributive MRI radiomics features from LGG/GBM linked to high TF were identified in TCGA using Least Absolute Shrinkage and Selection Operator (LASSO) regression. A logistic regression model was built, whose performance was analyzed with ROC in the TCGA/training and REMBRANDT/validation cohorts: AUC = 0.87 [CI95: 0.81-0.94, p < 0.0001] and AUC = 0.78 [CI95: 0.56-1.00, p = 0.02], respectively. In agreement with the key role of the coagulation cascade in gliomas, LGG patients with a high Radscore had lower overall and disease-free survival. The Radscore was linked to the presence of specific genomic alterations, the composition of the tumor coagulome and the tumor immune infiltrate. Our findings suggest that a non-invasive assessment of the hypercoagulable status of LGG/GBM is possible with MRI radiomics.

Stereotactic robot-assisted MRI-guided laser interstitial thermal therapy thalamotomy for medically intractable Parkinson's disease tremor: technical note and preliminary effects on 2 cases.

BACKGROUND: Medically intractable Parkinson's disease (PD) tremor is a common difficult clinical situation with major impact on patient's quality of life (QOL). Deep brain stimulation (DBS) is an effective therapy but is not an option for many patients. Less invasive lesional brain surgery procedures, such as thalamotomy, have proven to be effective in these indications. Here, we describe the technical nuances and advantages of stereotactic robot-assisted MRI-guided laser interstitial thermal therapy (MRIg-LITT) thalamotomy for medically intractable PD tremor. METHOD: We describe 2 patients with medically intractable PD tremor treated with stereotactic robot-assisted MRIg-LITT thalamotomy performed under general anesthesia with intraoperative electrophysiological testing. Pre and postoperative tremor scores were assessed using the Fahn-Tolosa-Marin tremor rating scale (TRS). RESULTS: At 3-month follow-up, both patients demonstrated significant improvement in tremor symptoms subjectively and according to the TRS (75% for both). Patients also had substantial improvements in their QOL (32.54% and 38%) according to the 39-item PD questionnaire. Both patients underwent uncomplicated MRIg-LITT thalamotomy. CONCLUSIONS: In patients with medically intractable PD tremor who are unsuitable candidates for DBS, thalamotomy utilizing a stereotactic robot, intraoperative electrophysiological testing, and laser ablation with real-time MRI guidance may be a viable treatment option. However, further studies with larger sample sizes and longer follow-up periods are necessary to confirm these preliminary results.

Intracranial Solitary Fibrous Tumour Management: A French Multicentre Retrospective Study.

BACKGROUND: Intracranial solitary fibrous tumour (iSFT) is an exceptional mesenchymal tumour with high recurrence rates. We aimed to analyse the clinical outcomes of newly diagnosed and recurrent iSFTs. METHODS: We carried out a French retrospective multicentre (n = 16) study of histologically proven iSFT cases. Univariate and multivariate Cox models were used to estimate the prognosis value of the age, location, size, WHO grade, and surgical extent on overall survival (OS), progression-free survival (PFS), and local recurrence-free survival (LRFS). RESULTS: Eighty-eight patients were included with a median age of 54.5 years. New iSFT cases were treated with gross tumour resection (GTR) (n = 75) or subtotal resection (STR) (n = 9) and postoperative radiotherapy (PORT) (n = 32, 57%). The median follow-up time was 7 years. The median OS, PFS, and LRFS were 13 years, 7 years, and 7 years, respectively. Forty-two patients experienced recurrence. Extracranial metastasis occurred in 16 patients. Median OS and PFS after the first recurrence were 6 years and 15.4 months, respectively. A higher histological grade was a prognosis factor for PFS (p = 0.04) and LRFS (p = 0.03). GTR influenced LRFS (p = 0.03). CONCLUSION: GTR provided benefits as a first treatment for iSFTs. However, approximately 40% of patients experienced relapse, which remains a challenging state.

Evaluation of Proton MR Spectroscopy for the Study of the Tongue Tissue in Healthy Subjects and Patients With Tongue Squamous Cell Carcinoma: Preliminary Findings.

Purpose: To noninvasively assess spectroscopic and metabolic profiles of healthy tongue tissue and in an exploratory objective in nontreated and treated patients with tongue squamous cell carcinoma (SCC). Methods: Fourteen healthy subjects (HSs), one patient with nontreated tongue SCC (NT-SCC), and two patients with treated tongue SCC (T-SCC) underwent MRI and single-voxel proton magnetic resonance spectroscopy (1H-MRS) evaluations (3 and 1.5T). Multi-echo-times 1H-MRS was performed at the medial superior part (MSP) and the anterior inferior part (AIP) of the tongue in HS, while 1H-MRS voxel was placed at the most aggressive part of the tumor for patients with tongue SCC. 1H-MRS data analysis yielded spectroscopic metabolite ratios quantified to total creatine. Results: In HS, compared to MSP and AIP, 1H-MRS spectra revealed higher levels of creatine, a more prominent and well-identified trimethylamine-choline (TMA-Cho) peak. However, larger prominent lipid peaks were better differentiated in the tongue MSP. Compared to HS, patients with NT-SCC exhibited very high levels of lipids and relatively higher values of TMA-Cho peak. Interestingly, patients with T-SCC showed almost nonproliferation activity. However, high lipids levels were measured, although they were relatively lower than lipids levels measured in patients with NT-SCC. Conclusion: The present study demonstrated the potential use of in-vivo 1H-MRS to noninvasively assess spectroscopic and metabolic profiles of the healthy tongue tissue in a spatial location-dependent manner. Preliminary results revealed differences between HS and patients with tongue NT-SCC as well as tongue T-SCC, which should be confirmed with more patients. 1H-MRS could be included, in the future, in the arsenal of tools for treatment response evaluation and noninvasive monitoring of patients with tongue SCC.

Pituitary apoplexy in the aftermath of a SARS-CoV-2 infection: a case series from Amiens University Hospital.

Objective: Since the outbreak of the COVID-19 pandemic, several cases of pituitary apoplexy (PA) following a SARS-CoV-2 infection have been described in several countries. Here, we describe a case series of PA occurring in the aftermath of a SARS-CoV-2 infection to alert physicians about possible neuro-endocrinological damage caused by the virus that can lead to visual sequelae and hypopituitarism. Design and methods: We retrospectively identified all the adult patients treated at Amiens University Hospital between March 2020 and May 2021 for PA confirmed by cerebral imaging and following an RT-PCR-confirmed SARS-CoV-2 infection. Results: Eight cases (six women, two men) occurred between March 2020 and May 2021 and were reviewed in this study. The mean age at diagnosis was 67.5 ± 9.8 years. Only one patient had a 'known' non-functional pituitary macroadenoma. The most common symptom of PA was a sudden headache. Brain imaging was typical in all cases. Only two patients required decompression surgery, whereas the others were managed conservatively. The clinical outcome was favorable for all patients but without recovery of their pituitary deficiencies. There was no diabetes insipidus. Conclusion: This case series, the largest in the literature, reinforces the strength, consistency, and coherence of the association between SARS-CoV-2 infection and PA. Our study provides support for the hypothesis that SARS-CoV-2 may be a new precipitating factor for PA. It is essential that practitioners be alerted about possible pituitary disease due to the virus so that such patients are recognized and appropriately managed, hence improving their prognosis.

Ellipsoid calculations versus manual tumor delineations for glioblastoma tumor volume evaluation.

In glioblastoma, the response to treatment assessment is essentially based on the 2D tumor size evolution but remains disputable. Volumetric approaches were evaluated for a more accurate estimation of tumor size. This study included 57 patients and compared two volume measurement methods to determine the size of different glioblastoma regions of interest: the contrast-enhancing area, the necrotic area, the gross target volume and the volume of the edema area. The two methods, the ellipsoid formula (the calculated method) and the manual delineation (the measured method) showed a high correlation to determine glioblastoma volume and a high agreement to classify patients assessment response to treatment according to RANO criteria. This study revealed that calculated and measured methods could be used in clinical practice to estimate glioblastoma volume size and to evaluate tumor size evolution.

[Toward precision surgery for Head and Neck tumors]. / Principe et applicabilité de la chirurgie de précision aux cancers de la tête et du cou.

Surgical resection is the most frequent curative treatment proposed to patients with head and neck cancers. It is currently integrated into specific therapeutic schemes and therapeutic stratification, but the surgical procedure itself as well as its evaluation do not rely on tumor biology. Here, we present a number of recent studies, mostly based on system analyses and genomics, that show how tumor analyses could help to: i) define the indications and the extent of surgical resections; ii) personalize the perioperative management; iii) facilitate the detection of post-surgical tumor recurrence. Overall, these studies provide a proof of principle that precision surgery, i.e. based on tumor biology, similarly to precision medicine, is applicable to head and neck cancers.

Title: Principe et applicabilité de la chirurgie de précision aux cancers de la tête et du cou. Abstract: La chirurgie est la modalité de traitement curatif la plus fréquemment utilisée dans les cancers de la tête et du cou. Elle est intégrée dans des schémas de stratification thérapeutique précis, mais la conduite de l'acte chirurgical et son évaluation ne tiennent, la plupart du temps, pas compte de la biologie tumorale. Nous présentons dans cette revue plusieurs études qui montrent comment les analyses de la biologie tumorale pourraient préciser les indications et le contour d'une résection chirurgicale, personnaliser la prise en charge péri-opératoire du patient, et faciliter la détection des récurrences tumorales. Ces études apportent ainsi une preuve de principe qu'une chirurgie de précision, c'est-à-dire adossée à la biologie tumorale, à la façon de la médecine de précision pour d'autres cancers, est applicable aux cancers de la tête et du cou.

Adult brainstem glioma differential diagnoses: an MRI-based approach in a series of 68 patients.

BACKGROUND: Brainstem gliomas are rare in adults. The diagnosis is often difficult, as some teams still consider brainstem biopsies dangerous and often avoid this procedure. The aim of this study was to describe differential diagnoses that can mimic brainstem glioma, to help clinicians avoid diagnostic and therapeutic mistakes, and to propose a diagnostic algorithm according to radiological presentations. METHODS: The French network of adult brainstem gliomas (GLITRAD) retrospectively collected all reported cases of differential diagnoses between 2006 and 2017. The inclusion criteria were as follows: age over 18 years, lesion epicenter in the brainstem, radiological pattern suggestive of a glioma and diagnostic confirmation (histopathological or not, depending on the disease). RESULTS: We identified a total of 68 cases. Most cases (58/68, 85%) presented as contrast-enhancing lesions. The most frequent final diagnosis in this group was metastases in 24/58 (41%), followed by central nervous system lymphoma in 8/58 (14%). Conversely, MRI findings revealed 10/68 nonenhancing lesions. The most frequent diagnosis in this group was demyelinating disease (3/10, 30%). CONCLUSION: The risk of diagnostic mistakes illustrates the need to consider the more systematic use of a brainstem biopsy when reasonably possible. However, we propose an MRI-based approach to the differential diagnosis of gliomas to limit the risk of misdiagnosis in cases where a biopsy is not a reasonable option.

Expression Analysis of α5 Integrin Subunit Reveals Its Upregulation as a Negative Prognostic Biomarker for Glioblastoma.

Integrin α5ß1 was suggested to be involved in glioblastoma (GBM) aggressiveness and treatment resistance through preclinical studies and genomic analysis in patients. However, further protein expression data are still required to confirm this hypothesis. In the present study, we investigated by immunofluorescence the expression of integrin α5 and its prognostic impact in a glioblastoma series of patients scheduled to undergo the Stupp protocol as first-line treatment for GBM. The integrin α5 protein expression level was estimated in each tumor by the mean fluorescence intensity (MFI) and allowed us to identify two subpopulations showing either a high or low expression level. The distribution of patients in both subpopulations was not significantly different according to age, gender, recursive partitioning analysis (RPA) prognostic score, molecular markers or surgical and medical treatment. A high integrin α5 protein expression level was associated with a high risk of recurrence (HR = 1.696, 95% CI 1.031-2.792, p = 0.0377) and reduced overall survival (OS), even more significant in patients who completed the Stupp protocol (median OS: 15.6 vs. 22.8 months; HR = 2.324; 95% CI 1.168-4.621, p = 0.0162). In multivariate analysis, a high integrin α5 protein expression level was confirmed as an independent prognostic factor in the subpopulation of patients who completed the temozolomide-based first-line treatment for predicting OS over age, extent of surgery, RPA score and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation (p = 0.029). In summary, for the first time, our study validates that a high integrin α5 protein expression level is associated with poor prognosis in GBM and confirms its potential as a therapeutic target implicated in the Stupp protocol resistance.

Role of hippocampal location and radiation dose in glioblastoma patients with hippocampal atrophy.

BACKGROUND: The hippocampus is a critical organ for irradiation. Thus, we explored changes in hippocampal volume according to the dose delivered and the location relative to the glioblastoma. METHODS: All patients were treated for glioblastoma with surgery, concomitant radiotherapy and temozolomide, and adjuvant temozolomide. Hippocampi were retrospectively delineated on three MRIs, performed at baseline, at the time of relapse, and on the last MRI available at the end of follow-up. A total of 98, 96, and 82 hippocampi were measured in the 49 patients included in the study, respectively. The patients were stratified into three subgroups according to the dose delivered to 40% of the hippocampus. In the group 1 (n = 6), the hippocampal D40% was < 7.4 Gy, in the group 2 (n = 13), only the Hcontra D40% was < 7.4 Gy, and in the group 3 (n = 30), the D40% for both hippocampi was > 7.4 Gy. RESULTS: Regardless of the time of measurement, homolateral hippocampal volumes were significantly lower than those contralateral to the tumor. Regardless of the side, the volumes at the last MRI were significantly lower than those measured at baseline. There was a significant correlation among the decrease in hippocampal volume regardless of its side, and Dmax (p = 0.001), D98% (p = 0.028) and D40% (p = 0.0002). After adjustment for the time of MRI, these correlations remained significant. According to the D40% and volume at MRIlast, the hippocampi decreased by 4 mm3/Gy overall. CONCLUSIONS: There was a significant relationship between the radiotherapy dose and decrease in hippocampal volume. However, at the lowest doses, the hippocampi seem to exhibit an adaptive increase in their volume, which could indicate a plasticity effect. Consequently, shielding at least one hippocampus by delivering the lowest possible dose is recommended so that cognitive function can be preserved. Trial registration Retrospectively registered.

Simultaneous Mapping of Vasculature, Hypoxia, and Proliferation Using Dynamic Susceptibility Contrast MRI, 18F-FMISO PET, and 18F-FLT PET in Relation to Contrast Enhancement in Newly Diagnosed Glioblastoma.

Conventional MRI plays a key role in the management of patients with high-grade glioma, but multiparametric MRI and PET tracers could provide further information to better characterize tumor metabolism and heterogeneity by identifying regions having a high risk of recurrence. In this study, we focused on proliferation, hypervascularization, and hypoxia, all factors considered indicative of poor prognosis. They were assessed by measuring uptake of 18F-3'-deoxy-3'-18F-fluorothymidine (18F-FLT), relative cerebral blood volume (rCBV) maps, and uptake of 18F-fluoromisonidazole (18F-FMISO), respectively. For each modality, the volumes and high-uptake subvolumes (hot spots) were semiautomatically segmented and compared with the contrast enhancement (CE) volume on T1-weighted gadolinium-enhanced (T1w-Gd) images, commonly used in the management of patients with glioblastoma. Methods: Dynamic susceptibility contrast-enhanced MRI (31 patients), 18F-FLT PET (20 patients), or 18F-FMISO PET (20 patients), for a total of 31 patients, was performed on preoperative glioblastoma patients. Volumes and hot spots were segmented on SUV maps for 18F-FLT PET (using the fuzzy locally adaptive bayesian algorithm) and 18F-FMISO PET (using a mean contralateral image + 3.3 SDs) and on rCBV maps (using a mean contralateral image + 1.96 SDs) for dynamic susceptibility contrast-enhanced MRI and overlaid on T1w-Gd images. For each modality, the percentages of the peripheral volumes and the peripheral hot spots outside the CE volume were calculated. Results: All tumors showed highly proliferated, hypervascularized, and hypoxic regions. The images also showed pronounced heterogeneity of both tracers regarding their uptake and rCBV maps, within each individual patient. Overlaid volumes on T1w-Gd images showed that some proliferative, hypervascularized, and hypoxic regions extended beyond the CE volume but with marked differences between patients. The ranges of peripheral volume outside the CE volume were 1.6%-155.5%, 1.5%-89.5%, and 3.1%-78.0% for 18F-FLT, rCBV, and 18F-FMISO, respectively. All patients had hyperproliferative hot spots outside the CE volume, whereas hypervascularized and hypoxic hot spots were detected mainly within the enhancing region. Conclusion: Spatial analysis of multiparametric maps with segmented volumes and hot spots provides valuable information to optimize the management and treatment of patients with glioblastoma.

Pseudoprogression versus true progression in glioblastoma patients: A multiapproach literature review. Part 2 - Radiological features and metric markers.

After chemoradiotherapy for glioblastoma, pseudoprogression can occur and must be distinguished from true progression to correctly manage glioblastoma treatment and follow-up. Conventional treatment response assessment is evaluated via conventional MRI (contrast-enhanced T1-weighted and T2/FLAIR), which is unreliable. The emergence of advanced MRI techniques, MR spectroscopy, and PET tracers has improved pseudoprogression diagnostic accuracy. This review presents a literature review of the different imaging techniques and potential imaging biomarkers to differentiate pseudoprogression from true progression.

Pseudoprogression versus true progression in glioblastoma patients: A multiapproach literature review: Part 1 - Molecular, morphological and clinical features.

With new therapeutic protocols, more patients treated for glioblastoma have experienced a suspicious radiologic image of progression (pseudoprogression) during follow-up. Pseudoprogression should be differentiated from true progression because the disease management is completely different. In the case of pseudoprogression, the follow-up continues, and the patient is considered stable. In the case of true progression, a treatment adjustment is necessary. Presently, a pseudoprogression diagnosis certainly needs to be pathologically confirmed. Some important efforts in the radiological, histopathological, and genomic fields have been made to differentiate pseudoprogression from true progression, and the assessment of response criteria exists but remains limited. The aim of this paper is to highlight clinical and pathological markers to differentiate pseudoprogression from true progression through a literature review.

Radiomics Method for the Differential Diagnosis of Radionecrosis Versus Progression after Fractionated Stereotactic Body Radiotherapy for Brain Oligometastasis.

Stereotactic radiotherapy (SRT) is recommended for treatment of brain oligometastasis (BoM) in patients with controlled primary disease. Where contrast enhancement enlargement occurs during follow-up, distinguishing between radionecrosis and progression presents a critical challenge. Without pathological confirmation, decision-making may be inappropriate and delayed. Quantitative imaging features extracted from routinely performed examinations are of interest in potentially addressing this problem. We explored the added value of the radiomics method for the differential diagnosis of these two entities. Twenty patients who received SRT for BoM, from any primary location, were included (8 radionecrosis, 12 progressions, pathologically confirmed). We assessed the clinical relevance of 1,766 radiomics features, extracted using IBEX software, from the first T1-weighted postcontrast magnetic resonance imaging (MRI) after SRT showing a lesion modification. We evaluated seven feature-selection methods and 12 classification methods in terms of respective predictive performance. The classification accuracy was measured using Cohen's kappa after leave-one-out cross-validation. In this work, the best predictive power reached was a Cohen's kappa of 0.68 (overall accuracy of 85%), expressing a strong agreement between the algorithm prediction and the histological gold standard. Prediction accuracy was 75% for radionecrosis, and 91% for progression. The area under a curve reached 0.83 using a bagging algorithm trained with the chi-square score features set. These findings indicated that the radiomics method is able to discriminate radionecrosis from progression in an accurate, early and noninvasive way. This promising study is a proof of concept, preceding a larger prospective study for defining a robust model to support decision-making in BoM. In summary, distinguishing between radionecrosis and progression is challenging without pathology. We built a classification model based on imaging data and machine learning. Using this model, we were able predict progression and radionecrosis in, respectively, 91% and 75% of cases.

ERK1/2 signaling regulates the immune microenvironment and macrophage recruitment in glioblastoma.

The tumor microenvironment is an important determinant of glioblastoma (GBM) progression and response to treatment. How oncogenic signaling in GBM cells modulates the composition of the tumor microenvironment and its activation is unclear. We aimed to explore the potential local immunoregulatory function of ERK1/2 signaling in GBM. Using proteomic and transcriptomic data (RNA seq) available for GBM tumors from The Cancer Genome Atlas (TCGA), we show that GBM with high levels of phosphorylated ERK1/2 have increased infiltration of tumor-associated macrophages (TAM) with a non-inflammatory M2 polarization. Using three human GBM cell lines in culture, we confirmed the existence of ERK1/2-dependent regulation of the production of the macrophage chemoattractant CCL2/MCP1. In contrast with this positive regulation of TAM recruitment, we found no evidence of a direct effect of ERK1/2 signaling on two other important aspects of TAM regulation by GBM cells: (1) the expression of the immune checkpoint ligands PD-L1 and PD-L2, expressed at high mRNA levels in GBM compared with other solid tumors; (2) the production of the tumor metabolite lactate recently reported to dampen tumor immunity by interacting with the receptor GPR65 present on the surface of TAM. Taken together, our observations suggest that ERK1/2 signaling regulates the recruitment of TAM in the GBM microenvironment. These findings highlight some potentially important particularities of the immune microenvironment in GBM and could provide an explanation for the recent observation that GBM with activated ERK1/2 signaling may respond better to anti-PD1 therapeutics.

Comparison between MRI-derived ADC maps and 18FLT-PET in pre-operative glioblastoma.

BACKGROUND AND PURPOSE: Among principal MRI sequences used for a better pre-therapeutic characterization of glioblastoma (GBM), DWI-derived ADC is expected to be a good parameter for the evaluation of cellularity, due to restricted water diffusivity. We aimed here to compare ADC maps to 18FLT-PET, a proliferation tracer, in GBM cases. MATERIALS AND METHODS: Patients underwent 18FLT-PET, followed by multiparametric magnetic resonance imaging (MRI) just prior to surgery. We analysed in this study twenty GBM confirmed patients. The 5th percentile (5p) of the ADC values were thresholded to define the ADCmin ROI, while the 95th percentile (95p) of the SUV FLT values were used to define the FLTmax ROI. The statistical and spatial correlations between these two groups of ROIs were analyzed. RESULTS: We did not observe any significant correlations between ADCmin and FLTmax cut-off values (R2=0.0285), neither between ADCmin and FLTmax ROIs (mean Dice=0.09±0.12). Mean ADC values in the FLTmax defined ROI were significantly higher than the values in the ADCmin ROI (P<0.001). Mean FLT values in the FLTmax ROI were significantly higher than the values in the ADCmin ROI (P<0.001). CONCLUSIONS: When comparing ADC maps to 18FLT uptake, we did not observe significant anatomical overlap nor correlation, between the regions of low ADC and high FLT disabling to clearly link ADC values to cellular proliferation. The exact significance of ADC maps in GBM has yet to be elaborated.

Development of a novel multiphysical approach for the characterization of mechanical properties of musculotendinous tissues.

At present, there is a lack of well-validated protocols that allow for the analysis of the mechanical properties of muscle and tendon tissues. Further, there are no reports regarding characterization of mouse skeletal muscle and tendon mechanical properties in vivo using elastography thereby limiting the ability to monitor changes in these tissues during disease progression or response to therapy. Therefore, we sought to develop novel protocols for the characterization of mechanical properties in musculotendinous tissues using atomic force microscopy (AFM) and ultrasound elastography. Given that TIEG1 knockout (KO) mice exhibit well characterized defects in the mechanical properties of skeletal muscle and tendon tissue, we have chosen to use this model system in the present study. Using TIEG1 knockout and wild-type mice, we have devised an AFM protocol that does not rely on the use of glue or chemical agents for muscle and tendon fiber immobilization during acquisition of transversal cartographies of elasticity and topography. Additionally, since AFM cannot be employed on live animals, we have also developed an ultrasound elastography protocol using a new linear transducer, SLH20-6 (resolution: 38 µm, footprint: 2.38 cm), to characterize the musculotendinous system in vivo. This protocol allows for the identification of changes in muscle and tendon elasticities. Such innovative technological approaches have no equivalent to date, promise to accelerate our understanding of musculotendinous mechanical properties and have numerous research and clinical applications.

The parapharyngeal adipose corpus: anatomic and radiologic study.

PURPOSE: Although the morphology of the parapharyngeal adipose corpus (PAC) has been already described, the clinical interest of its volume and weight in the genesis of obstructive sleep apnea syndrome (OSAS) is still controversial. The volume of the PAC has been determined in OSAS patients but not in a normal population. The aim of our study was to investigate the morphology of the PAC by dissection and MRI in a normal population and to determine if there is a relation between the dimensions and volume of the PAC and the Body Mass Index (BMI). METHODS: Thirty hemifaces of 15 fresh cadavers have been dissected after silicone injection with dissection of the external carotid artery and its main branches, with harvesting of the PAC. The PAC has been measured and weighed. Twenty-nine MRI of healthy subjects have been examined to determine the volume of the PAC, the palate-pharynx distance, and epiglottis-pharynx distance. RESULTS: In dissection study the weight of the PAC was 18.57 g ± 2.24, the vertical dimension (height) was 4.61 cm ± 0.51, the frontal dimension (width) was 1.62 cm ± 0.24. The blood supply of the PAC constituted of branches coming from the ascending palatal and ascending pharyngeal arteries. The volume of the PAC on the right side was 1.56 cm3 ± 0.38, on the left side 1.54 cm3 ± 0.37. Its horizontal greater dimension was 1.70 cm ± 0.07. CONCLUSIONS: There is a correlation between the volume of the PAC and the BMI in a normal population. A surgical resection of the PAC in OSAS patients by transoral robotic-assisted surgery can be proposed with preservation of the ascending palatal and ascending pharyngeal arteries.

Radiotherapy or Autologous Stem-Cell Transplantation for Primary CNS Lymphoma in Patients 60 Years of Age and Younger: Results of the Intergroup ANOCEF-GOELAMS Randomized Phase II PRECIS Study.

PURPOSE: To determine the efficacy and toxicity of chemoimmunotherapy followed by either whole-brain radiotherapy (WBRT) or intensive chemotherapy and autologous stem-cell transplantation (ASCT) as a first-line treatment of primary CNS lymphoma (PCNSL). PATIENTS AND METHODS: Immunocompetent patients (18 to 60 years of age) with untreated PCNSL were randomly assigned to receive WBRT or ASCT as consolidation treatment after induction chemotherapy consisting of two cycles of R-MBVP (rituximab 375 mg/m2 day (D) 1, methotrexate 3 g/m2 D1; D15, VP16 100 mg/m2 D2, BCNU 100 mg/m2 D3, prednisone 60 mg/kg/d D1-D5) followed by two cycles of R-AraC (rituximab 375 mg/m2 D1, cytarabine 3 g/m2 D1 to D2). Intensive chemotherapy consisted of thiotepa (250 mg/m2/d D9; D8; D7), busulfan (8 mg/kg D6 through D4), and cyclophosphamide (60 mg/kg/d D3; D2). WBRT delivered 40 Gy (2 Gy/fraction). The primary end point was 2-year progression-free survival. Cognitive outcome was the main secondary end point. Analysis was intention to treat in a noncomparative phase II trial. RESULTS: Between October 2008 and February 2014, 140 patients were recruited from 23 French centers. Both WBRT and ASCT met the predetermined threshold (among the first 38 patients in each group, at least 24 patients were alive and disease free at 2 years). The 2-year progression-free survival rates were 63% (95% CI, 49% to 81%) and 87% (95% CI, 77% to 98%) in the WBRT and ASCT arms, respectively. Toxicity deaths were recorded in one and five patients after WBRT and ASCT, respectively. Cognitive impairment was observed after WBRT, whereas cognitive functions were preserved or improved after ASCT. CONCLUSION: WBRT and ASCT are effective consolidation treatments for patients with PCNSL who are 60 years of age and younger. The efficacy end points tended to favor the ASCT arm. The specific risk of each procedure should be considered.

Predicting Current Thresholds for Pyramidal Tract Activation Using Volume of Activated Tissue Modeling in Patients Undergoing Deep Brain Stimulation Surgery.

BACKGROUND: The volume of activated tissue (VTA) model attempts to represent in 3 dimensions the diffusion of the current provided by the deep brain stimulation lead on brain structures. The objective of the present study was to assess the correlations among the VTA, activation of the corticospinal tract, and the intraoperative side effect (ISE) threshold. METHODS: This double-blind, single-center study was performed between September 2016 and July 2017. We identified 2 groups for statistical analysis: the entire study population and a subset of patients with additional diffusion tensor imaging (DTI) data for determining the location of the pyramidal tract. We determined the intensity threshold at which the VTA reached the border of the target nucleus (referred to as the VTAn) and the intensity threshold when the VTA reached the pyramidal tract (VTAndti). In each group of patients, we studied the correlations between the ISE threshold and the VTAn or VTAndti threshold. RESULTS: Fifteen patients were included in the study. In both groups, there was a significant correlation between the VTA intensity threshold and the ISE threshold (P = 0.018; r = 0.31 for VTAn in the entire study population). The correlation was stronger in the subset of patients with valid tractography data (P = 0.002; r = 0.5 for VTAndti). CONCLUSIONS: The present study is the first to show a relationship between the intensity threshold as determined by the use of the VTA and the ISE threshold. The correlation between the clinical features and the VTA appears to be stronger in the model based on a combination of high-resolution anatomic data and interpretable DTI data.