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Introduction: Approximately 10% of EGFR mutations (EGFRmuts) are uncommon (ucEGFRmuts). We aimed to collect real-world data about osimertinib for patients with ucEGFRmuts., Methods: This is a multicenter, retrospective study of ucEGFRmut (exon 20 insertions excluded) metastatic NSCLC treated with osimertinib as first EGFR inhibitor. The Response Evaluation Criteria in Solid Tumors and response assessment in neuro-oncology brain metastases brain objective response rate (ORR) were evaluated by the investigators. Median progression-free survival (mPFS), median overall survival, and median duration of response (mDOR) were calculated from osimertinib initiation. Mutations found at resistance were collected., Results: A total of 60 patients were included (22 centers, nine countries), with median age of 64 years, 75% females, and 83% Caucasian. The largest subgroups were G719X (30%), L861Q (20%), and de novo Thr790Met (T790M) (15%). The ORR was 61%, mPFS 9.5 months, mDOR 17.4 months, and median overall survival 24.5 months. Regarding patients with no concurrent common mutations or T790M (group A, n = 44), ORR was 60%, mPFS 8.6 months, and mDOR 11 months. For G719X, ORR was 47%, mPFS 8.8 months, and mDOR 9.1 months. For L861Q, ORR was 80%, mPFS 16 months, and mDOR 16 months. For de novo T790M, ORR was 44%, mPFS 12.7 months, and mDOR 46.2 months. Compound EGFRmut including common mutations had better outcome compared with only ucEGFRmut. For 13 patients with a response assessment in neuro-oncology brain metastases-evaluable brain metastases, brain ORR was 46%. For 14 patients, rebiopsy results were analyzed: four patients with additional EGFR mutation (C797S, D585Y, E709K), three with new TP53 mutation, one with c-Met amplification, one with PIK3CA mutation, and one with neuroendocrine transformation., Conclusions: Osimertinib was found to have an activity in ucEGFRmut with a high rate of disease control systemically and intracranially. Several resistance mechanisms were identified. This report comprises, to the best of our knowledge, the largest data set of its kind., (Copyright © 2022 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Introduction: Lung cancer remains the most frequent cause of brain metastases (BMs) and is responsible for high morbidity and mortality. Intracranial response to systemic treatments is inconsistent due to several mechanisms: genomic heterogeneity, blood-tumor barrier, and the brain-specific microenvironment. We conducted a study using data from the SAFIR02-LUNG trial. The primary objective was to compare the molecular profiles of non-small-cell lung cancer (NSCLC) with or without BMs. The secondary objective was to explore central nervous system (CNS) outcomes with various maintenance treatment regimens., Methods: In total, 365 patients harboring interpretable molecular data were included in this analysis. Clinical and biological data were collected. Genomic analyses were based on array-comparative genomic hybridization and next-generation sequencing (NGS) following the trial recommendations., Results: Baseline genomic analyses of copy number variations identified a 24-gene signature specific to lung cancer BM occurrence, all previously known to take part in oncogenesis. NGS analysis identified a higher proportion of KRAS mutations in the BM-positive group (44.3% versus 32.3%), especially G12C mutations (63% versus 47%). Protein interaction analyses highlighted several functional interactions centered on EGFR. Furthermore, the risk of CNS progression was decreased with standard pemetrexed maintenance therapy. The highest rate of CNS progression was observed with durvalumab, probably because of the specific intracranial immune microenvironment., Conclusion: This work identified a 24-gene signature specific to lung cancer with BM. Further studies are needed to precisely determine the functional implications of these genes to identify new therapeutic targets for the treatment of lung cancer with BM., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: AI brain tumour segmentation and brain extraction algorithms promise better diagnostic and follow-up of brain tumours in adults. The development of such tools for paediatric populations is restricted by limited training data but careful adaption of adult algorithms to paediatric population might be a solution. Here, we aim exploring the transferability of algorithms for brain (HD-BET) and tumour segmentation (HD-GLIOMA) in adults to paediatric imaging studies., Method: In a retrospective cohort, we compared automated segmentation with expert masks. We used the dice coefficient for evaluating the similarity and multivariate regressions for the influence of covariates. We explored the feasibility of automatic tumor classification based on diffusion data., Results: In 42 patients (mean age 7 years, 9 below 2 years, 26 males), segmentation was excellent for brain extraction (mean dice 0.99, range 0.85-1), moderate for segmentation of contrast-enhancing tumours (mean dice 0.67, range 0-1), and weak for non-enhancing T2-signal abnormalities (mean dice 0.41). Precision was better for enhancing tumour parts (p < 0.001) and for malignant histology (p = 0.006 and p = 0.012) but independent from myelinisation as indicated by the age (p = 0.472). Automated tumour grading based on mean diffusivity (MD) values from automated masks was good (AUC = 0.86) but tended to be less accurate than MD values from expert masks (AUC = 1, p = 0.208)., Conclusion: HD-BET provides a reliable extraction of the paediatric brain. HD-GLIOMA works moderately for contrast-enhancing tumours parts. Without optimization, brain tumor AI algorithms trained on adults and used on paediatric patients may yield acceptable results depending on the clinical scenario., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: Dynamic susceptibility contrast (DSC) and arterial spin labeling (ASL) perfusion MRI are applied in pediatric brain tumor grading, but their value for clinical daily practice remains unclear. We explored the ability of ASL and DSC to distinguish low- and high-grade lesions, in an unselected cohort of pediatric cerebral tumors., Methods: We retrospectively compared standard perfusion outcomes including blood volume, blood flow, and time parameters from DSC and ASL at 1.5T or 3T MRI scanners of 46 treatment-naive patients by drawing ROI via consensus by two neuroradiologists on the solid portions of every tumor. The discriminant abilities of perfusion parameters were evaluated by receiver operating characteristic (ROC) over the entire cohort and depending on the tumor location and the magnetic field., Results: ASL and DSC parameters showed overall low to moderate performances to distinguish low- and high-grade tumors (area under the curve: between 0.548 and 0.697). Discriminant abilities were better for tumors located supratentorially (AUC between 0.777 and 0.810) than infratentorially, where none of the metrics reached significance. We observed a better differentiation between low- and high-grade cancers at 3T than at 1.5-T. For infratentorial tumors, time parameters from DSC performed better than the commonly used metrics (AUC ≥ 0.8)., Conclusion: DSC and ASL show moderate abilities to distinguish low- and high-grade brain tumors in an unselected cohort. Absolute value of K2, TMAX, tMIP, and normalized value of TMAX of the DSC appear as an alternative to conventional parameters for infratentorial tumors. Three Tesla evaluation should be favored over 1.5-Tesla., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Introduction: The phenotypic heterogeneity of diffuse gliomas is still inconsistently explained by known molecular abnormalities. Here, we report the molecular and radiological features of diffuse grade WHO II and III gliomas involving the insula and its potential impact on prognosis., Methods: Clinical, pathological, molecular and neuro-radiological features of 43 consecutive patients who underwent a surgical resection between 2006 and 2013 for a grade II and III gliomas involving the insula was retrospectively analyzed., Results: Median age was 44.4 years. Eight patients had oligodendrogliomas, IDH mutant (IDH mut ) and 1p/19q-codeleted (6 grade II, 2 grade III). Twenty-eight patients had diffuse astrocytomas, IDH mut (22 grade II and 6 grade III) and seven patients had grade II diffuse astrocytomas, IDH wt (A-IDH wt ). Vimentin staining was exclusively recorded in tumor cells from A-IDH wt (p = 0.001). Mean cerebral blood volume (CBV) (p = 0.018), maximal value of CBV (p = 0.017) and ratio of the corrected CBV (p = 0.022) were lower for A-IDH wt . Volumetric segmentation of ADC allowed the identification of the tumor cores, which were smaller in A-IDH wt (p < 0.001). The tumor occurrences of A-IDH wt were exclusively located into the temporo-insular region. Median progression-free survival (PFS) and overall survival (OS) were 50.9 months (95% CI: 26.7-75.0) and 80.9 months (60.1-101.6). By multivariate analysis, A-IDH wt (p = 0.009; p = 0.019), 7p gain and 10q loss (p = 0.009; p = 0.016) and vimentin positive staining (p = 0.011; p = 0.029) were associated with poor PFS and OS respectively., Conclusions: Insular low-grade A-IDH wt presented with poor prognosis despite a smaller tumor core and no evidence of increased perfusion on MR imaging.

Background: Brain metastases (BM) are frequent in non-small cell lung cancer (NSCLC) patients, but there is a lack of evidence-based management of this patient group. We aimed to capture a snapshot of routine BM management in Europe to identify relevant research questions for future clinical trials., Methods: An EORTC Lung Cancer Group (LCG) online survey containing questions on NSCLC BM screening and treatment was distributed between 16/02/17 and 15/06/17 to worldwide EORTC LCG members, and through several European scientific societies in the thoracic oncology field., Results: A total of 462 European physician responses (394 institutions) were analysed (radiation oncologist: 53% [n = 247], pulmonologist: 26% [n = 119], medical oncologist: 18% [n = 84]; 84% with >5 years' experience in NSCLC). Italy (18%, n = 85), Netherlands (15%, n = 68), UK (14%, n = 66), and France (12%, n = 55) contributed most. 393 physicians (85%) screened neurologically asymptomatic patients for BM at diagnosis (52% using magnetic resonance imaging). Most often screened patients were those with a driver mutation (MUT+; 51%, n = 234), stage III (63%, n = 289), and IV (43%, n = 199). 158 physicians (34%) used a prognostic classification to guide initial treatment decisions, and in 50%, lowest prognostic-score threshold to receive treatment differed between MUT+ and non-driver mutation (MUT-) patients. MUT+ patients with >4 BM were more likely to receive stereotactic radiosurgery (SRS) compared with MUT- (27% versus. 21%; p < 0.01). Most physicians (90%) had access to SRS. After single BM surgery, 50% systematically prescribed SRS or WBRT, and 45% only in case of incomplete resection. The preferred treatment in neurologically asymptomatic treatment-naive patients diagnosed with >5 BM was systemic treatment (79%). Of all, 45%/49% physicians stated that all tyrosine kinase inhibitors and immune checkpoint blockers were discontinued (timing varied) during SRS/WBRT, respectively. Drugs most often continued during SRS/WBRT were erlotinib (44%/40%), gefitinib (39%/34%), afatinib (29%/25%), crizotinib (33%/26%) and anti-PD-(L)-1 (28%/22%)., Conclusion: BM management is highly variable in Europe: screening is not uniform, prognostic classifications are not often used and MUT+ NSCLC patients generally receive more intensive local treatment. Prospective assessment of BM management in MUT+ NSCLC patients is required., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Matrix metalloproteases MMP2 and MMP9 are involved in cancer angiogenesis and invasion. We recently demonstrated that plasma MMP2 and MMP9 levels could both predict response to bevacizumab in patients with recurrent high-grade glioma (HGG). We examined the potential relationship between MMP2/MMP9 plasma levels and glioma imaging characteristics. In this retrospective, monocentric study, MRI before bevacizumab administration for HGG patients was independently analyzed for contrast enhancement (CE) and FLAIR sequences. Contemporary MMP2 and MMP9 plasma levels were assessed using ELISA kits. We analyzed 28 patients with a median Karnofsky Performance Status of 70 (range 50-80). A diffuse pattern was observed in 14 patients (50%). We did not observe any correlation between baseline imaging features and plasma levels of MMP2 or MMP9. We found no association between baseline MMP levels and diffuse MRI patterns. In univariate analyses, diffuse pattern, multi-focal disease, tumor diameter, surface area, and volume had no impact on outcome, while the number of lobes involved in CE and crossing of the midline by CE were associated with a worse progression-free survival (p = 0.072 and p = 0.012, respectively) and overall survival (p = 0.012 and p < 0.001, respectively). In patients with recurrent high-grade glioma treated with a bevacizumab-based regimen, our exploratory analysis of multiple MRI tumor characteristics at baseline failed to detect a relationship between imaging feature and plasma levels of MMP2 and MMP9. Our results suggests that number of lobes involved in CE and crossing of the midline by CE are associated with outcome although the potential prognostic versus predictive role of these markers warrant further investigation.

Childhood brain tumors show great histological variability. The goal of this retrospective study was to assess the diagnostic accuracy of multimodal MR imaging (diffusion, perfusion, MR spectroscopy) in the distinction of pediatric brain tumor grades and types. Seventy-six patients (range 1 month to 18 years) with brain tumors underwent multimodal MR imaging. Tumors were categorized by grade (I-IV) and by histological type (A-H). Multivariate statistical analysis was performed to evaluate the diagnostic accuracy of single and combined MR modalities, and of single imaging parameters to distinguish the different groups. The highest diagnostic accuracy for tumor grading was obtained with diffusion-perfusion (73.24%) and for tumor typing with diffusion-perfusion-MR spectroscopy (55.76%). The best diagnostic accuracy was obtained for tumor grading in I and IV and for tumor typing in embryonal tumor and pilocytic astrocytoma. Poor accuracy was seen in other grades and types. ADC and rADC were the best parameters for tumor grading and typing followed by choline level with an intermediate echo time, CBV for grading and Tmax for typing. Multiparametric MR imaging can be accurate in determining tumor grades (primarily grades I and IV) and types (mainly pilocytic astrocytomas and embryonal tumors) in children.

Brain tumors are the second leading cause of cancer in children. Primary tumors predominate and are of very varied histological types. Their prognosis and treatment depend on the histological type and grade. The diagnostic approach to these includes analysis of the site of the lesion and appearances on computed tomography and MR, and taking account of the age and clinical features of the child. CT is used to diagnose the tumor in an emergency situation. Conventional MR provides a morphological approach and allows a staging assessment to be carried out before surgery. Advanced MR techniques (diffusion-weighted and perfusion imaging, MR spectroscopy) provide further information for the differential diagnosis, presumptive diagnosis of type and grade and to guide biopsy towards the most malignant areas in the lesion., (Copyright © 2014 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.)

Background and Purpose: Pretherapeutic determination of tumor grade and genotype in grade II and III oligodendroglial tumors is clinically important but is still challenging. Tumor grade and 1p/19q status are currently the 2 most important factors in therapeutic decision making for patients with these tumors. Histopathology and cMRI studies are still limited in some cases. In the present study, we were interested in determining whether the combination of PWI, DWI, and MR spectroscopy could help distinguish oligodendroglial tumors according to their histopathologic grade and genotype., Materials and Methods: We retrospectively reviewed 50 adult patients with grade II and III oligodendrogliomas and oligoastrocytomas who had DWI, PWI, and MR spectroscopy at short and long TE data and known 1p/19q status. Univariate analyses and multivariate random forest models were performed to determine which criteria could differentiate between grades and genotypes., Results: ADC, rCBV, rCBF, and rK2 were significantly different between grade II and III oligodendroglial tumors. DWI, PWI, and MR spectroscopy showed no significant difference between tumors with and without 1p/19q loss. Separation between tumor grades and genotypes with cMRI alone showed 31% and 48% misclassification rates, respectively. Multimodal MR imaging helps to determine tumor grade and 1p/19q genotype more accurately (misclassification rates of 17% and 40%, respectively)., Conclusions: Although multimodal investigation of oligodendroglial tumors has a lower contribution to 1p/19q genotyping compared with cMRI alone, it greatly improves the accuracy of grading of these neoplasms. Use of multimodal MR imaging could thus provide valuable information that may assist clinicians in patient preoperative management and treatment decision making.

Purpose: Focal cortical dysplasia (FCD), dysembryoplastic neuroepithelial tumors (DNTs), and gangliogliomas (GGs) share many clinical features, and the presurgical differential diagnosis of these lesions using conventional magnetic resonance imaging (MRI) is challenging in some cases. The purpose of this work was thus to evaluate the capacity of diffusion-weighted imaging (DWI) and proton magnetic resonance spectroscopy (MRS) to distinguish each lesion from the others., Methods: Seventeen children (mean age 9.0 ± 4.7 years), who had been referred for epilepsy associated with a brain tumor and operated, were selected. Preoperative MRI examinations were performed on a 1.5 T system and included anatomical images [T2-weighted, fluid-attenuated inversion recovery (FLAIR) and T1 pre- and post-injection images] as well as DWI and MRS [echo time (TE) = 30 and 135 ms]. Apparent diffusion coefficient (ADC) values were calculated in the lesion and healthy control. MRS relative quantification consisted in normalizing each metabolite by the sum (S) of all metabolites (S(TE=135 ms) = NAA+Cr+Cho; S(TE=30 ms) = NAA+Cr+Cho+Glx+mI). Univariate and multivariate analyses were performed in order to determine which criteria could differentiate the different epileptogenic brain lesions., Results: When taken alone, none of the MRI parameters was able to distinguish each disease from the others. Conventional MRI failed classifying two patients. When adding ADC to the linear discriminant analysis (LDA), one patient was still misclassified. Complete separation of the three groups was possible when combining conventional MRI, diffusion, and MRS either at long or short TE., Conclusion: This study shows the added-value of multimodal MRI and MRS in the presurgical diagnosis of epileptogenic brain lesions in children.

Background: Dysembryoplastic Neuroepithelial Tumours (DNT) are benign brain lesions arising during childhood that are characterized by early onset partial seizures, no neurological deficit and cortical location. Pathological diagnosis is easy when the glioneuronal element is present. Its absence might lead to the diagnosis of non-specific DNT or low-grade glioma (LGG)., Objective: The aim of this retrospective study was to analyse clinicopathological and molecular features of a series of cortical tumours, in order to find diagnostic and prognostic markers to better custom treatment next., Methods: Twenty four children with cortical neuroepithelial tumour were included. Clinical and radiological data were collected. Histological diagnosis was reviewed for all patients. 1p19q and p53 status were obtained by FISH and immunohistochemistry respectively. IDH1-2 gene mutations were assessed by DNA sequencing. CGH-array was performed in 6/24 samples., Results: We recorded 13 DNT and 11 cortical LGG. Median age at surgery was 11.5 years. Overall survival was 100% and event-free survival at 10 years was 70%. No tumour displayed chromosomal alteration or 1p19q deletion or p53 expression. Only one patient with grade-II oligoastrocytoma had an IDH1 mutation. No statistical difference was found between the two populations in terms of age, sex, tumour location, type of surgical resection, disease progression and clinical status at last follow-up. Only the occurrence of septations on preoperative MRI was significantly associated with pathological features of DNT., Conclusion: Patients with DNT and cortical LGG share excellent outcome. Our genetic analysis could not distinguish DNT from LGG. In particular, CGH-array analysis was strictly normal in both tumor types. In attempt to find molecular markers, diagnosis of these lesions remains difficult when the glioneuronal element is lacking.

During the pre-surgical evaluation of drug-resistant epilepsy, the assessment of the extent of the epileptogenic zone and its organization is a crucial objective. Indeed, the epileptogenic zone may be organized as a simple focal lesional site or as a more complex network (often referred to as the 'epileptogenic network') extending beyond the lesion. This distinction is particularly relevant in developmental lesions such as focal cortical dysplasias or dysembryoplastic neuroepithelial tumours and may determine both the surgical strategy and the prognosis. In this study, we have quantified the epileptogenic characteristic of brain structures explored by depth electrodes in 36 patients investigated by stereoelectroencephalography and suffering from focal drug-resistant epilepsy associated with focal cortical dysplasias or dysembryoplastic neuroepithelial tumours. This quantification was performed using the 'Epileptogenicity Index' method that accounts for both the propensity of a brain area to generate rapid discharges and the time for this area to get involved in the seizure. Epileptogenicity Index values range from 0 (no epileptogenicity) to 1 (maximal epileptogenicity). We determined Epileptogenicity Index from signals recorded in distinct brain structures including the lesional site. We studied the type of epileptogenic zone organization (focal versus network) and looked for a correlation with clinical data and post-surgical outcome. Mean Epileptogenicity Index in lesional regions was 0.87 (+/-0.25), and 0.29 (+/-0.30) in 'non-lesional' structures. The number of highly epileptogenic structures (defined by Epileptogenicity Index value >or=0.4) was 3.14 (+/-1.87) in the whole population. We found that 31% of patients had only one epileptogenic structure (N(EI>or=0.4) = 1), therefore disclosing a strictly focal epileptogenic zone organization while 25 patients had more than one epileptogenic region, disclosing a network (61%) or bilateral (8%) epileptogenic zone organization. We observed a trend for a difference in seizure outcome according to the type of epileptogenic zone organization. Indeed, 57% of patients with network organization and 87% with focal organization were seizure-free while none of those with bilateral organization became seizure-free. The determination of Epileptogenicity Index computed from electrophysiological signals recorded according to the stereoelectroencephalography technique is a novel tool. Results suggest that it can help in the delineation of the epileptogenic zone associated with brain lesions and that it could be used in the definition of the subsequent surgical resection.

Few studies exist in the literature on pediatric brain tumors examined with advances MRI techniques. The aim of this review is to try to find out some specific tissular characteristics of the main cerebral tumors encountered in children, especially through diffusion imaging, perfusion imaging and proton magnetic resonance spectroscopy (MRS). However, hemispheric cerebral tumors are not as common as in the adult population.

Purpose: To assess the combined value of diffusion-weighted imaging (DWI) and proton magnetic resonance spectroscopy (1H-MRS) in differentiating medulloblastoma, ependymoma, pilocytic astrocytoma, and infiltrating glioma in a pediatric population., Materials and Methods: A total of 17 children with untreated posterior fossa tumors (seven medulloblastoma, four infiltrating glioma, two ependymoma, and four pilocytic astrocytoma), were investigated with conventional MRI, DWI, and MRS using a single-voxel technique. Within the nonnecrotic tumor core, apparent diffusion coefficient (ADC) values using a standardized region of interest (ROI) were retrieved. Quantification of water signal and analysis of metabolite signals from MRS measurements in the same tumorous area were reviewed using multivariant linear discriminant analysis., Results: Combination of ADC values and metabolites, which were normalized using water as an internal standard, allowed discrimination between the four tumor groups with a likelihood below 1 x 10(-9). Positive predictive value was 1 in all cases. Tumors could not be discriminated when using metabolite ratios or ADC values alone, nor could they be differentiated using creatine (Cr) as an internal reference even in combination with ADC values., Conclusion: Linear discriminant analysis using DWI and MRS using water as internal reference, fully discriminates the four most frequent posterior fossa tumors in children., ((c) 2007 Wiley-Liss, Inc.)

Object: Thalamic tumors represent only 1 to 5% of brain neoplasms but frequently affect children. However, pediatric series are rare and go back to several years in spite of recent advances in the neuroradiological, pathological, and molecular fields., Methods: We report a series of 14 pediatric thalamic gliomas with clinical, neuroradiological, and pathological studies including p53 immunostaining in 11 cases and 1p19q status in three cases., Results: Our series included five pilocytic astrocytomas, seven oligodendrogliomas, and two glioblastomas. Pilocytic astrocytomas were characterized by strong contrast enhancement, lack of p53 expression, and excellent prognosis. Oligodendrogliomas frequently demonstrated an aspect of unilateral thalamic enlargement lacking or with slight contrast enhancement. Some of them expressed p53 or demonstrated 1p loss. Anaplastic oligodendrogliomas and glioblastomas displayed a poor outcome, with a mean survival of 8 months after surgery., Conclusion: Our series of pediatric thalamic gliomas clearly distinguishes pilocytic astrocytomas from anaplastic oligodendrogliomas regarding neuroimaging, pathology, and prognosis.

Background: Lung cancer accounts for about 50% of brain metastases, of which nearly 25% are eligible for neurosurgery, providing a neurological control rate of up to 70% when followed by whole brain radiation therapy. How to manage the primary lung carcinoma remains elusive., Methods: We undertook a retrospective study of consecutive patients who underwent surgical resection for synchronous brain metastases from non-small cell lung cancer in a single institution, to determine overall survival and prognostic factors, with particular attention to the treatment of the primary lung tumor., Results: Fifty-one patients underwent surgical resection of synchronous brain metastases from non-small cell lung cancer. Median survival was 13.2 months. Prognosis mainly depended of the treatment of the lung tumor, with a marked survival advantage in the 29 patients receiving a focal treatment (thoracic surgery or radiotherapy), compared to the 22 other patients: median, 1-year, and 2-year survival were 22.5 months, 69%, and 42%, versus 7.1 months, 33%, and 5%, respectively (p<0.001); response to pre-operative chemotherapy before focal treatment was the main favorable prognostic factor (p=0.023), and further identified patients who had benefit from resection of the lung tumor, with a significantly better outcome., Conclusions: Chemotherapy, by its therapeutic and prognostic value, may be considered as the cornerstone of the combined medical and surgical therapeutic sequence whereby brain metastasectomy is followed by chemotherapy and further focal treatment of the primary lung tumor in responders to chemotherapy.

Objective: Pilocytic astrocytomas (PA) are Grade I brain tumors characterized by an excellent prognosis. In some cases, however, the patient has a bad outcome. The aim of our study was to search for the clinicopathological factors underlying the prognosis for patients with this disease., Methods: We reviewed the clinical, neuroradiological, and histopathological features of 80 PAs (33 cerebellar, 18 optochiasmatic, 16 brainstem, 7 spinal cord, 3 thalamic, 2 optic nerve, and 1 hemispheric) in pediatric patients., Results: Pathological examination revealed 58 classic PAs and 20 pilomyxoid astrocytomas, which are a histological variant of PAs. Two cases remained unclassified. The mean overall follow-up period was 58 months, the 5-year progression-free survival rate was 75%, and the 5-year survival rates were 100 and 92% after total and partial removal. Univariate statistical analysis revealed that partial resection, optochiasmatic PA localization, and pilomyxoid variant were associated with a worse prognosis, but the latter two parameters were too closely related to the extent of resection to be independent prognostic factors in multivariate analysis. Among the patients who underwent partial surgical removal, only invasion of the surrounding structures was related to prognosis., Conclusion: PAs are benign tumors, but some clinicopathological factors, such as partial resection, optochiasmatic location, invasion of surrounding structures, and the pilomyxoid variant, have a worse prognosis.

Background and Purpose: Dysembryoplastic neuroepithelial tumors (DNTs) are benign lesions affecting children and are associated with epilepsy. The goal of our study was to better characterize the clinical-radiologic-pathologic spectrum of DNTs (complex and simple forms only) in a series of 14 children., Methods: Clinical, neuroradiologic, and pathologic features of all cases were retrospectively studied., Results: Eleven cases of complex and three cases of simple DNTs were identified. Mean follow-up was 87 months, and no recurrence was recorded except for one case of simple DNT. We found that some neuroradiologic features may be helpful to support the diagnosis of DNT: presence of "septations," triangular pattern of distribution, and absence of contrast enhancement., Conclusion: The evidence of the specific glioneuronal element is found by pathologic examination, but the typical neuroradiologic aspect of DNT suggests this diagnosis preoperatively. Radiologic examination may be helpful for the diagnosis of DNT when pathologic findings are inconclusive.

Fetal brain tumors are rare and teratoma is considered as the most common. Fetal MR Imaging is currently used to evaluate cases of ventricular dilatation. We report a case of cerebral immature teratoma detected by ultrasonography because of ventricular dilatation at 24 gestational weeks. MRI was the more accurate imaging method in depicting the tumor and its consequences on brain development as well as in taking a decision with regard to the management of pregnancy., (Copyright 2003 John Wiley & Sons, Ltd.)

Background and Purpose: Craniopharyngiomas are intra-cranial tumors, relatively frequent in children, expanding in the pituitary stalk axis, from the third ventricle to the sphenoid body. Plain films and CT scan generally show a calcified lesion, deforming the sella turcica. MRI improves tumor description and topographic and structural analysis of the lesion. The aim of this study is to analyze the MRI aspect of craniopharyngiomas in a pediatric population and to correlate findings with surgical data., Methods: MR and CT studies of 43 pediatric cases of histology-proven craniopharyngiomas were reviewed retrospectively. Tumor emergence, extensions and signal on different sequences were recorded. We searched for radio-surgical correlations., Results: Craniopharyngiomas can be classified into two groups: intra-sellar tumors and third ventricle floor tumors (infundibulum and tuber cinereum). Preferential routes of extension are observed in each group correlated with consistency (cystic and/or solid). Surgical data confirmed these results., Conclusions: MRI is crucial for the pre-therapeutic evaluation of craniopharyngiomas allowing not only a detailed description of the tumor but also guiding therapeutic decisions. This series demonstrated that craniopharyngiomas exhibit two different types of localization and behavior. Embryonic development of the tumor explains the topographical differences.

We studied 14 young people with newly diagnosed hemisphere tumors, aged from 3 to 20 years (average 10 years). All underwent surgery following MR imaging (MRI) and spectroscopy (MRS). The tumors studied were three glioblastomas, one each of ganglio-glioblastoma, primitive neuroectodermal tumor (PNET), rhabdoid teratoid tumor, pilocytic astrocytoma, ependymoma, anaplastic ependymoma, and gliomatosis cerebri, and four gangliogliomas. Four patients died; ten patients are alive (five with stable residual tumor, five with no evident tumor). Images and spectra were acquired on a 1.5-T imager. Proton MRS was performed before gadolinium injection in all but one case. Single-voxel techniques were utilized in all cases, using a spin-echo or STEAM sequence with a long echo time (135 or 270 ms). Peak areas of N-acetyl aspartate (NAA), choline (Cho), and creatine and phosphocreatine (Cr) were assessed. The NAA/Cho peak-area ratio was very low in the patients who died (mean +/- s.d. 0.20 +/- 0.14), and higher in the patients who are alive (0.74 +/- 0.47; P = 0.007 by two-tailed t-test). The Cr/Cho peak-area ratio also followed a similar trend for the two groups (mean +/- s.d. 0.17 +/- 0.07 and 0.49 +/- 0.30, respectively; P = 0.01 by two-tailed t-test).

Hyaluronan (HA) and the hyaluronan-binding glycoprotein hyaluronectin (HN) were measured in 23 gliomas and 8 meningiomas and their location was revisited in 35 tumours. A clear-cut difference was found in the HN/HA ratio values of glioblastomas (below 0.5) and that of astrocytomas (above 0.5 P < 0.001). Besides their location in the intercellular part of gliomas, HA and HN displayed a perivascular location in 1/3 astrocytomas, 17/24 glioblastomas, and 3/7 meningiomas, suggesting they could be produced also by the vascular stroma of tumours and that they would characterise the neoangiogenesis. All cultivated glioma cells tested produced HA in vitro, whereas only 1/11 cell lines produced HN, at a low level. The results obtained suggest that glioma HA and HN are produced by both cancer cells and vascular stroma cells, which contribute to the edification of the extracellular matrix. In meningiomas only the stroma would be responsible for HA and HN production.

Thirty intracranial tumours were explored by MRI, using T1- and T2-weighted sequences, before and after intravenous injection of Gd-DTPA. Two-thirds of the intra-axial tumours were accurately detected on one section plane by MRI without Gd-DTPA, but in one quarter of the cases Gd-DTPA only delineated precisely the tumour. On the other hand, Gd-DTPA failed to detect certain tumours (benign gliomas) or showed only a small part of them (mixed grade gliomas), while they were detected by MRI without contrast injection. However, in such cases Gd-DTPA was useful for the stereotaxic biopsy of the tumour. Gd-DTPA appears of lesser interest in extra-axial tumours. Gd-DTPA is thus valuable for the neuroradiological diagnosis of brain tumours, particularly to evaluate the grade of gliomas and to confirm the diagnosis of recurrent growths.

We studied various tumours of the nervous system by the immunofluorescence technique using an anti-brain specific alpha 2 glycoprotein antiserum (anti-NSA3 antiserum). We found the antigen in 24/27 astrocytomas and 4/4 oligodendrogliomas but in none of the 8 meningiomas tested. There was an identity between the astrocytoma/oligodendroglioma antigen and that of normal brain as shown by the immunoprecipitation technique. By the immunofluorescence technique using inhibition of the antiserum we demonstrated that the tumour antigen is devoid of some specific nervous system determinants present in normal brain.

A 55 year-old woman was admitted to hospital in January 1981 with transient expressive dysphasia. Past personal history was unremarkable except for a six-month history of renal colic and thrombophlebitis in the veins of the right leg. Computed tomographic scan of the head and carotid angiogram revealed a left calcified temporoparietal tumor. Because of pulmonary embolism it was decided to refute a cerebral biopsy. The patient also declined radiotherapy. In May 1983, a thorough workup revealed an incomplete fracture of the first lumbar vertebra and a diffuse demineralization of the rachis and pelvis. Four weeks later she developed temporal epilepsy and pulmonary embolism. A whole brain irradiation (60 Gy) was performed in August 1983. The patient's condition remained clinically stable until December 1984 when she was readmitted to hospital with a severe weight loss, diffuse osseous pain and pancytopenia. A bone marrow biopsy from the iliac crest showed a diffuse tumor involvement. Peroxidase-antiperoxidase staining using monoclonal antiserum to glial fibrillary acidic protein was strongly positive in numerous tumors cells. The pathological diagnosis was bone marrow metastasis by glioma. She died in March 1985, 4 years and 3 months after the first admission to hospital. Autopsy was not performed. A literature search reveals only 9 cases of extraneural spreading of astrocytomas and glioblastomas in the absence of previous craniotomy with post-mortem examination. The authors also comment on the clinical, pathological and histogenic aspects of extraneural metastasis of gliomas.

Glial fibrillary acidic protein (GFA) was assayed in nerve-tumour extracts and located in these tumours by indirect immunofluorescence study. We conclude that GFA is a specific marker of both malignant and normal astrocytes. Non-astrocytic tumours (oligodendroglioma, meningioma) do not contain GFA. Tumours with astrocytic differentiation potential (medulloblastoma) may contain GFA. Comparison of microscopic and GFA assays leads us to conclude that GFA concentration is proportional to the amount of malignant astrocytes in the tumour and inversely proportional to the necrotic area of a tumour. Normal tissue GFA and glioblastoma GFA were found to be immunologically identical.