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Background: The etiology of the central nervous system (CNS) tumors remains largely unknown. The role of pesticide exposure has been suggested by several epidemiological studies, but with no definitive conclusion., Objective: To analyze associations between occupational pesticide exposure and primary CNS tumors in adults in the CERENAT study., Methods: CERENAT is a multicenter case-control study conducted in France in 2004-2006. Data about occupational pesticide uses-in and outside agriculture-were collected during detailed face-to-face interviews and reviewed by experts for consistency and exposure assignment. Odds ratios (ORs) and 95% confidence intervals (95% CI) were estimated with conditional logistic regression., Results: A total of 596 cases (273 gliomas, 218 meningiomas, 105 others) and 1 192 age- and sex-matched controls selected in the general population were analyzed. Direct and indirect exposures to pesticides in agriculture were respectively assigned to 125 (7.0%) and 629 (35.2%) individuals and exposure outside agriculture to 146 (8.2%) individuals. For overall agricultural exposure, we observed no increase in risk for all brain tumors (OR 1.04, 0.69-1.57) and a slight increase for gliomas (OR 1.37, 0.79-2.39). Risks for gliomas were higher when considering agricultural exposure for more than 10 years (OR 2.22, 0.94-5.24) and significantly trebled in open field agriculture (OR 3.58, 1.20-10.70). Increases in risk were also observed in non-agricultural exposures, especially in green space workers who were directly exposed (OR 1.89, 0.82-4.39), and these were statistically significant for those exposed for over 10 years (OR 2.84, 1.15-6.99)., Discussion: These data support some previous findings regarding the potential role of occupational exposures to pesticides in CNS tumors, both inside and outside agriculture.

The effect of ELF-MF on human health is still controversial, particularly as regards long-term health effects like cancer. The literature does suggest, however, that they could be involved in the occurrence of brain tumors, although results concerning residential exposure are scarce. Our objective was to investigate the association between residential proximity to power lines and brain tumors among adults in France by using a geographical information system.CERENAT is a population-based case-control study carried out in France in 2004-2006. We used geographical data sources on power line location to create exposure scores based on distance between residence and power lines, and on the number of lines near residences. Conditional logistic regression for matched sets was used to estimate Odds Ratios (ORs) and 95% confidence intervals (95%CI).We found significant associations between cumulated duration living at <50 m to high voltage lines and: i) all brain tumors (OR 2.94; 95%CI 1.28-6.75); ii) glioma (OR 4.96; 95%CI 1.56-15.77). Further investigations are needed, particularly to improve the quality and availability of geographical and technical data on power lines., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Glioblastomas (GB) are the most common and lethal primary brain tumors. Significant progress has been made toward identifying potential risk factors for GB and diagnostic and prognostic biomarkers. However, the current standard of care for newly diagnosed GB, the Stupp protocol, has remained unchanged for over a decade. Large-scale translational programs based on a large clinicobiological database are required to improve our understanding of GB biology, potentially facilitating the development of personalized and specifically targeted therapies. With this goal in mind, a well-annotated clinicobiological database housing data and samples from GB patients has been set up in France: the French GB biobank (FGB)., Methods: The biobank contains data and samples from adult GB patients from 24 centers in France providing written informed consent. Clinical and biomaterial data are stored in anonymized certified electronic case report forms. Biological samples (including frozen and formalin-fixed paraffin-embedded tumor tissues, blood samples, and hair) are conserved in certified biological resource centers or tumor tissue banks at each participating center., Results: Clinical data and biological materials have been collected for 1087 GB patients. A complete set of samples (tumor, blood and hair) is available for 66%, and at least one frozen tumor sample is available for 88% of the GB patients., Conclusions: This large biobank is unique in Europe and can support the large-scale translational projects required to improve GB care. Additional biological materials, such as peritumoral brain zone and fecal samples, will be collected in the future, to respond to research needs.

Background: Glioblastoma is the most frequent primary malignant brain tumor. In daily practice and at whole country level, oncological care management for glioblastoma patients is not completely known., Objectives: To describe oncological patterns of care, prognostic factors, and survival for all patients in France with newly-diagnosed and histologically confirmed glioblastoma, and evaluate the impact of extended temozolomide use at the population level., Methods: Nationwide population-based cohort study including all patients with newly-diagnosed and histologically confirmed glioblastoma in France in 2008 and followed until 2015., Results: Data from 2053 glioblastoma patients were analyzed (male/female ratio 1.5, median age 64 years). Median overall survival (OS) was 11.2 [95% confidence interval (CI) 10.7-11.9] months. The first-line therapy and corresponding median survival (MS, in months) were: 13% did not receive any oncological treatment (biopsy only) (MS = 1.8, 95% CI 1.6-2.1), 27% received treatment without the combination of radiotherapy (RT)-temozolomide (MS = 5.9, 95% CI 5.5-6.6), 60% received treatment including the initiation of the concomitant phase of RT-temozolomide (MS = 16.4, 95% CI 15.2-17.4) whom 44% of patients initiated the temozolomide adjuvant phase (MS = 18.9, 95% CI 18.0-19.8). Only 22% patients received 6 cycles or more of adjuvant temozolomide (MS = 25.5, 95% CI 24.0-28.3). The multivariate analysis showed that the risk of mortality was significantly higher for the non-progressive patients who stopped at 6 cycles (standard protocol) than those who continued the treatment, hazard ratio = 1.5 (95% CI 1.2-1.9)., Conclusion: In non-progressive patients, prolonging the adjuvant temozolomide beyond 6 cycles may improve OS.

We assessed prognostic factors in relation to OS from progression in recurrent glioblastomas. Retrospective multicentric study enrolling 407 (training set) and 370 (external validation set) adult patients with a recurrent supratentorial glioblastoma treated by surgical resection and standard combined chemoradiotherapy as first-line treatment. Four complementary multivariate prognostic models were evaluated: Cox proportional hazards regression modeling, single-tree recursive partitioning, random survival forest, conditional random forest. Median overall survival from progression was 7.6 months (mean, 10.1; range, 0-86) and 8.0 months (mean, 8.5; range, 0-56) in the training and validation sets, respectively (p = 0.900). Using the Cox model in the training set, independent predictors of poorer overall survival from progression included increasing age at histopathological diagnosis (aHR, 1.47; 95% CI [1.03-2.08]; p = 0.032), RTOG-RPA V-VI classes (aHR, 1.38; 95% CI [1.11-1.73]; p = 0.004), decreasing KPS at progression (aHR, 3.46; 95% CI [2.10-5.72]; p < 0.001), while independent predictors of longer overall survival from progression included surgical resection (aHR, 0.57; 95% CI [0.44-0.73]; p < 0.001) and chemotherapy (aHR, 0.41; 95% CI [0.31-0.55]; p < 0.001). Single-tree recursive partitioning identified KPS at progression, surgical resection at progression, chemotherapy at progression, and RTOG-RPA class at histopathological diagnosis, as main survival predictors in the training set, yielding four risk categories highly predictive of overall survival from progression both in training (p < 0.0001) and validation (p < 0.0001) sets. Both random forest approaches identified KPS at progression as the most important survival predictor. Age, KPS at progression, RTOG-RPA classes, surgical resection at progression and chemotherapy at progression are prognostic for survival in recurrent glioblastomas and should inform the treatment decisions.

The effect of pesticides on human health is still controversial, particularly as regards long-term health effects like cancer. The literature does suggest, however, that they could be involved in the occurrence of brain tumors, although the results concerning residential exposure are scarce. Our objective was to investigate the association between residential proximity to agricultural pesticides and brain tumors among adults in France by using a geographical information system. CERENAT is a population-based case-control study carried out in France in 2004-2006. We used two geographical data sources on agricultural land use to create exposure scores based on crop surface areas near the residence, for open field crops, vineyards and orchards. Conditional logistic regression for matched sets was used to estimate Odds Ratios (ORs) and 95% confidence intervals (95%CI). We found a significant association between meningioma and proximity to open field crops above the 75th percentile (OR 2.30 95%CI 1.04-5.10). Non-significant associations were also found with proximity of vineyards above the 95th percentile (OR 1.90 95%CI 0.41-8.69) and orchards above the 95th percentile (OR 5.50, 95%CI 0.49-61.94). No significant association was found between glioma and proximity to agricultural land. Further investigations are needed, particularly to improve the quality and availability of geographical data on agricultural land use., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The incidence of glioblastoma (GBM) has increased in patients aged 70 years or older, and will continue to grow. Elderly GBM patients have been excluded from most clinical trials; furthermore, optimal care management as well as benefit/risk ratio of GBM treatments are still being debated. This study describes oncological patterns of care, prognostic factors, and survival for patients ≥ 70 years in France. We identified patients over 70 with newly diagnosed and histologically confirmed GBM on data previously published by the French Brain Tumor DataBase. We included 265 patients. Neurological deficits and mental status disorders were the most frequent symptoms. The surgery consisted of resection (RS n = 95) or biopsy (B n = 170); 98 patients did not have subsequent oncological treatment. After surgery, first-line treatment consisted of radiotherapy (RT n = 76), chemotherapy (CT n = 52), and concomitant radiochemotherapy (CRC n = 39). The median age at diagnosis was 76, 74, and 73 years, respectively, for the untreated, B + RT and/or CT, RS ± RT and/or CT groups. Median survival (in days, 95 % CI) with these main strategies, when analyzed according to surgical groups, was: B-CT n = 41, 199[155-280]; B-CRC n = 21, 318[166-480]; B-RT n = 37, 149[130-214]; RS-CT n = 11, 245[211-na]; RS-CRC n = 18, 372[349-593]; RS-RT n = 39, 269[218-343]. This population study for elderly GBM patients is one of the most important in Europe, and could be considered as a historical cohort to compare future treatments. Moreover, we can hypothesize that elderly patients (versus patients <70 years) are undertreated. Karnofsky performance status seems to be the most relevant clinical predictive factor, and RS and CRC have a positive impact on survival for elderly GBM patients in the general population, at least when feasible.

Unlabelled: The carcinogenic effect of radiofrequency electromagnetic fields in humans remains controversial. However, it has been suggested that they could be involved in the aetiology of some types of brain tumours., Objectives: The objective was to analyse the association between mobile phone exposure and primary central nervous system tumours (gliomas and meningiomas) in adults., Methods: CERENAT is a multicenter case-control study carried out in four areas in France in 2004-2006. Data about mobile phone use were collected through a detailed questionnaire delivered in a face-to-face manner. Conditional logistic regression for matched sets was used to estimate adjusted ORs and 95% CIs., Results: A total of 253 gliomas, 194 meningiomas and 892 matched controls selected from the local electoral rolls were analysed. No association with brain tumours was observed when comparing regular mobile phone users with non-users (OR=1.24; 95% CI 0.86 to 1.77 for gliomas, OR=0.90; 95% CI 0.61 to 1.34 for meningiomas). However, the positive association was statistically significant in the heaviest users when considering life-long cumulative duration (≥896 h, OR=2.89; 95% CI 1.41 to 5.93 for gliomas; OR=2.57; 95% CI 1.02 to 6.44 for meningiomas) and number of calls for gliomas (≥18,360 calls, OR=2.10, 95% CI 1.03 to 4.31). Risks were higher for gliomas, temporal tumours, occupational and urban mobile phone use., Conclusions: These additional data support previous findings concerning a possible association between heavy mobile phone use and brain tumours., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: The most-used prognostic scheme for malignant gliomas included only patients aged 18 to 70 years. The purpose of this study was to develop a prognostic model for patients ≥70 years of age with newly diagnosed glioblastoma., Methods: A total of 437 patients ≥70 years of age with newly diagnosed glioblastoma, pooled from 2 tertiary academic institutions, was identified for recursive partitioning analysis (RPA). The resulting prognostic model, based on the final pruned RPA tree, was validated using 265 glioblastoma patients ≥70 years of age from a data set independently compiled by a French consortium., Results: RPA produced 9 terminal nodes, which were pruned to 4 prognostic subgroups with markedly different median survivals: subgroup I = patients <75.5 years of age who underwent surgical resection (9.3 months); subgroup II = patients ≥75.5 years of age who underwent surgical resection (6.4 months); subgroup III = patients with Karnofsky performance status of 70 to 100 who underwent biopsy only (4.6 months); and subgroup IV = patients with Karnofsky performance status <70 who underwent biopsy only (2.3 months). Application of this prognostic model to the French cohort also resulted in significantly different (P < .0001) median survivals for subgroups I (8.5 months), II (7.7 months), III (4.3 months), and IV (3.1 months)., Conclusions: This model divides elderly glioblastoma patients into prognostic subgroups that can be easily implemented in both the patient care and the clinical trial settings. This purely clinical prognostic model serves as a backbone for the future incorporation of the increasing number of potential molecular prognostic markers., (Copyright © 2012 American Cancer Society.)

This work aimed to prospectively record all primary central nervous system tumor (PCNST) cases in France, for which histological diagnosis is available. The objectives were to (i) create a national registry and a network to perform epidemiological studies; (ii) implement clinical and basic research protocols; and (iii) harmonize the health care of patients affected by PCNST. For 5 years, 25 756 cases of newly diagnosed and histologically confirmed PCNST have been recorded. Histological diagnoses included glioma (48.9%), all other neuroepithelial tumors (5%), meningioma (28.8%), nerve sheath tumors (8.4%), lymphoma (3.2%) and others (5.7%). Cryopreservation was reported for 6018 PCNST specimens. Tumor resections (R) were performed in 78% cases, while biopsies accounted for 22%. Median age (MA), sex, percentage R and number of cryopreserved tumors were detailed for each histology; for example, out of 6053 glioblastomas (MA 63 years, male 59.4%, R 62%, 1611 were cryopreserved), and out of 37 atypical teratoid/rhabdoid tumors (MA 2 years, male 56.8%, R 94%, 17 were cryopreserved). This database or databank dedicated to PCNST cases contains detailed data on clinical, histological and other characteristics, such as the inclusion of data on cryopreserved specimens that are not available in other European registries. Therefore, this is a valuable resource that can be used for planning future epidemiological and clinical research., (© 2011 The Authors; Brain Pathology © 2011 International Society of Neuropathology.)

Background: To date, the etiology of primary tumors of the central nervous system (mainly gliomas and meningiomas) is poorly understood. The role of sex hormones has been suggested, based on clinical, experimental, biological, and epidemiological data., Objective: To review the epidemiological studies on the relation between hormonal factors and the occurrence of glioma and meningioma, in order to identify new research developments., Methods: Articles published until September 2010 were selected by considering exogenous and endogenous exposures and specific brain tumors. Standardized information was collected from 20 articles: 15 concerning gliomas and 13 meningiomas., Results: An increased glioma risk was observed with later menarche and menopause, while a reduced glioma risk was observed with hormone replacement therapy (HRT) and oral contraceptive use, despite duration of use had no effect on risk. Meningioma risk increased after menopause and with HRT use. No clear association was found with pregnancy and breastfeeding., Conclusion: Results are globally concordant with the biologic hypothesis assuming that female sex hormones are protective against glioma and may increase the risk of meningioma. However, new epidemiological studies should be conducted in order to confirm these associations and to refine the role of hormonal factors in brain etiology.

Background and Purpose: Glioblastoma, the most common malignant primary brain tumor in adults, is usually rapidly fatal. The current care standards for newly diagnosed glioblastoma consist, when feasible, in surgical resection, radiotherapy, and chemotherapy, as described in the Stupp protocol. Despite optimal treatment, nearly all malignant gliomas recur. If the tumor is symptomatic for mass effect, repeated surgery may be proposed., Methods: We retrospectively analyzed the survival of patients with histologically confirmed primary glioblastoma (WHO grade 4) who were operated in two centers between January 2004 and December 2007. All patients who underwent a second resection for recurrent glioblastoma were included., Results: During this period, 320 patients were operated in the two centers, with 240 surgical resections and 80 surgical biopsies. In the surgical resection group, 8.3% (20 patients) underwent a second surgical resection for glioblastoma. The mean age was 52 years. At the end of the study, seven patients were alive. The median survival was 24 months and progression-free survival was 7.5 months., Conclusions: The effect of resection of recurrent glioblastoma on survival has not been extensively studied. No randomized trials have been conducted. Our data were globally identical to other retrospective studies. Selected patients with recurrent glioblastoma may be candidates for repeated surgery when the situation appears favorable based on assessment of the individual patient's factors. Factors such medical history, neurological status, location of the tumor, and progression-free survival have been proven in retrospective studies to give better results., (Copyright 2009 Elsevier Masson SAS. All rights reserved.)