The role of [18 F]FDOPA PET as an adjunct to conventional MRI in the diagnosis of aggressive glial lesions.

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

Amino-acid PET as a prognostic tool after post Stupp protocol temozolomide therapy in high-grade glioma patients.

PURPOSE: This study aimed to evaluate the prognostic performance of amino-acid PET in high-grade gliomas (HGG) patients at the time of temozolomide (TMZ) treatment discontinuation, after the Stupp protocol. METHODS: The analysis included consecutive HGG patients with dynamic [18F]FDOPA PET imaging within 3 months of the end of TMZ therapy, post-Stupp protocol. Static and dynamic PET parameters, responses to RANO criteria for MRI and clinical and histo-molecular factors were correlated to progression-free (PFS). RESULTS: Thirty-two patients (59.4 [54.0;67.6] years old, 13 (41%) women) were included. Static PET parameters peak tumor-to-background ratio and metabolic tumor volume (respective thresholds of 1.9 and 1.5 mL) showed the best 84% accuracies for predicting PFS at 6 months (p = 0.02). These static PET parameters were also independent predictor of PFS in multivariate analysis (p ≤ 0.05). CONCLUSION: In HGG patients having undergone a Stupp protocol, the absence of significant PET uptake after TMZ constitutes a favorable prognostic factor.

Descriptive epidemiology of 30,223 histopathologically confirmed meningiomas in France: 2006-2015.

BACKGROUND AND OBJECTIVES: Meningioma is one of the most common neoplasm of the central nervous system. To describe the epidemiology of meningioma operated in France and, to assess grading and histopathological variability among the different neurosurgical centres. METHODS: We processed the French Brain Tumour Database (FBTDB) to conduct a nationwide population-based study of all histopathologically confirmed meningiomas between 2006 and 2015. RESULTS: 30,223 meningiomas cases were operated on 28,424 patients, in 61 centres. The average number of meningioma operated per year in France was 3,022 (SD ± 122). Meningioma was 3 times more common in women (74.1% vs. 25.9%). The incidence of meningioma increased with age and, mean age at surgery was 58.5 ± 13.9 years. Grade 1, 2, and 3 meningiomas accounted for 83.9%, 13.91% and, 2.19% respectively. There was a significant variability of meningioma grading by institutions, especially for grade 2 which spanned from 5.1% up to 22.4% (p < 0.001). Moreover, the proportion of grade 2 significantly grew over the study period (p < 0.001). There was also a significant variation in grade 1 subtypes diagnosis among the institutions (p < 0.001). 89.05% of the patients had solely one meningioma surgery, 8.52% two and, 2.43% three or more. The number of surgeries was associated to the grade of malignancy (p < 0.001). CONCLUSION: The incidence of meningioma surgery increased with age and, peaked at 58.5 years. They were predominantly benign with meningothelial subtype being the most common. However, there was a significant variation of grade 1 subtypes diagnosis among the centres involved. The proportion of grade 2 meningioma significantly grew over the study time, on contrary to malignant meningioma proportion, which remained rare and, stable over time around 2%. Likewise, there was a significant variability of grade 2 meningioma rate among the institutions.

Added value of [18F]FDOPA PET to the management of high-grade glioma patients after their initial treatment: a prospective multicentre study.

BACKGROUND: Diagnostic value of 3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine ([18F]FDOPA) PET in patients with suspected recurrent gliomas is recognised. We conducted a multicentre prospective study to assess its added value in the practical management of patients suspected of recurrence of high grade gliomas (HGG). METHODS: Patients with a proven HGG (WHO grade III and IV) were referred to the multidisciplinary neuro-oncology board (MNOB) during their follow-up after initial standard of care treatment and when MRI findings were not fully conclusive. Each case was discussed in 2 steps. For step 1, a diagnosis and a management proposal were made only based on the clinical and the MRI data. For step 2, the same process was repeated taking the [18F]FDOPA PET results into consideration. A level of confidence for the decisions was assigned to each step. Changes in diagnosis and management induced by [18F]FDOPA PET information were measured. When unchanged, the difference in the confidence of the decisions were assessed. The diagnostic performances of each step were measured. RESULTS: 107 patients underwent a total of 138 MNOB assessments. The proposed diagnosis changed between step 1 and step 2 in 37 cases (26.8%) and the proposed management changed in 31 cases (22.5%). When the management did not change, the confidence in the MNOB final decision was increased in 87 cases (81.3%). Step 1 had a sensitivity, specificity and accuracy of 83%, 58% and 66% and step 2, 86%, 64% and 71% respectively. CONCLUSION: [18F]FDOPA PET adds significant information for the follow-up of HGG patients in clinical practice. When MRI findings are not straightforward, it can change the management for more than 20% of the patients and increases the confidence level of the multidisciplinary board decisions.

Differentiating high-grade glioma progression from treatment-related changes with dynamic [18F]FDOPA PET: a multicentric study.

OBJECTIVES: Diagnostic accuracy of amino-acid PET for distinguishing progression from treatment-related changes (TRC) is currently based on single-center non-homogeneous glioma populations. Our study assesses the diagnostic value of static and dynamic [18F]FDOPA PET acquisitions to differentiate between high-grade glioma (HGG) recurrence and TRC in a large cohort sourced from two independent nuclear medicine centers. METHODS: We retrospectively identified 106 patients with suspected glioma recurrences (WHO GIII, n = 38; GIV, n = 68; IDH-mutant, n = 35, IDH-wildtype, n = 71). Patients underwent dynamic [18F]FDOPA PET/CT (n = 83) or PET/MRI (n = 23), and static tumor-to-background ratios (TBRs), metabolic tumor volumes and dynamic parameters (time to peak and slope) were determined. The final diagnosis was either defined by histopathology or a clinical-radiological follow-up at 6 months. Optimal [18F]FDOPA PET parameter cut-offs were obtained by receiver operating characteristic analysis. Predictive factors and clinical parameters were assessed using univariate and multivariate Cox regression survival analyses. RESULTS: Surgery or the clinical-radiological 6-month follow-up identified 71 progressions and 35 treatment-related changes. TBRmean, with a threshold of 1.8, best-differentiated glioma recurrence/progression from post-treatment changes in the whole population (sensitivity 82%, specificity 71%, p < 0.0001) whereas curve slope was only significantly different in IDH-mutant HGGs (n = 25). In survival analyses, MTV was a clinical independent predictor of progression-free and overall survival on the multivariate analysis (p ≤ 0.01). A curve slope > -0.12/h was an independent predictor for longer PFS in IDH-mutant HGGs CONCLUSION: Our multicentric study confirms the high accuracy of [18F]FDOPA PET to differentiate recurrent malignant gliomas from TRC and emphasizes the diagnostic and prognostic value of dynamic acquisitions for IDH-mutant HGGs. KEY POINTS: • The diagnostic accuracy of dynamic amino-acid PET, for distinguishing progression from treatment-related changes, is currently based on single-center non-homogeneous glioma populations. • This multicentric study confirms the high accuracy of static [18F]FDOPA PET images for differentiating progression from treatment-related changes in a homogeneous population of high-grade gliomas and highlights the diagnostic and prognostic value of dynamic acquisitions for IDH-mutant high-grade gliomas. • Dynamic acquisitions should be performed in IDH-mutant glioma patients to provide valuable information for the differential diagnosis of recurrence and treatment-related changes.

Semi-automated segmentation methods of SSTR PET for dosimetry prediction in refractory meningioma patients treated by SSTR-targeted peptide receptor radionuclide therapy.

OBJECTIVES: Tumor dosimetry with somatostatin receptor-targeted peptide receptor radionuclide therapy (SSTR-targeted PRRT) by 177Lu-DOTATATE may contribute to improved treatment monitoring of refractory meningioma. Accurate dosimetry requires reliable and reproducible pretherapeutic PET tumor segmentation which is not currently available. This study aims to propose semi-automated segmentation methods to determine metabolic tumor volume with pretherapeutic 68Ga-DOTATOC PET and evaluate SUVmean-derived values as predictive factors for tumor-absorbed dose. METHODS: Thirty-nine meningioma lesions from twenty patients were analyzed. The ground truth PET and SPECT volumes (VolGT-PET and VolGT-SPECT) were computed from manual segmentations by five experienced nuclear physicians. SUV-related indexes were extracted from VolGT-PET and the semi-automated PET volumes providing the best Dice index with VolGT-PET (Volopt) across several methods: SUV absolute-value (2.3)-threshold, adaptative methods (Jentzen, Otsu, Contrast-based method), advanced gradient-based technique, and multiple relative thresholds (% of tumor SUVmax, hypophysis SUVmean, and meninges SUVpeak) with optimal threshold optimized. Tumor-absorbed doses were obtained from the VolGT-SPECT, corrected for partial volume effect, performed on a 360° whole-body CZT-camera at 24, 96, and 168 h after administration of 177Lu-DOTATATE. RESULTS: Volopt was obtained from 1.7-fold meninges SUVpeak (Dice index 0.85 ± 0.07). SUVmean and total lesion uptake (SUVmeanxlesion volume) showed better correlations with tumor-absorbed doses than SUVmax when determined with the VolGT (respective Pearson correlation coefficients of 0.78, 0.67, and 0.56) or Volopt (0.64, 0.66, and 0.56). CONCLUSION: Accurate definition of pretherapeutic PET volumes is justified since SUVmean-derived values provide the best tumor-absorbed dose predictions in refractory meningioma patients treated by 177Lu-DOTATATE. This study provides a semi-automated segmentation method of pretherapeutic 68Ga-DOTATOC PET volumes to achieve good reproducibility between physicians. CLINICAL RELEVANCE STATEMENT: SUVmean-derived values from pretherapeutic 68Ga-DOTATOC PET are predictive of tumor-absorbed doses in refractory meningiomas treated by 177Lu-DOTATATE, justifying to accurately define pretherapeutic PET volumes. This study provides a semi-automated segmentation of 68Ga-DOTATOC PET images easily applicable in routine. KEY POINTS: • SUVmean-derived values from pretherapeutic 68Ga-DOTATOC PET images provide the best predictive factors of tumor-absorbed doses related to 177Lu-DOTATATE PRRT in refractory meningioma. • A 1.7-fold meninges SUVpeak segmentation method used to determine metabolic tumor volume on pretherapeutic 68Ga-DOTATOC PET images of refractory meningioma treated by 177Lu-DOTATATE is as efficient as the currently routine manual segmentation method and limits inter- and intra-observer variabilities. • This semi-automated method for segmentation of refractory meningioma is easily applicable to routine practice and transferrable across PET centers.

Characteristics of Anaplastic Oligodendrogliomas Short-Term Survivors: A POLA Network Study.

BACKGROUND: Anaplastic oligodendrogliomas IDH-mutant and 1p/19q codeleted (AO) occasionally have a poor outcome. Herein we aimed at analyzing their characteristics. METHODS: We retrospectively analyzed the characteristics of 44 AO patients with a cancer-specific survival <5 years (short-term survivors, STS) and compared them with those of 146 AO patients with a survival ≥5 years (classical survivors, CS) included in the POLA network. RESULTS: Compared to CS, STS were older (P = .0001), less frequently presented with isolated seizures (P < .0001), more frequently presented with cognitive dysfunction (P < .0001), had larger tumors (P = .= .003), a higher proliferative index (P = .= .0003), and a higher number of chromosomal arm abnormalities (P = .= .02). Regarding treatment, STS less frequently underwent a surgical resection than CS (P = .= .0001) and were more frequently treated with chemotherapy alone (P = .= .009) or with radiotherapy plus temozolomide (P = .= .05). Characteristics independently associated with STS in multivariate analysis were cognitive dysfunction, a number of mitosis > 8, and the absence of tumor resection. Based on cognitive dysfunction, type of surgery, and number of mitosis, patients could be classified into groups of standard (18%) and high (62%) risk of <5 year survival. CONCLUSION: The present study suggests that although STS poor outcome appears to largely result from a more advanced disease at diagnosis, surgical resection may be particularly important in this population.

Isolated intraocular relapses of primary cerebral lymphomas: An LOC network study.

Most relapses of primary central nervous system lymphoma (PCNSL) occur in the brain and are associated with a poor prognosis. Isolated intraocular relapses (IIORs) are rare and poorly described. We retrospectively selected from the French Lymphome Oculo-Cérébral database PCNSL patients who initially presented with cerebral localization and who experienced IIOR during the course of the disease. Of the 1472 patients included in the database, 55 patients presented an IIOR. Their median age was 68 years, and median Karnofsky Performance Status 80. IL-10 levels in the aqueous humor and/or in the vitreous were increased in 42/46 patients. 45/55 patients received systemic chemotherapy, and 11/55 received high-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) as consolidation treatment. After a median follow-up of 69 months, 42/55 patients had relapsed, including 90% of the patients who did not receive HCT-ASCT at IIOR and 40% of the patients who received HCT-ASCT at IIOR (p < 0.001). The first relapse after the initial IIOR was exclusively in the eye in 23/42 patients, and 29/42 patients had a subsequent brain relapse during the course of the disease. The median progression-free survival, brain-free survival and overall survival from IIOR were 12.2, 48.6 and 57.1 months, respectively. Isolated intraocular relapse is not exceptional in the course of PCNSL and deserves systematic ophthalmological follow-up. Its prognosis is much better than the prognosis of brain relapse, with an evolution close to that of primary vitreoretinal lymphoma. With the exception of patients who received HCT-ASCT at IIOR, almost all patients subsequently relapsed, often with other IIORs.

TEMOBIC: Phase II Trial of Neoadjuvant Chemotherapy for Unresectable Anaplastic Gliomas: An ANOCEF Study.

LESSONS LEARNED: Treatment with temozolomide and BCNU was associated with substantial response and survival rates for patients with unresectable anaplastic glioma, suggesting potential therapeutic alternative for these patients. The optimal treatment for unresectable large anaplastic gliomas remains debated. BACKGROUND: The optimal treatment for unresectable large anaplastic gliomas remains debated. METHODS: Adult patients with histologically proven unresectable anaplastic oligodendroglioma or mixed gliomas (World Health Organization [WHO] 2007) were eligible. Treatment consisted of BCNU (150 mg/m2 ) and temozolomide (110 mg/m2 for 5 days) every 6 weeks for six cycles before radiotherapy. RESULTS: Between December 2005 and December 2009, 55 patients (median age of 53.1 years; range, 20.5-70.2) were included. Forty percent of patients presented with wild-type IDH1 gliomas, and 30% presented with methylated MGMT promoter. Median progression-free survival (PFS), centralized PFS, and overall survival (OS) were 16.6 (95% confidence interval [CI], 12.8-20.3), 15.4 (95% CI, 10.0-20.8), and 25.4 (95% CI, 17.5-33.2) months, respectively. Complete and partial responses under chemotherapy were observed for 28.3% and 17% of patients, respectively. Radiotherapy completion was achieved for 75% of patients. Preservation of functional status and self-care capability (Karnofsky performance status [KPS] ≥70) were preserved until disease progression for 69% of patients. Grade ≥ 3 toxicities were reported for 52% of patients, and three deaths were related to treatment. By multivariate analyses including age and KPS, IDH mutation was associated with better prognostic for both PFS and OS, whereas MGMT promoter methylation was associated with better OS. CONCLUSION: The association of BCNU and temozolomide upfront is active for patients with unresectable anaplastic gliomas, but toxicity limits its use.

Integration of dynamic parameters in the analysis of 18F-FDopa PET imaging improves the prediction of molecular features of gliomas.

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

Molecular Profiling Reclassifies Adult Astroblastoma into Known and Clinically Distinct Tumor Entities with Frequent Mitogen-Activated Protein Kinase Pathway Alterations.

BACKGROUND: Astroblastoma (ABM) is a rare glial brain tumor. Recurrent meningioma 1 (MN1) alterations have been recently identified in most pediatric cases. Adolescent and adult cases, however, remain molecularly poorly defined. MATERIALS AND METHODS: We performed clinical and molecular characterization of a retrospective cohort of 14 adult and 1 adolescent ABM. RESULTS: Strikingly, we found that MN1 fusions are a rare event in this age group (1/15). Using methylation profiling and targeted sequencing, most cases were reclassified as either pleomorphic xanthoastrocytomas (PXA)-like or high-grade glioma (HGG)-like. PXA-like ABM show BRAF mutation (6/7 with V600E mutation and 1/7 with G466E mutation) and CD34 expression. Conversely, HGG-like ABM harbored specific alterations of diffuse midline glioma (2/5) or glioblastoma (GBM; 3/5). These latter patients showed an unfavorable clinical course with significantly shorter overall survival (p = .021). Mitogen-activated protein kinase pathway alterations (including FGFR fusion, BRAF and NF1 mutations) were present in 10 of 15 patients and overrepresented in the HGG-like group (3/5) compared with previously reported prevalence of these alterations in GBM and diffuse midline glioma. CONCLUSION: We suggest that gliomas with astroblastic features include a variety of molecularly sharply defined entities. Adult ABM harboring molecular features of PXA and HGG should be reclassified. Central nervous system high-grade neuroepithelial tumors with MN1 alterations and histology of ABM appear to be uncommon in adults. Astroblastic morphology in adults should thus prompt thorough molecular investigation aiming at a clear histomolecular diagnosis and identifying actionable drug targets, especially in the mitogen-activated protein kinase pathway. IMPLICATIONS FOR PRACTICE: Astroblastoma (ABM) remains a poorly defined and controversial entity. Although meningioma 1 alterations seem to define a large subset of pediatric cases, adult cases remain molecularly poorly defined. This comprehensive molecular characterization of 1 adolescent and 14 adult ABM revealed that adult ABM histology comprises several molecularly defined entities, which explains clinical diversity and identifies actionable targets. Namely, pleomorphic xanthoastrocytoma-like ABM cases show a favorable prognosis whereas high-grade glioma (glioblastoma and diffuse midline gliome)-like ABM show significantly worse clinical courses. These results call for in-depth molecular analysis of adult gliomas with astroblastic features for diagnostic and therapeutic purposes.

Complementary and alternative medicine use in glioma patients in France.

PURPOSE: Complementary and alternative medicine (CAM) use increases in cancer patients, including adult patients with diffuse gliomas. METHODS: Questionnaires addressing CAM use were distributed to adult patients with gliomas of WHO grades II-IV and ECOG performance score of 0-2 during hospital visits and filled in anonymously. The study was conducted in nine centers in France from May 2017 to May 2018. Descriptive cohort analyses and comparative analyses according to gender, age, WHO grade, and recurrent versus newly diagnosed disease were conducted. RESULTS: Two hundred twenty-seven questionnaires were collected; 135 patients (59%) were male. Median age was 48 years, 105 patients (46%) declared having glioblastoma, 99 patients (43%) declared having recurrent disease. Hundred-three patients (45%) had modified their alimentary habits after the glioma diagnosis. At the time of the questionnaire, 100 patients (44%) were on complementary treatment, mainly vitamins and food supplements, and 73 patients (32%) used alternative medicine approaches, mainly magnetism and acupuncture. In total, 154 patients (68%) declared using at least one of these approaches. Expenditures exceeding 100 € per month were reported by users in 14% for modification of alimentary habits, in 25% for complementary treatment, and in 18% for alternative medicines. All approaches were commonly considered as improving quality of life and experienced as efficient, notably those associated with more expenditures. CONCLUSIONS: CAM are frequently used by glioma patients in France. Underlying needs and expectations, as well as potential interactions with tumor-specific treatments, and financial and quality of life burden, should be discussed with patients and caregivers.

Association of patterns of care, prognostic factors, and use of radiotherapy-temozolomide therapy with survival in patients with newly diagnosed glioblastoma: a French national population-based study.

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.

[Development and deployment of a standardized pathology report in lung cancer, basing on a data management software: The PELICAN software]. / Développement et mise en place d'un compte rendu standardisé d'anatomopathologie pour les tumeurs pulmonaires à l'aide d'une application de saisie et d'export des données : l'application PELICAN.

INTRODUCTION: PELICAN (« Partager Éfficacement en Laboratoire les Informations des Comptes rendus ANatomopathologiques ¼) is a software which generates standardized reports and, in parallel, allows to automatically create a database that can be used for research purpose. This application has been used in our laboratory since 2014 for central nervous system tumors. The aim of this work was to extend it to another type of tumor, lung cancer. MATERIALS AND METHODS: The content of the pathology reports was previously defined using various standards (Société Française de Pathologie, Institut National du Cancer, WHO Classification 2015, …). A double codification was used with SNOMED and ADICAP codes. The PELICAN application is a Microsoft Excel file containing a software specifically developed for pathology laboratories, written in Visual Basic for Applications and respecting the CDA-R2 standard. RESULTS: After definition of the software specifications, a beta-version was installed in February 2018. After various updates, the 3.19 version was installed in July 2018. Almost all lung cancer surgical pathology reports are now generated with the PELICAN software; a total of 56 reports were validated at the time of writing this manuscript. The medical time for the generation of the report was globally the same or decreased for some pathologists. The secretarial time was greatly reduced. CONCLUSION: The PELICAN software is an easy to use tool that allows to generate standardized reports in pulmonary pathology and to feed a database that can be easily used for statistical purposes.

[Use of the PELICAN software for the creation and export of standardized pathology reports in central nervous system tumors: Example of meningiomas]. / Utilisation du logiciel PELICAN pour la saisie et l'export de comptes rendus standardisés dans les tumeurs du système nerveux central : application aux méningiomes.

INTRODUCTION: PELICAN ("Partager Efficacement en Laboratoire les Informations des Comptes rendus ANatomopathologiques") is a software, which generates standardized reports, and allows to automatically create a database. It has been used in central nervous system tumor pathology at the University Hospital of Nancy since 2014. The purpose of this article was to illustrate the use of this application for meningiomas, with a first statistical evaluation. MATERIALS AND METHODS: The export of data included all cases of meningiomas recorded in the PELICAN application until July 2018. The PELICAN application is a Microsoft Excel file containing a software, written in Visual Basic for Applications, and used by the pathologist to create the report. The main clinical data were collected from the Hérault Register census form. Follow-up was systematically reported for atypical meningiomas. RESULTS: Two hundred and ninety-five meningiomas were analyzed, including 250 grade I meningiomas, 42 grade II meningiomas, and 3 grade III meningiomas. Grade II meningiomas were characterized by a significantly higher proportion of men (P=0.002) and dural infiltration (P<0.001), a significant increase in the Ki-67 index (P<0.0001), and a significant decrease in progesterone receptor expression (P<0.001). In atypical meningiomas, a Ki-67 index of more than 20 % was significantly correlated with a shorter progression-free survival (P=0.032). CONCLUSION: The PELICAN software is an easy-to-use tool that allows to generate standardized reports and feed a database, opening very interesting perspectives from an epidemiological and scientific point of view.

Temozolomide Plus Bevacizumab in Elderly Patients with Newly Diagnosed Glioblastoma and Poor Performance Status: An ANOCEF Phase II Trial (ATAG).

LESSONS LEARNED: Results suggest that the combination of bevacizumab plus temozolomide is active in terms of response rate, survival, performance, quality of life, and cognition in elderly patients with glioblastoma multiforme with poor performance status.Whether this combination is superior to temozolomide alone remains to be demonstrated by a randomized study. BACKGROUND: The optimal treatment of glioblastoma multiforme (GBM) in patients aged ≥70 years with a Karnofsky performance status (KPS) <70 is not established. This clinical trial evaluated the efficacy and safety of upfront temozolomide (TMZ) and bevacizumab (Bev) in patients aged ≥70 years and a KPS <70. MATERIALS AND METHODS: Patients aged ≥70 years with a KPS <70 and biopsy-proven GBM were eligible for this multicenter, prospective, nonrandomized, phase II trial of older patients with impaired performance status. Treatment consisted of TMZ administered at 130-150 mg/m2 per day for 5 days every 4 weeks plus Bev administered at 10 mg/kg every 2 weeks. RESULTS: The trial included 66 patients (median age of 76 years; median KPS of 60). The median overall survival (OS) was 23.9 weeks (95% confidence interval [CI], 19-27.6), and the median progression-free survival (PFS) was 15.3 weeks (95% CI, 12.9-19.3). Twenty-two (33%) patients became transiently capable of self-care (i.e., KPS >70). Cognition and quality of life significantly improved over time during treatment. Grade ≥3 hematological adverse events occurred in 13 (20%) patients, high blood pressure in 16 (24%), venous thromboembolism in 3 (4.5%), cerebral hemorrhage in 2 (3%), and intestinal perforation in 2 (3%). CONCLUSION: This study suggests that TMZ + Bev treatment is active in elderly patients with GBM with low KPS and has an acceptable tolerance level.

Epidemiology for primary brain tumors: a nationwide population-based study.

Primary central nervous system tumors (PCNST) are rare tumors responsible for high mortality and morbidity. Their epidemiology is poorly known, and clinical data are scarcely analyzed at a national level. In this study, we aimed at providing descriptive epidemiological data and incidence rates for all histological subtypes of PCNST according to the WHO classification. We conducted a nationwide population-based study of all newly diagnosed and histologically confirmed PCNST in France, between 2006 and 2011. A total of 57,816 patients were included: male 46.4%, median age at diagnosis 56 years old (range 0-99). For all newly diagnosed PCNST with histological confirmation the crude incidence rate was 15.5/105 per 100,000 person-years. To enable international comparisons, standardized rates were calculated: 14.1/105 (population of reference: USA), 14.5/105 (population of reference: Europe), and 12.0/105 (population of reference: world). 23.4% of samples were cryopreserved. Resection was performed in 79.1% of cases. Results are detailed (incidence rate, sex ratio, median age at diagnosis, number of cryopreserved samples, and type of surgery) for each of the 143 histological subtypes of PCNST, including all rare tumors. For example, incidence rates (population of reference: USA) were 0.018/105 for anaplastic gangliogliomas, 0.054/105 for malignant meningiomas, and 0.036/105 for hemangiopericytomas. Our study is the first to describe incidence rates and epidemiological data for all histological subtypes of PCNST, including rare tumors, at a national level. Its methodology ensures the exhaustiveness of the data collection for histologically-proven cases. Histological population-based studies have many perspectives in the field of clinical epidemiology and research.

Incidental diffuse low-grade gliomas: from early detection to preventive neuro-oncological surgery.

Although a large amount of data supports early surgical resection for symptomatic diffuse low-grade glioma, the therapeutic strategy is still a matter of debate regarding incidentally discovered diffuse low-grade glioma. Indeed, early and "preventive" surgery has recently been proposed in asymptomatic patients with silent diffuse low-grade glioma with better outcomes. The present review discusses the importance of an early diagnosis and of a preventive surgical treatment to improve the outcomes of incidental diffuse low-grade glioma and suggests the possible relevance of a tailored screening policy.

Venous thrombosis in patients with high-grade glioma.

PURPOSE OF REVIEW: High-grade glioma (HGG) patients are at particularly high risk of venous thromboembolism (VTE) occurrence and recurrence. VTE is associated with worsened survival in these patients. At present, the main challenge when prescribing anticoagulants in HGG patients is to address the risk of intracranial hemorrhage and provide the optimal treatment. RECENT FINDINGS: Here, we discuss the latest biological findings and their potential implications for better classification in daily practice and stratification of patients in future trials according to their risk of developing a VTE. SUMMARY: To help clinicians, international guidelines have been provided for cancer patients, but their implementation remains suboptimal. We report here the specificities of VTE management in HGG patients relative to other cancer patients. Particular aspects such as anticoagulation under targeted therapies, primary and secondary prophylaxis, and the role of new oral anticoagulants are discussed as well.

Epileptic seizures in diffuse low-grade gliomas in adults.

Diffuse low-grade gliomas are highly epileptogenic brain tumours. We aimed to explore the natural course of epileptic seizures, their predictors and the prognostic significance of their occurrence in adult patients harbouring a diffuse low-grade glioma. An observational retrospective multicentre study examined 1509 patients with diffuse low-grade gliomas to identify mutual interactions between tumour characteristics, tumour course and epileptic seizures. At diagnosis, 89.9% of patients had epileptic seizures. Male gender (P = 0.003) and tumour location within functional areas (P = 0.001) were independent predictors of a history of epileptic seizures at diagnosis. Tumour volume, growth velocity, cortical location, histopathological subtype or molecular markers did not significantly affect epileptic seizure occurrence probability. Prolonged history of epileptic seizures (P < 0.001), insular location (P = 0.003) and tumour location close to functional areas (P = 0.038) were independent predictors of uncontrolled epileptic seizures at diagnosis. Occurrence of epileptic seizures (P < 0.001), parietal (P = 0.029) and insular (P = 0.002) locations were independent predictors of uncontrolled epileptic seizures after oncological treatment. Patient age (P < 0.001), subtotal (P = 0.007) and total (P < 0.001) resections were independent predictors of total epileptic seizure control after oncological treatment. History of epileptic seizures at diagnosis and total surgical resection were independently associated with increased malignant progression-free (P < 0.001 and P < 0.001) and overall (P < 0.001 and P = 0.016) survivals. Epileptic seizures are independently associated with diffuse low-grade glioma prognosis. Patients diagnosed with epileptic seizures and those with complete and early surgical resections have better oncological outcomes. Early and maximal surgical resection is thus required for diffuse low-grade gliomas, both for oncological and epileptological purposes.