Abstract
The diagnosis of anaplastic meningioma (AM) (WHO grade III) is based on the presence of a high mitotic index (MI) and/or overt anaplasia. Only few data exist about the reproducibility and ...prognostic value of overt anaplasia. Additionally, the prognostic value of H3K27me3 loss in AM has not yet been demonstrated. Our objectives were to evaluate the reproducibility and prognostic value of WHO criteria and H3K27me3 loss in a multicenter series of 66 AM. Interobserver reproducibility was good for the determination of WHO grade (Kappa = 0.671) and MI (intraclass correlation coefficient ICC = 0.649), and fair for assessment of overt anaplasia (Kappa = 0.366). Patients with meningiomas showing high MI had significantly shorter overall survival (OS) than patients with meningiomas showing overt anaplasia without high MI (p = 0.009). OS was significantly lower in case of overt anaplasia with low MI (<20/1.6 mm2) than in atypical meningiomas (p = 0.008). H3K27me3 loss was present in 10/47 (21%) of AM and independently associated with shorter OS (p = 0.036; Cox multivariate analysis), with a good reproducibility (Kappa = 0.643). In conclusion, the presence of overt anaplasia could give additional prognostic information in tumors lacking high MI. Finally, loss of H3K27me3 is an easy-to-use and reproducible marker of poorer prognosis.
Following recent studies underlining the differences between de novo and secondary anaplastic meningiomas and the prognostic value of telomerase reverse transcriptase (TERT) promoter mutation, we ...decided to conduct a multicenter retrospective study to address these questions and determine specific prognostic factors in each of these 2 anaplastic meningioma subgroups.
Among the 68 meningioma cases initially selected, only 57 were confirmed as anaplastic meningiomas after centralized pathological review. TERT promoter mutation analysis was performed in all cases.
Median overall survival was 2.6 years and 5-year survival rate was 10%. This study confirmed the better prognosis of de novo anaplastic meningiomas (28 tumors) compared with secondary anaplastic meningiomas (29 tumors) (P = 0.02). In the "de novo" group, meningiomas diagnosed on histological anaplasia alone had a better prognosis than those in patients with a high number of mitoses with or without anaplasia (P = 0.01). In the "secondary" group, tumors demonstrate very heterogeneous clinical courses leading to malignant transformation, and time to first relapse as a low-grade tumor was a strong predictor of overall survival (P = 0.0007). TERT promoter mutation in anaplastic meningiomas was rare (14%) and did not influence overall survival but was associated with a shorter recurrence-free survival in the secondary anaplastic meningioma subgroup (P = 0.02). The absence of TERT promoter methylation, although rare (3/33 cases), may be associated with prolonged overall survival (P = 0.02).
This study highlights the different prognoses of de novo and secondary anaplastic meningiomas with specific prognostic factors in each subgroup. The analysis of TERT mutation and methylation could provide additional prognostic insights.
Reporter gene-based strategies are widely used in experimental oncology. Bioluminescence imaging (BLI) using the firefly luciferase (Fluc) as a reporter gene and d-luciferin as a substrate is ...currently the most widely employed technique. The present paper compares the performances of BLI imaging with fluorescence imaging using the near infrared fluorescent protein (iRFP) to monitor brain tumor growth in mice. Fluorescence imaging includes fluorescence reflectance imaging (FRI), fluorescence diffuse
tomography (fDOT), and fluorescence molecular Imaging (FMT
). A U87 cell line was genetically modified for constitutive expression of both the encoding Fluc and iRFP reporter genes and assayed for cell, subcutaneous tumor and brain tumor imaging. On cultured cells, BLI was more sensitive than FRI; in vivo, tumors were first detected by BLI. Fluorescence of iRFP provided convenient tools such as flux cytometry, direct detection of the fluorescent protein on histological slices, and fluorescent tomography that allowed for 3D localization and absolute quantification of the fluorescent signal in brain tumors.
The new WHO classification of diffuse gliomas has been refined and now includes the 1p/19q codeletion,
IDH1/2
mutation, and histone H3-K27M mutation. Our objective was to assess the prognostic value ...of the updated 2016 WHO classification in the French POLA cohort. All cases of high-grade oligodendroglial tumors sent for central pathological review and included into the French nationwide POLA cohort were reclassified according to the updated 4th WHO classification. In total, 1041 patients were included, with a median age at diagnosis of 50.4 years (range 17.1–84.4). Based on the new histomolecular classification, diagnoses included anaplastic oligodendroglioma
IDH
mutant and 1p/19q-codeleted (32.5 %), anaplastic astrocytoma
IDH
mutant (
IDH
mut
) (11.0 %), anaplastic astrocytoma
IDH
wild type (
IDH
wt
) (5.3 %), glioblastoma
IDH
mut
(17.1 %), and glioblastoma
IDH
wt
(33.2 %). Ten patients presented with a diffuse midline tumor, H3 K27M mutant. The new WHO classification was prognostic for progression-free survival (PFS) and overall survival (OS) (
p
< 0.001). We did not find prognosis differences between grades III and IV for
IDH
mut
1p/19q intact and
IDH
wt
gliomas in univariate and multivariate analyses. Among anaplastic astrocytoma
IDH
wt
, cases with chromosome arm 7p gain and 10q loss (55 %) had shorter PFS than the others (
p
= 0.027). In conclusion, the new WHO histomolecular classification of diffuse gliomas presented with high prognostic value. Grading was not discriminant between grade III and IV high-grade gliomas.
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.
Radiotherapy for glioblastoma in the elderly Keime-Guibert, Florence; Chinot, Olivier; Taillandier, Luc ...
New England journal of medicine/The New England journal of medicine,
04/2007, Letnik:
356, Številka:
15
Journal Article
Recenzirano
Odprti dostop
There is no community standard for the treatment of glioblastoma in patients 70 years of age or older. We conducted a randomized trial that compared radiotherapy and supportive care with supportive ...care alone in such patients.
Patients 70 years of age or older with a newly diagnosed anaplastic astrocytoma or glioblastoma and a Karnofsky performance score of 70 or higher were randomly assigned to receive supportive care only or supportive care plus radiotherapy (focal radiation in daily fractions of 1.8 Gy given 5 days per week, for a total dose of 50 Gy). The primary end point was overall survival; secondary end points were progression-free survival, tolerance of radiotherapy, health-related quality of life, and cognition.
We randomly assigned 85 patients from 10 centers to receive either radiotherapy and supportive care or supportive care alone. The trial was discontinued at the first interim analysis, which showed that with a preset boundary of efficacy, radiotherapy and supportive care were superior to supportive care alone. A final analysis was carried out for the 81 patients with glioblastoma (median age, 73 years; range, 70 to 85). At a median follow-up of 21 weeks, the median survival for the 39 patients who received radiotherapy plus supportive care was 29.1 weeks, as compared with 16.9 weeks for the 42 patients who received supportive care alone. The hazard ratio for death in the radiotherapy group was 0.47 (95% confidence interval, 0.29 to 0.76; P=0.002). There were no severe adverse events related to radiotherapy. The results of quality-of-life and cognitive evaluations over time did not differ significantly between the treatment groups.
Radiotherapy results in a modest improvement in survival, without reducing the quality of life or cognition, in elderly patients with glioblastoma. (ClinicalTrials.gov number, NCT00430911 ClinicalTrials.gov.).
One of the most challenging aspects of the surgical treatment of tuberculum sellae meningioma is to control the involvement of the inferomedial side of the optic nerve, which is not directly ...visualized by an ipsilateral approach and thus requires optic nerve mobilization.
Between 2003 and 2017, 21 consecutive patients were operated on using this approach. The surgical technique is described and the visual outcomes, resection and recurrence rates, and complications are analyzed.
Twenty patients were included, with a median follow-up of 5.6 years. Regarding visual outcomes, among the 19 patients who had a visual impairment before surgery, 14 (74%) improved, 2 were stabilized (10%), and 2 (10%) showed a worsening of the most-compromised optic nerve and 1 (5%) of the less-compromised optic nerve. Gross total resection was achieved in 18 patients (90%) and 1 patient experienced recurrence 10 years after the initial surgery.
This approach allowed lower mobilization of the compromised optic nerve, better preservation of the vascularization of the visual pathways, and direct access to the inferomedial side of the optic nerve.
•The control of the intracanalar infiltration is one of the most challenging aspect of tuberculum sellae meningioma surgery.•The contralateral to the most compromised optic nerve approach provides a better visualization of this part of the tumor.•This approach led to high rates of visual improvement with an acceptable risk regarding the noncompromised optic nerve.
Although some countries have observed a stabilization in the incidence of CNS, an increasing incidence has been reported from multiple studies. Recent observations point out to the heterogeneity of ...incidence trends according to histological subtypes, gender and age-groups. Using a high-quality regional CNS tumor registry, this article describes the trends of CNS tumor incidence for main histological subtypes, including benign and malignant tumors, in the French department of Gironde from 2000 to 2012.
Crude and age-standardized incidence rates were calculated globally, by histological subtypes, malignant status, gender and age groups. For trends, annual percent changes (APC) were obtained from a piecewise log-linear model.
A total of 3515 CNS tumors was registered during the period. The incidence of overall CNS tumors was 19/100000 person-years (8.3/100000 for neuroepithelial tumors and 7.3/100000 for meningeal tumors). An increased incidence of overall CNS tumors was observed from 2000 to 2012 (APC = + 2.7%; 95%-confidence interval (CI): 1.8-3.7). This trend was mainly explained by an increase in the incidence of meningiomas over the period (APC = + 5.4%, 95%-CI: 3.8-7.0). The increased incidence rate of CNS tumors was more pronounced in female and in older patients even though the incidence rate increased in all age groups.
Part of the temporal variation may be attributed to improvement in registration, diagnosis and clinical practices but also to changes in potential risk factors. Thus, etiological studies on CNS tumors are needed to clarify this rising trend.
Abstract
Introduction
The first line of treatment for nonfunctioning pituitary adenoma (NFPA) is surgery. Adjuvant radiotherapy or surveillance and new treatment (second surgical operation or salvage ...radiotherapy) in case of recurrence are options discussed at the multidisciplinary tumor board. The purpose of this study was to evaluate the therapeutic outcome for each option.
Methods
The records of 256 patients followed with NFPA between 2007 and 2018 were retrospectively reviewed. Mean age at initial surgery was 55 years 18–86. Post-operative MRI found a residual tumor in 87% of patients. Mean follow-up was 12.1 years 0.8–42.7.
Results
After initial surgery, 40 patients had adjuvant radiotherapy. At 5, 10 and 15 years progression-free survival (PFS) was significantly different after surgery alone (77%, 58% and 40%) compared to surgery and adjuvant radiotherapy (84%, 78% and 78%) (HR = 0.24 0–0.53 p < 0.0005). Overall, after first, second or third surgical operation, 69 patients had adjuvant radiotherapy and 41 salvage radiotherapy. Five-year PFS was similar for adjuvant (90%) and salvage radiotherapy (97%) (p = 0.62). After a second surgical operation, 62% and 71% of patients were irradiated after 2 and 5 years respectively. The risk of corticotropic and thyrotropic deficiency rates were 38% and 59% after second or third surgical operation and 40% and 73% after radiotherapy. Brain tumors occurred in 4 patients: 1 meningioma present at initial surgery, and after radiotherapy, 1 neurinoma which appeared at 5 years, 1 glioblastoma at 13 years and 1 meningioma at 20 years.
Conclusion
Among patients treated by surgery for NFPA, a “wait-and-see” attitude should be an option since adjuvant radiotherapy is not superior to salvage radiotherapy. However, in case of recurrence or progression, the authors recommended delivery of salvage radiotherapy to avoid a second surgical operation.
Background
The majority of cavernous sinus lesions are meningiomas, for which treatment (fractioned radiotherapy or radiosurgery), if indicated, is usually initiated upon image-based diagnosis. ...However, this region can be affected by a wide variety of pathological processes and the risk of misdiagnosis exists. As pathological diagnosis can be obtained by biopsy through the
foramen ovale
in selected cases, we asked the question as to whether systematically performing this procedure before treatment would provide additional, relevant diagnostic information.
Methods
All the cases referred to our department between January 2008 and December 2019 for cavernous sinus lesions that were considered for treatment and anatomically suitable for transforamen ovale biopsy were included. Outcomes and subsequent treatment or follow-up data were collected.
Results
Thirty-five patients were included. Twenty-six were highly suspected to have meningioma or schwannoma at imaging, among whom biopsy allowed diagnosis confirmation in 17 cases (65%). For the nine patients for whom biopsy was indicated upon suspected malignancy or inflammatory disease on imaging, biopsy revealed three meningiomas and one lymphoma and was not contributory in five cases (56%), three of which underwent open surgery. Three patients (8.5%) had persistent neuralgia at the last follow-up.
Conclusions
When cavernous sinus meningioma or schwannoma is highly suspected upon predefined imaging criteria by an experienced neuroradiologist, invasive exploration before treatment does not seem to be indicated. Otherwise, transforamen ovale biopsy might be consider in selected cases as a minimally invasive option to obtain pathological analysis.
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