This study aimed to assess the correlation of temporal muscle thickness (TMT), measured on routine cranial magnetic resonance (MR) images, with lumbar skeletal muscles obtained on computed tomography ...(CT) images in brain metastasis patients to establish a new parameter estimating skeletal muscle mass on brain MR images.
We retrospectively analyzed the cross-sectional area (CSA) of skeletal muscles at the level of the third lumbar vertebra on computed tomography scans and correlated these values with TMT on MR images of the brain in two independent cohorts of 93 lung cancer and 61 melanoma patients (overall: 154 patients) with brain metastases.
Pearson correlation revealed a strong association between mean TMT and CSA in lung cancer and melanoma patients with brain metastases (0.733; p<0.001). The two study cohorts did not differ significantly in patient characteristics, including age (p = 0.661), weight (p = 0.787), and height (p = 0.123). However, TMT and CSA measures differed significantly between male and female patients in both lung cancer and melanoma patients with brain metastases (p<0.001).
Our data indicate that TMT, measured on routine cranial MR images, is a useful surrogate parameter for the estimation of skeletal muscle mass in patients with brain metastases. Thus, TMT may be useful for prognostic assessment, treatment considerations, and stratification or a selection factor for clinical trials in patients with brain metastases. Further studies are needed to assess the association between TMT and clinical frailty parameters, and the usefulness of TMT in patients with primary brain tumors.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Meningiomas are classified based on histological features, but genetic and epigenetic features are emerging as relevant biomarkers for outcome prediction and may supplement histomorphological ...evaluation. We investigated meningioma‐relevant mutations and their correlation with DNA methylation clusters and patient survival times. Formalin‐fixed and paraffin‐embedded samples of 126 meningioma patients (WHO grade I 52/126; 41.3%; WHO grade II: 48/126; 38.1%; WHO grade III: 26/126; 20.6%) were investigated. We analyzed NF2, TRAF7, KLF4, ARID, SMO, AKT, TERT promotor, PIK3CA, and SUFU mutations using panel sequencing and correlated them to DNA methylation classes (MC) determined using 850k EPIC arrays. The TRAKL mutation genotype was characterized by the presence of any of the following mutations: TRAF7, AKT1, and KLF4. Survival data including progression‐free survival (PFS) and overall survival (OS) was retrieved from chart review. Mutations were evident in 90/126 (71.4%) specimens with mutations in NF2 (39/126; 31.0%), TRAF7 (39/126; 31.0%) and KLF4 (25/126; 19.8%) being the most frequent ones. Two or more mutations were observed in 35/126 (27.8%) specimens. While TRAKL was predominantly found in benign MC, NF2 was associated with malign MC (p < 0.05). TRAF7, KLF4, and TRAKL mutation genotype were associated with improved PFS and OS (p < 0.05). TERT promotor methylation, intermediate, and malign MC were associated with impaired PFS and OS (p < 0.05). Methylation cluster showed better prognostic discrimination for PFS and OS (c‐index 0.77/0.75) than each of the individual mutations (c‐index 0.63/0.68). In multivariate analysis correcting for age, gender, MC, and WHO grade, none of the individual mutations except TERT remained an independent significant prognostic factor for PFS. Molecular profiling including mutational analysis and DNA methylation classification may facilitate more precise prognostic assessment and identification of potential targets for personalized therapy in meningioma patients.
Molecular profiling including meningioma relevant mutations and DNA methylation classification may facilitate more precise prognostic assessment and identification of potential targets for personalized therapy in meningioma patients.
The management of primary central nervous system (PCNSL) is one of the most controversial topics in neuro-oncology because of the complexity of the disease and the limited number of controlled ...studies available. In 2021, given recent advances and the publication of practice-changing randomized trials, the European Association of Neuro-Oncology (EANO) created a multidisciplinary task force to update the previously published evidence-based guidelines for immunocompetent adult patients with PCNSL and added a section on immunosuppressed patients. The guideline provides consensus considerations and recommendations for the treatment of PCNSL, including intraocular manifestations and specific management of the elderly. The main changes from the previous guideline include strengthened evidence for the consolidation with ASCT in first-line treatment, prospectively assessed chemotherapy combinations for both young and elderly patients, clarification of the role of rituximab even though the data remain inconclusive, of the role of new agents, and the incorporation of immunosuppressed patients and primary ocular lymphoma. The guideline should aid the clinicians in everyday practice and decision making and serve as a basis for future research in the field.
A scorecard to evaluate magnetic resonance imaging (MRI) findings during the course of leptomeningeal metastases (LM) has been proposed by the Response Assessment in Neuro-Oncology (RANO) group.
To ...explore the feasibility of the Leptomeningeal Assessment in Neuro-Oncology (LANO) scorecard, cerebrospinal MRIs of 22 patients with LM from solid tumors were scored by 10 neuro-oncologists and 9 neuroradiologists at baseline and at follow-up after treatment. Raters were blinded for clinical data including treatment. Agreement between raters of single items was evaluated using a Krippendorff alpha coefficient. Agreement between numerical parameters such as scores for changes between baseline and follow-up and total scores was evaluated by determining the intraclass coefficient of correlation.
Most raters experienced problems with the instructions of the scorecard. No acceptable alpha concordance coefficient was obtained for the rating of single items at baseline or follow-up. The most concordant ratings were obtained for spinal nodules. The concordances were worst for brain linear leptomeningeal enhancement and cranial nerve enhancement. Discordance was less prominent among neuroradiologists than among neuro-oncologists. High variability was also observed for evaluating changes between baseline and follow-up and for total scores.
Assessing response of LM by MRI remains challenging. Central imaging review is therefore indispensable for clinical trials. Based on the present results, we propose a new, simplified scorecard that will require validation using a similar approach as pursued here. The main challenges are to define measurable versus nonmeasurable (target) lesions and measures of change that allow assessment of response.
Abstract
BACKGROUND
Intraoperative histopathology and acquisition of multiple tissue samples in stereotactic biopsies results in a prolonged length of surgery and potentially increased complication ...rate.
OBJECTIVE
To investigate the clinical benefits of a novel strategy for stereotactic brain tumor biopsies with the assistance of 5-aminolevulinic acid (5-ALA) induced fluorescence.
METHODS
Patients that received 5-ALA prior to stereotactic biopsy of a suspected brain tumor were included. According to our strategy, the procedure was terminated in the case of strong fluorescence of the biopsy samples. In contrast, intraoperative histology was demanded in the case of vague/no fluorescence. Length of surgery, number of biopsy samples, diagnostic rate, and periprocedural complications were compared between these 2 groups.
RESULTS
Altogether, 79 patients were included, and strong fluorescence was present in 62 cases (79%), vague fluorescence was in 4 cases (5%), and no fluorescence was in 13 cases (16%). The diagnostic rate was comparable in biopsies with strong fluorescence without intraoperative histopathology and cases with vague/no fluorescence with intraoperative histopathology (98% vs 100%; P = 1.000). A significantly shorter length of surgery (41 vs 77 min; P < .001) and reduced average number of biopsy samples (3.6 vs 4.9; P = .011) was found in patients with strong compared to vague/no fluorescence. However, no statically significant difference in periprocedural complications between cases with strong and vague/no fluorescence was found (7% vs 18%; P = .166).
CONCLUSION
Our data demonstrate the clinical benefits of a novel strategy for stereotactic brain tumor biopsies with assistance of 5-ALA. Thus, this biopsy strategy will increase the efficiency of this standard neurosurgical procedure in the future.
OBJECTIVE Stereotactic needle biopsies are usually performed for histopathological confirmation of intracranial lymphomas to guide adequate treatment. During biopsy, intraoperative histopathology is ...an effective tool to avoid acquisition of nondiagnostic samples. In the last years, 5-aminolevulinic acid (5-ALA)-induced fluorescence has been increasingly used for visualization of diagnostic brain tumor tissue during stereotactic biopsies. Recently, visible fluorescence was reported in the first cases of intracranial lymphomas as well. The aim of this study is thus to investigate the technical and clinical utility of 5-ALA-induced fluorescence in a large series of stereotactic biopsies for intracranial lymphoma. METHODS This prospective study recruited adult patients who underwent frameless stereotactic needle biopsy for a radiologically suspected intracranial lymphoma after oral 5-ALA administration. During biopsy, samples from the tumor region were collected for histopathological analysis, and presence of fluorescence (strong, vague, or no fluorescence) was assessed with a modified neurosurgical microscope. In tumors with available biopsy samples from at least 2 different regions the intratumoral fluorescence homogeneity was additionally investigated. Furthermore, the influence of potential preoperative corticosteroid treatment or immunosuppression on fluorescence was analyzed. Histopathological tumor diagnosis was established and all collected biopsy samples were screened for diagnostic lymphoma tissue. RESULTS The final study cohort included 41 patients with intracranial lymphoma. Stereotactic biopsies with assistance of 5-ALA were technically feasible in all cases. Strong fluorescence was found as maximum level in 30 patients (75%), vague fluorescence in 2 patients (4%), and no visible fluorescence in 9 patients (21%). In 28 cases, samples were obtained from at least 2 different tumor regions; homogenous intratumoral fluorescence was found in 16 of those cases (57%) and inhomogeneous intratumoral fluorescence in 12 (43%). According to histopathological analysis, all samples with strong or vague fluorescence contained diagnostic lymphoma tissue, resulting in a positive predictive value of 100%. Analysis showed no influence of preoperative corticosteroids or immunosuppression on fluorescence. CONCLUSIONS The data obtained in this study demonstrate the technical and clinical utility of 5-ALA-induced fluorescence in stereotactic biopsies of intracranial lymphomas. Thus, 5-ALA can serve as a useful tool to select patients not requiring intraoperative histopathology, and its application should markedly reduce operation time and related costs in the future.
The period of event-free survival (EFS) within the same histopathological glioma grades may have high variability, mainly without a known cause. The purpose of this study was to reveal the prognostic ...value of quantified tumor blood flow (TBF) values obtained by arterial spin labeling (ASL) for EFS in patients with histopathologically proven astrocytomas independent of WHO (World Health Organization) grade. Twenty-four patients with untreated gliomas underwent tumor perfusion quantification by means of pulsed ASL in 3T. The clinical history of the patients was retrospectively extracted from the local database. Six patients had to be excluded due to insufficent follow-up data for further evaluation or histopathologically verified oligodendroglioma tumor components. Receiver operating characteristic (ROC) curves were used to define an optimal cut-off value of maximum TBF (mTBF) values for subgrouping in low-perfused and high-perfused gliomas. Kaplan-Meier curves and Cox proportional hazard regression model were used to determine the prognostic value of mTBF for EFS. An optimal mTBF cut-off value of 182 ml/100 g/min (sensitivity = 83%, specificity = 100%) was determined. Patients with low-perfused gliomas had significantly longer EFS compared to patients with high-perfused gliomas (p = 0.0012) independent of the WHO glioma grade. Quantified mTBF values obtained by ASL offer a new and totally non-invasive marker to prognosticate the EFS, independently on histopathological tumor grading, in patients with gliomas.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background: Meningiomas are the most common primary central nervous system malignancies accounting for 36% of all intracranial tumors. However, only 1% of meningioma is classified as malignant ...(anaplastic) meningioma. Due to their rarity, clinical management of these tumors presents several gaps. Methods: We carried out a narrative review aimed to investigate current knowledge of anaplastic meningioma focusing on their pathological and radiological diagnosis, molecular assessment, and loco-regional and systemic management. Results: The most frequent genetic alteration occurring in meningioma is the inactivation in the neurofibromatosis 2 genes (merlin). The accumulation of copy number losses, including 1p, 6p/q, 10q, 14q, and 18p/q, and less frequently 2p/q, 3p, 4p/q, 7p, 8p/q, and 9p, compatible with instability, is restricted to NF2 mutated meningioma. Surgery and different RT approaches represent the milestone of grade 3 meningioma management, while there is a marginal role of systemic therapy. Conclusions: Anaplastic meningiomas are rare tumors, and diagnosis should be suspected and confirmed by trained radiologists and pathologists. Despite the current marginal role of systemic therapy, it is possible that the increasing knowledge of molecular altered pathways of the disease will lead to the development of novel effective systemic treatments.
Medulloblastoma (MB) is a malignant embryonal tumor of the posterior fossa belonging to the family of primitive neuro-ectodermic tumors (PNET). MB generally occurs in pediatric age, but in 14–30% of ...cases, it affects the adults, mostly below the age of 40, with an incidence of 0.6 per million per year, representing about 0.4–1% of tumors of the nervous system in adults. Unlike pediatric MB, robust prospective trials are scarce for the post-puberal population, due to the low incidence of MB in adolescent and young adults. Thus, current MB treatments for older patients are largely extrapolated from the pediatric experience, but the transferability and applicability of these paradigms to adults remain an open question. Adult MB is distinct from MB in children from a molecular and clinical perspective. Here, we review the management of adult MB, reporting the recent published literature focusing on the effectiveness of upfront chemotherapy, the development of targeted therapies, and the potential role of a reduced dose of radiotherapy in treating this disease.
Temporal muscle thickness (TMT) was investigated as a novel surrogate marker on MRI examinations of the brain, to detect patients who may be at risk for sarcopenia. TMT was analyzed in a ...retrospective, normal collective cohort (
= 624), to establish standard reference values. These reference values were correlated with grip strength measurements and body mass index (BMI) in 422 healthy volunteers and validated in a prospective cohort (
= 130) of patients with various neurological disorders. Pearson correlation revealed a strong association between TMT and grip strength (retrospective cohort, ρ = 0.746;
< 0.001; prospective cohort, ρ = 0.649;
< 0.001). A low or no association was found between TMT and age (retrospective cohort, R
correlation coefficient 0.20;
< 0.001; prospective cohort, ρ = -0.199;
= 0.023), or BMI (retrospective cohort, ρ = 0.116;
= 0.042; prospective cohort, ρ = 0.227;
= 0.009), respectively. Male patients with temporal wasting and unintended weight loss, respectively, showed significantly lower TMT values (
= 0.04 and
= 0.015, unpaired
-test). TMT showed a high correlation with muscle strength in healthy individuals and in patients with various neurological disorders. Therefore, TMT should be integrated into the diagnostic workup of neurological patients, to prevent, delay, or treat sarcopenia.
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