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PURPOSE: In the randomized CeTeG/NOA-09 trial, lomustine/temozolomide (CCNU/TMZ) was superior to TMZ therapy regarding overall survival (OS) in MGMT promotor-methylated glioblastoma. Progression-free survival (PFS) and pseudoprogression rates (about 10%) were similar in both arms. Further evaluating this discrepancy, we analyzed patterns of postprogression survival (PPS) and MRI features at first progression according to modified RANO criteria (mRANO). METHODS: We classified the patients of the CeTeG/NOA-09 trial according to long vs. short PPS employing a cut-off of 18 months and compared baseline characteristics and survival times. In patients with available MRIs and confirmed progression, the increase in T1-enhancing, FLAIR hyperintense lesion volume and the change in ADC mean value of contrast-enhancing tumor upon progression were determined. RESULTS: Patients with long PPS in the CCNU/TMZ arm had a particularly short PFS (5.6 months). PFS in this subgroup was shorter than in the long PPS subgroup of the TMZ arm (11.1 months, p = 0.01). At mRANO-defined progression, patients of the CCNU/TMZ long PPS subgroup had a significantly higher increase of mean ADC values (p = 0.015) and a tendency to a stronger volumetric increase in T1-enhancement (p = 0.22) as compared to long PPS patients of the TMZ arm. CONCLUSION: The combination of survival and MRI analyses identified a subgroup of CCNU/TMZ-treated patients with features that sets them apart from other patients in the trial: short first PFS despite long PPS and significant increase in mean ADC values upon mRANO-defined progression. The observed pattern is compatible with the features commonly observed in pseudoprogression suggesting mRANO-undetected pseudoprogressions in the CCNU/TMZ arm of CeTeG/NOA-09.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Dacarbazina/uso terapêutico , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/tratamento farmacológico , Temozolomida/uso terapêutico , Glioblastoma/diagnóstico por imagem , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Lomustina/uso terapêutico , Imageamento por Ressonância Magnética , Antineoplásicos Alquilantes/uso terapêuticoRESUMO
PURPOSE: Multimodal therapies have significantly improved prognosis in glioma. However, in particular radiotherapy may induce long-term neurotoxicity compromising patients' neurocognition and quality of life. The present prospective multicenter study aimed to evaluate associations of multimodal treatment with neurocognition with a particular focus on hippocampal irradiation. METHODS: Seventy-one glioma patients (WHO grade 1-4) were serially evaluated with neurocognitive testing and quality of life questionnaires. Prior to (baseline) and following further treatment (median 7.1 years [range 4.6-11.0] after baseline) a standardized computerized neurocognitive test battery (NeuroCog FX) was applied to gauge psychomotor speed and inhibition, verbal short-term memory, working memory, verbal and non-verbal memory as well as verbal fluency. Mean ipsilateral hippocampal radiation dose was determined in a subgroup of 27 patients who received radiotherapy according to radiotherapy plans to evaluate its association with neurocognition. RESULTS: Between baseline and follow-up mean performance in none of the cognitive domains significantly declined in any treatment modality (radiotherapy, chemotherapy, combined radio-chemotherapy, watchful-waiting), except for selective attention in patients receiving chemotherapy alone. Apart from one subtest (inhibition), mean ipsilateral hippocampal radiation dose > 50 Gy (Dmean) as compared to < 10 Gy showed no associations with long-term cognitive functioning. However, patients with Dmean < 10 Gy showed stable or improved performance in all cognitive domains, while patients with > 50 Gy numerically deteriorated in 4/8 domains. CONCLUSIONS: Multimodal glioma therapy seems to affect neurocognition less than generally assumed. Even patients with unilateral hippocampal irradiation with > 50 Gy showed no profound cognitive decline in this series.
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Neoplasias Encefálicas , Glioma , Humanos , Adulto , Seguimentos , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/radioterapia , Qualidade de Vida , Estudos Prospectivos , Glioma/complicações , Glioma/radioterapia , Terapia CombinadaRESUMO
BACKGROUND: Treatment of relapsed or refractory primary CNS lymphoma (r/r PCNSL) is difficult, particularly in patients not eligible for high dose chemotherapy with autologous stem cell transplantation (HDC-ASCT). No standard treatment has been defined for these patients yet. METHODS: We retrospectively analyzed survival, prognostic factors, hospitalization time and Karnofsky performance score (KPS) before and after treatment in 54 r/r PCNSL patients with isolated cerebral relapse or progression (n = 23 refractory, n = 31 relapsed) not eligible for HDC-ASCT, who received heterogenous salvage treatments. RESULTS: Treatments were temozolomide (+ rituximab) (n = 21), high dose methotrexate (HD-MTX)-based therapy (n = 11), whole brain radiotherapy (WBRT)/focal radiotherapy (n = 11), other systemic treatments (n = 2) and best supportive care (BSC, n = 9). Median progression free survival (PFS) and overall survival (OS) were 2.6 months (95% CI 1.0-4.2 months) and 4.8 months (95% CI 3.3-6.3 months), respectively. Eight patients survived for ≥ 3 years (13.1%, n = 3 received temozolomide, n = 3 WBRT, n = 2 HD-MTX-based treatment). Application of any salvage treatment (vs. BSC), younger age at relapse and asymptomatic (vs. symptomatic) relapse were positive prognostic factors. No significant differences in OS were found for the different salvage treatments. Median hospitalization time for treatment was 15/13 days for temozolomide (+ rituximab)/radiotherapy compared to 55 days for HD-MTX-based therapy. Median KPS in assessable patients (n = 41) was 60 (range 30-100) before treatment and 50 (range 20-90) after treatment. In patients with response to treatment (n = 16) KPS improved from 60 (range 40-90) before treatment to 70 (range 50-90) after treatment, while patients with PD (n = 25) deteriorated from 60 (range 30-100) to 40 (range 20-70). CONCLUSION: Survival for this cohort of r/r PCNSL patients with isolated cerebral relapse or progression was poor. Considering long hospital stays associated with HD-MTX-based chemotherapy and neurotoxicity associated with WBRT, temozolomide might be worth considering with a chance of prolonged survival and avoidance of long hospitalization. Novel therapeutic agents are urgently needed to improve survival in r/r PCNSL patients.
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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.
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Neoplasias do Sistema Nervoso Central , Linfoma , Adulto , Humanos , Idoso , Terapia Combinada , Neoplasias do Sistema Nervoso Central/patologia , Protocolos de Quimioterapia Combinada Antineoplásica , Sistema Nervoso Central/patologia , Linfoma/tratamento farmacológicoRESUMO
Detection of tumor progression in patients with glioblastoma remains a major challenge. Extracellular vesicles (EVs) are potential biomarkers and can be detected in the blood of patients with glioblastoma. In our study, we evaluated the potential of serum-derived EVs from glioblastoma patients to serve as biomarker for tumor progression. EVs from serum of glioblastoma patients and healthy volunteers were separated by size exclusion chromatography and ultracentrifugation. EV markers were defined by using a proximity-extension assay and bead-based flow cytometry. Tumor progression was defined according to modified RANO criteria. EVs from the serum of glioblastoma patients (n = 67) showed an upregulation of CD29, CD44, CD81, CD146, C1QA and histone H3 as compared to serum EVs from healthy volunteers (P value range: <.0001 to .08). For two independent cohorts of glioblastoma patients, we noted upregulation of C1QA, CD44 and histone H3 upon tumor progression, but not in patients with stable disease. In a multivariable logistic regression analysis, a combination of CD29, CD44, CD81, C1QA and histone H3 correlated with RANO-defined tumor progression with an AUC of 0.76. Measurement of CD29, CD44, CD81, C1QA and histone H3 in serum-derived EVs of glioblastoma patients, along with standard MRI assessment, has the potential to improve detection of true tumor progression and thus could be a useful biomarker for clinical decision making.
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Vesículas Extracelulares , Glioblastoma , Humanos , Histonas , Proteínas Sanguíneas , Integrina beta1RESUMO
Due to the tumor itself or its therapy glioma patients may complain on cognitive impairment, while validated neuropsychological testing (NPT) capturing specific neuropsychological domains does not indicate "objective" dysfunction. Little is known on the relevance of this disturbance for patients' everyday life. We aimed to address whether glioma patients treated with state-of-the-art neurosurgical techniques complain on neuropsychological impairment and whether these subjective complaints are disclosed in formal NPT. We assessed both, "objective" and "subjective" neurocognitive functioning in 13 patients with newly diagnosed WHO grade 2 and 3 gliomas, operated between 06/2018 and 12/2020. All underwent both, preoperative and follow-up NPT as well as a semi-structured interview on subjective complaints and specific questionnaires (post-therapeutic) on attention, memory and executive functioning. On group level, no significant changes between preoperative and post-therapeutic NPT occurred. On the individual level, in 3/13 patients new post-therapeutic deficits in objective NPT were detected in specific domains (verbal memory, non-verbal memory, verbal fluency). By contrast, 8/13 patients reported on "subjective" memory impairments post-therapeutically. Furthermore, on specific questionnaires cognitive and emotional executive dysfunction and increased fatigue occurred in patients relative to normative data. Although the findings have to be replicated in larger populations, a discrepancy between "subjective" and "objective" measures was evident. While subjective neurocognitive impairment may simply not represent a true dysfunction, an alternative explanation might be that established standardized NPT is not suitable to detect subtle dysfunction in this population. "Subjective" and "objective" neurocognitive functioning might represent distinct constructs, which should complement each other in patient-centered Neuro-Oncology.
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Disfunção Cognitiva , Glioma , Humanos , Autorrelato , Glioma/complicações , Glioma/cirurgia , Glioma/patologia , Testes Neuropsicológicos , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/psicologia , Função Executiva , CogniçãoRESUMO
BACKGROUND: Brain tumor related epilepsy (BTRE) is a common complication of cerebral tumors and its incidence is highly dependent on the type of tumor, ranging from 10-15% in brain metastases to > 80% in low grade gliomas. Clinical management is challenging and has to take into account aspects beyond the treatment of non-tumoral epilepsy. MAIN BODY: Increasing knowledge about the pathophysiology of BTRE, particularly on glutamatergic mechanisms of oncogenesis and epileptogenesis, might influence management of anti-tumor and BTRE treatment in the future. The first seizure implies the diagnosis of epilepsy in patients with brain tumors. Due to the lack of prospective randomized trials in BTRE, general recommendations for focal epilepsies currently apply concerning the initiation of antiseizure medication (ASM). Non-enzyme inducing ASM is preferable. Prospective trials are needed to evaluate, if AMPA inhibitors like perampanel possess anti-tumor effects. ASM withdrawal has to be weighed very carefully against the risk of seizure recurrence, but can be achievable in selected patients. Permission to drive is possible for some patients with BTRE under well-defined conditions, but requires thorough neurological, radiological, ophthalmological and neuropsychological examination. CONCLUSION: An evolving knowledge on pathophysiology of BTRE might influence future therapy. Randomized trials on ASM in BTRE with reliable endpoints are needed. Management of withdrawal of ASMs and permission to drive demands thorough diagnostic as well as neurooncological and epileptological expertise.
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Although >10% of primary CNS lymphoma (PCNSL) patients are ≥80 years, data on this population are limited. We analyzed 19 consecutive octogenarians with PCNSL treated with high-dose methotrexate (HD-MTX)-based chemotherapy at our institution concerning outcome, prognostic factors and living conditions at six-month follow-up for 11 patients alive and in remission. Seven patients received intracerebroventricular (ICV) treatment additional to systemic therapy. Median follow-up was 27.3 months. Median overall survival was 16.3 months. Positive prognosticators of survival were application of ICV treatment (p = 0.033) and female gender (p = 0.015). All 11 patients alive and in remission at 6-month follow-up were living at home with a median Karnofsky performance score of 60 (range 50-90) and a median instrumental activities of daily living score of 3 (range 1-8). HD-MTX-based polychemotherapy including ICV treatment was feasible in this population, patients in remission needed moderate support in everyday live.
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Neoplasias do Sistema Nervoso Central , Linfoma , Idoso de 80 Anos ou mais , Humanos , Feminino , Metotrexato/uso terapêutico , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/etiologia , Estudos Retrospectivos , Prognóstico , Atividades Cotidianas , Resultado do Tratamento , Linfoma/diagnóstico , Linfoma/tratamento farmacológico , Linfoma/etiologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
PURPOSE: Cognitive functioning represents an essential determinant of quality of life. Since significant advances in neuro-oncological treatment have led to prolonged survival it is important to reliably identify possible treatment-related neurocognitive dysfunction in brain tumor patients. Therefore, the present study specifically evaluates the effects of standard treatment modalities on neurocognitive functions in glioma patients within two years after surgery. METHODS: Eighty-six patients with World Health Organization (WHO) grade 1-4 gliomas were treated between 2004 and 2012 and prospectively followed within the German Glioma Network. They received serial neuropsychological assessment of attention, memory and executive functions using the computer-based test battery NeuroCog FX. As the primary outcome the extent of change in cognitive performance over time was compared between patients who received radiotherapy, chemotherapy or combined radio-chemotherapy and patients without any adjuvant therapy. Additionally, the effect of irradiation and chemotherapy was assessed in subgroup analyses. Furthermore, the potential impact of the extent of tumor resection and histopathological characteristics on cognitive functioning were referred to as secondary outcomes. RESULTS: After a median of 16.8 (range 5.9-31.1) months between post-surgery baseline neuropsychological assessment and follow-up assessment, all treatment groups showed numerical and often even statistically significant improvement in all cognitive domains. The extent of change in cognitive functioning showed no difference between treatment groups. Concerning figural memory only, irradiated patients showed less improvement than non-irradiated patients (p = 0.029, η2 = 0.06). Resected patients, yet not patients with biopsy, showed improvement in all cognitive domains. Compared to patients with astrocytomas, patients with oligodendrogliomas revealed a greater potential to improve in attentional and executive functions. However, the heterogeneity of the patient group and the potentially selected cohort may confound results. CONCLUSION: Within a two-year post-surgery interval, radiotherapy, chemotherapy or their combination as standard treatment did not have a detrimental effect on cognitive functions in WHO grade 1-4 glioma patients. Cognitive performance in patients with adjuvant treatment was comparable to that of patients without.
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Neoplasias Encefálicas , Glioma , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/terapia , Cognição , Progressão da Doença , Glioma/tratamento farmacológico , Glioma/terapia , Humanos , Testes Neuropsicológicos , Qualidade de VidaRESUMO
PURPOSE: The role of obesity in glioblastoma remains unclear, as previous analyses have reported contradicting results. Here, we evaluate the prognostic impact of obesity in two trial populations; CeTeG/NOA-09 (n = 129) for MGMT methylated glioblastoma patients comparing temozolomide (TMZ) to lomustine/TMZ, and GLARIUS (n = 170) for MGMT unmethylated glioblastoma patients comparing TMZ to bevacizumab/irinotecan, both in addition to surgery and radiotherapy. METHODS: The impact of obesity (BMI ≥ 30 kg/m2) on overall survival (OS) and progression-free survival (PFS) was investigated with Kaplan-Meier analysis and log-rank tests. A multivariable Cox regression analysis was performed including known prognostic factors as covariables. RESULTS: Overall, 22.6% of patients (67 of 297) were obese. Obesity was associated with shorter survival in patients with MGMT methylated glioblastoma (median OS 22.9 (95% CI 17.7-30.8) vs. 43.2 (32.5-54.4) months for obese and non-obese patients respectively, p = 0.001), but not in MGMT unmethylated glioblastoma (median OS 17.1 (15.8-18.9) vs 17.6 (14.7-20.8) months, p = 0.26). The prognostic impact of obesity in MGMT methylated glioblastoma was confirmed in a multivariable Cox regression (adjusted odds ratio: 2.57 (95% CI 1.53-4.31), p < 0.001) adjusted for age, sex, extent of resection, baseline steroids, Karnofsky performance score, and treatment arm. CONCLUSION: Obesity was associated with shorter survival in MGMT methylated, but not in MGMT unmethylated glioblastoma patients.
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Neoplasias Encefálicas , Glioblastoma , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/terapia , Metilação de DNA , Metilases de Modificação do DNA/genética , Metilases de Modificação do DNA/metabolismo , Enzimas Reparadoras do DNA/genética , Enzimas Reparadoras do DNA/metabolismo , Glioblastoma/complicações , Glioblastoma/diagnóstico , Glioblastoma/terapia , Humanos , Obesidade/complicações , Prognóstico , Temozolomida/uso terapêuticoRESUMO
High-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) is reportedly an effective treatment strategy in relapsed or refractory primary CNS lymphoma (r/r PCNSL); however, only selected patients are eligible for this treatment. We retrospectively analyzed outcome, prognostic factors, and toxicity in 59 patients with r/r PCNSL planned to receive HCT-ASCT at our institution between January 2005 and December 2021 (n = 33 < 65 years; n = 26 ≥ 65 years). Median follow-up was 65 months (95% CI 21−109). Median age was 63 years (range 29−76), median Karnofsky performance score (KPS) was 80 (range 30−100). In the entire cohort of 59 patients, median overall survival (OS) was 14 months (95% CI 0−37). In 50/59 (84.7%) patients who completed HCT-ASCT, median progression free survival (PFS) was 12 months (95% CI 3−21) and median OS 30 months (95% CI 0−87). 1-year, 2-year, and 5-year OS rates of 61.2%, 52.3% and 47.1%, respectively, were observed. Six patients (10.2%) died related to treatment (1 during induction treatment, 5 post HCT-ASCT). Age was not prognostic. On univariate analysis, KPS ≥ 80 (p = 0.019) and complete or partial remission before HCT-ASCT (p = 0.026) were positive prognosticators of OS; on multivariate analysis, KPS (p = 0.043) and male gender (p = 0.039) had an impact on OS. The 5-year OS rate in patients with progressive or stable disease after induction treatment was 32.7%. In summary, HCT-ASCT was effective and feasible in this cohort of r/r PCNSL patients. Clinical state, remission status before HCT-ASCT, and gender influenced survival, whereas age did not influence outcome in this study.
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Brain tumors may represent devastating diseases and neuro-oncological research in the past solely focused on development of better treatments to achieve disease control. The efficacy of tumor-directed treatment was evaluated by progression-free and overall survival. However, as neuro-oncological treatment became more effective, preservation and improvement of quality of life (QoL) was noticed to represent an important additional outcome measure. The need to balance between aggressive tumor-directed treatment and preservation of QoL was increasingly acknowledged in brain tumor patients. QoL is comprised by many determinants; one of those may have been rather neglected so far: social cognition. Since diagnosis and treatment of brain tumors represent demanding life situations, patients may experience increased psychosocial burden and the negative consequences of illness on well-being may be buffered by intact social relationships. These skills to build and maintain supportive social relationships essentially depend on the ability to empathize with others and to recognize and appropriately address social conflicts, i.e., "sociocognitive functioning". Therefore, sociocognitive functions may influence QoL and treatment outcome. In this article, we review the literature on psychosocial burden and sociocognitive functioning in adult brain tumor patients.
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BACKGROUND: Glioblastoma is the most frequent and malignant primary brain tumor. Even in the subgroup with O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and favorable response to first-line therapy, survival after relapse is short (12 months). Standard therapy for recurrent MGMT-methylated glioblastoma is not standardized and may consist of re-resection, re-irradiation, and chemotherapy with temozolomide (TMZ), lomustine (CCNU), or a combination thereof. Preclinical results show that meclofenamate (MFA), originally developed as a nonsteroidal anti-inflammatory drug (NSAID) and registered in the USA, sensitizes glioblastoma cells to temozolomide-induced toxicity via inhibition of gap junction-mediated intercellular cytosolic traffic and demolishment of tumor microtube (TM)-based network morphology. METHODS: In this study, combined MFA/TMZ therapy will be administered (orally) in patients with first relapse of MGMT-methylated glioblastoma. A phase I component (6-12 patients, 2 dose levels of MFA + standard dose TMZ) evaluates safety and feasibility and determines the dose for the randomized phase II component (2 × 30 patients) with progression-free survival as the primary endpoint. DISCUSSION: This study is set up to assess toxicity and first indications of efficacy of MFA repurposed in the setting of a very difficult-to-treat recurrent tumor. The trial is a logical next step after the identification of the role of resistance-providing TMs in glioblastoma, and results will be crucial for further trials targeting TMs. In case of favorable results, MFA may constitute the first clinically feasible TM-targeted drug and therefore might bridge the idea of a TM-targeted therapeutic approach from basic insights into clinical reality. TRIAL REGISTRATION: EudraCT 2021-000708-39 . Registered on 08 February 2021.
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Glioblastoma , Antineoplásicos Alquilantes/efeitos adversos , Metilases de Modificação do DNA/uso terapêutico , Enzimas Reparadoras do DNA/genética , Enzimas Reparadoras do DNA/uso terapêutico , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Humanos , Ácido Meclofenâmico/uso terapêutico , Recidiva Local de Neoplasia , Temozolomida/efeitos adversos , Proteínas Supressoras de Tumor/uso terapêuticoRESUMO
BACKGROUND AND PURPOSE: Consensus criteria for autoimmune limbic encephalitis (ALE) allow for a diagnosis even without neuronal antibodies (Abs), but it remains unclear which clinical features should prompt neuronal Ab screening in temporal lobe epilepsy patients. The aim of the study was to investigate whether patients with temporal lobe seizures associated with additional symptoms or signs of limbic involvement may harbor neuronal Abs, and which clinical features should prompt neuronal Ab screening in these patients. METHODS: We identified 47 patients from a tertiary epilepsy center with mediotemporal lobe seizures and additional features suggestive of limbic involvement, including either memory deficits, psychiatric symptoms, mediotemporal magnetic resonance imaging (MRI) hyperintensities or inflammatory cerebrospinal fluid (CSF). Neuronal Ab testing was carried out at two independent reference laboratories (Bielefeld-Bethel, Germany, and Barcelona, Spain). All brain MRI scans were assessed by two reviewers independently. RESULTS: Temporal lobe seizures were accompanied by memory deficits in 35/46 (76%), psychiatric symptoms in 27/42 (64%), and both in 19/42 patients (45%). Limbic T2/fluid-attenuated inversion recovery signal hyperintensities were found in 26/46 patients (57%; unilateral: n = 22, bilateral: n = 4). Standard CSF studies were abnormal in 2/37 patients (5%). Neuronal Abs were confirmed in serum and/or CSF in 8/47 patients (17%) and were directed against neuronal cell-surface targets (leucine-rich glioma inactivated protein 1: n = 1, contactin-associated protein-2: n = 1, undetermined target: n = 3) or glutamic acid decarboxylase in its 65-kD isoform (n = 3, all with high titers). Compared to Ab-negative patients, those who harbored neuronal Abs were more likely to have uni- or bilateral mediotemporal MRI changes (8/8, 100% vs. 18/38, 47%; p = 0.01, Fisher's exact test). CONCLUSIONS: In patients with temporal lobe seizures and additional limbic signs, 17% had neuronal Abs affirming ALE diagnosis. Mediotemporal MRI changes were found in all Ab-positive cases and had a positive likelihood ratio of 2.11 (95% confidence interval 1.51-2.95).
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Epilepsia do Lobo Temporal , Encefalite Límbica , Autoanticorpos , Doenças Autoimunes , Epilepsia do Lobo Temporal/complicações , Epilepsia do Lobo Temporal/diagnóstico por imagem , Humanos , Encefalite Límbica/diagnóstico , Encefalite Límbica/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Transtornos da Memória/complicações , Convulsões/complicações , Convulsões/etiologia , Lobo Temporal/diagnóstico por imagemAssuntos
Neoplasias do Sistema Nervoso Central , Linfoma não Hodgkin , Biópsia , Medula Óssea , HumanosRESUMO
Patients with primary central nervous system lymphoma (PCNSL) not fulfilling inclusion criteria for clinical trials represent an underreported population. Thirty-four consecutive PCNSL patients seen at our center between 2005 and 2019 with exclusion criteria for therapeutic trials were analyzed (non-study patients) and compared with patients from the G-PCNSL-SG-1 (German PCNSL Study Group 1) study (study patients), the largest prospective multicenter trial on PCNSL, comprising 551 patients. Median follow up was 68 months (range 1-141) in non-study patients and 51 months (1-105) in study patients. Twenty-seven/34 (79.4%) non-study patients received high dose methotrexate (HDMTX), while seven/34 (20.6%) with a glomerular filtration rate (GFR) < 50 mL/min did not. Median overall survival (OS) was six months (95% confidence interval [CI] 0-21 months) in those 34 non-study patients. The 27 non-study patients treated with HDMTX were compared with 526/551 G-PCNSL-SG-1 study patients who had received HDMTX as well. Median OS was 20 months (95% CI 0-45)/21 months (95% CI 18-25) in 27 non-study/526 study patients (p = 0.766). Favorable prognostic factors in non-study patients were young age, application of HDMTX and early response on magnet resonance imaging (MRI). If HDMTX-based chemotherapy can be applied, long-term disease control is possible even in patients not qualifying for clinical trials. Initial response on early MRI might be useful for decision on treatment continuation.