Diagnostic Algorithm for Intracranial Lesions in the Emergency Department: Effectiveness of the Relative Brain Volume and Hounsfield Unit Value Measured by Perfusion Tomography.

Background Early treatment of intracranial lesions in the emergency department is crucial, but it can be challenging to differentiate between them. This differentiation is essential because the treatment of each type of lesion is different. Cerebral computed tomography perfusion (CTP) imaging can help visualize the vascularity of brain lesions and provide absolute quantification of physiological parameters. Compared to magnetic resonance imaging, CTP has several advantages, such as simplicity, wide availability, and reproducibility. Purpose This study aimed to assess the effectiveness of Hounsfield units (HU) in measuring the density of hypercellular lesions and the ability of CTP to quantify hemodynamics in distinguishing intracranial space-occupying lesions. Methods A retrospective study was conducted from March 2016 to March 2022. All patients underwent CTP and CT scans, and relative cerebral blood volume (rCBV) and HU were obtained for intracranial lesions. Results We included a total of 244 patients in our study. This group consisted of 87 (35.7%) individuals with glioblastomas (GBs), 48 (19.7%) with primary central nervous system lymphoma (PCNSL), 45 (18.4%) with metastases (METs), and 64 (26.2) with abscesses. Our study showed that the HUs for METs were higher than those for GB (S 57.4% and E 88.5%). In addition, rCBV values for PCNSL and abscesses were lower than those for GB and METs. The HU in PCNSL was higher than those in abscesses (S 94.1% and E 96.6%). Conclusion PCT parameters provide valuable information for diagnosing brain lesions. A comprehensive assessment improves accuracy. Combining rCBV and HU enhances diagnostic accuracy, making it a valuable tool for distinguishing between lesions. PCT's widespread availability allows for the use of both anatomical and functional information with high spatial resolution for diagnosing and managing brain tumor patients.

Epidemiology of Intracranial Meningiomas in Mexico: Cohort of the National Institute of Neurology and Neurosurgery During the Last Decade.

Introduction Meningiomas have been described as slow-growing neoplasms with benign behavior derived from the connective tissue surrounding the brain and spinal cord. Meningiomas represent one-third of primary central nervous system (CNS) tumors. The World Health Organization (WHO) initially classified them into three groups based on their histopathological characteristics, recently incorporating molecular patterns. Small cohorts have been reported in Latin America compared to the international literature. Ignoring the epidemiology of meningiomas in this region and considering this limitation, we aim to study the epidemiology of meningiomas in our country, Mexico. Material and methods A historical cohort was carried out on 916 patients diagnosed with intracranial meningiomas from January 2008 to January 2021, considering sociodemographic, topographic, and histopathological characteristics. Results In this study, 69.4% (n=636) of patients were women with a mean overall age of 47.53 (SD=14.85) years; 79.6% (n=729) of the lesions were supratentorial with convexity meningiomas being the most prevalent at 32.6% (n=299). Histopathologically, transitional (45.7%) (n=419), meningothelial (22.1%) (n=202), and fibroblastic (16.7%) (n=153) meningiomas were the most frequent. We found significant differences between men and women in age (p=0.01), infra or supratentorial presentation (p<0.001), location of the lesion (p<0.001), and histopathological characteristics (p<0.001). Conclusions Our results are consistent with what has been reported; however, until now, it appears as the largest series reported in our country and Latin America.

Relative cerebral blood volume as response predictor in the treatment of recurrent glioblastoma with anti-angiogenic therapy.

BACKGROUND: Glioblastoma is one of the most common brain tumors in adult populations, usually carrying a poor prognosis. While several studies have researched the impact of anti-angiogenic therapies, especially anti-VEFG treatments in glioblastoma, few have attempted to assess its progress using imaging studies. PURPOSE: We attempted to analyze whether relative cerebral blood volume (rCBV) from dynamic susceptibility-weighted contrast-enhanced MRI (DSC-MRI) could predict response in patients with glioblastoma undergoing Bevacizumab (BVZ) treatment. METHODS: We performed a retrospective study evaluating patients with recurrent glioblastoma receiving anti-angiogenic therapy with BVZ between 2012 and 2017 in our institution. Patients were scheduled for routine MRIs at baseline and first-month follow-up visits. Studies were processed for DSC-MRI, cT1, and FLAIR images, from which relative cerebral blood volume measurements were obtained. We assessed patient response using the Response Assessment in Neuro-Oncology (RANO) working group criteria and overall survival. RESULTS: 40 patients were included in the study and were classified as Bevacizumab responders and non-responders. The average rCBV before treatment was 4.5 for both groups, and average rCBV was 2.5 for responders and 5.4 for non-responders. ROC curve set a cutoff point of 3.7 for rCBV predictive of response to BVZ. Cox Multivariate analysis only showed rCBV as a predictive factor of OS. CONCLUSION: A statistically significant difference was found in rCBV between patients who responded and those who did not respond to BVZ treatment. rCBV may be a low-cost and effective marker to assess response to Bevacizumab treatment in GBM.

Assessing the Malignancy Risk of a Meningioma by Its Location.

BACKGROUND: Meningiomas represent 30% of primary intracranial tumors. The current incidence is up to 4.5 cases per 100,000 habitants worldwide. Although there is no prognostic difference among benign histopathological subtypes, atypical meningiomas and malignant meningiomas (WHO grade II and III respectively) may extend to the adjacent brain parenchyma, dura mater, and osseous tissue with a recurrence score (21-49%). This manuscript analyzes the malignancy risk according to neoplastic localization through a logistic retrospective analysis from a total sample of 452 patients with grade I, II, and III (WHO) meningiomas. METHODS: Detailed data collection through a three-year retrospective analysis (January 2008 to December 2011) was applied at Mexico's National Neurology and Neurosurgery Institute including patients with intracranial or spinal-cord meningioma, preoperative imaging study availability and post-surgical histopathological diagnosis. Formal written consent was not required with a waiver by the appropriate national research ethics committee in accordance with the provisions of the regulations of the general health law of Mexico. RESULTS: Convexity lesions displayed an increased risk of malignancy turning for non-benign meningiomas with an odds ratio of 3.1 (95% CI 1.6 to 5.7, p=0.0002) meanwhile skull-base meningiomas present an inverse risk with an odds ratio of 0.4 (95% CI 0.2 to 0.9, p=0.02), as well as spinal-cord meningiomas with an odds ratio of 0.3 (95% CI 0.1 to 0.9). CONCLUSION: Skull base and spinal cord meningiomas usually have benign behavior, meanwhile grade II or III meningiomas within this location are rare. The present work provides an additional criterion for decision making, according to the meningioma's location.

Clinical, Therapeutic, and Prognostic Experience in Patients With Glioblastoma.

BACKGROUND: Glioblastoma (GB) represents the most aggressive type of glioma with a poor prognosis despite the therapies used. As of today, data availability for therapeutic and prognosis experiences is limited. The cornerstone for this study is to create a framework overview of Mexico´s experience throughout 17 years of research. METHODS: Retrospective analysis from 2000 to 2017 including patients with a histological diagnosis of GB was performed. Data were collected from the ABC Medical Center and the Neurology and Neurosurgery National Institute. RESULTS: One hundred and thirty-seven patients were included with a mean age of 54 years. Histological diagnosis was made in all patients, of which 58.1% had a total resection, 31.6% had a partial resection, and 10.3% of them underwent biopsy. In all cases, patients received treatment under the following conditions: 10 patients were treated exclusively with stereotactic radiotherapy (RT). In 55 patients, a combination of RT and TMZ was used, the other 40 patients received RT plus CBP. Eighteen patients RT added to nitrosourea medication and lastly, 14 patients received a combination of RT/TMZ and Bevacizumab, a monoclonal antibody that inhibits the formation of blood vessels (BVZ). The progression-free survival (PFS) and overall survival (OS) were higher in the RT/TMZ/BVZ group (16.5 to 22.9 months) and the RT/TMZ group (11 to 17 months), the prognostic parameters included: Isocitrate dehydrogenase 1 mutation (IDH1), usage of BVZ and TMZ in the PLS and OS, considering as well, age range (<70 years) as a favorable prognostic factor. CONCLUSIONS: GB represents the most frequent intracranial neoplasia. Combined fractionated stereotactic RT added to Temozolomide and Bevacizumab received in our population reports favorable and superior results compared to the ones described in the literature. Further studies are necessary to know the biological behavior of our population.

Panorama general de la terapia electroconvulsiva: indicaciones y funcionamiento / Electroconvulsive Therapy Overview: Indications and How it Works

Resumen La terapia electroconvulsiva (TEC) constituye una de las modalidades terapéuticas disponibles para el tratamiento de padecimientos psiquiátricos como depresión, manía, esquizofrenia y estados de catatonia. Incluso se considera la terapia con resultados más eficaces y rápidos para pacientes con padecimientos como depresión resistente, ideación suicida recurrente, psicosis aguda y padecimientos que llegan a ser mortales como el síndrome neuroléptico maligno. La TEC es una terapia de estimulación cerebral en la cual la respuesta terapéutica se logra a través de la generación de un estímulo eléctrico con una intensidad suficiente para producir una crisis convulsiva encefálica controlada, logrando una respuesta neurobiológica y neuroquímica positiva favorable. Este artículo enfoca la utilidad de la TEC en el tratamiento de distintos padecimientos neuropsiquiátricos, sus principios fisiopatológicos, la técnica utilizada, sus principales complicaciones y, sobre todo, una descripción global de su utilización, su eficacia y seguridad, así como la experiencia de su uso en nuestra institución. Constituye uno de los pocos artículos en México con este contenido que consideramos fundamental como parte del conocimiento de todos los profesionales de la salud.

Abstract The electroconvulsive therapy (ECT) constitutes one of the many treatment modalities available for management of psychiatric illnesses like depression, mania, schizophrenia, and catatonic states. It is even considered the single most effective and fastest treatment modality for patients with conditions like antidepressant-resistant depression, recurring suicidal ideations, acute psychoses, and potentially fatal conditions like malignant neuroleptic syndrome. ECT is a brain-stimulation therapy in which the therapeutic goal can be achieved through generating an electrical stimulus with enough intensity to produce a controlled seizure, achieving a positive and favorable neurobiological and neurochemical response. This article focuses on the use of ECT in treating the various neuropsychiatric conditions, its pathophysiological principles, the employed technique, its main complications and overall a description of its use, its efficiency and safety, as to the experience of its employment in our institution. This comprises one of the few articles in Mexico with this kind of content that we deem fundamental as part of the general knowledge for healthcare professionals.

Role of Overweight, Obesity, and Comorbidities in the Prognosis of Patients With Breast Cancer With Brain Metastases.

INTRODUCTION: Breast cancer (BC) is the most common cancer in women, and the incidence of brain metastasis (BM) from BC ranges from 20% to 30%, with a median survival of 10 to 15 months. Previous reports have shown that the presence of obesity or diabetes negatively impacts survival. The present study investigates the association between obesity or diabetes mellitus (DM) and overall survival of patients with BC with BM. MATERIALS AND METHODS: A database from 2 referral centers for the period of July 2014 to February 2018 was analyzed. The inclusion criteria were as follows: patients who had a confirmed diagnosis of BC with BM were followed and treated at these centers. Demographic data, body weight and height, clinical and oncologic history, functional status, prognostic scales, and prognoses were examined. RESULTS: A total of 228 patients were included. The median age at BM was 50 years; the median survival after diagnosis was 12.1 months; 108 patients had a body mass index (BMI) ≥ 25, and 40 (17%) patients had DM. The association between survival and the presence of BMI > 25 exhibited a P value of 0.3. DISCUSSION: We found no association between overweight, obesity, or DM and survival in patients with BC with BM. The role of obesity in cancer is a robust research topic, as there are many questions to be answered. CONCLUSION: Obesity as a prognostic indicator should be further studied, because we found no association between overall survival and either patients with BM from BC with a BMI > 25 or those with normal weight.

Clinical manifestations and location of brain metastases as prognostic markers.

BACKGROUND: Brain metastases (BM) are a frequent complication of cancer and are regularly seen in clinical practice. New treatment modalities are improving survival after diagnosis of BM. However, symptoms are rarely reported and their significance is not well established. The aim of the present study was to investigate neurologic indicators as prognostic markers in patients with brain metastases. PATIENTS AND METHODS: A prospectively acquired database from 2 referral centers was analyzed. All patients had had at least 2 neuro-oncologic consultations and magnetic resonance imaging to confirm the diagnosis. Patients were classified according to universally used prognostic scores, gender, primary tumor, localization of BM, and clinical complaints. Univariate and multivariate analysis was used to evaluate associations. RESULTS: A total of 570 patients were included; 71% were female, and 91% had solid tumors. Median survival was 11 months (95% confidence interval 9.4-12.6). Of 1322 parenchymal lesions, 78% were supratentorial, and were most commonly in the frontal lobe. The most common symptoms were headache, vision changes, and weakness. Brain metastases in the brainstem were associated with a worse prognosis (P = 0.04). Visual complaints (P = 0.005), altered mental status, (P < 0.0001) and cranial neuropathy (P 0.001) were also associated with a poor outcome, as were poor performance status, more than 1 brain metastases, meningeal carcinomatosis, and uncontrolled primary cancer. CONCLUSIONS: Both presenting symptoms and the location of brain metastases have prognostic significance and should be further studied, both as independent prognostic predictors and in conjunction with other factors used in prognostic scores.

The Comparative Treatment of Intraventricular Chemotherapy by Ommaya Reservoir vs. Lumbar Puncture in Patients With Leptomeningeal Carcinomatosis.

Object: Leptomeningeal Carcinomatosis (LCM) represents a state of systemic malignant disease with poor prognosis. The purpose of this study is to compare overall survival (OS) between intraventricular chemotherapy through Ommaya reservoir (OR) and chemotherapy through lumbar puncture (LP) in LCM. Patients and Methods: Forty adult patients with LCM were included. All patients underwent lumbar puncture and Magnetic resonance imaging (MRI). Thirty patients received chemotherapy through LP and 10 undergone colocation of Ommaya reservoir for intraventricular chemotherapy. Results: The most common symptom was headache (Present in 50%). The cranial nerves most affected were VI and VII. Leptomeningeal enhancement was the most frequent finding in MRI. The OS in the LP group was 4 months and Ommaya group was 9.2 months (p = 0.0006; CI:1.8-3), with statistical differences in favor to Intraventricular treatment. Proportional hazard regression showed that receiving chemotherapy through Ommaya reservoir was a protective factor (Hazard ratio = 0.258, Standard Error = 0.112, p = 0.002 and 95% CI 0.110-0.606). Using KPS as a factor did not affect the hazard ratio of Ommaya reservoir itself. Conclusions: OS was significantly higher in patients with Ommaya reservoir in spite of Karnofsky Performance Status (KPS) previous to chemotherapy. Therefore, intraventricular chemotherapy should be preferred over lumbar puncture chemotherapy administration if there are resources available.

[Primary Tumors of the Central Nervous System. Clinical Experience at a Third Level Center].

Background: Central nervous system (CNS) tumors are a group of neoplasms that originate from various cells in the CNS. The increasing incidence and prevalence of this type of tumor in developing countries are striking; however, there are few current studies in Latin America including Mexico estimating the impact of these pathological entities on the general population. Objective: The objective of the study was to study the characteristics of primary CNS tumors over a period of 52 years. Methods: A review of records from patients with a histopathological diagnosis of CNS neoplasm over a period of 52 years was conducted at a tertiary-care academic medical center. Patients were grouped by sex, age, and the tumor's anatomical location. Results: A sample of 9615 patients with tumor lesions was obtained; 51% were female, 49% were male, and their mean age was 42 years. The tumors with the highest prevalence were neuroepithelial tumors (38.6%), followed by meningeal tumors (22.8%). Neuroepithelial tumors accounted for 64% in the group of patients under 40 years of age and 56% among those above 40 years of age. The most frequently involved location was supratentorial, in 78.9% of cases. Conclusions: Although retrospective in nature and based on a small sample, this study reports the epidemiology and characteristics of primary brain tumors in the Mexican population.

Factors associated with long-term survival in central nervous system metastases.

BACKGROUND: Cancer is a leading cause of death worldwide; central nervous system metastases (CNSm) are amongst the most common complications of cancer and are associated with high morbidity and mortality. The aim of the study was to associate clinic and oncologic characteristics with the possibility of survival for ≥ 1 year. MATERIALS AND METHODS: A prospective cohort in two referral centers recollected clinical and oncologic data from patients diagnosed with CNSm. Chronic metastases were defined as those patients that survived for ≥ 12 months after the diagnosis of CNSm. RESULTS: Of 613 patients with CNSm, 554 had solid tumors as the primary cancer and were included; 405 (73%) were women, the most common primary cancer site were breast, lung and urologic. Chronic CNSm were found in 260 (47%) and were compared to those who did not. After multivariate logistic regression analysis, variables associated with good prognosis (living > 12 months) were: female sex (HR 0.55), single CNSm (HR 0.39), diagnosis of CNSm during initial extension studies or during presentation of cancer (HR 0.43), and occipital location (HR 0.62). CONCLUSIONS: Long-term survival in patients with CNSm remains a topic of debate; their bad prognosis could be changing towards improvement. Clinical findings are typically overlooked in CNSm reports and prognostic scales. After our findings, we propose to include them in forthcoming studies to aid prognostic considerations. Factors associated with prolonged survival found in our study include female gender, timing of CNSm diagnosis, occipital lobe location, and single CNSm.

Cytotoxicity induced by carbon nanotubes in experimental malignant glioma.

Despite multiple advances in the diagnosis of brain tumors, there is no effective treatment for glioblastoma. Multiwalled carbon nanotubes (MWCNTs), which were previously used as a diagnostic and drug delivery tool, have now been explored as a possible therapy against neoplasms. However, although the toxicity profile of nanotubes is dependent on the physicochemical characteristics of specific particles, there are no studies exploring how the effectivity of the carbon nanotubes (CNTs) is affected by different methods of production. In this study, we characterize the structure and biocompatibility of four different types of MWCNTs in rat astrocytes and in RG2 glioma cells as well as the induction of cell lysis and possible additive effect of the combination of MWCNTs with temozolomide. We used undoped MWCNTs (labeled simply as MWCNTs) and nitrogen-doped MWCNTs (labeled as N-MWCNTs). The average diameter of both pristine MWCNTs and pristine N-MWCNTs was ~22 and ~35 nm, respectively. In vitro and in vivo results suggested that these CNTs can be used as adjuvant therapy along with the standard treatment to increase the survival of rats implanted with malignant glioma.

Methotrexate and temozolomide versus methotrexate, procarbazine, vincristine, and cytarabine for primary CNS lymphoma in an elderly population: an intergroup ANOCEF-GOELAMS randomised phase 2 trial.

BACKGROUND: No standard chemotherapy regimen exists for primary CNS lymphoma, reflecting an absence of randomised studies. We prospectively tested two promising methotrexate-based regimens, one more intensive and a milder regimen, for primary CNS lymphoma in the elderly population, who account for most patients. METHODS: In this open-label, randomised phase 2 trial, done in 13 French institutions, we enrolled immunocompetent patients who had neuroimaging and histologically confirmed newly diagnosed primary CNS lymphoma, were aged 60 years and older, and had a Karnofsky performance scale score of 40 or more. Participants were stratified by Karnofsky performance scale score (<60 vs ≥60) and treating institution and randomly assigned (1:1) to receive methotrexate (3·5 g/m(2)) with temozolomide (150 mg/m(2)) or methotrexate (3·5 g/m(2)), procarbazine (100 mg/m(2)), vincristine (1·4 mg/m(2)), and cytarabine (3 mg/m(2)). Neither regimen included radiotherapy; both included prophylactic G-CSF and corticosteroids. The primary endpoint was 1-year progression-free survival. Analysis was intent to treat, in a non-comparative phase 2 trial design. This study is registered with ClinicalTrials.gov, number NCT00503594. FINDINGS: Between July 16, 2007, and March 25, 2010, 98 patients were enrolled, of whom 95 were randomly assigned and analysed; 48 to methotrexate with temozolomide and 47 to methotrexate, procarbazine, vincristine, and cytarabine. 1-year progression-free survival was 36% (95% CI 22-50) in the methotrexate, procarbazine, vincristine, and cytarabine group and 36% (22-50) in the methotrexate with temozolomide group; median progression-free survival was 9·5 months (95% CI 5·3-13·8) versus 6·1 months (3·8-11·9), respectively. Objective responses were noted in 82% (95% CI 68-92) of patients in the methotrexate, procarbazine, vincristine, and cytarabine group versus 71% (55-84) of patients in the methotrexate with temozolomide group. Median overall survival was 31 months (95% CI 12·2-35·8) in the methotrexate, procarbazine, vincristine, and cytarabine group and 14 months (8·1-28·4) in the methotrexate with temozolomide group. No differences were noted in toxic effects between the two groups. The most common grades 3 and 4 toxicities in both groups were liver dysfunction (21 [4%] in the the methotrexate and temozolomide group and 18 [38%] in the methotrexate, procarbazine, vincristine, and cytarabine group), lymphopenia (14 [29%] and 14 [30%]), and infection (six [13%] and seven [15%]). To date, 33 (69%) patients in the methotrexate and temozolomide group have died, versus 31 (55%) in the methotrexate, procarbazine, vincristine and cytarabine group. Quality-of-life evaluation (QLQ-C30 and BN20) showed improvements in most domains (p=0·01-0·0001) compared with baseline in both groups. Prospective neuropsychological testing showed no evidence of late neurotoxicity. INTERPRETATION: In this study of two different methotrexate-based combination regimens in elderly patients, the efficacy endpoints tended to favour the methotrexate, procarbazine, vincristine, and cytarabine group. Both regimens were associated with similar, moderate toxicity, but quality of life improved with time, suggesting pursuing treatment in these poor prognosis patients is worthwhile. New alternatives are needed to improve response duration in this population. FUNDING: Schering-Plough/Merck and French Government.

[First Mexican consensus on recommendations of the multidisciplinary care of patients with glioblastoma multiforme (GBM): Mexican Interdisciplinary Group on Neuro-Oncology Research (GIMINO)]. / Primer consenso mexicano sobre recomendaciones de la atención multidisciplinaria del paciente con glioblastoma multiforme (GBM). Grupo Interdisciplinar Mexicano de Investigación en Neurooncología (GIMINO).

Glioblastoma multiforme is one of the most aggressive central nervous system tumors and with worse prognosis. Until now,treatments have managed to significantly increase the survival of these patients, depending on age, cognitive status, and autonomy of the individuals themselves. Based on these parameters, both initial or recurrence treatments are performed, as well as monitoring of disease by imaging studies. When the patient enters the terminal phase and curative treatments are suspended, respect for the previous wishes of the patient and development and implementation of palliative therapies must be guaranteed.

[Anti-N-Methyl-D-aspartate receptor encephalitis (anti-NMDAR): a case report]. / Encefalitis por anticuerpos antirreceptor de N-metil-D-aspartato (anti-NMDAR): reporte de un caso.

Anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDAR) is an autoimmune disorder characterized by neuropsychiatric symptoms, hyperkinetic movements, and even central hypoventilation. Anti-NMDAR encephalitis is a recently described disease, but is already considered one of the most frequent etiologies of noninfectious encephalitis. We report the case of 16-year-old man in which it the presence of anti-NMDAR antibodies in the absence of a neoplasm was identified. Disease course and gradual recovery, as well as a brief review of the syndrome, is presented. To our knowledge this is the first proven case of anti-NMDAR encephalitis in Mexico.

Primary leptomeningeal lymphoma: International Primary CNS Lymphoma Collaborative Group report.

OBJECTIVE: To evaluate clinical presentation, optimal diagnostic evaluation and treatment, and outcome in primary leptomeningeal lymphoma, a rare form of primary CNS lymphoma without parenchymal or systemic involvement. METHODS: The International Primary CNS Lymphoma Collaborative Group, a multidisciplinary group of physicians with a particular interest in primary CNS lymphoma, retrospectively identified cases of lymphoma isolated to the leptomeninges as diagnosed by CSF cytology, flow cytometry, or biopsy, without systemic or parenchymal brain/spinal cord lymphoma or immunodeficiency. RESULTS: Forty-eight patients were identified, with median age at diagnosis of 51 years and median Eastern Cooperative Oncology Group performance status of 2. Presenting symptoms were multifocal in 68%. Leptomeningeal enhancement was seen in 74% and CSF profile was abnormal in all cases. CSF cytology detected malignant lymphocytes in 67%. Flow cytometry identified monoclonal population in 80%, as did receptor gene rearrangement studies in 71%. Sixty-two percent had B-cell lymphoma, 19% T-cell, and 19% unclassified. Treatment varied and included fractionated radiotherapy (36%), systemic chemotherapy (78%), and intra-CSF chemotherapy (66%), with 66% receiving ≥ 2 modalities. Seventy-one percent had a favorable clinical response; ultimately, 44% received salvage treatment. Median overall survival was 24 months, with 11 patients still alive at 50 months follow-up. CONCLUSION: Primary leptomeningeal lymphoma is a rare form of primary CNS lymphoma. Patients usually present with multifocal symptoms, with evidence of leptomeningeal enhancement and diagnostic CSF analysis. Although treatment is highly variable, patients have a better prognosis than previously reported and a subset may be cured.

Recurrent mutations of MYD88 and TBL1XR1 in primary central nervous system lymphomas.

PURPOSE: Our objective was to identify the genetic changes involved in primary central nervous system lymphoma (PCNSL) oncogenesis and evaluate their clinical relevance. EXPERIMENTAL DESIGN: We investigated a series of 29 newly diagnosed, HIV-negative, PCNSL patients using high-resolution single-nucleotide polymorphism (SNP) arrays (n = 29) and whole-exome sequencing (n = 4) approaches. Recurrent homozygous deletions and somatic gene mutations found were validated by quantitative real-time PCR and Sanger sequencing, respectively. Molecular results were correlated with prognosis. RESULTS: All PCNSLs were diffuse large B-cell lymphomas, and the patients received chemotherapy without radiotherapy as initial treatment. The SNP analysis revealed recurrent large and focal chromosome imbalances that target candidate genes in PCNSL oncogenesis. The most frequent genomic abnormalities were (i) 6p21.32 loss (HLA locus), (ii) 6q loss, (iii) CDKN2A homozygous deletions, (iv) 12q12-q22, and (v) chromosome 7q21 and 7q31 gains. Homozygous deletions of PRMD1, TOX, and DOCK5 and the amplification of HDAC9 were also detected. Sequencing of matched tumor and blood DNA samples identified novel somatic mutations in MYD88 and TBL1XR1 in 38% and 14% of the cases, respectively. The correlation of genetic abnormalities with clinical outcomes using multivariate analysis showed that 6q22 loss (P = 0.006 and P = 0.01) and CDKN2A homozygous deletion (P = 0.02 and P = 0.01) were significantly associated with shorter progression-free survival and overall survival. CONCLUSIONS: Our study provides new insights into the molecular tumorigenesis of PCNSL and identifies novel genetic alterations in this disease, especially MYD88 and TBL1XR1 mutations activating the NF-κB signaling pathway, which may be promising targets for future therapeutic strategies.

Response assessment in recurrent glioblastoma treated with irinotecan-bevacizumab: comparative analysis of the Macdonald, RECIST, RANO, and RECIST + F criteria.

Traditionally, the most widely used criteria for response assessment in glioblastoma have been Macdonald and the Response Evaluation Criteria In Solid Tumors (RECIST). Recently, new criteria addressing contrast enhancement and fluid-attenuated inversion recovery (FLAIR)/T2 hyperintensity have been defined (the Response Assessment in Neuro-Oncology criteria) to better evaluate the effect of antiangiogenic therapy. Whether FLAIR/T2 imaging could also be helpful to refine RECIST criteria remains unresolved. This study proposed the RECIST + F criteria and compared the 4 methods (Macdonald, RECIST, RANO, and RECIST + F) to determine their agreement in identifying response and progression of recurrent glioblastomas to irinotecan-bevacizumab. Patients with recurrent glioblastoma treated with second-line irinotecan-bevacizumab were eligible. Clinical status, corticosteroid dose, and 1-dimensional and 2-dimensional measurements of tumor contrast enhancement and FLAIR hyperintensity were retrospectively assessed. Response and progression were determined according to each set of criteria. Seventy-eight patients were included. Response rates ranged from 34.2% with RECIST + F to 44.7% with Macdonald criteria. Agreement among the 4 methods in determining response and type of progression was high (kappa statistic > 0.75). One-third of patients exhibited nonenhancing progression with stable or improved contrast enhancement. Median progression-free survival was predicted by RECIST, at 13.6 weeks; RECIST + F, 12.3; Macdonald, 12.7; and RANO, 11.7 (P = .840). Intra- and interobserver correlations were high for both contrast enhancement and FLAIR hyperintensity measurements. There was a strong concordance among the different methods in determining response and progression to irinotecan-bevacizumab. Criteria integrating FLAIR hyperintensity tended, however, to reduce response rates and progression-free survival compared with criteria considering only contrast enhancement. The 1-dimensional approach appeared to be as valid as the 2-dimensional approach.

Prophylactic intrathecal chemotherapy in primary CNS lymphoma.

The role of prophylactic intrathecal chemotherapy in the treatment of primary central nervous system lymphoma remains controversial. We report a retrospective single center study of a cohort of 69 patients with primary central nervous system lymphoma who had been treated with a regimen that combined high intravenous doses of Methotrexate, CCNU, procarbazine and methylprednisolone. Before 2000, patients systematically received intrathecal prophylaxis including Methotrexate, cytarabine, and hydrocortisone delivered either by intraventricular or lumbar injection along with the systemic chemotherapy (group A, n = 39). After this date, the procedure was changed and intrathecal chemotherapy was withdrawn from the protocol (group B, n = 30). The median age and Karnofsky index were comparable in both groups. At the time of analysis, we found no significant difference between patients with and without intrathecal prophylaxis in terms of objective response rate, patterns of relapse, progression-free survival or overall survival. In our study, intrathecal prophylaxis withdrawal from a high dose intravenous Methotrexate-based chemotherapy regimen did not influence disease control and outcome of primary central nervous system lymphoma. Further studies prospectively investigating the role of intrathecal chemoprophylaxis are warranted for this disease.