Background The EANO ESMO guidelines have proposed a classification of leptomeningeal metastases (LM) from solid cancers based on clinical, magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) cytology presentation. MRI patterns are classified as linear, nodular, both, or neither. Type I LM is defined by positive CSF cytology (confirmed LM) whereas type II LM is defined by typical clinical and MRI signs (probable or possible LM). Here we explored the clinical utility of these LM subtypes. Patients and methods We retrospectively assembled data from 254 patients with newly diagnosed LM from solid tumors. Survival curves were derived using the Kaplan-Meier method and compared by Log-rank test. Results Median age at LM diagnosis was 56 years. Typical clinical LM features were noted in 225 patients (89%); 13 patients (5%) were clinically asymptomatic. Tumor cells in the CSF were observed in 186 patients (73%) whereas the CSF was equivocal in 24 patients (9.5%) and negative in 44 patients (17.5%). Patients with confirmed LM had inferior outcome compared with patients with probable or possible LM (p=0.006). Type I patients had inferior outcome than type II patients (p=0.002). Nodular disease on MRI was a negative prognostic factor in type II LM (p=0.014), but not in type I LM. Administration of either intrathecal pharmacotherapy (p=0.020) or systemic pharmacotherapy (p=0.0004) was associated with improved outcome in type I LM, but not in type II LM. Conclusion The EANO ESMO LM subtypes are highly prognostic and should be considered for stratification and overall design of clinical trials.

The presence of barriers, such as the blood–brain barrier (BBB) and brain–tumor barrier (BTB), limits the penetration of antineoplastic drugs into the brain, resulting in poor response to treatments. Many techniques have been developed to overcome the presence of these barriers, including direct injections of substances by intranasal or intrathecal routes, chemical modification of drugs or constituents of BBB, inhibition of efflux pumps, physical disruption of BBB by radiofrequency electromagnetic radiation (EMP), laser-induced thermal therapy (LITT), focused ultrasounds (FUS) combined with microbubbles and convection enhanced delivery (CED). However, most of these strategies have been tested only in preclinical models or in phase 1–2 trials, and none of them have been approved for treatment of brain tumors yet. Concerning the treatment of brain metastases, many molecules have been developed in the last years with a better penetration across BBB (new generation tyrosine kinase inhibitors like osimertinib for non-small-cell lung carcinoma and neratinib/tucatinib for breast cancer), resulting in better progression-free survival and overall survival compared to older molecules. Promising studies concerning neural stem cells, CAR-T (chimeric antigen receptors) strategies and immunotherapy with checkpoint inhibitors are ongoing.

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To report the efficacy and tolerability of lacosamide as an add-on treatment in patients with gliomas and uncontrolled seizures despite conventional antiepileptic drugs (AEDs). We conducted an observational study on 71 patients to describe patterns of response to lacosamide and the association between clinico-pathological factors and seizure control. We observed at 3, 6 and 9 months a seizure reduction ≥ 50% in 74.6, 76 and 86.2% of patients and a seizure freedom in 42.2, 43 and 50%, respectively. The median number of seizures in the 3 months before treatment was 13, and decreased to 3 between baseline and 6 months, and to 0.5 between 6 and 9 months. The best seizure response was observed at 3 months (62%). Sixty per cent of patients displayed the maximum seizure control with doses of lacosamide of 100-250 mg/day, while 21% needed doses up to 400 mg/day. Seizure reduction ≥ 50% and seizure freedom were higher in patients who received lacosamide as first add-on compared to those who received a later adjunctive therapy. A reduction ≥ 50% of seizures was observed in a proportion of patients with progressive disease on MRI. Age > 45 years (OR 0.11, 95% CI 0.02-0.63, p = 0.013) was a significant predictor of seizure freedom at 9 months on multivariate analysis. The study suggests that lacosamide, when added to any baseline AEDs, is effective in obtaining a high seizure reduction and seizure freedom regardless of the tumor activity and response to antineoplastic therapies.

The aim of the study was to estimate the value of detecting pepsinogen (PG) I, PGII and gastrin-17 (G-17) levels in serum for chronic atrophic gastritis (CAG) screening and to determine the clinical applicability of combined measurement of serum G-17, pepsinogens (PGI, PGII) and PGI/PGII ratio (PGR) as a screening test for CAG. The PGI, PGII and G-17 levels were detected by ELISA in 68 patients with CAG and 86 healthy volunteers who underwent gastroscopy for gastroduodenal diseases at Taizhou Municipal Hospital between January 2016 and December 2016. Concentrations of all measured serum markers were lower in patients with CAG in comparison to healthy volunteers and achieved statistical significance (p<0.01) in PGI (93.25 vs. 126.98) and PGR (12.67 vs. 17.09). Receiver operating characteristic (ROC) curve analysis revealed the optimal cutoff values for PGI, PGII, PGR and G-17 at 98.10 μg/l, 6.92 ng/l, 15.77 and 1.94 pmol/l, with sensitivities of 72.10%, 58.10%, 61.60% and 59.30%, and specificities of 61.8%, 51.50%, 77.90% and 55.90%, respectively. The areas under the curve (AUCs) of PGI, PGR and G-17 were 0.728, 0.726 and 0.556, respectively. The increase of AUC was observed only in PGR and G-17 combination (0.741) with increased sensitivity (69.10% vs. 61.60%) of screening for CAG, whereas the specificity was reduced (72.10% vs. 77.90%) in comparison to PGR alone. Combination of serum indicators can raise the diagnostic accuracy of CAG in some respects. However, further research including a larger sample size is necessary in order to accurately determine the sensitivity and specificity of combined detection of serum indicators.

The management of breast cancer (BC) has rapidly evolved in the last 20 years. The improvement of systemic therapy allows a remarkable control of extracranial disease. However, brain (BM) and leptomeningeal metastases (LM) are frequent complications of advanced BC and represent a challenging issue for clinicians. Some prognostic scales designed for metastatic BC have been employed to select fit patients for adequate therapy and enrollment in clinical trials. Different systemic drugs, such as targeted therapies with either monoclonal antibodies or small tyrosine kinase molecules, or modified chemotherapeutic agents are under investigation. Major aims are to improve the penetration of active drugs through the blood–brain barrier (BBB) or brain–tumor barrier (BTB), and establish the best sequence and timing of radiotherapy and systemic therapy to avoid neurocognitive impairment. Moreover, pharmacologic prevention is a new concept driven by the efficacy of targeted agents on macrometastases from specific molecular subgroups. This review aims to provide an overview of the clinical and molecular factors involved in the selection of patients for local and/or systemic therapy, as well as the results of clinical trials on advanced BC. Moreover, insight on promising therapeutic options and potential directions of future therapeutic targets against BBB and microenvironment are discussed.

Patients with leptomeningeal metastases (LM) from non-small cell lung cancer (NSCLC) have a poor outcome with survival of less than 1 year regardless of advancements in treatment strategy. In the past, some randomized clinical trials have been conducted with heterogeneous inclusion criteria, diagnostic parameters, response evaluation and primary endpoints. Efforts to develop a standardized magnetic resonance imaging (MRI) assessment and liquid biopsy techniques to monitor disease evolution in plasma or cerebrospinal fluid (CSF) are underway. This review aims to cover the main clinical and diagnostic challenges of LM from NSCLC, in particular the role of MRI, CSF cytology and liquid biopsy for the diagnosis and monitoring of the disease, as well as the most recent clinical trials on targeted therapies. Targeted therapy, such as epidermal growth factor receptor tyrosine kinase inhibitors and anaplastic lymphoma kinase rearranged inhibitors, represent a feasible treatment with encouraging results in terms of disease control and survival. For ineligible patients, immune checkpoint inhibitors could represent a therapeutic option with acceptable tolerance, although clinical trials focused on LM from NSCLC are lacking and represent a research focus for the future.

BACKGROUND The EANO ESMO guidelines have proposed a classification of leptomeningeal metastases (LM) based on clinical (typical/atypical), cytological (positive/negative/equivocal) and MRI (A linear, B nodular, C linear and nodular, D normal or hydrocephalus only) presentation. Type I LM is defined by the presence of tumor cells in the cerebrospinal fluid (CSF) (confirmed LM) whereas type II LM is defined by typical clinical and MRI signs (probable or possible LM). Here we explored the clinical utility of these EANO ESMO LM subtypes. PATIENTS AND METHODS We retrospectively assembled data from 254 patients with newly diagnosed LM from different solid tumors, including as main primary tumors breast cancer (n=98, 45%), lung cancer (n=65, 25.5%) and melanoma (n=51, 13.5%). Survival curves were estimated using the Kaplan-Meier method and compared by Log-rank test. RESULTS Median age at LM diagnosis was 56.5 years (range 20–82 years). Typical clinical LM symptoms or signs were noted in 225 patients (88.5%); only 13 patients (5%) were clinically asymptomatic. The most common MRI subtype was A seen in 117 patients (46%). Types B (n=33, 13%), C (n=54, 21%) and D (n=50, 19.5%) were less common. Tumor cells were observed in the CSF in 186 patients (73%) whereas the CSF was equivocal in 24 (9.5%) and negative in 44 (17.5%) patients. Patients with confirmed LM had inferior outcome than patients with probable or possible LM (p=0.0063). Type I patients had inferior outcome than type II patients (p=0.0019). Nodular disease was a negative prognostic factor in type II LM, but not in type I LM (p=0.0138). CONCLUSION The presence of tumor cells in the CSF appears to have a greater prognostic role than the neuroimaging presentation. EANO ESMO LM subtypes are highly prognostic and should be considered in the design of clinical trials.