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Purpose To investigate the biophysical meaning of Diffusion Kurtosis Imaging (DKI) parameters via correlations with the perfusion parameters obtained from a long Dynamic Contrast Enhanced MRI scan, in head and neck (HN) cancer. Methods Twenty two patients with newly diagnosed HN tumor were included in the present retrospective study. Some patients had multiple lesions, therefore a total of 26 lesions were analyzed. DKI was acquired using 5b values at 0, 500, 1000,1500 and 2000 s/mm2. DCE-MRI was obtained with 130 dynamic volumes, with a temporal resolution of 5 s, to achieve a long scan time (>10 min). The apparent diffusion coefficient Dapp and apparent diffusional kurtosis Kapp were calculated voxel-by-voxel, removing the point at b value = 0 to eliminate possible perfusion effects on the parameter estimations. The transfer constants Ktrans and Kep, ve, and the histogram-based entropy (En) and interquartile range (IQR) of each DCE-MRI parameter were quantified. Correlations between all variables were investigated by the Spearman’s Rho correlation test. Results Moderate relationships emerged between Dapp and Kep (Rho = − 0.510, p = 0.009), and between Dapp and ve (Rho = 0.418, p = 0.038). En(Kep) was significantly related to Kapp (Rho = 0.407, p = 0.043), while IQR(Kep) showed an inverse association with Dapp (Rho = -0.422, p = 0.035). Conclusions A weak to intermediate correlation was found between DKI parameters and both Kep and ve. The kurtosis was associated to the intratumoral heterogeneity and complexity of the capillary permeability, expressed by En(Kep).

Introduction: The standard surgical procedures for patients with early-stage NSCLC is lobectomy-associated radical lymphadenectomy performed by using the thoracotomy approach. In the last few years, minimally invasive techniques have increasingly strengthened their role in lung cancer treatment, especially in the early stage of the disease. Although the lobectomy technique has been accepted, controversy still surrounds lymph node dissection. In our study, we analyze the rate of upstaging early non-small cell lung cancer patients who underwent radical surgical treatment using the robotic and the VATS techniques compared to the standard thoracotomy approach.Methods and Materials: We retrospectively reviewed patients who underwent a lobectomy and radical lymphadenectomy at our Institute between 2010 and 2019. We selected 505 patients who met the inclusion criteria of the study: 237 patients underwent robotic surgery, 158 patients had thoracotomy, and 110 patients were treated with VATS. We analyzed the demographic features between the groups as well as the nodal upstaging rate after pathological examination, the number of dissected lymph nodes and the ratio of dissected lymph nodes to metastatic lymph nodes of the three groups.Results: The patients of the three groups were homogenous with respect to age, sex, and histology. The postoperative major morbidity rate was significantly higher in the thoracotomy group, and hospital stay was significantly longer. The percentage of the mediastinal nodal upstaging rate and the number of dissected lymph nodes was significantly higher in the robotic group compared with the VATS group. The ratio of dissected lymph nodes to metastatic lymph nodes was significantly lower compared with the VATS group and the thoracotomy group.Discussion: The prognostic impact of the R(un) status is still highly debated. A surgical approach that allows better results in terms of resection has still not been defined. Our results show that robotic surgery is a safe and feasible approach especially regarding the accuracy of mediastinal lymphadenectomy. These findings can lead to defining a more precise pathological stage of the disease and, if necessary, to more accurate postoperative treatment.

Background The 8th edition of tumor, node, metastasis (TNM) classification incorporates depth of invasion evaluation in the staging of oral cavity squamous cell carcinoma, since it is a predictor of nodal metastasis and an independent prognostic factor. Although the histopathological definition of depth of invasion is clear, an accurate method for its radiological assessment has not yet been validated. Purpose To investigate the role of MRI-derived depth of invasion evaluation in staging oral tongue squamous cell carcinoma and to assess the inter-reader agreement and the radiological–pathological correlation. Material and Methods We retrospectively reviewed 43 patients with oral tongue squamous cell carcinoma who underwent preoperative MRI. The MRI-derived depth of invasion was measured by two radiologists, each with a different degree of experience in head and neck imaging. The pathological depth of invasion was recorded from histopathological reports. The inter-reader and the radiological–histopathological correlations for the depth of invasion were evaluated with Bland–Altman plots, the intraclass correlation coefficients (ICC), and the paired samples test; agreements for T staging were assessed using the Kappa coefficient. Results Inter-reader reliability was excellent for the MRI-derived depth of invasion (ICC = 0.91), very good between MRI-derived depth of invasion and pathological depth of invasion (ICC = 0.89 for the experienced reader, 0.86 for the inexperienced reader). Both readers reached a good agreement regarding T staging (kappa value = 0.70). Furthermore, the agreement between radiological and pathological T staging was good (kappa value = 0.74 for the experienced reader, 0.60 for the inexperienced reader). Conclusion MRI-derived depth of invasion should be measured in the pretreatment assessment of oral tongue squamous cell carcinoma as it has an excellent inter-reader reliability and nearly excellent radiological–pathological correlation.

Patients with relapse of recurrent glioma have a poor outcome and limited treatment options. The aim of this study is to investigate the clinical benefit and tolerability of weekly intravenous administration of carboplatin-based monotherapy in adult glioma patients who had progressed from previous chemotherapy lines based on temozolomide and nitrosoureas. This was a single-arm, phase II study. Eligibility criteria included progressive or recurrent glioma after radiotherapy and chemotherapy-based treatments and Karnofsky performance status (KPS) > 60. Thirty-two patients (median age 43.5 years) were enrolled to receive weekly carboplatin monotherapy in an intravenous method of administration. The median duration of response was 7.3 months with an overall disease control rate of 31.3%. Median progression-free survival was 2.3 months while overall survival was 5.5 months. Pre-treatment with corticosteroids (i.e. dexamethasone) was associated to clinical benefit in 43.8% of patients. Patients achieving clinical benefit exhibited a longer progression-free survival (4.6 vs. 1.5 months; p > 0.001) and overall survival (7.9 vs. 3.2 months; p = 0.041) compared with those not achieving clinical benefit. Our findings show that single agent, weekly, intravenous administration of carboplatin may have a role in patients with recurrent glioma and suggest that pre-treatment with corticosteroids may confer survival benefit.

Symptomatic metastatic spine disease (MSD), is a challenging disease involving 3%-20% of patients with bone metastases. Different surgical options are available and must be tailored to the general and neurologic conditions of the patients. Open kyphoplasty (OKP) refers to decompressive hemilaminectomy, associated with a contralateral percutaneous kyphoplasty, and in some cases, to a posterior stabilization. The aim of the study was to critically review our experience during the last decade with OKP in patients with cancer.Fifty-three patients with cancer underwent OKP for symptomatic MSD. The Tokuhashi score and Spinal Instability Neoplastic Score were calculated for each patient. Length of hospital stay, perioperative complications, incidence of adjacent-level fractures, and median survival after surgery were evaluated. Karnofsky Performance Status, visual analog scale, and Dennis Pain Score were calculated preoperatively, postoperatively, and at last follow-up.Median Tokuhashi score and Spinal Instability Neoplastic Score were 10 and 10, respectively. The mean volume of filling material inserted was 3.6 mL. Median operative time was 180 minutes. Complications included 8 leakages (15%), 2 permanent motor deficits (3.8%), and 2 asymptomatic pulmonary embolisms (3.8%). Mean length of hospital stay was 7 days. A significant improvement was observed in Karnofsky Performance Status, visual analog scale score, and Dennis Pain Score (P0.0001). Median follow-up was 16 months and overall survival 22 months.OKP was an effective treatment of symptomatic MSDs in selected oncologic patients with low Tokuhashi scores. It relieved lateral epidural compressions, expanded indications of palliative surgery in patients who were not otherwise surgical candidates, and rapidly dealt with cement leakages.

BackgroundThe first goal of the study was to analyse the antibody titre 7 days after the second dose of BNT162b2 vaccine in a group of 248 healthcare workers (HCW). The second goal was to analyse how the antibody titre changes in correlation with age, gender and BMI.MethodsParticipants were assigned to receive the priming dose at baseline and booster dose at day 21. Blood and nasopharyngeal swabs were collected at baseline and 7 days after second dose of vaccine.Findings248 HWCs were analysed, 158 women (63.7%) and 90 men (36.3%). After the second dose of BNT162b2 vaccine, 99.5% of participants developed a humoral immune response.The geometric mean concentration of antibodies among the vaccinated subjects after booster dose (285.9 AU/mL 95% CI: 249.5-327.7); was higher than that of human convalescent sera (39.4 AU/mL, 95% CI: 33.1-46.9), with pInterpretationThese findings imply that females, lean and young people have an increased capacity to mount humoral immune responses compared to males, overweight and the older population. Although further studies are needed, this data may have important implications for the development of vaccination strategies for COVID-19, particularly in obese people.FundingNone

Isocitrate dehydrogenase (IDH) mutant and wildtype glioblastoma multiforme (GBM) often show overlapping features on magnetic resonance imaging (MRI), representing a diagnostic challenge. Deep learning showed promising results for IDH identification in mixed low/high grade glioma populations, however, a GBM-specific model is still lacking in the literature. Our aim was to develop a GBM-tailored deep-learning model for IDH prediction by applying convoluted neural networks (CNN) on multiparametric MRI. We selected 100 adult patients with pathologically demonstrated WHO grade IV gliomas and IDH testing. MRI sequences included: MPRAGE, T1, T2, FLAIR, rCBV and ADC. The model consisted of a 4-block 2D CNN, applied to each MRI sequence. Probability of IDH mutation was obtained from the last dense layer of a softmax activation function. Model performance was evaluated in the test cohort considering categorical cross-entropy loss (CCEL) and accuracy. Calculated performance was: rCBV (accuracy 83%, CCEL 0.64), T1 (accuracy 77%, CCEL 1.4), FLAIR (accuracy 77%, CCEL 1.98), T2 (accuracy 67%, CCEL 2.41), MPRAGE (accuracy 66%, CCEL 2.55). Lower performance was achieved on ADC maps. We present a GBM-specific deep-learning model for IDH mutation prediction, with a maximal accuracy of 83% on rCBV maps. Highest predictivity achieved on perfusion images possibly reflects the known link between IDH and neoangiogenesis through the hypoxia inducible factor.

Background: Eribulin shows some activity in controlling brain metastasis in breast cancer. Methods: This observational, multicenter study evaluated brain disease control rates, survival and safety in patients with brain metastatic breast cancer treated with eribulin in clinical practice. Results: A total of 34 patients were enrolled (mean age 49 years, 91% with visceral metastases) and 29 were evaluable for brain disease. Fourteen achieved disease control and showed a longer time without progression: 10 months (95% CI: 2.3–17.7) versus 4 months (95% CI: 3.3–4.7) in the control group (p = 0.029). Patients with clinical benefits at 6 months had longer survival. Leukopenia and neutropenia were the most frequent grade 3–4 toxicities. Conclusion: Eribulin confirms its effectiveness in patients with brain metastatic breast cancer. Further studies on larger cohorts are needed to confirm the results.

Background: The first goal of the study was to analyse the antibody titre 21 days after the first dose of the BNT162b2 vaccine in a group of 252 healthcare workers (HCW). The second goal was to analyse how the antibody titre changes in correlation with age, gender and body mass index (BMI). Methods: Participants had a nasopharyngeal swab for SARS-CoV-2 and were assessed for the presence of SARS-CoV-2 antibodies at baseline and 21 days after the BNT162b2 priming dose. Results: First dose of BNT162b2 activated immune responses in 98% of the participants. Five HWC had no increase in antibody titre 21 days after the first dose. Antibody titre was greater in young (p = 0.002; 56 p = 0.001). Higher antibody levels were detected in underweight vs. pre-obesity group (p = 0.026) and in normal-weight vs. pre-obesity group (p = 0.007). This association was confirmed after adjusting for age (p = 0.0001) and gender (p = 0.00001). Conclusions: Our study demonstrates that a single dose of BNT162b2 activates the immune response, and being young and normal-weight correlate positively with this response. Larger specifically designed clinical trials are needed to validate these results.

BACKGROUND AND PURPOSE Glioblastoma (GBM) is an aggressive primary CNS neoplasm with poor overall survival (OS) despite standard of care. On MRI, GBM is usually characterized by an enhancing portion (CET) (surgery target) and a nonenhancing surrounding (NET). Extent of resection is a long debated issue in GBM, with recent evidence suggesting that both CET and NET should be resected in

Craniosynostosis-microphthalmia linked to BCOR haploinsufficiency.

Objectives To investigate the correlation between histogram-based Dynamic Contrast-Enhanced magnetic resonance imaging (DCE-MRI) parameters and positron emission tomography with 18F-fluorodeoxyglucose (18F-FDG-PET) values in oropharyngeal squamous cell carcinoma (OPSCC), both in primary tumors (PTs) and in metastatic lymph nodes (LNs). Methods 52 patients with a new pathologically-confirmed OPSCC were included in the present retrospective cohort study. Imaging including DCE-MRI and 18F-FDG PET/CT scans were acquired in all patients. Both PTs and the largest LN, if present, were volumetrically contoured. Quantitative parameters, including the transfer constants, Ktrans and Kep, and the volume of extravascular extracellular space, ve, were calculated from DCE-MRI. The percentiles (P), P10, P25, P50, P75, P90, and skewness, kurtosis and entropy were obtained from the histogram-based analysis of each perfusion parameter. Standardized uptake values (SUV), SUVmax, SUVpeak, SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were calculated applying a SUV threshold of 40%. The correlations between all variables were investigated with the Spearman-rank correlation test. To exclude false positive results under multiple testing, the Benjamini-Hockberg procedure was applied. Results No significant correlations were found between any parameters in PTs, while significant associations emerged between Ktrans and 18F-FDG PET parameters in LNs. Conclusions Evident relationships emerged between DCE-MRI and 18F-FDG PET parameters in OPSCC LNs, while no association was found in PTs. The complex relationships between perfusion and metabolic biomarkers should be interpreted separately for primary tumors and lymph-nodes. A multiparametric approach to analyze PTs and LNs before treatment is advisable in head and neck squamous cell carcinoma (HNSCC).

To retrospectively evaluate the value of whole-lesion histogram analysis of apparent diffusion coefficient (ADC) maps in differentiating between lymphoma and metastatic squamous cell carcinoma (SCC) of unknown clinical primary in neck nodes. A total of 39 patients, 20 affected by lymphoma and 19 affected by metastatic non-nasopharyngeal SCC, were included in this retrospective study. All patients underwent MR imaging with a 1.5 T scanner system, including diffusion-weighted imaging (DWI) with three different b values (b = 0, 500 and 800 s/mm2). The entire tumor volume was manually delineated on the ADC maps, using the T2-weighted images and DWIs with b = 800 s/mm2 as a guide to the lesion location. The Mann–Whitney rank-sum test for independent samples was performed to compare the histogram parameters of patients with lymphoma and SCC. The SCCs showed significantly higher median ADC (ADCmedian) and mean ADC (ADCmean) values, compared to lymphomas (p

Bevacizumab (BV), a neutralizing monoclonal antibody against the vascular endothelial growth factor ligand, is recognized as a potent anti-angiogenic agent with antitumor activity. The aim of this single-center, retrospective, longitudinal study was to investigate the possible predictive value of baseline demographic, clinical and laboratory parameters for early 3-month response to BV therapy in patients with recurrent glioma. Forty-nine patients with recurrent glioma received BV at 10 mg/kg intravenously every 3 weeks alone or in association with chemotherapy were included in this study. Blood samples were collected from all patients before the first (baseline), the second and the third administration of BV. After 3 months of BV therapy, patients with partial response were defined as responders whereas patients with stable or progressive disease were defined as non-responders. The median overall follow-up was 8 months (range 1-73), the median overall survival (OS) was 8 months (95% CI 6-10) and the median progression free survival (PFS) was 4 months (95% CI 3-5). Thirty-five % of patients were responders and showed significantly lower von Willebrand factor (VWF) levels than non-responders at all sample times (p

Purpose To investigate the relationship between the Diffusion Kurtosis Imaging (DKI) parameters and conventional metrics provided by Diffusion-weighted imaging (DWI) in patients affected by Brain or Head and Neck (HN) cancer. Methods Ten patients affected by brain tumor and nine patients with HN tumor underwent a pre-treatment MR examination at 3 T. The largest tumor section was manually contoured by two expert neuroradiologists. The apparent diffusion coefficient (Dapp) and apparent diffusional kurtosis (Kapp) parameters were determined at the voxel level by using the DKI model, and compared to the apparent diffusion coefficient (ADC) and the tissue diffusion coefficient (Dmono) obtained from mono-exponential fitting methods. The Akaike Information Criteria (AIC) was calculated to assess the quality of the fitting methods. Cross-correlations between all the variables were assessed using the Spearman rank test. Results Increased Kapp values were found in each lesion. All parameters were strongly related, in particular an inverse relationship emerged between median values of Kapp and Dapp/Dmono/ADC in both patient groups, while Dapp showed positive correlations with Dmono and ADC. From the analysis at the voxel level, significant inverse associations were found between Kapp and Dmono within the lesions, while a weak or moderate association emerged between Kapp and ADC or Dapp. Conclusions A significant association between the apparent diffusional kurtosis Kapp and the tissue diffusion coefficient Dmono emerged for both brain and HN tumors at 3 T, suggesting that both variables may consistently reflect deeper insight into the microstructural characteristics of tumors.

To investigate the predictive role of Intravoxel Incoherent Motion Diffusion-Weighted Imaging (IVIM-DWI) parameters on cervical nodal response to chemo-radiotherapy (CRT) of head and neck squamous cell carcinoma (HNSCC).Patients with pathologically confirmed HNSCC were included in the present prospective study, having at least one positive cervical lymph node (LN). They received concomitant CRT and underwent three serial IVIM-DWI investigations: before, at mid-treatment and after treatment completion. Tissue diffusion coefficient D, perfusion-related diffusion coefficient D* and perfusion fraction f were calculated by a bi-exponential fit. The two-sided Mann-Whitney rank test was used to compare the imaging parameters of patients with regional failure (RF) and regional control (RC). A p value lower than 0.05 was considered to be statistically significant.Thirty-four patients were accrued. Twenty-four out of 34 LN (70.6%) showed persistent RC after a median follow-up time of 27.6 months (range: 12.0-50.2 months), while ten cases of RF (29.4%) were confirmed with a median time of 6.8 months (range: 1.5-19.5 months). Patients with RC showed significantly lower pre-treatment D values compared to the RF patients (p=0.038). At mid-treatment, the patients with RF showed significantly higher D values (p=0.025), and exhibited larger percent reductions in f and the product D*×f from the baseline (p=0.008 and0.001, respectively). No additional information was provided by the examination at the end of treatment.Pre-treatment and mid-treatment IVIM-DWI showed potential for prediction of treatment response of cervical LN in HNSCC patients.

Brain metastases (BMs) are the most common cause of malignant central nervous system (CNS) tumors in adults. In the recent past, patients with BMs were excluded from clinical trials, but now, with the advent of new biological and immunological drugs, their inclusion is more common. In the last era response and progression criteria used across clinical trials have defined the importance to consider not only measurement changes of brain lesions but also the modification of parameters related to the metastases such as metabolism of tissue and its pathological features. Magnetic resonance imaging (MRI) represents the first choice in the evaluation of BMs; the computed tomography (CT) scan will be made only in case of MRI's contraindication. CT, MRI and positron emission tomography (PET-CT), may be used to monitor response to treatment as part of clinical and radiological follow up. In the evaluation of response to treatment, MRI shows superior accuracy in comparison to CT; PET-CT is useful in particularly in cases of BMs underwent to locoregional therapies in the differential diagnosis between recurrence or radionecrosis. Now is possible to use functional imaging as CT-perfusion, dynamic susceptibility contrast (DSC) MR imaging, dynamic contrast-enhanced (DCE) MR imaging, diffusion-weighted MR imaging and MR-Spectroscopy in the evaluation of treatment response; these imaging techniques can provide qualitative and quantitative imaging parameters that allow pathophysiologic correlation. In the evaluation of the response to immunotherapy treatments, the immune-related response criteria (irRC) are considered as the gold standard. The irRC utilizes bidimensional measurements, quantifying the tumor dimension using a product of the longest diameter and the longest perpendicular diameter. We analyze clinical and radiological criteria to better define outcome of drugs for BMs from solid tumors in the new era of biological and immunological therapies.

Aim: This multicenter, retrospective study evaluates the clinical benefit (CB) of bevacizumab, alone or in combination, in recurrent gliomas (RG). Patients & methods: The CB was measured as a reduction of corticosteroid dosage and an improvement ≥20 points in the Karnofsky Performance Status lasting ≥3 months. Results: We collected data of 197 RG patients. A CB was observed in 120, patients without significant differences between patients treated with bevacizumab alone or in combination. The rate of patients who achieved a CB and free from progression at 1 year was 21.5 versus 1.4% in patients who did not report CB. Conclusion: The majority of RG patients treated with bevacizumab reported CB. Moreover, patients with CB showed improved survival.

Background and purpose Patients with a history of brain radiotherapy can experience acute stroke-like syndromes related to the delayed effects of brain radiation, including stroke-like migraine attacks after radiation therapy syndrome, peri-ictal pseudoprogression and acute late-onset encephalopathy after radiation therapy syndrome. The aim of this study was to collect evidence on the long-term outcome and treatment of these conditions, whose knowledge is undermined by their rarity and fragmented description. Methods Cases were collected, both prospectively and retrospectively, amongst six neuro-oncology departments. Inclusion criteria were as follows: (i) history of brain radiotherapy (completed at least 6 months before the acute episode); (ii) new onset of acute/subacute neurological symptoms; (iii) exclusion of all etiologies unrelated to brain irradiation. A review of current literature on stroke-like syndromes was performed to corroborate our findings. Results Thirty-two patients with acute neurological conditions attributed to the delayed effects of radiation were identified, including 26 patients with stroke-like syndromes. Patients with stroke-like syndromes commonly presented with a mosaic of symptoms, including focal deficits (77%), encephalopathy (50%), seizures (35%) and headache (35%). Seventy-three percent of them had acute consistent magnetic resonance imaging alterations. Treatment included high-dose steroids in 65% of cases. Twenty-two patients recovered completely (85%). Sixteen patients (62%) experienced relapses (median follow-up 3.5 years). A literature review identified 87 additional stroke-like cases with similar characteristics. Conclusions Stroke-like events related to brain irradiation may be associated with permanent sequelae. Steroids are often administered on empirical grounds, as they are thought to accelerate recovery. Relapses are common, highlighting the need to elaborate adequate prevention strategies.

Spinal intradural tumors are usually removed with laminectomy/laminotomy with a midline dural incision. Pain, discomfort, postoperative kyphosis, and instability may be minimized with unilateral microsurgery.Seventy patients with schwannoma (73 tumors) and 27 patients with meningioma (29 tumors) were operated on with unilateral hemilaminectomy (June 2000 to March 2014). Surgery was generally kept to 1 or 2 levels, removing all the craniocaudal ligamentum flavum. Careful radioscopic identification is mandatory; in thoracolumbar schwannomas, the tumor may be mobile; in the prone position, it may move cranially than appears on magnetic resonance imaging. The dura was opened paramedially, and the tumor was dissected and removed either en bloc or piecemeal after ultrasonic debulking. Neurophysiologic monitoring was performed. The tumor was approached tangentially with no cord rotation or minimal manipulation. Average duration of surgery was 160 minutes (100-320 minutes). Removal was total in 72 of 73 schwannomas; Simpson grade was 1 in 10 meningiomas and 2 in 19.Patients with no complications were discharged on day 5-7. Ten patients had orthostatic headaches; 2 had pseudomeningocele that required reoperation. Pain improvement (Dennis Scale) was significant either at discharge or at follow-up (P0.0001 schwannomas, P0.001 meningiomas). Neurologic results (McCormick Scale, Karnofsky Performance Score) were excellent/good: of 39 patients with preoperative neurologic impairment, 19 recovered completely, 17 had minor spasticity, and 3 had moderate spasticity but autonomous ambulation. Sphincters recovered in 5 of 10 patients At follow-up, average Karnofsky Performance Score improved from 60 to 90 (P0.0001) and the McCormick score decreased from 121 to 55 (P0.0001). No spinal instability was observed.Neurologic and oncologic results were good and postoperative pain and discomfort were reduced. Stability was preserved with a unilateral technique. No bracing was necessary, permitting early rehabilitation.

Background: Brain metastases develop in approximately 10–25% of patients with metastatic breast cancer (MBC) and are associated with a very poor prognosis. Case Report: We report the case of a 40-year-old woman with MBC and associated lung, bone, liver, and brain metastases, who experienced a time to progression of several months with eribulin after whole-brain radiotherapy (WBRT), 2 lines of chemotherapy, and 1 line of hormonal therapy, maintaining a good toxicity profile. Discussion: Eribulin, in association with local treatment such as WBRT, can be well tolerated and effective in achieving a long progression-free survival and a good control of brain metastases in patients with MBC who have received multiple lines of treatment. The vascular remodeling properties of eribulin, combined with brain radiotherapy, might facilitate the passage of eribulin across the blood brain barrier, improving brain response. Conclusion: Our anecdotal experience suggests that eribulin may have a potentially beneficial effect on brain metastases while maintaining a good systemic control of the disease in patients with MBC.

This is a case report of a 40-year-old woman who, after conservative breast cancer treatment, developed a HER2 positive solitary brain metastasis in the left temporal lobe, without extracranial --zdisease. She underwent surgery resection followed by stereotactic radiotherapy and, because of early brain progression, she was submitted to the first line therapy with pertuzumab, trastuzumab and weekly paclitaxel. After six months of treatment, a brain magnetic resonance imaging revealed a complete disappearance of brain recurrence, which persisted for more than 24 months.

The aim of this study is to investigate whether early changes in tumor volume and perfusion measurements derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) may predict response to antiangiogenic therapy in recurrent high-grade gliomas.Twenty-seven patients who received bevacizumab every 3 weeks were enrolled in the study. For each patient, three MRI scans were performed: at baseline, after the first dose, and after the fourth dose of bevacizumab. The entire tumor volume (V(tot)), as well as contrast-enhanced and noncontrast-enhanced tumor subvolumes (V(CE-T1) and V(NON-CE-T1), respectively) were outlined using post-contrast T1-weighted images as a guide for the tumor location. Histogram analysis of normalized IAUGC (nIAUGC) and transfer constant K(trans) maps were performed. Each patient was classified as a responder patient if he/she had a partial response or a stable disease or as a nonresponder patient if he/she had progressive disease.Responding patients showed a larger reduction in V(NON-CE-T1) after a single dose, compared to nonresponding patients. Tumor subvolumes with increased values of nIAUGC and K(trans), after a single dose, significantly differed between responders and nonresponders. The radiological response was found to be significantly associated to the clinical outcome. After a single dose, V(tot) was predictive of overall survival (OS), while V(CE-T1) showed a tendency of correlation with OS.Tumor subvolumes with increased nIAUGC and K(trans) showed the potential for improving the diagnostic accuracy of DCE. Early assessments of the entire tumor volume, including necrotic areas, may provide complementary information of tumor behavior in response to anti-VEGF therapies and is worth further investigation.

OBJECTIVES Epilepsy heavily affects the quality of life (QoL) of patients with brain tumor because in addition to taking treatments for the oncological illness, patients are required to live with the long-term taking of antiepileptic drugs (AEDs). The AEDs' adverse effects are common in these patients and can negatively influence their perceptions of their QoL.We conducted an observational pilot study in patients with brain tumor-related epilepsy to verify efficacy, tolerability, and impact on QoL and global neurocognitive performances of zonisamide (ZNS) in add-on. MATERIALS AND METHODS We recruited 13 patients (5 females, 8 males; mean age, 49.6 years) presenting uncontrolled seizures. At first visit and at final follow-up at 6 months, patients underwent neurological examination, evaluation of adverse events, and cognitive and QoL tests. A seizure diary was given. RESULTS Eight patients underwent chemotherapy, 3 underwent radiotherapy, and 5 had disease progression. Mean dosage of ZNS at final follow-up was 300 mg/d.Of 9 patients who reached the sixth month follow-up, the mean weekly seizure number before ZNS had been 3.2 ± 5.0, and at final follow-up, the mean weekly seizure number was 0.18 ± 0.41 (P = 0.05).Compared with baseline, we observed stability in all cognitive domains, except for verbal fluency that significantly worsened.Results on QoL tests showed that QoL remained unchanged over time, which could indicate that ZNS did not influence the patients' perceived QoL. CONCLUSIONS Zonisamide as add-on in our patients seems to be well tolerated and efficacious in controlling seizures. Despite having limitations represented by the fact that our study is observational, with a small study population and a short follow-up period, our results confirm that when choosing an AED, in addition to efficacy, the drug's effect on patients' QoL also needs to be considered, especially for patients facing many psychosocial challenges, such as those with brain tumor-related epilepsy.

Background Cancer is a mosaic of tumor cell subpopulations, where only a minority is responsible for disease recurrence and cancer invasiveness. We focused on one of the most aggressive circulating tumor cells (CTCs) which, from the primitive tumor, spreads to the central nervous system (CNS), evaluating the expression of prognostic and putative cancer stem cell markers in breast cancer (BC) leptomeningeal metastasis (LM). Methods Flow cytometry immunophenotypic analysis of cerebrospinal fluid (CSF) samples (4.5 ml) was performed in 13 consecutive cases of BCLM. Syndecan-1 (CD138), MUC-1 (CD227) CD45, CD34, and the putative cancer stem cell markers CD15, CD24, CD44, and CD133 surface expression were evaluated on CSF floating tumor cells. The tumor-associated leukocyte population was also characterized. Results Despite a low absolute cell number (8 cell/μl, range 1–86), the flow cytometry characterization was successfully conducted in all the samples. Syndecan-1 and MUC-1 overexpression was documented on BC cells in all the samples analyzed; CD44, CD24, CD15, and CD133 in 77%, 75%, 70%, and 45% of cases, respectively. A strong syndecan-1 and MUC-1 expression was also documented by immunohistochemistry on primary breast cancer tissues, performed in four patients. The CSF tumor population was flanked by T lymphocytes, with a different immunophenotype between the CSF and peripheral blood samples (P ≤ 0.02). Conclusions Flow cytometry can be successfully employed for solid tumor LM characterization even in CSF samples with low cell count. This in vivo study documents that CSF floating BC cells overexpress prognostic and putative cancer stem cell biomarkers related to tumor invasiveness, potentially representing a molecular target for circulating tumor cell detection and LM treatment monitoring, as well as a primary target for innovative treatment strategies. The T lymphocyte infiltration, documented in all CSF samples, suggests a possible involvement of the CNS lymphatic system in both lymphoid and cancer cell migration into and out of the meninges, supporting the extension of a new form of cellular immunotherapy to LM. Due to the small number of cases, validation on large cohorts of patients are warranted to confirm these findings and to evaluate the impact and value of these results for diagnosis and management of LM. Electronic supplementary material The online version of this article (doi:10.1186/s13058-017-0827-4) contains supplementary material, which is available to authorized users.

Objective Brain tumor-related epilepsy (BTRE) is often drug resistant and patients can be forced to take polytherapy that can adversely affect their quality of life (QoL). Lacosamide (LCM) is a new antiepileptic drug (AED) used as adjunctive therapy in patients with partial seizures with or without secondary generalization, with a favorable pharmacokinetic profile that seems to be effective and well tolerated. Therefore it represents a possible therapeutic choice for patients with BTRE. We propose a prospective study with a historical control group to evaluate the effect of LCM as add-on therapy on seizure control and quality of life in patients with BTRE. This study has been designed to test the superiority of Lacosamide over Levetiracetam as an add-on. We compared a prospective cohort of 25 patients treated with Lacosamide with a historical control group (n = 19) treated with Levetiracetam as an add-on. Methods We recruited 25 adult patients (M 18, F 7; mean age 41.9) affected by BTRE with uncontrolled partial-onset seizures treated with AED polytherapy. We added LCM as an add-on. Patients were evaluated at baseline, after 3 months and at 6 months. This population has been compared with a historical control group of 19 BTRE adult patients (M 13, F 6; median age 48.0, range: 28–70) with uncontrolled partial-onset seizures treated with LEV as add-on. The patients underwent QoL, mood and adverse events tests (Adverse Event Profile-AEP) and evaluation of seizure frequency. Results Twelve patients had high grade gliomas, and thirteen had low grade gliomas. During follow-up, thirteen patients underwent chemotherapy, three radiotherapy and five patients had disease progression. Nine patients had simple partial seizures, eight had complex partial seizures, and eight had secondary generalized seizures. Fifteen patients were in monotherapy and ten in polytherapy with AEDs. LCM was added up to reach the maximum dosage of 400 mg/die (mean final dose 300 mg/die). Four patients dropped out due to poor compliance and 1 for inefficacy. In the historical control group treated with LEV (mean final dose 2000 mg/die) 12 patients had high-grade gliomas, and 7 had low grade gliomas. Thirteen patients were in monotherapy and 6 in polytherapy with AEDs. In the 22 patients evaluable of 25 patients treated with LCM, we observed at final follow-up 7 patients seizure free, 12 with a significant reduction of seizures ≥ 50%, 2 stable and 1 patient with number of seizures increased. Mean seizure frequency at baseline compared with baseline period: the mean number of seizures significantly decreased from baseline (9.4) to final follow-up (1.2) (P = 0.005). The Responder Rate was 86.4%. Comparing responder rate of 22 evaluable patients with LCM with responder rate of 19 patients with LEV we didn't observe significant differences (p = 0.31). In our patients treated with LCM we didn't observe significant difference at 3 and 6 months in QoL tests results; we observe a significant reduction in the mean score of Karnofsky Performance Status (KPS) and Barthel Index (BI) between baseline and 6 months of follow-up (KPS p = 0.003; BI p = 0.007). No clinical side effects were observed. Conclusion Comparing the LCM with the historical group treated with LEV in add-on, we observed that LCM seems to have a higher clinical efficacy than LEV. In our patients, we did not observe any significant changes in QoL tests, indicating stability in all quality of life domains explored, despite the objective worsening in their functional status. Although this is a small series with a relatively short follow-up, our data indicates that LCM in add-on in patients with BTRE appears to be as effective as LEV in add-on, without impact on mood and quality of life.

About 20–40 % of patients with brain tumor have seizures; all of whom must be treated with antiepileptic drugs (AEDs) that can cause side effects which may influence quality of life (QoL). However, little data are available regarding the weight of epilepsy on QoL in brain tumor (BT) patients, despite the fact that epilepsy is considered the most important risk factor for long-term disability in this patient population. Aim of this study is to explore the weight of epilepsy in BT patients, and to identify which factors might contribute to their epilepsy burden, as expressed by them only at their first visit in a specialized epilepsy center, in order to have a snapshot for that moment in their care cycle. We reviewed medical charts and results from a battery of tests (routinely given at our outpatient center), administered to 100 consecutive BTRE patients at their first visit, followed from 2007 to 2010. Our results reveal: (1) neurological performances and global neurocognitive status were not influenced by factors related to neoplastic disease or to epilepsy (2) side effects, cognitive deficits, and QoL concerns, as well as patients’ perception of these, were significantly related to polytherapy, especially in patients who had been taking AEDs for a period longer that 6 months (3) the seizure number did not influence patients’ QoL. We found that the weight of epilepsy in BTRE patients was related to AED therapy. Our study highlights the fact that epilepsy in our patients adds a significant burden, and suggests the need to give the proper attention to patients’ concerns regarding the challenges that this pathology might present. Nevertheless, future studies could be designed with a follow-up period and with a patient stratification in order to better understand the weight of epilepsy for these patients.

Purpose To investigate the relationships between imaging parameters derived from intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and HPV status in oropharyngeal squamous cell carcinoma (OPSCC). Materials and Methods 73 patients with a new diagnosis of OPSCC were enrolled in the present study. MRI including IVIM-DWI with nine b value (range 0–800 s/mm2) was acquired in all patients. Primary tumor (PT) and the largest metastatic lymph node (LN), if present, were volumetrically contoured and the tissue diffusion coefficient Dt, perfusion fraction f and perfusion-related diffusion coefficient D* were estimated by a bi-exponential fit. The apparent diffusion coefficient (ADC) was also estimated by a mono-exponential fit. The predictive power of the most relevant patient/tumor characteristics and image-based features in determining the HPV status was assessed. Results 67 PTs and 67 metastatic LNs were analyzed. Significant differences in ADC and Dt values among HPV-positive and HPV-negative patients were found for PTs (p = 0.003 and p Conclusion Significant correlations were found between IVIM-DWI and HPV status in OPSCCs. The perfusion-free diffusion coefficient, Dt, may better reflect the HPV-related tumor differences compared to ADC, whereas the perfusion-related parameters were not able to reliably discriminate HPV-positive from HPV-negative OPSCC.

The objectives of this study were to assess the diffusion parameters derived from intravoxel incoherent motion (IVIM) MRI in head and neck squamous cell carcinoma (HNSCC) and to investigate the agreement between different methods of tumor delineation and two numerical methods to extract the perfusion fraction f. Thirty-seven untreated patients with histopathologically confirmed primary HNSCC were included retrospectively in the study. The entire volume of the primary tumor was outlined on diffusion-weighted images using co-registered morphological images as a guide to the tumor location. Apparent diffusion coefficient (ADC) and IVIM diffusion parameters were estimated considering the largest tumor section as well as the entire tumor volume. A bi-exponential fit was implemented to extract f, D (pure diffusion coefficient) and D* (pseudo-diffusion coefficient). A second simplified method, based on an asymptotic extrapolation, was used to determine f. The agreement between ADC and IVIM diffusion parameters derived from the delineation of single and multiple slices, and between the two f estimations, was assessed by Bland-Altman plots. The inter-slice variability of ADC and IVIM diffusion parameters was evaluated. The Kruskal-Wallis test was used to investigate whether the tumor location had a statistically significant influence on the values of the parameters. Comparing the tumor delineation methods, a better accordance was found for ADC and D, with a mean percentage difference of less than 2%. Larger discrepancies were found for f and D*, with mean differences of 4.5% and 5.5%, respectively. When comparing the two f estimation methods, small mean differences were found (

Objective. An open pilot study to evaluate the effect of pregabalin (PGB) as add-on therapy on seizure control, quality of life, and anxiety in patients with brain tumour-related epilepsy (BTRE). Materials and methods. We recruited 25 consecutive patients with BTRE and uncontrolled seizures. At baseline and during follow-up, patients underwent a complete physical and neurological examination and were evaluated using the QOLIE 31P (V2), EORTC QLQ C30, Adverse Events Profile, and Hamilton Anxiety Rating Scale (HAM-A). At baseline, a seizure diary was given. Results. During follow-up, 17 patients underwent chemotherapy, none underwent radiotherapy, 9 had disease progression, and 3 died. Mean duration of follow-up was 4.1 months. Mean PGB dosage was 279 mg/day. At baseline, mean weekly seizure frequency was 5.3 (±10) and at last available follow-up visit was 2.8±5. This difference was statistically significant ( p=0.016). The responder rate was 76%. Ten patients dropped out; 4 as a result of seizure worsening, 1 as a result of unchanged seizure frequency, 3 as a result of a lack of compliance, and 2 as a result of side effects. Based on the QOLIE-31-P, a significant improvement of the subscale “seizure worry” ( p=0.004) and a significant decrease in distress scores related to AEDs and social life ( p=0.009 and p=0.008, respectively) were observed. A significant decrease in HAM-A score ( p=0.002) was documented. Conclusions. These data indicate that PGB may represent a valid alternative as add-on treatment in this patient population, based on its efficacy on seizure control and anxiety.

We conducted a prospective, observational study to verify the efficacy, tolerability and impact on quality of life, mood and global neurocognitive performances of oxcarbazepine monotherapy in patients with brain tumor-related epilepsy (BTRE). Patients were followed for 12 months. We recruited 25 patients (11 females 14 males; mean age 49.7) affected with BTRE (17 de novo patients and 7 in monotherapy with other antiepileptics) and introduced oxcarbazepine monotherapy because of uncontrolled seizures and/or side effects. At first visit, patients underwent neurological examination, Qolie 31P V2, EORTC QLQC30, Zung self-depression rating scale (ZSDRS) and adverse events profile. A seizure diary was given to each patient. Follow-up duration was 1-12 months (mean 7.1 months, 5 patients died and 10 dropped out). Totals of 16 patients underwent both chemotherapy and radiotherapy, 4 chemotherapy only, 1 radiotherapy only, and 4 did not undergo any systemic therapy. Mean dosage of oxcarbazepine was 1,230 mg/day (min 600, max 2,100 mg/day). McNemar's test showed a significant difference in seizure freedom rate (P = 0.002) between baseline and final follow-up in the intent-to-treat population. Six patients (24%) had serious side effects and one patient (4%) mild. Logistic regression revealed that, in our study, chemotherapy and radiotherapy did not affect the efficacy of OXC in seizure outcome (P = 0.658). The test evaluation at final follow-up showed a significant improvement in ZSDRS (P = 0.011) and no change over time. Oxcarbazepine seems to be efficacious in controlling seizures and in improving mood in patients with BTRE, but special caution should be taken when it is administered during radiotherapy.

The energy absorbed from the radio-frequency fields of mobile telephones depends strongly on distance from the source. The authors' objective in this study was to evaluate whether gliomas occur preferentially in the areas of the brain having the highest radio-frequency exposure. The authors used 2 approaches: In a case-case analysis, tumor locations were compared with varying exposure levels; in a case-specular analysis, a hypothetical reference location was assigned for each glioma, and the distances from the actual and specular locations to the handset were compared. The study included 888 gliomas from 7 European countries (2000-2004), with tumor midpoints defined on a 3-dimensional grid based on radiologic images. The case-case analyses were carried out using unconditional logistic regression, whereas in the case-specular analysis, conditional logistic regression was used. In the case-case analyses, tumors were located closest to the source of exposure among never-regular and contralateral users, but not statistically significantly. In the case-specular analysis, the mean distances between exposure source and location were similar for cases and speculars. These results do not suggest that gliomas in mobile phone users are preferentially located in the parts of the brain with the highest radio-frequency fields from mobile phones.

We performed a case series analysis to evaluate the effects of levetiracetam (LEV) monotherapy on seizures, adverse events, cognitive functioning and quality of life (QoL) in patients with brain tumor-related epilepsy (BTRE). We also explored the possible effects of systemic therapies on the efficacy of LEV. Twenty-nine patients were followed (13 female, 16 male; age 24–75 years) with 12 months of follow-up. Patients were evaluated by QoL and neuropsychological tests. At final follow-up, mean LEV dosage was 1991.4 mg/day. Among patients who reached the final follow-up of 12 months (n = 15), 1 patient had ≥50% reduction of seizure frequency (SF), and 14/15 were seizure free. The difference in presence/absence of seizures between baseline and final follow-up was significant (p < 0.001). Responder rate was 100%. We observed five side-effects: four mild (reversible) and one severe. Logistic regression revealed that chemotherapy and radiotherapy did not affect the efficacy of LEV in seizure outcome (p = 0.999). The following statistically significant observations emerged by tests’ evaluation: less worry about seizures, effects of antiepileptic, and ability to maintain social functions. Our data suggest that seizure occurrence can be an important warning sign that the clinician should heed throughout the duration of the illness. Patients with BTRE represent a unique patient population that presents difficulties regarding management of two very different pathologies: epilepsy on the one hand, and brain tumor on the other. Our data indicate that LEV, in patients with BTRE, is safe and efficacious, with positive impact on QoL.

The aim of the study was to evaluate efficacy, safety and impact on life expectancy of levetiracetam (LEV), oxcarbazepine (OXC) and topiramate (TPM) monotherapy in patients with seizures related to brain metastases. We conducted a prospective observational study on 70 patients with brain metastases. Thirteen patients were excluded because they were in prophylactic therapy with antiepileptics, nine patients did not return to our Center. A total of 48 patients with epilepsy related to brain metastases were enrolled. Patients were treated with LEV, OXC and TPM in monotherapy and followed until their death. Eighteen patients dropped out. Therefore, we followed 30 patients. Mean duration of follow-up was 6.1 months. Upon visiting the patients prior to their death (i.e. last visit preceding the death of the patients), we observed a significant reduction (P < 0.001) in the mean monthly seizure frequency; with 19 patients (63.3%) obtaining complete seizure control in the whole population. A significant improvement of seizure frequency was also observed considering each antiepileptic treatment group separately. Median survival time was similar among the three groups of patients and was similar to Class I of prognostic factors of Radiation Therapy Oncology Group. Logistic regression showed that systemic treatments did not influence the antiepileptics' efficacy on seizure control (P = 0.614). In conclusion, regarding the use of newer antiepileptics in patients with seizures related to brain metastases, our data indicate that LEV, OXC and TPM significantly reduce seizure frequency (independently of systemic treatment), produce few side effects and appear not to affect life expectancy.

In order to evaluate the activity of gemcitabine as radiosensitizer for newly diagnosed glioblastoma multiforme (GBM), a prospective single-center phase II study was conducted.Eligible patients were required to have histologically proven GBM with evaluable and/or measurable disease after surgery. They were treated by standard cranial irradiation plus concomitant fixed dose rate gemcitabine given intravenously at 175 mg/m(2) weekly for 6 weeks. After chemo-radiotherapy, irrespective of tumor response, patients went on to receive oral temozolomide at 150-200 mg/m(2) for 5 days every 28 days.Twenty-three patients were enrolled. Median age was 57 years (range 43-72) and median Karnofsky performance status was 90 (range 70-100). Seventeen patients had received subtotal resection of the tumor, while six patients had biopsied-only tumors. Four patients responded to treatment (17.5%) with additional 14 (61%) experiencing stable disease for an overall disease control rate of 78.5%. Median progression-free and overall survival were 6.8 and 10.1 months, respectively. The concomitant radiotherapy-gemcitabine combination was well tolerated and severe adverse events were rare, consisting of grade 3 neutropenia and hypertransaminasemia in two cases each. Twenty patients were assessable for methylguanine methyltransferase (MGMT) promoter methylation, 11 of which were found methylated. In the methylated and unmethylated cohorts, disease control was obtained in 10/11 patients (91%) and 7/9 patients (77.5%), respectively.Concomitant radiotherapy-gemcitabine is active and well tolerated in newly diagnosed glioblastoma multiforme. Activity is observed both in tumors with methylated and unmethylated MGMT promoter.

Recent reports on large number of patients with brain metastases report that Whole Brain Radiotherapy (WBRT) and Radiosurgery (RS) should be the treatments of choice, particularly in multiple lesions cases. Among the prognostic factors, the cerebellar location was never considered, although this results in hydrocephalus, brain stem compression, ataxia, intracranial hypertension.We evaluated 44 patients with cerebellar metastases operated over 6 years. Primary lesions were: Lung (15), Breast (12), Gastrointestinal (9), Gut (3), Ovary (2), Melanoma (1), Salivary gland carcinoma (1), Unknown (1). Lesions were3 cm in 11 cases,or =3 cm in 33. Average KPS scoring at admission was 69.9. Twenty nine scoredor =70, 1570.Two patients died for surgical complications, 2 died within 1 months for other causes, 2 were lost to follow up. Eight had postoperative hematoma requiring reoperation, 1 had an occipital infarction. Average KPS scoring at discharge was 76.4, P0.002. Those patients that had complications scored less, the difference is significant (P0.008). Median survival was 8 months, 1 year survival rate 29.9%. Survival was correlated with either admission or discharge KPS (or =70 vs.70): P = 0.05 and P = 0.0001 respectively. None of the other parameters considered reached statistical significance.Open microneurosurgery is probably still the most effective therapy in improving survival and KPS in patients with large cerebellar metastases, given that the proper surgical technique is used and that complications do not occur. Specific data on cerebellar metastases as an independent subgroup are needed from radiosurgical series.

In patients with newly diagnosed glioblastoma multiforme (GBM), concurrent chemo-radiotherapy with temozolomide is the new standard of care. In the present phase I study we investigated the association of gemcitabine, a cell-cycle antimetabolite with radiosensitizing properties, with radiotherapy (RT) in the first line treatment. Gemcitabine was delivered at a fixed dose-rate of 10 mg/m(2)/min weekly for 6 weeks starting 24-72 h prior to, and then concomitantly with RT (2.0 Gy per fraction, total dose 60 Gys). The primary end-point was the identification of dose-limiting toxicity (DLT), and maximum tolerated dose (MTD). Planned dose levels of gemcitabine started from 200 mg/m(2)/weekly (level 1), with sequential dose escalations of 25 mg/m(2). Ten patients were enrolled, all with evaluable disease after surgery. Six patients were male, median age was 55 years (44-75), and median baseline Karnofsky performance status was 85 (70-100). Four patients entered level 1, one patient being excluded from the study because of early disease progression. At this level, two of three patients developed progressive neurological deterioration, potentially related to the experimental treatment. On this basis gemcitabine dose was prudentially reduced to 175 mg/m(2)/weekly in the subsequent step (level -1). No DLT was encountered in the six patients enrolled at this level. Interestingly, at this dose only two grade three toxicities (one neutropenia and one raise in serum transaminases) were reported. Thus, fixed dose-rate gemcitabine at 175 mg/m(2)/weekly is the recommended regimen for further evaluation in a phase II study that is presently in progress.

The management of elderly glioblastoma (GBM) remains controversial for under-representation in controlled trials, for modest tolerance of treatments, and higher rate of side effects. Age was identified as an important prognostic factor for survival, mainly in patients with poor performance status. The presence of co-morbidities (CM) represents an important issue in elderly because the correlation with frailty, and the role as predictor of disability and mortality. The aim of this study was to evaluate the impact of CM on outcome of elderly GBM. METHODS: Patients affected by GBM with age ≥ 65 years have been enrolled in a prospective study. For each patient, CM were identified with the Cumulative Illness Rating Scale (CIRS). RESULTS: Sixty-six elderly patients affected by GBM were enrolled into the study. The average age at diagnosis was 73 years (range 65-87). The median PFS at 12 months has been 8 months, with a rate of 29.1% patients free of progression at 1 year. The median OS has been 18 months (95% CI 13-23), with a survival rate of 35% at 2 years. The univariate analysis showed that the severity of CM is a strong predictor of disease progression (HR = 1.24, 95% CIs from 1.11 to 1.38, p = 0.000). Multivariate analysis confirmed that the severity of CM (HR = 1.24 for each increase of CIRS score, 95% CIs from 1.11 to 1.38, p = 0.000) is an independent predictor of disease progression. In addition, higher score of CM and age higher than 75 years are associated with short survival. DISCUSSION: We observed that high CM score is an independent predictor of disease progression and shorter survival. The evaluation of CM should drive therapeutic decisions in elderly GBM. In subgroups of elderly GBM without high score of CM, standard treatments should be considered. Further studies on elderly GBM are warranted to confirm these data.

O6-methylguanine-DNA-methyltransferase (MGMT) has emerged as a relevant predictor of therapeutic response and good prognosis in patients with glioblastoma (GBM). Transcriptionally active MGMT rapidly removes the alkyl adducts, preventing the formation of cross-links and thereby causing resistance to alkylating drugs. Studies with pyrosequencing (PSQ) showed that this technique has a higher reproducibility and sensitivity than other techniques. However, the definition of a prognostically relevant threshold for the percentage of MGMT methylation remains one of the most critical issues in the use of PSQ analysis. The aim of this study was to define the cut-off value correlated with good favourable prognostic outcomes. We retrospectively analyzed 51 patients (33 males, 18 females) with GBM who underwent surgery or biopsy. The Receiver Operating Characteristics analysis showed that the best possible criteria for PSQ-detected percentage of MGMT methylation that predicted progression-free survival (PFS) and overall survival (OS) were 19% and 13%, respectively. Patients with ≤19% of PSQ-detected MGMT had a shorter PFS (HR: 0.24,p<0.01); those ones with ≤13% had a shorter OS (HR: 0.33,p<0.05). Our study reinforces the importance of MGMT in the management of GBM patients, but future studies with larger sample sizes are warranted to confirm our findings.

Background The optimal treatment for low-grade glioma (LGG) is still controversial. Recent data indicate a potential influence of chemotherapy on the natural evolution of these tumors, allowing for the deferral of more aggressive therapies. Patients and methods Forty-three patients affected with LGG (29 astrocytoma, four oligodendroglioma and 10 mixed oligo-astrocytoma) were treated with temozolomide (TMZ) at the time of documented clinical and radiological progression. McDonald’s response criteria were utilized to evaluate TMZ activity. Thirty patients (69.7%) had previously received radiotherapy; 16 (37.2%) had received prior chemotherapy. Clinical benefit was evaluated measuring seizure control, reduction in steroid dose and modification of Karnofsky performance status and Barthel index. Quality of life was assessed with the QLQ-C30 questionnaire. Results We observed a complete response in four patients, 16 partial responses, 17 stable disease (with four minor response) and six progressive disease. Median duration of response was 10 months [95% confidence interval (CI) 8–12], with a 76% rate of progression free survival (PFS) at 6 months, and a 39% rate of PFS at 12 months. A relevant clinical benefit was observed particularly in patients presenting epilepsy. Conclusions The high response rate of 47% (95% CI 31% to 61%) confirms that TMZ chemotherapy is a valid option in the treatment of progressive LGG. The present preliminary results seem interesting and warrant further evaluation of TMZ clinical activity in a larger series of progressive LGG.

INTRODUCTION: Malignant gliomas are the most unfavourable brain tumours. Recent evidence suggests that extensive tumour removal is associated with better survival. The current treatment is complete as possible resection of the contrast-enhancing tumour tissue, followed by adjuvant treatment with radiotherapy and chemotherapy. As it appears difficult to distinguish between infiltration tumour and normal tissue, specially in recurrent tumours, the radical removal becomes harmful. Techniques to visualize the borderline tumour intraoperatively are helpful. More recently, fluorescence guidance has taken advantage of intrinsic metabolic and structural changes that occur within malignant glioma by exploiting the eme biosynthetic pathway and a natural biochemical in that pathway, 5-aminolevulinic acid (5-ALA). METHODS: Since the end of 2009, in our Institute 54 patients were operated on using fluorescence guided tumour resection. Preoperatively, all enrolled patients had MRI showing contrast enhancing lesions. MRI within 72 hours after surgery and thereafter at 3-month interval was performed. 32 patients were newly diagnosed tumour, 22 were recurrent malignant glioma. An oral dose of 20 mg 5-ALA /kg body weight was administered to each patient. By a NC4 OPMI Pentero operating microscope (Zeiss), enabled switching from xenon light to violet-blue light for visualizing fluorescence, the surgical resection was performed. Histology was in 48 glioblastoma (1 gliosarcoma), in 4 anaplastic oligodendroglioma, in 1 oligodendroglioma I WHO and in 1 pleomorphic xanthoastrocytoma. All the patients, as first line treatment, were submitted to radiotherapy and chemotherapy; in recurrent tumours second and in some cases third line treatments were administered. The follow-up ranged from 2 years to 8 months. RESULTS: In all cases the yellow fluorescence due to 5-ALA in cortical vessels was seen. In 47 glioblastoma, 4 anaplastic oligodendroglioma and 1 xanthoastrocytoma the tumour tissue showed intraoperative red fluorescence. Specially in recurrent tumours, the fluorescence-guided surgery was helpful to identify, inside the gliotic tissue, some areas with active tumour from perilesional “healthy” brain. Furthermore, after surgery no relevant neurological deficit caused by 5-ALA guided resection were observed. Early postoperative MRI confirmed gross total resection without contrast enhancment in 80 % of patients. At the follow-up 24 patients are still alive. CONCLUSIONS: The 5-ALA was helpful to localize the tumour on the cortex and extended resection of infiltrating tumour, specially in recurrence. Patients affected by glioblastoma are elctive for this technique. Extended resections by 5-ALA fluorescence guide does not impair neurological functions and can impact on the overall survival of patients affected by malignant glioma.

OBJECTIVES: Brain tumor-related epilepsy (BTRE) is often drug resistant and patients can be forced to take polytherapy. This study evaluates both the efficacy of zonisamide (ZNS) as an add-on antiepileptic drug and the cognitive profile in patients with BTRE who have uncontrolled seizures. METHODS: We followed 11 patients for 6 months (age raging from 32 to 61). They underwent neurological visit with seizure count at baseline, after 6 weeks, 3 and 6 months. A battery of neuropsychological tests was administered at baseline and after 6 months. RESULTS: Seven patients had high-grade gliomas, three patients had meningioma, and one patient had cerebral metastases. Four patients had simple partial seizures, four had complex partial seizures and three had complex partial, secondary generalized seizures. Mean dosage of ZNS was 300 mg/day. Seven patients were in chemotherapy. Mean seizure number in the month prior to administration of ZNS was 16.2. At the last follow-up available, mean seizure number was 4.5/month (responder rate= 87%). Three patients dropped out for scarce compliance. No side effects were observed. At baseline, four patients had memory deficits. CONCLUSION: Our data seems to indicate that ZNS has a good efficacy in patients with BTRE.Neuropsychological tests at last follow-up are ongoing.

OBJECTIVE: To determine whether early monitoring of the effects of bevacizumab in patients with recurrent high-grade gliomas, by the Parametric Response Map derived from Dynamic Contrast-Enhanced MRI (DCE-MRI), may be a predictor of the response to treatment assessed through conventional MRI follow-up. METHODS: 20 patients have been enrolled in the present study. For each patient two DCE-MRI examinations, before and after the first dose of bevacizumab, were acquired. The region of interest was defined on the IAUGC (Initial Area Under Gadolinium Concentration) maps, using co-registered T1-weighted contrast-enhanced images as a guide to the tumour location. For both perfusion parameters, the parametric response map (PRM) (1) was calculated. The PRM is a voxel-wise analytic method allowing to identify and quantify the regions wherein the parameter value increased, decreased or remained stable, during or after therapy. The modifications of hyper and hypo-perfused sub-volumes, including tumour necrosis, was assessed within the lesion using a volumetric histogram analysis. The significance of changes in the different perfusion metrics, observed at baseline and during treatment, was established. The relationships between changes in perfusion and morphological MRI modifications at first follow-up were investigated. On the same patients, serial evaluations of plasma and serum VEGF levels and Von Willebrand factor (vWF) antigen were performed at the same time points. RESULTS: Early significant reductions in both IAUGC and Ktrans values, after a single dose of bevacizumab, were observed. Both the PRMs and the histogram modifications indicated the normalizing effect of bevacizumab on tumour pathological vasculature. An improvement in hypoxia after a single dose of bevacizumab seems to be predictive of a greater reduction in T1-weighted contrast-enhanced volumes at first follow-up and a better response to treatment. Circulating plasma levels of VEGF and vWF antigen significantly increased in all patients after a single dose of bevacizumab. Preliminary results showed a tendency to a significant relationship between changes in median IAUGC and in levels of vWF antigen, while no correlation was found between changes in tumour size and circulating parameters. CONCLUSIONS: Early monitoring of the modifications induced on perfusion maps, derived from DCE-MRI, as well as the variations of vWF antigen, may provide useful information to document and predict the effect of anti-angiogenic agents. REFERENCE: 1. Galban, C.J. et al. Prospective analysis of parametric response map-derived MRI biomarkers: identification of early and distinct glioma response patterns not predicted by standard radiographic assessment. CLIN CANCER RES. 2011 Jul 15;17(14):4751-4760.

In order to get a correct diagnosis, biopsy is fundamental in oncological orthopedic surgery. If for other tumors, like liver and lung, the possibility to spread malignant cells through biopsy track is well known, it was less evident for bone tumors. This case report study focuses this problem; radiologists and orthopedics have to maintain a high suspicion level while checking post-biopsy imaging. Recurrence can be considered a negative prognostic factor for outcome patients.

Background – Zonisamide (ZNS) is an antiepileptic drug (AED) with broad spectrum action that demonstrated a good efficacy in controlling seizures as add-on in adult and pediatric epilepsy. To date there have been no studies on ZNS in patients with brain tumor-related epilepsy (BTRE). Aim of the study – To evaluate efficacy and tolerability of ZNS as add-on in BTRE. Methods– We followed six patients suffering from BTRE who had already been treated with other AEDs and who had had not experienced adequate seizure control. Three patients underwent chemotherapy while being treated with ZNS. Mean duration of follow-up was 8 months. Results – Mean seizure number in the last month prior to the introduction of ZNS had been 27.7/month. ZNS mean dosage was of 283.3 mg/day. At last follow-up, the mean seizure number was reduced to 8.8/month. Responder rate was 83.3%.Two patients discontinued the drug because of side effects. There were no other reported side effects. Conclusions – Preliminary data on the use of ZNS in add-on in patients with BTRE indicate that this drug may represent a valid alternative as add-on in this particular patient population. However, larger samples are necessary to draw definitive conclusions.