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Introduction: To assess the diagnostic accuracy of CESM and 3T MRI compared to full-field digital mammography (FFDM), plus US, in the evaluation of advanced breast lesions. Materials and Methods: Consenting women with suspicious findings underwent FFDM, US, CESM and 3T MRI. Breast lesions were histologically assessed, with histology being the gold standard. Two experienced breast radiologists, blinded to cancer status, read the images. Diagnostic accuracy of (1) CESM as an adjunct to FFDM and US, and (2) 3T MRI as an adjunct to CESM compared to FFDM and US, was assessed. Measures of accuracy were sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV). Results: There were 118 patients included along with 142 histologically characterized lesions. K agreement values were 0.69, 0.68, 0.63 and 0.56 for concordance between the gold standard and FFDM, FFDM + US, CESM and MRI, respectively (p < 0.001, for all). K concordance for CESM was 0.81 with FFDM + US and 0.73 with MRI (p value < 0.001 for all). Conclusions: CESM may represent a valuable alternative and/or an integrating technique to MRI in the evaluation of breast cancer patients.

To evaluate the quality of the reports of loco-regional staging computed tomography (CT) or magnetic resonance imaging (MRI) in head and neck (HN) cancer.Consecutive reports of staging CT and MRI of all HN cancer cases from 2018 to 2020 were collected. We created lists of quality indicators for tumor (T) for each district and for node (N). We marked these as 0 or 1 in the report calculating a report score (RS) and a maximum sum (MS) of each list. Two radiologists and two otolaryngologists in consensus classified reports as low quality (LQ) if the RS fell in the percentage range 0-59% of MS and as high quality (HQ) if it fell in the range 60-100%, annotating technique and district. We evaluated the distribution of reports in these categories.Two hundred thirty-seven reports (97 CT and 140 MRI) of 95 oral cavity, 52 laryngeal, 47 oropharyngeal, 19 hypo-pharyngeal, 14 parotid, and 10 nasopharyngeal cancers were included. Sixty-six percent of all the reports were LQ for T, 66% out of all the MRI reports, and 65% out of all CT reports were LQ. Eight-five percent of reports were HQ for N, 85% out of all the MRI reports, and 82% out of all CT reports were HQ. Reports of oral cavity, oro-nasopharynx, and parotid were LQ, respectively, in 76%, 73%, 100% and 92 out of cases.Reports of staging CT/MRI in HN cancer were LQ for T description and HQ for N description.

The aim of this paper is to define the pre-treatment radiological characteristics of oropharyngeal squamous cell carcinoma (OPSCC) using morphological and non-morphological magnetic resonance imaging (MRI), based on HPV status, in a single-institution cohort. In total, 100 patients affected by OPSCC were prospectively enrolled in the present study. All patients underwent 1.5T MR with standard sequences, including diffusion-weighted imaging with and intravoxel incoherent motion (IVIM-DWI) technique and a dynamic contrast-enhanced (DCE) MRI. For all patients, human papillomavirus (HPV) status was available. No statistically significant differences in the volume of primary tumors (PTs) and lymph nodes (LNs) were observed based on HPV status. When comparing the two patient groups, no significant differences were found for the PT radiologic characteristics (presence of well-defined borders, exophytic growth, ulceration, and necrosis) and LN morphology (solid/cystic/necrotic). Tumor subsite, smoking status, and alcohol intake significantly differed based on HPV status, as well as ADC and Dt values of both PTs and LNs. We detected no significant difference in DCE-MRI parameters by HPV status. Based on a multivariate logistic regression model, the combination of clinical factors, such as tumor subsite and alcohol habits, with the perfusion-free diffusion coefficient Dt of LNs, may help to accurately discriminate OPSCC by HPV status.

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.

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 Literature data suggests that age, gender and body mass index (BMI) could be associated with difference in immune responses to vaccines. The first goal of the study was to analyze the antibody titre seven days after the second dose of BNT162b2 vaccine in a group of 248 healthcare workers (HCWs). The second goal was to analyze how antibody titre changes in correlation with age, gender, BMI and hypertension. Methods An immunogenicity evaluation was carried out among HCWs vaccinated at the Istituti Fisioterapici Ospitalieri (IFO), Rome, Italy. All HCWs were asked to be vaccinated by the Italian national vaccine campaign at the beginning of 2021. 260 vaccinated HCWs were enrolled in the study. All eligible participants were assigned to receive the priming dose in two weeks' time and the booster dose exactly 21 days thereafter. Blood and nasopharyngeal swabs were collected at baseline and 7 days after second dose of vaccine. Quantitative measurements of IgG antibodies against S1/S2 antigens of SARS-CoV-2 were performed with a commercial chemiluminescent immunoassay. Presence of SARS-Cov-2 in nasopharyngeal swab was determined by commercial RT-PCR testing. Findings 248 HWCs were analyzed, 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 p

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.

BackgroundThe differentiation between benign and malignant parotid lesions is crucial to defining the treatment plan, which highly depends on the tumor histology. We aimed to evaluate the role of MRI-based radiomics using both T2-weighted (T2-w) images and Apparent Diffusion Coefficient (ADC) maps in the differentiation of parotid lesions, in order to develop predictive models with an external validation cohort.Materials and MethodsA sample of 69 untreated parotid lesions was evaluated retrospectively, including 37 benign (of which 13 were Warthin’s tumors) and 32 malignant tumors. The patient population was divided into three groups: benign lesions (24 cases), Warthin’s lesions (13 cases), and malignant lesions (32 cases), which were compared in pairs. First- and second-order features were derived for each lesion. Margins and contrast enhancement patterns (CE) were qualitatively assessed. The model with the final feature set was achieved using the support vector machine binary classification algorithm.ResultsModels for discriminating between Warthin’s and malignant tumors, benign and Warthin’s tumors and benign and malignant tumors had an accuracy of 86.7%, 91.9% and 80.4%, respectively. After the feature selection process, four parameters for each model were used, including histogram-based features from ADC and T2-w images, shape-based features and types of margins and/or CE. Comparable accuracies were obtained after validation with the external cohort.ConclusionsRadiomic analysis of ADC, T2-w images, and qualitative scores evaluating margins and CE allowed us to obtain good to excellent diagnostic accuracies in differentiating parotid lesions, which were confirmed with an external validation cohort.

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

The Intra-Voxel Incoherent Motion (IVIM) model is largely adopted to estimate slow and fast diffusion coefficients of water molecules in biological tissues, which are used in cancer applications. The most reported fitting approach is a voxel-wise segmented non-linear least square, whereas Bayesian approaches with a direct fit, also considering spatial regularization, were proposed too. In this work a novel segmented Bayesian method was proposed, also in combination with a spatial regularization through a Conditional Autoregressive (CAR) prior specification. The two segmented Bayesian approaches, with and without CAR specification, were compared with two standard least-square and a direct Bayesian fitting methods. All approaches were tested on simulated images and real data of patients with head-and-neck and rectal cancer. Estimation accuracy and maps noisiness were quantified on simulated images, whereas the coefficient of variation and the goodness of fit were evaluated for real data. Both versions of the segmented Bayesian approach outperformed the standard methods on simulated images for pseudo-diffusion (D∗ ) and perfusion fraction (f), whilst the segmented least-square fitting remained the less biased for the diffusion coefficient (D). On real data, Bayesian approaches provided the less noisy maps, and the two Bayesian methods without CAR generally estimated lower values for f and D∗ coefficients with respect to the other approaches. The proposed segmented Bayesian approaches were superior, in terms of estimation accuracy and maps quality, to the direct Bayesian model and the least-square fittings. The CAR method improved the estimation accuracy, especially for D∗ .

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).

BACKGROUND 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 MATERIAL AND METHODS This was a single arm, Phase II study. Eligibility criteria included progressive or recurrent malignant glioma after radiotherapy and chemotherapy-based treatments and Karnofsky Performance Status (KPS) > 60. RESULTS Thirty-two patients (median age: 43.5 y) were enrolled to receive weekly carboplatin monotherapy in intravenous mode of administration. The median duration of response was 7.3 months with an overall disease control rate of 31.3%. Median progression-free survival (PFS) was 2.3 months while overall survival (OS) was 5.5 months. Patients achieving clinical benefit exhibited a longer PFS (4.6 vs 1.5 months; p>0.001) and OS (7.9 vs 3.2 months; p=0.041) compared to those not achieving clinical benefit. CONCLUSION Our findings show that single agent, weekly, intravenous carboplatin may have a role in the treatment patients with recurrent malignant glioma

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.

Purpose In the treatment of Head-and-Neck Squamous Cell Carcinoma (HNSCC), the early prediction of residual malignant lymph nodes (LNs) is currently required. Here, we investigated the potential of a multi-modal characterization (combination of CT, T2w-MRI and DW-MRI) at baseline and at mid-treatment, based on texture analysis (TA), for the early prediction of LNs response to chemo-radiotherapy (CRT). Methods 30 patients with pathologically confirmed HNSCC treated with CRT were considered. All patients underwent a planning CT and two serial MR examinations (including T2w and DW images), one before and one at mid-CRT. For each patient the largest malignant LN was selected and within each LN, morphological and textural features were estimated from T2w-MRI and CT, besides a quantification of the apparent diffusion coefficient (ADC) from DW-MRI. After a median follow-up time of 26.6 months, 19 LNs showed regional control, while 11 LNs showed regional failure at a median time of 4.6 months. Linear discriminant analysis was used to test the accuracy of the image-based features in predicting the final response. Results Pre-treatment features showed higher predictive power than mid-CRT features, the ADC having the highest accuracy (80%); CT-based indices were found not predictive. When ADC was combined with TA, the classification performance increased (accuracy = 82.8%). If only T2w-MRI features were considered, the best combination of pre-CRT indices and their variation reached an equivalent accuracy (81.8%). Conclusion Our results may suggest that TA on T2w-MRI and ADC can be combined together to obtain a more accurate prediction of response to CRT.

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.

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.

Background Data on efficacy of bevacizumab (B) beyond first-line taxane -including regimen (BT) as first-line treatment are lacking. Although preclinical results that anti-angiogenic agents combined with hormonal therapy (HT) could be active, no clinical data exist about combination of maintenance Bevacizumab (mBev) with HT. Methods Thirty-five patients who experienced a response after first-line BT, were given mBev at the dose of 15 mg/kg every 3 weeks. Among 30 pts with hormonal receptor-positive metastatic breast cancer (MBC), 20 (66.6%) received HT with mBev (mHTBev). Objective of the study was the outcome and safety of mBev and in two groups of patients receiving HT or not. Results Complete response and partial response was achieved/maintained in 4 (11.4%) and 13 (37.1%) patients, respectively (overall response rate: 48.5%). Clinical benefit was obtained on 23 patients (65.7%). Median of mBev PFS and clinical benefit were 6.8 months (95% CI: 0.8-12.7) and 17.1 months (95% CI :12.2-21.9), respectively. Median PFS of patients who received mHTBev was longer than mBev without HT (13 months and 4.1 months, respectively, p = 0.05). The most common severe toxicities were proteinuria (11.4%) and hypertension (8.5%). No additional toxicity was observed with HTBev. Conclusion Maintenance bevacizumab with or without anti-hormonal therapy in patients with hormone receptor positive breast cancer is tolerable and associated with long-term clinical outcome; these results encourage the strategy of prolonging bevacizumab until progression in combination with anti-hormonal agents.

Objective: Different perfusion metrics were investigated to determine the accuracy of Perfusion CT (PCT) in differentiating recurrence of brain metastases from radiation necrosis in patients who previously underwent stereotactic radiation therapy (SRT). Patients and Methods: Twenty patients previously treated with SRT underwent PCT examination of the brain. Normalized Cerebral Blood Volume (nCBV) values within the region of interest (ROI) were calculated. Fractional volumes at nCBV values between 1.0 and 2.25, defined as V 1.0-V 2.25, were derived as alternative metrics and compared to the conventional method based on the mean CBV value within the lesion (nCBV mean). The Mann-Whitney test was used to compare the two patient's groups with recurrence and radiation necrosis with respect to the different nCBV metrics. Predictive powers and optimal thresholds for both the nCBV mean and the V 1.0-V 2.25 were evaluated using the Receiver Operating Characteristic Curves. The gold standard was represented either by the histopathological examination or the Magnetic Resonance (MR) imaging follow-up longer than six months. Results and Conclusion: The differences between the patient's group with recurrence and that with radiation necrosis resulted statistically significant for all the metrics, showing the lowest p-value for V 1.75 and V 2. The metrics based on the fractional volumes were found to show higher predictive powers, with the highest value of 0.96 for V 2.0. Quantitative analysis of the CBV map deriving different metrics may potentially improve the diagnostic accuracy of PCT in differentiating brain metastasis recurrence from radiation necrosis. © 2011 Elsevier Ireland Ltd. All rights reserved

Background To evaluate the therapeutic strategies commonly employed in the clinic for the management of brain metastases (BMs) and to correlate disease outcome with type of treatment and therapeutic resources available at the treating center. Methods Four Cancer centres participated to the survey. Data were collected through a questionnaire filled in by one physician for each centre. Results Clinical data regarding 290 cancer patients with BMs from solid tumors were collected. Median age was 59 and 59% of patients had ≤ 3 brain metastases. A local approach (surgery and stereotactic radiosurgery) was adopted in 31% of patients. The local approach demonstrated to be superior in terms of survival compared to the regional/systemic approach (whole brain radiotherapy and chemotherapy, p = Conclusions In clinical practice, local strategies should be integrated in the management of brain metastases. Proper selection of patients who are candidate to local treatments is of crucial importance.

Background Adequate surgery still remains the only curative treatment of chordoma. Interesting clinical data on advanced disease with molecularly targeted therapies were reported. Methods We described the clinical outcome of a series of chordoma patients followed at Regina Elena National Cancer Centre of Rome from 2004 to 2008. Results Twenty-five consecutive patients with sacral (11 patients), spine (13 patients), and skull base (1 patient) chordoma went to our observation. Six patients (24%) had primary disease, 14(56%) a recurrent disease, and 5(20%) a metastatic spreading. Surgery was the primary option for treatment in 22 out of 25 patients. Surgical margins were wide in 5 (23%) and intralesional in 17(77%) patients; 3 out of 4 in-house treated patients obtained wide margins. After first surgery, radiotherapy (protons or high-energy photons) were delivered to 3 patients. One out of the 5 patients with wide margins is still without evidence of disease at 20 months from surgery; 2 patients died without evidence of disease after 3 and 36 months from surgery. Sixteen out of 17 (94%) patients with intralesional margins underwent local progression at a median time of 18 months with a 2-year local progression-free survival of 47%. The 5-year metastasis-free survival rate was 78.3%. Seventeen patients with locally advanced and/or metastatic disease expressing platelet-derived growth factor receptor (PDGFR) β were treated with imatinib mesylate. A RECIST stabilization of the disease was the best response observed in all treated cases. Pain relief with reduction in analgesics use was obtained in 6 out of 11 (54%) symptomatic patients. The 5- and 10-year survival rates of the entire series of patients were 76.7 and 59.7%, respectively. Conclusions Despite progress of surgical techniques and the results obtained with targeted therapy, more effort is needed for better disease control. Specific experience of the multidisciplinar therapeutic team is, however, essential to succeed in improving patients' outcome.

Herpes simplex encephalitis (HSE) is a life-threatening condition with high mortality. The pathogenesis underlying the reactivation of latent herpes simplex virus (HSV) remains undefined. We present the case of a 55-year-old female who developed HSE type 1 during brain irradiation and antioedematous dexamethasone treatment for leptomeningeal metastasized breast tumor with epileptic seizures. During the radiotherapy (RT), after a total of 32 Gray administrated in 16 fractions, our patient developed cognitive impairment and partial epileptic status without fever. Two days later the patient’s clinical conditions had deteriorated and high fever manifested. A diagnosis of HSE type 1 was made by a positive cerebrospinal fluid polymerase chain reaction. Antiviral therapy with high doses of acyclovir was practiced for four weeks but the comatose state persisted. The patient died 59 days after the last RT fraction. The temporal relationship of RT to the occurrence of HSE suggests that cranial irradiation may play a role in the reactivation of latent HSV. Although antiviral therapy resistance is infrequent in immunocompetent patients, it is one of the main problems in immunocompromized patients.

Background Seizure control doesn't represent the only challenging goal in patients with brain tumor-related epilepsy. Side effects have often taken precedence for patients' quality of life. Methods We performed an observational retrospective study on patients with brain tumor-related epilepsy: 35 who had assumed oxcarbazepine monotherapy and 35 patients who had undergone treatment with traditional antiepileptic drugs. Primary variable of efficacy was the mean seizure frequency per month and safety variables were the drop-out for side effects and total incidence of side effects. We applied the Propensity Score technique to minimize selection bias. Results Our results showed a similar efficacy of oxcarbazepine and traditional antiepileptic drugs over time, but the difference in safety and tolerability between the two groups was significant: traditional AEDs caused more side effects, both serious and non serious. Conclusion This study highlights the importance of taking into consideration not only seizure control but also the appearance of side effects when choosing antiepileptic drugs in this patients population.

Background In recurrent malignant gliomas (MGs), a high rate of haematological toxicity is observed with the use of fotemustine at the conventional schedule (100 mg/m2 weekly for 3 consecutive weeks followed by triweekly administration after a 5-week rest period). Also, the impact of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status on fotemustine activity has never been explored in the clinical setting. Methods 40 patients with recurrent pretreated MG were identified as being treated with fotemustine at doses ranging from 65 mg/m2 to 100 mg/m2. Patients were classified into 3 groups according to the dose of fotemustine received, from the lowest dosage received in group A, to the highest in group C. Analysis of MGMT promoter methylation in tumor tissue was successfully performed in 19 patients. Results Overall, 20% of patients responded to treatment, for a disease control rate (DCR, responses plus stabilizations) of 47.5%. Groups A and B experienced a response rate of 40% and 26.5% respectively, while the corresponding value for group C was 10%. Out of 19 patients, MGMT promoter was found methylated in 12 cases among which a DCR of 66.5% was observed. All 7 patients with unmethylated MGMT promoter were progressive to fotemustine. Conclusion Low-dose fotemustine at 65–75 mg/m2 (induction phase) followed by 75–85 mg/m2 (maintenance phase) has an activity comparable to that of the conventional schedule. By determination of the MGMT promoter methylation status patients might be identified who are more likely to benefit from fotemustine chemotherapy.