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Simple Summary: This research was conducted to evaluate the impact of ipilimumab treatment in patients with metastatic melanoma when monotherapy with PD-1 inhibitors has failed. In particular, the aim was to evaluate the efficacy of ipilimumab in this setting based on the presence or absence of BRAF or NRAS mutations. The present study could allow us to understand when salvage treatment with ipilimumab would have the best impact, although an analysis on a larger patient cohort would be necessary. Background: When monotherapy with PD-1 inhibitors in metastatic melanoma fails, there are currently no standard second-line choices. In case of the unavailability of clinical trials, ipilimumab represents a possible alternative treatment. Methods: We collected data of 44 patients who received ipilimumab after the failure of PD-1 inhibitors from July 2017 to May 2023 at our Institute. Overall survival (OS), progression-free survival (PFS), and post-progression survival (PPS) based on BRAF or NRAS mutation status, sex, and the presence of brain metastases were estimated using the Kaplan–Meier method. Cox regression was used to evaluate independence in multivariate analysis. The objective response rate (ORR) was estimated based on RECIST 1.1. Results: Among the 44 patients enrolled in this study, 28 BRAF-wildtype, 9 BRAF-mutated, and 7 NRAS-mutated patients were identified. OS analysis showed a significant difference between wildtype and BRAF- or NRAS-mutated patients: 23.2 months vs 5.3 and 4.59, respectively, p = 0.017. The presence of brain metastases and BRAF or NRAS mutation were independent factors for mortality in multivariate analysis. Conclusions: In case of failure to enroll patients in innovative clinical trials, second-line ipilimumab still represents an effective therapy in patients with metastatic wildtype melanoma and in the absence of brain metastases. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aims to compare effectiveness and cost profile in non-small-cell lung cancer (NSCLC) patients harboring synchronous brain metastases (BMs) who received non-chemo first-line systemic therapy with or without advanced radiotherapy (aRT). A total of 177 lung cancer patients, of whom 58 were treated with systemic treatment (either TKIs or pembrolizumab) plus aRT (STRT) and 119 with systemic treatment alone, were selected. The addition of aRT to systemic treatment was associated with a significantly better OS (p = 0.020) and PFS (p = 0.041) than systemic therapy alone. The incremental cost-effectiveness ratio (ICER) value indicated an average cost of €3792 for each month of survival after STRT and confirmed clinical effectiveness but higher healthcare costs. This real-world study suggests that upfront aRT in this setting represents a valid treatment strategy, boosting the efficacy of emerging drug classes with sustainable costs for the health service. Aim: Healthcare administrative databases represent a valuable source for real-life data analysis. The primary aim of this study is to compare effectiveness and cost profile in non-small-cell lung cancer (NSCLC) patients harboring synchronous brain metastases (BMs) who received non-chemo first-line systemic therapy with or without advanced radiotherapy (aRT). Methods: Diagnostic ICD-9-CM codes were used for identifying all patients with a new diagnosis of lung cancer between 2012 and 2019. Among these, patients who had started a first-line systemic treatment with either TKIs or pembrolizumab, alone or in combination with intensity-modulated or stereotactic RT, were selected. Clinical outcomes investigated included overall survival (OS), progression-free survival (PFS), and time-to-treatment failure (TTF). The cost outcome was defined as the average per capita cumulative healthcare direct costs of the treatment, including all inpatient and outpatient costs. Results: The final cohort included 177 patients, of whom 58 were treated with systemic treatment plus aRT (STRT) and 119 with systemic treatment alone. The addition of aRT to systemic treatment was associated with a significantly better OS (p = 0.020) and PFS (p = 0.041) than systemic therapy alone. The ICER (incremental cost-effectiveness ratio) value indicated an average cost of €3792 for each month of survival after STRT treatment and confirmed clinical effectiveness but higher healthcare costs. Conclusions: This real-world study suggests that upfront aRT for NCLSC patients with synchronous BMs represents a valid treatment strategy, boosting the efficacy of novel and emerging drug classes with sustainable costs for the health service. Translational relevance: The present real-world study reports that the use of upfront advanced radiotherapyaRT and new-generation systemic agents, such as TKIs and pembrolizumab, may have higher oncological control and an improved cost-effectiveness profile than the use of new-generation systemic agents alone in NCLSC patients with synchronous brain metastases. Acquired evidence can also be used to inform policymakers that adding advanced radiotherapy results is a sustainable cost for the health service. Since approximately 50% of patients do not meet RCT inclusion criteria, a significant proportion of them is receiving treatment that is not evidence-informed; therefore, these results warrant further studies to identify the best radiotherapy timing and possible dose escalation approaches to improving treatment efficacy in patient subgroups not typically represented in randomized controlled trials. [ABSTRACT FROM AUTHOR]

Simple Summary: The landscape of treatment of patients with melanoma brain metastases (MBM) is continually evolving. We report the real-world data on 531 internationally treated patients with MBM before and after 2017 and their prognosis and treatment outcomes before the introduction of combined immunotherapy. We aimed to analyze trends in survival probability and their relevance to the currently used prognostic index, melanoma mol-GPA, and to some presumed prognostic and predictive factors not included in mol-GPA, such as symptoms occurrence and use of steroids. We have observed significant improvement in the survival of patients with the poorest mol-GPA prognosis. In our prognostic model, the presence of symptoms associated with brain metastases predicted a worse response to immune checkpoint inhibitors; however, symptoms without steroid use did not have prognostic significance. The prognosis of patients with MBM has been improving over the years due to the introduction of modern local and systemic treatment options across all mol-GPA prognostic groups. Stage IV melanoma patients develop melanoma brain metastases (MBM) in 50% of cases. Their prognosis is improving, and its understanding outside the context of clinical trials is relevant. We have retrospectively analyzed the clinical data, course of treatment, and outcomes of 531 subsequent stage IV melanoma patients with BM treated in five reference Italian and Polish melanoma centers between 2014 and 2021. Patients with MBM after 2017 had a better prognosis, with a significantly improved median of overall survival (OS) after 2017 in the worst mol-GPA prognostic groups (mol-GPA ≤ 2): a median OS >6 months and HR 0.76 vs. those treated before 2017 (CI: 0.60–0.97, p = 0.027). In our prognostic model, mol-GPA was highly predictive for survival, and symptoms without steroid use did not have prognostic significance. Local therapy significantly improved survival regardless of the year of diagnosis (treated before or after 2017), with median survival >12 months. Systemic therapy improved outcomes when it was combined with local therapy. Local surgery was associated with improved OS regardless of the timing related to treatment start (i.e., before or after 30 days from MBM diagnosis). Local and systemic treatment significantly prolong survival for the poorest mol-GPA prognosis. Use of modern treatment modalities is justified in all mol-GPA prognostic groups. [ABSTRACT FROM AUTHOR]

Anaplastic lymphoma kinase (ALK) fusions identify a limited subset of non–small cell lung cancer (NSCLC) patients, whose therapeutic approach have been radically changed in recent years. However, diagnostic procedures and clinical-radiological responses to specific targeted therapies remain heterogeneous and intrinsically resistant or poor responder patients exist. A total of 290 patients with advanced NSCLC defined as ALK+ by immunohistochemistry (IHC) and/or fluorescent in situ hybridisation (FISH) test and treated with single or sequential multiple ALK inhibitors (ALKi) from 2011 to 2017 have been retrospectively retrieved from a multicentre Italian cancer network database. In 55 patients with enough leftover tumour tissue, specimens were analysed with both targeted and customised next generation sequencing panels. Identified fusion variants have been correlated with clinical outcomes. Of the 55 patients, 24 received crizotinib as first-line therapy, 1 received ceritinib, while 30 received chemotherapy. Most of the patients (64%) received ALKi in sequence. An ALK fusion variant was identified in 73% of the cases, being V3 variant (E6A20) the most frequent, followed by V1 (E13A20) and more rare ones (e.g. E6A19). In three specimens, four new EML4-ALK fusion breakpoints have been reported. Neither fusion variants nor brain metastases were significantly associated with overall survival (OS), while it was predictably longer in patients receiving a sequence of ALKi. The presence of V1 variant was associated with progression-free survival (PFS) improvement when crizotinib was used (p = 0.0073), while it did not affect cumulative PFS to multiple ALKi. Outcomes to sequential ALKi administration were not influenced by fusion variants. Nevertheless, in V1+ patients a prolonged clinical benefit was observed. Fusion variant identification by NGS technology may add relevant information about rare chromosomal events that could be potentially correlated to worse outcomes. • NGS platforms add relevant information to refine diagnosis of ALK+ NSCLC patients. • RNA-based technologies allow the identification of rare/unknown EML4-ALK fusions. • Fusion variants correlate with clinical outcomes to single/sequential ALKi. • Molecular stratification of ALK+ patients may inform clinical strategies. [ABSTRACT FROM AUTHOR]

Introduction: Glioma is the most common primary brain cancer in adults. Long-term and progression-free survivals are dependent on the type and grade of glioma, as well as on the extent of resection and postoperative treatments. In Italy, it is unclear how long follow-up care should last and whether the primary care sector is either willing or able to take this on. The aim is to determine pathways of follow-up care and evaluate the professional attitude of doctors to prescribe to patient visits and exams after surgery.Methods: A retrospective study was performed on patients with glioma II and III who underwent surgery at tertiary care Neurological Institute Besta of Milan (FINCB) from 2012 to 2020. Data were collected through electronic medical records and inserted in an ad hoc developed database.Results: Three pathways have been identified: a common preliminary pathway (from the pre-operative visit to surgery) for all patients undergoing surgery for gliomas II and III and two follow-up pathways (with or without second surgery).Conclusions: FINCB has developed care pathways that are sometimes personalized according to the doctor's expertise and attitude to prescribe new examinations. Given the lack of guidelines on this issue, we can cautiously conclude that it is necessary to identify whether, in addition to standard care, personalized supportive care intervention and pathway plan can significantly improve patients' outcome. [ABSTRACT FROM AUTHOR]

Introduction: Primary brain tumors (PBTs) account for approximately 2% of all cancers and are associated with significant morbidity and mortality. However, only few epidemiological studies focus on PBTs in Italy. The aim of this study was to evaluate incidence, temporal trend, and survival rate of all PBTs in the province of Catania during the study period. Methods: All patients diagnosed with PBTs in the province of Catania during the 2003-2016 were identified through the local cancer registry. All cases were classified by histology according to 2007 WHO classification of central nervous system tumors, using the International Classification of Diseases for Oncology, 3rd edition codes. The incidence rate (IR) was calculated for all PBTs and by gender, histology, age-groups, and behavior. Trend analysis was performed using a piecewise log-linear model. Results: A total of 3,819 cases were identified with a female/male ratio of 1.45. The IR for all PBTs was 25.3/100,000 person-years (95% confidence interval 24.5–26.1). Most PBTs were nonmalignant (59.5%, IR = 15.0) with a female predominance. Conversely, malignant tumors (32.4%, IR = 8.2) were more common among men, with a female/male ratio of 0.9. The most frequently reported histology was meningioma (39.0%, IR = 9.8), followed by glioblastoma (11.6%, IR = 2.9). A peak of incidence was found in the 75–84 years age-group, with an IR of 77.6/100,000 person-years. Overall, no increase in incidence was observed along the study period. Conclusions: The IR of PBTs in the province of Catania is close to incidence reported worldwide. Further studies on risk factors are necessary. [ABSTRACT FROM AUTHOR]

The aim of this multi-center, retrospective/prospective cohort observational study was to evaluate outcomes in routine clinical practice of first-line chemo-immunotherapy with cis/carboplatin, pemetrexed and pembrolizumab in patients with advanced non-squamous non-small cell lung cancer (NSCLC) in 33 Italian centers. The outcome measure was to evaluate overall survival (OS) in a real-world patient population. Secondary endpoints were: progression-free survival (PFS), objective response rate (ORR), duration of response (DoR) and incidence of treatment-related adverse events (AEs). 1068 patients were enrolled at the time of data cut-off (January 31st, 2023), and 812 (76.0%) belonged to the retrospective cohort. Median age was 66 years (27−85), ECOG PS was ≥ 2 in 91 (8.6%) patients; 254 (23.8%) patients had brain metastases at baseline; 38 (3.6%) patients had tumor with PD-L1 expression ≥ 50%. After a median follow-up of 17.0 months (95% CI, 16.1–17.9), median OS was 16.1 months (95% CI, 14.4–18.8) and PFS was 9.9 months (95% CI, 8.8–11.2). Median DoR (n = 493) was 14.7 months (95% CI, 13.6–17.1). ORR was 43.4% (95% CI, 40.4–46.4). Any-grade AEs occurred in 636 (59.6%) patients and grade ≥ 3 in 253 (23.7%) patients. Most common grade ≥ 3 AEs were neutropenia (6.3%) and anemia (6.3%). First-line chemo-immunotherapy was effective and tolerable in this large, real-world Italian study of patients with advanced non-squamous NSCLC. Our results were in line with the KEYNOTE-189 registration study, also considering the low number of PD-L1 ≥ 50% patients included in our study. [Display omitted] • Chemo-immunotherapy is the standard front-line treatment for advanced non-squamous NSCLC. • Real-world data about platinum, pemetrexed and pembrolizumab regimen are needed. • We conducted a retrospective-prospective real-world study in 33 Italian Centers. • KEYNOTE-189 regimen was effective and safe in daily clinical practice. [ABSTRACT FROM AUTHOR]

Objective: Patients with seizures and epilepsies comorbid with cerebrovascular disorders (CVDs) or brain tumors (BTs) are managed by different specialists, including neurologists with expertise in epilepsy (epileptologists), CVDs, and neuro-oncology, as well as neurologists without special expertise (general neurologists), and also emergency room physicians (EPs), intensive care physicians, and neurosurgeons. It has never been studied how these specialists interact for the treatment of seizures or epilepsy in these patients.Methods: A survey was used to investigate how patients with such comorbidities are managed in hospitals in Italy.Results: One hundred and twenty-eight specialists from hospitals in all parts of Italy filled in a questionnaire. Epileptologists were in charge of treatment of epilepsy in about 50% of cases while acute seizures were treated mainly by general neurologists (52% of cases). Diagnostic, therapeutic, and assistance pathways (PDTAs) for CVD and BT epilepsies were declared by physicians in about half of the hospitals while in about a quarter, there were only informal agreements and, in the remaining hospitals, there were no agreements between specialists. CVD neurologists, specialists in internal medicine, and EP were most often in charge of treatment of epilepsy comorbid with CVD. General neurologists, neuro-oncologists, and neurosurgeons were included in teams that manage BT epilepsies while epileptologists were included only in a small percentage of hospitals.Conclusions: Clinical decisions on epilepsy or seizures in patients with such comorbidities are often handled by different specialists. A new team culture and PDTAs are needed to guarantee high standards of diagnostic and therapeutic procedures. [ABSTRACT FROM AUTHOR]

Objective: Brain metastases (BMs) from biliary tract cancer (BTC) are extremely rare. The aim of our study was to report the incidence of BMs in patients with BTC. Methods: We retrospectively analyzed a series of 450 patients with BTC. Presence of brain lesions was investigated only when symptoms were evident. Cumulative incidence, median overall survival (OS) from detection of BMs, median OS from cancer diagnosis, and median time from cancer diagnosis to detection of BMs were evaluated. Results: In our series, 6 patients developed BMs with an incidence of about 1.4%. Median OS from detection of BMs and from cancer diagnosis was, respectively, 3.7 (0.9-17.8) and 23 (9.9-57.6) months. Median time between cancer diagnosis and detection of BMs was 13.6 (7.3-52.8) months. Moreover, we observed a significant association between BMs and bone metastases (particularly vertebral lesions). Discussion: Despite the retrospective design, this is the first study evaluating the incidence of BMs among patients with BTC in Western countries. BMs from BTC remain atypical, although their incidence is probably a little higher than previously assumed. Patients with BMs had poor prognosis. Unpredictably, bone involvement occurred in 5 out of 6 patients. [ABSTRACT FROM AUTHOR]

Epilepsy is the most common comorbidity in patients with brain tumors. Study Aims: To define characteristics of brain tumor-related epilepsy (BTRE) patients and identify patterns of care. Nationwide, multicenter retrospective cohort study. Medical records of BTRE patients seen from 1/1/2010 to 12/31/2011, followed for at least one month were examined. Information included age, sex, tumor type/treatments, epilepsy characteristics, antiepileptic drugs (AEDs). Time to modify first AED due to inefficacy and/or toxicity was assessed with the Kaplan-Meier method and Cox proportional hazard models were used to identify predictors of treatment outcome. Enrolled were 808 patients (447 men, 361 women) from 26 epilepsy centers. Follow-up ranged 1 to 423 months (median 18 months). 732 patients underwent surgery, 483 chemotherapy (CT), 508 radiotherapy. All patients were treated with AEDs. Levetiracetam was the most common drug. 377 patients (46.7%) were still on first drug at end of follow-up, 338 (41.8%) needed treatment modifications (uncontrolled seizures, 229; side effects, 101; poor compliance, 22). Treatment discontinuation for lack of efficacy was associated with younger age, chemotherapy, and center with <20 cases. Treatment discontinuation for side effects was associated with female sex, enzyme-inducing drugs and center with > 20 cases. About one-half of patients with BTRE were on first AED at end of follow-up. Levetiracetam was the most common drug. A non enzyme-inducing AED was followed by a lower risk of drug discontinuation for SE. [ABSTRACT FROM AUTHOR]

Most reports emphasize that tumors and their treatments affect sexual function. To date, no studies have focused on sexual functioning in patients with brain tumors. Our study’s objective is to describe the sexual sphere of patients with brain tumors and examine the possible differences between patients who reported sexual dysfunctions and those who did not with respect to their psychological and functional status. We tested 46 patients with brain tumors. We used anad hocquestionnaire to assess patients’ subjective perception of their own sexual sphere. To assess patients’ psychological status, we used the following questionnaires:Hospital Anxiety and Depression Scale;Psychological Distress Inventory;EORTC QLQ-C30; EORTC QLQ-BN20.Fifty-eight percent of patients reported sexual disturbance. Our data showed that a lack of or decrease in sexual desire is the most common sexual problem reported by our patients (56%). Patients with sexual problems reported higher levels of anxiety and depression and a worse self-reported quality of life (QoL) than did those who did not perceive adverse changes in their sexual sphere. In addition, we found that patients with a better performance status (KPS) reported more changes in sexual behaviors than did those who had performance difficulties. Of the patients, 15.2% received information regarding possible changes in the sexual sphere by physicians. Additionally, 10.8 of 15.2% of the patients reported having explicitly requested information from physicians. The study demonstrated a relation between QoL and sexual function. Therefore, it would be important to encourage clinicians to ask questions regarding patients’ sexual issues, thus providing them with an opportunity to expose their difficulties and receive adequate support. [ABSTRACT FROM PUBLISHER]

Incidence of neuroepithelial Primary Brain Tumors (nPBT) varies, ranging from 7.3 to 11.6 cases/100,000/year across Europe. We present incidence and survival of nPBT in the Emilia-Romagna region (ER), Italy. This study is the largest in Southern Europe. Specialists in neurosurgery, neurology, neuroradiology, oncology, radiotherapy, genetics, and pathology of ER notified all suspected nPBT adult cases residing in ER (4,337,966 inhabitants) observed during 2009. Furthermore, through ICD-9 discharge codes, we identified and reviewed all possible cases. Neuroepithelial PBT diagnosis was based on histological or radiological findings. We included 400 incident nPBT cases, of which 102 (25%) were retrospectively identified. These latter were significantly older. The standardized incidence was 10.5/100,000/year (95% CI 9.4-11.5), higher for men. It was 9.2/100,000/year (95% CI 8.3-10.2) for astrocytic tumors, 0.6/100,000/year (95% CI 0.4-0.9) for oligodendroglial tumors, and 7.1 (95% CI 6.3-8.0) for glioblastoma (GBM). Among GBM patients, median survival was 249 days if prospectively identified vs. 132 days when identified through ICD-9 codes (p < 0.0001). The incidence of nPBT in the ER region is among the highest in the literature. Older patients were more likely to escape an active surveillance system. This should be considered when comparing incidence rates across studies, giving the increasing number of elderly people in the general population. [ABSTRACT FROM AUTHOR]

When investigating the association between brain tumors and use of mobile telephones, accurate data on tumor position are essential, due to the highly localized absorption of energy in the human brain from the radio-frequency fields emitted. We used a point process model to investigate this association using information that included tumor localization data from the INTERPHONE Study (Australia, Canada, Denmark, Finland, France, Germany, Israel, Italy, Japan, New Zealand, Norway, Sweden, and the United Kingdom). Our main analysis included 792 regular mobile phone users diagnosed with a glioma between 2000 and 2004. Similar to earlier results, we found a statistically significant association between the intracranial distribution of gliomas and the self-reported location of the phone. When we accounted for the preferred side of the head not being exclusively used for all mobile phone calls, the results were similar. The association was independent of the cumulative call time and cumulative number of calls. However, our model used reported side of mobile phone use, which is potentially influenced by recall bias. The point process method provides an alternative to previously used epidemiologic research designs when one is including localization in the investigation of brain tumors and mobile phone use. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme is one of the most frequent and aggressive primary tumors in the central nervous system, representing >60% of all brain tumors in adults. Despite treatment, prognosis remains poor with most if not all patients experiencing disease recurrence and a 2-year survival rate of 27%. At present, no confirmed standard treatment exists for recurrent glioblastoma. Regorafenib is one of the few options available, based on results from the REGOMA trial. In the present study, a real-life retrospective investigation on the role of regorafenib in patients with recurrent glioblastoma (>60 years old) from two main Oncological Units in South Italy (Azienda Ospedaliera Universitaria Luigi Vanvitelli, Naples, Italy and Ospedale Civile San Giovanni di Dio, Frattamaggiore, Naples, Italy), was performed. The primary endpoint was overall survival (OS), whereas progression-free survival (PFS), objective response rate and disease control were secondary endpoints. Survival was then analyzed according to age, isocitrate dehydrogenase (IDH) and methylated methylguanine-DNA-methyltransferase (MGMT) status. A total of 56 patients met the eligibility criteria. The intention to treat population median PFS (mPFS) was 4.1 months and median OS (mOS) was 6.8 months. Age did not appear to have a significant influence on mPFS. mOS in MGMT-methylated patients was improved compared with that of the unmethylated group (7.7 months vs. 5.6 months). Both mOS and mPFS were longer in IDH-mutant patients. The present study was one of the first real life analyses of regorafenib in recurrent glioblastoma. The results were in line with the REGOMA trial. Age did not appear to be a prognostic factor, thus suggesting that treatment choice should not be different in elderly. MGMT methylation appeared to influence OS. To the best of our knowledge, this was the first report of regorafenib activity in older patients and, while the results were statistically significant, these should be confirmed in further studies. [ABSTRACT FROM AUTHOR]

Background: In 2017, the European Association of Neuro-Oncology (EANO) published the guideline for palliative care in adults with glioma. The Italian Society of Neurology (SIN), the Italian Society for Palliative Care (SICP), and the Italian Association for Neuro-Oncology (AINO) joined forces to update the guideline, and adapt it to the Italian context., Aim: We involved patients, caregivers, and (herein presented) healthcare professionals (HPs) in the formulation of the guideline clinical questions., Design and Participants: Online survey of Italian HPs experienced in the care of patients with glioma. Participants rated the importance of 14 pre-specified intervention topics on a 0/10 scale and gave their free comments., Results: Of 244 participants, 149 (61%) were palliative medicine (PM) HPs and 95 Neuro HPs. Their mean age was 48.9 years, 63% were women, and 48% had over 12 years of experience in the care of glioma patients. Physicians were 68%, followed by nurses (28%), psychologists (7%), therapists (3%), and social workers (2%). Most HPs rated the pre-specified topics as important (score ≥ 7) or critical (score ≥ 9), with some differences between PM and Neuro HP groups. There were 58 free comments: 46 (78%) on nine pre-specified topics, and 13 on four new topics, three of which were guideline-pertinent ("caregiver's support and education"; "family physician's training in neuro-oncology"; and "PM HPs' training in neuro-oncology")., Conclusions: Participation in the survey was high and information-rich, between-group rating differences reflecting HP background. Participants endorsed the 14 intervention topics devised by the guideline panel and identified three additional topics., (© 2023. Fondazione Società Italiana di Neurologia.)

Background/aim: Meningiomas of the anterior cranial fossa are often diagnosed after impaired visual function occurrence. Some epidemiologic studies suggest an association between exogenous or endogenous hormones and meningioma risk. The aim of this study is to briefly review the literature and relate a case report. Patient and methods: This study presents a case of a 51-year-old woman with a moderate visual loss of 6/10 and markedly constricted visual field in the right eye. A normal visual acuity and peripheral reduction of visual field in the left eye was documented. During medical interview, she reported a prolonged assumption of oral contraceptive. Her visual deterioration had progressed over the previous 3 months and was associated with occasional headache. MRI scanning showed a small optic pathway meningioma. Results: After various examinations, it was decided to ‘wait and see’ and no therapy was administered. The patient noticed a progressive improvement in the vision in her right eye, with corresponding improvement in the bilateral visual field. Conclusion: The case reports on the spontaneous resolution of visual loss due to the volume reduction of the anterior visual pathway compressive intracranial meningioma after interruption of prolonged assumption of oral contraceptive and focuses on the correlation between sexual hormone pathway and intracranial meningioma. [ABSTRACT FROM AUTHOR]

Background: Brain metastases are the most common brain tumors, being one of the most frequent neurological complications of systemic cancer and an important cause of morbidity and mortality. Stereotactic Radiosurgery is efficacious and safe in treatment of brain metastases, with good local control rates and low adverse effects rate. Large brain metastases present some issues in balancing local control and treatment-related toxicity. Adaptive staged-dose GammaKnife Radiosurgery (ASDGKRS) has shown to be a safe and effective treatment for large brain metastases. Methods: We retrospectively analyzed and compared with data from review of literature our series of patients treated with Adaptive staged-dose GammaKnife Radiosurgery for large brain metastases in ASST Grande Ospedale Metropolitano Niguarda, Milan - Italy, between February 2018 and May 2020. Results: Forty patients with large brain metastases underwent Adaptive staged-dose GammaKnife Radiosurgery, with median prescription dose of 12Gy and a median interval between stages of 30 days. At 3-months follow-up the survival rate was 75,0% with a local control rate of 100%. At 6-months follow-up the survival rate was 75,0% with a local control rate of 96.7%. The mean volume reduction was 21.81 cm3 ( 16.76 - 26.86; IC95%). The difference between baseline volume and 6-months follow-up volume was statistically significant. Conclusions: Adaptive staged-dose GammaKnife Radiosurgery is a safe, non invasive and effective treatment for brain metastases, with a low rate of side effects. Large prospective trials are needed to strengthen data obtained about the effectiveness and safety of this technique in managing large brain metastases. [ABSTRACT FROM AUTHOR]

Aim: Brain metastases (BMs) are a common event in the progression of many human cancers. The aim of this study was to evaluate the potential prognostic factors for the clinical identification of a subgroup of patients that could benefit from whole brain conformal radiotherapy (WBRT). Materials and Methods: From January 2010 to February 2014, 80 patients with a diagnosis of BMs underwent WBRT at our Radiation Oncology Department, San Luigi Hospital, Italy. Among them, 36 medical records were retrospective reviewed. Gender, age, Karnofsky performance status (KPS), number of BMs on computed tomography and/or magnetic resonance images, presence or absence of perilesional edema, presence or absence of necrosis pattern, and histology of primary tumor were analyzed. Univariate and multivariate analyses were performed. Results: In our cohort of patients, significant prognostic factors for 20 months overall survival was KPS > 70, while a statistical trend (P = 0.098) was registered regarding primary breast. Conclusion: WBRT can be still considered a standard and effective treatment in patients with BMs. High KPS and breast cancer primary tumor seem to be useful parameters for characterize a subgroup of patients with more favorable prognosis. [ABSTRACT FROM AUTHOR]

The main aims of this study were to evaluate the intensity of stress, anxiety and depression as well as the effectiveness of coping strategies adopted pre-operatively in brain neoplasm patients. A descriptive-explorative study design was undertaken. During 2008, patients admitted to a large Italian hospital neurosurgical unit with their first ( n = 21) or recurrent ( n = 15) brain neoplasm, on the day before their surgical procedure, were consecutively recruited into the study. The Perceived Stress Scale, the Hospital Anxiety and Depression Scale and the Jalowiec Coping Scale were administered via face-to-face interview. Patients with their first occurrence of neoplasm perceived the same stress intensity as those with recurrent neoplasm (mean ± standard deviation: 14.9 ± 6.7 versus 17.2 ± 8.8, p = 0.36). They also reported the same likelihood of anxiety at a borderline level (odds ratio (OR) 4.88, 95%CI 0.42 to 40.97, p = 0.06) and at a clinically relevant level (OR 0.32, 95%CI 0.01 to 5.37, p = 0.35) as well as the same likelihood of depression at a borderline level (OR 1.25, 95%CI 0.20 to 8.40, p = 0.78). Only one case of clinically relevant depression emerged among patients at their first diagnosis. Patients at their first occurrence, as well as those at recurrence, reported that they adopted optimistic coping strategies (mean 2.20, 95%CI 2.01 to 2.38 versus mean 1.96, 95%CI 1.71 to 2.20) and sought support (mean 1.81, 95%CI 1.58 to 2.05 versus mean 1.89, 95%CI 1.63 to 2.15). According to the findings of this exploratory study, on the pre-operative day, brain neoplasm patients at their first diagnosis and at recurrence wish to confront the situation: they adopt optimistic coping strategies, they seek support and they wish to take a constructive problem-solving approach. Knowledge of the intensity of stress, anxiety and depression as well as the coping strategies adopted by the patients is important for clinicians in their efforts to tailor care to patients' individual needs. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background. Venous thromboembolism (VTE) and brain metastases (MTS) are significant clinical problems in the cancer patient population. Brain MTS and deep vein thrombosis are life-threatening conditions because of the risk of fatal endocranic hypertension and pulmonary embolism. Low molecular weight heparin (LMWH) is a major treatment for cancer patients suffering from VTE with regard to the management of the acute phase and subsequent secondary prophylaxis. Treatment with anticoagulants is feared because of the risk of triggering a massive intracranial hemorrhage.Methods. The medical records of patients with hypercoagulability-related complications and carrying brain MTS treated with LMWH, in a 10-year period, were scrutinized. The authors aimed to focus on the occurrence of intracranial hemorrhage in anticoagulated patients; furthermore, data were collected with regard to the characteristics of the administered LMWHs along with the duration and dosing of the anticoagulative treatment.Results. A total of 38 patients (pts) carrying an intracranial metastatic tumor were administered LMWHs: calcium nadroparin (32 pts); enoxaparin (2 pts); reviparin (2 pts); parnaparin (2 pts). Reason for LMWH therapy: deep vein thrombosis and/or pulmonary embolism (15 pts); superficial thrombophlebitis (15 pts); intracardiac thrombus (1 pt); mild DIC (5 pts); acute DIC (1 pt); Raynaud phenomenon (1 pt); atrial fibrillation (1 pt). Median duration of LMWH therapy: 13 weeks (range 1–52). None of the patients developed clinical and/or radiographic findings imputable to intracranial hemorrhage.Conclusion. There is no standard medical approach for the management of patients who require anticoagulant treatment and are suffering from brain MTS. These patients as necessary, might be anticoagulated with LMWH and its dose reduction is to be considered. [ABSTRACT FROM PUBLISHER]

Simple Summary: Neurofibromatosis type 1 is a relatively frequent neurocutaneous and tumor predisposition syndrome, which has been associated with a variety of neurological manifestations, including an increased incidence of seizures. Epilepsy in NF1 has been investigated over time by a number of studies, but most of these works were performed on small samples and often suffered from selection biases. Our study aimed to provide additional epidemiologic, clinical, and molecular data to the literature by retrospectively analyzing a large cohort of consecutive unselected patients affected with NF1. Such data may provide a better insight into the matter to other authors and clinicians alike. An increased lifetime risk of epilepsy has been reported in neurofibromatosis type 1 (NF1) patients, ranging between 4% and 14%. To further analyze the correlation between NF1 and epilepsy, we retrospectively reviewed the epidemiologic, clinical, radiological, and molecular data of 784 unselected patients diagnosed with NF1 and referred to the neurofibromatosis outpatient clinics at the University Hospital of Padua. A crude prevalence of epilepsy of 4.7% was observed. In about 70% of cases, seizures arose in the context of neuroradiological findings, with the main predisposing factors being cerebral vasculopathies and hydrocephalus. In the absence of structural abnormalities, the prevalence of epilepsy was found to be 1.27%, which is approximately equal to the total prevalence in the general population. NF1 patients with seizures exhibit a higher incidence of intellectual disability and/or developmental delay, as well as of isolated learning disabilities. The comparison of causative NF1 mutations between the two groups did not reveal a specific genotype–phenotype correlation. Our data refine the current knowledge on epileptological manifestations in NF1 patients, arguing against the hypothesis that specific mechanisms, inherent to neurofibromin cellular function, might determine an increased risk of epilepsy in this condition. [ABSTRACT FROM AUTHOR]

Summary: Objective: To verify if, in the last two decades, there have been any changes in epidemiological, clinical, diagnostic, therapeutic and prognostic aspects of patients with brain abscess. Method: We studied retrospectively 100 patients discharged over a 17-year period from Ca’ Foncello Regional Hospital, Treviso, Italy with a diagnosis of brain abscess. Results: Post-surgical abscesses were more frequent than those related to contiguous infections and the spectrum of etiologic agents was very heterogeneous. A cerebral neoplasm was the initial neuroradiological diagnosis in 13 patients; 72 patients underwent a neurosurgical procedure. A comatose state at presentation was associated with an unfavourable outcome. Conclusion: With the exception of some epidemiological aspects, which varied from the literature, in spite of the improvements in diagnostic procedures and treatment, no significant changes occurred in the prognosis of patients with brain abscess. [Copyright &y& Elsevier]

To determine whether the occurrence of first and second primary malignancies in first-degree relatives of cancer patients aged 0–25 years (probands) differed from that in the general population, a cohort study was carried out on 860 relatives of 265 probands living in the province of Trieste, Italy. During the follow-up period (median duration = 28 years, 25th–75th percentile = 20–34), the relatives developed 103 first primary cancers vs. 88.9 expected for a standardized incidence ratio (SIR) of 1.2 (p = 0.2). Significantly elevated risks were found for melanoma in the parents of probands aged 15–25 years with melanoma (SIR = 15.0, p = 0.002), for hemolymphatic malignancies in the fathers of probands aged 0–14 years with brain tumors (SIR = 13.3, p = 0.0005) and for hemolymphatic cancers in relatives as a whole of probands aged 15–25 years with lymphomas (SIR = 4.5, p = 0.01). During the follow-up period, 7 relatives with a first primary cancer had a subsequent malignancy vs. 4.2 expected for an SIR of 1.7 (p = 0.3). Our results indicate that young cancer patients per se should not to be considered as a factor that usually increases the risk of developing malignant tumors among their first-degree relatives, except when a known cancer family syndrome or predisposition is recognized. © 2003 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The natural history of neuroectodermal tumors is still debated as far as prognostic factors are concerned; the same uncertainty applies to the optimal radiotherapy schedule and even more to the presumptive additive effect of chemotherapy. The rarity of these tumors and the heterogeneity of management make interpretation of literature data also more difficult. We evaluated clinical course in a cohort of 39 patients, including 31 with medulloblastoma (MB) and 8 with primitive neuroectodermal tumors (PNET). All patients were treated with radiotherapy, a standardized chemotherapy protocol including PCV scheme, and a second-line chemotherapy with cisplatin and etoposide (VP16) at recurrence. In 27 patients, intrathecal chemotherapy was also delivered. Median follow-up was 10.8 years. Overall, PNET had a worse outcome as compared to MB: median survival times were 42.8 vs. 92.6 months, respectively (p = 0.05). At 5 years, 45% of MB patients are alive. No significant difference in disease-free period was found between patients of different age, desmoplastic variant, tumor localization, or extent of surgery. Patients considered to be "high risk" had a significantly shorter disease-free period as compared with low-risk patients (27 vs. 54.7 months, p = 0.04). Systemic or intrathecal chemotherapy did not influence progression-free survival (PFS). However, in the majority of chemotherapy-treated patients, a low-dose craniospinal radiotherapy was also delivered. This combination of treatments may have avoided the expected increased percentage of failure. Moreover, more than half of recurrent patients had a partial response to chemotherapy that extended survival for approximately 3 years. Repeated surgery and chemotherapy at recurrence favorably influenced survival time. [ABSTRACT FROM AUTHOR]

Brain tumours (BTs) are one of the most frequent tumour types in young people. We explored the association between tap water, exposure to trihalomethanes (THM) and nitrate and neuroepithelial BT risk in young people. Analysis of tap water consumption were based on 321 cases and 919 appendicitis controls (10–24 years old) from 6 of the 14 participating countries in the international MOBI-Kids case-control study (2010–2016). Available historical residential tap water concentrations of THMs and nitrate, available from 3 countries for 86 cases and 352 controls and 85 cases and 343 for nitrate, respectively, were modelled and combined with the study subjects' personal consumption patterns to estimate ingestion and residential exposure levels in the study population (both pre- and postnatal). The mean age of participants was 16.6 years old and 56% were male. The highest levels and widest ranges for THMs were found in Spain (residential and ingested) and Italy and in Korea for nitrate. There was no association between BT and the amount of tap water consumed and the showering/bathing frequency. Odds Ratios (ORs) for BT in relation to both pre- and postnatal residential and ingestion levels of THMs were systematically below 1 (OR = 0.37 (0.08–1.73)) for postnatal average residential THMs higher than 66 μg/L. For nitrate, all ORs were above 1 (OR = 1.80 (0.91–3.55)) for postnatal average residential nitrate levels higher than 8.5 mg/L, with a suggestion of a trend of increased risk of neuroepithelial BTs with increasing residential nitrate levels in tap water, which appeared stronger in early in life. This, to our knowledge, is the first study on this topic in young people. Further research is required to clarify the observed associations. • Brain tumours are one of the most frequent tumour types in young people. • Trihalomethanes and nitrate are possible carcinogens. • To our knowledge, this is the first study focusing on this topic in young people. • We found a possible increased risk for nitrate, and no association for trihalomethanes. [ABSTRACT FROM AUTHOR]

The role of parental occupational exposure in childhood brain tumors was investigated in a population-based case-control study grouping 251 cases and 601 controls from three European centers: Milan (Italy), Paris (France), and Valencia (Spain). Parental occupational exposure to solvents and polycyclic aromatic hydrocarbons (PAH) during the five-year period before birth was estimated using a job-exposure matrix developed earlier in the same countries. Odds ratios (OR) of brain tumors for each occupation and occupational exposure were estimated by logistic regression, adjusting for child's age, gender, exposure to tobacco smoke and ionizing radiation, mother's age and years of schooling, and center. The risk of childhood brain tumors rose when fathers worked in agriculture (OR = 2.2, 95 percent confidence interval [CI] = 1.0-4.7) and motor-vehicle-related occupations. In the latter group, the risk increased for primitive neuroectodermal tumors in particular (OR = 2.7, CI = 1.1-6.6). Astroglial tumors were more frequent among children of mothers in health services (OR = 2.2, CI = 1.0-4.9). Paternal exposure to PAHs was associated with an increased, but not dose-related, risk of primitive neuroectodermal tumors (OR = 2.0, CI = 1.0-4.0), and maternal exposure to solvents at a high level was associated with an increased risk of both astroglial (OR = 2.3, CI = 0.9-5.8) and primitive neuroectodermal tumors (OR = 3.2, CI = 1.0-10.3). [ABSTRACT FROM AUTHOR]

The editor focuses on breast cancer among women diagnosed in 2012 along with metastatic breast cancer (MBC) associated with prognosis. Topics include the aim of therapy of MBC to control symptoms while decreasing toxicities to prolong survival, eribulin mesylate which is a synthetic analog of halichondrin B isolated from a marine sponge and effectiveness of eribulin.

In this multicenter, observational study, the authors assessed the prevalence of neuropsychiatric side effects from medications in subjects with tumor-related epilepsy. Levetiracetam was found to have the highest prevalence of such side effects. [ABSTRACT FROM AUTHOR]

Metastatic disease is a common complication of the most advanced malignancies. It may compromise the patients' quality of life, often posing a greater risk than the primary disease itself. Currently, several different therapeutic approaches are available to palliate or cure (single metastasis with primary neoplasm under control - radical surgery) secondary disease. In particular, radiation therapy is widely used, as it often leads to full or at least partial functional recovery, depending on the number and location of metastases. The aim of our study was to evaluate whether clinical improvement subsequent to radiation therapy may be related to anatomical recovery of the site of metastasis in cancer patients with metastatic disease. Given the heterogeneity of the diseases considered and the general complex conditions of the patients, a single method could not be used to evaluate the response to radiation treatment and its correlation with the performance status (PS). Thus, depending on the specific disease being assessed, we divided the patients into different groups. Patients in the same group were followed up with the same methods. This correlation was noted in a very high percentage of patients, predominantly in patients with vertebral and brain metastases. Moreover, we investigated the use of magnetic resonance imaging (MRI)-diffusion weighted imaging (DWI) in the study of spinal metastases. We propose its use in the local evaluation of vertebral secondary lesions, both in the diagnostic phase and during the assessment of treatment efficacy. [ABSTRACT FROM AUTHOR]

QUESTION How do patients describe their experiences before, during, and immediately after awake craniotomy? DESIGN Qualitative study using a phenomenological approach. SETTING Neurosurgical unit in a hospital in Udine, Italy. PARTICIPANTS Purposeful sample of 21 patients >18 years of age (age range 20-63 y, 52% women) who had a brain neoplasm, no language or cognitive disabilities, and were to have surgery under local anaesthesia. METHODS Patients participated in 2 individual interviews (1 on the day before and 1 on the day after surgery), each lasting 30-60 minutes. Interviews were audiotaped and transcribed. Data were analysed thematically. MAIN FINDINGS 4 themes described patients' experiences of awake craniotomy. (1) Patients focused on self-preservation before surgery. They felt that having surgery under local anaesthesia was almost non-negotiable because they believed it would reduce collateral damage and prevent disabilities. However, they also felt they had an active role in decisions: "It is my role during the operation to help the neurosurgeon understand where it is dangerous to touch and where he should be operating." Most patients were more afraid of potential movement deficits after surgery than language or speech deficits. Some felt anguish or terror, whereas others were confident of the surgical outcome. No patients talked about their prognosis, survival, or potential cognitive deficits. (2) Patients also described working out their intraoperative role before surgery. They coped with intense feelings about the surgery by using the support of family or others and doing things to prepare for surgery or distract themselves (eg, write, pray, watch television). Patients often wanted to protect their families: "The world is not only falling apart for me but also for my family. I'm keeping them out of it." They felt emotional when imagining the surgery and were afraid of not being able to control their actions during the procedure. They focused on their own role in surgery rather than thinking about the procedure per se. Patients needed time alone to prepare for their role in surgery but also needed to spend time with family. (3) During surgery, it was important for patients to keep the situation under control. Although patients felt impotent, they concentrated on the activities of others, waited anxiously for their first task, and took on their required role immediately. Patients vividly remembered the craniotomy, including the noise, vibrations, and uncomfortable position. It was important for patients to have information during surgery. They tried to remain in control and imagine what was being done at each stage of surgery. They listened to surgical staff talking to one another, talked directly to the surgeon, and were reassured when surgeons gave positive feedback. 3 patients did not feel any pain, 1 had severe pain, and the others had moderate pain. (4) After surgery, patients focused on reassuring themselves and others. They were surprised to feel so well, although they were tired and relieved to meet with family and return to a kind of normality. They did not talk about their illness but took stock of their feelings and language or motor disabilities. They described their experience as "unreal" and "out of this world." CONCLUSION 4 themes described the experience of awake craniotomy for patients before, during, and after surgery: self-preservation, working out the intraoperative role, keeping the situation under control, and reassuring themselves and others. [ABSTRACT FROM AUTHOR]