Epileptogenesis and Tumorigenesis in Glioblastoma: Which Relationship?

Epilepsy is reported in 29–52% of patients with glioblastoma (GBM) and has an important role in the natural history of this tumor and patients’ life quality. Although GBM is less epileptogenic than lower-grade gliomas, seizures are usually more difficult to control with common antiseizure medications; drug resistance is found in 20% of cases. Recent studies suggest that seizures at the onset of GBM could be a possible favorable independent prognostic factor in patients. Moreover, a growing body of evidence shows that many molecular mechanisms that influence epileptogenesis often regulate GBM growth and invasiveness, sometimes favoring or counteracting the tumor, respectively. The better-characterized players include glutamate, gamma-aminobutyric acid, aquaporin-4, and hypoxia-activated molecules. However, currently available data on the molecular basis of epileptogenesis, tumorigenesis, and their relationship is incomplete or discordant and further research is urgently needed on this topic

Radiation-induced breast angiosarcoma: report of two patients after accelerated partial breast irradiation (APBI) and review of the literature

BACKGROUND: Angiosarcoma may rarely complicate radiotherapy of breast cancer. This so-called radiation-induced angiosarcoma (RIAS) occurs in less than 0.3% of patients that underwent breast conservation surgeries, usually years after completion of radiotherapy. CASE PRESENTATION: we introduce two cases of invasive ductal carcinoma who underwent lumpectomy and accelerated partial breast irradiation (APBI) as an alternative protocol to whole breast irradiation (WBI). They received adjuvant partial breast radiotherapy on tumor cavity for a total dose of 38.5 Gy in 10 fractions in 5 days using 3D-external-beam RT. In both cases, RIAS occurred eight years after radiotherapy, in the sub-cicatricial area in one patient and outside the irradiated area in the other one. They both underwent radical surgery and chemotherapy was performed in one patient. DISCUSSION: The underlying mechanism for development of RIAS is not well known, but its incidence seems to be increasing. RIAS after partial breast irradiation is very rare and has been reported in two cases so far. As it may be suggested in case 2, it is still a matter of debate if the risk of radiation-induced sarcoma is radiation-dose dependent. Although mastectomy is considered as a standard treatment, choice of treatment should be made according to the patient’s specifications. CONCLUSION: There are very few studies in the literature that report RIAS after APBI. Present study is the only one reporting two cases after the external 3D technique APBI. Prognosis of RIAS remains poor. Only a careful evaluation in a multidisciplinary context can offer to the patients the best result in terms of local control and surviva

Efficacy and Tolerability of Perampanel in Brain Tumor-Related Epilepsy: A Systematic Review

(1) Background: Epilepsy is a frequent comorbidity in patients with brain tumors, in whom seizures are often drug-resistant. Current evidence suggests that excess of glutamatergic activity in the tumor microenvironment may favor epileptogenesis, but also tumor growth and invasiveness. The selective non-competitive -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist perampanel (PER) was demonstrated to be efficacious and well-tolerated in patients with focal seizures. Moreover, preclinical in vitro studies suggested a potential anti-tumor activity of this drug. In this systematic review, the clinical evidence on the efficacy and tolerability of PER in brain tumor-related epilepsy (BTRE) is summarized. (2) Methods: Five databases and two clinical trial registries were searched from inception to December 2022. (3) Results: Seven studies and six clinical trials were included. Sample size ranged from 8 to 36 patients, who received add-on PER (mean dosage from 4 to 7 mg/day) for BTRE. After a 6–12 month follow-up, the responder rate (% of patients achieving seizure freedom or reduction 50% of seizure frequency) ranged from 75% to 95%, with a seizure freedom rate of up to 94%. Regarding tolerability, 11–52% of patients experienced non-severe adverse effects (most frequent: dizziness, vertigo, anxiety, irritability). The retention rate ranged from 56% to 83%. However, only up to 12.5% of patients discontinued the drug because of the adverse events. (4) Conclusions: PER seems to be efficacious, safe, and well-tolerated in patients with BTRE. Further randomized studies should be conducted in more homogeneous and larger populations, also evaluating the effect of PER on tumor progression, overall survival, and progression-free survival

Dyspnoea in a 72-year-old woman

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Radiotherapy for the Primary Tumor in Patients with Metastatic Rectal Cancer

Patients with metastatic rectal cancer (mRC) have a poor prognosis and suffer from several symptoms like bleeding, pain, and obstruction. Radiation therapy (RT) has been used both for palliation and improvement of overall survival (OS) in potentially curable patients. However, treatment in this setting is debated and a recent literature review included only studies published before 2000. Therefore, an analysis of literature was performed including only studies published in recent years (2010\ue2\u80\u932016) to better evaluate the effect of modern RT in these patients. The analysis of nine reviewed studies (six retrospective and three phase II) showed that RT is able to achieve pain, bleeding, and obstruction response rate of 79, 87, and 78%, respectively. Moreover, in patients receiving radio-chemo-surgical combined modality treatment, median survivals ranging between 30 and 38\uc2\ua0months were recorded, with 5-year survival up to 55% of patients. RT was generally well tolerated with the most common reported side effect being diarrhea/proctitis. Further studies in this field are needed to establish the best therapeutic sequences, to define the optimal RT dose and fractionation, and to evaluate the clinical results in terms of quality of life (QoL)

Serological response to hepatitis B virus vaccine in HIV-infected children in Tanzania

BACKGROUND: HIV-infected children have a lower seroconversion rate to hepatitis B virus (HBV) immunization than healthy children. Previous studies have produced conflicting results on CD4 cell counts as predictors of vaccine response. No study has evaluated the response rate to HBV vaccination in HIV-infected children receiving highly active antiretroviral therapy (HAART). Our aim was to vaccinate HIV-infected children living in a close community and to investigate the anamnestic response rate after vaccination with its predictors. METHODS: Eighty-four HIV-positive children aged 1-10 years who were negative for antibodies to the HBV core antigen (anti-HBc) completed immunization with three doses of 5 microg HBVAXPRO (Aventis, Milan, Italy). Quantitative testing for antibodies to the HBV surface antigen (anti-HBs) was performed: a seroprotective titre was defined as anti-HBs>10 mUI/mL. RESULTS: After the vaccination, the anti-HBs seroconversion rate was 59.5%. It was higher in individuals in Centers for Disease Control and Prevention (CDC) immune category 1 than in those in CDC categories 2 and 3. Seroconversion was found in 70.8% of HAART-treated and 44.4% of treatment-na\uefve children. In multivariable models, HAART use and absolute CD4 cell counts were independently associated with probability of seroconversion and with higher anti-HBs titres. CONCLUSIONS: We found a higher seroconversion rate compared with previous studies in HIV-infected children. In children who are candidates to receive antiretroviral therapy, it may be advisable to defer HBV vaccination until after treatment initiation

Adenoid Cystic Carcinoma/Basal Cell Carcinoma of the Prostate: Overview and Update on Rare Prostate Cancer Subtypes

Adenoid cystic carcinoma/basaloid cell carcinoma of the prostate (ACC/BCC) is a very rare variant of prostate cancer with uncertain behavior. Few cases are reported in the literature. Data on treatment options are scarce. The aim of our work was to retrospectively review the published reports. Thirty-three case reports or case series were analyzed (106 patients in total). Pathological features, management, and follow-up information were evaluated. Despite the relatively low level of evidence given the unavoidable lack of prospective trials for such a rare prostate tumor, the following considerations were made: prostate ACC/BCC is an aggressive tumor often presenting with locally advanced disease and incidental diagnosis occurs during transurethral resection of the prostate for urinary obstructive symptoms. Prostate-specific antigen was not a reliable marker for diagnosis nor follow-up. Adequate staging with Computed Tomography (CT) scan and Magnetic Resonance Imaging (MRI) should be performed before treatment and during follow-up, while there is no evidence for the use of Positron Emission Tomography (PET). Radical surgery with negative margins and possibly adjuvant radiotherapy appear to be the treatments of choice. The response to androgen deprivation therapy was poor. Currently, there is no evidence of the use of truly effective systemic therapies

Individually optimized stereotactic radiotherapy for pancreatic head tumors: A planning feasibility study

AimAim of this study was to perform a planning feasibility analysis of a 3-level dose prescription using an IMRT-SIB technique.BackgroundRadiation therapy of locally advanced pancreatic cancer should administer a minimum dose to the duodenum and a very high dose to the vascular infiltration areas to improve the possibility of a radical resection.Materials and methodsFifteen patients with pancreatic head adenocarcinoma and vascular involvement were included. The duodenal PTV (PTVd) was defined as the GTV overlapping the duodenal PRV. Vascular CTV (CTVv) was defined as the surface of contact or infiltration between the tumor and vessel plus a 5[[ce:hsp sp="0.25"/]]mm margin. Vascular PTV (PTVv) was considered as the CTVv plus an anisotropic margin. The tumor PTV (PTVt) was defined as the GTV plus a margin including the PTVv and excluding the PTVd. The following doses were prescribed: 30[[ce:hsp sp="0.25"/]]Gy (6[[ce:hsp sp="0.25"/]]Gy/fraction) to PTVd, 37.5[[ce:hsp sp="0.25"/]]Gy (7.5[[ce:hsp sp="0.25"/]]Gy/fraction) to PTVt, and 45[[ce:hsp sp="0.25"/]]Gy (9[[ce:hsp sp="0.25"/]]Gy/fraction) to PTVv, respectively. Treatment was planned with an IMRT technique.ResultsThe primary end-point (PTVv Dmean[[ce:hsp sp="0.25"/]]>[[ce:hsp sp="0.25"/]]90%) was achieved in all patients. PTVv D98%[[ce:hsp sp="0.25"/]]>[[ce:hsp sp="0.25"/]]90% was achieved in 6 patients (40%). OARs constraints were achieved in all patients.ConclusionsAlthough the PTVv D95%[[ce:hsp sp="0.25"/]]>[[ce:hsp sp="0.25"/]]95% objective was achieved only in 40% of patients, the study showed that in 100% of patients it was possible to administer a strongly differentiated mean/median dose. Prospective trials based on clinical application of this strategy seem to be justified in selected patients without overlap between PTVd and PTVv

State of the Art in Combination Immuno/Radiotherapy for Brain Metastases: Systematic Review and Meta-Analysis

Objectives: Common origins for brain metastases (BMs) are melanoma, lung, breast, and renal cell cancers. BMs account for a large share of morbidity and mortality caused by these cancers. The advent of new immunotherapeutic treatments has made a revolution in the treatment of cancer patients and particularly, as a new concept, if it is combined with radiotherapy, may lead to considerably longer survival. This systematic review and meta-analysis aimed to evaluate the survival rate and toxicities of such a combination in brain metastases. Methods: To perform a systematic review of the literature until January 2021 using electronic databases such as PubMed, Cochrane Library, and Embase; the Newcastle–Ottawa Scale was used to evaluate the quality of cohort studies. For data extraction, two reviewers extracted the data blindly and independently. Hazard ratio with 95% confidence interval (CI), fixed-effect model, and inverse-variance method was calculated. The meta-analysis has been evaluated with the statistical software Stata/MP v.16 (The fastest version of Stata). Results: In the first step, 494 studies were selected to review the abstracts, in the second step, the full texts of 86 studies were reviewed. Finally, 28 studies were selected consisting of 1465 patients. The addition of IT to RT in the treatment of brain metastasis from melanoma and non-small-cell lung carcinoma was associated with a 39% reduction in mortality rate and has prolonged overall survival, with an acceptable toxicity profile. The addition of IT to RT compared with RT alone has a hazard ratio of 0.39(95% CI 0.34–0.44). Conclusions: A combination of immuno/radiotherapy (IR) for the treatment of patients with BMs from melanoma and non-small-cell lung carcinoma has prolonged overall survival and reduced mortality rate, with acceptable toxicity. In terms of timing, RT seems to have the best effect on the result when performed before or simultaneously with immunotherapy