Newly Diagnosed Multifocal GBM: A Monocentric Experience and Literature Review

Simple SummaryGlioblastoma is an aggressive brain tumor with a dismal prognosis. In a minority of cases, it presents with multiple lesions already at the time of diagnosis, affecting patients’ survival and treatment. Our retrospective study aims to increase the current understanding and define a treatment for this sub-entity, to improve patient survival. Chemoradiotherapy is a also safe and efficacy treatment in patients with multiple lesions. Survival advantages from extensive resection remain unclear.AbstractGlioblastomas with multiple foci at presentation (mGBMs) account for 2–35% of all GBMs. mGBMs have limited existing data and no standardized treatment. This study aims to determine their incidence, demographic and clinical features, outcome, and prognostic factors in terms of overall survival. We performed a monocentric retrospective study, reviewing patients treated at the Istituto Oncologico Veneto. Inclusion criteria were: new diagnosis of GBM and presence of multiple lesions on pre-treatment MRI. ECOG PS was used to evaluate clinical condition, RANO criteria for radiological assessment, and CTCAE v5.0 for treatment-related adverse events. The incidence of newly diagnosed mGBM was 7.2% and the study population consisted of 98 patients. Median age was 63 years, M:F ratio of 1.8:1, and a surgical approach was undertaken in 73 patients (mostly partial resection). MGMT was methylated in 47.5%, and 82 patients received active oncological treatment (65.9% radiotherapy plus temozolomide (RT + TMZ)). The disease control rate with RT + TMZ was 63%. Median OS of the entire study population was 10.2 months (95% CI 6.6–13.8), and median PFS was 4.2 months (95% CI 3.2–5.2). The ECOG PS, the extent of resection, and the RT + TMZ were significant prognostic factors in the univariate analysis for OS, but only the RT + TMZ was a significant independent OS predictor in the multivariate analysis (HR = 3.1, 95% IC 1.3–7.7, p = 0.014). The incidence of mGBM is not rare. RT + TMZ is confirmed to be an independent prognostic factor for survival and a safe and effective treatment. When feasible, RT + TMZ should be considered as a possible first-line treatment. The role of the extent of resection is still unclear.     

Targeted agents for HER2-positive breast cancer in older adults: current and future perspectives

ABSTRACT

Introduction: One-third of breast cancer (BC) cases worldwide occur in women aged 65 years and older, with 10 to 15% overexpressing the human epidermal growth factor receptor 2 (HER2). Although several HER2-targeted therapies have been developed, the lack of data regarding their use in older patients hampers evidence-based decision-making for this population.

Areas Covered: We review current evidence on the efficacy and safety of HER2-targeted therapies in older adults with BC, focusing on approved therapies such as trastuzumab, lapatinib, pertuzumab, ado-trastuzumab-emtansine, and neratinib. Additionally, we discuss drugs under development to target the HER2-receptor, and to overcome resistance to existing therapies. Finally, we highlight the cardiotoxicity of HER2-targeted drugs among older adults.

Expert Opinion: Older adults are underrepresented in trials of HER2-targeted therapies in BC. We propose strategies to increase recruitment of older adults in clinical trials in order to increase the evidence base to treat this growing population.     

Melanotic Neuroectodermal Tumor of Infancy: the Use of Immunohistochemical Analysis

The Melanotic Neuroectodermal Tumor of Infancy (MNTI) is an asymptomatic, pigmented neoplasm characterized by a fast and locally aggressive growth along with a rare tissue formation. In the diagnostic process, the use of imaging exams can suggest a local destruction suggestive of malignancy, a sign of bone remodeling and expansion. Therefore, as any early diagnosis minimizes risks and improves the prognosis of treatment for the patient, the aim of this study was, based on a clinical case report, to corroborate the use of histopathological analysis associated with immunohistochemistry. Thus, we conclude that the immunohistochemical exam is of great importance for a better complementation of the MNTI diagnosis process. In addition, it can reveal signs of possible aggressive growth.     

Valorization of Grape Pomace and Berries as a New and Sustainable Dietary Supplement: Development,Characterization, and Antioxidant Activity Testing

Grape pomace and berries represent natural sources of phytochemicals that can increase the quality of life of consumers by contributing to the prevention of chronic diseases; thus, the development of a dietary supplement was necessary. The raw material (r.m.) used for the development of the dietary supplement consisted of dried and powdered bilberries (Vaccinium myrtillus L.), red currants (Ribes rubrum L.), and red fermented pomaces (Vitis vinifera L.) from Feteasca Neagra and Cabernet Sauvignon cultivars. The particle size distribution, powder flow, total phenolic content (TPC), HPLC-DAD phenolic profile assessment, and radical scavenging assay (RSA) were employed for the analysis of the raw material. After encapsulation, the average mass and uniformity of mass, the disintegration, and the uniformity of content for the obtained capsules were performed to obtain a high-quality dietary supplement. All the assays performed complied to the compendial requirements and the TPC was determined at 9.07 ± 0.25 mg gallic acid equivalents/g r.m. and RSA at 48.32 ± 0.74%. The highest quantities of phenolic compounds determined were 333.7 ± 0.50 µg/g r.m. for chlorogenic acid, followed by rutin, ferulic acid, and (+)-catechin with 198.9 ± 1.60 µg/g r.m., 179.8 ± 0.90 µg/g r.m. and 118.7 ± 0.75 µg/g r.m., respectively. The results of this study can be used for the manufacturing and assessing of pilot scale-up capsule batches and thinking of quality assurance, we recommend that the industrial batch extracts should be standardized in polyphenols, and the manufacturing process should be validated.     

Safety and Efficacy of Eucaloric Very Low-Carb Diet (EVLCD) in Type 1 Diabetes: A One-Year Real-Life Retrospective Experience

A eucaloric very low carbohydrate diet (EVLCD) is a diet with a daily caloric intake equal to the total daily energy expenditure (TDEE) with a carbohydrate content of <50 g/day. The literature on very low carbohydrate diets (VLCD) in type 1 diabetes (DM 1) is limited, although recently published scientific studies have highlighted their safety and efficacy in managing DM 1. In this retrospective analysis, we report the clinical data of 33 patients affected by DM 1 carrying out insulin therapy who switched voluntarily from their usual diet (high carb, low fat) to an EVLCD. Our aim is to evaluate the glycemic control, the amount of insulin needed in order to maintain glycemic control and safety of EVLCD. The switch improved glycemic control (mean glycated hemoglobin decreased from 8.3% to 6.8% (p < 0.01). The number of patients who reached a glycated hemoglobin value of <7% increased statistically from 12% to 57% (p < 0.01), and there was a statistically significant decrease (p < 0.01) in the units of daily insulin (from 36.7± 14.9 IU to 28.9 ±9.1 IU) A reduction from 54% to 24% in clinical level 2 hypoglycemia episodes was reported. No cases of severe hypoglycemia or ketoacidosis were observed. The results of the study support that EVLCD in DM 1 seems safe and effective when adopted under tight medical supervision.     

Evaluation of placental protein modifications in normotensive and spontaneously hypertensive rats

Hypertension in pregnancy is often associated to placental deficiency. Therefore several physiopathological modifications occur to sustain fetal well-being through protective mechanisms. Here, we used spontaneously hypertensive rat (SHR) and normotensive Wistar-Kyoto (WKY) counterpart to evaluate in late gestation (d 20) modification of placental proteins involved in adaptation to hypertension. Placenta from WKY and SHR was excised for the evaluation of protein changes by Western blot analysis and zymography. In particular, we showed in SHR placentas an increase in angiotensin receptor type 1 and a decrease in angiotensin converting enzyme. Conversely, inducible nitric oxide synthase expression was increased, while constitutive endothelial nitric oxide synthase was similar in both groups. Placentas from SHR showed a reduced protein expression in both peroxisome proliferators-activated receptors-alpha and -gamma. Pro-metalloproteinase-9 activity was not significantly modified, whereas both pro-metalloproteinase-2 and its active form present a higher activity in SHR placentas. Moreover, at the end of pregnancy, cyclooxygenase-2 expression decreased in SHR placentas. These data may provide new insights into the placental adaptive mechanisms that take place during pregnancy in SHR.     

Time-course analyses addressing the acquisition of DBA lectin reactivity in mouse lymphoid organs and uterus during the first week of pregnancy

Terminal differentiation of uterine natural killer (uNK) cells is induced in humans and mice at the time of endometrial decidualization. In mice, commitment to this lineage is first recognized at gestation day (gd)5.5 when small, non-granulated lymphocytes in the mesometrial decidua basalis become histochemically reactive with the lectin Dolichlos biflorus agglutinin (DBA). Transplantation experiments in mice have shown that the self-renewing progenitors of uNK cells are present in peripheral rather than uterine tissues. While lymphoid tissues of virgin mice lack DBA lectin reactive putative uNK cell precursors or progenitors, peripheral organs have not been systematically examined in female mice during early pregnancy while the uNK cell population is becoming established. Here we report such a study in gd0.5–7.5 random bred mice. Only mesenteric lymph nodes showed a transient gain in DBA lectin reactive lymphocytes between gd0.5 and 4.5. These cells had cytoplasmic but almost no surface DBA lectin reactivity. This study indicates that the decidual environment is unique and locally promotes DBA lectin surface expression in terminally differentiating uNK cells.