Optimizing CDK4/6 inhibitors in advanced HR+/HER2- breast cancer: A personalized approach.

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) are now a backbone of treatment for hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. CDK4/6i plus ET is more effective than ET alone in this setting; however, the risk of grade 3-4 adverse events also increases. Approved agents in this class have similar efficacies, but important differences due to their structural and pharmacological properties. We review biomarkers and discuss determinants to inform a rational approach to therapy choice when selecting the most appropriate ET and CDK4/6i partners. We also identify subgroups that may benefit from specific ET-CDK4/6i combinations and discuss strategies to overcome resistance. This personalized approach aims to minimize treatment-related toxicities that may affect patient QoL and compliance, and ultimately therapy efficacy.

Accounting for environmental and fishery management factors when standardizing CPUE data from a scientific survey: A case study for Nephrops norvegicus in the Pomo Pits area (Central Adriatic Sea).

Abundance and distribution of commercial marine resources are influenced by environmental variables, which together with fishery patterns may also influence their catchability. However, Catch Per Unit Effort (CPUE) can be standardized in order to remove most of the variability not directly attributable to fish abundance. In the present study, Generalized Additive Models (GAMs) were used to investigate the effect of some environmental and fishery covariates on the spatial distribution and abundance of the Norway lobster Nephrops norvegicus within the Pomo/Jabuka Pits (Central Adriatic Sea) and to include those that resulted significant in a standardization process. N. norvegicus is a commercially important demersal crustacean, altering its catchability over the 24-h cycle and seasons according to its burrowing behavior. A historically exploited fishing ground for this species, since 2015 subject to specific fisheries management measures, is represented by the meso-Adriatic depressions, which are also characterized by particular oceanographic conditions. Both the species behaviour and the features of this study area influence the dynamics of the population offering a challenging case study for a standardization modelling approach. Environmental and catch data were obtained during scientific trawl surveys properly designed to catch N. norvegicus, thus improving the quality of the model input data. Standardization of CPUE from 2 surveys from 2012 to 2019 was conducted building two GAMs for both biomass and density indices. Bathymetry, fishing pressure, dissolved oxygen and salinity proved to be significant drivers influencing catch distribution. After cross validations, the tuned models were then used to predict new indices for the study area and the two survey series by means of informed spatial grids, composed by constant surface cells, to each of which are associated average values of environmental parameters and specific levels of fishing pressure, depending on the management measures in place. The predictions can be used to better describe the structure and the spatio-temporal distribution of the population providing valuable information to evaluate the status of such an important marine resource.

Impact of estrogen receptor levels on outcome in non-metastatic triple negative breast cancer patients treated with neoadjuvant/adjuvant chemotherapy.

Although 1% is the recommended cut-off to define estrogen receptor (ER) positivity, a 10% cut-off is often used in clinical practice for therapeutic purposes. We here evaluate clinical outcomes according to ER levels in a monoinstitutional cohort of non-metastatic triple-negative breast cancer (BC) patients undergoing (neo)adjuvant chemotherapy. Clinicopathological data of 406 patients with ER < 10% HER2-negative BC treated with (neo)adjuvant chemotherapy between 01/2000 and 04/2019 were collected. Patients were categorized in ER-negative (ER < 1%; N = 364) and ER-low positive (1-9%, N = 42). At a median follow-up of 54 months, 88 patients had relapsed and 64 died. No significant difference was observed in invasive relapse-free survival (iRFS) and overall survival (OS) according to ER expression levels, both at univariate and multivariate analysis (5-years iRFS 74.0% versus 73.1% for ER-negative and ER-low positive BC, respectively, p = 0.6; 5-years OS 82.3% versus 76.7% for ER-negative and ER-low positive BC, respectively, p = 0.8). Among the 165 patients that received neoadjuvant chemotherapy, pathological complete response rate was similar in the two cohorts (38% in ER-negative, 44% in ER-low positive, p = 0.498). In conclusion, primary BC with ER1-9% shows similar clinical behavior to ER 1% BC. Our results suggest the use of a 10% cut-off, rather than <1%, to define triple-negative BC.

Preliminary results on the occurrence and anatomical distribution of microplastics in wild populations of Nephrops norvegicus from the Adriatic Sea.

This study reports the shapes, dimensional classes, types and counts of microplastics (MPs) found in 23 individuals of N. norvegicus collected from two wild populations of the Adriatic Sea (Mediterranean basin). The focus was on three different anatomical compartments (gut, hepatopancreas and tail), which were analysed separately. MPs were found in all the investigated individuals with an average of about 17 MPs/individual. Fragments were predominant over fibers with a ratio of about 3:1. The majority of MPs were in the dimensional range 50-100 µm. The predominant polymers were polyester, polyamide 6, polyvinyl chloride and polyethylene, which together constitute about 61% of all the MPs found. Fragments were more concentrated in the hepatopancreas, with no significant difference between gut and tail, while fibers were more concentrated in the gut than in the tail with hepatopancreas somehow in between. The dimensional class of the MPs influences their anatomical distribution. There were no statistical differences among individuals from the two sampling sites. Sex of the individual did not influence the level of retained MPs, while length had a very marginal effect. The information reported here contributes to understanding of the possible risks linked to human consumption of different tissues from contaminated Norway lobsters.

Four lines of anaplastic lymphoma kinase inhibitors and brain radiotherapy in a long-surviving non-small-cell lung cancer anaplastic lymphoma kinase-positive patient with leptomeningeal carcinomatosis.

Lung cancer is the most common tumor and the leading cause of cancer-related death worldwide. Approximately 6.7% of non-small-cell lung cancers (NSCLCs) show anaplastic lymphoma kinase (ALK) rearrangement and could benefit from ALK-targeted treatment. Various anti-ALK drugs have been developed during the past years, but it is actually controversial which sequence and which ALK inhibitor is recommended for a single patient. Leptomeningeal carcinomatosis (LC) is associated with a poor prognosis, with an overall survival of 2-4 months for treated patients. The data about LC management derive mainly from retrospective studies, being an exclusion criterion for most trials. Intrathecal chemotherapy and whole-brain radiotherapy (WBRT), associated with a systemic treatment, are the most commonly used approach. Here we present a case of NSCLC harboring an ALK translocation treated with four lines of ALK inhibitors and receiving WBRT for LC, showing an overall survival of ∼5 years from the diagnosis of metastatic disease. This case report focuses mainly on several controversial clinical aspects, that is, the sequence of treatment in ALK-positive NSCLC, the ALK inhibitors' efficacy on brain disease and beyond progression, the management of LC, and the role of WBRT despite the risk of cognitive impairment.

Pharmacogenetic Approach to Toxicity in Breast Cancer Patients Treated with Taxanes.

BACKGROUND: Taxanes are widely used to treat breast cancer patients. Taxanes are metabolized in human liver by the cytochrome CYP3A and are substrate of ATP-binding cassette multidrug transporters ABCB1. Single-nucleotide polymorphisms (SNPs) in genes involved in taxanes' metabolism could affect the inter-individual variability in reported toxicities. MATERIALS AND METHODS: In this retrospective study, 152 women, affected by breast cancer and receiving a taxane-based chemotherapy, were enrolled. A peripheral blood sample was taken for genotyping the following polymorphisms: CYP3A4* 1B (A>G), CYP3A5 *3 (G>A) and ABCB1 (C1236T; C3435T). RESULTS: We observed an association between ABCB1 3435 T/T and lower grade of toxicities (p=0.05). No other association were found for CYP 3A4 *1B, 3A5*3 and ABCB1 C1236T. CONCLUSION: ABCB1 3435 T/T seems to be associated to lower rate of toxicity in patients receiving taxanes. Further prospective and larger studies should be performed to clarify the role of this polymorphism.

Unexpected long survival of brain oligometastatic non-small cell lung cancer (NSCLC) treated with multimodal treatment: a single-center experience and review of the literature.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. Fifty percent of the cases are metastatic at diagnosis and about 20% develop brain metastasis. The brain involvement represents a negative prognostic factor. However, some patients could benefit from locoregional treatments of metastatic foci and experience an unexpected long survival or healing. In the previous years some classifications were proposed to identify patients' prognostic category, according to stage of the primary tumor, the timing of metastases occurrence (synchronous or metachronous) and the number of metastatic sites. Several data show a benefit in patients receiving resection of both the primary tumor and brain metastases. Whole brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS) are the selected options in most cases. Overall, literature data showed highly variable outcome, with an overall survival (OS) ranging from 5.9 to 68 months. No data from randomized and homogeneous trials are currently available. Therefore, a growing interest in this field is observed. Different trials investigating the effectiveness of local treatments and studies analyzing biological mechanisms are ongoing. In this report we analyze literature data and we explore the current field of study. Furthermore, we show a single institutional experience of multimodal management of stage IV NSCLC with brain metastases, experiencing an unexpected long survival. We conclude that a better knowledge of this subpopulation of patients and new studies in this field can lead to distinguish the patients who can benefit from local treatment from those with poor prognosis.

[Assessment of pain associated to common invasive procedures and nurse's opinion]. / Valutazione della percezione del dolore da procedura invasiva e opinione degli infermieri.

UNLABELLED: Assessment of pain associated to common invasive procedures and nurse's opinion. INTRODUCTION: Invasive diagnostic and therapeutic procedures (IDTP) may be painful and cause physical and emotional discomfort. AIM: An observational study was conducted in three medical wards of S. Giovanni Battista Hospital, to a) assess pain and discomfort experienced by patients during IDTPs and nurses' opinion; b) describe frequency and outcomes of the administration of analgesics and anxiolitics. METHODS: Pain was assessed with a Numeric Rating Scale (NRS) before and after IDTPs and patients were asked to describe the main causes of pain/discomfort experienced. Nurses expressed their opinion on pain and discomfort caused by a list of IDTPs. Means and DS sere calculated for each IDTP. RESULTS: Data on 186 patients and 200 IDTPs were collected. The most performed IDTPs were EGDS (18%), blood gas analysis (14%) and colonoscopy (12.5%). The most painful were Bone Marrow Biopsy (BOM) (NRS 7.05) and colonoscopy (NRS 6.44); those more anxiety provoking the BOM (NRS 7.26) and bronchoscopy (NRS 5.09). No analgesic or insufficient dosages were administered before some IDTPs and 56% patients would have liked it. Nurses rated patients pain and fear/anxiety significantly higher than patients. CONCLUSIONS: Acute pain, fear and anxiety are poorly controlled; the lack of protocols for pain control may be responsible for the different levels of discomfort experienced.