Clinical Benefits and Utility of Pretherapeutic DPYD and UGT1A1 Testing in Gastrointestinal Cancer: A Secondary Analysis of the PREPARE Randomized Clinical Trial.

Importance: To date, the clinical benefit and utility of implementing a DPYD/UGT1A1 pharmacogenetic-informed therapy with fluoropyrimidines and/or irinotecan have not been prospectively investigated.

Objective: To examine clinically relevant toxic effects, hospitalizations, and related costs while preserving treatment intensity and efficacy outcomes in patients with gastrointestinal cancer.

Design, Setting, And Participants: This nonprespecified secondary analysis stems from Pre-Emptive Pharmacogenomic Testing for Preventing Adverse Drug Reactions (PREPARE), a multicenter, controlled, open, block-randomized, crossover implementation trial conducted from March 7, 2017, to June 30, 2020, and includes data from Italy according to a sequential study design.

Factors influencing 5-year persistence to adjuvant endocrine therapy in young women with breast cancer.

Purpose: Although younger age has been negatively associated with persistence to adjuvant endocrine therapy (ET), factors contributing to non-persistence remain poorly understood. We assessed factors associated with non-persistence to ET and described the 5-year trajectories of quality of life (QoL) and symptoms in young women (≤40 years) with hormone receptor-positive breast cancer (BC).

Methods: We retrieved data on clinical characteristics and non-persistence from the medical annual records in the European cohort of the "Helping Ourselves, Helping Others: The Young Women's BC Study" (IBCSG 43-09 HOHO).

Multiorgan failure caused by pembrolizumab and axitinib in a woman affected by metastatic clear cell renal cell carcinoma: A case report and literature review.

Rationale: Treatment with a combination of immune checkpoint inhibitors (ICIs) (pembrolizumab or nivolumab) and oral Tyrosine Kinase Inhibitors (TKI) targeting angiogenesis (axitinib, cabozantinib or lenvatinib) has shown benefits in terms of efficacy and survival in metastatic renal cell carcinoma (mRCC), with a favorable toxicity profile. However, some rare and serious treatment-related adverse events can be difficult to manage.

Patient Concerns: Here we report the first case of an mRCC patient who, after only 2 administrations of pembrolizumab-axitinib, experienced severe multiorgan failure (MOF) with heart failure, oliguria and acute hepatitis requiring aggressive supportive treatment in intensive care unit.

Sex-related differences in serum biomarker levels predict the activity and efficacy of immune checkpoint inhibitors in advanced melanoma and non-small cell lung cancer patients.

Background: Immune Checkpoint Inhibitors (ICIs) lead to durable response and a significant increase in long-term survival in patients with advanced malignant melanoma (MM) and Non-Small Cell Lung Cancer (NSCLC). The identification of serum cytokines that can predict their activity and efficacy, and their sex interaction, could improve treatment personalization.

Methods: In this prospective study, we enrolled immunotherapy-naïve patients affected by advanced MM and NSCLC treated with ICIs.

Predicting heroin potency from the analysis of paraphernalia: A tool for overdose prevention projects.

In recent years, fatal and non-fatal heroin-related overdoses have increased in northeastern Italy, and the change in potency of heroin available at street level has been identified as a prominent factor associated with acute toxicity. Two very different products, high-potency and low-potency heroin were becoming available on the street, and no clear morphological characteristics could be used to easily distinguish them. A theoretical model for predicting heroin potency from rapid analysis of cigarette filters was developed as part of an overdose prevention project.

Concomitant Drugs Prognostic Score in Patients With Metastatic Renal Cell Carcinoma Receiving Ipilimumab and Nivolumab in the Compassionate Use Program in Italy: Brief Communication.

A concomitant drug-based score was developed by our group and externally validated for prognostic and predictive purposes in patients with advanced cancer treated with immune checkpoint inhibitors (ICIs). The model considers the use of three classes of drugs within a month before initiating ICI, assigning score 1 for each between proton pump inhibitor and antibiotic administration until a month before immunotherapy initiation and score 2 in case of corticosteroid intake. In the present analysis, the drug score was validated in a prospective population of 305 patients with metastatic renal cell carcinoma treated with ipilimumab plus nivolumab in the first-line setting.

Employment trajectories of young women with breast cancer: an ongoing prospective cohort study in Italy and Switzerland.

Purpose: Despite extensive research on cancer and work-related outcomes, evidence from longitudinal cohort studies is limited, especially in young women with breast cancer (BC). We aimed to investigate employment trajectories in young BC survivors and to identify potential factors associated with changes in work activity.

Methods: The HOHO European prospective multicenter cohort study enrolled 300 young women (≤ 40 years) with newly diagnosed BC.

Multicenter Real-World Study on Effectiveness and Early Discontinuation Predictors in Patients With Non-small Cell Lung Cancer Receiving Nivolumab.

Background: Real-world (RW) evidence on nivolumab in pretreated patients with non-small cell lung cancer (NSCLC) by matching data from administrative health flows (AHFs) and clinical records (CRs) may close the gap between pivotal trials and clinical practice.

Methods: This multicenter RW study aims at investigating median time to treatment discontinuation (mTTD), overall survival (mOS) of nivolumab in pretreated patients with NSCLC both from AHF and CR; clinical-pathological features predictive of early treatment discontinuation (etd), budget impact (BI), and cost-effectiveness analysis were investigated; mOS in patients receiving nivolumab and docetaxel was assessed.

Results: Overall, 237 patients with NSCLC treated with nivolumab were identified from AHFs; mTTD and mOS were 4.

Clinical profile and mortality of Sars-Cov-2 infection in cancer patients across two pandemic time periods (Feb 2020-Sep 2020; Sep 2020-May 2021) in the Veneto Oncology Network: The ROVID study.

Introduction: We analyzed a cohort of patients with cancer and Sars-Cov-2 infection from the Veneto Oncology Network registry across two pandemic time periods.

Materials And Methods: 761 patients with cancer and SARS-CoV-2 infection were included.

Results: 198 patients were diagnosed during the first pandemic time period (TP1; February 2020 September 2020), 494 during TP2 before the vaccination campaign (TP2/pre-vaccination; September 2020-21 February 2021) and 69 in TP2/post-vaccination (22 February 2021-15 May 2021).

Gut-oriented interventions in patients with multiple sclerosis: fact or fiction?

Objective: Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating, disimmune disease of the central nervous system whose etiology and pathogenesis remain poorly understood, due to its complex and multifactorial nature. Evidence of a bidirectional connection linking the gut microbiome with the intestinal barrier and the immune system (the gut-brain axis) may have implications for the pathogenesis of inflammatory demyelinating diseases such as MS. This narrative review summarizes the evidence for the gut-brain axis involvement in the pathogenesis of MS and examines the role of gut-oriented interventions in MS.

Eutopic endometrium from women with endometriosis and chlamydial endometritis share immunological cell types and DNA repair imbalance: A transcriptome meta-analytical perspective.

The aim of this study was to identify the key similarities between the eutopic endometrium of women with endometriosis and chlamydia-induced endometritis taking into account tissue microenvironment heterogeneity, transcript gene profile, and enriched pathways. A meta-analysis of whole transcriptome microarrays was performed using publicly available data, including samples containing both glandular and stromal endometrial components. Control samples were obtained from women without any reported pathological condition.

Comparing population trend estimates of migratory birds from breeding censuses and capture data at a spring migration bottleneck.

Europe has a well-established network of breeding bird monitoring that is used to produce supranational indices of population trends for many species. However, a comparison of breeding bird censuses with other methods may be beneficial to confirm the validity of such indices. The aim of this study was to assess the value of standardized capture data of migratory birds at migration bottlenecks as an indicator of the effective breeding populations.

A Randomized-Controlled Phase 2 Study of the MET Antibody Emibetuzumab in Combination with Erlotinib as First-Line Treatment for EGFR Mutation-Positive NSCLC Patients.

Introduction: The hepatocyte growth factor receptor mesenchymal-epithelial transition (MET) is reported to be a negative prognostic marker in EGFR-mutant NSCLC and involved in resistance to EGFR inhibitors. Emibetuzumab, a humanized immunoglobulin G4 monoclonal bivalent MET antibody, blocks ligand-dependent and ligand-independent hepatocyte growth factor/MET signaling. This phase 2 study compared erlotinib with and without emibetuzumab in first-line treatment of EGFR-mutant metastatic NSCLC.

Maintenance with lanreotide in small-cell lung cancer expressing somatostatine receptors: A multicenter, randomized, phase 3 trial.

Objectives: Considering the frequent expression of somatostatine receptors, we designed the G04.2011 trial to investigate the efficacy of the somatostatine analogue lanreotide in maintenance for SCLC patients after response to standard treatment.

Materials And Methods: A multicenter, randomized, phase 3 trial was conducted in SCLC expressing somatostatine receptors at baseline Octreoscan, responding after platinum-based chemotherapy with/without radiotherapy.

From Diagnostic-Therapeutic Pathways to Real-World Data: A Multicenter Prospective Study on Upfront Treatment for -Positive Non-Small Cell Lung Cancer (MOST Study).

Introduction: Gefitinib, erlotinib, and afatinib represent the approved first-line options for epidermal growth factor receptor ()-mutant non-small cell lung cancer (NSCLC). Because pivotal trials frequently lack external validity, real-world data may help to depict the diagnostic-therapeutic pathway and treatment outcome in clinical practice.

Methods: MOST is a multicenter observational study promoted by the Veneto Oncology Network, aiming at monitoring the diagnostic-therapeutic pathway of patients with nonsquamous -mutant NSCLC.

New Phytotoxic Cassane-like Diterpenoids from Eragrostis plana.

Eragrostis plana (Nees) is an allelopathic plant with invasive potential in South American pastures. To isolate and identify phytotoxic compounds from leaves and roots of E. plana, a bioassay-directed isolation of the bioactive constituents was performed.

The Genotype for DPYD Risk Variants in Patients With Colorectal Cancer and the Related Toxicity Management Costs in Clinical Practice.

Lack of information on the clinical utility of preemptive DPYD screening before fluoropyrimidine treatment is a major barrier preventing its use in clinical practice. This study aimed to define the association between DPYD variants and fluoropyrimidine-related toxicity management costs. A cost analysis was conducted on the toxicities experienced by 550 patients with colorectal cancer treated with fluoropyrimidine-based chemotherapy.

A Clinical-Genetic Score to Identify Surgically Resected Colorectal Cancer Patients Benefiting From an Adjuvant Fluoropyrimidine-Based Therapy.

There are clinical challenges related to adjuvant treatment in colorectal cancer (CRC) and novel molecular markers are needed for better risk stratification of patients. Our aim was to integrate our previously reported clinical-genetic prognostic score with new immunogenetic markers of 5-year disease-free survival (DFS) to evaluate the recurrence risk stratification before fluoropyrimidine (FL)-based adjuvant therapy. The study population included a total of 270 stage II-III CRC patients treated with adjuvant FL with (FL + OXA, = 119) or without oxaliplatin (FL, = 151).

Retrospective Assessment of a Serum Proteomic Test in a Phase III Study Comparing Erlotinib plus Placebo with Erlotinib plus Tivantinib (MARQUEE) in Previously Treated Patients with Advanced Non-Small Cell Lung Cancer.

Background: The VeriStrat test provides accurate predictions of outcomes in all lines of therapy for patients with non-small cell lung cancer (NSCLC). We investigated the predictive and prognostic role of VeriStrat in patients enrolled on the MARQUEE phase III trial of tivantinib plus erlotinib (T+E) versus placebo plus erlotinib (P+E) in previously treated patients with advanced NSCLC.

Methods: Pretreatment plasma samples were available for 996 patients and were analyzed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry to generate VeriStrat labels (good, VS-G, or poor, VS-P).

The role of immune microenvironment in small-cell lung cancer: Distribution of PD-L1 expression and prognostic role of FOXP3-positive tumour infiltrating lymphocytes.

Introduction: The prognosis of small-cell lung cancer (SCLC) is dismal and new effective therapies are needed. Immunotherapy looks promising, but no molecular predictive markers are currently available, and data on immune microenvironment are very limited.

Methods: We retrospectively analysed 104 SCLC cases.

Second-line Treatment of Advanced Non-small Cell Lung Cancer Non-oncogene Addicted: New Treatment Algorithm in the Era of Novel Immunotherapy.

Background: Most patients with advanced non-small cell lung cancer (NSCLC) have a poor prognosis and receive limited benefit from conventional treatments, especially in later lines of therapy. In recent years, several novel therapies have been approved for second- and third-line treatment of advanced NSCLC beyond old chemotherapy agents (docetaxel and pemetrexed) and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI, erlotinib). In particular, the new antiangiogenetics (nindetanib and ramucirumab) in combination with docetaxel and immunotherapy (nivolumab, pembrolizumab and atezolizumab) have been recently approved and represent new treatment options.