The Safety and Suitability of DNA Sequencing of Tissue Biopsies Performed on Patients Referred to a Phase I Unit.

Background: Early-phase clinical trials offer a unique opportunity for patients with cancer. These trials often mandate biopsies to collect tumor tissue for research purposes, requiring patients to undergo invasive procedures. Some trials mandate molecular prescreening, but the success of these analyses relies on the quality and quantity of the tested materials.

Molecular tumor board in patients with metastatic breast cancer.

Purpose: Comprehensive genomic profiling is becoming increasingly important in the management of patients with metastatic breast cancer (mBC). Real-world clinical outcomes from applying molecular tumor boards (MTBs) recommendations in this context remain limited. Accordingly, we conducted a retrospective, single-institution analysis to evaluate the clinical impact of discussing patients affected by mBC at the MTB.

Genomic and clinical landscape of metastatic hormone receptors-positive breast cancers carrying ESR1 alterations.

Background: Somatic genetic alterations of the estrogen receptor 1 gene (ESR1) are enriched in endocrine therapy-resistant, estrogen receptor-positive (ER+) metastatic breast cancer (mBC). Herein, we investigated and compared the clinical and genomic landscape of ESR1-mutant (ESR1) and ESR1 wild type (ESR1) ER+/ human epidermal growth factor receptor 2 (HER2)- mBCs.

Methods: Clinical and genomic data were retrieved from cBioPortal using the publicly-available MSK MetTropism dataset.

Characteristics of arthritis in patients with familial Mediterranean fever.

Background: Many of the familial Mediterranean fever (FMF) patients present with arthritis during attacks, which may vary in its characteristics.

Aims: In this study, we aimed to describe and characterise arthritis in FMF patients.

Methods: We used our hospital's record system to retrospectively identify FMF patients with arthritis who presented to our clinic between 2005 and 2020.

Unfavorable carcinoma of unknown primary with a gastrointestinal profile: a retrospective study.

Background: Carcinoma of unknown primary (CUP) with a gastrointestinal profile is categorized by the European Society of Medical Oncology (ESMO) guidelines into favorable and unfavorable subsets. Favorable CUPs benefit from site-specific chemotherapy (CT), while the optimal treatment for unfavorable CUPs is still undefined.

Materials And Methods: We conducted a single-center retrospective study to describe outcomes of patients with CUP with a gastrointestinal profile referred to our center from January 2000 to August 2023.

Interstitial lung disease in patients enrolled in early-phase clinical trials: the ILDE study.

Background: Interstitial lung disease (ILD) encompasses a heterogeneous group of disorders sharing pathophysiological inflammatory mechanisms, leading to parenchymal distortions. The prevalence of ILD with new cancer drugs is underreported: the identification of potential determinants is priority.

Materials And Methods: ILDE is a retrospective study aimed at describing the clinical course and potential determinants of ILD in patients receiving experimental treatments.

Assessing the Relevance of Non-molecular Prognostic Systems for Myelodysplastic Syndrome in the Era of Next-Generation Sequencing.

Background: The Molecular International Prognostic Scoring System (IPSS-M) has improved the prediction of clinical outcomes for myelodysplastic syndromes (MDS). The Artificial Intelligence Prognostic Scoring System for MDS (AIPSS-MDS), based on classical clinical parameters, has outperformed the IPSS, revised version (IPSS-R). For the first time, we validated the IPSS-M and other molecular prognostic models and compared them with the established IPSS-R and AIPSS-MDS models using data from South American patients.

Effect of age on safety and efficacy of novel cancer drugs investigated in early-phase clinical trials.

Background: Elderly patients are underrepresented in clinical trials, particularly in early-phase studies. Our study assessed the safety and efficacy of novel anti-cancer treatments investigated in early-phase clinical trials, comparing outcomes between younger and elderly patients.

Methods: This retrospective study analyzed data from patients enrolled in phase I/II trials at our center between January 2014 and April 2021.

Deleterious alterations in homologous recombination repair genes and efficacy of platinum-based chemotherapy in biliary tract cancers.

Background: Platinum-based chemotherapy represents the standard first-line treatment for biliary tract cancers (BTC). Deficits in genes involved in the homologous recombination (HR) and DNA damage response (DDR) may confer higher sensitivity to platinum agents.

Methods: We retrospectively included patients affected by BTC from 2 Italian institutions.

The evolving landscape of metastatic HER2-positive, hormone receptor-positive Breast Cancer.

Therapeutic agents targeting Human Epidermal Growth Factor Receptor 2 (HER2) demonstrated to positively impact the prognosis of HER2-positive breast cancer. HER2-positive breast cancer can present either as hormone receptor-negative or positive, defining Triple-positive breast cancer (TPBC). TPBC demonstrate unique gene expression profiles, showing reduced HER2-driven gene expression, as recapitulated by a higher proportion of Luminal-type intrinsic subtypes.

Clinical actionability of BRCA2 alterations in uterine leiomyosarcoma: a molecular tumor board case report and a cBioPortal comprehensive analysis.

Background: Uterine leiomyosarcoma (uLMS) represents one of the most common sarcoma histotypes, demonstrating an overall dismal prognosis. Previous studies reported uLMS to carry recurrent somatic BRCA2 homozygous deletions, related to significant clinical benefits from the use of PARP inhibitors.

Methods: To investigate the prevalence in uLMS of genomic alterations (alt) in BRCA2 and other homologous recombination (HR) and DNA damage response (DDR) genes, cBioPortal was accessed and data were retrieved from studies including pan-sarcoma histologies.

Cancers of Unknown Primary Origin: Real-World Clinical Outcomes and Genomic Analysis at the European Institute of Oncology.

Background: Cancer of unknown primary origin (CUP) poses a significant challenge due to poor clinical outcomes and limited treatment options. As such, further definition of clinicopathological factors and genomic profile to better adapt treatment strategies is required.

Methods: Medical records were interrogated to retrospectively include CUP with available clinical and genomics data at the European Institute of Oncology.

Use of FreeStyle Libre for continuous glucose monitoring in adult horses.

Objectives: To evaluate the feasibility of using the FreeStyle Libre (a continuous glucose monitoring system [CGMS]) for instantaneous continuous monitoring of interstitial glucose in adult horses and examine the applicability and accuracy of this system in horses submitted to combined glucose-insulin test (CGIT).

Design: Laboratory measurements and continuous glucose monitoring system (CGMS) readings were analyzed using a 2 × 2 factorial statistical model with repeated measures over time. This analysis assessed the effects of the test (factor 1), group (factor 2), and their interactions (test × group, test × time, and group × time).

Beyond PD(L)-1 Blockade in Microsatellite-Instable Cancers: Current Landscape of Immune Co-Inhibitory Receptor Targeting.

High microsatellite instability (MSI-H) derives from genomic hypermutability due to deficient mismatch repair function. Colorectal (CRC) and endometrial cancers (EC) are the tumor types that more often present MSI-H. Anti-PD(L)-1 antibodies have been demonstrated to be agnostically effective in patients with MSI-H cancer, but 50-60% of them do not respond to single-agent treatment, highlighting the necessity of expanding their treatment opportunities.

Derivation of two human induced pluripotent stem cell lines carrying a missense mutation in FHL1 (c.377G > A, p.C126Y) linked to familial muscular dystrophy.

FHL1 gene locates in the Xq26 region and encodes for four and half LIM domain protein 1. It plays a crucial role in muscle cells and mutations in FHL1 are related to muscular dystrophy (MD). Peripheral blood mononuclear cells (PBMCs) were obtained from 2 family patients with MD that carry a pathogenic missense mutation in FHL1 (c.

Comparative Assessment of Oxidative and Antioxidant Parameters in Mule and Horse Neonates during Their First Month of Extrauterine Adaptation.

After parturition, a rapid transition occurs from the intrauterine to the extrauterine milieu, exposing neonates to physiological circumstances characterized by oxidative conditions that instigate the generation of reactive oxygen species. These free radicals play pivotal roles in physiological processes; however, an imbalance between their production and the removal of antioxidants can result in severe cellular damage. The main objective of this study was to compare the oxidative and antioxidant profiles in mule and horse neonates immediately post-parturition, as well as at subsequent time points (1, 6, 12, and 24 h, 7 and 30 days) during their extrauterine existence.

Immune-Related Adverse Event Likelihood Score Identifies "Pure" IRAEs Strongly Associated With Outcome in a Phase I-II Trial Population.

Background: Immune-related adverse events (IRAE) pose a significant diagnostic and therapeutic challenge in patients treated with immune-oncology (IO) drugs. IRAEs have been suggested to correlate with better outcome, but studies are conflicting. Estimating the true incidence of IRAEs is particularly difficult in the early phase I/II trial setting.

Variant allele frequency: a decision-making tool in precision oncology?

Precision oncology requires additional predictive biomarkers for targeted therapy selection. Variant allele frequency (VAF), measuring the proportion of variant alleles within a genomic locus, provides insights into tumor clonality in somatic genomic testing, yielding a strong rationale for targeting dominant cancer cell populations. The prognostic and predictive roles of VAF have been evaluated across different studies.

Evaluation of the Geographical Accessibility of Genome-Matched Clinical Trials on a National Experience.

Background: Molecular-driven oncology allows oncologists to identify treatments that match a cancer's genomic profile. Clinical trials are promoted as an effective modality to deliver a molecularly matched treatment. We explore the role of geographical accessibility in Italy, and its impact on patient access to clinical trials.

Baseline Tumor Size as Prognostic Index in Patients With Advanced Solid Tumors Receiving Experimental Targeted Agents.

Background: Baseline tumor size (BTS) has been associated with outcomes in patients with cancer treated with immunotherapy. However, the prognostic impact of BTS on patients receiving targeted therapies (TTs) remains undetermined.

Methods: We reviewed data of patients with advanced solid tumors consecutively treated within early-phase clinical trials at our institution from 01/2014 to 04/2021.

A demand-offer critical analysis of current drug development. Phase I drugs versus TCGA sequencing data.

Background: Phase I clinical trials have become increasingly critical to regulatory approvals of novel agents. In phase I drug development, a global problem of unknown magnitude is the multiplicity of similar drugs being investigated against the same target, colloquially known as the 'me too' phenomenon.

Methods: Ranging from December 2020 to December 2022 we annotated phase I clinical trials present on clinicaltrials.