Ultrasensitive ctDNA detection for preoperative disease stratification in early-stage lung adenocarcinoma.

Circulating tumor DNA (ctDNA) detection can predict clinical risk in early-stage tumors. However, clinical applications are constrained by the sensitivity of clinically validated ctDNA detection approaches. NeXT Personal is a whole-genome-based, tumor-informed platform that has been analytically validated for ultrasensitive ctDNA detection at 1-3 ppm of ctDNA with 99.

Tissue- and liquid-biopsy based NGS profiling in advanced non-small-cell lung cancer in a real-world setting: the IMMINENT study.

Introduction: To date, for all non-small cell lung cancer (NSCLC) cases, it is recommended to test for driver alterations to identify actionable therapeutic targets. In this light, comprehensive genomic profiling (CGP) with next generation sequencing (NGS) has progressively gained increasing importance in clinical practice. Here, with the aim of assessing the distribution and the real-world frequency of gene alterations and their correlation with patient characteristics, we present the outcomes obtained using FoundationOne (F1CDx) and FoundationLiquid CDx (F1L/F1LCDx) NGS-based profiling in a nationwide initiative for advanced NSCLC patients.

Transcriptional Phenocopies of Deleterious KEAP1 Mutations Correlate with Survival Outcomes in Lung Cancer Treated with Immunotherapy.

Purpose: Co-occurring mutations in KEAP1 and STK11/KRAS have emerged as determinants of survival outcomes in patients with non-small cell lung cancer (NSCLC) treated with immunotherapy. However, these mutational contexts identify a fraction of nonresponders to immune checkpoint inhibitors. We hypothesized that KEAP1 wild-type tumors recapitulate the transcriptional footprint of KEAP1 mutations and that this KEAPness phenotype can determine immune responsiveness with higher precision compared to mutation-based models.

Exploring the interplay of excitatory and inhibitory interactions in the Kuramoto model on circle topologies.

In the field of collective dynamics, the Kuramoto model serves as a benchmark for the investigation of synchronization phenomena. While mean-field approaches and complex networks have been widely studied, the simple topology of a circle is still relatively unexplored, especially in the context of excitatory and inhibitory interactions. In this work, we focus on the dynamics of the Kuramoto model on a circle with positive and negative connections paying attention to the existence of new attractors different from the synchronized state.

Pembrolizumab-based first-line treatment for PD-L1-positive, recurrent or metastatic head and neck squamous cell carcinoma: a retrospective analysis.

Background: The KEYNOTE-048 trial showed that pembrolizumab-based first-line treatment for R/M HNSCC led to improved OS in the PD-L1 CPS ≥ 1 population when compared to the EXTREME regimen. However, the R/M HNSCC real-world population is generally frailer, often presenting with multiple comorbidities, worse performance status and older age than the population included in phase III clinical trials.

Methods: This is a retrospective, single-centre analysis of patients with R/M HNSCC treated with pembrolizumab-based first-line treatment.

Analysis of predictive factors of unforeseen nodal metastases in resected clinical stage I NSCLC.

Background: Despite notable advances made in preoperative staging, unexpected nodal metastases after surgery are still significantly detected. In this study we aim to analyze the upstaging rate in patients with clinical stage I NSCLC without evidence of nodal disease in the preoperative staging who underwent lobectomy and radical lymphadenectomy.

Methods: Patients who underwent lobectomy and systematic lymphadenectomy for clinical stage I NSCLC were evaluated.

Surgical and survival outcomes with perioperative or neoadjuvant immune-checkpoint inhibitors combined with platinum-based chemotherapy in resectable NSCLC: A systematic review and meta-analysis of randomised clinical trials.

The use of neoadjuvant or perioperative anti-PD(L)1 was recently tested in multiple clinical trials. We performed a systematic review and meta-analysis of randomised trials comparing neoadjuvant or perioperative chemoimmunotherapy to neoadjuvant chemotherapy in resectable NSCLC. Nine reports from 6 studies were included.

Genetic Basis, New Diagnostic Approaches, and Updated Therapeutic Strategies of the Syndromic Aortic Diseases: Marfan, Loeys-Dietz, and Vascular Ehlers-Danlos Syndrome.

Syndromic aortic diseases (SADs) encompass various pathological manifestations affecting the aorta caused by known genetic factors, such as aneurysms, dissections, and ruptures. However, the genetic mutation underlying aortic pathology also gives rise to clinical manifestations affecting other vessels and systems. As a consequence, the main syndromes currently identified as Marfan, Loeys-Dietz, and vascular Ehlers-Danlos are characterized by a complex clinical picture.

Palliative sedation and time to death in home palliative care: retrospective analysis.

Objectives: We described time to death and rates of palliative sedation during home palliative care leveraging a retrospective cohort of patients with advanced cancer.

Methods: The cohort consists of 143 patients with solid or haematological malignancies admitted to home palliative care in the Tuscany region in central Italy. Only patients for whom a date of death was available were included.

KRAS G12C mutation and risk of disease recurrence in stage I surgically resected lung adenocarcinoma.

KRAS G12C mutations are found in about 12-13% of LUAD samples and it is unclear whether they are associated with worse survival outcomes in resected, stage I LUAD. We assessed whether KRAS-G12C mutated tumours had worse DFS when compared to KRAS-nonG12C mutated tumours and to KRAS wild-type tumours in a cohort of resected, stage I LUAD (IRE cohort). We then leveraged on publicly available datasets (TCGA-LUAD, MSK-LUAD) to further test the hypothesis in external cohorts.

Non-small-cell lung cancer: how to manage - and -rearranged disease.

Oncogene addiction in non-small-cell lung cancer (NSCLC) has profound diagnostic and therapeutic implications. , and rearrangements are found in about 2-7%, 1-2% and 0.2% of unselected NSCLC samples, respectively; however, their frequency is markedly higher in younger and never-smoker patients with adenocarcinoma histology.

Advanced non-small-cell lung cancer: how to manage and exon 20 insertion mutation-positive disease.

exon 20 insertion mutations (Ex20ins) and 2 mutations characterize an oncogene-addicted subtype of non-small-cell lung cancer (NSCLC) typically associated with a never or light smoking history, female sex, and adenocarcinoma histology. Nevertheless, Ex20ins-mutant and 2-mutant advanced NSCLCs are still difficult to treat for various reasons. First, there is a need for sophisticated diagnostic tools (e.

Technology and technique for left ventricular assist device optimization: A Bi-Tech solution.

Background: We investigated the synergistic effect of the new cone-bearing design of Jarvik 2000 (Jarvik Heart Inc., NY) together with a minimally-invasive approach to outcomes of LVAD patients.

Methods: We retrospectively reviewed all patients from 5 institutions involved in the Jarvik 2000 Italian Registry, from October 2008 to October 2016.

Analysis of Molecular Biomarkers in Resected Early-Stage Non-Small Cells Lung Cancer: A Narrative Review.

Next-generation sequencing has become a cornerstone in clinical oncology practice and is recommended for the appropriate use of tailored therapies in NSCLC. While NGS has already been standardised in advanced-stage NSCLC, its use is still uncommon in the early stages. The recent approval of Osimertinib for resected EGFR-mutated NSCLC in an adjuvant setting has launched the hypothesis that other targeted therapies used in metastatic patients can also lead to improved early-stage outcomes of NSCLC.

The Potential Role of Genomic Signature in Stage II Relapsed Colorectal Cancer (CRC) Patients: A Mono-Institutional Study.

Purpose: The absolute benefit of adjuvant chemotherapy in stage II CRC is only 3-4%. The identification of biomarkers through molecular profiling could identify patients who will more benefit from adjuvant chemotherapy.

Patients And Methods: This retrospective analysis examined tissue blocks from 17 patients affected by relapsed stage II CRC, whose comprehensive genomic profiling of tumors was conducted through next-generation sequencing (NGS) via Roche-FoundationOne.

PANHER study: a 20-year treatment outcome analysis from a multicentre observational study of HER2-positive advanced breast cancer patients from the real-world setting.

Background: The evolution of therapeutic landscape of human epidermal growth factor receptor-2 (HER2)-positive breast cancer (BC) has led to an unprecedented outcome improvement, even if the optimal sequence strategy is still debated. To address this issue and to provide a picture of the advancement of anti-HER2 treatments, we performed a large, multicenter, retrospective study of HER2-positive BC patients.

Methods: The observational PANHER study included 1,328 HER2-positive advanced BC patients treated with HER2 blocking agents since June 2000 throughout July 2020.