0000000000260924
AUTHOR
Francesco Pepe
The prognostic impact of tumor mutational burden (TMB) in the first-line management of advanced non-oncogene addicted non-small-cell lung cancer (NSCLC): a systematic review and meta-analysis of randomized controlled trials
Background The role of tumor mutational burden (TMB) is still debated for selecting advanced non-oncogene addicted non-small-cell lung cancer (NSCLC) patients who might benefit from immune checkpoint inhibitors (ICIs). Of note, TMB failed to predict a benefit in overall survival (OS) among such patients. Materials and methods The purpose of this meta-analysis was to compare efficacy outcomes among first-line immune-oncology (IO) agents versus standard platinum-based chemotherapy (CT) within two subgroups (TMB-low and TMB-high on either tissue or blood). We collected hazard ratios (HRs) to evaluate the association for progression-free survival (PFS) and OS, with the relative 95% confidence i…
The significance of epidermal growth factor receptor uncommon mutations in non-small cell lung cancer: A systematic review and critical appraisal
Uncommon epidermal growth factor receptor (EGFR) mutations collectively account for 10% of EGFR mutations, harboring heterogeneous molecular alterations within exons 18-21 with clinically variable responses to EGFR tyrosine kinase inhibitors (TKIs) in advanced Non-Small Cell Lung Cancer (NSCLC) patients. In addition, with the introduction of different NGS gene approach an improvement of EGFR mutations detection was reported. Today, no specific studies have prospectively evaluated uncommon sensitizing mutations in detail and no firm standard of care has been established in the first-line setting. The aim of this comprehensive review is to critically consider the clinical role of uncommon EGF…
TargetPlex FFPE-Direct DNA Library Preparation Kit for SiRe NGS panel: An international performance evaluation study
AimNext generation sequencing (NGS) represents a key diagnostic tool to identify clinically relevant gene alterations for treatment-decision making in cancer care. However, the complex manual workflow required for NGS has limited its implementation in routine clinical practice. In this worldwide study, we validated the clinical performance of the TargetPlex FFPE-Direct DNA Library Preparation Kit for NGS analysis. Impressively, this new assay obviates the need for separate, labour intensive and time-consuming pre-analytical steps of DNA extraction, purification and isolation from formalin-fixed paraffin embedded (FFPE) specimens in the NGS workflow.MethodsThe TargetPlex FFPE-Direct DNA Libr…
KRAS mutations testing in non-small cell lung cancer: the role of Liquid biopsy in the basal setting
In advanced stage non-small cell lung cancer (NSCLC) patients, Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) testing may soon acquire a predictive significance to select patients for AMG510 treatment. Since tissue samples are not always available, liquid biopsy may represent a viable option for KRAS testing. Here, we review the last three years clinical practice performed on 194 plasma based liquid biopsies by next generation sequencing (NGS) SiRe(®) panel. In particular, 36 (18.6%) KRAS mutated cases were identified, with an overall median allelic frequency of 5.0% (ranging between 0.2% and 46.8%). No concomitant mutations were observed in the other NSCLC clinical relevant genes includ…
Molecular Diagnostics: Innovative Technologies for Clinical and Translational Research
In recent years, cancer patients’ treatment has profoundly changed due to a better comprehension of the biological processes underlying tumor development and progression. Several tumors are defined as “oncogene addicted” meaning that they are strictly dependent on oncogene activation for their own survival. This discovery has indeed led the way to the development of target therapies that are able to specifically kill cancer cells sparing normal cells from toxicity. For these reasons, nowadays, treatment decision is strictly dependent on the molecular characterization of the tumor that can be achieved through different technologies. Within this chapter, we will discuss the main technologies …
A narrative review on the implementation of liquid biopsy as a diagnostic tool in thoracic tumors during the COVID-19 pandemic.
Objective: In this review, we evaluate the role of liquid biopsy in managing lung cancer patients during the still ongoing coronavirus disease 2019 (COVID-19) healthcare emergency. Background: The novel influenza coronavirus (severe acute respiratory syndrome coronavirus or SARSCoV-2) has upended several aspects of our lives, including medical activities. In this setting, many routine cancer diagnostic and therapeutic procedures have been suspended, leading to delays in diagnosis, treatments, and, ultimately, increases in cancer mortality rates. Equally drastic has been the impact of COVID-19 on clinical trials, many of which have been stalled or have never begun. This has left many patient…
ESPRESSO highlights the binary nature of the ultra-metal-poor giant HE 0107-5240
Context. The vast majority of the known stars of ultra low metallicity ([Fe=H] >-4:5) are known to be enhanced in carbon, and belong to the 'low-carbon band' (A(C) = log(C=H) + 12 7:6). It is generally, although not universally, accepted that this peculiar chemical composition reflects the chemical composition of the gas cloud out of which these stars were formed. The first ultra-metalpoor star discovered, HE 0107-5240, is also enhanced in carbon and belongs to the 'low-carbon band'. It has recently been claimed to be a long-period binary, based on radial velocity measurements. It has also been claimed that this binarity may explain its peculiar composition as being due to mass transfer fro…
Next generation diagnostic algorithm in non-small cell lung cancer predictive molecular pathology: The KWAY Italian multicenter cost evaluation study
Abstract Aims The KWAY project aims to investigate the economic sustainability of the up-front NGS technologies adoption in the analysis of clinically relevant molecular alterations in NSCLC patients. Methods The diagnostic workflow and the related sustained costs of five Italian referral centers were assessed in four different evolving scenarios were analyzed. For each scenario, two alternative testing strategies were evaluated: the Maximized Standard strategy and the Maximized NGS strategy. Results For each center, the robustness of obtained results was verified through a deterministic sensitivity analysis, observing the variation of total costs based on a variation of ±20 % of the input …
Tumor mutational burden on cytological samples: A pilot study.
Background Immune-checkpoint inhibitors (ICIs) represent an important treatment option for patients who have advanced stage non-small cell lung cancer (NSCLC). Currently, evaluation of the expression level of programmed death-ligand 1 (PD-L1) has proven highly successful as a positive predictive biomarker for ICIs. In addition to PD-L1, other promising predictive biomarkers are emerging, including high tumor mutational burden (TMB-H). However, measuring TMB-H remains challenging for several reasons, among which is the difficulty in obtaining adequate tissue material from NSCLC patients. There are no data in the current literature regarding the possibility of adopting cell blocks (CBs) for T…