Detecting ALK, ROS1, and RET fusions and the METΔex14 splicing variant in liquid biopsies of non-small-cell lung cancer patients using RNA-based techniques.

ALK, ROS1, and RET fusions and MET∆ex14 variant associate with response to targeted therapies in non-small-cell lung cancer (NSCLC). Technologies for fusion testing in tissue must be adapted to liquid biopsies, which are often the only material available. In this study, circulating-free RNA (cfRNA) and extracellular vesicle RNA (EV-RNA) were purified from liquid biopsies.

Cancer as an infective disease: the role of EVs in tumorigenesis.

Cancer is conventionally considered an evolutionary disease where tumor cells adapt to the environment and evolve eventually leading to the formation of metastasis through the seeding and growth of metastasis-initiating cells in distant organs. Tumor cell and tumor-stroma communication via soluble factors and extracellular vesicles (EVs) are essential for the success of the metastatic process. As the field of EVs advances, growing data support the role of tumor-derived EVs not only in modifying the microenvironment to facilitate tumor progression but also in inducing changes in cells outside the primary tumor that may lead to a malignant transformation.

Circulating Tumor DNA as a Cancer Biomarker: An Overview of Biological Features and Factors That may Impact on ctDNA Analysis.

Cancer cells release nucleic acids, freely or associated with other structures such as vesicles into body fluids, including blood. Among these nucleic acids, circulating tumor DNA (ctDNA) has emerged as a minimally invasive biomarker for tumor molecular profiling. However, certain biological characteristics of ctDNA are still unknown.

KRAS p.G12C mutation occurs in 1% of EGFR-mutated advanced non-small-cell lung cancer patients progressing on a first-line treatment with a tyrosine kinase inhibitor.

Background: KRAS is mutated in ∼30% of non-small-cell lung cancer (NSCLC) but it has also been identified as one of the mechanisms underlying resistance to tyrosine kinase inhibitors (TKIs) in EGFR-positive NSCLC patients. Novel KRAS inhibitors targeting KRAS p.G12C mutation have been developed recently with promising results.

NGS-based liquid biopsy profiling identifies mechanisms of resistance to ALK inhibitors: a step toward personalized NSCLC treatment.

Despite impressive and durable responses, nonsmall cell lung cancer (NSCLC) patients treated with anaplastic lymphoma kinase (ALK) inhibitors (ALK-Is) ultimately progress due to development of resistance. Here, we have evaluated the clinical utility of circulating tumor DNA (ctDNA) profiling by next-generation sequencing (NGS) upon disease progression. We collected 26 plasma and two cerebrospinal fluid samples from 24 advanced ALK-positive NSCLC patients at disease progression to an ALK-I.

Phase II clinical trial with metronomic oral vinorelbine and tri-weekly cisplatin as induction therapy, subsequently concomitant with radiotherapy (RT) in patients with locally advanced, unresectable, non-small cell lung cancer (NSCLC). Analysis of survival and value of ctDNA for patient selection.

Background: Little progress has been achieved in non-small cell lung cancer (NSCLC) patients with unresectable stage III disease and new drug schemes are warranted.

Material And Methods: In this open-label, single-arm, phase II trial 65 treatment-naïve stage III NSCLC deemed surgically unresectable by a multidisciplinary team were treated with 2 cycles of induction cisplatin at 80 mg/m every 21 days plus metronomic oral vinorelbine at 50 mg/day every Monday, Wednesday and Friday. During the concomitant treatment with thoracic radiotherapy cisplatin was administered in the same manner but oral vinorelbine was reduced to 30 mg/day.

Comprehensive cross-platform comparison of methods for non-invasive EGFR mutation testing: results of the RING observational trial.

Several platforms for noninvasive EGFR testing are currently used in the clinical setting with sensitivities ranging from 30% to 100%. Prospective studies evaluating agreement and sources for discordant results remain lacking. Herein, seven methodologies including two next-generation sequencing (NGS)-based methods, three high-sensitivity PCR-based platforms, and two FDA-approved methods were compared using 72 plasma samples, from EGFR-mutant non-small-cell lung cancer (NSCLC) patients progressing on a first-line tyrosine kinase inhibitor (TKI).

ctDNA analysis reveals different molecular patterns upon disease progression in patients treated with osimertinib.

Background: Several clinical trials have demonstrated the efficacy and safety of osimertinib in advanced non-small-cell lung cancer (NSCLC). However, there is significant unexplained variability in treatment outcome.

Methods: Observational prospective cohort of 22 pre-treated patients with stage IV NSCLC harboring the epidermal growth factor receptor () p.

Clinical utility of liquid biopsy for the diagnosis and monitoring of NSCLC patients.

Background: Genomic rearrangement in anaplastic lymphoma kinase () gene occurs in 3-7% of patients with non-small-cell lung cancer (NSCLC). The detection of this alteration is crucial as positive NSCLC patients benefit from inhibitors, which improve both the patient's quality of life and overall survival (OS) compared to traditional chemotherapy.

Content: In routine clinical practice, rearrangements are detected using tissue biopsy.

Applying Data Science methods and tools to unveil healthcare use of lung cancer patients in a teaching hospital in Spain.

Purpose: Our primary goal was to study the use of outpatient attendances by lung cancer patients in Hospital Universitario Puerta de Hierro Majadahonda (HUPHM), Spain, by leveraging our Electronic Patient Record (EPR) and structured clinical registry of lung cancer cases as well as assessing current Data Science methods and tools.

Methods/patients: We applied the Cross-Industry Standard Process for Data Mining (CRISP-DM) to integrate and analyze activity data extracted from the EPR (9.3 million records) and clinical data of lung cancer patients from a previous registry that was curated into a new, structured database based on REDCap.

Prognostic value of quantitative ctDNA levels in non small cell lung cancer patients.

Background: Circulating tumor DNA (ctDNA) levels correlate well with tumor bulk. In this paper we aim to estimate the prognostic value of the dynamic quantification of ctDNA levels.

Materials And Methods: A total of 251 serial plasma samples from 41 non-small-cell lung cancer patients who carried an activating EGFR mutation were analysed by digital PCR.

Concordance between circulating tumor cells and clinical status during follow-up in anaplastic lymphoma kinase (ALK) non-small-cell lung cancer patients.

Background: The identification of anaplastic lymphoma kinase (ALK) rearrangements is found in approximately 5% of non-small-cell lung cancers (NSCLCs). However, the development of liquid biopsies as a diagnostic tool is less developed in these cases. This study investigates the use of CTCs during treatment, together with an extended follow-up to correlate with clinical evolution.