Circulating tumour DNA and risk of recurrence in patients with asymptomatic versus symptomatic colorectal cancer.

Background: Multiple initiatives aim to develop circulating tumour DNA (ctDNA) tests for early cancer detection in asymptomatic individuals. The few studies describing ctDNA-testing in both asymptomatic and symptomatic patients report lower ctDNA detection in the asymptomatic patients. Here, we explore if asymptomatic patients differ from symptomatic patients e.

Error-Corrected Deep Targeted Sequencing of Circulating Cell-Free DNA from Colorectal Cancer Patients for Sensitive Detection of Circulating Tumor DNA.

Circulating tumor DNA (ctDNA) is a promising biomarker, reflecting the presence of tumor cells. Sequencing-based detection of ctDNA at low tumor fractions is challenging due to the crude error rate of sequencing. To mitigate this challenge, we developed ultra-deep mutation-integrated sequencing (UMIseq), a fixed-panel deep targeted sequencing approach, which is universally applicable to all colorectal cancer (CRC) patients.

Beyond basics: Key mutation selection features for successful tumor-informed ctDNA detection.

Tumor-informed mutation-based approaches are frequently used for detection of circulating tumor DNA (ctDNA). Not all mutations make equally effective ctDNA markers. The objective was to explore if prioritizing mutations using mutational features-such as cancer cell fraction (CCF), multiplicity, and error rate-would improve the success rate of tumor-informed ctDNA analysis.

DREAMS: deep read-level error model for sequencing data applied to low-frequency variant calling and circulating tumor DNA detection.

Circulating tumor DNA detection using next-generation sequencing (NGS) data of plasma DNA is promising for cancer identification and characterization. However, the tumor signal in the blood is often low and difficult to distinguish from errors. We present DREAMS (Deep Read-level Modelling of Sequencing-errors) for estimating error rates of individual read positions.

Impact of Whole Genome Doubling on Detection of Circulating Tumor DNA in Colorectal Cancer.

Objective: Circulating tumor DNA (ctDNA) is a candidate biomarker of cancer with practice-changing potential in the detection of both early and residual disease. Disease stage and tumor size affect the probability of ctDNA detection, whereas little is known about the influence of other tumor characteristics on ctDNA detection. This study investigates the impact of tumor cell whole-genome doubling (WGD) on the detection of ctDNA in plasma collected preoperatively from newly diagnosed colorectal cancer (CRC) patients.

Comparing single-target and multitarget approaches for postoperative circulating tumour DNA detection in stage II-III colorectal cancer patients.

Circulating tumour DNA (ctDNA) detection for postoperative risk stratification in cancer patients has great clinical potential. However, low ctDNA abundances complicates detection. Multitarget (MT) detection strategies have been developed to increase sensitivity.

Error Characterization and Statistical Modeling Improves Circulating Tumor DNA Detection by Droplet Digital PCR.

Background: Droplet digital PCR (ddPCR) is a widely used and sensitive application for circulating tumor DNA (ctDNA) detection. As ctDNA is often found in low abundance, methods to separate low-signal readouts from noise are necessary. We aimed to characterize the ddPCR-generated noise and, informed by this, create a sensitive and specific ctDNA caller.

cGAS-STING pathway expression as a prognostic tool in NSCLC.

Background: Disease recurrence in localized lung adenocarcinoma is a major obstacle for improving the overall outcome of lung cancer. Thus, better prognostic biomarkers are needed to identify patients at risk. In order to clear cancer, immune detection of tumor cells is of vital importance.

Development of blood-based biomarker tests for early detection of colorectal neoplasia: Influence of blood collection timing and handling procedures.

Introduction: Blood-based, cancer-associated biomarkers are susceptible to a variety of well-known preanalytical factors. The influence of bowel preparation before a diagnostic colonoscopy on biomarker levels is, however, poorly investigated. The present study assessed the influence of bowel preparation on colorectal cancer-associated biomarkers.

Correlation between early dynamics in circulating tumour DNA and outcome from FOLFIRI treatment in metastatic colorectal cancer.

Chemotherapy resistance remains a challenge in the clinical management of metastatic colorectal cancer (mCRC). Here, early changes in cell-free circulating tumour DNA (ctDNA) levels were explored as a marker of therapeutic efficacy. Twenty-four mCRC patients were enrolled and treated with FOLFIRI based first-line therapy.

Total cell-free DNA, carcinoembryonic antigen, and C-reactive protein for assessment of prognosis in patients with metastatic colorectal cancer.

In late-stage metastatic colorectal cancer, difficult treatment decisions should incorporate a thorough evaluation of the patient's general condition and subject for shared decision making. Assessment of the individual patients' prognosis is valuable in this setting. The aim was to analyze the prognostic value of plasma levels of total cell-free DNA, carcinoembryonic antigen and C-reactive protein in 97 heavily pretreated patients with metastatic colorectal cancer.

A method for treatment monitoring using circulating tumour DNA in cancer patients without targetable mutations.

Background: The potentials of circulating tumour DNA (ctDNA) have been studied for non-invasive disease monitoring in patients with targetable mutations. However, the majority of cancer patients harbour no targetable mutations. A workflow including targeted next-generation sequencing (NGS) and droplet digital PCR (ddPCR) could be used for monitoring treatment in these patients.

Measuring KRAS Mutations in Circulating Tumor DNA by Droplet Digital PCR and Next-Generation Sequencing.

Measuring total cell-free DNA (cfDNA) or cancer-specific mutations herein has presented as new tools in aiding the treatment of cancer patients. Studies show that total cfDNA bears prognostic value in metastatic colorectal cancer (mCRC) and that measuring cancer-specific mutations could supplement biopsies. However, limited information is available on the performance of different methods.

The T790M resistance mutation in EGFR is only found in cfDNA from erlotinib-treated NSCLC patients that harbored an activating EGFR mutation before treatment.

Background: Lung cancer patients with an activating mutation in the EGFR (epidermal growth factor receptor) can develop resistance to erlotinib treatment, which is often mediated by the T790M resistance mutation in EGFR. The difficulties in obtaining biopsies at progression make it challenging to investigate the appearance of the T790M mutation at progression in large patient cohorts. We have used cell free DNA (cfDNA) from patients treated with erlotinib to investigate if the development of a T790M mutation coincides with the presence of an activating EGFR mutation in the pre-treatment blood sample.

Increased PD-L1 expression in erlotinib-resistant NSCLC cells with gene amplification is reversed upon MET-TKI treatment.

Introduction: Cancer cells can achieve immune evasion by expressing the programmed death receptor 1 ligand (PD-L1) on the cell surface. Blockade of the receptor (PD-1) can avert this evasion. Here we aim at investigating PD-L1 expression in erlotinib-resistant lung cancer cells with () gene amplification.

Correlation between circulating mutant DNA and metabolic tumour burden in advanced non-small cell lung cancer patients.

Background: Mutated circulating cell-free DNA (cfDNA) has been suggested as a surrogate marker of tumour burden and aggressiveness of disease. We examined the association between the level of plasma mutant cfDNA and metabolic tumour burden (MTB) measured by F-fluoro-D-glucose positron emission tomography/computed tomography (F-FDG PET/CT). Furthermore, the presence of mutant cfDNA was correlated with patient survival.

Early Change in FDG-PET Signal and Plasma Cell-Free DNA Level Predicts Erlotinib Response in EGFR Wild-Type NSCLC Patients.

Introduction: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are a treatment option in the second- or third-line palliative setting in EGFR wild-type (wt) non-small cell lung cancer (NSCLC) patients. However, response rates are low, and only approximately 25% will achieve disease control. Early prediction of treatment resistance could accelerate discontinuation of ineffective treatment and reduce unnecessary toxicity.

Increase in soluble PD-1 is associated with prolonged survival in patients with advanced EGFR-mutated non-small cell lung cancer treated with erlotinib.

Objectives: The central immune co-inhibitory programmed cell death receptor/ligand 1 (PD-1/PD-L1) pathway plays a key role in tumor immune evasion in non-small cell lung cancer (NSCLC). Soluble PD-1 (sPD-1) can be detected in the blood, and preclinical evidence suggests that sPD-1 blocks PD-1/-L1 interaction and improves anti-tumor immunity. The present study compares the concentration of sPD-1 in the serum of advanced NSCLC patients with Epidermal Growth Factor Receptor (EGFR) mutation prior to erlotinib treatment and at the time of progression and correlates these results to patient outcome.

The role of epithelial to mesenchymal transition in resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer.

Inhibition of the epidermal growth factor receptor (EGFR) is an important strategy when treating non-small cell lung cancer (NSCLC) patients. However, intrinsic resistance or development of resistance during the course of treatment constitutes a major challenge. The knowledge on EGFR-directed tyrosine kinase inhibitors (TKIs) and their biological effect keeps increasing.

Ultra-micro samples can be used for mRNA quantification of lung cancer biomarkers.

Background: Isolating sufficient material for molecular testing remains challenging in non-small cell lung cancer (NSCLC). The use of new ultra-microsamples (uMS) is proven sufficient for DNA and mRNA detection, but whether uMS are useful for quantifying mRNA expression is unknown. We investigated if uMS from lung cancer patients can be used to generate quantitative data on mRNA expression.

Dasatinib and Doxorubicin Treatment of Sarcoma Initiating Cells: A Possible New Treatment Strategy.

Background. One of the major challenges affecting sarcoma treatment outcome, particularly that of metastatic disease, is resistance to chemotherapy. Cancer-initiating cells are considered a major contributor to this resistance.

Genetic polymorphism in the epidermal growth factor receptor gene predicts outcome in advanced non-small cell lung cancer patients treated with erlotinib.

Objectives: Epidermal growth factor receptor (EGFR) mutations are important predictors of treatment response to tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC). However, some patients with mutations do not respond and some patients without mutations show response. We therefore need additional biomarkers to improve the selection of these patients for treatment.