Early Detection of Ovarian Cancer Using Cell-Free DNA Fragmentomes and Protein Biomarkers.

There is an unmet need for effective ovarian cancer screening and diagnostic approaches that enable earlier-stage cancer detection and increased overall survival. We have developed a high-performing accessible approach that evaluates cfDNA fragmentomes and protein biomarkers to detect ovarian cancer.

High Prevalence of Chromosomal Rearrangements and LINE Retrotranspositions Detected in Formalin-Fixed, Paraffin-Embedded Colorectal Cancer Tissue.

Structural variants (SVs) caused by chromosomal rearrangements in common fragile sites or long interspersed nuclear element (LINE) retrotranspositions are highly prevalent in colorectal cancer. However, methodology for the targeted detection of these SVs is lacking. This article reports the use of formalin-fixed, paraffin-embedded targeted-locus capture (FFPE-TLC) sequencing as a novel technology for the targeted detection of tumor-specific SVs.

Integrated noninvasive diagnostics for prediction of survival in immunotherapy.

Background: Integrating complementary diagnostic data sources promises enhanced robustness in the predictive performance of artificial intelligence (AI) models, a crucial requirement for future clinical validation/implementation. In this study, we investigate the potential value of integrating data from noninvasive diagnostic modalities, including chest computed tomography (CT) imaging, routine laboratory blood tests, and clinical parameters, to retrospectively predict 1-year survival in a cohort of patients with advanced non-small-cell lung cancer, melanoma, and urothelial cancer treated with immunotherapy.

Patients And Methods: The study included 475 patients, of whom 444 had longitudinal CT scans and 475 had longitudinal laboratory data.

Early evaluation of the effectiveness and cost-effectiveness of ctDNA-guided selection for adjuvant chemotherapy in stage II colon cancer.

Background: Current patient selection for adjuvant chemotherapy (ACT) after curative surgery for stage II colon cancer (CC) is suboptimal, causing overtreatment of high-risk patients and undertreatment of low-risk patients. Postoperative circulating tumor DNA (ctDNA) could improve patient selection for ACT.

Objectives: We conducted an early model-based evaluation of the (cost-)effectiveness of ctDNA-guided selection for ACT in stage II CC in the Netherlands to assess the conditions for cost-effective implementation.

Interleukin-6 in relation to early recurrence in primary, localized soft tissue sarcoma: An addition for existing risk classification systems?

Background: Several inflammatory markers have gained interest as prognostic factors for cancer. The aim of this study is to evaluate the inflammatory markers interleukin-6 (IL-6), C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as predictive markers for aggressive behavior and early recurrences in primary, localized soft tissue sarcoma (STS).

Methods: 115 STS patients were retrospectively reviewed.

Optimising primary molecular profiling in non-small cell lung cancer.

Introduction: Molecular profiling of NSCLC is essential for optimising treatment decisions, but often incomplete. We assessed the efficacy of protocolised molecular profiling in the current standard-of-care (SoC) in a prospective observational study in the Netherlands and measured the effect of providing standardised diagnostic procedures. We also explored the potential of plasma-based molecular profiling in the primary diagnostic setting.

Can blood-based markers predict RECIST progression in non-small cell lung cancer treated with immunotherapy?

Purpose: In this study, we aimed to evaluate the potential of routine blood markers, serum tumour markers and their combination in predicting RECIST-defined progression in patients with stage IV non-small cell lung cancer (NSCLC) undergoing treatment with immune checkpoint inhibitors.

Methods: We employed time-varying statistical models and machine learning classifiers in a Monte Carlo cross-validation approach to investigate the association between RECIST-defined progression and blood markers, serum tumour markers and their combination, in a retrospective cohort of 164 patients with NSCLC.

Results: The performance of the routine blood markers in the prediction of progression free survival was moderate.

External Quality Assessment on Molecular Tumor Profiling with Circulating Tumor DNA-Based Methodologies Routinely Used in Clinical Pathology within the COIN Consortium.

Background: Identification of tumor-derived variants in circulating tumor DNA (ctDNA) has potential as a sensitive and reliable surrogate for tumor tissue-based routine diagnostic testing. However, variations in pre(analytical) procedures affect the efficiency of ctDNA recovery. Here, an external quality assessment (EQA) was performed to determine the performance of ctDNA mutation detection work flows that are used in current diagnostic settings across laboratories within the Dutch COIN consortium (ctDNA on the road to implementation in The Netherlands).

Risk factors and implications associated with ultrasound-diagnosed nephrocalcinosis in cats with chronic kidney disease.

Background: Microscopic nephrocalcinosis is a common pathological feature of chronic kidney disease (CKD) in cats. Detection of macroscopic nephrocalcinosis using ultrasonography and its implications remain unexplored.

Objectives: Identify risk factors associated with ultrasound-diagnosed nephrocalcinosis and evaluate the influence of nephrocalcinosis on CKD progression.

Evaluating the effectiveness of pre-operative diagnosis of ovarian cancer using minimally invasive liquid biopsies by combining serum human epididymis protein 4 and cell-free DNA in patients with an ovarian mass.

Objective: To assess the feasibility of scalable, objective, and minimally invasive liquid biopsy-derived biomarkers such as cell-free DNA copy number profiles, human epididymis protein 4 (HE4), and cancer antigen 125 (CA125) for pre-operative risk assessment of early-stage ovarian cancer in a clinically representative and diagnostically challenging population and to compare the performance of these biomarkers with the Risk of Malignancy Index (RMI).

Methods: In this case-control study, we included 100 patients with an ovarian mass clinically suspected to be early-stage ovarian cancer. Of these 100 patients, 50 were confirmed to have a malignant mass (cases) and 50 had a benign mass (controls).

A scenario-drafting study to explore potential future implementation pathways of circulating tumor DNA testing in oncology.

Circulating tumor DNA (ctDNA) detection has multiple promising applications in oncology, but the road toward implementation in clinical practice is unclear. We aimed to support the implementation process by exploring potential future pathways of ctDNA testing. To do so, we studied four ctDNA-testing applications in two cancer types and elicited opinions from 30 ctDNA experts in the Netherlands.

A phase 2 trial combining afatinib with cetuximab in patients with EGFR exon 20 insertion-positive non-small cell lung cancer.

Background: Epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations are the third most common EGFR mutations in patients with non-small cell lung cancer (NSCLC) and are associated with primary resistance to EGFR tyrosine kinase inhibitors (TKIs). There is evidence of activity of combining EGFR TKIs with monoclonal antibodies. This study reports on the efficacy and safety of afatinib in combination with cetuximab.

Presumed residual thymic tissue is a common finding in thoracic computed tomography in adult dogs.

Residual thymic tissue is a common incidental finding in thoracic CT of human adults. To determine whether presumed residual thymic tissue is also a common incidental finding in adult dogs, a two part-study was performed. The first part was a prospective, descriptive design where CT examination was performed in six canine cadavers within 24 h after death and presumed residual thymic tissue was examined pathologically.

Squamous Cell Carcinoma Antigen in the Follow-up of Patients With Head and Neck Cancer.

Objective: to determine if the tumor marker squamous cell carcinoma antigen (SCC-Ag) observed over time may contribute to the early detection of recurrence, metastasis, and second primary tumors in the follow-up of patients with head and neck squamous cell carcinoma (HNSCC).

Study Design: A retrospective analysis of patients with HNSCC and at least one SCC-Ag measurement was conducted. Hazard ratios (HRs) were used to determine the correlation between SCC-Ag and an event.

Chronic Pancreas Allograft Rejection Followed by Successful HLA-Incompatible Islet Alloautotransplantation: A Novel Strategy?

The purpose of pancreas or islet transplantation is to restore glycemic control in order to mitigate diabetes-related complications and prevent severe hypoglycemia. Complications from chronic pancreas allograft rejection may lead to transplantectomy, even when the endocrine function remains preserved. We present first evidence of a successful HLA incompatible islet re-transplantation with islets isolated from a rejecting pancreas allograft after simultaneous kidney pancreas transplantation.

The Clinical Utility of Post-Transplant Monitoring of Donor-Specific Antibodies in Stable Renal Transplant Recipients: A Consensus Report With Guideline Statements for Clinical Practice.

Solid phase immunoassays improved the detection and determination of the antigen-specificity of donor-specific antibodies (DSA) to human leukocyte antigens (HLA). The widespread use of SPI in kidney transplantation also introduced new clinical dilemmas, such as whether patients should be monitored for DSA pre- or post-transplantation. Pretransplant screening through SPI has become standard practice and DSA are readily determined in case of suspected rejection.

IMPemBra: a phase 2 study comparing pembrolizumab with intermittent/short-term dual MAPK pathway inhibition plus pembrolizumab in patients with melanoma harboring the BRAFV600 mutation.

Background: Continuous combination of MAPK pathway inhibition (MAPKi) and anti-programmed death-(ligand) 1 (PD-(L)1) showed high response rates, but only limited improvement in progression-free survival (PFS) at the cost of a high frequency of treatment-related adverse events (TRAE) in patients with BRAF-mutated melanoma. Short-term MAPKi induces T-cell infiltration in patients and is synergistic with anti-programmed death-1 (PD-1) in a preclinical melanoma mouse model. The aim of this phase 2b trial was to identify an optimal regimen of short-term MAPKi with dabrafenib plus trametinib in combination with pembrolizumab.

Screening approaches for lung cancer by blood-based biomarkers: Challenges and opportunities.

Lung cancer (LC) is one of the leading causes for cancer-related deaths in the world, accounting for 28% of all cancer deaths in Europe. Screening for lung cancer can enable earlier detection of LC and reduce lung cancer mortality as was demonstrated in several large image-based screening studies such as the NELSON and the NLST. Based on these studies, screening is recommended in the US and in the UK a targeted lung health check program was initiated.

De novo designed ice-binding proteins from twist-constrained helices.

Attaining molecular-level control over solidification processes is a crucial aspect of materials science. To control ice formation, organisms have evolved bewildering arrays of ice-binding proteins (IBPs), but these have poorly understood structure-activity relationships. We propose that reverse engineering using de novo computational protein design can shed light on structure-activity relationships of IBPs.