Prospective, multicenter validation of a platform for rapid molecular profiling of central nervous system tumors.

Molecular data integration plays a central role in central nervous system (CNS) tumor diagnostics but currently used assays pose limitations due to technical complexity, equipment and reagent costs, as well as lengthy turnaround times. We previously reported the development of Rapid-CNS, an adaptive-sampling-based nanopore sequencing workflow. Here we comprehensively validated and further developed Rapid-CNS for intraoperative use.

A nationwide comprehensive genomic profiling and molecular tumor board platform for patients with advanced cancer.

The Belgian Approach for Local Laboratory Extensive Tumor Testing (BALLETT) study assessed the feasibility of using comprehensive genomic profiling (CGP) in clinical decision-making for patients with advanced cancers. This multi-center study enrolled 872 patients from 12 Belgian hospitals. CGP was performed on tumor tissues using a standardized CGP panel (523 genes) across nine laboratories with success in 93% of patients and a median turnaround time of 29 days.

Surveillance of Disease Progression in Metastatic Breast Cancer by Molecular Counting of Circulating Tumor DNA Using Plasma-SeqSensei Breast Cancer in Vitro Diagnostics Assay.

Circulating tumor DNA (ctDNA) quantification surpasses cancer antigen 15 to 3 for metastatic breast cancer surveillance. Clinical translation, however, is limited because of uncertainties about the optimal method and clinically valid ctDNA decision thresholds. Plasma-SeqSensei Breast Cancer IVD kit (PSS) is a novel assay for ctDNA molecular counting, detecting ≥0.

Successful Multimodal Therapy with Intracerebral Liposomal Amphotericin B and Systemic High-Dose Isavuconazole in Proven Disseminated Aspergillosis.

We report the case of a 32-year-old man receiving chemotherapeutics for an acute B-lymphoblastic leukemia who developed proven cerebral and pulmonary aspergillosis with . Because of progressive fungal disease with neurological deterioration despite adequate systemic antifungal therapy and surgical debridement, intracerebral administration of liposomal amphotericin B was initiated at 5 mg twice weekly. This led to improvement of the cerebral infection.

DeltaMSI: artificial intelligence-based modeling of microsatellite instability scoring on next-generation sequencing data.

Background: DNA mismatch repair deficiency (dMMR) testing is crucial for detection of microsatellite unstable (MSI) tumors. MSI is detected by aberrant indel length distributions of microsatellite markers, either by visual inspection of PCR-fragment length profiles or by automated bioinformatic scoring on next-generation sequencing (NGS) data. The former is time-consuming and low-throughput while the latter typically relies on simplified binary scoring of a single parameter of the indel distribution.

Cancer Registration, Molecular Marker Status, and Adherence to the WHO 2016 Classification of Pathology Reports for Glioma Diagnosed during 2017-2019 in Belgium.

Introduction: The objective of this study was to cross-check and, if necessary, adjust registered ICD-O-3 topography and morphology codes with the findings in pathology reports available at the Belgian Cancer Registry (BCR) for glioma patients. Additionally, integration of molecular markers in the pathological diagnosis and concordance with WHO 2016 classification is investigated.

Methods: Since information regarding molecular tests and corresponding conclusions are not available as structured data at population level, a manual screening of all pseudonymized pathology reports available at the BCR for registered glioma patients (2017-2019) was conducted.

Application of an Ultrasensitive NGS-Based Blood Test for the Diagnosis of Early-Stage Lung Cancer: Sensitivity, a Hurdle Still Difficult to Overcome.

Diagnosis of lung cancer requires histological examination of a tissue sample, which in turn requires an invasive procedure that cannot always be obtained. Circulating tumor DNA can be reliably detected in blood samples of advanced-stage lung cancer patients and might also be a minimally invasive alternative for early-stage lung cancer detection. We wanted to explore the potential of targeted deep sequencing as a test for the diagnosis of early-stage lung cancer in combination with imaging.

The Use of Pan-Tropomyosin Receptor Kinase Immunohistochemistry as a Screening Tool for the Detection of Neurotrophic Tropomyosin-Related Kinase Fusions: Real-World Data from a National Multicentric Retrospective Study.

Introduction: The neurotrophic tropomyosin-related kinase (NTRK) genes encode the tropomyosin receptor kinases (TRKs). Patients with solid tumors harboring an oncogenic NTRK fusion are eligible for treatment with TRK inhibitors. NTRK fusion is often associated with TRK overexpression.

Shallow whole-genome sequencing: a useful, easy to apply molecular technique for CNA detection on FFPE tumor tissue-a glioma-driven study.

Copy number alterations (CNAs) have increasingly become part of the diagnostic algorithm of glial tumors. Alterations such as homozygous deletion of CDKN2A/B, 7 +/ 10 - chromosome copy number changes or EGFR amplification are predictive of a poor prognosis. The codeletion of chromosome arms 1p and 19q, typically associated with oligodendroglioma, implies a more favorable prognosis.

Inter-observer agreement for the histological diagnosis of invasive lobular breast carcinoma.

Invasive lobular breast carcinoma (ILC) is the second most common breast carcinoma (BC) subtype and is mainly driven by loss of E-cadherin expression. Correct classification of BC as ILC is important for patient treatment. This study assessed the degree of agreement among pathologists for the diagnosis of ILC.

Interobserver variability in the assessment of stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative invasive breast carcinoma influences the association with pathological complete response: the IVITA study.

High stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative breast cancer (TNBC) are associated with pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). Histopathological assessment of sTILs in TNBC biopsies is characterized by substantial interobserver variability, but it is unknown whether this affects its association with pCR. Here, we aimed to investigate the degree of interobserver variability in an international study, and its impact on the relationship between sTILs and pCR.

Comparison of microsatellite instability detection by immunohistochemistry and molecular techniques in colorectal and endometrial cancer.

DNA mismatch repair deficiency (dMMR) testing is crucial for diagnosing Lynch syndrome and detection of microsatellite unstable (MSI) tumors eligible for immunotherapy. The aim of this study was to compare the relative diagnostic performance of three molecular MSI assays: polymerase chain reaction (PCR), MSI testing by Idylla and next-generation-sequencing (NGS) on 49 tumor samples (28 colorectal and 21 endometrial adenocarcinomas) versus immunohistochemistry (IHC). Discrepancies were investigated by MLH1 methylation analysis and integrated with germline results if available.

Shallow-depth sequencing of cell-free DNA for Hodgkin and diffuse large B-cell lymphoma (differential) diagnosis: a standardized approach with underappreciated potential.

Shallow-depth sequencing of cell-free DNA, a cheap and standardized approach to obtain molecular information on tumors non-invasively, is insufficiently explored for lymphoma diagnosis and disease follow-up. This study collected 318 samples, including longitudinal liquid and paired solid biopsies, from a prospectively recruited cohort of 38 Hodgkin lymphoma (HL) and 85 aggressive B-cell non- HL patients, represented by 81 diffuse large B-cell lymphoma (DLBCL) cases. Following sequencing, copy number alterations and viral read fractions were derived and analyzed.

Immunohistochemistry as a screening tool for NTRK gene fusions: results of a first Belgian ring trial.

A Belgian ring trial for pan-TRK immunohistochemistry (IHC) staining was organised to harmonise pan-TRK IHC staining protocols and interpretation. As a reference method, the VENTANA pan-TRK Assay (clone EPR17341) on the Benchmark Ultra platform was selected. Six samples were selected: 2 negative, 2 fusion positive and 2 samples with wild-type endogenous TRK expression.

Shallow whole-genome sequencing of plasma cell-free DNA accurately differentiates small from non-small cell lung carcinoma.

Background: Accurate lung cancer classification is crucial to guide therapeutic decisions. However, histological subtyping by pathologists requires tumor tissue-a necessity that is often intrinsically associated with procedural difficulties. The analysis of circulating tumor DNA present in minimal-invasive blood samples, referred to as liquid biopsies, could therefore emerge as an attractive alternative.

Interobserver variability in upfront dichotomous histopathological assessment of ductal carcinoma in situ of the breast: the DCISion study.

Histopathological assessment of ductal carcinoma in situ, a nonobligate precursor of invasive breast cancer, is characterized by considerable interobserver variability. Previously, post hoc dichotomization of multicategorical variables was used to determine the "ideal" cutoffs for dichotomous assessment. The present international multicenter study evaluated interobserver variability among 39 pathologists who performed upfront dichotomous evaluation of 149 consecutive ductal carcinomas in situ.

Risk of Development of More-advanced Lesions in Patients With Inflammatory Bowel Diseases and Dysplasia.

Background & Aims: Patients with inflammatory bowel diseases (IBD) have increased risks of dysplasia and colitis-associated cancer (CAC). We evaluated the risk of development of high-grade dysplasia (HGD) or CAC after diagnosis of dysplasia using data from a national cohort of patients with IBD.

Methods: We performed a multicenter retrospective analysis of data collected from 7 tertiary referral regional or academic centers in Belgium.

Foreign body granuloma reaction following SIRT mimicking peritoneal metastases: a word of caution.

Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver malignancy with poor survival rates. Surgical resection is the only curative treatment option, yet only a small portion of cases are resectable. In unresectable situations, suggested therapy consists of a systemic chemotherapy regimen with cisplatinum and gemcitabine.

Antitumoral activity of tyrosine kinase inhibitors in patients with non-small cell lung cancer harbouring rare epidermal growth factor receptor mutations.

Introduction: Mutations in the epidermal growth factor receptor (EGFR) have been reported as predictive markers of tumour response to tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC). Although the "common" EGFR mutations have been associated with response to EGFR-TKIs, the correlation with response to treatment for many other rare mutations is still unclear. The aim of this study was to investigate the clinical significance of rare and complex mutations, and the efficacy of EGFR-TKIs in this selected group of patients.

Transfusion-induced serum sickness.

Background: Transfusion-induced serum sickness reactions are rarely reported in the literature. The Type III hypersensitivity reaction to heterologous proteins involves deposition of complement and immune complexes in small vessel walls resulting in a leukocytoclastic vasculitis. A case of a multiply transfused patient with several episodes of serum sickness reactions is presented.