Comparing deep learning and pathologist quantification of cell-level PD-L1 expression in non-small cell lung cancer whole-slide images.

Programmed death-ligand 1 (PD-L1) expression is currently used in the clinic to assess eligibility for immune-checkpoint inhibitors via the tumor proportion score (TPS), but its efficacy is limited by high interobserver variability. Multiple papers have presented systems for the automatic quantification of TPS, but none report on the task of determining cell-level PD-L1 expression and often reserve their evaluation to a single PD-L1 monoclonal antibody or clinical center. In this paper, we report on a deep learning algorithm for detecting PD-L1 negative and positive tumor cells at a cellular level and evaluate it on a cell-level reference standard established by six readers on a multi-centric, multi PD-L1 assay dataset.

Clinical outcomes and molecular profiling of advanced metastatic castration-resistant prostate cancer patients treated with Ac-PSMA-617 targeted alpha-radiation therapy.

Introduction: Targeted alpha-radiation therapy (TAT) with Ac-labeled prostate-specific membrane antigen (PSMA) ligands is a promising novel treatment option for metastatic castration-resistant prostate cancer (mCRPC) patients. However, limited data are available on efficacy, quality of life (QoL), and pretherapeutic biomarkers. The aim of this study was to evaluate the efficacy of Ac-PSMA TAT and impact on QoL in advanced mCRPC, and to explore predictive biomarkers on pretherapeutic metastatic tissue biopsies.

Glucose and glutamine metabolism in relation to mutational status in NSCLC histological subtypes.

Background: Both hypoxia and oncogenic mutations rewire tumor metabolism. In this study, glucose and glutamine metabolism-related markers were examined in stage I - resectable stage IIIA non-small cell lung cancer (NSCLC). Furthermore, expression of metabolism-related markers was correlated with mutational status to examine mutations associated with rewired tumor metabolism.

Tumor Delineation and Quantitative Assessment of Glucose Metabolic Rate within Histologic Subtypes of Non-Small Cell Lung Cancer by Using Dynamic F Fluorodeoxyglucose PET.

Purpose To assess whether dynamic fluorine 18 (F) fluorodeoxyglucose (FDG) positron emission tomography (PET) has added value over static F-FDG PET for tumor delineation in non-small cell lung cancer (NSCLC) radiation therapy planning by using pathology volumes as the reference standard and to compare pharmacokinetic rate constants of F-FDG metabolism, including regional variation, between NSCLC histologic subtypes. Materials and Methods The study was approved by the institutional review board. Patients gave written informed consent.

Irreversible Respiratory Failure in a Full-Term Infant with Features of Pulmonary Interstitial Glycogenosis as Well as Bronchopulmonary Dysplasia.

Pulmonary interstitial glycogenosis (PIG) is a rare interstitial lung disease in the newborns. We report on the clinical presentation and pathological findings of a full-term male infant with pulmonary hypertension requiring extracorporeal membrane oxygenation (ECMO). An open lung biopsy demonstrated interstitial changes resembling pulmonary interstitial glycogenosis as well as bronchopulmonary dysplasia (BPD), without convincing evidence of maturational arrest, infection, alveolar proteinosis, or alveolar capillary dysplasia.

Mediastinal staging in daily practice: endosonography, followed by cervical mediastinoscopy. Do we really need both?

Objectives: In patients with lung cancer, endosonography has emerged as a minimally invasive method to obtain cytological proof of mediastinal lymph nodes, suspicious for metastases on imaging. In case of a negative result, it is currently recommended that a cervical mediastinoscopy be performed additionally. However, in daily practice, a second procedure is often regarded superfluous.

EBUS and EUS guided fine needle aspirations for molecular diagnostic analysis in lung cancer.

In daily clinical practice the diagnosis of lung cancer is often based on cytological specimens. These cytological samples are increasingly obtained by ultrasound-guided techniques with fine needle aspirations. Recent developments have shown that transesophageal ultrasound guided fine needle aspiration (EUS-FNA) and endobronchial ultrasound guided transbronchial fine needle aspiration (EBUS-TBNA) are minimally invasive diagnostic and staging procedures that have shown to be highly sensitive and accurate.

Differences in metabolism between adeno- and squamous cell non-small cell lung carcinomas: spatial distribution and prognostic value of GLUT1 and MCT4.

Background: Hypoxia leads to changes in tumor cell metabolism such as increased glycolysis. In this study, we examined the spatial distribution of the glycolysis and hypoxia related markers glucose transporter 1 (GLUT1) and monocarboxylate transporter 4 (MCT4) expression in relation to the vasculature in stage I, II and resectable stage IIIA NSCLC. Furthermore, associations of these markers with survival were investigated.

Timeliness of lung cancer diagnosis and treatment in a rapid outpatient diagnostic program with combined 18FDG-PET and contrast enhanced CT scanning.

Introduction: Delays in the diagnosis of lung cancer are under debate and may affect outcome. The objectives of this study were to compare various delays in a rapid outpatient diagnostic program (RODP) for suspected lung cancer patients with those described in literature and with guideline recommendations, to investigate the effects of referral route and symptoms on delays, and to establish whether delays were related to disease stage and outcome.

Methods: A retrospective chart study was conducted of all patients with suspected lung cancer, referred to the RODP of our tertiary care university clinic between 1999 and 2009.

A brief retrospective report on the feasibility of epidermal growth factor receptor and KRAS mutation analysis in transesophageal ultrasound- and endobronchial ultrasound-guided fine needle cytological aspirates.

Introduction: Molecular testing for epidermal growth factor receptor (EGFR) and KRAS mutations is of increasing clinical importance in daily practice. In this study, we aimed to investigate the yield and applicability of molecular testing for KRAS and EGFR mutations in cytologic specimens obtained by EUS or endobronchial ultrasound (EBUS)-guided fine needle aspiration (FNA).

Methods: We selected all patients with an EUS- or EBUS-guided FNA positive for lung adenocarcinoma from the database of our tertiary care center for endosonography.

The role of (18)F-FDG PET in the differentiation between lung metastases and synchronous second primary lung tumours.

Purpose: In lung cancer patients with multiple lesions, the differentiation between metastases and second primary tumours has significant therapeutic and prognostic implications. The aim of this retrospective study was to investigate the potential of (18)F-FDG PET to discriminate metastatic disease from second primary lung tumours.

Methods: Of 1,396 patients evaluated by the thoracic oncology group between January 2004 and April 2009 at the Radboud University Nijmegen Medical Centre, patients with a synchronous second primary lung cancer were selected.

Differences in screening history, tumour characteristics and survival between women with screen-detected versus not screen-detected cervical cancer in the east of The Netherlands, 1992-2001.

Objective: In The Netherlands, despite a national screening programme since 1996, invasive cervical cancers have been detected in screened and non-screened women. The aim of this study was to determine differences between Pap-smear history, tumour characteristics and survival of patients with a tumour detected by the screening programme (SP) or outside the screening programme (OSP) in the region of the Comprehensive Cancer Centre Stedendriehoek Twente in the period 1992-2001.

Study Design: In this period, 263 cervical cancer cases in women aged 30-60 were selected from the regional cancer registry.