Adjuvant (chemo)radiotherapy for patients with head and neck cancer: can comorbidity risk scores predict outcome?

Purpose: This study compares the objective American Society of Anesthesiologists (ASA) and Adult Comorbidity Evaluation-27 (ACE-27) scores with the subjective Eastern Cooperative Oncology Group performance status (ECOG PS) for patient outcome prediction.

Methods: We retrospectively analyzed head and neck squamous cell carcinoma patients treated with adjuvant (chemo)radiotherapy at the LMU Munich from June 2008 to June 2015. The study focused on associations between patient outcomes; treatment failures; known risk factors (including human papillomavirus [HPV] status and tumor stage); and the comorbidity indices ECOG-PS, ASA score, and ACE-27.

Metabolic pathway-based subtypes associate glycan biosynthesis and treatment response in head and neck cancer.

Head and Neck Squamous Cell Carcinoma (HNSCC) is a heterogeneous malignancy that remains a significant challenge in clinical management due to frequent treatment failures and pronounced therapy resistance. While metabolic dysregulation appears to be a critical factor in this scenario, comprehensive analyses of the metabolic HNSCC landscape and its impact on clinical outcomes are lacking. This study utilized transcriptomic data from four independent clinical cohorts to investigate metabolic heterogeneity in HNSCC and define metabolic pathway-based subtypes (MPS).

Molecular characterization of the evolution of premalignant lesions in the upper aerodigestive tract.

Introduction: Early relapse and development of metastatic disease are some of the primary reasons for the poor prognosis of patients with head and neck squamous cell carcinoma (HNSCC). HNSCC is a heterogeneous disease which may develop in large premalignant fields of genetically altered cells. Yet knowing which individuals will progress and develop clinically significant cancers during their lifetimes remains one of the most important challenges of reducing HNSCC morbidity and mortality.

Receptor transfer between immune cells by autoantibody-enhanced, CD32-driven trogocytosis is hijacked by HIV-1 to infect resting CD4 T cells.

Immune cell phenotyping frequently detects lineage-unrelated receptors. Here, we report that surface receptors can be transferred from primary macrophages to CD4 T cells and identify the Fcγ receptor CD32 as driver and cargo of this trogocytotic transfer. Filamentous CD32 nanoprotrusions deposit distinct plasma membrane patches onto target T cells.

Impact of F-FDG PET Intensity Normalization on Radiomic Features of Oropharyngeal Squamous Cell Carcinomas and Machine Learning-Generated Biomarkers.

We aimed to investigate the effects of F-FDG PET voxel intensity normalization on radiomic features of oropharyngeal squamous cell carcinoma (OPSCC) and machine learning-generated radiomic biomarkers. We extracted 1,037 F-FDG PET radiomic features quantifying the shape, intensity, and texture of 430 OPSCC primary tumors. The reproducibility of individual features across 3 intensity-normalized images (body-weight SUV, reference tissue activity ratio to lentiform nucleus of brain and cerebellum) and the raw PET data was assessed using an intraclass correlation coefficient (ICC).

Why Do Men Reject Adjuvant Radiotherapy following Radical Prostatectomy? A Systematic Survey.

Introduction: The aim of this study was to investigate non-adherence rates to adjuvant radiotherapy (aRT) after radical prostatectomy (RP) and to obtain patient reported reasons for rejecting aRT despite recommendation by a multidisciplinary team discussion (MTD).

Methods: In a retrospective monocentric analysis, we identified 1,197 prostate cancer patients who underwent RP between 2014 and 2022 at our institution, of which 735 received a postoperative MTD recommendation. Patients with a recommendation for aRT underwent a structured phone interview with predefined standardised qualitative and quantitative questions and were stratified into "adherent" (aRT performed) and "non-adherent" groups (aRT not performed).

Hyperspectral imaging for monitoring of free flaps of the oral cavity: A feasibility study.

Objectives: Hyperspectral imaging (HSI) provides spectral information about hemoglobin, water and oxygen supply and has thus great potential in perfusion monitoring. The aim of the present study was to investigate the feasibility of HSI in the postoperative monitoring of intraoral free flaps.

Methods: The 14 patients receiving reconstructive head and neck surgery with a radial forearm free flap were included.

Wigner Distribution Deconvolution Adaptation for Live Ptychography Reconstruction.

We propose a modification of Wigner distribution deconvolution (WDD) to support live processing ptychography. Live processing allows to reconstruct and display the specimen transmission function gradually while diffraction patterns are acquired. For this purpose, we reformulate WDD and apply a dimensionality reduction technique that reduces memory consumption and increases processing speed.

5'-Ectonucleotidase CD73/NT5E supports EGFR-mediated invasion of HPV-negative head and neck carcinoma cells.

Background: Epithelial-to-mesenchymal transition (EMT) of malignant cells is a driving force of disease progression in human papillomavirus-negative (HPV-negative) head and neck squamous cell carcinomas (HNSCC). Sustained hyper-activation of epidermal growth factor receptor (EGFR) induces an invasion-promoting subtype of EMT (EGFR-EMT) characterized by a gene signature ("'EGFR-EMT_Signature'") comprising 5´-ectonucleotidase CD73. Generally, CD73 promotes immune evasion via adenosine (ADO) formation and associates with EMT and metastases.

The observational clinical registry (cohort design) of the European Reference Network on Rare Adult Solid Cancers: The protocol for the rare head and neck cancers.

Introduction: Care for head and neck cancers is complex in particular for the rare ones. Knowledge is limited and histological heterogeneity adds complexity to the rarity. There is a wide consensus that to support clinical research on rare cancer, clinical registries should be developed within networks specializing in rare cancers.

Isolation and characterization of head and neck cancer-derived peritumoral and cancer-associated fibroblasts.

Introduction: Head and neck squamous cell carcinomas (HNSCC) are characterized by strong cellular and molecular heterogeneity and treatment resistance entailing poor survival. Besides cell-intrinsic properties, carcinoma cells receive important cues from non-malignant cells within the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are a major component of the TME that impact on the molecular make-up of malignant cells and have a decisive function in tumor progression.

DeepClassPathway: Molecular pathway aware classification using explainable deep learning.

Objective: HPV-associated head and neck cancer is correlated with favorable prognosis; however, its underlying biology is not fully understood. We propose an explainable convolutional neural network (CNN) classifier, DeepClassPathway, that predicts HPV-status and allows patient-specific identification of molecular pathways driving classifier decisions.

Methods: The CNN was trained to classify HPV-status on transcriptome data from 264 (13% HPV-positive) and tested on 85 (25% HPV-positive) head and neck squamous carcinoma patients after transformation into 2D-treemaps representing molecular pathways.

A transcriptomic map of EGFR-induced epithelial-to-mesenchymal transition identifies prognostic and therapeutic targets for head and neck cancer.

Background: Epidermal growth factor receptor (EGFR) is both a driver oncogene and a therapeutic target in advanced head and neck squamous cell carcinoma (HNSCC). However, response to EGFR treatment is inconsistent and lacks markers for treatment prediction. This study investigated EGFR-induced epithelial-to-mesenchymal transition (EMT) as a central parameter in tumor progression and identified novel prognostic and therapeutic targets, and a candidate predictive marker for EGFR therapy response.

Simultaneous metabolite MALDI-MSI, whole exome and transcriptome analysis from formalin-fixed paraffin-embedded tissue sections.

Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) allows spatial analysis of proteins, metabolites, or small molecules from tissue sections. Here, we present the simultaneous generation and analysis of MALDI-MSI, whole-exome sequencing (WES), and RNA-sequencing data from the same formalin-fixed paraffin-embedded (FFPE) tissue sections. Genomic DNA and total RNA were extracted from (i) untreated, (ii) hematoxylin-eosin (HE) stained, and (iii) MALDI-MSI-analyzed FFPE tissue sections from three head and neck squamous cell carcinomas.

Integration of p16/HPV DNA Status with a 24-miRNA-Defined Molecular Phenotype Improves Clinically Relevant Stratification of Head and Neck Cancer Patients.

Human papillomavirus (HPV)-driven head and neck squamous cell carcinomas (HNSCC) generally have a more favourable prognosis. We hypothesized that HPV-associated HNSCC may be identified by an miRNA-signature according to their specific molecular pathogenesis, and be characterized by a unique transcriptome compared to HPV-negative HNSCC. We performed miRNA expression profiling of two p16/HPV DNA characterized HNSCC cohorts of patients treated by adjuvant radio(chemo)therapy (multicentre DKTK-ROG = 128, single-centre LMU-KKG = 101).

Analysis of genetic variants of frequently mutated genes in human papillomavirus-negative primary head and neck squamous cell carcinoma, resection margins, local recurrences and corresponding circulating cell-free DNA.

Background: Head and neck squamous cell carcinoma remains a substantial burden to global health. Despite evolving therapies, 5-year survival is <50% and unlike in other cancers, reliable molecular biomarkers to guide treatment do not exist.

Methods: We performed targeted panel next-generation sequencing to analyse somatic variants from primary and recurrent tumour tissue, corresponding resection margins and cell-free DNA from intra-operatively collected plasma samples from eight patients with human papillomavirus-negative head and neck squamous cell carcinoma.

Lessons learned: the first consecutive 1000 patients of the CCCMunich Molecular Tumor Board.

Purpose: In 2016, the University of Munich Molecular Tumor Board (MTB) was implemented to initiate a precision oncology program. This review of cases was conducted to assess clinical implications and functionality of the program, to identify current limitations and to inform future directions of these efforts.

Methods: Charts, molecular profiles, and tumor board decisions of the first 1000 consecutive cases (01/2016-03/2020) were reviewed.

Diagnostic accuracy of preoperative lymph node staging of bladder cancer according to different lymph node locations: A multicenter cohort from the European Association of Urology - Young Academic Urologists.

Background: The preoperative lymph node (LN) staging of bladder cancer (BCa) addresses the subsequent therapeutic strategy and influences patient's prognosis. However, sparce evidence exists regarding the accuracy of conventional cross-sectional imaging, such as computed tomography or magnetic resonance imaging, in correctly detect LN status. We aimed to assess the diagnostic accuracy of conventional cross-sectional imaging in detecting preoperative LN involvement among BCa patients treated with radical cystectomy and pelvic lymph node dissection.

Immediate radical cystectomy versus BCG immunotherapy for T1 high-grade non-muscle-invasive squamous bladder cancer: an international multi-centre collaboration.

Purpose: To compare cancer-specific mortality (CSM) and overall mortality (OM) between immediate radical cystectomy (RC) and Bacillus Calmette-Guérin (BCG) immunotherapy for T1 squamous bladder cancer (BCa).

Methods: We retrospectively analysed 188 T1 high-grade squamous BCa patients treated between 1998 and 2019 at fifteen tertiary referral centres. Median follow-up time was 36 months (interquartile range: 19-76).

Liquid BIOpsy for MiNimal RESidual DiSease Detection in Head and Neck Squamous Cell Carcinoma (LIONESS)-a personalised circulating tumour DNA analysis in head and neck squamous cell carcinoma.

Background: Head and neck squamous cell carcinoma (HNSCC) remain a substantial burden to global health. Cell-free circulating tumour DNA (ctDNA) is an emerging biomarker but has not been studied sufficiently in HNSCC.

Methods: We conducted a single-centre prospective cohort study to investigate ctDNA in patients with p16-negative HNSCC who received curative-intent primary surgical treatment.

Therapy-Related Transcriptional Subtypes in Matched Primary and Recurrent Head and Neck Cancer.

Purpose: The genetic relatedness between primary and recurrent head and neck squamous cell carcinomas (HNSCC) reflects the extent of heterogeneity and therapy-driven selection of tumor subpopulations. Yet, current treatment of recurrent HNSCC ignores the molecular characteristics of therapy-resistant tumor populations.

Experimental Design: From 150 tumors, 74 primary HNSCCs were RNA sequenced and 38 matched primary/recurrent tumor pairs were both whole-exome and RNA sequenced.