Differential prognostic association of systemic inflammatory biomarkers on survival outcomes in head and neck squamous cell carcinoma patients by human papillomavirus status.

Systemic inflammatory response (SIR) markers are prognostic in various cancers. In a prospective cohort study (2006-2019) involving 2044 head and neck squamous cell carcinomas (HNSCC) patients, we assessed the prognostic associations of SIR markers at diagnosis, including NLR (neutrophil-to-lymphocyte ratio), PLR (platelet-to-lymphocyte ratio), LMR (lymphocyte-to-monocyte ratio), NMR (neutrophil-to-monocyte ratio), SII (systemic immune-inflammation index), eosinophil and WBC (white blood cell) levels, with progression-free (PFS) and overall survival (OS). Training (two-thirds randomly selected patients) and withheld test sets were created.

Prognostic and predictive effects of TP53 co-mutation in patients with non-small cell lung cancer with rare treatable driver mutations.

Background: TP53 mutations (TP53-MUT) are common in NSCLC and have been reported as predictive of response and prognostic of poor outcome in EGFR-mutant NSCLC. The impact of TP53-MUT in NSCLCs with rarer driver mutations and approved targeted treatments is unclear.

Methods: Records of 436 patients were reviewed and associations between TP53 status, demographics, and outcomes (overall response [ORR], survival [OS] and progression-free survival [PFS], and incidence of brain metastases [BM]), were investigated.

Pathogenic germline variants in small cell lung cancer: A systematic review and meta-analysis.

This systematic review and meta-analysis examined the prevalence and clinical impact of germline variants in small cell lung cancer (SCLC). Primary objectives included estimating the prevalence of germline variants in SCLC patients, while secondary objectives focused on their effects on patient outcomes. A comprehensive search was conducted in Ovid MEDLINE, EMBASE, and gray-literature databases (as of July 2024).

Development of a patient reported outcomes based machine learning model to predict recurrences in head and neck cancer.

Introduction: Recurrence rates among Head and Neck Cancer (HNC) patients are high, with earlier detection associated with improved survival. Patient-reported outcomes (PROs) have increasingly been found to predict patient care needs. Here, we examine whether PROs specific to HNC patients or general can predict disease progression using Machine Learning (ML) algorithms.

Machine Learning Models of Early Longitudinal Toxicity Trajectories Predict Cetuximab Concentration and Metastatic Colorectal Cancer Survival in the Canadian Cancer Trials Group/AGITG CO.17/20 Trials.

Purpose: Cetuximab (CET), targeting the epidermal growth factor receptor, is a systemic treatment option for patients with colorectal cancer. One known predictive factor for CET efficacy is the presence of CET-related rash; other putative toxicity factors include fatigue and nausea. Analysis of early CET-associated toxicities may reveal patient subpopulations that clinically benefit from long-term CET treatment.

TLR4 downregulation protects against cisplatin-induced ototoxicity in adult and pediatric patients with cancer.

Cisplatin causes permanent hearing loss or cisplatin-induced ototoxicity in over 50% of treated patients with cancer, leading to significant social and functional limitations. Interindividual variability in developing hearing loss suggests the role of genetic predispositions to cisplatin-induced hearing loss. We investigated genetic associations between cisplatin-induced ototoxicity and toll-like receptor 4 (TLR4), an immune receptor known to mediate inflammatory responses to cisplatin.

Performance of 8 Smoking Metrics for Modeling Survival in Head and Neck Squamous Cell Carcinoma.

Importance: Cigarette smoking is a strong risk factor for mortality in patients diagnosed with head and neck squamous cell carcinoma (HNSCC). However, little evidence supports which smoking metric best models the association between smoking and survival in HNSCC.

Objective: To determine which smoking metric best models a linear association between smoking exposure and overall survival (OS) in patients with HNSCC.

Deep learning-based clustering for endotyping and post-arthroplasty response classification using knee osteoarthritis multiomic data.

Objectives: Primary knee osteoarthritis (KOA) is a heterogeneous disease with clinical and molecular contributors. Biofluids contain microRNAs and metabolites that can be measured by omic technologies. Multimodal deep learning is adept at uncovering complex relationships within multidomain data.

Cell and transcriptomic diversity of infrapatellar fat pad during knee osteoarthritis.

Objectives: In this study, we employ a multiomic approach to identify major cell types and subsets, and their transcriptomic profiles within the infrapatellar fat pad (IFP), and to determine differences in the IFP based on knee osteoarthritis (KOA), sex and obesity status.

Methods: Single-nucleus RNA sequencing of 82 924 nuclei from 21 IFPs (n=6 healthy control and n=15 KOA donors), spatial transcriptomics and bioinformatic analyses were used to identify contributions of the IFP to KOA. We mapped cell subclusters from other white adipose tissues using publicly available literature.

Multi-Institutional Comparison of Quality of Life Between Open Versus Endoscopic Skull Base Approaches.

Objectives: The primary objective of this prospective review was to compare quality of life between patients undergoing endoscopic and open skull base approaches.

Study Type And Design: Prospective Review.

Methods: Five centers recruited consecutive patients treated surgically for skull base neoplasms between 2012 to 2018.

Analysis of outcomes in resected early-stage NSCLC with rare targetable driver mutations.

Background: Given advancements in adjuvant treatments for non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK)-targeted therapies, it is important to consider postoperative targeted therapies for other early-stage oncogene-addicted NSCLC. Exploring baseline outcomes for early-stage NSCLC with these rare mutations is crucial.

Objectives: This study aims to assess relapse-free survival (RFS) and overall survival (OS) in patients with resected early-stage NSCLC with rare targetable driver mutations.

Programmed Cell Death-Ligand 1 Expression and Clinical Outcomes Among Patients with Resected, Early-Stage Non-Small Cell Lung Cancer: A Real-World Study.

Treatment options for non-small cell lung cancer (NSCLC) are evolving, given recent and expected approvals of immune checkpoint inhibitors (ICIs) targeting programmed cell death-(ligand) 1 (PD-1/PD-L1). We retrospectively evaluated outcomes among patients with resected stage IB-IIIA NSCLC tumors expressing PD-L1 using PALEOS (Pan-cAnadian Lung cancEr Observational Study) data (2016-2019). Key outcomes included PD-L1 expression rate and treatment patterns, recurrence, and median overall (mOS) and disease-free survival (mDFS) among PD-L1+ patients.

Adaptive Universal Principles for Real-world Observational Studies (AUPROS): an approach to designing real-world observational studies for clinical, epidemiologic, and precision oncology research.

The field of precision oncology has witnessed several advances that stimulated the development of new clinical trial designs and the emergence of real-world data (RWD) as an important resource for evidence generation in healthcare decision-making. Here, we highlight our experience with an innovative approach to a set of Adaptive, Universal Principles for Real-world Observational Studies (AUPROS). To demonstrate the utility of these principles, we used a mixed-methods approach to assess three studies that follow AUPROS at Princess Margaret Cancer Centre: (1) Molecular Epidemiology of ThorAcic Lesions (METAL), (2) Translational Head And NecK Study (THANKS), and (3) CAnadian CAncers With Rare Molecular Alterations (CARMA; NCT04151342).

Smoking and alcohol by HPV status in head and neck cancer: a Mendelian randomization study.

HPV-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) are recognized as distinct entities. There remains uncertainty surrounding the causal effects of smoking and alcohol on the development of these two cancer types. Here we perform multivariable Mendelian randomization (MR) to evaluate the causal effects of smoking and alcohol on the risk of HPV-positive and HPV-negative HNSCC in 3431 cases and 3469 controls.

The role of genetic variants in the prediction of hearing loss due to cisplatin chemoradiotherapy.

Background: Concomitant high-dose cisplatin with radiotherapy is commonly used for treating head and neck squamous cell carcinoma (HNSCC). Cisplatin, often used with radiotherapy, is known for causing irreversible sensorineural hearing loss, with individual variability suggesting a genetic component. This study aims to enhance the predictive ability of the clinical prediction model for cisplatin-induced hearing loss (CIHL) in HNSCC patients, as outlined in Theunissen et al.

Reproducibility of Assessment of Lepidic (Noninvasive) Patterns in Lung Adenocarcinoma With Cytokeratin Immunostain Compared With Hematoxylin and Eosin and the Proposed New International Association for the Study of Lung Cancer (IASLC) Algorithm.

Introduction: Lepidic growth is considered noninvasive in lung nonmucinous adenocarcinoma, whereas other patterns are invasive. Considerable interobserver variability in assessing "invasion" has been reported. We assessed the utility of cytokeratin 7 (CK7) stain and recently proposed International Association for the Study of Lung Cancer criteria to improve assessment of noninvasion in lung adenocarcinoma.

Clinical Predictors of Cisplatin Chemoradiation-Induced Ototoxicity in HPV-Positive Oropharyngeal Squamous Cell Carcinoma: A Case-Control Study.

Background: Cisplatin-based chemoradiation is a standard treatment for many patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), an etiologically distinct subset of head and neck cancer. Although associated with good long-term survival, clinical risk factors for ototoxicity have been understudied in this population. This study aimed to evaluate clinical predictors associated with ototoxicity in HPV-positive OPSCC patients treated with cisplatin chemoradiation.

Early microRNA and metabolite changes after anterior cruciate ligament reconstruction surgery.

Objectives: Anterior cruciate ligament (ACL) reconstruction after injury does not prevent post-traumatic osteoarthritis (PTOA). Circulating microRNA (miRNA) and metabolite changes emerging shortly after ACL injury and reconstruction remain insufficiently defined, potentially harbouring early cues contributing to PTOA evolution. Moreover, their differential expression between females and males also may influence PTOA's natural trajectory.

COVID-19 vaccine immunogenicity and safety surrounding fourth and subsequent vaccine doses in patients with hematologic malignancies.

Background: Immune response to COVID-19 vaccine is diminished in patients with hematologic malignancy. There is limited data regarding response to vaccine doses in these patients.

Purpose: To quantify the humoral immune response engendered by 4th and subsequent doses of SARS-CoV-2 vaccination as measured by anti-Spike (anti-S) antibody levels, based on dried blood spot (DBS) testing, in patients with hematologic malignancies.

Development and Standardization of an Osteoradionecrosis Classification System in Head and Neck Cancer: Implementation of a Risk-Based Model.

Purpose: Osteoradionecrosis of the jaw (ORN) can manifest in varying severity. The aim of this study is to identify ORN risk factors and develop a novel classification to depict the severity of ORN.

Methods: Consecutive patients with head and neck cancer (HNC) treated with curative-intent intensity-modulated radiation therapy (IMRT) (≥45 Gy) from 2011 to 2017 were included.

Comparison of Ga-DOTATATE Positron Emmited Tomography/Computed Tomography and Gadoxetic Acid-Enhanced Magnetic Resonance Imaging for the Detection of Liver Metastases from Well-Differentiated Neuroendocrine Tumors.

This study aimed to compare the detection of neuroendocrine tumor liver metastases (NLMs) in hepatobiliary-specific contrast-enhanced MRI (pMR) versus Ga-DOTATATE PET/CT (DT-PET). This retrospective study cohort included 30 patients with well-differentiated neuroendocrine tumors who underwent both DT-PET and pMR. Two readers independently assessed NLMs count, SUVmax on DT-PET, and signal characteristics on pMR.

Analysis of prognostic germline polymorphisms in patients with advanced hepatocellular carcinoma.

Background: The prognosis of hepatocellular carcinoma (HCC) is influenced by both tumor and patient specific factors. Current therapies of advanced HCC target angiogenesis and immune evasion, however there are no clinically useful biomarkers to guide clinicians.

Methods: Our aim in this retrospective cohort study was to validate single nucleotide polymorphisms (SNPs) prognostic of outcome in advanced HCC from the literature, and to analyze exploratory SNPs chosen from evaluation of the HCC tumor immune microenvironment.

Dental Extractions Before Radiation Therapy and the Risk of Osteoradionecrosis in Patients With Head and Neck Cancer.

Importance: Patients with head and neck cancer undergo extraction of teeth with poor prognoses to minimize post-radiation therapy (RT) extractions, which are known to cause osteoradionecrosis (ORN). However, many patients are required to start RT before the extraction sites are completely healed. The role of pre-RT extractions in the development of ORN has been disputed in literature.