Pancreatic Adenocarcinoma: Long-Term Outcomes of Adjuvant Therapy in the ESPAC4 Phase III Trial.

Purpose: The ESPAC4 trial showed that adjuvant chemotherapy with gemcitabine plus capecitabine (GemCap) produced longer overall survival (OS) than gemcitabine monotherapy. Subsequently, the PRODIGE24-CCTG PA.6 trial showed even longer survival for modified fluorouracil, folinic acid, irinotecan, and oxaliplatin (mFOLFIRINOX) than gemcitabine but had more restrictive eligibility criteria.

The potential clinical utility of Whole Genome Sequencing for patients with cancer: evaluation of a regional implementation of the 100,000 Genomes Project.

Background: The 100,000 Genomes Project established infrastructure for Whole Genome Sequencing (WGS) in the United Kingdom.

Methods: A retrospective study of cancer patients recruited to the 100,000 Genomes Project by the West Midlands Genomics Medicine Centre, evaluating clinical relevance of results.

Results: After excluding samples with no sequencing data (1678/4851; 34.

Neoadjuvant immunotherapy for dMMR and pMMR colorectal cancers: therapeutic strategies and putative biomarkers of response.

Approximately 15% of locally advanced colorectal cancers (CRC) have DNA mismatch repair deficiency (dMMR), resulting in high microsatellite instability and a high tumour mutational burden. These cancers are frequently sensitive to therapy with immune-checkpoint inhibitors (ICIs) in the metastatic setting. This sensitivity seems to be even more pronounced in locally advanced disease, and organ preservation has become a realistic aim in ongoing clinical trials involving patients with dMMR rectal cancer.

Squamous Cell Carcinoma in Never Smokers: An Insight into SMARCB1 Loss.

Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) constituting 85% of cases. Among NSCLCs, squamous cell carcinoma (SqCC) is strongly associated with smoking. However, lung cancer in never smokers (LCINS) represents approximately 25% of lung cancer cases globally and shows increasing incidence, particularly in East Asia.

Extended pleurectomy decortication and chemotherapy versus chemotherapy alone for pleural mesothelioma (MARS 2): a phase 3 randomised controlled trial.

Background: Extended pleurectomy decortication for complete macroscopic resection for pleural mesothelioma has never been evaluated in a randomised trial. The aim of this study was to compare outcomes after extended pleurectomy decortication plus chemotherapy versus chemotherapy alone.

Methods: MARS 2 was a phase 3, national, multicentre, open-label, parallel two-group, pragmatic, superiority randomised controlled trial conducted in the UK.

MHC Class II is Induced by IFNγ and Follows Three Distinct Patterns of Expression in Colorectal Cancer Organoids.

Unlabelled: Tumor-specific MHC class II (tsMHC-II) expression impacts tumor microenvironmental immunity. tsMHC-II positive cancer cells may act as surrogate antigen-presenting cells and targets for CD4 T cell-mediated lysis. In colorectal cancer, tsMHC-II negativity is common, in cell lines due to promoter methylation.

A population-scale temporal case-control evaluation of COVID-19 disease phenotype and related outcome rates in patients with cancer in England (UKCCP).

Patients with cancer are at increased risk of hospitalisation and mortality following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the SARS-CoV-2 phenotype evolution in patients with cancer since 2020 has not previously been described. We therefore evaluated SARS-CoV-2 on a UK populationscale from 01/11/2020-31/08/2022, assessing case-outcome rates of hospital assessment(s), intensive care admission and mortality.

Deep immune B and plasma cell repertoire in non-small cell lung cancer.

Introduction: B cells, which have long been thought to be minor players in the development of anti-tumor responses, have been implicated as key players in lung cancer pathogenesis and response to checkpoint blockade in patients with lung cancer. Enrichment of late-stage plasma and memory cells in the tumor microenvironment has been shown in lung cancer, with the plasma cell repertoire existing on a functional spectrum with suppressive phenotypes correlating with outcome. B cell dynamics may be influenced by the inflammatory microenvironment observed in smokers and between LUAD and LUSC.

Spatial determination and prognostic impact of the fibroblast transcriptome in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma has a poor clinical outcome and responses to immunotherapy are suboptimal. Stromal fibroblasts are a dominant but heterogenous population within the tumor microenvironment and therapeutic targeting of stromal subsets may have therapeutic utility. Here, we combine spatial transcriptomics and scRNA-Seq datasets to define the transcriptome of tumor-proximal and tumor-distal cancer-associated fibroblasts (CAFs) and link this to clinical outcome.

TIGIT-based immunotherapeutics in lung cancer.

In this review, we explore the biology of the TIGIT checkpoint and its potential as a therapeutic target in lung cancer. We briefly review a highly selected set of clinical trials that have reported or are currently recruiting in non-small cell and small cell lung cancer, a disease transformed by the advent of PD-1/PD-L1 checkpoint blockade immunotherapy. We explore the murine data underlying TIGIT blockade and further explore the reliance of effective anti-TIGIT therapy on DNAM-1(CD226)-positive activated effector CD8+ T cells.

The evolution of lung cancer and impact of subclonal selection in TRACERx.

Lung cancer is the leading cause of cancer-associated mortality worldwide. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome.

The evolution of non-small cell lung cancer metastases in TRACERx.

Metastatic disease is responsible for the majority of cancer-related deaths. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis.

The Gut Microbiome, Microsatellite Status and the Response to Immunotherapy in Colorectal Cancer.

There is increasing evidence in a range of cancer types that the microbiome plays a direct role in modulating the anti-cancer immune response both at the gut level and systemically. Differences in the gut microbiota have been shown to correlate with differences in immunotherapy responses in a range of non-gastrointestinal tract cancers. DNA mismatch repair-deficient (dMMR) colorectal cancer (CRC) is radically different to DNA mismatch repair-proficient (pMMR) CRC in clinical phenotype and in its very good responses to immunotherapy.

Tissue-Resident Memory T Cells in Pancreatic Ductal Adenocarcinoma Coexpress PD-1 and TIGIT and Functional Inhibition Is Reversible by Dual Antibody Blockade.

Pancreatic ductal adenocarcinoma (PDAC) has a poor clinical outlook. Responses to immune checkpoint blockade are suboptimal and a much more detailed understanding of the tumor immune microenvironment is needed if this situation is to be improved. Here, we characterized tumor-infiltrating T-cell populations in patients with PDAC using cytometry by time of flight (CyTOF) and single-cell RNA sequencing.

The Cancer Research UK Stratified Medicine Programme as a model for delivering personalised cancer care.

Genomic screening is routinely used to guide the treatment of cancer patients in many countries. However, several multi-layered factors make this effort difficult to deliver within a clinically relevant timeframe. Here we share the learnings from the CRUK-funded Stratified Medicine Programme for advanced NSCLC patients, which could be useful to better plan future studies.

Germline genetic variation and predicting immune checkpoint inhibitor induced toxicity.

Immune checkpoint inhibitor (ICI) therapy has revolutionised the treatment of various cancer types. ICIs reinstate T-cell function to elicit an anti-cancer immune response. The resulting immune response can however have off-target effects which manifest as autoimmune type serious immune-related adverse events (irAE) in ~10-55% of patients treated.

Association of SARS-CoV-2 Spike Protein Antibody Vaccine Response With Infection Severity in Patients With Cancer: A National COVID Cancer Cross-sectional Evaluation.

Importance: Accurate identification of patient groups with the lowest level of protection following COVID-19 vaccination is important to better target resources and interventions for the most vulnerable populations. It is not known whether SARS-CoV-2 antibody testing has clinical utility for high-risk groups, such as people with cancer.

Objective: To evaluate whether spike protein antibody vaccine response (COV-S) following COVID-19 vaccination is associated with the risk of SARS-CoV-2 breakthrough infection or hospitalization among patients with cancer.

COVID-19: Third dose booster vaccine effectiveness against breakthrough coronavirus infection, hospitalisations and death in patients with cancer: A population-based study.

Purpose: People living with cancer and haematological malignancies are at an increased risk of hospitalisation and death following infection with acute respiratory syndrome coronavirus 2. Coronavirus third dose vaccine boosters are proposed to boost waning immune responses in immunocompromised individuals and increase coronavirus protection; however, their effectiveness has not yet been systematically evaluated.

Methods: This study is a population-scale real-world evaluation of the United Kingdom's third dose vaccine booster programme for cancer patients from 8th December 2020 to 7th December 2021.

Vaccine effectiveness against COVID-19 breakthrough infections in patients with cancer (UKCCEP): a population-based test-negative case-control study.

Background: People with cancer are at increased risk of hospitalisation and death following infection with SARS-CoV-2. Therefore, we aimed to conduct one of the first evaluations of vaccine effectiveness against breakthrough SARS-CoV-2 infections in patients with cancer at a population level.

Methods: In this population-based test-negative case-control study of the UK Coronavirus Cancer Evaluation Project (UKCCEP), we extracted data from the UKCCEP registry on all SARS-CoV-2 PCR test results (from the Second Generation Surveillance System), vaccination records (from the National Immunisation Management Service), patient demographics, and cancer records from England, UK, from Dec 8, 2020, to Oct 15, 2021.

Mortality Among Adults With Cancer Undergoing Chemotherapy or Immunotherapy and Infected With COVID-19.

Importance: Large cohorts of patients with active cancers and COVID-19 infection are needed to provide evidence of the association of recent cancer treatment and cancer type with COVID-19 mortality.

Objective: To evaluate whether systemic anticancer treatments (SACTs), tumor subtypes, patient demographic characteristics (age and sex), and comorbidities are associated with COVID-19 mortality.

Design, Setting, And Participants: The UK Coronavirus Cancer Monitoring Project (UKCCMP) is a prospective cohort study conducted at 69 UK cancer hospitals among adult patients (≥18 years) with an active cancer and a clinical diagnosis of COVID-19.