Single-cell AI-based detection and prognostic and predictive value of DNA mismatch repair deficiency in colorectal cancer.

Testing for DNA mismatch repair deficiency (MMRd) is recommended for all colorectal cancers (CRCs). Automating this would enable precision medicine, particularly if providing information on etiology not captured by deep learning (DL) methods. We present AIMMeR, an AI-based method for determination of mismatch repair (MMR) protein expression at a single-cell level in routine pathology samples.

Standardizing data collection in adjuvant colon cancer trials: A consensus project from the IDEA and ACCENT international consortia and national experts.

Background: Despite contributions provided by the recent clinical trials, several issues and challenges still remain unsolved in adjuvant colon cancer (CC). Hence, further studies should be planned to better refine risk assessment as well as to establish the optimal treatment strategy in the adjuvant setting. However, it is necessary to request adequate, contemporary and relevant variables and report them homogeneously in order to bring maximal information when analyzing their prognostic value.

Prognostic and Predictive Value of Immunoscore in Stage III Colorectal Cancer: Pooled Analysis of Cases From the SCOT and IDEA-HORG Studies.

Purpose: Immunoscore (IS) is prognostic in stage III colorectal cancer (CRC) and may predict benefit of duration (6 3 months) of adjuvant infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy. We sought to determine IS prognostic and predictive value in stage-III CRC treated with adjuvant FOLFOX or oral capecitabine and infusional oxaliplatin (CAPOX) in the SCOT and IDEA-HORG trials.

Methods: Three thousand sixty-one cases had tumor samples, of which 2,643 (1,792 CAPOX) were eligible for IS testing.

JAK/STAT3 represents a therapeutic target for colorectal cancer patients with stromal-rich tumors.

Colorectal cancer (CRC) is a heterogenous malignancy underpinned by dysregulation of cellular signaling pathways. Previous literature has implicated aberrant JAK/STAT3 signal transduction in the development and progression of solid tumors. In this study we investigate the effectiveness of inhibiting JAK/STAT3 in diverse CRC models, establish in which contexts high pathway expression is prognostic and perform in depth analysis underlying phenotypes.

Multiplex analysis of intratumoural immune infiltrate and prognosis in patients with stage II-III colorectal cancer from the SCOT and QUASAR 2 trials: a retrospective analysis.

Background: Tumour-infiltrating CD8 cytotoxic T cells confer favourable prognosis in colorectal cancer. The added prognostic value of other infiltrating immune cells is unclear and so we sought to investigate their prognostic value in two large clinical trial cohorts.

Methods: We used multiplex immunofluorescent staining of tissue microarrays to assess the densities of CD8, CD20, FoxP3, and CD68 cells in the intraepithelial and intrastromal compartments from tumour samples of patients with stage II-III colorectal cancer from the SCOT trial (ISRCTN59757862), which examined 3 months versus 6 months of adjuvant oxaliplatin-based chemotherapy, and from the QUASAR 2 trial (ISRCTN45133151), which compared adjuvant capecitabine with or without bevacizumab.

Accounting for intensity variation in image analysis of large-scale multiplexed clinical trial datasets.

Multiplex immunofluorescence (mIF) imaging can provide comprehensive quantitative and spatial information for multiple immune markers for tumour immunoprofiling. However, application at scale to clinical trial samples sourced from multiple institutions is challenging due to pre-analytical heterogeneity. This study reports an analytical approach to the largest multi-parameter immunoprofiling study of clinical trial samples to date.

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.

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.

Long-Term Outcomes and Exploratory Analyses of the Randomized Phase III BILCAP Study.

Purpose: The BILCAP study described a modest benefit for capecitabine as adjuvant therapy for curatively resected biliary tract cancer (BTC), and capecitabine has become the standard of care. We present the long-term data and novel exploratory subgroup analyses.

Methods: This randomized, controlled, multicenter, phase III study recruited patients age 18 years or older with histologically confirmed cholangiocarcinoma or muscle-invasive gallbladder cancer after resection with curative intent and an Eastern Cooperative Oncology Group performance status of < 2.

Patients' Preferences for 3 Months vs 6 Months of Adjuvant Chemotherapy for Colon Cancer.

Background: SCOT was an international, randomized phase 3 trial of 3 months vs 6 months of adjuvant chemotherapy with oxaliplatin and a fluoropyrimidine in patients with colorectal cancer. We sought patients' preferences for 3 months vs 6 months of adjuvant chemotherapy in the SCOT trial.

Methods: SCOT participants from Australia and New Zealand completed a validated questionnaire (at 3 and 18 months) to elicit the minimum survival benefits judged necessary to make an extra 3 months of adjuvant chemotherapy worthwhile, based on their experience.

Three Versus Six Months of Adjuvant Doublet Chemotherapy for Patients With Colorectal Cancer: A Multi-Country Cost-Effectiveness and Budget Impact Analysis.

Background: The Short Course Oncology Treatment (SCOT) trial demonstrated non-inferiority, less toxicity, and cost-effectiveness from a UK perspective of 3 versus 6 months of oxaliplatin-based chemotherapy for patients with colorectal cancer. This study assessed the cost-effectiveness of shorter treatment and the budget impact of implementing trial findings from the perspectives of all countries recruited to SCOT: Australia, Denmark, New Zealand, Spain, Sweden, and the United Kingdom.

Patients And Methods: Individual cost-utility analyses were performed from the perspective of each country.

Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): a phase 3, open-label, randomised, controlled trial.

Background: Advanced biliary tract cancer has a poor prognosis. Cisplatin and gemcitabine is the standard first-line chemotherapy regimen, but no robust evidence is available for second-line chemotherapy. The aim of this study was to determine the benefit derived from second-line FOLFOX (folinic acid, fluorouracil, and oxaliplatin) chemotherapy in advanced biliary tract cancer.

The Glasgow Microenvironment Score associates with prognosis and adjuvant chemotherapy response in colorectal cancer.

Background: The Glasgow Microenvironment Score (GMS) combines peritumoural inflammation and tumour stroma percentage to assess interactions between tumour and microenvironment. This was previously demonstrated to associate with colorectal cancer (CRC) prognosis, and now requires validation and assessment of interactions with adjuvant therapy.

Methods: Two cohorts were utilised; 862 TNM I-III CRC validation cohort, and 2912 TNM II-III CRC adjuvant chemotherapy cohort (TransSCOT).

Adjuvant chemotherapy in colon cancer: state of the art and future perspectives.

Purpose Of Review: This article will review the results of recent studies, which have investigated the duration of adjuvant chemotherapy and also suggest, which aspects of adjuvant treatment need investigation in future studies.

Recent Findings: The IDEA collaboration investigated whether the duration of adjuvant chemotherapy with an oxaliplatin doublet could be reduced from 6 to 3 months. Although this study did not demonstrate noninferiority for 3 months treatment, it did show noninferiority for patients receiving 3 months CAPOX chemotherapy and for those patients with low-risk stage III disease receiving 3 months' treatment.

Histological phenotypic subtypes predict recurrence risk and response to adjuvant chemotherapy in patients with stage III colorectal cancer.

Histological 'phenotypic subtypes' that classify patients into four groups (immune, canonical, latent and stromal) have previously been demonstrated to stratify survival in a stage I-III colorectal cancer (CRC) pilot cohort. However, clinical utility has not yet been validated. Therefore, this study assessed prognostic value of these subtypes in additional patient cohorts along with associations with risk of recurrence and response to chemotherapy.

Capecitabine compared with observation in resected biliary tract cancer (BILCAP): a randomised, controlled, multicentre, phase 3 study.

Background: Despite improvements in multidisciplinary management, patients with biliary tract cancer have a poor outcome. Only 20% of patients are eligible for surgical resection with curative intent, with 5-year overall survival of less than 10% for all patients. To our knowledge, no studies have described a benefit of adjuvant therapy.

Patterns of progression, treatment of progressive disease and post-progression survival in the New EPOC study.

Background: The addition of cetuximab (CTX) to perioperative chemotherapy (CT) for operable colorectal liver metastases resulted in a shorter progression-free survival. Details of disease progression are described to further inform the primary study outcome.

Methods: A total of 257 KRAS wild-type patients were randomised to CT alone or CT with CTX.

Quality of life, long-term survivors and long-term outcome from the ABC-02 study.

Background: The ABC-02 (Advanced Biliary Tract Cancer) study established cisplatin and gemcitabine (CisGem) as the standard first-line chemotherapy for patients with locally advanced or metastatic biliary tract cancer (BTC). We examine quality of life (QoL), describe the long-term survivors and provide a long-term outcome.

Methods: A total of 410 BTC patients were randomised to receive either CisGem or gemcitabine alone (Gem); 324 patients consented to complete EORTC QLQ-C30 and EORTC QLQ-PAN26 QoL questionnaires; 268 (83%) patients returned at least one QoL questionnaire (134 in each arm).

A randomised, open-label phase II trial of afatinib versus cetuximab in patients with metastatic colorectal cancer.

Purpose: This randomised phase II trial aimed to compare efficacy of the irreversible ErbB family blocker, afatinib, with cetuximab in patients with KRAS wild-type metastatic colorectal adenocarcinoma (mCRC) with progression following oxaliplatin- and irinotecan-based regimens. Efficacy in patients with KRAS mutations was also evaluated.

Patients And Methods: Patients with KRAS wild-type tumours were randomised 2:1 to afatinib (40 mg/day, increasing to 50 mg/day if minimal toxicity) or cetuximab weekly (400 mg/m2 loading dose, then 250 mg/m2/week) according to number of previous chemotherapy lines.

Gemcitabine and capecitabine with or without telomerase peptide vaccine GV1001 in patients with locally advanced or metastatic pancreatic cancer (TeloVac): an open-label, randomised, phase 3 trial.

Background: We aimed to assess the efficacy and safety of sequential or simultaneous telomerase vaccination (GV1001) in combination with chemotherapy in patients with locally advanced or metastatic pancreatic cancer.

Methods: TeloVac was a three-group, open-label, randomised phase 3 trial. We recruited patients from 51 UK hospitals.

Systemic chemotherapy with or without cetuximab in patients with resectable colorectal liver metastasis: the New EPOC randomised controlled trial.

Background: Surgery for colorectal liver metastases results in an overall survival of about 40% at 5 years. Progression-free survival is increased with the addition of oxaliplatin and fluorouracil chemotherapy. The addition of cetuximab to these chemotherapy regimens results in an overall survival advantage in patients with advanced disease who have the KRAS exon 2 wild-type tumour genotype.