Pembrolizumab Versus chemotherapy in microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer: 5-year follow-up from the randomized phase 3 KEYNOTE-177 study.

Background: Results from the phase 3 KEYNOTE-177 study established pembrolizumab as a new first-line standard of care for microsatellite instability-high or mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC). Previous results from KEYNOTE-177 showed a statistically significant and clinically meaningful improvement in progression-free survival (PFS) with pembrolizumab versus chemotherapy ± bevacizumab/cetuximab in MSI-H/dMMR mCRC. Results after >5 years of follow-up are reported.

Adjuvant immunotherapy in patients with resected gastric and oesophagogastric junction cancer following preoperative chemotherapy with high risk for recurrence (ypN+ and/or R1): European Organisation of Research and Treatment of Cancer (EORTC) 1707 VESTIGE study.

Background: Patients with gastro-oesophageal adenocarcinoma with tumour-positive lymph nodes (ypN+) or positive surgical margins (R1) following neoadjuvant chemotherapy and resection are at high risk of recurrence. Adjuvant nivolumab is effective in oesophageal/oesophagogastric junction cancer and residual pathological disease following chemoradiation and surgery. Immune checkpoint inhibition has shown efficacy in advanced gastro-oesophageal cancer.

Risk of bowel obstruction in patients with colon cancer responding to immunotherapy: an international case series.

Background: Immunotherapy is used routinely for treating deficient mismatch repair (dMMR) colon cancer (CC). This case series highlights an emerging safety issue, where patients develop bowel obstruction associated with immunotherapy response.

Patients And Methods: Patients with dMMR CC who developed bowel obstruction while responding to immunotherapy were retrospectively identified.

Homopolymer switches mediate adaptive mutability in mismatch repair-deficient colorectal cancer.

Mismatch repair (MMR)-deficient cancer evolves through the stepwise erosion of coding homopolymers in target genes. Curiously, the MMR genes MutS homolog 6 (MSH6) and MutS homolog 3 (MSH3) also contain coding homopolymers, and these are frequent mutational targets in MMR-deficient cancers. The impact of incremental MMR mutations on MMR-deficient cancer evolution is unknown.

Biomarkers of systemic inflammation provide additional prognostic stratification in cancers of unknown primary.

Background: Biomarkers of systemic inflammation have been shown to predict outcomes in patients with cancer of unknown primary (CUP). We sought to validate these findings in patients with confirmed CUP (cCUP) and explore their role alongside existing clinicopathological prognostic categories.

Patients And Methods: CUP oncologist from across the United Kingdom were invited to include patients with cCUP referred to their local CUP multidisciplinary team.

Comprehensive Examination of Cholangiocarcinoma Patients Treated with Novel Targeted Therapies after Extended Molecular Profiling on Liquid Biopsies.

Background: Cholangiocarcinoma (CCA) is associated with poor outcomes and limited treatment options, leading to increased use of targeted therapies for its management. Here, we performed one of the largest single-centre reviews evaluating outcomes following personalised targeted agents in CCA patients.

Methods: All consecutive CCA patients receiving systemic therapy between January 2010 and April 2023 at UCLH were included.

A Practical Guide to Clinical Studies in Veterinary Oncology.

This article explains the authors' experiences about opportunities, perspectives, and considerations required to initiate clinical studies in a veterinary oncology practice. These details include the infrastructure required for appropriate study training for all staff. Negotiation of scope of work and fees for service with study sponsors is also discussed.

Genetic and immune landscape evolution in MMR-deficient colorectal cancer.

Mismatch repair-deficient (MMRd) colorectal cancers (CRCs) have high mutation burdens, which make these tumours immunogenic and many respond to immune checkpoint inhibitors. The MMRd hypermutator phenotype may also promote intratumour heterogeneity (ITH) and cancer evolution. We applied multiregion sequencing and CD8 and programmed death ligand 1 (PD-L1) immunostaining to systematically investigate ITH and how genetic and immune landscapes coevolve.

Novel genomic prognostic biomarkers for dogs with cancer.

Background: Growing evidence from dogs and humans supports the abundance of mutation-based biomarkers in tumors of dogs. Increasing the use of clinical genomic diagnostic testing now provides another powerful data source for biomarker discovery.

Hypothesis: Analyzed clinical outcomes in dogs with cancer profiled using SearchLight DNA, a cancer gene panel for dogs, to identify mutations with prognostic value.

The immunomodulatory role of IDO1-Kynurenine-NAD pathway in switching cold tumor microenvironment in PDAC.

Pancreatic ductal adenocarcinoma (PDAC) is the most common exocrine tumor of the pancreas characterized by late diagnosis, adverse overall 5-year survival, a higher propensity for metastatic disease, and lack of efficacy of systemic therapy options. These adverse outcomes can be partly attributed to complex tumor microenvironment (TME). Over the past decade, immunotherapy has revolutionized the management of certain cancers; thus far, the immunologically 'non-inflamed' tumor microenvironment in PDACs has proven to be challenging.

Client perceptions improve with collaborative care when managing dogs with cancer: a Collaborative Care Coalition study.

Objective: Collaboration between primary care veterinarians (pcVets) and veterinary oncologists is common for dogs diagnosed with cancer, but no data exist that explore dog owner utilization and perceptions of collaborative care. The objectives were to describe dog owner perceptions of the value of collaborative veterinary cancer care and identify drivers of a positive collaborative care experience between the pcVet and oncologic specialists.

Sample: 890 US dog owners who had pets diagnosed with cancer in the past 3 years.

Optimized immunosuppression to prevent graft failure in renal transplant recipients with HLA antibodies (OuTSMART): a randomised controlled trial.

Background: 3% of kidney transplant recipients return to dialysis annually upon allograft failure. Development of antibodies (Ab) against human leukocyte antigens (HLA) is a validated prognostic biomarker of allograft failure. We tested whether screening for HLA Ab, combined with an intervention to improve adherence and optimization of immunosuppression could prevent allograft failure.

Nutritional index for immune-checkpoint inhibitor in patients with metastatic gastro-esophageal junction/gastric cancer.

Background: Nutritional status is strongly associated to prognosis in metastatic gastrooesophageal junction (mGOJ)/gastric cancer (GC) patients. The aim of the present study was to develop an immune-checkpoint inhibitor (ICI)-specific nutritional index (NI).

Methods: Ten serum and anthropometric nutritional markers derived from blood tests or CT scans were analyzed at baseline in patients treated with second-line ICI and correlated with overall survival (OS).

Pembrolizumab in Asian patients with microsatellite-instability-high/mismatch-repair-deficient colorectal cancer.

The phase 3 KEYNOTE-177 study evaluated pembrolizumab versus chemotherapy with or without bevacizumab or cetuximab in patients with newly diagnosed, microsatellite-instability-high (MSI-H)/mismatch-repair-deficient (dMMR) metastatic colorectal cancer (mCRC). Primary endpoints were progression-free survival (PFS) per RECIST v1.1 by blinded independent central review (BICR) and overall survival (OS).

The phenotype of HLA-binding B cells from sensitized kidney transplant recipients correlates with clinically prognostic patterns of interferon-γ production against purified HLA proteins.

B cells play crucial roles in cell-mediated alloimmune responses. In vitro, B cells can support or regulate indirect T-cell alloreactivity in response to donor antigens on ELISpot and these patterns associate with clinical outcome. Previous reports of associations between B-cell phenotype and function have examined global phenotypes and responses to polyclonal stimuli.

Comparison of resident and intern salaries with the current living wage as a quantitative estimate of financial strain among postgraduate veterinary trainees.

Objective: To compare resident and intern salaries with current regional living wages as a quantitative estimate of financial strain.

Sample: 152 residency programs and 141 internship programs listed with the Veterinary Internship and Residency Matching Program for the 2021-2022 training year.

Procedures: Data were collected for program annual salary and location.

Trifluridine/Tipiracil in Metastatic Colorectal Cancer: A UK Multicenter Real-world Analysis on Efficacy, Safety, Predictive and Prognostic Factors.

Background: The orally administered combination trifluridine/tipiracil has been approved as third line treatment in mCRC, demonstrating survival benefit and acceptable toxicity profile in the phase III RECOURSE study.

Patient And Methods: We performed a multicenter retrospective real-world analysis of patients with mCRC receiving trifluridine/tipiracil between 2016 and 2019 in eight cancer centers across the United Kingdom.

Results: A total of 236 patients were included with median age of 69 years.

Immunogenomics of Colorectal Cancer Response to Checkpoint Blockade: Analysis of the KEYNOTE 177 Trial and Validation Cohorts.

Background & Aims: Colorectal cancer (CRC) shows variable response to immune checkpoint blockade, which can only partially be explained by high tumor mutational burden (TMB). We conducted an integrated study of the cancer tissue and associated tumor microenvironment (TME) from patients treated with pembrolizumab (KEYNOTE 177 clinical trial) or nivolumab to dissect the cellular and molecular determinants of response to anti- programmed cell death 1 (PD1) immunotherapy.

Methods: We selected multiple regions per tumor showing variable T-cell infiltration for a total of 738 regions from 29 patients, divided into discovery and validation cohorts.