Perioperative chemotherapy superior to preoperative chemoradiotherapy for locally advanced EAC
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Nivolumab plus chemotherapy or ipilimumab in gastroesophageal cancer: exploratory biomarker analyses of a randomized phase 3 trial
First-line nivolumab-plus-chemotherapy demonstrated superior overall survival (OS) and progression-free survival versus chemotherapy for advanced gastroesophageal adenocarcinoma with programmed death ligand 1 combined positive score ≥ 5, meeting both primary end points of the randomized phase 3 CheckMate 649 trial. Nivolumab-plus-ipilimumab provided durable responses and higher survival rates versus chemotherapy; however, the prespecified OS significance boundary was not met. To identify biomarkers predictive of differential efficacy outcomes, post hoc exploratory analyses were performed using whole-exome sequencing and RNA sequencing. Nivolumab-based therapies demonstrated improved efficacy versus chemotherapy in hypermutated and, to a lesser degree, Epstein–Barr virus-positive tumors compared with chromosomally unstable and genomically stable tumors. Within the KRAS-altered subgroup, only patients treated with nivolumab-plus-chemotherapy demonstrated improved OS benefit versus chemotherapy. Low stroma gene expression signature scores were associated with OS benefit with nivolumab-based regimens; high regulatory T cell signatures were associated with OS benefit only with nivolumab-plus-ipilimumab. Our analyses suggest that distinct and overlapping pathways contribute to the efficacy of nivolumab-based regimens in gastroesophageal adenocarcinoma.
Exploring metabolic reprogramming in esophageal cancer: the role of key enzymes in glucose, amino acid, and nucleotide pathways and targeted therapies
Esophageal cancer (EC) is one of the most common malignancies worldwide with the character of poor prognosis and high mortality. Despite significant advancements have been achieved in elucidating the molecular mechanisms of EC, for example, in the discovery of new biomarkers and metabolic pathways, effective treatment options for patients with advanced EC are still limited. Metabolic heterogeneity in EC is a critical factor contributing to poor clinical outcomes. This heterogeneity arises from the complex interplay between the tumor microenvironment and genetic factors of tumor cells, which drives significant metabolic alterations in EC, a process known as metabolic reprogramming. Understanding the mechanisms of metabolic reprogramming is essential for developing new antitumor therapies and improving treatment outcomes. Targeting the distinct metabolic alterations in EC could enable more precise and effective therapies. In this review, we explore the complex metabolic changes in glucose, amino acid, and nucleotide metabolism during the progression of EC, and how these changes drive unique nutritional demands in cancer cells. We also evaluate potential therapies targeting key metabolic enzymes and their clinical applicability. Our work will contribute to enhancing knowledge of metabolic reprogramming in EC and provide new insights and approaches for the clinical treatment of EC.
Hot beverage intake and oesophageal cancer in the UK Biobank: prospective cohort study
Drinking maté, a type of tea consumed at a very hot temperature in South America has been considered as a risk factor for oesophageal squamous cell carcinoma (ESCC).
An axis-specific mitral annuloplasty ring eliminates mitral regurgitation allowing mitral annular motion in an ovine model
Current mitral annuloplasty rings fail to restrict the anteroposterior distance while allowing dynamic mitral annular changes. We designed and manufactured a mitral annuloplasty ring that demonstrated axis-specific, selective flexibility to meet this clinical need. The objectives were to evaluate ex vivo biomechanics of this ring and to validate the annular dynamics and safety after ring implantation in vivo.
Impact of low muscle mass and myosteatosis on treatment toxicity and survival outcomes in non-resectable pancreatic cancer patients treated with chemoradiotherapy
Low skeletal muscle mass and impaired muscle quality (myosteatosis) have been associated with poor outcomes in cancer patients. This study aimed to evaluate the impact of pre-therapeutic low muscle mass and myosteatosis on chemoradiotherapy (CRT)-induced toxicity and survival outcomes in patients with non-resectable pancreatic cancer (PC).
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