The incidence of oesophageal cancer, in particular adenocarcinoma, has markedly increased over the last four decades with adenocarcinoma becoming the dominant subtype in the West, and mortality rates are high. Nevertheless, overall survival of patients with oesophageal cancer has doubled in the past 20 years, with earlier diagnosis and improved treatments benefiting those patients who can be treated with curative intent. Advances in endotherapy, surgical approaches, and multimodal and other combination therapies have been reported. New vistas have emerged in targeted therapies and immunotherapy, informed by new knowledge in genomics and molecular biology, which present opportunities for personalised cancer therapy and novel clinical trials. This review focuses exclusively on the curative intent treatment pathway, and highlights emerging advances.

Textbook outcome (TBO) is a composite measure of a number of peri-operative and clinical outcomes in oesophagogastric malignancy. It has previously been shown that TBOs are associated with improved overall survival in both oesophageal and gastric cancer. The influence of a minimally invasive approach (MIA) on TBO is not well defined. The purpose of this study is to validate TBO in our population, examine the influence of a MIA on achieving a TBO, and the impact of TBO on long-term survival. 269 patients undergoing oesophagectomy and 258 patients undergoing subtotal or total gastrectomy were included in this study. Demographic, clinical and pathological differences between patients with and without a TBO were compared using univariable and multivariable analysis. Overall survival for those with and without a TBO was examined. The influence of MIA on overall survival and TBO was determined using Cox proportional hazard models. Patients undergoing oesophagectomy and gastrectomy were significantly more likely to achieve a TBO when MIA was used (p = 0.01 and 0.001 respectively). When MIA is included as an outcome measure patients achieving a TBO show improved overall survival in both oesophageal and gastric cancer. MIA, clear resection margins and no unplanned admission to critical care are the strongest predictors of overall survival from the putative bundle of TBO parameters. Minimally invasive surgery is associated with improved TBO. Completion of a minimally invasive approach should be considered for inclusion as a textbook parameter.

Transcriptional control is the major determinant of cell fate. The steroid receptor coactivator (SRC)-1 enhances the activity of the estrogen receptor in breast cancer cells, where it confers cell survival benefits. Here, we report that a global analysis of SRC-1 target genes suggested that SRC-1 also mediates transcriptional repression in breast cancer cells. Combined SRC-1 and HOXC11 ChIPseq analysis identified the differentiation marker, CD24, and the apoptotic protein, PAWR, as direct SRC-1/HOXC11 suppression targets. Reduced expression of both CD24 and PAWR was associated with disease progression in patients with breast cancer, and their expression was suppressed in metastatic tissues. Investigations in endocrine-resistant breast cancer cell lines and SRC-1^−/−/PyMT mice confirmed a role for SRC-1 and HOXC11 in downregulation of CD24 and PAWR. Through bioinformatic analysis and liquid chromatography/mass spectrometry, we identified AP1 proteins and Jumonji domain containing 2C (JMD2C/KDM4C), respectively, as members of the SRC-1 interactome responsible for transcriptional repression. Our findings deepen the understanding of how SRC-1 controls transcription in breast cancers. Cancer Res; 74(9); 2533–44. ©2014 AACR.

Introduction: Although the benefits of post-operative rehabilitation in cancer surgery are well established, the role of prehabilitation is less defined. Oesophagogastric cancers present a unique opportunity to study the impact of prehabilitation during the neoadjuvant window, whether with chemotherapy or chemoradiotherapy (NCT) in patients who are frequently nutritionally depleted. This trial examines the impact of a community-based exercise programme on patient fitness during and after the neoadjuvant window. Methods: A pragmatic, randomized controlled multicentre trial was undertaken in three centres. Inclusion criteria were patients aged at least 18 years planned for NCT and esophagectomy or gastrectomy. Participants were randomized 1:1 to an exercise prehabilitation group (EX) or to usual care (UC). The primary endpoint was cardiorespiratory fitness between baseline and pre-surgery time point using the 6-minute walk test (MVT). Secondary endpoints included a hand dynamometer, 10-s sit-to-stand, activity behaviour, body mass index, semi-structured interviews, questionnaires assessing the quality of life, surgical fear, general self-efficacy and mastery. Results: Between March 2019 and December 2020, 71 participants were recruited: EX (n=36) or UC (n=35). From baseline to pre-surgery, the difference-in-difference (DID) for EX showed a significant improvement in 6MWT of 50.7 m (P=0.05) compared to UC [mean (SD): 522.1 m (+/−104.3) to 582.1 m (+/−108) vs. 497.5 m (+/−106.3) to 506.0 m (+/−140.4). There was no statistically significant DID for secondary outcome measures. Conclusions: This community exercise prehabilitation programme significantly improves physical fitness for surgery, is feasible and provides a standardized framework for the prescription of exercise in oesophagogastric cancer patients undergoing NCT.