Oesophageal adenocarcinoma:In the era of extended lymphadenectomy,is the value of neoadjuvant therapy being attenuated?

BACKGROUND Neoadjuvant chemotherapy(NACT)and oesophagectomy is the standard of care for resectable oesophageal adenocarcinomas.Survival outcomes following resection have been improving over time while NACT remain largely unchanged.Indeed,a recent meta-analysis of randomized control trials did not demonstrate a survival benefit in adding NACT,raising the possibility that improved surgical techniques may be reducing the perceived effectiveness of NACT.AIM To compare the effect of addition of NACT to a standardized surgery and lymphadenectomy on overall and disease-free survival in patients undergoing curative oesophagectomy for oesophageal adenocarcinoma.METHODS Patient data were analysed from a prospectively maintained surgical survival database.Demographic,surgical,and survival outcomes were compared between groups according to treatment and nodal count.RESULTS The data of 243 consecutive patients were identified.79 patients were given NACT and 162 had surgery only.The NACT group were younger,and there was less frequent stage I adenocarcinoma.Overall survival was similar between NACT and surgery only groups(5YS:48.7%vs 42.5%;P=0.113),as was diseasefree survival(5YS:40.6%vs 39.9%;P=0.635).There were≥30 nodes removed in 46 patients,and<30 in 197 patients,but were otherwise similar.There was improved survival in patients with≥30 nodes removed than those with<30 nodes(5YS:64.4%vs 40.7%;P=0.015),and a better disease-free survival that neared significance(5YS:54.9%vs 36.6%;P=0.078).CONCLUSION NACT did not appear to affect overall or disease-free survival.However,an overall survival benefit was observed in patients with≥30 lymph nodes removed,and a benefit in disease-free survival which was not significant.

Potential of damage associated molecular patterns in synergising radiation and the immune response in oesophageal cancer

BACKGROUND There is an intimate crosstalk between cancer formation,dissemination,treatment response and the host immune system,with inducing tumour cell death the ultimate therapeutic goal for most anti-cancer treatments.However,inducing a purposeful synergistic response between conventional therapies and the immune system remains evasive.The release of damage associated molecular patterns(DAMPs)is indicative of immunogenic cell death and propagation of established immune responses.However,there is a gap in the literature regarding the importance of DAMP expression in oesophageal adenocarcinoma(OAC)or by immune cells themselves.AIM To investigate the effects of conventional therapies on DAMP expression and to determine whether OAC is an immunogenic cancer.METHODS We investigated the levels of immunogenic cell death-associated DAMPs,calreticulin(CRT)and HMGB1 using an OAC isogenic model of radioresistance.DAMP expression was also assessed directly using ex vivo cancer patient T cells(n=10)and within tumour biopsies(n=9)both pre and post-treatment with clinically relevant chemo(radio)therapeutics.RESULTS Hypoxia in combination with nutrient deprivation significantly reduces DAMP expression by OAC cells in vitro.Significantly increased frequencies of T cell DAMP expression in OAC patients were observed following chemo-(radio)therapy,which was significantly higher in tumour tissue compared with peripheral blood.Patients with high expression of HMGB1 had a significantly better tumour regression grade(TRG 1-2)compared to low expressors.CONCLUSION In conclusion,OAC expresses an immunogenic phenotype with two distinct subgroups of high and low DAMP expressors,which correlated with tumour regression grade and lymphatic invasion.It also identifies DAMPs namely CRT and HMGB1 as potential promising biomarkers in predicting good pathological responses to conventional chemo(radio)therapies currently used in the multimodal management of locally advanced disease.