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Editorial comment on the MAGIC trial and the Cancer Genome Atlas (TCGA) publication on genomic characterization of oesophageal cancer

Commentary by Prof. Florian Lordick and Dr. Elizabeth Smyth

Oesophageal squamous cell carcinoma (OSCC) and adenocarcinoma (OAC) share an anatomic location but have distinct risk factors and epidemiology, and patients with either histology are frequently treated with identical chemotherapy, chemoradiotherapy and surgical approaches. The Cancer Genome Atlas (TCGA) publication on oesophageal cancer provides empirical evidence of the key differences between oesophageal OSCC) and OAC (REF). Using multiplatform analysis techniques, the TCGA authors demonstrate that OSCC tumours are more similar to squamous cell carcinoma of the head and neck than to OAC, whereas OAC tumours are molecularly indistinguishable from the chromosomally unstable (CIN) group of gastric cancers identified in the previous gastric cancer TCGA report. These findings suggest that in future, treatment approaches for OSCC and OAC might diverge from the current common approach; this will also be important to consider when designing future clinical trials. 

How understanding the interaction between specific molecular subgroups and current treatment standards can help to select gastric cancer patients for perioperative chemotherapy is provided in a manuscript describing the relationship between mismatch repair status, perioperative chemotherapy and survival in the MAGIC trial (Smyth et al.). Patients who had operable mismatch repair deficient tumours (8% of gastric cancers), had excellent survival when treated with surgery alone, but did not appear to benefit from perioperative chemotherapy, unlike patients with mismatch repair proficient tumours. This was a retrospective analysis of a prospective clinical trial, and although not practice changing, is thought provoking. More research is required to determine what the best treatment for patients with operable mismatch repair deficient gastric cancer; as immuno-oncology treatments have demonstrated excellent response rates in other mismatch repair deficient tumours, this could be an interesting option to explore. 

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