Gastrointestinal (GI) toxicity is a common and costly side effect of chemoradiation and is frequently dose-limiting for treatment of upper GI cancers. Interpatient variability in severity of symptoms indicates that toxicity risk markers exist and could be utilised to personalise treatment.
This study aimed to identify immune response genes as markers predictive of severe chemoradiation-induced GI toxicity in patients with oesophageal adenocarcinoma.
Study participants were recruited from South Australia’s 2 major hospitals. RNA was extracted from whole blood collected prior to therapy and 84 innate and adaptive immune response genes were profiled using PCR array. GI toxicity was documented during the first cycle of chemoradiation and graded according to the NCI CTCAE v 4.0. Tumour response was graded according to the AJCC Cancer Staging Manual 7th edition.
Males diagnosed with oesophageal adenocarcinoma (N=19) and gastro/oesophageal junctional adenocarcinoma (N=10) were recruited between November 2009 and November 2014. All participants were treated with chemoradiation. Most common GI toxicities reported were oral mucositis (42.3%), nausea and vomiting (76.9%), diarrhoea (19.2%). PCR array indicated significant up regulation of TNF (1.45-fold, p=0.035) and TLR6 (1.87-fold, p=0.038) in patients with GI toxicity grade ≥3 (n=6) compared to grade ≤1 (n=10). There was no relationship between toxicity and response to chemoradiation.
Initial results indicate that baseline expression of key mediators of inflammatory tissue damage are measurably different in peripheral blood of patients with an elevated risk of developing severe GI toxicity prior to therapy. Analysis is ongoing.