297. ASSESSING BLOOD-BASED BIOMARKERS IN OESOPHAGEAL CANCER PATIENTS RECEIVING NEOADJUVANT CHEMORADIOTHERAPY

Abstract

Background Oesophageal cancer is the sixth most common cause of cancer-related deaths globally. It has a significant rate of mortality despite the multimodal approach to treatment. Neo-adjuvant chemoradiotherapy is standard of care but there is a clinical need for new therapies. HER2-targeted therapies and immune checkpoint inhibitors targeting the PD-1/PD-L1 axis have emerged as treatment strategies of significant interest in recent years. This study focuses on exploring potential plasma-based biomarkers (growth factors, cytokines, soluble (s) PD-L1) in patients (pts) with oesophageal cancer receiving standard of care neo-adjuvant therapy and stratified based on HER2 expression and pathological complete response (pCR). Methods 50 pts with oesophageal cancer who are eligible for neoadjuvant therapy were recruited. Blood samples were taken pre-treatment, on the first day of the 2nd cycle and post-neoadjuvant treatment. Plasma was extracted within four hours of blood draw and stored at -800C. 20 matched pre- and post-treatment samples were included in this analysis. HER2 status (IHC 3+ (n=3), IHC 2+ (n=5), IHC 1+ (n=3), IHC 0 (n=6) was available for 17 pts. 3 pts achieved a pCR but no HER2 IHC data was available. The levels (pg/ml) of 21 analytes were assessed using the Human Growth Factor Luminex Performance Assay and a Luminex MagPix system. Changes were significant if p<0.05, paired student’s t test. Results Twenty-one biomarkers of response were assessed in the final analysis. Platelet-derived growth factor (PDGF)-AA and PDGF AA/BB displayed the highest concentration levels of the tested analytes but levels did not change pre-and post-treatment. GRO-b (CXCL2) and vascular endothelial growth factor (VEGF) displayed a numerical increase post-treatment but this did not prove significant (p<0.05). Tumour-necrosis factor-related apoptosis-inducing ligand (TRAIL) protein decreased significantly post-therapy (p=0.038). PD-L1 levels significantly increased in the post-treatment cycles (paired t-test p=0.0029), especially in pts with HER2+ status. TRAIL or sPD-L1 levels were not significantly different when categorised by HER2 IHC or pCR status. Conclusion The increase in sPD-L1 and reduction in TRAIL levels in the peripheral blood of oesophageal cancer patients following neoadjuvant therapy suggests treatment alters factors associated with immune-suppression and the induction of tumour cell death. Further investigation in a larger cohort is warranted.