The identification and evaluation of predictive and prognostic biomarkers in order to personalise treatment pathways for patients diagnosed with pancreatic cancer.

Abstract

Pancreatic cancer survival has stagnated in recent years, with only 12% of patients alive after five years. The majority of patients present with either locally advanced or metastatic disease, that is not amenable to surgery. For patients with locally advanced disease, treatment involves neoadjuvant chemotherapy (NAC) with the view to shrink the tumour away from vital vasculature to allow for surgery to occur. The success of this approach, combined with poor survival outcomes has seen the introduction of NAC in patients with earlier (upfront or borderline resectable) disease. Whether this approach of NAC leads to a survival advantage over upfront surgery in this cohort of early pancreatic cancer patients, is debatable.

A retrospective cohort analysis was conducted to help answer this question. This identified that for all patients there was no survival difference between neoadjuvant chemotherapy and upfront surgery, however, in patients with early disease (stage 1a), treatment with upfront surgery resulted in longer survival than NAC.

To ascertain whether any biomarkers can assist with selecting the ideal upfront modality for each patient, a series of discovery experiments were conducted in both tumour tissue and blood to identify any novel prognostic or predictive biomarkers. In tissue, TGM2 (Transglutaminase 2) and OSMR (Oncostatin M receptor) were highlighted as a potential pathway involved in chemoresistance and CA125 expression on biopsy and surgical samples were found to be poor prognostic biomarkers. In blood, low levels of TNF-α (Tumour necrosis factor-) in patients were predictive of chemoresistance whereas higher levels of neutrophil lymphocyte ratio and eotaxin predicted for shorter overall survival.

Whilst these results are promising, validation of these findings in a larger cohort of patients is needed, to enable use of these biomarkers as prognostic and predictive tools to guide treatment that may result in more meaningful survival gains.