The role of serum tumour markers, inflammation-based markers and circulating tumour cells as surrogate biomarkers of early response to neoadjuvant systemic treatment in patients with resectable gastric cancer.

Abstract

Introduction: Gastric cancer is associated with poor prognosis. Approximately 2/3 of the patients are diagnosed with locally advanced disease. Currently in Europe the preferred management of locally advanced gastric cancer is perioperative platinum-based chemotherapy. According to previously published data, such treatment is associated with improved relapse-free survival (RFS) as well as overall survival (OS) compared to surgery alone. It is unclear whether all patients should undergo preoperative treatment and what the optimal timing of such therapy should be. There are no biomarkers available for clinical practice to predict early response to the induction treatment. In a situation where treatment is not effective such markers could allow us to avoid exposing patients to the potential toxicity of unnecessary chemotherapy and perform earlier surgery. We planned a prospective biomarker study in order to develop a replicable pharmacodynamic marker. Methods: This is an academic, nonrandomized, prospective study, conducted in the Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology in Warsaw, Poland. The aim of the study is to evaluate the clinical application of serum markers as biomarkers of early response to neoadjuvant systemic treatment in patients with resectable gastric cancer. The recruitment for the study started in January 2017 and is expected to be completed in April 2018. The eligibility criteria are as follows: age of 18 years or older, male or female diagnosed with resectable gastric cancer and qualified by multidisciplinary team for preoperative treatment (ECF or CF regimen). Exclusion criteria are inflammatory or autoimmune disease, chronic intake of steroids, immunosuppressive therapy or any other malignancy. The target accrual is capped at 80 patients. The primary endpoint is to identify a marker (single or set of), assessed at 3 weeks after the start of the pre-operative treatment, which would allow to improve the R0 resection ratio by 20%. The protocol of treatment follows the clinical practice of the site. Surgery is scheduled to take place 3-5 weeks after completion of the third (ECF) or second (CF) cycle of chemotherapy. Computed tomography evaluation is performed within 21 days prior to the first cycle of chemotherapy and within 10 days before gastrectomy. The response to neoadjuvant treatment will be expressed as curative - R0 resection rate and histopathological grading of response in postoperative specimens. Parameters considered to be clinically important were frequency of the radical gastrectomy (R0) and lack of synchronous metastases during surgery (M0) based on serum markers levels using ROC curves. Before each cycle of chemotherapy and prior to surgery, blood samples are obtained to assess the following parameters: C-reactive protein, interleukins (IL-1b, IL-6, IL-8, IL -10), LMR - lymphocyte to monocyte ratio, NLR -neutrophil to lymphocyte ratio, dNLR - lymphocyte to neutrophil ratio, PLR - platelet to lymphocyte ratio, Glasgow Prognostic Score, F(fibrinogen)-NLR score, D-dimer, fibrinogen, albumin, cancer antigens CA 19-9, CEA, CA 125 and circulating tumour cells. Results: Conclusion:.