Interleukin-6 as a Predictive Factor of Pathological Response to FLOT Regimen Systemic Treatment in Locally Advanced Gastroesophageal Junction or Gastric Cancer Patients

Simple Summary The response rate after neoadjuvant chemotherapy (NAC) remains limited. Moreover, there are currently no biomarkers enabling an individual prediction of therapeutic efficacy. The aim of this study was the identification of serum biomarkers of early response to NAC. The elevated level of IL-6 prior to treatment and cycle 2 of the FLOT regimen might be a predictor of pathological response to NAC in locally advanced gastric cancer (GC) or gastroesophageal junction (GEJ) cancer. The results were obtained from a small group of patients and currently cannot be used in everyday clinical practice. Confirmation of the results in a larger group of patients seems to be essential from a clinical point of view, bearing in mind that IL-6 plays a significant role in gastric cancer biology, particularly in metastasis formation and in the mechanism of chemotherapeutic resistance.Abstract Background: Perioperative treatment is a gold standard in locally advanced gastric cancer or GEJ cancer in the Western population. Unfortunately, the response rate after neoadjuvant chemotherapy (NAC) remains limited. Moreover, there are currently no biomarkers enabling an individual prediction of therapeutic efficacy. The aim of this study was the identification of serum biomarkers of early response to NAC. Methods: We conducted this prospective study in the MSCNRIO in Warsaw, Poland. A total of 71 patients and 15 healthy volunteers gave informed consent. Complete blood count, carcinoembryonic antigen (CEA), carcinoma antigen 125 (CA125), carcinoma antigen 19.9 (CA19.9), and fibrinogen (F) were measured at baseline and before every cycle. Circulating tumour cells (CTCs) and interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10) were measured in a pilot group of 40 patients at baseline and before cycle two (C2) and cycle three (C3). Results: Of all the measured parameters, only the IL-6 serum level was statistically significant. The IL-6 level before C2 of chemotherapy was significantly decreased in the complete pathological response (pCR) vs. the non-pCR group (3.71 pg/mL vs. 7.63 pg/mL, p = 0.004). In all patients with an IL-6 level below 5.0 pg/mL in C2, tumour regression TRG1a/1b according to the Becker classification and ypN0 were detected in postoperative histopathological specimens. The IL-6 level before C1 of chemotherapy was significantly elevated in ypN+ vs. ypN0 (7.69 pg/mL vs. 2.89 pg/mL, p = 0.022). Conclusions: The trial showed that an elevated level of IL-6 prior to treatment and C2 might be a predictor of pathological response to NAC.