P-231Proinflammatory cytokines as predictive factors for response to chemotherapy or mental disorders present in colorectal cancer patients

Introduction: Colorectal cancer (CRC) represents a major public health problem, being the second cause of death in the world. Psychological disorders are frequently observed in patients with cancer, as a consequence of either the disease or the treatment side effects which affects the compliance to treatment, quality of life and survival of these patients. Several studies revealed that proinflammatory cytokines released either by tumor or immune host cells are not only related to tumor cells proliferation, angiogenesis, and tumor progression, but are also involved in the appearance of mental disorders. The objective of our study was to evaluate the presence of psychological symptoms in correlation with serum proinflammatory cytokines levels in patients with advanced or metastatic CRC. Correlation between serum levels of proinflammatory cytokines at treatment initiation and tumor response to chemotherapy was another objective of study. Methods: Forty-nine patients undergoing chemotherapy for locally advanced or metastatic CRC were included in the study. All patients received standard chemotherapy (oxaliplatin plus 5-fluorouracil and bevacizumab) for 6 cycles. The control group was composed of 10 healthy volunteers. The Ethics Committee of the The Oncology Institute “Prof. Dr. Ion Chiricuţă” and “Iuliu Hatieganu” University of Medicine Cluj-Napoca, Romania, approved the study and all patients signed a consent form. Patients were evaluated for anxiety, depression, pain and serum level of proinflammatory cytokines before receiving standard chemotherapy. Tumor response to treatment was assessed after six cycles of chemotherapy. Pain intensity was evaluated through visual analogue scale, whereas depression and anxiety levels were assessed with Beck Depression and State-Trait Anxiety Inventories. Serum levels of IL-6, IL-8 and IL10 were measured by enzyme-linked immunosorbent assay (ELISA). Correlations between patient demographic characteristics, pain evaluation, mental disorders, response to chemotherapy and serum levels of cytokines were realized using Fisher’s test, t-test and Chi-squared test χ2. Results: The results revealed a significant level of anxiety and depression in our patients. Depression levels were moderate to increased in 53% of patients and high levels of anxiety were found in 25% of patients. Pain was moderate in 45% and high in 12% of patients. The overall response rate was 59%. Levels of anxiety and depression did not correlate with demographic characteristics of patients, but there was a high incidence of psychological disorders in young male patients from urban areas. The patients with CRC had high serum levels of IL-6 and IL-8, whereas IL-10 was underexpressed compared to the healthy control group. There was a positive correlation between serum levels of IL-8 and depression. Moreover, levels of IL-8 before treatment correlated with progressive disease. Conclusion: These results indicate that circulatory proinflammatory cytokines are involved in tumor proliferation and mental disorders. Additionally, IL-8 could be considered a predictive factor of response to chemotherapy in patients with CRC. A better understanding of the molecules involved in the pathogenesis of symptoms could improve the quality of life and the survival of CRC patients.