What are the Predictive Factors in the Risk and Severity of Chemotherapy-Induced Gastrointestinal Toxicity?

Damage to the mucous membranes of the GI tract by chemotherapy is known as mucositis or chemotherapy-induced gastrointestinal toxicity (CIGT). Injury can occur anywhere along the GI tract, or may be localized to a particular region, depending on the chemotherapy regimen. CIGT has huge clinical and economic implications affecting >50% of cancer patients, and can necessitate treatment reductions and/or treatment breaks. Patients that experience severe CIGT have twice the infection risk leading to a fourfold higher chance of death and threefold longer hospital stays, compromising survival and creating a burden on patients’ quality of life. Economically, US data from 2012 estimated a combined cost of US$15,500 for each hospitalization due to severe CIGT, adding millions to healthcare expenditure [1]. Patients with CIGT typically experience severe consequences including, but not limited to, oral mucositis, increased infection rates and diarrhea [2]. Currently, there is no prophylactic intervention available for CIGT and its severity varies widely across patients receiving identical therapy. Thus there is an urgent need to be able to accurately predict which patients may develop CIGT and its severity. In light of our recent preclinical and clinical research [3,4], we propose that mediators in the Toll-like receptor 4 (TLR4) signaling pathway may provide specific predictive markers of CIGT risk and severity.