A pilot study of longitudinal serum cytokine and angiogenesis factor levels as markers of therapeutic response and survival in patients with head and neck squamous cell carcinoma

Background. Head and neck squamous cell carcinomas (HNSCCs) were previously shown to express a repertoire of cytokines and angiogenesis factors that contribute to malignant pathogenesis and are detectable in serum. Pretreatment and posttreatment serum levels of cytokines and angiogenesis factors were evaluated as markers for outcome in patients with HNSCC. Methods. Baseline cytokine and factor levels of 29 patients with HNSCC were compared with those of 15 age-matched and sex-matched controls, and pretreatment and posttreatment levels of 22 of the patients eligible for treatment and followed for a median of 37 months were compared. Results. Mean serum concentrations of interleukin (IL)-6, IL-8, hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and growth regulated oncogene 1 (GRO-1) were increased in patients with HNSCC, but elevation of these factors was not associated with clinical outcome. However, changes in first posttreatment serum cytokine levels were observed for many of the patients consistent with response, progression, and survival. Later increases in IL-6 or HGF were observed in patients who had a relapse and inflammatory or infectious complications. A relationship between the change in the pretreatment and first posttreatment cytokine measurement with survival was detected for HGF, IL-8, IL-6, and VEGF using a Cox-proportional hazards model (p = .004, p = .06, p = .10, and p = .11). The association between longitudinal decreases in IL-6, IL-8, VEGF, and HGF throughout the follow-up with survival was detected with a time-dependent Cox model (p = .01, .07, .08, and .05, respectively). Conclusions. Longitudinal changes in serum HGF, IL-6, IL-8, and VEGF were detected with treatment response, relapse, or complications in individual patients and were associated with survival, with HGF showing the strongest relationship with survival. HGF, IL-6, IL-8, and VEGF merit investigation as markers of response, survival, and recurrence in larger prospective studies.