S. J. Judge1, M. Yanagisawa1, T. Henderson1, S. Thorpe2, A. M. Monjazeb4, W. J. Murphy3, R. J. Canter1 1UC Davis,Surgical Oncology,Sacramento, CA, USA 2UC Davis,Orthopedic Oncology,Sacramento, CA, USA 3UC Davis,Dermatology, Laboratory Of Cancer Immunology,Sacramento, CA, USA 4UC Davis,Radiation Oncology,Sacramento, CA, USA
Introduction: With the expanding use of immunotherapy for cancer therapy, including soft tissue sarcomas (STS), there is a growing need for biomarkers of response and prognosis. We have previously demonstrated that changes in circulating levels of TNF-alpha (TNF-α), Interferon-gamma (IFN-γ), and Interleukin-6 (IL-6) predict metastasis-free survival in STS patients receiving preoperative sorafenib and radiotherapy (RT). The objective of the current study was to determine the impact of baseline cytokine expression on prognosis and risk of malignancy in STS.
Methods: From March 2013 to February 2015, 33 patients with suspicious soft tissue tumors underwent pre-treatment measurements of serum cytokine/chemokine expression, including IFN-γ, TNF-α, IL-2, IL-6, G-CSF, GM-CSF, EGF, IL-4, IL-8, IL-10, FGF, TGF-α, PDGF, TNF-?, sIL-2rα, and VEGF. Based on our previous data, we focused the analysis on IFN-γ, TNF-α, IL-2, IL-6 levels to predict risk of malignancy/stage (benign, low grade, high grade), metastasis free survival and overall survival. Parametric and non-parametric statistics were used as appropriate.
Results: Of the 33 patients, the majority was female (52%) and had retroperitoneal tumors (67%). Five patients (15%) had benign disease, 16 (48%) low grade STS, and 12 (36%) high grade STS. With a median follow up of 27 months, 9 (27%) experienced distant recurrence, and 4 (12%) died of disease. There were no significant differences in baseline cytokine levels between benign and malignant STS or between low grade and high grade malignant STS (See Figure). There were no significant differences in baseline cytokine levels between patients who developed metastases and those who did not, with the exception of IFN-gamma which was significantly higher in non metastatic STS compared to metastatic STS (mean ±SD: 125 ±216 vs 14 ±16 pg/mL; p = 0.05).
Conclusion: In this cohort of heterogeneous soft tissue tumor and STS patients, with the exception of IFN- γ, baseline levels of circulating Th1 cytokines do not predict risk of malignancy/extent of disease and do not predict with metastasis-free survival or overall survival. Although changes in cytokine levels with treatment may predict response to therapy/immunotherapy, better biomarkers of baseline prognosis are needed.
