Intraoperative radiation therapy (IORT) is an ascending treatment approach which provides targeted radiation, reduced local recurrence and induction of an anti-tumor effect by activating an immune response. Aim of our study is to characterize the immunological signature represented by the cytokine profile in the cerebrospinal fluid (CSF) after IORT of cerebral metastases.
We analyzed the cytokine patterns in 37 CSF samples obtained from 10 patients with tumor resection and IORT. Samples were taken at four time points: 1. intraoperatively, before tumor resection and IORT, 2. intraoperatively, after tumor resection, before IORT, 3. intraoperatively, after tumor resection and IORT, 4. ~24 hours postoperatively from drainage. Samples were tested using a multiplex immunoassay (CodePlex Secretome - Human Innate Immune Panel provided by IsoPlexis) according to the manufacturer"s instructions. Levels of EGF, GM-CSF, Granzyme B, IFN-γ, IL-1β, IL-4, IL-6, IL-7, IL-8, IL-10, IL-15, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF-BB, sCD137, TNF-α and VEGF were measured and quantified using IsoSpeak software. The Wilcoxon-Test was used for statistical analysis.
An increase of signal intensity was observed for 16 of the 19 analyzed cytokines (84%), of which 7 (37%) displayed significant differences between baseline and postoperative time points: IL-1β, IL-6, IL-8, IP-10, MCP-1, MIP-1β and VEGF. Except for IP-10, a gradual increase for the four time points was seen for these cytokines.
Our study allows first conclusions about changes in the cytokine profile of cerebrospinal fluid after IORT of cerebral metastases. The results indicate that IL-1β, IL-6, IL-8, IP-10, MCP-1, MIP-1β and VEGF are involved in the inflammatory response induced by exposure to ionizing radiation of the tumor bed during surgery. The results are limited since no control group was tested, yet. Currently, we are setting up such a control group which included patients with resection of cerebral metastases without IORT.