Plasmatic Cytokine Levels in Lung Cancer Patients Undergoing Definitive Radiation Therapy

Abstract

To assess the kinetics of plasmatic cytokines during the course of definitive radiation therapy (RT) for locally-advanced or early-stage Non-Small Cell Lung Cancer (NSCLC). This prospective study was conducted with the approval of our Institutional Review Board, and was conducted on 28 lung cancer patients: 15 early-stage NSCLC patients underwent to Stereotactic Body RT (SBRT) consisting of 52 Gy in 8 fractions; 13 locally-advanced NSCLC patients underwent to radical Intensity Modulated Radiation Therapy (IMRT) consisting of 60 Gy in 25 fractions. All patients were treated with helical tomotherapy. For patients undergoing to SBRT, EDTA-peripheral blood samples were collected at the following time: first day of SBRT (TFd), last day of SBRT (TLd) and 45 days (T45d) after the end of SBRT. For patients undergoing IMRT, blood samples were collected at the following time: first day (TFd), at two weeks (T2w), at four weeks (T4w), last day (TLd), and 45 days (T45d) after the completion of RT course. A multiplex parametric technology was used for quantification of the following cytokines: IL-1, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17A, EGF, FGF-2, INF-γ, MIP-1α, MIP-1β, TGF-α, TNF-α, VEGF, PDGF-α, and PDGF-β. Cytokine levels measured at different RT time were compared using a two-tailed Student's t test; statistical significance was claimed for p < 0.05. No difference in baseline levels of cytokines was documented between SBRT (early-stage) patients and IMRT (locally-advanced) patients. For SBRT patients, a mean IL-10 and IL-7 plasma level reduction of 5 pg/mL (p < 0.05) and 2 pg/mL (p < 0.05), respectively, was noted between TLd and TFd. IL-10 and IL-17 returned to pre-RT levels 45 days after completion of SBRT. For IMRT patients, a statistically significant (p < 0.05) mean plasma level reduction was noted between T4w and TFd for all the following cytokines: IL-1 (4 pg/mL), IL-1ra (33 pg/mL), IL-2 (5 pg/mL), IL-12 (35 pg/mL), IL-13 (4 pg/mL), FGF-2 (42 pg/mL), MIP-1α (2 pg/mL), MIP-1β (13 pg/mL), TGF-α (2 pg/mL), TNF-α (7 pg/mL), VEGF (105 pg/mL), PDGF-α (3784 pg/mL), and PDGF-β (47875 pg/mL). All theses cytokines returned to pre-RT levels the last day (TLd) of IMRT, and stayed stable 45 days after the completion of RT. The present study was conducted to examine the effect of different schedule of radiation therapy on levels of inflammatory markers in NSCLC patients. We have shown that several cytokines are sensitive to irradiation. A reduction of plasmatic cytokine levels during the course of radiation therapy both for early-stage and locally advanced NSCLC patients was documented. If such cytokine kinetics might have an impact in outcome or in radiation-related toxicity has to be investigated.