Trovo M, Giaj-Levra N, Furlan C, Bortolin M T, Muraro E, Polesel J, Minatel E, Tedeschi R, Filippi A R, Alongi F, Ricardi U
Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Aviano, Italy.
Radiation Oncology, Sacro Cuore Don Calabria Hospital, Via Don A. Sempreboni 5, Negrar, 37024, Verona, Italy.
Clin Transl Oncol. 2016 Oct;18(10):1003-10. doi: 10.1007/s12094-015-1473-x. Epub 2015 Dec 21.
To assess kinetics of plasmatic cytokines during radiation therapy (RT) for locally advanced and early-stage non-small cell lung cancer (NSCLC).
This prospective study was conducted on 15 early-stage NSCLC underwent to extreme hypofractionated regimen (52 Gy in 8 fractions) with stereotactic body RT (SBRT), and 13 locally advanced NSCLC underwent to radical moderated hypofractionated regimen (60 Gy in 25 fractions) with intensity modulated RT (IMRT). For patients undergoing SBRT, peripheral blood samples were collected on the first day of SBRT (TFd), the last day (TLd) and 45 days (T45d) after the end of SBRT. For patients undergoing IMRT, blood samples were collected at: TFd, 2 weeks (T2w), 4 weeks (T4w), TLd, and T45d. The following cytokines were measured: 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, and VEGF. Cytokine levels measured in different RT time and compared.
No difference in baseline levels of cytokines was documented between patient radiation approaches (except for MIP-1α). For SBRT patients, a mean reduction of IL-10 and IL-17 plasma level was documented between TLd and TFd, respectively (p < 0.05). For IMRT patients, a statistically significant (p < 0.05) mean plasma level reduction was documented between T4w and TFd for all the following cytokines: IL-1, IL-1ra, IL-2, IL-12, FGF-2, MIP-1α, MIP-1β, TGF-α, TNF-α, VEGF.
SBRT and IMRT induce different plasmatic cytokine changes in NSCLC patients, supporting hypothesis that RT regimes of dose schedules and techniques have different impacts on the host immune response.
评估局部晚期和早期非小细胞肺癌(NSCLC)患者在放射治疗(RT)期间血浆细胞因子的动力学变化。
本前瞻性研究纳入了15例接受立体定向体部放疗(SBRT)的极端低分割方案(8次分割,共52 Gy)的早期NSCLC患者,以及13例接受调强放疗(IMRT)的根治性适度低分割方案(25次分割,共60 Gy)的局部晚期NSCLC患者。对于接受SBRT的患者,在SBRT的第一天(TFd)、最后一天(TLd)以及SBRT结束后45天(T45d)采集外周血样本。对于接受IMRT的患者,在以下时间点采集血样:TFd、2周(T2w)、4周(T4w)、TLd和T45d。检测以下细胞因子:白细胞介素-1(IL-1)、白细胞介素-1受体拮抗剂(IL-1ra)、白细胞介素-2(IL-2)、白细胞介素-4(IL-4)、白细胞介素-5(IL-5)、白细胞介素-6(IL-6)、白细胞介素-7(IL-7)、白细胞介素-8(IL-8)、白细胞介素-10(IL-10)、白细胞介素-12(IL-12)、白细胞介素-13(IL-13)、白细胞介素-15(IL-15)、白细胞介素-17A(IL-17A)、表皮生长因子(EGF)、成纤维细胞生长因子-2(FGF-2)、干扰素-γ(INF-γ)、巨噬细胞炎性蛋白-1α(MIP-1α)、巨噬细胞炎性蛋白-1β(MIP-1β)、转化生长因子-α(TGF-α)、肿瘤坏死因子-α(TNF-α)和血管内皮生长因子(VEGF)。对不同放疗时间点检测的细胞因子水平进行比较。
除MIP-1α外,不同放疗方式的患者细胞因子基线水平无差异。对于接受SBRT的患者,TLd和TFd之间IL-10和IL-17血浆水平分别出现平均下降(p < 0.05)。对于接受IMRT的患者,以下所有细胞因子在T4w和TFd之间血浆水平出现具有统计学意义(p < 0.05)的平均下降:IL-1、IL-1ra、IL-2、IL-12、FGF-2、MIP-1α、MIP-1β、TGF-α、TNF-α、VEGF。
SBRT和IMRT在NSCLC患者中诱导不同的血浆细胞因子变化,支持了放疗剂量方案和技术对宿主免疫反应有不同影响这一假说。