非小细胞肺癌质子-光子混合放疗计划的可行性研究

Feasibility study of combined proton-photon radiotherapy for non-small-cell lung cancer

目的比较非小细胞肺癌(NSCLC)质子调强放射治疗(IMPT)和光子调强放射治疗(IMRT)的剂量学参数和正常组织并发症概率(NTCP),并探讨质子-光子混合放疗在NSCLC中的可行性和最佳模式。方法回顾性选取2020年11月至2022年4月于中国科学技术大学附属第一医院离子医学中心放疗科行根治性放疗NSCLC病人共8例,对8例病人分别制作IMPT和IMRT计划,IMPT计划采用的相对生物学效应(RBE)值为1.1,处方剂量为60 GyE/30次,对优化后计划的剂量学参数,放射性肺炎、食管毒性、2年死亡率指标的NTCP结果进行比较并分析,根据NTCP阈值或ΔNTCP的阈值方式选择合适的质子-光子混合放疗模式。结果所有NSCLC病人的IMPT及IMRT计划均符合要求,剂量体积直方图剂量学参数显示IMPT和IMRT计划的适形性指数[1.28(1.13,1.43)比1.12(1.05,1.18),P=0.068]和均匀性指数[0.09(0.08,0.15)比0.11(0.08,0.16),P=0.327]均差异无统计学意义,IMPT对比IMRT计划患肺平均剂量[9.38(4.28,13.78)Gy比12.27(7.95,15.41)Gy,P=0.012]、心脏平均剂量[5.59(1.01,8.50)Gy比8.23(6.61,15.82)Gy,P=0.012]、食管平均剂量[10.53(0.04,21.62)Gy比13.05(3.84,23.69)Gy,P=0.036]有降低(P<0.05)。此外IMPT计划的双肺V_(5 Gy)、双肺V_(20 Gy)、双肺V_(30 Gy)、患肺V_(5 Gy)、患肺V_(20 Gy)、心脏V_(30 Gy)、心脏V_(40 Gy)和脊髓D2%均明显降低(P<0.05)。IMPT可以将病人放射性肺炎[8.35(3.36,15.80)%比12.80(6.51,19.53)%,P=0.012]、食管毒性[20.43(0.21,42.58)%比26.03(5.43,46.30)%,P=0.036]及2年死亡率[43.28(34.58,48.27)%比48.78(42.74,56.20)%,P=0.012]的概率显著降低,ΔNTCP值分别为3.33(3.08,4.42)%,5.22(1.51,9.17)%和5.96(3.02,11.13)%。最后选择观察指标的NTCP阈值或ΔNTCP的阈值确定质子-光子混合放疗模式,结果显示使用ΔNTCP阈值方式进行混合更具优势。结论质子-光子混合放疗计划是可行的,可增加NSCLC病人的治疗获益和质子治疗可及性,选择ΔNTCP阈值方式进行混合放疗更具方便性及实用性。

Objective To compare the dosimetric parameters and normal tissue complication probability(NTCP)of intensity modulated proton therapy(IMPT)and intensity modulated radiation therapy(IMRT)for non-small cell lung cancer(NSCLC),and to explore the feasibility and optimal model of combined proton-photon radiotherapy in NSCLC.Methods The IMPT and IMRT plans were made for 8 NSCLC patients in the Radiotherapy and Oncology Department of the Ion Medicine Center of The First Affiliated Hospital of University of Science and Technology of China from November 2020 to April 2022 who underwent radical radiotherapy,respectively.The relative biological effectiveness(RBE)of the IMPT plan was 1.1,and the prescription dose was 60 GyE/30 fractions.The two plans were evaluated and compared according to the dosimetric parameters,and evaluated the NTCP of radiation pneumonia,esophageal toxicity,and 2-year mortality.Finally,the NTCP results were analyzed and selected the appropriate combined proton-photon radiotherapy models.Results All NSCLC patients met the requirements,and the dose volume histogram dosimetric parameters showed no statistically significant differences in the conformity index[1.28(1.13,1.43)vs.1.12(1.05,1.18),P=0.068]and homogeneity index[0.09(0.08,0.15)vs.0.11(0.08,0.16),P=0.327]of the IMPT and IMRT plans.There was a statistically significant decrease in IMPT compared to the IMRT plan for mean lung dose[9.38(4.28,13.78)Gy vs.12.27(7.95,15.41)Gy,P=0.012],mean heart dose[5.59(1.01,8.50)Gy vs.8.23(6.61,15.82)Gy,P=0.012],and esophageal mean dose[10.53(0.04,21.62)Gy vs.13.05(3.84,23.69).In addition,the IMPT plan showed significant reductions in bilateral lung V_(5 Gy),bilateral lung V_(20 Gy),bilateral lung V_(30 Gy),ipsilateral lung V_(5 Gy),ipsilateral lung V_(20 Gy),heart V_(30 Gy),heart V_(40 Gy)and spinal cord D2%(P<0.05).IMPT can significantly reduce the NTCP of radiation pneumonia[8.35(3.36,15.80)%vs.12.80(6.51,19.53)%,P=0.012],esophageal toxicity[20.43(0.21,42.58)%vs.26.03(5.43,46.30)%,P=0.036]and 2-year mortality[43.28(34.58,48.27)%vs.48.78(42.74,56.20)%,P=0.012],and theΔNTCP values were 3.33(3.08,4.42)%,5.22(1.51,9.17)%and 5.96(3.02,11.13)%,respectively.Finally,two methods were chosen:NTCP thresholds orΔNTCP threshold for observation indicator,to select the combined proton-photon radiotherapy models.Conclusions The combined proton-photon radiotherapy plan is feasible.The threshold value ofΔNTCP can be set according to the patient,to increase the treatment benefit of NSCLC patients and the accessibility of proton therapy.