局部晚期和转移性胰腺癌患者少分次同步剂量递增放疗疗效观察

Clinical outcomes of hypofractionated simultaneous integrated boost radiotherapy for locally advanced and metastatic pancreatic cancer

背景放疗是局部晚期和转移性胰腺癌重要的局部治疗手段,但以根治性为目的的最佳剂量分次模式尚未确定。目的观察以根治性为目的的少分次同步剂量递增(simultaneous integrated boost,SIB)螺旋断层放疗对局部晚期和转移性胰腺癌患者的疗效和毒性反应,探索最佳的剂量分次模式。方法收集2011年1月-2014年4月解放军总医院第一医学中心经病理证实不能手术的胰腺癌和转移性胰腺癌患者19例,肿瘤计划靶区容积(plan target volume,PTV)和大体靶区容积(gross target volume,GTV)分别接受少分次同步剂量递增螺旋断层放疗。GTV包括原发肿瘤和局部转移的淋巴结。PTV在GTV的基础上在轴位方向外放0.5~0.8 cm,在长轴方向外放0.5~1.0 cm。观察的主要终点指标包括肿瘤局部控制率、剂量限制性毒性和剂量容积限制,次要终点指标包括局部无进展生存和总生存。生物学等效剂量(biological equivalent dose,BED)按照α/β=10进行评估。结果19例局部晚期和转移性胰腺癌患者采用少分次剂量递增螺旋断层放疗的处方剂量为50~60 Gy/17~23 f,接受的中位BED10为81(范围78~90)Gy。中位随访时间10.7(范围3.1~64.1)个月,肿瘤局部控制率84%,中位局部无进展生存期为8.1(95%CI:5.8~10.5)个月,中位总生存期为10.7(95%CI:3.4~17.9)个月。胃和十二指肠受照的中位最大剂量分别为56(范围33~69)Gy和52(范围22~59)Gy。十二指肠剂量限制性毒性出血发生率为5%(1/19),相应的剂量容积限制分别为BED1070 Gy在0.03 cm3、63 Gy在0.50 cm3、55 Gy在2.62 cm3、48 Gy在6.33 cm3。结论少分次同步剂量递增螺旋断层放疗是局部晚期和转移性胰腺癌患者耐受良好的有效治疗模式,值得临床进一步研究。

Background Radiotherapy is an important local treatment for locally advanced and metastatic pancreatic cancer,but the optimal dose fractionation mode for radical purpose is not yet determined.Objective To evaluate clinical outcomes and severe adverse events in hypofractionated simultaneous integrated boost(SIB)Helical Tomotherapy with an intent to cure patients with locally advanced,inoperable and metastatic pancreatic cancer,so as to develop a novel dose-fraction model for these entities.Methods From January 2011 to April 2014,19 patients with pathologically confirmed,locally advanced,inoperable pancreatic adenocarcinoma and metastatic pancreatic cancer,who received hypofractionated SIB radiotherapy from planning target volume(PTV)to gross target volume(GTV)using Helical Tomotherapy,were enrolled in this study.Radiation therapy was directed to the primary tumor and metastatic lesions with a margin of 0.5 to 0.8 cm in axial plane and 0.5 to 1.0 cm in longitudinal plane.Primary end points included tumor local control,determination of dose-limiting toxicity and limitation of dose and volume,and the secondary end points included progression free survival and overall survival.The biological equivalent doses(BED10)were evaluated whenα/βwas equal to 10.Results With a median follow-up of 10.7 months,19 patients with locally advanced,inoperable and metastatic pancreatic cancer were treated with hypofractionatd SIB using Helical Tomotherapy.The prescribed dose-fraction was 50-60 Gy/17-23 f with the median BED10 of 81 Gy(range,78-90 Gy).The tumor local control rate was 84%.The median local progression-free survival(LPFS)and median overall survival(mOS)were 8.1 months(95%CI:5.8-10.5 months)and 10.7 months(95%CI:3.4-17.9 months)for the entities,respectively.The median maximum dose(Dmax)exposed on stomach was 56 Gy(range:33-69 Gy),while on duodenum was 52 Gy(range:22-59 Gy).The incidence of dose limited toxicity(DLT)of duodenal hemorrhage was 5%(1/19).The corresponding duodenum dose-volume limitations at BED10 were 0.03 cm3 at 70 Gy,0.50 cm3 at 63 Gy,2.62 cm3 at 55 Gy and 6.33 cm3 at 48 Gy,respectively.Conclusion Hypofractionated SIB radiotherapy using Helical Tomotherapy is a well tolerable and effective way to treat locally advanced,inoperable and metastatic pancreatic cancer.The hypofractionated SIB models need to be warranted in further study.