目的:报告接受质子或光子放疗的大型不可切除肝细胞癌(HCC)患者的临床和剂量学特征。
方法:我们回顾性分析了159例>5cm非转移性HCC患者的结局和剂量学指标,这些患者在2014年至2018年间接受了质子(N=105)或光子(N=54)的确定性放疗。使用相同的剂量处方标准对105名质子治疗的患者进行了额外的光子计划,以进行组内剂量测定比较。
结果:经过47个月的中位随访,生物有效剂量(BED10)≥75Gy的患者表现出明显更好的局部控制(LC,2年:85.6%与20.5%,P<0.001),无进展生存期(PFS,中位数7.4vs.3.2个月,P<0.001),和总体生存率(OS,中位数18.1vs.7.3个月,P<0.001)与BED10<75Gy的那些相比。值得注意的是,接受质子治疗的患者的BED10明显更高(96vs.67Gy,P<0.001)和改善的LC(2年:88.5%vs.33.8%,P<0.001),PFS(中位数7.4与3.3个月,P=0.001),和OS(中位数18.9与8.3个月,P<0.001)比接受光子放射治疗的人。此外,用质子治疗的患者肝脏V1明显降低(P<0.001),平均上消化道(UGI)剂量(P<0.001),和平均脾剂量(P<0.001),放射性肝病发病率显著降低(P=0.007),≥3级UGI出血(P=0.001),和≥3级淋巴细胞减少(P=0.003)。在多变量分析中,质子放疗与优越的LC一致相关(P<0.001),PFS(P<0.001),OS(P<0.001)。在组内剂量比较中,光子计划显示出显著更高的平均肝脏剂量(MLD,P<0.001)与实际递送的质子治疗相比,其中72例(69%)的MLD超过28Gy,需要降低目标剂量。
结论:在大肝癌放疗的背景下,较高的目标BED10与结局改善相关.值得注意的是,质子治疗已经证明了提供消融剂量的能力,同时也伴随着较少的严重毒性实例。
OBJECTIVE: Our purpose was to report the clinical and dosimetric attributes of patients with large unresectable hepatocellular carcinoma (HCC) undergoing proton or photon radiation therapy.
METHODS: We retrospectively analyzed the outcomes and dosimetric indices of 159 patients with >5 cm nonmetastatic HCC who underwent definitive radiation therapy using either protons (N = 105) or photons (N = 54) between 2014 and 2018. Additional photon plans were performed in the 105 proton-treated patients using the same dose prescription criteria for intragroup dosimetric comparison.
RESULTS: After a median follow-up of 47 months, patients with biologically effective dose (BED10) ≥ 75 Gy exhibited significantly better local control (LC; 2-year: 85.6% vs 20.5%; P < .001), progression-free survival (PFS; median, 7.4 vs 3.2 months; P < .001), and overall survival (OS; median, 18.1 vs 7.3 months; P < .001) compared with those with BED10 < 75 Gy. Notably, proton-treated patients had a significantly higher BED10 (96 vs 67 Gy; P < .001) and improved LC (2-year: 88.5% vs 33.8%; P < .001), PFS (median, 7.4 vs 3.3 months; P = .001), and OS (median, 18.9 vs 8.3 months; P < .001) than those undergoing photon radiation therapy. Furthermore, patients treated with protons had significantly lower V1 of the liver (P < .001), mean upper gastrointestinal tract dose (P < .001), and mean splenic dose (P < .001), with significantly decreased incidences of radiation-induced liver disease (P = .007), grade ≥3 upper gastrointestinal bleeding (P = .001), and grade ≥3 lymphopenia (P = .003). On multivariate analysis, proton radiation therapy consistently correlated with superior LC (P < .001), PFS (P < .001), and OS (P < .001). In intragroup dosimetric comparison, photon plans demonstrated significantly higher mean liver dose (P < .001) compared with actually delivered proton treatments, and 72 (69%) of them had mean liver dose exceeding 28 Gy, which necessitated target dose de-escalation.
CONCLUSIONS: In the context of large HCC radiation therapy, a higher target BED10 was associated with improved outcomes. Notably, proton therapy has demonstrated the capability to deliver ablative doses while also being accompanied by fewer instances of severe toxicity.