Harvard Radiation Oncology Program, Massachusetts General Hospital, Boston, Massachusetts; Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
Int J Radiat Oncol Biol Phys. 2019 Sep 1;105(1):64-72. doi: 10.1016/j.ijrobp.2019.01.076. Epub 2019 Jan 23.
Ablative radiation therapy is increasingly being used for hepatocellular carcinoma (HCC) resulting in excellent local control rates; however, patients without evidence of disease progression often die from liver failure. The clinical benefit of proton- over photon-based radiation therapy is unclear. We therefore sought to compare clinical outcomes of proton versus photon ablative radiation therapy in patients with unresectable HCC.
This is a single-institution retrospective study of patients treated during 2008 to 2017 with nonmetastatic, unresectable HCC not previously treated with liver-directed radiation therapy and who did not receive further liver-directed radiation therapy within 12 months after completion of index treatment. The primary outcome, overall survival (OS), was assessed using Cox regression. Secondary endpoints included incidence of non-classic radiation-induced liver disease (defined as increase in baseline Child-Pugh score by ≥2 points at 3 months posttreatment), assessed using logistic regression, and locoregional recurrence, assessed using Fine-Gray regression for competing risks. All outcomes were measured from radiation start date.
The median follow-up was 14 months. Of 133 patients with median age 68 years and 75% male, 49 (37%) were treated with proton radiation therapy. Proton radiation therapy was associated with improved OS (adjusted hazard ratio, 0.47; P = .008; 95% confidence interval [CI], 0.27-0.82). The median OS for proton and photon patients was 31 and 14 months, respectively, and the 24-month OS for proton and photon patients was 59.1% and 28.6%, respectively. Proton radiation therapy was also associated with a decreased risk of non-classic radiation-induced liver disease (odds ratio, 0.26; P = .03; 95% CI, 0.08-0.86). Development of nonclassic RILD at 3 months was associated with worse OS (adjusted hazard ratio, 3.83; P < .001; 95% CI, 2.12-6.92). There was no difference in locoregional recurrence, including local failure, between protons and photons.
Proton radiation therapy was associated with improved survival, which may be driven by decreased incidence of posttreatment liver decompensation. Our findings support prospective investigations comparing proton versus photon ablative radiation therapy for HCC.
消融性放射治疗越来越多地用于治疗肝细胞癌（HCC），从而获得了极好的局部控制率；然而，没有疾病进展证据的患者往往死于肝功能衰竭。质子与光子放射治疗的临床获益尚不清楚。因此，我们旨在比较质子与光子消融性放射治疗在不可切除 HCC 患者中的临床结果。
这是一项单机构回顾性研究，纳入了 2008 年至 2017 年期间接受非转移性、不可切除 HCC 治疗的患者，这些患者之前未接受过肝定向放射治疗，并且在完成指数治疗后 12 个月内未接受进一步的肝定向放射治疗。主要结局是总生存（OS），采用 Cox 回归进行评估。次要终点包括非典型放射性肝损伤的发生率（定义为治疗后 3 个月时基线 Child-Pugh 评分增加≥2 分），采用逻辑回归进行评估，以及局部区域复发，采用 Fine-Gray 回归进行竞争风险评估。所有结局均从放射治疗开始日期进行测量。
中位随访时间为 14 个月。在 133 名中位年龄为 68 岁、75%为男性的患者中，有 49 名（37%）接受了质子放射治疗。质子放射治疗与改善 OS 相关（调整后的风险比，0.47；P=.008；95%置信区间 [CI]，0.27-0.82）。质子和光子患者的中位 OS 分别为 31 个月和 14 个月，24 个月时的 OS 分别为 59.1%和 28.6%。质子放射治疗也与非典型放射性肝损伤的风险降低相关（比值比，0.26；P=.03；95%CI，0.08-0.86）。3 个月时发生非典型 RILD 与较差的 OS 相关（调整后的风险比，3.83；P<.001；95%CI，2.12-6.92）。质子和光子之间在局部区域复发（包括局部失败）方面没有差异。
质子放射治疗与生存改善相关，这可能是由于治疗后肝功能失代偿的发生率降低所致。我们的发现支持前瞻性研究比较质子与光子消融性放射治疗 HCC。
