ImportanceMost patients with locally advanced hepatocellular carcinoma (HCC) recur within the liver following systemic therapy.ObjectiveTo determine whether stereotactic body radiation therapy (SBRT) improves outcomes in patients with locally advanced HCC compared with sorafenib alone.Design, Setting, and ParticipantsThis multicenter phase 3 randomized clinical trial randomized patients with HCC 1:1 to sorafenib or SBRT followed by sorafenib, stratified by performance status, liver function, degree of metastases, and macrovascular invasion. Eligible patients had HCC unsuitable for or refractory to standard local-regional therapies and were candidates for first-line systemic therapy. Data were collected from April 2013 to March 2021, and data were analyzed from July 2022 to August 2023.InterventionPersonalized SBRT, 27.5 to 50 Gy in 5 fractions.Main Outcomes and MeasuresThe primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS), adverse events, and quality of life.ResultsOf 193 patients randomized, 177 were eligible. Accrual was stopped early due to a change in standard-of-care systemic therapy. Of 177 included patients, 150 (84.7%) were male, and the median (IQR) age was 66 (60-72) years. Macrovascular invasion was seen in 131 (74.0%). As of July 1, 2022, the median OS was 12.3 months (90% CI, 10.6-14.3) with sorafenib vs 15.8 months (90% CI, 11.4-19.2) following SBRT and sorafenib (hazard ratio [HR], 0.77; 90% CI, 0.59-1.01; 1-sided P = .06). Adjusting for stratification factors, OS was improved with SBRT (HR, 0.72; 95% CI, 0.52-0.99; 2-sided P = .04). Median PFS was improved from 5.5 months (95% CI, 3.4-6.3) with sorafenib to 9.2 months (95% CI, 7.5-11.9) with SBRT and sorafenib (HR, 0.55; 95% CI, 0.40-0.75; 2-sided P < .001). Treatment-related grade 3 or higher adverse events were seen in 37 of 88 (42%) and 39 of 83 (47%) of patients treated with sorafenib vs SBRT and sorafenib, respectively (P = .52). There were 2 treatment-related deaths in the sorafenib group (death not otherwise specified and liver failure) and 1 in the SBRT and sorafenib group (lung infection). At 6 months, improved quality of life was seen in 2 of 20 (10%) and 6 of 17 (35%) of patients treated with sorafenib and SBRT and sorafenib, respectively.Conclusions and RelevanceIn this phase 3 randomized clinical trial, among patients with locally advanced HCC, SBRT was associated with a clinically important but not statistically significant improved overall survival compared with sorafenib alone.Trial RegistrationClinicalTrials.gov Identifier: NCT01730937

中文翻译：

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立体定向放疗与单独使用索拉非尼治疗肝细胞癌


重要性大多数局部晚期肝细胞癌 （HCC） 患者在全身治疗后在肝脏内复发。目的确定与单独使用索拉非尼相比，立体定向放射治疗 （SBRT） 是否能改善局部晚期 HCC 患者的预后。设计、设置和参与者这项多中心 3 期随机临床试验将 HCC 患者 1：1 随机分配至索拉非尼或 SBRT 组，然后用索拉非尼，按体能状态、肝功能、转移程度和大血管浸润分层。符合条件的患者患有不适合标准局部区域治疗或难治性 HCC，并且是一线全身治疗的候选者。2013 年 4 月至 2021 年 3 月收集数据，并于 2022 年 7 月至 2023 年 8 月分析数据。主要结局和测量主要终点是总生存期 （OS）。次要终点是无进展生存期 （PFS） 、不良事件和生活质量。结果在随机分配的 193 例患者中，177 例符合条件。由于标准护理全身治疗的变化，应计提前停止。在纳入的 177 例患者中，150 例 （84.7%） 为男性，中位 （IQR） 年龄为 66 （60-72） 岁。131 例 （74.0%） 观察到大血管浸润。截至 2022 年 7 月 1 日，索拉非尼组的中位 OS 为 12.3 个月 （90% CI，10.6-14.3），而 SBRT 和索拉非尼组的中位 OS 为 15.8 个月 （90% CI，11.4-19.2） （风险比 [HR]，0.77;90% CI，0.59-1.01;1 侧 P = .06）。调整分层因素后，SBRT 改善了 OS （HR，0.72;95% CI，0.52-0.99;2 侧 P = .04）。中位 PFS 从索拉非尼组的 5.5 个月 （95% CI， 3.4-6.3） 改善到 SBRT 和索拉非尼组的 9.2 个月 （95% CI， 7.5-11.9） （HR， 0.55;95% CI， 0.40-0.75;2 面 P < .001）。接受索拉非尼治疗与 SBRT 和索拉非尼治疗的患者中，88 名中有 37 名 （42%） 和 83 名患者中有 39 名 （47%） 出现与治疗相关的 3 级或更高级别的不良事件 （P = .52）。索拉非尼组有 2 例治疗相关死亡 （未另行说明的死亡和肝功能衰竭），SBRT 和索拉非尼组 1 例 （肺部感染）。在 6 个月时，接受索拉非尼治疗的患者中有 2 名 （10%） 和 17 名患者中有 6 名 （35%） 的生活质量分别得到改善。结论和相关性在这项 3 期随机临床试验中，在局部晚期 HCC 患者中，与单独使用索拉非尼相比，SBRT 与临床重要但无统计学意义的总生存期改善相关。试验注册临床试验。gov 标识符： NCT01730937