Stereotactic Body Radiotherapy vs Sorafenib Alone in Hepatocellular Carcinoma: The NRG Oncology/RTOG 1112 Phase 3 Randomized Clinical Trial.

Background

To determine whether stereotactic body radiation therapy (SBRT) improves outcomes in patients with locally advanced HCC compared with sorafenib alone.

确定立体定向体部放射治疗（SBRT）是否能改善仅接受索拉非尼治疗的局部晚期HCC患者的预后。

DESIGN, SETTING, AND PARTICIPANTS: This 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.

设计、设置和参与者：这项多中心III期随机临床试验按照1:1的比例将HCC患者随机分配到索拉非尼组或立体定向放射治疗(SBRT)后接受索拉非尼治疗，根据体能状态、肝功能、转移程度和大血管侵犯进行分层。

Eligible patients had HCC unsuitable for or refractory to standard local-regional therapies and were candidates for first-line systemic therapy.

符合条件的患者患有不适合或对标准局部-区域性治疗无反应的HCC，并且是第一线系统治疗的候选人。

Data were collected from April 2013 to March 2021, and data were analyzed from July 2022 to August 2023.

数据收集时间为2013年4月至2021年3月，数据分析时间为2022年7月至2023年8月。

intervention

Personalized SBRT, 27.5 to 50 Gy in 5 fractions.

个性化立体定向放射治疗（SBRT），剂量为27.5至50 Gy，分5次给予。

main_outcomes_and_measures

The primary end point was overall survival(OS).

主要终点是总生存（OS）。

Secondary end points were progression-free survival(PFS), adverse events, and quality of life.

次要终点包括无进展生存（PFS）、不良事件和生活质量。

Results

Of 193 patients randomized, 177 were eligible.

在随机化的193名患者中，有177名患者符合入选标准。

Accrual was stopped early due to a change in standard-of-care systemic therapy.

由于系统治疗的标准护理方案发生变化，提前停止了患者招募。

Of 177 included patients, 150 (84.7%) were male, and the median (IQR) age was 66 (60-72) years.

在纳入的177名患者中，有150名（84.7%）为男性，中位年龄为66岁（四分位数间距为60-72岁）。

Macrovascular invasion was seen in 131 (74.0%).

在131名（74.0%）患者中观察到大血管侵犯。

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).

截至2022年7月1日，接受索拉非尼治疗的中位总生存期为12.3个月（90%置信区间，10.6-14.3个月），而在立体定向放疗（SBRT）后接受索拉非尼治疗的中位总生存期为15.8个月（90%置信区间，11.4-19.2个月）（风险比[HR]，0.77；90%置信区间，0.59-1.01；单侧P = .06）。

Adjusting for stratification factors, OS was improved with SBRT (HR, 0.72; 95% CI, 0.52-0.99; 2-sided P = .04).

在调整分层因素后，接受SBRT治疗的总生存期有所改善（HR，0.72；95%置信区间，0.52-0.99；双侧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).

无进展生存期（PFS）的中位数从使用索拉非尼的5.5个月（95%置信区间，3.4-6.3个月）提高到联合使用SBRT和索拉非尼的9.2个月（95%置信区间，7.5-11.9个月）（风险比，HR，0.55；95%置信区间，0.40-0.75；双侧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).

在分别接受索拉非尼和SBRT联合索拉非尼治疗的患者中，观察到3级或更高级别的治疗相关不良事件在88名患者中有37例（42%），在83名患者中有39例（47%）（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).

在索拉非尼组中有2例治疗相关死亡（未指明的死亡和肝衰竭），而在SBRT和索拉非尼组中有1例（肺部感染）。

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.

在6个月时，接受索拉非尼治疗的20名患者中有2名（10%）和接受SBRT联合索拉非尼治疗的17名患者中有6名（35%）生活质量得到改善。

conclusions_and_relevance

In 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 survivalcompared with sorafenib alone.

在这项III期随机临床试验中，对于局部晚期肝细胞癌患者，立体定向放射治疗（SBRT）与单独使用索拉非尼相比，总生存期有临床意义的改善，但统计学上不显著。

trial_registration

ClinicalTrials.gov Identifier: NCT01730937.

ClinicalTrials.gov 注册号：NCT01730937。