Table_1_Overall survival in advanced hepatocellular carcinoma treated with concomitant systemic therapy and stereotactic body radiation therapy or systemic therapy alone.docx

IntroductionFirst-line systemic therapy (ST) options for advanced hepatocellular carcinoma (HCC) include tyrosine kinase inhibitors and immunotherapy (IO). Evolving data suggest prolonged overall survival (OS) when ST is combined with stereotactic body radiation therapy (SBRT), although evidence is significantly limited in HCC populations. We hypothesized that advanced HCC patients in the National Cancer Database (NCDB) would have improved OS when receiving ST+SBRT vs ST alone.
MethodsStage III/IV HCC patients diagnosed from 2010-2020 and treated with first-line ST±SBRT were identified from the NCDB. The primary endpoint was OS from date of diagnosis stratified by the receipt of SBRT (ST+SBRT vs ST alone). Survival was estimated using Kaplan-Meier methodology and compared via log-rank. Multivariate analysis (MVA) was performed by Cox regression.
ResultsOf 10,505 eligible patients with stage III disease, 115 (1.1%) received ST+SBRT and 10,390 (98.9%) received ST alone. Of 9,617 eligible patients with stage IV disease, 127 (1.3%) received ST+SBRT and 9,490 (98.7%) received ST alone. Median follow-up time was 6.8 months. Baseline characteristics were similar between cohorts. Patients with stage III disease receiving ST+SBRT had improved median OS (12.62 months vs 8.38 months) and higher rates of survival at 1-year (53.0% vs 38.7%) and 2-years (27.0% vs 20.7%) compared to those receiving ST alone (log-rank P=0.0054). Similarly, patients with stage IV disease receiving ST+SBRT had improved median OS (11.79 months vs 5.72 months) and higher rates of survival at 1-year (49.6% vs 26.2%) and 2-years (23.6% vs 12.0%) (log-rank P<0.0001). On MVA, receipt of SBRT predicted improved OS (HR=0.748, 95%CI 0.588-0.951; P=0.0178) and receipt of IO trended towards improved OS (HR=0.859, 95%CI 0.735-1.003; P=0.0538).
ConclusionIn advanced HCC, patients receiving ST+SBRT had improved OS compared to those receiving ST alone. Prospective clinical trials are warranted to better identify HCC populations which may benefit from combined modality therapy.

引言 晚期肝细胞癌（hepatocellular carcinoma，HCC）的一线系统治疗（systemic therapy，ST）方案包括酪氨酸激酶抑制剂（tyrosine kinase inhibitors）与免疫治疗（immunotherapy，IO）。越来越多的研究数据显示，将系统治疗与体部立体定向放射治疗（stereotactic body radiation therapy，SBRT）联合应用可延长患者总生存期（overall survival，OS），但针对肝细胞癌人群的相关证据仍十分有限。本研究假设，在美国国家癌症数据库（National Cancer Database，NCDB）收录的晚期肝细胞癌患者中，接受系统治疗联合SBRT（ST+SBRT）的患者较仅接受系统治疗的患者总生存期更优。
方法 从美国国家癌症数据库（NCDB）中筛选出2010-2020年确诊、接受一线系统治疗±体部立体定向放射治疗（SBRT）的Ⅲ/Ⅳ期肝细胞癌患者。主要研究终点为自确诊日期起算的总生存期（OS），并按是否接受SBRT（ST+SBRT组 vs 仅系统治疗组）进行分层分析。生存情况采用Kaplan-Meier法进行估计，组间比较采用log-rank检验；多因素分析（multivariate analysis，MVA）采用Cox回归模型。
结果 共有10505例符合入组标准的Ⅲ期肝细胞癌患者，其中115例（1.1%）接受了ST+SBRT治疗，10390例（98.9%）仅接受系统治疗。另有9617例符合入组标准的Ⅳ期肝细胞癌患者，其中127例（1.3%）接受ST+SBRT治疗，9490例（98.7%）仅接受系统治疗。中位随访时间为6.8个月。两组患者的基线特征均衡可比。相较于仅接受系统治疗的患者，接受ST+SBRT的Ⅲ期患者中位总生存期更长（12.62个月 vs 8.38个月），1年生存率（53.0% vs 38.7%）与2年生存率（27.0% vs 20.7%）更高（log-rank P=0.0054）。同样，接受ST+SBRT的Ⅳ期患者中位总生存期亦更优（11.79个月 vs 5.72个月），1年生存率（49.6% vs 26.2%）与2年生存率（23.6% vs 12.0%）更高（log-rank P<0.0001）。多因素分析结果显示，接受SBRT治疗是总生存期改善的独立预测因素（风险比hazard ratio，HR=0.748，95%置信区间confidence interval，CI：0.588-0.951；P=0.0178），而免疫治疗（IO）亦呈现出改善总生存期的趋势（HR=0.859，95%CI：0.735-1.003；P=0.0538）。
结论 对于晚期肝细胞癌患者，接受ST+SBRT联合治疗的患者总生存期优于仅接受系统治疗的患者。未来需开展前瞻性临床试验，以进一步明确可从该联合治疗方案中获益的肝细胞癌人群。