ImportancePrevious studies showed that 42% to 50% of patients with locally advanced hepatocellular carcinoma (HCC) achieved complete remission (CR) after combined locoregional therapy (LRT) plus immunotherapy (IO). However, data on predictors of CR and long-term clinical outcomes without surgery and after discontinuation of IO are lacking.ObjectiveTo assess the long-term clinical outcomes among patients with unresectable HCC who achieved CR after LRT-IO and were placed on a watch-and-wait protocol.Design, Setting, and ParticipantsThis cohort study included patients with unresectable HCC who achieved CR after LRT-IO in 2 prospective studies between January 2018 and December 2022. The time of data cutoff was June 2023. Radiologic CR was defined per modified Response Evaluation Criteria in Solid Tumors. All patients underwent close surveillance after CR without surgical interventions, and IO was discontinued.ExposureAll patients had received stereotactic body radiotherapy followed by anti–programmed cell death protein 1 or anti–programmed death ligand 1 therapy. Forty-nine patients had received a dose of transarterial chemoembolization before stereotactic body radiotherapy.Main Outcomes and MeasuresThe primary outcome was the 3-year overall survival (OS) rate. Secondary outcomes included the 3-year time-to-progression rate, 3-year local control rate, and relapse pattern. Factors associated with CR were analyzed using multivariate analyses.ResultsA total of 63 patients were enrolled (58 male [92.1%]; median age, 69 years [range, 18-90 years]); 38 patients (60.3%) had macrovascular invasion, and the median tumor diameter was 10 cm (range, 3.8-31.1 cm). The median follow-up time was 34.7 months (95% CI, 6.5-64.6 months). Twenty-nine patients (46.0%) achieved CR. The patients achieving CR had a significantly better 3-year OS rate than patients not achieving CR (75.5% [95% CI, 58.2%-98.3%] vs 28.1% [95% CI, 7.4%-29.4%]; P < .001). Among the 29 patients with CR, the 3-year time-to-progression rate was 58.7% (95% CI, 38.7%-79.1%) and the 3-year local control rate was 90.5% (95% CI, 78.2%-100%). Ten patients (34.5%) developed recurrence; among them, 6 (60.0%) with solitary intrahepatic disease relapse underwent curative surgical treatment. The absence of tumor vascular invasion (odds ratio, 0.30; 95% CI, 0.10-0.89) and the sum of the largest lesion diameters of 8 cm or less (odds ratio, 0.26; 95% CI, 0.07-0.98) were associated with CR.Conclusions and RelevanceThis cohort study of LRT-IO with long-term follow-up data found a durable response in patients with locally advanced unresectable HCC. Long-term survival was attainable in patients with radiologic CR. Further randomized clinical trials are warranted.

中文翻译：

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对肝细胞癌的局部区域治疗加免疫治疗完全缓解


重要性先前的研究表明，42% 至 50% 的局部晚期肝细胞癌 （HCC） 患者在局部区域联合治疗 （LRT） 加免疫治疗 （IO） 后达到完全缓解 （CR）。然而，缺乏关于 CR 的预测因子和不手术和停止 IO 后的长期临床结局的数据。目的评估 LRT-IO 后达到 CR 并接受观察和等待方案的不可切除 HCC 患者的长期临床结局。设计、设置和参与者该队列研究包括 2018 年 1 月至 2022 年 12 月期间在 LRT-IO 后达到 CR 的 2 项前瞻性研究中的不可切除 HCC 患者。数据截止时间为 2023 年 6 月。放射学 CR 是根据修改后的实体瘤反应评估标准定义的。所有患者在 CR 后均接受密切监测，无手术干预，并停止 IO。暴露所有患者均接受立体定向放疗，随后接受抗程序性细胞死亡蛋白 1 或抗程序性死亡配体 1 治疗。49 例患者在立体定向放疗前接受了一剂经动脉化疗栓塞术。主要结局和测量主要结局是 3 年总生存率 （OS）。次要结局包括 3 年进展时间、 3 年局部控制率和复发模式。使用多变量分析分析与 CR 相关的因素。结果共纳入 63 例患者 （58 例男性 [92.1%];中位年龄 69 岁 [范围，18-90 岁]）;38 例患者 （60.3%） 有大血管浸润，中位肿瘤直径为 10 cm （范围，3.8-31.1 cm）。中位随访时间为 34.7 个月 （95% CI，6.5-64.6 个月）。29 例患者 （46.0%） 达到 CR。 达到 CR 的患者 3 年 OS 率显著优于未达到 CR 的患者 （75.5% [95% CI，58.2%-98.3%] vs 28.1% [95% CI，7.4%-29.4%];P < .001）。在 29 例 CR 患者中，3 年进展时间为 58.7% （95% CI，38.7%-79.1%），3 年局部控制率为 90.5% （95% CI，78.2%-100%）。10 例患者 （34.5%） 出现复发;其中 6 例 （60.0%） 孤立性肝内疾病复发接受了根治性手术治疗。无肿瘤血管浸润 （OR ratio， 0.30;95% CI， 0.10-0.89） 和最大病灶直径为 8 cm 或更小 （OR 比值比，0.26;95% CI， 0.07-0.98） 与 CR 相关。结论和相关性这项具有长期随访数据的 LRT-IO 队列研究发现，局部晚期不可切除的 HCC 患者具有持久的反应。放射学 CR 患者可获得长期生存。需要进一步的随机临床试验。