Introduction The progression patterns, dispositions, and outcomes of patients with advanced hepatocellular carcinoma (HCC) who achieved durable responses with immunotherapy remain poorly characterized. Methods Patients with advanced HCC who received immune checkpoint inhibitor (ICI)-based immunotherapy and achieved durable responses were retrospectively included. A durable response was defined as partial response (PR) or stable disease (SD) per RECIST 1.1 for more than 8 months after initiation of immunotherapy. Oligoprogression and polyprogression were defined as progression at ≤3 and >3 lesions, respectively. Results A total of 91 durable responders (63 PR and 28 SD) were identified. The majority had chronic viral hepatitis (n = 69, 75.8%). Forty-seven (51.6%) and 44 (48.4%) patients received the index immunotherapy as first-line and second- or beyond-line therapy, respectively. Fifty-four (59.3%) patients subsequently developed progression, with a predominant pattern of oligoprogression (66.7%). The median overall survival (OS) was 46.2 months (95% CI: 34.1-58.3). For patients with subsequent progression, employment of locoregional therapy (LRT) for progression was associated with prolonged OS (univariate analysis: hazard ratio [HR] 0.397, p = 0.009; multivariate analysis: HR 0.363, p = 0.050). Patients with oligoprogression who received LRT showed longer median OS than those who did not (48.4 vs. 20.5 months, p < 0.001). In contrast, the median OS of patients with polyprogression who received LRT was not different from those without LRT (27.7 vs. 25.5 months, p = 0.794). Conclusion Approximately 60% of the post-immunotherapy durable responders of HCC subsequently develop progression. Proactive LRT may further rescue patients who develop subsequent oligoprogression. Prospective studies are mandatory to clarify the proper management of durable responders with subsequent progression.

中文翻译：

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晚期肝细胞癌免疫治疗后持久反应者的结果 - 重点是寡进展的局部区域治疗。


引言 通过免疫治疗获得持久反应的晚期肝细胞癌 （HCC） 患者的进展模式、倾向和结果仍然描述不佳。方法 回顾性纳入接受基于免疫检查点抑制剂 （ICI） 的免疫治疗并取得持久反应的晚期 HCC 患者。持久反应定义为免疫治疗开始后 8 个月以上的部分反应 （PR） 根据 RECIST 1.1 或疾病稳定 （SD）。寡进展和多进展分别定义为 ≤3 和 >3 病灶的进展。结果 共确定了 91 例持久应答者 （63 例 PR 和 28 例 SD）。大多数患有慢性病毒性肝炎 （n = 69， 75.8%）。47 例 （51.6%） 和 44 例 （48.4%） 患者分别接受了指数免疫治疗作为一线和二线或超线治疗。54 例 （59.3%） 患者随后出现进展，以寡进展为主 （66.7%）。中位总生存期 （OS） 为 46.2 个月 （95% CI： 34.1-58.3）。对于后续进展的患者，采用局部区域治疗 （LRT） 治疗进展与 OS 延长相关 （单变量分析：风险比 [HR] 0.397，p = 0.009;多变量分析：HR 0.363，p = 0.050）。接受 LRT 的寡进展患者比未接受 LRT 的患者显示中位 OS 更长 （48.4 vs. 20.5 个月，p < 0.001）。相比之下，接受 LRT 的多进展患者的中位 OS 与未接受 LRT 的患者没有差异 （27.7 vs. 25.5 个月，p = 0.794）。结论 大约 60% 的免疫治疗后持久反应者 HCC 随后发展为进展。 主动 LRT 可能会进一步挽救随后发生寡进展的患者。前瞻性研究是强制性的，以阐明对后续进展的持久反应者的适当管理。