Wang Feiqian, Numata Kazushi, Komiyama Satoshi, Miwa Haruo, Sugimori Kazuya, Ogushi Katsuaki, Moriya Satoshi, Nozaki Akito, Chuma Makoto, Ruan Litao, Maeda Shin
Ultrasound Department, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Gastroenterological Center of Yokohama City University Medical Center, Yokohama, Japan.
Front Oncol. 2022 May 4;12:843680. doi: 10.3389/fonc.2022.843680. eCollection 2022.
The present study aimed to evaluate the efficacy and safety of combined lenvatinib (first-line systemic therapy) and radiofrequency ablation (RFA) therapy in patients with intermediate-stage hepatocellular carcinoma with beyond up-to-seven criteria and Child-Pugh Class A liver function (CP A B2-HCC).
Twenty-two patients with CP A B2-HCC were enrolled in the study. The patients had no history of systemic treatment. For the initial lenvatinib administration in this study, all of the patients had an adequate course of treatment (no less than two weeks) and were administered the recommended dose. Of them, 13 were treated by means of lenvatinib monotherapy (monotherapy group), while the 9 patients with no contraindication to RFA operation and who had consented to RFA received initial lenvatinib plus subsequent RFA (combination group). The clinical outcomes that were considered to evaluate the treatments included tumor response, prognosis (recurrence and survivals), and possible adverse events (serum liver enzymes and clinically visible complications).
The combination group exhibited a higher object response rate (9/9, 100%) as best tumor response than the monotherapy group (10/13, 76.9%). Longer progression-free survival (PFS) (12.5 months) and overall survival (OS) (21.3) were demonstrated in the combination group than in the monotherapy group (PFS: 5.5 months; OS:17.1 months). The combination group achieved a higher PFS rate (1-year: 74.1%) and OS rate (2-year: 80%) than the monotherapy group (1-year PFS rate: 0%; 2-year OS rate: 25.6%; for PFS, p<0.001; for OS, p=0.022). The treatment strategy was the independent factor for PFS (HR: 18.215 for monotherapy, p =0.010), which was determined by Cox regression analysis, suggesting that a combination strategy may reduce tumor progression when compared to the use of lenvatinib alone. There were no statistically significant intergroup differences that were observed in terms of adverse events, with the exception of ALT elevation (p=0.007) in the combination group.
Our newly proposed combination therapy may potentially be effective and safe for CP A B2-HCC beyond up-to-seven criteria. A larger scale, multicenter, prospective study is warranted to confirm our findings.
本研究旨在评估乐伐替尼（一线全身治疗）联合射频消融（RFA）治疗对具有超过七项标准且肝功能为Child-Pugh A级（CP A B2-HCC）的中期肝细胞癌患者的疗效和安全性。
22例CP A B2-HCC患者纳入本研究。这些患者无全身治疗史。在本研究中，所有患者在初始使用乐伐替尼时均接受了足够疗程（不少于两周）的治疗，并给予推荐剂量。其中，13例采用乐伐替尼单药治疗（单药治疗组），而9例无RFA手术禁忌且同意接受RFA的患者接受了初始乐伐替尼加后续RFA治疗（联合治疗组）。用于评估治疗效果的临床指标包括肿瘤反应、预后（复发和生存情况）以及可能的不良事件（血清肝酶和临床可见并发症）。
联合治疗组作为最佳肿瘤反应的客观缓解率（9/9，100%）高于单药治疗组（10/13，76.9%）。联合治疗组的无进展生存期（PFS）（12.5个月）和总生存期（OS）（21.3个月）均长于单药治疗组（PFS：5.5个月；OS：17.1个月）。联合治疗组的1年PFS率（74.1%）和2年OS率（80%）高于单药治疗组（1年PFS率：0%；2年OS率：25.6%；PFS方面，p<0.001；OS方面，p = 0.022）。通过Cox回归分析确定，治疗策略是PFS的独立因素（单药治疗的HR：18.215，p = ），这表明与单独使用乐伐替尼相比，联合治疗策略可能会降低肿瘤进展。除联合治疗组的ALT升高（p = 0.007）外，两组在不良事件方面未观察到统计学上的显著差异。
我们新提出的联合治疗方案对于超过七项标准的CP A B2-HCC可能具有潜在的有效性和安全性。有必要开展更大规模多中心前瞻性研究以证实我们的发现。 （注：原文中“p = ”处似乎缺失具体数值）
