Yang Zijian, Suda Goki, Maehara Osamu, Ohara Masatsugu, Yoshida Sonoe, Hosoda Shunichi, Kimura Megumi, Kubo Akinori, Tokuchi Yoshimasa, Fu Qingjie, Yamada Ren, Kitagataya Takashi, Suzuki Kazuharu, Kawagishi Naoki, Nakai Masato, Sho Takuya, Natsuizaka Mitsuteru, Morikawa Kenichi, Ogawa Koji, Ohnishi Shunsuke, Sakamoto Naoya
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo 060-8589, Japan.
Laboratory of Molecular and Cellular Medicine, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
Cancers (Basel). 2022 Jan 4;14(1):232. doi: 10.3390/cancers14010232.
Serum growth factor changes and their effect on prognosis during lenvatinib for unresectable hepatocellular carcinoma (HCC) remain underexplored. The sequential changes in serum growth factors during lenvatinib for unresectable HCC were evaluated in 58 patients using complete clinical data, and preserved serum was used to investigate changes in FGF-19, ANG-2, HGF, VEGF, and EGF. Patients with a complete response (CR), partial response (PR), and stable disease (SD) were evaluated for growth factor changes between the best response and progressive disease (PD) points, classified based on these changes, and evaluated by post progression survival (PPS). A total of 8, 24, 18, and 8 patients showed CR, PR, SD, and PD, respectively. Multivariate analysis revealed that age, relative dose intensity, and baseline ANG-2 were significantly associated with treatment response. Growth factor changes between the best response and PD points revealed that patients could be classified into four groups based on the EGF, ANG-2, and HGF changes. Although patient characteristics at baseline and PD, their response to lenvatinib, and PFS were similar among those groups, patients with an increase in all growth factors had significantly shorter PPS (median PPS was 553, 323, and 316 versus 173 days in groups 1-4 = 0.032). We revealed that the evaluation of the changes in growth factors during lenvatinib could predict PPS.
在乐伐替尼治疗不可切除肝细胞癌（HCC）期间，血清生长因子的变化及其对预后的影响仍未得到充分研究。利用完整的临床数据对58例患者在乐伐替尼治疗不可切除HCC期间血清生长因子的序贯变化进行了评估，并使用保存的血清来研究成纤维细胞生长因子19（FGF-19）、血管生成素2（ANG-2）、肝细胞生长因子（HGF）、血管内皮生长因子（VEGF）和表皮生长因子（EGF）的变化。对完全缓解（CR）、部分缓解（PR）和疾病稳定（SD）的患者，评估最佳缓解与疾病进展（PD）点之间的生长因子变化，根据这些变化进行分类，并通过进展后生存期（PPS）进行评估。分别有8例、24例、18例和8例患者表现为CR、PR、SD和PD。多因素分析显示，年龄、相对剂量强度和基线ANG-2与治疗反应显著相关。最佳缓解与PD点之间的生长因子变化显示，根据EGF、ANG-2和HGF的变化，患者可分为四组。尽管这些组之间的基线和PD时的患者特征、对乐伐替尼的反应以及无进展生存期（PFS）相似，但所有生长因子均升高的患者的PPS显著缩短（第1 - 4组的中位PPS分别为553天、323天、316天和173天；P = 0.032）。我们发现，评估乐伐替尼治疗期间生长因子的变化可以预测PPS。
