Ando Yuwa, Yamauchi Masami, Suehiro Yosuke, Yamaoka Kenji, Kosaka Yumi, Fuji Yasutomo, Uchikawa Shinsuke, Kodama Kenichiro, Morio Kei, Fujino Hatsue, Nakahara Takashi, Ono Atsushi, Murakami Eisuke, Kawaoka Tomokazu, Takahashi Shoichi, Tsuge Masataka, Hiramatsu Akira, Imamura Michio, Chayama Kazuaki, Aikata Hiroshi
Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minamiku, Hiroshima, 734-8551, Japan.
Department of Clinical Oncology, Hiroshima Prefectural Hospital, Hiroshima, Japan.
Clin J Gastroenterol. 2020 Oct;13(5):867-872. doi: 10.1007/s12328-020-01099-3. Epub 2020 Feb 4.
Hepatocellular carcinoma (HCC) has limited systemic treatment options and a poor prognosis. The immune checkpoint inhibitor pembrolizumab was recently approved for the treatment of solid tumors with microsatellite instability (MSI). However, its clinical utility for the management of HCC remains to be clarified. Here, we present a case of unresectable HCC with MSI that showed an impressive response to pembrolizumab treatment. A 64-year-old man with chronic HCV infection was diagnosed with a large HCC. His severe liver dysfunction and poor performance status prevented any treatment option other than sorafenib. However, sorafenib failed after a few days due to the rapid progression of the tumor. Based on the finding of MSI in a biopsy specimen, immunotherapy using pembrolizumab was initiated. A dramatic improvement in his general condition and a reduction in tumor size were observed after the initiation of pembrolizumab treatment. Among a cohort of 50 consecutive patients with advanced HCC who were refractory to standard systemic therapy, MSI was found only in the present case. Immune checkpoint blockade therapy induced prominent anti-tumor effects in HCC with MSI. Screening for defects in DNA mismatch repair function may be warranted in HCC patients despite the low frequency of MSI.
肝细胞癌（HCC）的全身治疗选择有限，预后较差。免疫检查点抑制剂派姆单抗最近被批准用于治疗微卫星不稳定（MSI）的实体瘤。然而，其在HCC治疗中的临床效用仍有待阐明。在此，我们报告一例不可切除的MSI-HCC病例，该病例对派姆单抗治疗表现出显著反应。一名64岁慢性丙型肝炎病毒感染男性被诊断为巨大HCC。他严重的肝功能不全和较差的体能状态排除了除索拉非尼之外的任何治疗选择。然而，由于肿瘤快速进展，索拉非尼在数天后失效。基于活检标本中MSI的发现，开始使用派姆单抗进行免疫治疗。派姆单抗治疗开始后，观察到其一般状况显著改善，肿瘤大小缩小。在连续50例对标准全身治疗难治的晚期HCC患者队列中，仅在本病例中发现MSI。免疫检查点阻断疗法在MSI-HCC中诱导出显著的抗肿瘤效应。尽管MSI发生率较低，但对HCC患者进行DNA错配修复功能缺陷筛查可能是必要的。
