Iijima Yuki, Hirotsu Yosuke, Amemiya Kenji, Higashi Seishi, Miyashita Yoshihiro, Omata Masao
Lung Cancer and Respiratory Disease Center, Yamanashi Prefectural Central Hospital, 1-1-1 Fujimi, Kofu-City, Yamanashi, 400-8506, Japan.
Genome Analysis Center, Yamanashi Prefectural Central Hospital, 1-1-1 Fujimi, Kofu-City, Yamanashi, 400-8506, Japan.
Respir Med Case Rep. 2017 Jun 5;22:31-33. doi: 10.1016/j.rmcr.2017.05.015. eCollection 2017.
A 77-year-old Japanese man presented to our hospital with a 1-month history of low back pain and was diagnosed as having stage IV mutation-positive lung adenocarcinoma. After treatment with EGFR tyrosine kinase inhibitor and cytotoxic chemotherapy, nivolumab was started as fourth-line therapy. Remarkable regression of the primary tumor was observed, suggesting high anti-tumor activity of nivolumab. We retrospectively investigated the change in circulating tumor DNA (ctDNA) variant allele fractions in serial plasma samples before and after the nivolumab therapy. Targeted sequencing analysis showed tumor-derived and mutations detectable in plasma, and the timing of decrease was only 5 days, much earlier than the appearance of radiological changes. Overall, these results suggest that ctDNA might reflect tumor burden and might be a surrogate marker of the therapeutic efficacy of immune checkpoint therapy.
一名77岁的日本男性因腰痛1个月前来我院就诊，被诊断为IV期突变阳性肺腺癌。在接受表皮生长因子受体酪氨酸激酶抑制剂和细胞毒性化疗后，开始使用纳武单抗作为四线治疗。观察到原发肿瘤明显消退，提示纳武单抗具有较高的抗肿瘤活性。我们回顾性研究了纳武单抗治疗前后系列血浆样本中循环肿瘤DNA（ctDNA）变异等位基因分数的变化。靶向测序分析显示血浆中可检测到肿瘤来源的 和 突变，下降时间仅为5天，比影像学变化出现的时间早得多。总体而言，这些结果表明ctDNA可能反映肿瘤负荷，可能是免疫检查点治疗疗效的替代标志物。
