Guo Hanfei, Qian Lei, Chen Xiao, Zhao Yuguang, Song Wei, Guan Yanjie, Cui Jiuwei
Cancer Center, The First Hospital of Jilin University, Changchun 130021, China.
Open Med (Wars). 2021 Dec 15;17(1):53-60. doi: 10.1515/med-2021-0404. eCollection 2022.
Clinical treatment is challenging for elderly patients with lung cancer who cannot tolerate chemotherapy, do not have cancer driver genes, and have low expression of PD-L1. Since these patients are usually excluded from clinical studies, evidence-based medicine supporting the use of immunotherapy is lacking. Considering the potentially limited clinical benefits and high associated risk of hyperprogressive disease, determining an appropriate treatment is an urgent clinical challenge. We report a 71 year-old male patient diagnosed with advanced lung adenocarcinoma lacking key driving genes (, , and ), and low expression of PD-L1 on tumor cells (10-15%). The tumor tissue showed a low level of microsatellite instability, low tumor mutational burden, and no DNA mismatch repair deficiency on whole-exome sequencing (WES). However, a high blood tumor mutational burden was detected. After considering the biomarkers of therapeutic effect and ruling out the risk of hyperprogressive disease, pembrolizumab 200 mg was administered every 3 weeks for a year (17 cycles). The disease remained stable for >39 months, and adverse effects were mild and well-tolerated. Therefore, a comprehensive biomarker evaluation, especially in elderly patients lacking driving genes, is essential. Liquid biopsy technology and WES may be useful for overcoming the limitations of tissue biopsy.
对于无法耐受化疗、没有癌症驱动基因且程序性死亡受体配体1（PD-L1）表达低的老年肺癌患者，临床治疗具有挑战性。由于这些患者通常被排除在临床研究之外，缺乏支持使用免疫疗法的循证医学依据。考虑到潜在的有限临床获益和高进展性疾病相关风险，确定合适的治疗方法是一项紧迫的临床挑战。我们报告了一名71岁男性患者，诊断为晚期肺腺癌，缺乏关键驱动基因（ 、 和 ），肿瘤细胞上PD-L1表达低（10%-15%）。肿瘤组织显示微卫星不稳定性水平低、肿瘤突变负荷低，全外显子测序（WES）未发现DNA错配修复缺陷。然而，检测到血液肿瘤突变负荷高。在考虑治疗效果生物标志物并排除高进展性疾病风险后，每3周给予帕博利珠单抗200mg，持续一年（17个周期）。疾病稳定超过39个月，不良反应轻微且耐受性良好。因此，尤其是对于缺乏驱动基因的老年患者，进行全面的生物标志物评估至关重要。液体活检技术和WES可能有助于克服组织活检的局限性。
