Dong Changqing, Cheng Wanwan, Zhang Meiling, Li Si, Zhao Lele, Chen Dongsheng, Qin Yong, Xiao Mingzhe, Fang Shencun
Department of Thoracic Surgery, Nanjing Chest hospital, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China.
Department of Respiratory Medicine, Nanjing Chest hospital, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China.
Front Oncol. 2022 Oct 17;12:992596. doi: 10.3389/fonc.2022.992596. eCollection 2022.
To evaluate the potential treatment for patients with non-small cell lung cancer (NSCLC) and rare malignant pulmonary lymphangitis carcinomatosis (PLC), our study provided a genomic profile and clinical outcome of this group of patients.
We retrospectively reviewed patients with NSCLC who developed PLC. The genomic alterations, tumor mutation burden (TMB), and microsatellite instability (MSI) based on DNA-based next-generation sequencing were reviewed and compared in a Chinese population with lung adenocarcinomas (Chinese-LUAD cohort). Clinical outcomes after exploratory anlotinib treatment and factors influencing survival are summarized.
A total of 564 patients with stage IV NSCLC were reviewed, and 39 patients with PLC were included. Genomic profiling of 17 adenocarcinoma patients with PLC (PLC-LUAD cohort) revealed , , and as the three most frequently altered genes. was less mutated in PLC-LUAD than Chinese-LUAD cohort of 778 patients (35.3% vs. 60.9%, ). was mutated more often in the PLC-LUAD cohort (11.8% vs. 1.8%, ). Two patients presented with high tumor mutational burden (TMB-H, 10 mutations/MB). Combing alterations in the patient with squamous cell carcinoma, the most altered pathways of PLC included cell cycle/DNA damage, chromatin modification, the RTK/Ras/MAPK pathway and VEGF signaling changes. Fourteen of the participants received anlotinib treatment. The ORR and DCR were 57.1% and 92.9%, respectively. Patients achieved a median progression-free survival of 4.9 months and a median overall survival of 7 months. The adverse effects were manageable. In patients with adenocarcinoma, the mPFS (5.3 months vs. 2.6 months) and mOS (9.9 months vs. 4.5 months) were prolonged in patients receiving anlotinib treatment compared to those receiving other treatment strategies ().
Patients with PLC in NSCLC demonstrated distinct genetic alterations. The results improve our understanding of the plausible genetic underpinnings of tumorigenesis in PLC and potential treatment strategies. Exploratory anlotinib treatment achieved considerable benefits and demonstrated manageable safety.
为评估非小细胞肺癌（NSCLC）合并罕见恶性肺淋巴管癌病（PLC）患者的潜在治疗方法，我们的研究提供了该组患者的基因组概况和临床结局。
我们回顾性分析了发生PLC的NSCLC患者。基于DNA的二代测序技术，对中国肺腺癌患者群体（中国肺腺癌队列）中的基因组改变、肿瘤突变负荷（TMB）和微卫星不稳定性（MSI）进行了回顾和比较。总结了探索性使用安罗替尼治疗后的临床结局以及影响生存的因素。
共回顾了564例IV期NSCLC患者，其中39例合并PLC。对17例合并PLC的腺癌患者（PLC-LUAD队列）进行基因组分析发现， 、 和 是三个最常发生改变的基因。PLC-LUAD队列中 的突变率低于778例患者的中国肺腺癌队列（35.3%对60.9%， ）。PLC-LUAD队列中 的突变更为常见（11.8%对1.8%）。两名患者表现出高肿瘤突变负荷（TMB-H，每兆碱基10个突变）。结合鳞状细胞癌患者的改变，PLC中改变最多的通路包括细胞周期/DNA损伤、染色质修饰、RTK/Ras/MAPK通路和VEGF信号变化。14名参与者接受了安罗替尼治疗。客观缓解率（ORR）和疾病控制率（DCR）分别为57.1%和92.9%。患者的中位无进展生存期为4.9个月，中位总生存期为7个月。不良反应可控。在腺癌患者中，与接受其他治疗策略的患者相比，接受安罗替尼治疗的患者的中位无进展生存期（5.3个月对2.6个月）和中位总生存期（9.9个月对4.5个月）有所延长（ ）。
NSCLC合并PLC的患者表现出独特的基因改变。这些结果提高了我们对PLC肿瘤发生可能的遗传基础和潜在治疗策略的理解。探索性使用安罗替尼治疗取得了显著疗效，且安全性可控。
