Dynamics of tumor in situ fluid circulating tumor DNA in recurrent glioblastomas forecasts treatment efficacy of immune checkpoint blockade coupled with low-dose bevacizumab.

IF 2.7 3区医学 Q3 ONCOLOGY Journal of Cancer Research and Clinical Oncology Pub Date : 2024-10-18 DOI:10.1007/s00432-024-05997-8

Dayang Wang, Jiubing Zhang, Chaojie Bu, Guanzheng Liu, Guangzhong Guo, Ziyue Zhang, Guangming Lv, Zhiyuan Sheng, Zhaoyue Yan, Yvshuai Gao, Meiyun Wang, Gang Liu, Ruijiao Zhao, Tianxiao Li, Chunxiao Ma, Xingyao Bu

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Abstract

Purpose: Immune checkpoint blockade (ICB) therapies have shown efficacy in various tumors, but long-term responses in glioblastoma are less than 10%. Quantifying tumor in situ fluid circulating tumor DNA (TISF-ctDNA) and therapeutic dynamics may enable real-time GBM disease burden evaluation. This study explores the potential of tumor in situ fluid circulating tumor DNA (TISF-ctDNA) dynamics in predicting treatment efficacy.

Methods: TISF and peripheral blood samples were collected from patients with recurrent glioblastoma (rGBM) undergoing tislelizumab (a programmed death 1 inhibitor) combined with low-dose bevacizumab (an anti-vascular endothelial growth factor antibody) treatment before and during each immunotherapy cycle. Biomarkers evaluated included TISF-ctDNA, measured using Next Generation Sequencing (NGS), and host inflammation markers such as the platelet-to-lymphocyte ratio (PLR).

Results: All 32 patients received tislelizumab plus low-dose bevacizumab regularly. The median progression-free survival (PFS) was 4.0 months, and overall survival (OS) was 22.3 months. An analysis of 19 patients with continuous evaluable TISF showed baseline TISF-ctDNA abundance did not correlate with OS (p = 0.23) or PFS (p = 0.23). However, a change in TISF-ctDNA maximal Somatic Variant Allelic Frequency (MVAF) after six treatment cycles predicted both PFS (p = 0.02) and OS (p < 0.0001). Lower baseline PLR also correlated with better survival outcomes.

Conclusion: The combination of tislelizumab and low-dose bevacizumab therapy appears to be effective in extending both OS and PFS in rGBM patients. Continuous TISF-ctDNA testing shows potential utility in complementing radiological monitoring. The temporal change pattern of TISF MVAF is more predictive of immunotherapy response than imaging. PLR before immunotherapy can screen patients likely to benefit from tislelizumab plus low-dose bevacizumab therapy.

Trial registration: The trial registration number: NCT05502991; Date of registration: 2022-08-14.

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复发性胶质母细胞瘤中肿瘤原位液循环肿瘤DNA的动态变化预测免疫检查点阻断联合小剂量贝伐珠单抗的疗效

目的：免疫检查点阻断（ICB）疗法已在多种肿瘤中显示出疗效，但胶质母细胞瘤的长期应答率不足10%。对肿瘤原位液循环肿瘤DNA（TISF-ctDNA）和治疗动态进行量化可实现对GBM疾病负担的实时评估。本研究探讨了肿瘤原位液循环肿瘤DNA（TISF-ctDNA）动态预测疗效的潜力：方法：在每个免疫治疗周期之前和期间，收集接受替赛珠单抗（一种程序性死亡1抑制剂）联合低剂量贝伐珠单抗（一种抗血管内皮生长因子抗体）治疗的复发性胶质母细胞瘤（rGBM）患者的TISF和外周血样本。评估的生物标志物包括使用新一代测序技术（NGS）测量的TISF-ctDNA和宿主炎症标志物，如血小板与淋巴细胞比值（PLR）：所有32名患者均定期接受替斯利珠单抗加小剂量贝伐珠单抗治疗。中位无进展生存期（PFS）为 4.0 个月，总生存期（OS）为 22.3 个月。对19名连续可评估TISF的患者进行的分析表明，基线TISF-ctDNA丰度与OS（P = 0.23）或PFS（P = 0.23）无关。然而，六个治疗周期后，TISF-ctDNA最大体细胞变异等位基因频率（MVAF）的变化可预测PFS（p = 0.02）和OS（p 结论：TISF-ctDNA丰度与OS（p = 0.23）和PFS（p = 0.23）不相关：替斯利珠单抗和小剂量贝伐珠单抗联合治疗似乎能有效延长rGBM患者的OS和PFS。连续的 TISF-ctDNA 检测显示出对放射学监测的潜在补充作用。TISF MVAF的时间变化模式比影像学更能预测免疫疗法的反应。免疫治疗前的PLR可以筛选出可能从替斯利珠单抗加小剂量贝伐单抗治疗中获益的患者：试验注册号：NCT05502991NCT05502991；注册日期：2022-08-14。

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来源期刊

Journal of Cancer Research and Clinical Oncology 医学-肿瘤学

CiteScore

4.00

自引率

2.80%

发文量

577

审稿时长

2 months

期刊介绍： The "Journal of Cancer Research and Clinical Oncology" publishes significant and up-to-date articles within the fields of experimental and clinical oncology. The journal, which is chiefly devoted to Original papers, also includes Reviews as well as Editorials and Guest editorials on current, controversial topics. The section Letters to the editors provides a forum for a rapid exchange of comments and information concerning previously published papers and topics of current interest. Meeting reports provide current information on the latest results presented at important congresses. The following fields are covered: carcinogenesis - etiology, mechanisms; molecular biology; recent developments in tumor therapy; general diagnosis; laboratory diagnosis; diagnostic and experimental pathology; oncologic surgery; and epidemiology.