Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.
German Cancer Consortium (DKTK), partner site Tübingen, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Nat Commun. 2024 Oct 9;15(1):8750. doi: 10.1038/s41467-024-52923-0.
Immune checkpoint inhibitors (ICI) have significantly improved overall survival in melanoma patients. However, 60% experience severe adverse events and early response markers are lacking. Circulating tumour DNA (ctDNA) is a promising biomarker for treatment-response and recurrence detection. The prospective PET/LIT study included 104 patients with palliative combined or adjuvant ICI. Tumour-informed sequencing panels to monitor 30 patient-specific variants were designed and 321 liquid biopsies of 87 patients sequenced. Mean sequencing depth after deduplication using UMIs was 6000x and the error rate of UMI-corrected reads was 2.47×10. Variant allele fractions correlated with PET/CT MTV (rho=0.69), S100 (rho=0.72), and LDH (rho=0.54). A decrease of allele fractions between T1 and T2 was associated with improved PFS and OS in the palliative cohort (p = 0.008 and p < 0.001). ctDNA was detected in 76.9% of adjuvant patients with relapse (n = 10/13), while all patients without progression (n = 9) remained ctDNA negative. Tumour-informed liquid biopsies are a reliable tool for monitoring treatment response and early relapse in melanoma patients with ICI.
免疫检查点抑制剂 (ICI) 显著改善了黑色素瘤患者的总生存期。然而，60%的患者经历严重的不良反应，并且缺乏早期反应标志物。循环肿瘤 DNA (ctDNA) 是一种有前途的治疗反应和复发检测的生物标志物。前瞻性 PET/LIT 研究纳入了 104 例姑息性联合或辅助 ICI 的患者。设计了针对 30 个患者特异性变异的肿瘤信息测序面板，并对 87 例患者的 321 份液体活检样本进行了测序。使用 UMIs 重复数据删除后，平均测序深度为 6000x，UMI 校正读数的错误率为 2.47×10。变异等位基因分数与 PET/CT MTV（rho=0.69）、S100（rho=0.72）和 LDH（rho=0.54）相关。姑息性队列中，T1 和 T2 之间等位基因分数的降低与 PFS 和 OS 的改善相关（p=0.008 和 p<0.001）。复发的辅助治疗患者中，76.9%（n=10/13）检测到 ctDNA，而所有无进展的患者（n=9）均为 ctDNA 阴性。肿瘤信息液体活检是监测黑色素瘤患者 ICI 治疗反应和早期复发的可靠工具。
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