循环 KRAS G12D 但不是 G12V 与转移性胰腺导管腺癌的生存相关。

Circulating KRAS G12D but not G12V is associated with survival in metastatic pancreatic ductal adenocarcinoma.

机构信息

Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA.

Personalis, Inc., Menlo Park, CA, USA.

出版信息

Nat Commun. 2024 Jul 9;15(1):5763. doi: 10.1038/s41467-024-49915-5.

DOI:10.1038/s41467-024-49915-5

PMID:38982051

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11233636/

Abstract

While high circulating tumor DNA (ctDNA) levels are associated with poor survival for multiple cancers, variant-specific differences in the association of ctDNA levels and survival have not been examined. Here we investigate KRAS ctDNA (ctKRAS) variant-specific associations with overall and progression-free survival (OS/PFS) in first-line metastatic pancreatic ductal adenocarcinoma (mPDAC) for patients receiving chemoimmunotherapy ("PRINCE", NCT03214250), and an independent cohort receiving standard of care (SOC) chemotherapy. For PRINCE, higher baseline plasma levels are associated with worse OS for ctKRAS G12D (log-rank p = 0.0010) but not G12V (p = 0.7101), even with adjustment for clinical covariates. Early, on-therapy clearance of G12D (p = 0.0002), but not G12V (p = 0.4058), strongly associates with OS for PRINCE. Similar results are obtained for the SOC cohort, and for PFS in both cohorts. These results suggest ctKRAS G12D but not G12V as a promising prognostic biomarker for mPDAC and that G12D clearance could also serve as an early biomarker of response.

摘要

虽然高水平的循环肿瘤 DNA（ctDNA）与多种癌症的不良预后相关，但 ctDNA 水平与生存之间的变异特异性差异尚未得到研究。在这里，我们研究了接受化疗免疫治疗（"PRINCE"，NCT03214250）的一线转移性胰腺导管腺癌（mPDAC）患者和接受标准治疗（SOC）化疗的独立队列中，ctKRAS 变异特异性与总生存期（OS）/无进展生存期（PFS）的相关性。对于 PRINCE，更高的基线血浆水平与 ctKRAS G12D 的 OS 更差相关（对数秩检验 p = 0.0010），但与 G12V 无关（p = 0.7101），即使调整了临床协变量。早期治疗中 G12D 的清除（p = 0.0002），而不是 G12V（p = 0.4058），与 PRINCE 的 OS 强烈相关。SOC 队列也得到了类似的结果，并且在两个队列中都得到了 PFS 的结果。这些结果表明，ctKRAS G12D 而非 G12V 是 mPDAC 的有前途的预后生物标志物，并且 G12D 的清除也可以作为反应的早期生物标志物。