Sarcoma Translational Research Laboratory, Vall d'Hebron Institute of Oncology (VHIO).
Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain.
Curr Opin Oncol. 2024 Jul 1;36(4):282-290. doi: 10.1097/CCO.0000000000001040. Epub 2024 Apr 19.
This review explores the role of circulating tumor (ct)DNA as a biomarker for clinical decision-making and monitoring purposes in metastatic gastrointestinal stromal tumor (GIST) patients. We discuss key insights from recent clinical trials and anticipate the future perspectives of ctDNA profiling within the clinical landscape of GIST.
The identification and molecular characterization of KIT/platelet-derived growth factor receptor alpha (PDGFRA) mutations from ctDNA in metastatic GIST is feasible and reliable. Such identification through ctDNA serves as a predictor of clinical outcomes to tyrosine-kinase inhibitors (TKIs) in metastatic patients. Additionally, conjoined ctDNA analysis from clinical trials reveal the evolving mutational landscapes and increase in intratumoral heterogeneity across treatment lines. Together, this data positions ctDNA determination as a valuable tool for monitoring disease progression and guiding therapy in metastatic patients. These collective efforts culminated in the initiation of a ctDNA-based randomized clinical trial in GIST, marking a significant milestone in integrating ctDNA testing into the clinical care of GIST patients.
The dynamic field of ctDNA technologies is rapidly evolving and holds significant promise for research. Several trials have successfully validated the clinical utility of ctDNA in metastatic GIST, laying the foundations for its prospective integration into the routine clinical management of GIST patients.
本综述探讨了循环肿瘤 DNA(ctDNA)作为转移性胃肠间质瘤(GIST)患者临床决策和监测目的的生物标志物的作用。我们讨论了最近临床试验的关键见解,并预测了 ctDNA 分析在 GIST 临床领域的未来前景。
从转移性 GIST 的 ctDNA 中鉴定和分子特征化 KIT/血小板衍生生长因子受体α(PDGFRA)突变是可行且可靠的。这种通过 ctDNA 进行的鉴定可作为转移性患者对酪氨酸激酶抑制剂(TKI)的临床结局的预测因子。此外,来自临床试验的联合 ctDNA 分析揭示了治疗线之间不断变化的突变景观和肿瘤内异质性的增加。总之,这些数据表明 ctDNA 测定是监测转移性患者疾病进展和指导治疗的有价值的工具。这些共同努力促成了 GIST 中基于 ctDNA 的随机临床试验的启动,标志着将 ctDNA 检测纳入 GIST 患者临床护理的重要里程碑。
ctDNA 技术的动态领域正在迅速发展,具有很大的研究潜力。几项试验已经成功验证了 ctDNA 在转移性 GIST 中的临床实用性,为其前瞻性整合到 GIST 患者的常规临床管理奠定了基础。