Song Ga-Young, Park Joo Heon, Kang Sae-Ryung, Han Seung Jung, Jung Youjin, Son Minuk, Jang Ho Cheol, Kim Mihee, Ahn Seo-Yeon, Jung Sung-Hoon, Ahn Jae-Sook, Lee Je-Jung, Kim Hyeoung-Joon, Yang Deok-Hwan
Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Medical School of Chonnam National University, Hwasun-gun 58128, Jeollanam-do, Republic of Korea.
Department of Laboratory Medicine, Chonnam National University Hwasun Hospital, Medical School of Chonnam National University, Hwasun-gun 58128, Jeollanam-do, Republic of Korea.
Cancers (Basel). 2025 May 22;17(11):1734. doi: 10.3390/cancers17111734.
BACKGROUND/OBJECTIVES: Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for non-invasive tumor monitoring in diffuse large B-cell lymphoma (DLBCL).
In this study, 52 patients with newly diagnosed advanced-stage DLBCL treated with R-CHOP underwent serial ctDNA analysis at baseline, interim (after three cycles), and end of treatment. The prognostic significance of ctDNA dynamics was evaluated, and its predictive value was compared with the PET/CT response.
Targeted next-generation sequencing revealed baseline ctDNA in 98.1% of patients, with 74.7% concordance to tumor tissue genotyping. Higher baseline ctDNA levels correlated with elevated LDH, older age, and high IPI scores. A ≥2-log reduction in ctDNA at interim was significantly associated with improved overall survival ( = 0.004), though not with progression-free survival. Notably, combining interim ctDNA dynamics with PET/CT results enhanced the predictive accuracy for treatment outcomes, particularly among patients with partial metabolic responses.
These findings support the clinical utility of ctDNA for dynamic risk assessment in DLBCL, and suggest that integrating ctDNA with imaging biomarkers may guide more personalized therapeutic strategies. Further validation using highly sensitive ctDNA assays is warranted to optimize its role in routine clinical practice.
背景/目的：循环肿瘤DNA（ctDNA）已成为弥漫性大B细胞淋巴瘤（DLBCL）无创肿瘤监测的一种有前景的生物标志物。
在本研究中，52例接受R-CHOP治疗的新诊断晚期DLBCL患者在基线、中期（三个周期后）和治疗结束时接受了系列ctDNA分析。评估了ctDNA动态变化的预后意义，并将其预测价值与PET/CT反应进行了比较。
靶向二代测序显示98.1%的患者基线存在ctDNA，与肿瘤组织基因分型的一致性为74.7%。较高的基线ctDNA水平与乳酸脱氢酶升高、年龄较大和国际预后指数（IPI）评分较高相关。中期ctDNA水平降低≥2个对数与总生存期改善显著相关（P = 0.004），但与无进展生存期无关。值得注意的是，将中期ctDNA动态变化与PET/CT结果相结合可提高治疗结果的预测准确性，尤其是在部分代谢反应患者中。
这些发现支持ctDNA在DLBCL动态风险评估中的临床应用，并表明将ctDNA与影像生物标志物相结合可能指导更个性化的治疗策略。有必要使用高灵敏度ctDNA检测进行进一步验证，以优化其在常规临床实践中的作用。
