Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, 100142, China.
Jichenjunchuang Clinical Laboratory, Hangzhou, Zhejiang, China.
BMC Med. 2022 Oct 25;20(1):369. doi: 10.1186/s12916-022-02562-3.
Circulating tumor DNA (ctDNA) has been proven to be a promising tumor-specific biomarker in solid tumors, but its clinical utility in risk stratification and early prediction of relapse for diffuse large B cell lymphoma (DLBCL) has not been well explored.
Here, using a lymphoma-specific sequencing panel, we assessed the prognostic and predictive utilities of ctDNA measurements before, during, and after first-line therapy in 73 Chinese DLBCL patients.
The pretreatment ctDNA level serving as an independent prognostic factor for both progression-free survival (PFS, adjusted HR 2.47; p = 0.004) and overall survival (OS, adjusted HR 2.49; p = 0.011) was confirmed in our cohort. Furthermore, the patients classified as molecular responders who presented a larger decrease in ctDNA levels after the initial two treatment cycles had more favorable PFS (unreached vs. 6.25 months; HR 5.348; p = 0.0015) and OS (unreached vs. 25.87; HR 4.0; p = 0.028) than non-responders. In addition, interim ctDNA clearance may be an alternative noninvasive method of positron emission tomography and computed tomography (PET-CT) for predicting better PFS (HR 3.65; p = 0.0033) and OS (HR 3.536; p = 0.016). We also demonstrated that posttreatment ctDNA was a sensitive indicator for detecting minimal residual disease (MRD) in patients with a high risk of recurrence (HR 6.471; p = 0.014), who were otherwise claimed to achieve radiographic CR (complete remission).
CtDNA is a promising noninvasive tool for prognosis prediction, response assessment, and early relapse prediction of first-line treatment in DLBCL patients.
循环肿瘤 DNA（ctDNA）已被证明是实体瘤中一种有前途的肿瘤特异性生物标志物，但它在弥漫性大 B 细胞淋巴瘤（DLBCL）中的风险分层和早期复发预测中的临床应用尚未得到充分探索。
在这里，我们使用淋巴瘤特异性测序面板，评估了 73 例中国 DLBCL 患者一线治疗前、治疗中和治疗后的 ctDNA 测量在预后和预测方面的效用。
在我们的队列中，预处理 ctDNA 水平是无进展生存期（PFS，调整后的 HR 2.47；p=0.004）和总生存期（OS，调整后的 HR 2.49；p=0.011）的独立预后因素。此外，在最初两个治疗周期后 ctDNA 水平下降较大的患者被归类为分子应答者，他们具有更有利的 PFS（未达到 vs. 6.25 个月；HR 5.348；p=0.0015）和 OS（未达到 vs. 25.87；HR 4.0；p=0.028）。此外，中期 ctDNA 清除可能是预测更好的 PFS（HR 3.65；p=0.0033）和 OS（HR 3.536；p=0.016）的替代非侵入性正电子发射断层扫描和计算机断层扫描（PET-CT）方法。我们还表明，治疗后 ctDNA 是检测高复发风险（HR 6.471；p=0.014）患者微小残留病（MRD）的敏感指标，这些患者被认为达到了影像学完全缓解（CR）。
ctDNA 是一种有前途的非侵入性工具，可用于预测 DLBCL 患者一线治疗的预后、反应评估和早期复发预测。
