Division of Medical Oncology, Department of Internal Medicine, Korea University Medical Center, Korea University College of Medicine, Seoul, Republic of Korea; Cancer Research Institute, Korea University, Seoul, Republic of Korea.
Department of Nuclear Medicine, Korea University Medical Center, Korea University College of Medicine, Seoul, Republic of Korea; Department of Molecular Medicine and Biopharmaceutical Science, WCU Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea.
Lung Cancer. 2019 Aug;134:158-166. doi: 10.1016/j.lungcan.2019.06.014. Epub 2019 Jun 13.
This study unravels the significance of cell-free DNA (cfDNA) quantification as a promising measure of the biological behavior/aggressiveness of tumors. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) measured by positron emission tomography/computed tomography scan enable a precise assessment of metabolic tumor burden. However, their clinical implications in identifying patients who need more aggressive treatment in advanced non-small cell lung cancer (NSCLC) are not fully understood.
In the current prospective trial, we analyzed 101 newly diagnosed advanced NSCLC (stage III-IV) patients with measurable baseline MTV, TLG, and cfDNA quantification. The best cut-offs for cfDNA levels, MTV, and TLG to predict progression-free survival and overall survival were determined using X-tile analysis.
There were significant positive correlations between cfDNA and MTV (r = 0.488, p < 0.001) and between cfDNA and TLG (r = 0.554, p < 0.001). High-cfDNA levels and high-MTV/TLG negatively correlated with overall survival (OS) (all p < 0.001). Patients with high-MTV showed similar median OS irrespective of their cfDNA levels (low-cfDNA vs. high-cfDNA=9.2 vs 6.6 months; p > 0.05). However, patients with low-MTV and low-cfDNA levels showed longer OS than those with low-MTV and high-cfDNA levels (low-cfDNA vs. high-cfDNA=49.3 vs 11.5 months; p < 0.001). The patient group with low-TLG also showed similar trends. The cfDNA level was an independent prognostic factor for OS by Cox-proportional hazard analysis.
Although the patients with high metabolic tumor burden had a poor prognosis, regardless of the biological behavior/aggressiveness of the tumor, patients with low metabolic tumor burden and high cfDNA levels showed a poor prognosis. Taken together, this study indicates a stronger prognostic value of baseline cfDNA levels in identifying patients with advanced NSCLC and personalizing their treatment strategies for better survival.
本研究揭示了游离 DNA（cfDNA）定量作为评估肿瘤生物学行为/侵袭性的一种有前途的指标的意义。正电子发射断层扫描/计算机断层扫描测量的代谢肿瘤体积（MTV）和总病变糖酵解（TLG）可精确评估代谢肿瘤负荷。然而，它们在识别需要更积极治疗的晚期非小细胞肺癌（NSCLC）患者方面的临床意义尚不完全清楚。
在目前的前瞻性试验中，我们分析了 101 例基线可测量 MTV、TLG 和 cfDNA 定量的新诊断为晚期 NSCLC（III-IV 期）的患者。使用 X-tile 分析确定 cfDNA 水平、MTV 和 TLG 预测无进展生存期和总生存期的最佳截断值。
cfDNA 与 MTV（r=0.488，p<0.001）和 cfDNA 与 TLG（r=0.554，p<0.001）之间存在显著正相关。高 cfDNA 水平和高 MTV/TLG 与总生存期（OS）呈负相关（均 p<0.001）。高-MTV 患者无论 cfDNA 水平如何，其 OS 中位数均相似（低 cfDNA 与高 cfDNA=9.2 与 6.6 个月；p>0.05）。然而，低-MTV 和低 cfDNA 水平的患者 OS 长于低-MTV 和高 cfDNA 水平的患者（低 cfDNA 与高 cfDNA=49.3 与 11.5 个月；p<0.001）。低-TLG 的患者组也呈现出类似的趋势。Cox 比例风险分析显示 cfDNA 水平是 OS 的独立预后因素。
尽管高代谢肿瘤负荷的患者预后较差，但无论肿瘤的生物学行为/侵袭性如何，低代谢肿瘤负荷和高 cfDNA 水平的患者预后较差。综上所述，本研究表明基线 cfDNA 水平在识别晚期 NSCLC 患者并制定更个体化的治疗策略以提高生存率方面具有更强的预后价值。
