不明原发癌中循环游离 DNA 改变的治疗可操作性。
Therapeutic Actionability of Circulating Cell-Free DNA Alterations in Carcinoma of Unknown Primary.
机构信息
Center for Personalized Cancer Therapy, University of California San Diego Moores Cancer Center, La Jolla, CA.
Guardant Health, Redwood City, CA.
出版信息
JCO Precis Oncol. 2021 Nov 3;5. doi: 10.1200/PO.21.00011. eCollection 2021.
UNLABELLED
Cancer of unknown primary (CUP) is a metastatic disease with unidentifiable primary tumor. Somatic alterations can be assessed noninvasively via liquid biopsies interrogating cell-free DNA (cfDNA).
METHODS
We evaluated 1,931 patients with CUP with a cfDNA next-generation sequencing panel (73-74 genes).
RESULTS
Overall, 1,739 patients (90%) had ≥ 1 cfDNA alteration. We then explored alteration actionability (per the levels of evidence from the OncoKB database); 825 patients (47.4% of 1,739) had level 1, level 2, or resistance/R1 alterations. Among 40 clinically annotated patients with CUP who had cfDNA evaluated, higher degrees of matching treatment to alterations (Matching Score > 50% ≤ 50%) was the only variable predicting improved outcome: longer median progression-free survival (10.4 2.5 months; = .002), overall survival (13.4 5.7 months; = .07, trend), and higher clinical benefit rate (stable disease ≥ 6 months/partial response/complete response; 83% 25%; = .003).
CONCLUSION
In summary, cfDNA frequently reveals strong level-of-evidence actionable alterations in CUP, and high degrees of matching to therapy correlates with better outcomes.
目的：评估通过液体活检检测游离 DNA（cfDNA）进行的非侵入性检测，在癌症未知原发灶（CUP）患者中检测体细胞改变的临床应用价值。
方法：我们评估了 1931 例 CUP 患者的 cfDNA 下一代测序panel（73-74 个基因）。
结果：总体而言，1739 例患者（90%）存在≥1 个 cfDNA 改变。然后我们研究了改变的可操作性（根据 OncoKB 数据库的证据级别）；825 例患者（1739 例的 47.4%）存在 1 级、2 级或耐药/ R1 改变。在 40 例具有可评估 cfDNA 的临床注释的 CUP 患者中，更高程度的改变匹配治疗（Matching Score＞50%≤50%）是唯一预测改善预后的变量：更长的中位无进展生存期（10.4±2.5 个月；P=.002）、总生存期（13.4±5.7 个月；P=.07，趋势）和更高的临床获益率（稳定疾病≥6 个月/部分缓解/完全缓解；83%比 25%；P=.003）。
结论：总之，cfDNA 频繁揭示 CUP 中具有强烈证据级别的可操作改变，并且与治疗的高度匹配与更好的结果相关。
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