Center for Personalized Cancer Therapy, University of California San Diego Moores Cancer Center, La Jolla, CA.
Guardant Health, Redwood City, CA.
JCO Precis Oncol. 2021 Nov 3;5. doi: 10.1200/PO.21.00011. eCollection 2021.
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).
We evaluated 1,931 patients with CUP with a cfDNA next-generation sequencing panel (73-74 genes).
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).
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。
