Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts.
Weill Cornell Medicine, New York, New York.
Clin Cancer Res. 2022 Jun 13;28(12):2579-2586. doi: 10.1158/1078-0432.CCR-21-3951.
We sought to determine whether the detection of circulating tumor DNA (ctDNA) in samples of patients undergoing chemotherapy for advanced leiomyosarcoma (LMS) is associated with objective response or survival.
Using ultra-low-passage whole-genome sequencing (ULP-WGS) of plasma cell-free DNA from patients treated on a prospective clinical trial, we tested whether detection of ctDNA evaluated prior to the start of therapy and after two cycles of chemotherapy was associated with treatment response and outcome. Associations between detection of ctDNA and pathologic measures of disease burden were evaluated.
We found that ctDNA was detectable by ULP-WGS in 49% patients prior to treatment and in 24.6% patients after two cycles of chemotherapy. Detection of pretreatment ctDNA was significantly associated with a lower overall survival [HR, 1.55; 95% confidence interval (CI), 1.03-2.31; P = 0.03] and a significantly lower likelihood of objective response [odds ratio (OR), 0.21; 95% CI, 0.06-0.59; P = 0.005]. After two cycles of chemotherapy, patients who continued to have detectable levels of ctDNA experienced a significantly worse overall survival (HR, 1.77; 95% CI, 1-3.14; P = 0.05) and were unlikely to experience an objective response (OR, 0.05; 95% CI, 0-0.39; P = 0.001).
Our results demonstrate that detection of ctDNA is associated with outcome and objective response to chemotherapy in patients with advanced LMS. These results suggest that liquid biopsy assays could be used to inform treatment decisions by recognizing patients who are likely and unlikely to benefit from chemotherapy. See related commentary by Kasper and Wilky, p. 2480.
我们旨在确定在接受晚期平滑肌肉瘤（LMS）化疗的患者的样本中检测循环肿瘤 DNA（ctDNA）是否与客观缓解或生存相关。
使用来自前瞻性临床试验患者的血浆无细胞 DNA 的超低通量全基因组测序（ULP-WGS），我们测试了在开始治疗前和两个化疗周期后检测 ctDNA 是否与治疗反应和结果相关。评估了检测到的 ctDNA 与疾病负担的病理测量之间的关系。
我们发现，在治疗前，49%的患者可以通过 ULP-WGS 检测到 ctDNA，而在两个化疗周期后，24.6%的患者可以检测到。治疗前检测到 ctDNA 与总生存期显著降低相关[风险比（HR），1.55；95%置信区间（CI），1.03-2.31；P=0.03]，客观缓解的可能性显著降低[优势比（OR），0.21；95%CI，0.06-0.59；P=0.005]。在两个化疗周期后，继续检测到 ctDNA 水平的患者总生存期明显更差（HR，1.77；95%CI，1-3.14；P=0.05），且不太可能获得客观缓解（OR，0.05；95%CI，0-0.39；P=0.001）。
我们的结果表明，在晚期 LMS 患者中，检测 ctDNA 与化疗的结果和客观缓解相关。这些结果表明，液体活检检测可以通过识别可能受益于化疗和可能不受益于化疗的患者，用于告知治疗决策。另见 Kasper 和 Wilky 的相关评论，第 2480 页。
