Translational Immunology Unit, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Department of Advanced Diagnostics, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Ann Surg Oncol. 2024 Dec;31(13):9265-9271. doi: 10.1245/s10434-024-16147-2. Epub 2024 Sep 7.
Sporadic desmoid fibromatosis (DF) is a rare locally aggressive tumor characterized by mutation in exon 3 of CTNNB1 (T41A, S45F, and S45P). Standard of care is active surveillance (AS), but 30% require treatment. DF clinical course is unpredictable and identification of prognostic markers is needed to tailor strategy. In this prospective study, we investigated the consistency between mutation detected in tumor biopsies with that detected in plasma by digital droplet PCR (ddPCR) and the association between circulating tumor DNA (ctDNA) abundancy with clinical outcome.
A total of 56 patients and 10 healthy donors were included. CTNNB1 mutation status of DF biopsies was determined by Sanger and in case of WT CTNNB1 with NGS. In matched plasma samples at enrollment and during AS at specific timepoints, we evaluated cfDNA quantity and ctDNA.
ctDNA levels were measured in 46 patients with CTNNB1 mutation. Detection rate for T41A, S45F and S45P was 68%, 42% and 100%, respectively. S45P variant has been detected in all patients with S45P mutation. Longitudinal assessment of ctDNA during AS in nine patients (four with regression and five with progression as first event according to RECIST) showed a concordance between the event and ctDNA level change in six out of nine patients tested (4/5 with progression and 2/4 with regression).
Results of ctDNA analysis support its potential clinical implementation as diagnostic tool in specific clinical scenarios where biopsy can be challenging. A prospective clinical trial needs to be performed to evaluate the potential role of ctDNA as predictive biomarker.
散发性硬纤维瘤（DF）是一种罕见的局部侵袭性肿瘤，其特征是 CTNNB1 外显子 3 突变（T41A、S45F 和 S45P）。标准治疗方法是主动监测（AS），但有 30%的患者需要治疗。DF 的临床病程是不可预测的，需要确定预后标志物来制定策略。在这项前瞻性研究中，我们研究了肿瘤活检中检测到的突变与数字液滴 PCR（ddPCR）检测到的血浆突变之间的一致性，以及循环肿瘤 DNA（ctDNA）丰度与临床结果之间的关系。
共纳入 56 名患者和 10 名健康供体。DF 活检的 CTNNB1 突变状态通过 Sanger 法确定，如果 CTNNB1 为 WT，则通过 NGS 法确定。在入组时和 AS 期间的特定时间点，我们评估了配对血浆样本中的 cfDNA 量和 ctDNA。
在 46 名携带 CTNNB1 突变的患者中测量了 ctDNA 水平。T41A、S45F 和 S45P 的检出率分别为 68%、42%和 100%。所有携带 S45P 突变的患者均检测到 S45P 变体。对 9 名患者（4 名根据 RECIST 标准首次出现缓解，5 名出现进展）在 AS 期间进行 ctDNA 的纵向评估显示，在 9 名患者中有 6 名（5 名进展，4 名缓解）的 ctDNA 水平变化与事件一致。
ctDNA 分析的结果支持其作为活检具有挑战性的特定临床情况下的诊断工具的潜在临床应用。需要进行前瞻性临床试验来评估 ctDNA 作为预测生物标志物的潜在作用。
