Objectives:The purpose of the study is to determine whetherFOXL2circulating tumor DNA can be used as a prognostic biomarker and marker for monitoring treatment response in patients with an adult-type granulosa cell tumor (aGCT).Methods:Plasma samples of patients included in the multicenter GRANULOSA study were collected before and after surgery for primary or recurrent aGCT, during follow-up, and during systemic treatment. The presence of ctDNA containing theFOXL2 402C>Gmutation was analyzed in 284 samples from 20 primary and 34 recurrent aGCT patients, using digital droplet PCR. Clinical data were retrieved from electronic patient records, and patients were followed through January 2025.Results:FOXL2mutant ctDNA was detected in 28 of 54 patients (48%). In primary aGCT, recurrences were more frequently seen in patients with detectable ctDNA (33% vs. 18%), and ctDNA remained detectable postoperatively in some cases despite complete cytoreduction. In recurrent aGCT patients, detectable ctDNA was associated with significantly worse overall survival (p= 0.023), and the postoperative presence of ctDNA following complete debulking surgery was significantly associated with a shorter recurrence-free survival (4.7 vs. 11.6 months,p= 0.025).Conclusions:FOXL2mutant ctDNA could be a prognostic biomarker in aGCT, being associated with worse overall survival in recurrent aGCT patients. In addition, the presence of ctDNA after surgery could reflect the presence of minimal residual disease, negatively impacting the disease course. The implementation ofFOXL2ctDNA measurement in clinical practice may help to identify high-risk aGCT patients.
目的：本研究旨在探讨FOXL2循环肿瘤DNA是否可作为成人型颗粒细胞瘤（aGCT）患者的预后生物标志物及治疗反应监测指标。方法：收集多中心GRANULOSA研究中纳入的原发性或复发性aGCT患者术前、术后、随访期间及全身治疗过程中的血浆样本。采用数字液滴PCR技术对20例原发性及34例复发性aGCT患者的284份样本进行FOXL2 402C>G突变ctDNA检测。临床数据来源于电子病历系统，患者随访持续至2025年1月。结果：54例患者中28例（48%）检测到FOXL2突变ctDNA。在原发性aGCT中，ctDNA阳性患者的复发率更高（33% vs. 18%），部分病例即使实现完全肿瘤细胞减灭术后仍可检测到ctDNA。在复发性aGCT患者中，ctDNA阳性与总生存期显著缩短相关（p=0.023），而完全减瘤术后ctDNA持续存在与无复发生存期显著缩短相关（4.7个月 vs. 11.6个月，p=0.025）。结论：FOXL2突变ctDNA可作为aGCT的预后生物标志物，其存在与复发性aGCT患者较差的总生存期相关。此外，术后ctDNA的存在可能反映微小残留病灶，对疾病进程产生负面影响。将FOXL2 ctDNA检测应用于临床实践可能有助于识别高危aGCT患者。
The Prognostic Value of FOXL2 Mutant Circulating Tumor DNA in Adult Granulosa Cell Tumor Patients
肿瘤(癌症)患者之家