Background: High-grade serous ovarian cancer (HGSC) is the most common and aggressive subtype of ovarian cancer. Despite initial response to platinum-based chemotherapy, most patients relapse. Cytoreductive surgery at relapse has been shown to improve survival in selected patients, but the biological mechanisms underlying recurrence and resistance remain unclear. This study aimed to investigate whether the mutational profile of HGSC changes from diagnosis to relapse, and to evaluate treatment patterns and survival outcomes in a cohort undergoing cytoreductive surgery. Methods: Sixteen patients with HGSC who underwent cytoreductive surgery at both diagnosis and relapse were included. Matched tumor tissue samples (n= 32) were collected and sequenced using a 501-gene cancer panel. Only pathogenic or likely pathogenic variants were registered. Clinical data, treatment history, and survival outcomes were obtained from medical records, with a median follow-up of 63 months. Results: All patients harbored pathogenic or likely pathogenic mutations, most frequently inTP53(88%) andBRCA1/2(38%). The mutational landscape was largely stable, with 15 of 16 patients (94%) showing no mutational changes between diagnosis and relapse. One patient acquired aNOTCH2mutation at relapse. Complete resection was achieved in 88% of relapse surgeries. Median time to first relapse was 32 months, and overall survival was prolonged, with 87.5% of patients alive at last follow-up.BRCAmutated patients showed longer time to relapse, and overall follow-up compared toBRCAwild-type cases. Conclusions: The somatic mutational profile of HGSC remains remarkably stable from diagnosis to relapse. Clinically, this stability suggests that repeat mutational sequencing at relapse is unlikely to yield new actionable findings and may have limited value in guiding treatment decisions. Instead, resistance mechanisms likely arise from epigenetic or non-genetic changes, underscoring the need for future research in these areas and the continued importance of optimal surgical management in selected patients.
背景：高级别浆液性卵巢癌（HGSC）是最常见且最具侵袭性的卵巢癌亚型。尽管患者初期对铂类化疗有反应，但多数会复发。研究表明，对特定患者进行复发期肿瘤细胞减灭术可改善生存，但复发与耐药的生物学机制尚不明确。本研究旨在探讨HGSC从初诊到复发的突变谱是否发生变化，并评估接受肿瘤细胞减灭术患者的治疗模式与生存结局。 方法：纳入16例在初诊及复发时均接受肿瘤细胞减灭术的HGSC患者。收集匹配的肿瘤组织样本（n=32），采用501基因癌症panel进行测序。仅记录致病性或可能致病性变异。临床资料、治疗史及生存结局从病历中获取，中位随访时间为63个月。 结果：所有患者均携带致病性或可能致病性突变，最常见于TP53（88%）和BRCA1/2（38%）。突变谱整体保持稳定，16例患者中15例（94%）在初诊与复发间未出现突变改变。1例患者在复发时获得NOTCH2突变。88%的复发手术实现完全切除。首次复发中位时间为32个月，总生存期延长，末次随访时87.5%患者存活。与BRCA野生型病例相比，BRCA突变患者复发时间及总随访时间更长。 结论：HGSC的体细胞突变谱从初诊到复发保持高度稳定。临床意义上，这种稳定性提示复发期重复突变测序不太可能获得新的可干预发现，对治疗决策的指导价值有限。耐药机制更可能源于表观遗传或非遗传性改变，这强调未来需加强这些领域的研究，并持续重视对特定患者实施优化手术治疗的重要性。
Ovarian Cancer in the Era of Precision Surgery and Targeted Therapies
肿瘤(癌症)患者之家