de Jong J M, Hoogendam J P, Braat A J A T, Zweemer R P, Gerestein C G
Department of Gynaecological Oncology, University Medical Center Utrecht, Utrecht, the Netherlands.
Department of Nuclear Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
Gynecol Oncol. 2021 Aug;162(2):517-525. doi: 10.1016/j.ygyno.2021.05.017. Epub 2021 May 28.
Epithelial ovarian cancer (EOC) is often diagnosed late, with a 5-year relative survival of 30.2% for patients with metastatic disease. Residual disease following cytoreductive surgery is an important predictor for poor survival. EOC is characterized by diffuse peritoneal metastases and depositions of small size, challenging a complete resection. Targeted fluorescence imaging is a technique to enhance tumor visualization and can be performed intraoperatively. Folate receptor alpha (FRα) and human epidermal growth factor receptor 2 (HER2) are overexpressed in EOC in 80% and 20% of the cases, respectively, and have been previously studied as a target for intraoperative imaging.
To systematically review the literature on the feasibility of FRα and HER2 targeted fluorescence-guided cytoreductive surgery (FGCS) in women with EOC.
PubMed and Embase were searched for human and animal studies on FGCS targeting either HER2 or FRα in either women with EOC or animal models of EOC. Risk of bias and methodological quality were assessed with the SYRCLE and MINORS tool, respectively.
All animal studies targeting either FRα or HER2 were able to detect tumor deposits using intraoperative fluorescence imaging. One animal study targeting HER2 compared conventional cytoreductive surgery (CCS) to FGCS and concluded that FGCS, either without or following CCS, resulted in statistically significant less residual disease compared to CCS alone. Human studies on FGCS showed an increased detection rate of tumor deposits. True positives ranged between 75%-77% and false positives between 10%-25%. Lymph nodes were the main source of false positive results. Sensitivity was 85.9%, though only reported by one human study.
FGCS targeting either HER2 or FRα appears to be feasible in both EOC animal models and patients with EOC. FGCS is a promising technique, but further research is warranted to validate these results and particularly study the survival benefit.
上皮性卵巢癌（EOC）通常在晚期才被诊断出来，转移性疾病患者的5年相对生存率为30.2%。减瘤手术后的残留病灶是生存不良的重要预测指标。EOC的特征是弥漫性腹膜转移和小尺寸沉积物，这对完全切除构成挑战。靶向荧光成像技术可增强肿瘤可视化，且可在术中进行。叶酸受体α（FRα）和人表皮生长因子受体2（HER2）分别在80%和20%的EOC病例中过表达，此前已作为术中成像的靶点进行研究。
系统评价FRα和HER2靶向荧光引导减瘤手术（FGCS）在EOC女性患者中的可行性。
检索PubMed和Embase数据库，查找关于在EOC女性患者或EOC动物模型中靶向HER2或FRα的FGCS的人体和动物研究。分别使用SYRCLE和MINORS工具评估偏倚风险和方法学质量。
所有靶向FRα或HER2的动物研究均能够通过术中荧光成像检测到肿瘤沉积物。一项靶向HER2的动物研究将传统减瘤手术（CCS）与FGCS进行了比较，得出结论：无论是否在CCS之后进行FGCS，与单独的CCS相比，FGCS导致的残留病灶在统计学上显著减少。关于FGCS的人体研究显示肿瘤沉积物的检出率有所提高。真阳性率在75%-77%之间，假阳性率在10%-25%之间。淋巴结是假阳性结果的主要来源。敏感性为85.9%，不过仅在一项人体研究中报告。
靶向HER2或FRα的FGCS在EOC动物模型和EOC患者中似乎都是可行的。FGCS是一项有前景的技术，但需要进一步研究来验证这些结果，特别是研究其生存获益情况。
