OVI-DETECT Liquid Biopsies for Improving the Pre-operative Diagnosis of Ovarian Cancer
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 450
- 试验地点
- 4
- 主要终点
- The diagnostic accuracy of the developed algorithm
研究概览
简要总结
An accurate preoperative diagnosis of an ovarian tumor is important for the patients' surgical work-up, proper referral to oncological centers and for the patients' mental wellbeing since uncertainty about the nature (benign vs malignant) of an ovarian tumor may cause anxiety. Currently, the Risk of Malignancy Index (RMI), with a cut-off value of 200, is often used in the Netherlands to select patients with an increased risk of ovarian cancer that should be referred to an oncologic center. However sensitivity and specificity of the RMI-score are far from optimal. Around 40% of the referred patients have benign disease in final pathological examination. Therefore, other models have been developed, such as the IOTA (International Ovarian Tumor Analysis) consortium algorithms, but these models require training, expertise and are subjective. To determine the nature of an ovarian tumor, histological examination is the golden standard. However, a pre-operative biopsy of an ovarian tumor is undesirable because of the risk of spill of tumor cells in the abdominal cavity. Therefore, there is an urgent need for non-invasive diagnostic tools to determine the nature of an ovarian tumor pre-operatively. Liquid biopsies could be such a non-invasive tool. Currently, circulating tumor DNA (ctDNA) circulating tumor cells (CTC), microRNA (miRNA) and tumor-educated platelets (TEPs) are available and can function as a potential blood-based biosource for (early) cancer diagnostics. Previous studies show promising results of liquid biopsies are used in (early) detection of cancer, also for ovarian cancer.
Therefore, a diagnostic algorithm will be developed using ct-DNA and TEPs as liquid biomarkers in combination with the existing ultrasound models (RMI and IOTA-models) and tumor markers (CA125 and HE4) to differentiate between early ovarian cancer and benign ovarian tumors pre-operatively.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness. There is no extra burden/risk for the patients in this study. Five extra vials of blood will be collected from each participant and two questionnaires will be filled out.
详细描述
In the Netherlands 7600 women are annually diagnosed with an ovarian tumor. Only 5% of these tumors are malignant in the final histology assessment. This means that a general gynecologist is confronted with a patient with low stage ovarian cancer less than once a year. Therefore an accurate preoperative diagnosis of an ovarian tumor is challenging. This accurate pre-operative diagnosis is important because patients with an ovarian carcinoma have to undergo extensive surgery in an oncology center, performed by a gynecologist-oncologist.
The current preoperative possibilities to distinguish benign and malignant ovarian tumors are based on classification systems containing clinical, biochemical and ultrasound characteristics. For example, predictive ultrasound models developed by the IOTA (International Ovarian Tumor Analysis) consortium have been widely used. However, these models require training and expertise and are therefore not always easy to implement. The predictive value of current serum-biomarkers such as CA-125 is limited because this biomarker is not increased in 50% of early stage ovarian carcinoma and CA-125 may also have increased in benign gynecological conditions such as endometriosis.
Current Dutch guidelines make use of the Risk of Malignancy Index (RMI) to determine whether the risk of ovarian carcinoma is increased. This score is based on the concentration of CA125, specific ultrasound characteristics and menopausal status.
According to Dutch guidelines, patients with ovarian tumor are referred to oncology centers if the RMI is increased (>200). The published sensitivity and specificity of RMI in a non-selected population of patients with ovarian tumors is 72% and 92%, respectively. However, the population treated in the oncology centers is enriched with patients with RMI >200. In this selected population, our own prelimenary data show that the sensitivity is 84% for RMI and the specificity is only 51%. This means that the incidence of malignancy within this population is 40%. This is unacceptably low because this implies that half of the patients with benign tumors referred to oncology centers undergo unnecessarily extensive surgery and these patients become unnecessarily emotionally burdened with the possibility of getting cancer.
Tissue biopsies are an important tool in the treatment of ovarian carcinoma because theses procedures can confirm or rule out the presence of a malignancy preoperative. At an early stage, however, tissue biopsy is considered as an unwanted invasive procedure, as this procedure can cause tumor spreading and has an invasive character for patients.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Age ≥18 years
- •Presence of a ovarian tumor and referred to specialized center for surgery based on:
- •Any ultrasound model e.g. RMI-scoring model ; IOTA-rules
- •Subjective assessment of the referring gynecologist
- •Normal Glomerular Filtration Rate (GFR): >60ml/min/1,73m2
- •General criteria: a. Understanding of Dutch language b. Fit for surgery (WHO 1-2) c. Written informed consent
排除标准
- •Suspicion of advanced-stage of disease, e.g. ascites or peritoneal depositions
- •History of cancer (excl. BCC) within 5 years prior to inclusion
- •Multiple malignancies at the same time
结局指标
主要结局
The diagnostic accuracy of the developed algorithm
时间窗: 3 -4 years
The diagnostic accuracy of the developed algorithm, displayed as sensitivity and specificity.
次要结局
- Psychological Burden (I)(3 -4 years)
- Psychological Burden (II)(3 -4 years)
- Cost-effective analysis (I)(3 -4 years)
- Psychological Burden (VI)(3 -4 years)
- Cost-effective analysis (II)(3 -4 years)
- Psychological Burden (III)(3 -4 years)
- Cost-effective analysis (III)(3 -4 years)
- Psychological Burden (IV)(3 -4 years)
- Psychological Burden (V)(3 -4 years)