Preoperative ctDNA Levels Are Associated With Poor Overall Survival in Patients With Ovarian Cancer.

BACKGROUND/AIM: Circulating tumor DNA (ctDNA), which is shed from cancer cells into the bloodstream, offers a potential minimally invasive approach for cancer diagnosis and monitoring. This research aimed to assess the preoperative ctDNA levels in ovarian tumors patients' plasma and establish correlations with clinicopathological parameters and patient prognosis. PATIENTS AND METHODS: Tumor DNA was extracted from ovarian tumor tissue from 41 patients. Targeted sequencing using a panel of 127 genes recurrently mutated in cancer was performed to identify candidate somatic mutations in the tumor DNA. SAGAsafe digital PCR (dPCR) assays targeting the candidate mutations were used to measure ctDNA levels in patient plasma samples, obtained prior to surgery, to evaluate ctDNA levels in terms of mutant copy number/ml and variant allele frequency. RESULTS: Somatic mutations were found in 24 tumor samples, 17 of which were from ovarian cancer patients. The most frequently mutated gene was TP53. Preoperative plasma ctDNA levels were detected in 14 of the 24 patients. With higher stage, plasma ctDNA mutant concentration increased (p for trend <0.001). The overall survival of cancer patients with more than 10 ctDNA mutant copies/ml in plasma was significantly worse (p=0.008). CONCLUSION: Pre-operative ctDNA measurement in ovarian cancer patients' plasma holds promise as a predictive biomarker for tumor staging and prognosis.

Risks of non-ovarian cancers in women with borderline ovarian tumor: a national cohort study in Sweden.

BACKGROUND: Associations between different cancer types are known. The affirmation of the risk for non-ovarian cancer after ovarian borderline tumors (BOT) is, however, sparse. AIM: To analyze the risk of subsequent or simultaneous cancers in women with BOTs compared with the general female Swedish population. METHODS: An open cohort study (1995-2018) was conducted where a diagnosis of BOTs as well as subsequent or simultaneous cancer diagnoses were obtained from the Swedish Cancer Register and matched to the Total Population Register. Each woman with BOT was followed until non-ovarian cancer, death or emigration and could only be included once for the outcome. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) for specific non-ovarian cancers were analyzed. RESULTS: The 4998 women with serous and mucinous BOTs were diagnosed during 1995-2018 with a mean age of 55.7 years (SD 16.0) at diagnosis. Compared with the general female population, women with BOTs had increased risks for non-ovarian cancer in colon (SIR = 2.5; 95% CI 2.0-3.1), rectum (SIR = 1.7; 95% CI 1.1-2.5), small intestine (SIR = 5.0; 95% CI 2.3-9.5), cervix (SIR = 2.5; 95% CI 1.4-4.2), endometrium (SIR = 2.4; 95% CI 1.9-3.1), pancreas (SIR = 2.3; 95% CI 1.4-3.5), upper aerodigestive tract (SIR = 2.2; 95% CI 1.2-3.8), lung (SIR = 1.8; 95% CI 1.4-2.3), kidney (SIR = 2.3; 95% CI 1.4-3.7) and bladder (SIR = 1.8; 95% CI 1.1-2.8). Among women with serous BOTs, the risk of thyroid gland cancer (SIR = 3.1; 95% CI 1.2-6.4) was also increased. Lung and pancreas cancer showed increased risks more than 1 year after a diagnosis of BOT. CONCLUSIONS: This Swedish population-based study demonstrated an increased risk of multiple malignancies including lung and pancreatic cancers beyond the first year of diagnosis in patients with borderline ovarian tumors (BOTs), suggesting a potential shared etiology.

A Multiplex Biomarker Assay Improves the Prediction of Survival in Epithelial Ovarian Cancer.

BACKGROUND/AIM: Epithelial ovarian cancer (EOC) is usually diagnosed in advanced stages and has a high mortality rate. In this study, we used the proximity extension assay from Olink Proteomics to search for new plasma protein biomarkers to predict overall survival (OS) in patients with EOC. MATERIALS AND METHODS: Peripheral blood samples were obtained preoperatively from 116 EOC patients undergoing primary debulking surgery: 28 early EOC cases (FIGO stage I-II) and 88 advanced EOC cases (FIGO stage III-IV). Proteins were measured using the Olink Oncology II and Inflammation panels. In total, 177 unique protein biomarkers were analysed. Cross-validation and LASSO regression were combined to select prediction models for OS. RESULTS: The model including age and the three-biomarker combination of neurotrophin-3 (NT-3)+transmembrane glycoprotein NMB (GPNMB)+mesothelin (MSLN) predicted worse OS with AUC=0.79 (p=0.004). Adding cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) to the model further improved performance (AUC=0.83; p=0.003). In a postoperative model including age and stage (III+IV vs. I+II), the three-biomarker panel of chemokine (C-C motif) ligand 28 (CCL28)+T-cell leukaemia/lymphoma protein 1A (TCL1A)+GPNMB improved the prediction of OS (from AUC=0.83 to AUC=0.90; p=0.05). In the postoperative model including age and dichotomized stage (III vs. I+II), the biomarkers CCL28 and GPNMB1 improved the prediction of OS (AUC=0.86; p<0.001). The combination of high levels of both CA125 and HE4 predicted worse survival (p=0.05). CONCLUSION: In this explorative study evaluating the performance of plasma protein biomarkers in predicting OS, we found that adding biomarkers, especially NT-3, to the panel improved the prediction of OS.

Circulating Markers of Neutrophil Extracellular Traps (NETs) in Patients With Ovarian Tumors.

BACKGROUND/AIM: Inflammation is a hallmark of cancer, and the role of neutrophils and neutrophil extracellular traps (NETs) in cancer and cancer-associated thrombosis has attracted a lot of interest. The NET-specific marker H3Cit has been found to be elevated in the plasma of patients with malignancies, suggesting NETs markers as novel cancer biomarkers. This study aimed to determine the levels of NETs markers (H3Cit and dsDNA) in the plasma of women with adnexal masses. PATIENTS AND METHODS: Peripheral blood samples were obtained from 199 patients admitted for primary surgery of adnexal masses. Patients were grouped according to tumor type and stage. Plasma levels of H3Cit-DNA, dsDNA, and CA125 were quantified. RESULTS: Plasma levels of H3Cit-DNA and dsDNA were not elevated in women with borderline or malignant ovarian tumors compared with those of the benign group. Increased levels of CA125 were found in the borderline and ovarian cancer group (ptrend<0.001). In Cox regression analysis, CA125 levels dichotomized at 326 IU/ml (median) were associated with worse overall survival (HR=1.9; 95%CI=1.03-3.36; p=0.038). No differences were found in the survival analyses of malignant ovarian tumors by analyzing the dsDNA and H3Cit-DNA levels. CONCLUSION: There is no association between NETs markers and ovarian tumors.

Areas to Improve Quality of Life After Ovarian Tumor Surgery and Adjuvant Treatment.

BACKGROUND/AIM: To evaluate quality of life (QoL) in women treated for ovarian tumors one year after laparotomy. PATIENTS AND METHODS: The validated quality of life questionnaires (EORTC QLQ-C30 and QLQ-OV28) were sent to women who had undergone laparotomy due to ovarian tumors 12 months after surgery. The answers were analyzed and grouped according to the ovarian tumor histology (benign, borderline and cancer). RESULTS: A total of 621 patients (87.5% out of 710) agreed to participate in the study. Ovarian cancer patients experienced statistically worse QoL one year after laparotomy in several analyzed parameters, including financial difficulties, compared to patients treated for benign and borderline tumors. CONCLUSION: Women with ovarian cancer still need further cancer rehabilitation and support one year after diagnosis to improve their QoL. The novel finding was that ovarian cancer patients suffered from financial difficulties even in a free of charge health care system.