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Translational research/biomarkers
2022-RA-627-ESGO Preoperative circulating tumor DNA level is associated to poor overall survival in patients with ovarian cancer
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  1. Arturas Dobilas1,
  2. Pia Leandersson2,
  3. Yilun Chen3,4,
  4. Miguel Alcaide4,
  5. Christian Brueffer3,4,
  6. Lao H Saal3,4,5 and
  7. Christer Borgfeldt1
  1. 1Department of Obstetrics and Gynecology, Skåne University Hospital, Lund University, Lund, Sweden
  2. 2Reproductive Medicine Center, Skåne University Hospital, Malmo, Sweden
  3. 3Division of Oncology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden
  4. 4SAGA Diagnostics AB, Lund, Sweden
  5. 5Lund University Cancer Center, Medicon Village, Lund, Sweden

Abstract

Introduction/Background Circulating tumor DNA (ctDNA), which is shed from tumor cells into the blood, is a promising minimal-invasive method for cancer diagnostics and monitoring. The aim of this study was to evaluate preoperative ctDNA levels in the plasma of patients with ovarian cancer and correlate the levels to clinico-pathological parameters and patient outcome.

Methodology 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 tumors, of which seven were from patients with borderline, and 17 with invasive cancer diagnosis. TP53 was the most frequently mutated gene. Fifteen of 24 patients had detectable ctDNA levels in pre-operative plasma. Plasma ctDNA mutant concentration increased with higher stage (ptrend <0.001). Cancer patients with more than 10 ctDNA mutant copies/mL in plasma prior to surgery had significantly worse overall survival (p=0.008).

Abstract 2022-RA-627-ESGO Figure 1
Abstract 2022-RA-627-ESGO Figure 1

Waterfall plot of validated somatic mutations in the patient tumors. Genes are indicated in rows and samples in columns. Mutated samples are show according to mutation type. Patient and tumor clinopathological variables are shown below the patient IDs

Abstract 2022-RA-627-ESGO Figure 2
Abstract 2022-RA-627-ESGO Figure 2

Plasma circulating tum or (ctDNA) mutant concentration increased with higher stage (ptrend<0.001).Concentrations of circulating tumor DNA (ctDNA) in stage III and stage IV OvCa were significantly higher compared with stage I OvCa (p=0.025 and p=0.007 respectively) Bars include highest and lowest values, except outliers (o), which are 1.5 to 3 box lengths from the end of the box, and extremes (*) which are more than 3 box lengths from the end of the box

Conclusion Measuring ctDNA in pre-operative plasma may be useful as a predictive biomarker for tumor staging and prognosis in ovarian cancer patients.

https://doi.org/10.1136/ijgc-2022-ESGO.868

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