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805P Tumor-informed ctDNA detection as a predictive marker for postoperative residual disease in epithelial ovarian cancer: A feasibility study

Grimm, Christoph ; Paspalj, Valentina ; Postl, Magdalena ; Saal, Lao LU orcid ; Brueffer, Christian LU orcid ; Segui Gracia, Nuria ; Alcaide, Miguel ; Polterauer, Stephan ; Oton, Lucia and Chen, Yilun LU , et al. (2023) In Annals of Oncology 34(Suppl 2). p.536-536
Abstract
Background
Complete tumor resection is the most relevant prognostic factor for overall survival in high grade serous ovarian cancer (HGSOC) patients. The current standard for classification of postoperative residual disease (RD) is surgeon´s subjective evaluation at the end of surgery. Thus, a reliable objective predictive marker is currently missing.

Methods
In this prospective single-center feasibility study, patients with HGSOC, who underwent surgery between July 2021 to December 2022, were included. Tumor tissue was assessed intraoperatively and blood samples were performed preoperatively, at day 2 and 10 postoperatively and subsequently at cycle 1, 3 and 6 of chemotherapy. Low-coverage whole genome sequencing (WGS)... (More)
Background
Complete tumor resection is the most relevant prognostic factor for overall survival in high grade serous ovarian cancer (HGSOC) patients. The current standard for classification of postoperative residual disease (RD) is surgeon´s subjective evaluation at the end of surgery. Thus, a reliable objective predictive marker is currently missing.

Methods
In this prospective single-center feasibility study, patients with HGSOC, who underwent surgery between July 2021 to December 2022, were included. Tumor tissue was assessed intraoperatively and blood samples were performed preoperatively, at day 2 and 10 postoperatively and subsequently at cycle 1, 3 and 6 of chemotherapy. Low-coverage whole genome sequencing (WGS) was used to identify structural variants (SV), single nucleotide variants (SNVs) and indels in tumor tissue in order to develop personalized digital PCR (dPCR) fingerprint assays.

Results
So far, 33 patients are included in the present analysis, with a median follow up time of 7 (IQR 2-10) months. In all tumor samples, dPCR assays were successfully developed and validated, with a median of 5 biomarkers (SVs and SNVs) per patient. For each patient, an individual SV profile could be established, which remained largely constant throughout multiple tumor localizations of each patient. 32/33 (97%) patients had circulating tumor DNA (ctDNA) detected at baseline at levels ranging from 0.0005 - 31% VAF. Three (10%) patients have been lost to follow without postoperative ctDNA samples. ctDNA was persistently detected in all patients with macroscopic tumor residuals. A significant decrease in ctDNA was observed in all patients with stage I-IIIB disease who had macroscopic complete resection (8 patients). In 8/22 (36%) patients with complete resection, ctDNA decreased below the detection limit. Clinical follow up is ongoing, and analysis of longitudinal samples will be presented at the congress.

Conclusions
In this feasibility study, tumor-informed ctDNA was preoperatively detectable in 97% participants. In patients with multiple tumor biopsies, the fingerprint could be used for monitoring of each location. A decrease in ctDNA detection correlated with complete tumor resection.

Legal entity responsible for the study
Medical University of Vienna.

Funding
SAGA Diagnostics. (Less)
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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Ovarian cancer, Gynecological cancer disease, Minimal residual disease, Liquid biopsy, ctDNA
in
Annals of Oncology
volume
34
issue
Suppl 2
article number
805P
pages
536 - 536
publisher
Oxford University Press
ISSN
1569-8041
DOI
10.1016/j.annonc.2023.09.1981
language
English
LU publication?
no
id
43f82ca1-f46a-460b-b485-687fa09cf58e
date added to LUP
2023-10-27 22:38:54
date last changed
2023-10-30 07:46:21
@misc{43f82ca1-f46a-460b-b485-687fa09cf58e,
  abstract     = {{Background<br/>Complete tumor resection is the most relevant prognostic factor for overall survival in high grade serous ovarian cancer (HGSOC) patients. The current standard for classification of postoperative residual disease (RD) is surgeon´s subjective evaluation at the end of surgery. Thus, a reliable objective predictive marker is currently missing.<br/><br/>Methods<br/>In this prospective single-center feasibility study, patients with HGSOC, who underwent surgery between July 2021 to December 2022, were included. Tumor tissue was assessed intraoperatively and blood samples were performed preoperatively, at day 2 and 10 postoperatively and subsequently at cycle 1, 3 and 6 of chemotherapy. Low-coverage whole genome sequencing (WGS) was used to identify structural variants (SV), single nucleotide variants (SNVs) and indels in tumor tissue in order to develop personalized digital PCR (dPCR) fingerprint assays.<br/><br/>Results<br/>So far, 33 patients are included in the present analysis, with a median follow up time of 7 (IQR 2-10) months. In all tumor samples, dPCR assays were successfully developed and validated, with a median of 5 biomarkers (SVs and SNVs) per patient. For each patient, an individual SV profile could be established, which remained largely constant throughout multiple tumor localizations of each patient. 32/33 (97%) patients had circulating tumor DNA (ctDNA) detected at baseline at levels ranging from 0.0005 - 31% VAF. Three (10%) patients have been lost to follow without postoperative ctDNA samples. ctDNA was persistently detected in all patients with macroscopic tumor residuals. A significant decrease in ctDNA was observed in all patients with stage I-IIIB disease who had macroscopic complete resection (8 patients). In 8/22 (36%) patients with complete resection, ctDNA decreased below the detection limit. Clinical follow up is ongoing, and analysis of longitudinal samples will be presented at the congress.<br/><br/>Conclusions<br/>In this feasibility study, tumor-informed ctDNA was preoperatively detectable in 97% participants. In patients with multiple tumor biopsies, the fingerprint could be used for monitoring of each location. A decrease in ctDNA detection correlated with complete tumor resection.<br/><br/>Legal entity responsible for the study<br/>Medical University of Vienna.<br/><br/>Funding<br/>SAGA Diagnostics.}},
  author       = {{Grimm, Christoph and Paspalj, Valentina and Postl, Magdalena and Saal, Lao and Brueffer, Christian and Segui Gracia, Nuria and Alcaide, Miguel and Polterauer, Stephan and Oton, Lucia and Chen, Yilun and Hofstetter, Gerda and Müllauer, Leonhard}},
  issn         = {{1569-8041}},
  keywords     = {{Ovarian cancer; Gynecological cancer disease; Minimal residual disease; Liquid biopsy; ctDNA}},
  language     = {{eng}},
  month        = {{10}},
  note         = {{Conference Abstract}},
  number       = {{Suppl 2}},
  pages        = {{536--536}},
  publisher    = {{Oxford University Press}},
  series       = {{Annals of Oncology}},
  title        = {{805P Tumor-informed ctDNA detection as a predictive marker for postoperative residual disease in epithelial ovarian cancer: A feasibility study}},
  url          = {{http://dx.doi.org/10.1016/j.annonc.2023.09.1981}},
  doi          = {{10.1016/j.annonc.2023.09.1981}},
  volume       = {{34}},
  year         = {{2023}},
}