(P 05) CONCORDANCE OF GENOMIC ALTERATIONS WITH CIRCULATING TUMOR DNA: INITIAL FINDINGS FROM A PILOT STUDY

Author(s)

Joanna Vitfell-Rasmussen, MD (she/her/hers)

MD
Department of Oncology, Herlev University Hospital
Herlev, Hovedstaden, Denmark

Co-Author(s)

Ninna Aggerholm-Pedersen, Associate professor, PhD, MD

Senior consultant, MD, Associate Professor
Department of Oncology, Aarhus University Hospital
Aarhus, Midtjylland, Denmark
Bodil Elisabeth E. Engelmann, MD, PhD (she/her/hers)

MD
Department of Oncology, Herlev University Hospital
Herlev, Hovedstaden, Denmark
Niels Junker, MD, PhD

Chief Physician
Department of Oncology, Herlev University Hospital
Herlev, Hovedstaden, Denmark
CB

Christina Brun Knudsen, BSN

Department of Oncology, Herlev University Hospital
Herlev, Hovedstaden, Denmark
MM

Malene Mai Nørbak, Medical laboratory technologist

Center for Genomic Medicine, Copenhagen University Hospital, Rigshospitalet
Copenhagen, Hovedstaden, Denmark
LB

Lise Barlebo Ahlborn, PhD

Center for Genomic Medicine, Copenhagen University Hospital, Rigshospitalet
Copenh, Hovedstaden, Denmark
AC

Anand Chainsukh Loya, MD, PhD

Department of Pathology, Copenhagen University Hospital, Rigshospitalet
Copenhagen, Hovedstaden, Denmark
MR

Maria Rossing, MD, PhD

Center for Genomic Medicine, Copenhagen University Hospital, Rigshospitalet
Copenhagen, Hovedstaden, Denmark
AK

Anders Krarup-Hansen, N/A, Associate professor, PhD, MD

Consultant, Associate Professor
Department of Oncology, Herlev University Hospital
Herlev, Hovedstaden, Denmark

Objective: The precise role of circulating tumor DNA (ctDNA) has yet to be investigated in sarcomas. This pilot study investigated the concordance between ctDNA and genomic alterations in archival tumor tissue in patients with sarcoma.

Methods: Patients with metastatic sarcoma and a high tumor burden harboring a genomic alteration in archival tumour tissue were included from the Department of Oncology at Herlev University Hospital. For ctDNA analysis, 40 ml of blood were collected in BCT STRECK tubes from each patient. Plasma was investigated using either digital droplet PCR (ddPCR) with the QX200 ddPCR system from Bio-Rad, employing patient-specific primers, or next-generation sequencing with the TruSight Oncology 500 ctDNA (TSO500 ctDNA) Illumina assay.

Results: In total, 20 patients were included, 14 (70%) were males, with a mean age of 55 years. Dedifferentiated liposarcoma (25%) and leiomyosarcoma (20%) were the most common subtypes.
CtDNA was analyzed using TSO500 ctDNA in 14 patients and ddPCR in 10 patients. CtDNA was detected in 10 (71%) patients with TSO500 ctDNA and in five (50%) patients with ddPCR. The most common genomic alteration identified with ddPCR was an MDM2 amplification (40%).
Both analyses were used in four patients, with no ctDNA detected in two of them. In the remaining patients, an EGFR mutation was identified with ddPCR, and an NRAS mutation with TSO500 ctDNA.
There was a concordance in five (45%) out of 14 patients between genomic alterations in archival tumor tissue and those found in plasma with TSO500 ctDNA. The following three mutations and three fusions were identified: TP53, TERT, KDM5C, PAX3-CRB1, NAB2-STAT6 and EWSR1-WT1.
Progressive disease was confirmed in 12 (60%) out of 20 patients at the time of blood sample collection with ctDNA detected in 11 (92%) of these.

Conclusion: CtDNA can be detected in patients with sarcoma using the TSO500 ctDNA assay and ddPCR. Additionally, patients with progressive disease are more likely to shed ctDNA.