title: Use of liquid biopsies to monitor disease progression in a sarcoma patient: a case report.
abstract: Many patients experience local recurrence or metastases after receiving potentially curative treatment, and early detection of these events is important for disease control. Recent technological advances make it possible to use blood plasma containing circulating cell-free tumour DNA (ctDNA) as a liquid biopsy. In this case report we show how serial liquid biopsies can be used to monitor the disease course and detect disease recurrence in a sarcoma patient.
  
  
  
  A 55-year-old male presented with a rapidly growing, painful palpable mass in the left groin region, and a biopsy revealed a high-grade malignant spindle cell sarcoma. No metastases were detected on radiologic imaging scans. Using targeted resequencing with a custom 900 cancer gene panel, eight somatic mutations among them KRAS and NF1, were identified in the primary tumour. Targeted resequencing of plasma cell-free DNA (ctDNA) collected before and after surgery and at disease progression confirmed the presence of six of eight mutations at all three time points. The ctDNA level, estimated from the somatic allele frequencies of these six mutations, was high in plasma taken at the time of surgery, at levels similar to the primary tumour. Detection of low levels of ctDNA three days after surgery indicated persistent microscopic disease. Repeated radiologic imaging six weeks postoperatively showed widespread metastatic disease in the lungs, skeleton and the pelvic region. At this time point there was a dramatic increase in the ctDNA level, reflecting the disease progression of the patient. The patient had an unusually aggressive cancer, and succumbed to the disease 13 weeks after surgery.
  
  
  
  This case report demonstrated that targeted resequencing of ctDNA from longitudinal collected plasma can be used to monitor disease progression in a soft tissue sarcoma patient, including manifestation of metastatic disease. The ctDNA represented the genomic profile of the tumour, supporting clinical use of liquid biopsies to identify tumour-specific mutations as well as recurrent disease.
authors.affiliation: Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. heidina@rr-research.no.
authors.forename: Heidi M
authors.initials: HM
authors.lastname: Namløs
authors.affiliation: Department of Surgery, Oslo University Hospital, Oslo, Norway.
authors.forename: Olga
authors.initials: O
authors.lastname: Zaikova
authors.affiliation: Department of Pathology, Oslo University Hospital, Oslo, Norway.
authors.forename: Bodil
authors.initials: B
authors.lastname: Bjerkehagen
authors.affiliation: Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: Daniel
authors.initials: D
authors.lastname: Vodák
authors.affiliation: Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.|Institute of Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.|Norwegian Cancer Genomics Consortium (CancerGenomics.no), Oslo, Norway.
authors.forename: Eivind
authors.initials: E
authors.lastname: Hovig
authors.affiliation: Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.|Norwegian Cancer Genomics Consortium (CancerGenomics.no), Oslo, Norway.
authors.forename: Ola
authors.initials: O
authors.lastname: Myklebost
authors.affiliation: Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.|Department of Oncology, Oslo University Hospital, Oslo, Norway.
authors.forename: Kjetil
authors.initials: K
authors.lastname: Boye
authors.affiliation: Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. Leonardo.Meza-Zepeda@rr-research.no.|Norwegian Cancer Genomics Consortium (CancerGenomics.no), Oslo, Norway. Leonardo.Meza-Zepeda@rr-research.no.|Genomics Core Facility, Department of Core Facilities, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. Leonardo.Meza-Zepeda@rr-research.no.
authors.forename: Leonardo A
authors.initials: LA
authors.lastname: Meza-Zepeda
mesh_terms: D004247:DNA / Q000097:blood*; D004252:DNA Mutational Analysis; D018450:Disease Progression; D006801:Humans; D000073890:Liquid Biopsy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D012509:Sarcoma / Q000097:blood / Q000175:diagnosis* / Q000235:genetics
chemical_list: D004247:DNA
keywords: Cancer; Case report; Circulating cell-free DNA; KRAS; NF1; ThunderBolts; ctDNA