title: Safety and utility of image-guided research biopsies in relapsed high-grade serous ovarian carcinoma-experience of the BriTROC consortium.
abstract: BACKGROUND
  Investigating tumour evolution and acquired chemotherapy resistance requires analysis of sequential tumour material. We describe the feasibility of obtaining research biopsies in women with relapsed ovarian high-grade serous carcinoma (HGSC).
  
  
  METHODS
  Women with relapsed ovarian HGSC underwent either image-guided biopsy or intra-operative biopsy during secondary debulking, and samples were fixed in methanol-based fixative. Tagged-amplicon sequencing was performed on biopsy DNA.
  
  
  RESULTS
  We screened 519 patients in order to enrol 220. Two hundred and two patients underwent successful biopsy, 118 of which were image-guided. There were 22 study-related adverse events (AE) in the image-guided biopsies, all grades 1 and 2; pain was the commonest AE. There were pre-specified significant AE in 3/118 biopsies (2.5%). 87% biopsies were fit-for-purpose for genomic analyses. Median DNA yield was 2.87 μg, and was higher in biopsies utilising 14 G or 16 G needles compared to 18 G. TP53 mutations were identified in 94.4% patients.
  
  
  CONCLUSIONS
  Obtaining tumour biopsies for research in relapsed HGSC is safe and feasible. Adverse events are rare. The large majority of biopsies yield sufficient DNA for genomic analyses-we recommend use of larger gauge needles and methanol fixation for such biopsies, as DNA yields are higher but with no increase in AEs.
authors.affiliation: Cancer Research UK Cambridge Institute, Cambridge CB2 0RE, UK.
authors.forename: T
authors.initials: T
authors.lastname: Goranova
authors.affiliation: Institute of Cancer Sciences, University of Glasgow, G61 1QH, UK.
authors.forename: D
authors.initials: D
authors.lastname: Ennis
authors.affiliation: Cancer Research UK Cambridge Institute, Cambridge CB2 0RE, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: Piskorz
authors.affiliation: Cancer Research UK Cambridge Institute, Cambridge CB2 0RE, UK.
authors.forename: G
authors.initials: G
authors.lastname: Macintyre
authors.affiliation: Cancer Research UK Clinical Trials Unit, Glasgow G12 0YN, UK.
authors.forename: L A
authors.initials: LA
authors.lastname: Lewsley
authors.affiliation: Cancer Research UK Clinical Trials Unit, Glasgow G12 0YN, UK.
authors.forename: J
authors.initials: J
authors.lastname: Stobo
authors.affiliation: Cancer Research UK Clinical Trials Unit, Glasgow G12 0YN, UK.
authors.forename: C
authors.initials: C
authors.lastname: Wilson
authors.affiliation: Department of Radiology, Gartnavel General Hospital, Glasgow G12 0YN, UK.
authors.forename: D
authors.initials: D
authors.lastname: Kay
authors.affiliation: Beatson West of Scotland Cancer Centre, Glasgow G12 0YN, UK.
authors.forename: R M
authors.initials: RM
authors.lastname: Glasspool
authors.affiliation: Barts Cancer Institute, London EC1M 6BQ, UK.|University College Hospital, London WC1E 6BD, UK.
authors.forename: M
authors.initials: M
authors.lastname: Lockley
authors.affiliation: Barts Cancer Institute, London EC1M 6BQ, UK.
authors.forename: E
authors.initials: E
authors.lastname: Brockbank
authors.affiliation: Guy's Hospital, London SE1 9RT, UK.
authors.forename: A
authors.initials: A
authors.lastname: Montes
authors.affiliation: Bristol Haematology and Oncology Centre, Bristol BS2 8ED, UK.
authors.forename: A
authors.initials: A
authors.lastname: Walther
authors.affiliation: City Hospital, Birmingham B18 7QH, UK.
authors.forename: S
authors.initials: S
authors.lastname: Sundar
authors.affiliation: St Mary's Hospital, Manchester M13 9WL, UK.
authors.forename: R
authors.initials: R
authors.lastname: Edmondson
authors.affiliation: St James Hospital, Leeds LS9 7TF, UK.
authors.forename: G D
authors.initials: GD
authors.lastname: Hall
authors.affiliation: The Christie Hospital, Manchester M20 4BX, UK.
authors.forename: A
authors.initials: A
authors.lastname: Clamp
authors.affiliation: Edinburgh Cancer Research Centre, Edinburgh EH4 2XR, UK.
authors.forename: C
authors.initials: C
authors.lastname: Gourley
authors.affiliation: Mount Vernon Cancer Centre, Northwood HA6 2RN, UK.
authors.forename: M
authors.initials: M
authors.lastname: Hall
authors.affiliation: Imperial College, London W12 0HS, UK.
authors.forename: C
authors.initials: C
authors.lastname: Fotopoulou
authors.affiliation: Imperial College, London W12 0HS, UK.
authors.forename: H
authors.initials: H
authors.lastname: Gabra
authors.affiliation: Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
authors.forename: S
authors.initials: S
authors.lastname: Freeman
authors.affiliation: Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
authors.forename: L
authors.initials: L
authors.lastname: Moore
authors.affiliation: Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
authors.forename: M
authors.initials: M
authors.lastname: Jimenez-Linan
authors.affiliation: Cancer Research UK Clinical Trials Unit, Glasgow G12 0YN, UK.
authors.forename: J
authors.initials: J
authors.lastname: Paul
authors.affiliation: Cancer Research UK Cambridge Institute, Cambridge CB2 0RE, UK.|Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
authors.forename: J D
authors.initials: JD
authors.lastname: Brenton
authors.affiliation: Institute of Cancer Sciences, University of Glasgow, G61 1QH, UK.|Beatson West of Scotland Cancer Centre, Glasgow G12 0YN, UK.
authors.forename: I A
authors.initials: IA
authors.lastname: McNeish
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics* / Q000556:secondary*; D058534:Class I Phosphatidylinositol 3-Kinases; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis* / Q000302:isolation & purification; D066246:ErbB Receptors / Q000235:genetics; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D061705:Image-Guided Biopsy / Q000009:adverse effects / Q000295:instrumentation; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000473:pathology* / Q000556:secondary; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008875:Middle Aged; D060787:Neoplasm Grading; D009852:Omentum / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology*; D051059:PTEN Phosphohydrolase / Q000235:genetics; D010146:Pain / Q000209:etiology; D010534:Peritoneal Neoplasms / Q000473:pathology* / Q000556:secondary; D010537:Peritoneum / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm; C117307:KRAS protein, human; D016159:Tumor Suppressor Protein p53; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D016283:Proto-Oncogene Proteins p21(ras)