title: Intraoperative Assessment of Tumor Resection Margins in Breast-Conserving Surgery Using18F-FDG Cerenkov Luminescence Imaging: A First-in-Human Feasibility Study.
abstract: In early-stage breast cancer, the primary treatment option for most women is breast-conserving surgery (BCS). There is a clear need for more accurate techniques to assess resection margins intraoperatively, because on average 20% of patients require further surgery to achieve clear margins. Cerenkov luminescence imaging (CLI) combines optical and molecular imaging by detecting light emitted by18F-FDG. Its high-resolution and small size imaging equipment make CLI a promising technology for intraoperative margin assessment. A first-in-human study was conducted to evaluate the feasibility of18F-FDG CLI for intraoperative assessment of tumor margins in BCS.Methods:Twenty-two patients with invasive breast cancer received18F-FDG (5 MBq/kg) 45-60 min before surgery. Sentinel lymph node biopsy was performed using an increased99mTc-nanocolloid activity of 150 MBq to facilitate nodal detection against the γ-probe background signal (cross-talk) from18F-FDG. The cross-talk and99mTc dose required was evaluated in 2 lead-in studies. Immediately after excision, specimens were imaged intraoperatively in an investigational CLI system. The first 10 patients were used to optimize the imaging protocol; the remaining 12 patients were included in the analysis dataset. Cerenkov luminescence images from incised BCS specimens were analyzed postoperatively by 2 surgeons blinded to the histopathology results, and mean radiance and margin distance were measured. The agreement between margin distance on CLI and histopathology was assessed. Radiation doses to staff were measured.Results:Ten of the 12 patients had an elevated tumor radiance on CLI. Mean radiance and tumor-to-background ratio were 560 ± 160 photons/s/cm2/sr and 2.41 ± 0.54, respectively. All 15 assessable margins were clear on CLI and histopathology. The agreement in margin distance and interrater agreement was good (κ = 0.81 and 0.912, respectively). Sentinel lymph nodes were successfully detected in all patients. The radiation dose to staff was low; surgeons received a mean dose of 34 ± 15 μSv per procedure.Conclusion:Intraoperative18F-FDG CLI is a promising, low-risk technique for intraoperative assessment of tumor margins in BCS. A randomized controlled trial will evaluate the impact of this technique on reexcision rates.
authors.affiliation: Division of Cancer Studies, King's College London, London, United Kingdom.|Department of Breast Surgery, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
authors.forename: Maarten R
authors.initials: MR
authors.lastname: Grootendorst
authors.affiliation: Division of Cancer Studies, King's College London, London, United Kingdom.|Department of Breast Surgery, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Cariati
authors.affiliation: Division of Cancer Studies, King's College London, London, United Kingdom.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Pinder
authors.affiliation: Department of Breast Surgery, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Kothari
authors.affiliation: Division of Cancer Studies, King's College London, London, United Kingdom.|Department of Breast Surgery, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Douek
authors.affiliation: Department of Breast Surgery, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
authors.forename: Tibor
authors.initials: T
authors.lastname: Kovacs
authors.affiliation: Department of Breast Surgery, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
authors.forename: Hisham
authors.initials: H
authors.lastname: Hamed
authors.affiliation: Anesthetic Department, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
authors.forename: Amit
authors.initials: A
authors.lastname: Pawa
authors.affiliation: Day Surgery Unit, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
authors.forename: Fiona
authors.initials: F
authors.lastname: Nimmo
authors.affiliation: Division of Cancer Studies, King's College London, London, United Kingdom.
authors.forename: Julie
authors.initials: J
authors.lastname: Owen
authors.affiliation: Department of Breast Surgery, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
authors.forename: Vernie
authors.initials: V
authors.lastname: Ramalingam
authors.affiliation: Department of Breast Surgery, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
authors.forename: Sweta
authors.initials: S
authors.lastname: Sethi
authors.affiliation: Department of Breast Surgery, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Mistry
authors.affiliation: Sagentia Ltd., Cambridge, United Kingdom.
authors.forename: Kunal
authors.initials: K
authors.lastname: Vyas
authors.affiliation: Lightpoint Medical Ltd., Chesham, United Kingdom.
authors.forename: David S
authors.initials: DS
authors.lastname: Tuch
authors.affiliation: Medical Physics Department, St George's Hospital, London, United Kingdom.
authors.forename: Alan
authors.initials: A
authors.lastname: Britten
authors.affiliation: Division of Cancer Studies, King's College London, London, United Kingdom.
authors.forename: Mieke
authors.initials: M
authors.lastname: Van Hemelrijck
authors.affiliation: Division of Imaging Sciences and Biomedical Engineering, King's College London, London, United Kingdom; and.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Cook
authors.affiliation: Department of Nuclear Medicine, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
authors.forename: Chris
authors.initials: C
authors.lastname: Sibley-Allen
authors.affiliation: Department of Nuclear Medicine, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Allen
authors.affiliation: Division of Cancer Studies, King's College London, London, United Kingdom arniepurushotham@gmail.com.|Department of Breast Surgery, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
authors.forename: Arnie
authors.initials: A
authors.lastname: Purushotham
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000601:surgery*; D005240:Feasibility Studies; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008163:Luminescent Measurements / Q000379:methods*; D000072662:Margins of Excision; D015412:Mastectomy, Segmental / Q000379:methods*; D008875:Middle Aged; D016343:Monitoring, Intraoperative / Q000379:methods; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D025321:Surgery, Computer-Assisted / Q000379:methods; D016896:Treatment Outcome
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
keywords: 18F-FDG; Cerenkov luminescence imaging; breast-conserving surgery; sentinel lymph node biopsy; tumor margins