Intraoperative assessment of tumor resection margins in breast-conserving surgery using 18F-FDG cerenkov luminescence imaging: A first-in-human feasibility study

Maarten R. Grootendorst, Massimiliano Cariati, Sarah E. Pinder, Ashutosh Kothari, Michael Douek, Tibor Kovacs, Hisham Hamed, Amit Pawa, Fiona Nimmo, Julie Owen, Vernie Ramalingam, Sweta Sethi, Sanjay Mistry, Kunal Vyas, David S. Tuch, Alan Britten, Mieke Van Hemelrijck, Gary J. Cook, Chris Sibley-Allen, Sarah AllenArnie Purushotham*

*Corresponding author for this work

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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 by 18F-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 of 18F-FDG CLI for intraoperative assessment of tumor margins in BCS. Methods: Twenty-two patients with invasive breast cancer received 18F-FDG (5 MBq/kg) 45-60 min before surgery. Sentinel lymph node biopsy was performed using an increased 99mTc-nanocolloid activity of 150 MBq to facilitate nodal detection against the g-probe background signal (cross-talk) from 18F-FDG. The cross-talk and 99mTc 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 6 160 photons/s/cm2/sr and 2.41 6 0.54, respectively. All 15 assessable margins were clear on CLI and histopathology. The agreement in margin distance and interrater agreement was good (k 5 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 6 15 mSv per procedure. Conclusion: Intraoperative 18F-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.

Original languageEnglish
Pages (from-to)891-898
Number of pages8
JournalJournal of Nuclear Medicine
Volume58
Issue number6
Early online date8 Dec 2016
DOIs
Publication statusPublished - 1 Jun 2017

Keywords

  • F-FDG
  • Breast-conserving surgery
  • Cerenkov luminescence imaging
  • Sentinel lymph node biopsy
  • Tumor margins

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