Intraoperative [18F]FDG flexible autoradiography for tumour margin assessment in breast-conserving surgery: a first-in-human multicentre feasibility study

Abstract

Introduction In women undergoing breast-conserving surgery (BCS), 20–25% require a re-operation as a result of incomplete tumour resection. An intra-operative technique to assess tumour margins accurately would be a major advantage. A novel method for intraoperative margin assessment was developed by applying a thin flexible scintillating film to specimens—flexible autoradiography (FAR) imaging. A single-arm, multi-centre study was conducted to evaluate the feasibility of intraoperative [18F]FDG FAR for the assessment of tumour margins in BCS. Methods Eighty-eight patients with invasive breast cancer undergoing BCS received ≤ 300 MBq of [18F]FDG 60–180 min pre-operatively. Following surgical excision, intraoperative FAR imaging was performed using the LightPath® Imaging System. The first 16 patients were familiarisation patients; the remaining 72 patients were entered into the main study. FAR images were analysed post-operatively by three independent readers. Areas of increased signal intensity were marked, mean normalised radiances and tumour-to-tissue background (TBR) determined, agreement between histopathological margin status and FAR assessed and radiation dose to operating theatre staff measured. Subgroup analyses were performed for various covariates, with thresholds set based on ROC curves. Results Data analysis was performed on 66 patients. Intraoperative margin assessment using FAR was completed on 385 margins with 46.2% sensitivity, 81.7% specificity, 8.1% PPV, 97.7% NPV and an overall accuracy of 80.5%, detecting both invasive carcinoma and DCIS. A subgroup analysis based on [18F]FDG activity present at time of imaging revealed an increased sensitivity (71.4%), PPV (9.3%) and NPV (98.4%) in the high-activity cohort with mean tumour radiance and TBR of 126.7 ± 45.7 photons/s/cm2/sr/MBq and 2.1 ± 0.5, respectively. Staff radiation exposure was low (38.2 ± 38.1 µSv). Conclusion [18F]FDG FAR is a feasible and safe technique for intraoperative tumour margin assessment. Further improvements in diagnostic performance require optimising the method for scintillator positioning and/or the use of targeted radiopharmaceuticals. Trial registration: Identifier: NCT02666079. Date of registration: 28 January 2016. URL: https://clinicaltrials.gov/ct2/show/NCT02666079. ISRCTN registry: Reference: ISRCTN17778965. Date of registration: 11 February 2016. URL: http://www.isrctn.com/ISRCTN17778965.

Imaging skins: stretchable and conformable on-organ beta particle detectors for radioguided surgery

“…Out of the positive findings, we saw that state-of-the-art research in the related field proved that such detectors carry a sensitivity suitable for clinical translation [67]. Other research group demonstrated that the imaging skins could improve spatial resolution compared to a flat scintillator when conforming to the geometry of the specimen [46,52].…”

“…Though they did not disclose the specifications of their material, they were able to detect activity at 0.9 kBq ml −1 for 18 F using a 6 µm flexible scintillator. In [67], a 12 µm thick version of the scintillator was used to detect tumour margins in breast-conservation surgery (BCS). They successfully proved that their technique was efficient for the intraoperative assessment of excised surgical specimens.…”

“…In the research presented here, the detectors were used ex-vivo through autoradiography [46,52,67]. However, employing a similar detection method during surgeries poses numerous challenges, particularly in MIS.…”

Comparison of “click-to-sense” assay with frozen section analysis using simulated surgical margins in breast cancer patients

“…Recently, radio-frequency spectroscopy (MarginProbe® device [22,23]) and bioimpedance spectroscopy (ClearEdge™ device [24]) have been shown to be useful for real-time intraoperative assessment of the surgical margins in BCS in clinical trials. In addition, [ 18 F] FDG flexible autoradiography (FAR) imaging with the LightPath® Imaging System was evaluated in its feasibility of intraoperative assessment of the surgical margins in BCS in the multi-centre study [25]. These modalities, however, have disadvantage in their inability to assess the cancer cell morphology unlike the CTS assay.…”

Radiation Protection and Occupational Exposure on 68Ga-PSMA-11–Based Cerenkov Luminescence Imaging Procedures in Robot-Assisted Prostatectomy

“…Other intraoperative CLI include the use of 2-[ 18 F]FDG for the identification of surgical margins in breast conserving surgery. From published studies, there is evidence that a pre-operative administration of about 300 MBq of 2-[ 18 F]FDG would deliver maximal personal equivalent doses of 34.0 -61.8 µSv (14,29). Interestingly, if the Fluorine-18 decay characteristics and assuming an administration of 300 MBq are substituted in our model, we obtain exposure levels of 51.3, 15.3 and 4.6 µSv per procedure for the first surgical assistant, scrub nurse and robotic surgeon, respectively.…”