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

Patriek A.G.T. Jurrius; Maarten R. Grootendorst; Marika Krotewicz; Massimiliano Cariati; Ashutosh Kothari; Neill Patani; Paulina Karcz; Monika Nagadowska; Kunal N. Vyas; Arnie Purushotham; Maria Turska-d’Amico

doi:10.1186/s13550-021-00759-w

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

Patriek A.G.T. Jurrius^*, Maarten R. Grootendorst, Marika Krotewicz, Massimiliano Cariati, Ashutosh Kothari, Neill Patani, Paulina Karcz, Monika Nagadowska, Kunal N. Vyas, Arnie Purushotham, Maria Turska-d’Amico

^*Corresponding author for this work

Comprehensive Cancer Centre

Research output: Contribution to journal › Article › peer-review

8 Citations (Scopus)

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.

Original language	English
Article number	28
Journal	EJNMMI Research
Volume	11
Issue number	1
DOIs	https://doi.org/10.1186/s13550-021-00759-w
Publication status	Published - 18 Mar 2021

Keywords

Breast cancer
Breast-conserving surgery
Flexible autoradiography
Margin assessment
Re-operation rate

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1186/s13550-021-00759-w

Cite this

Jurrius, P. A. G. T., Grootendorst, M. R., Krotewicz, M., Cariati, M., Kothari, A., Patani, N., Karcz, P., Nagadowska, M., Vyas, K. N., Purushotham, A., & Turska-d’Amico, M. (2021). Intraoperative [¹⁸F]FDG flexible autoradiography for tumour margin assessment in breast-conserving surgery: a first-in-human multicentre feasibility study. EJNMMI Research, 11(1), Article 28. https://doi.org/10.1186/s13550-021-00759-w

@article{2897c1fad0684014bcf40bd6541135a0,

title = "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{\textregistered} 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.",

keywords = "Breast cancer, Breast-conserving surgery, Flexible autoradiography, Margin assessment, Re-operation rate",

author = "Jurrius, {Patriek A.G.T.} and Grootendorst, {Maarten R.} and Marika Krotewicz and Massimiliano Cariati and Ashutosh Kothari and Neill Patani and Paulina Karcz and Monika Nagadowska and Vyas, {Kunal N.} and Arnie Purushotham and Maria Turska-d{\textquoteright}Amico",

note = "Funding Information: The recruitment period was limited by the duration of the grant funding, thereby limiting the patient recruitment figures. This has resulted in a limited number of true positive margins, impacting on the ability to evaluate the diagnostic accuracy of FAR. Funding Information: This study received funding from the European Union's Horizon 2020 SME Instrument Programme under Grant Agreement No 698263. Funding Information: Professor Arnie Purushotham is joint chief investigator for the Experimental Cancer Medicine Centre which is jointly funded by Cancer Research UK and the National Institute for Health Research. Maarten R. Grootendorst and Kunal N. Vyas are both employees of and shareholders in Lightpoint Medical Ltd. There are no other relevant potential conflicts of interest to declare. Publisher Copyright: {\textcopyright} 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = mar,

day = "18",

doi = "10.1186/s13550-021-00759-w",

language = "English",

volume = "11",

journal = "EJNMMI Research",

issn = "2191-219X",

publisher = "BioMed Central",

number = "1",

}

Jurrius, PAGT, Grootendorst, MR, Krotewicz, M, Cariati, M, Kothari, A, Patani, N, Karcz, P, Nagadowska, M, Vyas, KN, Purushotham, A & Turska-d’Amico, M 2021, 'Intraoperative [¹⁸F]FDG flexible autoradiography for tumour margin assessment in breast-conserving surgery: a first-in-human multicentre feasibility study', EJNMMI Research, vol. 11, no. 1, 28. https://doi.org/10.1186/s13550-021-00759-w

TY - JOUR

T1 - Intraoperative [18F]FDG flexible autoradiography for tumour margin assessment in breast-conserving surgery

T2 - a first-in-human multicentre feasibility study

AU - Jurrius, Patriek A.G.T.

AU - Grootendorst, Maarten R.

AU - Krotewicz, Marika

AU - Cariati, Massimiliano

AU - Kothari, Ashutosh

AU - Patani, Neill

AU - Karcz, Paulina

AU - Nagadowska, Monika

AU - Vyas, Kunal N.

AU - Purushotham, Arnie

AU - Turska-d’Amico, Maria

N1 - Funding Information: The recruitment period was limited by the duration of the grant funding, thereby limiting the patient recruitment figures. This has resulted in a limited number of true positive margins, impacting on the ability to evaluate the diagnostic accuracy of FAR. Funding Information: This study received funding from the European Union's Horizon 2020 SME Instrument Programme under Grant Agreement No 698263. Funding Information: Professor Arnie Purushotham is joint chief investigator for the Experimental Cancer Medicine Centre which is jointly funded by Cancer Research UK and the National Institute for Health Research. Maarten R. Grootendorst and Kunal N. Vyas are both employees of and shareholders in Lightpoint Medical Ltd. There are no other relevant potential conflicts of interest to declare. Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/3/18

Y1 - 2021/3/18

N2 - 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.

AB - 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.

KW - Breast cancer

KW - Breast-conserving surgery

KW - Flexible autoradiography

KW - Margin assessment

KW - Re-operation rate

UR - http://www.scopus.com/inward/record.url?scp=85102771663&partnerID=8YFLogxK

U2 - 10.1186/s13550-021-00759-w

DO - 10.1186/s13550-021-00759-w

M3 - Article

AN - SCOPUS:85102771663

SN - 2191-219X

VL - 11

JO - EJNMMI Research

JF - EJNMMI Research

IS - 1

M1 - 28

ER -