Real Time Tissue Characterisation Using Mass Spectrometry REI-EXCISE iKnife Study

Study Overview
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Brief Summary
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REI-EXCISE is a multicentre, prospective, non-randomised feasibility study, aimed to evaluate the diagnostic accuracy of rapid ionisation mass spectroscopy using an iKnife device. The iKnife will collect vapour, a by-product of surgery, which will pass through the mass spectrometer machine for analysis in order to evaluate what is normal and what is cancerous breast tissue.

Detailed Description
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There is an urgent need to address high rates of close or positive margins and re-operative breast cancer surgery, which commonly results from the inability of the surgeon to rapidly and reliably evaluate resection margin status intra-operatively. This study therefore seeks to address this problem by aiming to develop a method for near real time, in vivo intra-operative tissue classification that may be used by breast surgeons as an intelligent knife (or iKnife) to better guide oncological margin control. The method known as Rapid Evaporative Ionisation Mass Spectrometry (REIMS) technology uses mass spectrometric and chemometric analysis of the tissue specific ionic content of the surgical diathermy smoke plume for the rapid identification of dissected breast tissues. There are no additional treatment interventions as part of REI-EXCISE. The main study procedures are breast conserving surgery using the REIMS iKnife for mass spectral analysis of each surgical margin and correlation between the results of a software recognition algorithm that capitalised on the spectral data (i.e. iKnife margin = positive / negative) with conventional histopathological assessment. False positive iKnife data will be further interrogated with digital droplet polymerase chain reaction and imprint cytology assessment.

Official Title
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Rapid Evaporative Ionisation Mass Spectrometry for Examination of Circumferential Surgical Excision Margins

Conditions
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Breast Cancer, Surgery

Intervention / Treatment
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* Other: REIMS iKnife


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BCS for ductal carcinoma in situ (B5a) BCS for invasive ductal carcinoma (B5b) BCS for invasive lobular carcinoma (B5b) B3 lesions undergoing surgical excision Exclusion Criteria: Pregnant or lactating 18 years or younger Diagnostic excision biopsy for classical lobular carcinoma in situ (LCIS) (current practice is that classical LCIS at a surgical resection margin would not mandate wider excision) Or if the patient is diagnosed with • Non-epithelial breast tumour (phyllodes, lymphoma) Note on patients receiving Neo-adjuvant Chemotherapy (NACT): Patients selecting to receive NACT will be eligible for participation. However, the data for patients receiving NACT will be analysed separately as a pre-planned subgroup and these patients will not contribute data to the n=35 patients with positive margins required for this feasibility trial. Data from NACT cases have not been used to generate the validated multispectral database since eccentric fibrosis made the histological analysis more complex, which limited the number of patients in whom tissue was available for research.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: REIMS iKnife|Use of REIMS iKnife in breast conserving surgery|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic accuracy | The diagnostic accuracy of rapid ionisation mass spectroscopy for oncological margin status will be measured during breast conserving surgery (BCS) (n=35 patients with positive margins). The primary end-point will allow to report accuracy (sensitivity and specify) of rapid ionisation mass spectroscopy to distinguish between patients with at least one close or positive margin and those without close or positive margin. | Data collected during recruitment period: 1st June 2017 until 31st May 2019 i.e. 24 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of procedure duration using REIMS | This study will quantify whether REIMS adds significantly to the intra-operative time taken to perform breast conserving surgery. Thus, the data generated with REI-EXCISE trial will report the difference in specimen excision time using iKnife as compared to conventional electrosurgery. | Data collected during recruitment period: 1st June 2017 until 31st May 2019 i.e. 24 months. | 
| REIMS technology user satisfaction | This study will be collecting data to understand if end-users are sufficiently satisfied with REIMS technology framework (including modified hand-piece) , and are willing to use it routinely during breast conserving surgery (BCS). This will be conveyed by analysing the end user questionnaire completed by the surgeons to infer if they are satisfied with the use of REIMS instrumentation in vivo to perform BCS. | Data collected during recruitment period: 1st June 2017 until 31st May 2019 i.e. 24 months. | 
| Accuracy of predicting oncological status | The intra-operative REIMS analysis will be used to accurately predict/measure the oncological status of the surface of the wide local excision cavity. The data will be reported as the proportion of patients with all close or positive margins correctly detected as positive by iKnife and as the proportion of patients with no margin malignancy correctly detected by iKnife among the true negative patients. | Data collected during recruitment period: 1st June 2017 until 31st May 2019 i.e. 24 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tumours, Breast conserving surgery, Margin assessment technology, Mass spectrometry