Clinical trial NCT03432429: Real Time Tissue Characterisation Using Mass Spectrometry REI-EXCISE iKnife Study
Official title: Rapid Evaporative Ionisation Mass Spectrometry for Examination of Circumferential Surgical Excision Margins
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Breast Cancer
Surgery
Keywords: Tumours
Breast conserving surgery
Margin assessment technology
Mass spectrometry
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: Cancer Research UK
name: Waters Corporation
First posted: 2018-02-14
Enrollment: 158
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients undergoing breast conserving surgery (BCS) for invasive or non-invasive breast cancer.

There is no upper age limit. We believe that older adults represent a group for whom multiple operations could represent a significant perioperative risk and therefore might stand to benefit from iKnife as much if not more so than younger patients. The lower age limit is 18 for the purposes of adequate informed consent to take part in this trial. A breast cancer diagnosis in adolescence is extremely rare.

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Diagnostic accuracy
timeFrame: Data collected during recruitment period: 1st June 2017 until 31st May 2019 i.e. 24 months.
Secondary outcomes:
measure: Assessment of procedure duration using REIMS
timeFrame: Data collected during recruitment period: 1st June 2017 until 31st May 2019 i.e. 24 months.
measure: REIMS technology user satisfaction
timeFrame: Data collected during recruitment period: 1st June 2017 until 31st May 2019 i.e. 24 months.
measure: Accuracy of predicting oncological status
timeFrame: Data collected during recruitment period: 1st June 2017 until 31st May 2019 i.e. 24 months.
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust (Chelsea)
city: London
country: United Kingdom
facility: Imperial College NHS Foundation Trust, Charing Cross Hospital
city: Sutton
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust (Sutton)
Study officials:
affiliation: Department of Surgery & Cancer, Imperial College London
name: Daniel Leff
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Metabolism, Digestion and Reproduction, Imperial College London
name: Zoltan Takats
role: PRINCIPAL_INVESTIGATOR
References: