Title: Can Rapid Evaporative Ionisation Mass Spectrometry provide accurate and reliable information on oncological margin status during Trans-Oral Robotic Surgery for recurrent or second primary Head and Neck Squamous Cell Carcinoma?
Funder: Department of Health and Social Care

Abstract: Research QuestionCan Rapid Evaporative Ionisation Mass Spectrometry provide accurate and reliable information on oncological margin status during Trans-Oral Robotic Surgery for recurrent or second primary Head and Neck Squamous Cell Carcinoma?BackgroundSalvage surgery is an important treatment option for resectable recurrent or second primary head and neck squamous cell cancer (HNSCC), but conventional approaches often require morbid access procedures. Transoral Robotic Surgery (TORS) offers advantages in the salvage setting, by avoiding access procedures,but concerns remain about its ability to consistently resect recurrent tumours with clear margins. Rapid Evaporative Ionisation Mass Spectrometry (REIMS) is a technique that analyses the vapour generated as a byproduct of surgical energy devices to produce metabolomic spectra. The signals generated by malignant and benign tissue are readily distinguishable, and provide real-time feedback to an operating surgeon on the margin status of the resection. REIMS has been demonstrated to work in bowel, brain and breast cancer; our preliminary ex-vivo work shows that it can distinguish HNSCC from adjacent normal tissue with 97.7% sensitivity and 99.2% specificity. It has not yet been evaluated in vivo.AimsTo show that REIMS provides clinically and biologically meaningful information during resection of HNSCC that can influence decision-making and outcomes for patientsPrimary ObjectiveDemonstrate that in vivo positive margins indicated by REIMS during TORS for sHNSCC correlate with the gold standard of histopathological evaluation.Secondary objectives Establish the feasibility of a prospective clinical trial to evaluate oncological and functional outcomes for TORS with REIMS. Characterise the biology underpinning metabolomic differences between malignant and benign tissue Evaluate metabolic changes characterising HPV-positive and HPV-negative OPSCC.MethodsThis developmental project will use an IDEAL phase 2a methodology to iteratively refine a protocol for collecting REIMS data during TORS. Patients aged 18 and over with recurrent or second primary HNSCC, deemed by the MDT at the Royal Marsden Hospital as suitable for TORS, will be invited to participate. Patients who have metastatic disease or are unfit for surgery will be excluded. During the salvage TORS procedure, we will analyse the vapour generated by cautery using REIMS. The operative video, resection specimen markings and REIMS data will be correlated and compared with the definitive histology to define the diagnostic accuracy of REIMS. Additional tumour and normal samples will be collected and used to refine REIMS algorithms and determine spatial resolution of signals using laser desorption/ionisation REIMS (LDI-REIMS).Delivery TimelineThe proposed fellowship will be undertaken by a surgical trainee taking time out of programme for research. The candidate enrolled for the PhD in December 2019, so the project is expected to be completed by winter 2022.Impact and DisseminationOptimisation of REIMS with TORS will allow progression to evaluating REIMS in other HNSCC contexts, with potential to reduce positive margin rates and therefore the need for multimodality treatment, with commensurate improvement in morbidity and mortality. We will disseminate results to professionals through presentation and publication in high impact fora, and to the public via patient groups and social media.

Lay abstract: AimThe aim of this research project is to develop and test a technology that can detect cancer during robotic surgical operations to remove cancer of the head and neck. Background Head and neck cancer is common, and can affect the tongue, throat and voicebox. Treatment varies depending on where the cancer starts, but is most commonly a combination of chemotherapy and radiotherapy. If, after this treatment, the cancer comes back (recurrence) or another cancer grows nearby (second primary), the best treatment option is salvage surgery. Conventional salvage surgery often involves procedures used to access the tumour - these procedures can cause lots of problems, including serious infection of the jawbones, and great difficulty chewing or swallowing. A surgeon-controlled robot overcomes the need for access procedures, and can be useful for salvage surgery, but it can be hard to tell the difference between tumour and normal tissue. Our team at Imperial College London has developed a technology called Rapid Evaporative Ionisation Mass Spectrometry (REIMS) that uses the vapour generated as a normal byproduct of surgery, and can use it to detect the difference between cancer and normal tissue. This research project aims to test whether REIMS can detect cancer during robotic salvage surgery for recurrent or second primary head and neck cancer Research Methods Our study methods are based on recommendations from the IDEAL collaboration, designed to help surgeons develop surgical innovations. We will invite selected patients with recurrent or second primary head and neck cancer to participate alongside their normal surgical treatment. Participation will be completely voluntary. During surgery, the vapour generated will be analysed by REIMS. If REIMS suggests that the surgeon might leave some cancer behind, they will take more tissue in this area to ensure the patient has the best chance of cure. Later, the results given by REIMS will be compared with the final results give by the specialist pathologist, to see how accurate it is. We will also take small samples of the tumour and nearby normal tissue, to allow us to continue to develop and test REIMS in the laboratory. Patient and public involvement Patient groups in Birmingham and London have been consulted regularly throughout the development of this project, and have provided useful feedback on the protocol and the lay summary. Both patient groups were excited about the potential of this device in head and neck cancer. They particularly liked that information could be gained using the vapour generated as a side-product of surgery, avoiding more invasive treatments. Dissemination Once the research has been conducted, we will share it widely with other specialist doctors and scientists working on head and neck cancer by presenting at conferences and submitting results for publication in specialist scientific journals. To inform patients and the wider public, we will create online written and video content to explain the results to the wider public, using platforms including Twitter and Youtube. If this method proves useful, our second aim is to develop studies that can prove that REIMS works during other surgical procedures for head and neck cancer.

Research activity codes: 6.4 SURGERY
Health categories: CANCER AND NEOPLASMS