Award Title: LOOC - Lymphatic mapping Of Oropharyngeal Cancer
Funder: Medical Research Council

Abstract: Cancer at the back of the mouth and throat is usually discovered after it has spread to lymph glands in the neck. Treatment therefore involves dealing with both the original tumour (in the mouth/throat) and the spread cancer in the lymph glands._x000D_
This type of cancer sometimes spreads to both sides of the neck, not just the side on which the original tumour was located. The decision as to whether to treat the other side of the neck as well depends on various factors including the aggressiveness of the tumour, whether the patient smokes and whether or not the HPV virus is present in the tumour. This is inevitably inexact, and assessing the likelihood of the cancer spreading to the other side of the neck always involves an element of estimation. Some patients end up being treated unnecessarily on both sides (often with severe and lasting effects on swallowing, meaning they have to use a feeding tube), while others receive treatment on one side only but the cancer comes back on the other side._x000D_
This study will provide more accurate information on which to base the decision as to whether to treat_x000D_
the other side of the neck. The study will use a procedure known as sentinel node biopsy (SNB) to establish (with a high degree of accuracy) whether or not the cancer has spread to the other side of the neck. The study will be in_x000D_
two stages. The first stage is the imaging stage. A radioactive substance called Lymphoseek will be injected into_x000D_
the tumour. Lymphoseek moves quickly into the lymph nodes and can then be detected using a handheld gamma camera. The first nodes the Lymphoseek moves into are the “sentinel” nodes. Patients already undergo an examination under anaesthetic (EUA) and the patients in the study will have the Lymphoseek injected and the sentinel nodes detected during this EUA. The use of the handheld camera is relatively new so all of the patients in the study will also have a CT scan the next day to double check whether the handheld camera identified the sentinel nodes correctly._x000D_
The second stage of the study, the surgery stage, will involve a new group of patients having the imaging procedure. Those who do have sentinel nodes in the other side of the neck will have them removed during the EUA. Those nodes will then be examined thoroughly for signs of cancer. A separate limb of stage one of the study will involve some patients whose main tumours are easily accessible also having their tumour injected with Lymphoseek under local anaesthetic in an outpatient clinic. In the study this will take place several days after the initial injection with Lymphoseek. If this procedure is found to be acceptable to patients, it would mean that patients could have the Lymphoseek injected before the EUA, thereby allowing time for the sentinel nodes to be identified by CT scan so that they can be removed during the EUA. This will provide a way to ensure that, even if the handheld camera cannot be used, the sentinel nodes can still be removed while the patient is under anaesthetic for the EUA._x000D_
If the study is successful, the patient will be able to have much more accurate information about whether their cancer has, or might, spread to the other side of the neck, without having to undergo an additional general anaesthetic.

Lay Abstract: BACKGROUND:_x000D_
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Oropharyngeal cancers (OPC) affects tonsil, tongue base, soft palate, and pharynx. OPC is predicted to become the most common form of head and neck cancer worldwide with epidemic proportions in the next decade. Patients usually respond well to treatment despite most presenting with involved (metastatic) lymph nodes at diagnosis. Patients with metastatic disease are offered treatment to both sides of the neck without evidence of metastasis on the contralateral side, due to risk of occult (non-radiographically apparent) metastasis. Treatment related morbidity affects survivor’s quality of life but can be significantly improved when only one side of the neck is treated. Lymphatic mapping and sentinel node biopsy (SNB) could be used to diagnose occult metastasis in the contralateral neck and thus guide treatment to those that would benefit from it._x000D_
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SNB and lymphatic tumour mapping:_x000D_
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SNB is a surgical staging procedure in which sentinel lymph nodes (SLN) are identified by lymphatic mapping of an injected radiotracer detected on Single Photon Emission Computed Tomography (SPECT). SNB is recognised in OPC but due to combination of difficult access to the tumour and the outpatient gantry-based SPECT imaging equipment, traditional lymphatic mapping requires transfer between departments under general anaesthetic preventing use in routine practice. New technology may allow one-stop injection and imaging in OPC._x000D_
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STUDY AIMS:_x000D_
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•Validate lymphatic mapping protocol in OPC using new technology (Lymphoseek, freehand SPECT (fhSPECT))_x000D_
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•Establish lymphatic drainage pattern and occult metastatic rate in the contralateral neck in OPC_x000D_
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DESIGN:_x000D_
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Multicentre phase II surgical imaging study_x000D_
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1.IMAGING PHASE (n=75): Develops an imaging protocol to establish lymphatic drainage pattern in a population of patients with proven unilateral neck metastasis from OPC during routine examination under anaesthetic (EUA). Four peritumoural injections of Lymphoseek are given followed by freehand SPECT (fhSPECT)scan under GA. SPECT/CT scan (gold standard for lymphatic mapping) will be carried out the next day._x000D_
Outcome – rate of contralateral drainage. Accuracy of fhSPECT Vs. SPECT/CT. Number of contralateral nodes on SPECT/CT will be used as the denominator in calculating the sensitivity of fhSPECT in independently verified images. fhSPECT should achieve sensitivity >94% Minimum of 20/75 patients demonstrate contralateral drainage to proceed to surgical stage._x000D_
Imaging substudy: Develops a secondary imaging protocol in case of <94% sensitivity of intraoperative fhSPECT Twenty patients from imaging phase with easily accessible tumours will be invited to undergo a second imaging intervention. A single injection of Lymphoseek is given in clinic followed by fhSPECT and SPECT/CT._x000D_
Comparator – SPECT/CT performed in initial phase_x000D_
Outcome – Sensitivity of outpatient imaging (single injection, fhSPECT and SPECT/CT) compared to gold standard (SPECT/CT from initial phase). Acceptability of outpatient injection compared to under GA._x000D_
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2. SURGICAL PHASE (n=75): Investigates feasibility of surgically staging the contralateral neck. A new study group of patients will be invited to participate. During EUA excision of contralateral nodes identified on imaging* is undertaken (sentinel node biopsy). Serial sectioning of excised (sentinel) nodes to identify micrometastasis. Outcome is occult metastatic rate of contralateral nodes (positive sentinel node biopsy). Contralateral drainage rate will be identified in the imaging phase, expected SNB positive rate of excised nodes 25-40%. Outcome of this study will prove feasibility of future research in which management of the contralateral neck is based on surgical staging_x000D_
*protocol based on result of imaging phase

Research Activity Codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health Categories: CANCER AND NEOPLASMS