Lymphatic Mapping Of Oropharyngeal Cancer

Study Overview
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Brief Summary
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A multi-centre validation study to evaluate whether a new imaging and surgical protocol would work as well as the current god standard in identifying sentinel nodes in patients with oropharyngeal cancer.

Detailed Description
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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. 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. This study will provide more accurate information on which to base the decision as to whether to treat 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 two stages. The first stage is the imaging stage. A radioactive substance called Lymphoseek will be injected into the tumour. Lymphoseek moves quickly into the lymph nodes and can then be detected using a handheld gamma camera. The first nodes that Lymphoseek moves into are the sentinel nodes. Patients already undergo an examination under anaesthetic (EUA); the patients participating in the study will have the Lymphoseek injected additionally 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. 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. 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.

Official Title
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Prospective, Multi-Centre, Phase II Validation Study for a Lymphatic Imaging Protocol in Establishing Drainage Patterns in Patients With Oropharyngeal Cancer

Conditions
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Oropharyngeal Cancer

Intervention / Treatment
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* Procedure: Imaging procedure
* Procedure: Surgical procedure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults aged 18 or over New diagnosis of OPC - all anatomical subsites and HPV status accepted Unilateral metastatic nodes equating to AJCC TNM8 clinical staging N1-N2b for P16 negative and N1 for P16 positive patients. Exclusion Criteria: Suspicious bilateral nodes on imaging Previous radiotherapy or surgery to the neck Second primary oropharyngeal tumours Distant metastasis (e.g. lung, bone) Pregnancy and lactation Inability to give informed consent Allergy to lymphatic tracers

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Imaging Phase<br>During routine examination under anaesthetic 4 x peritumoural injection of Lymphoseek (lymphatic mapping tracer) followed by freehand SPECT scan | Procedure: Imaging procedure<br>* During routine examination under anaesthetic 4 x peritumoural injection of Lymphoseek (lymphatic mapping tracer) followed by freehand SPECT scan<br>|
| Experimental: Surgical Phase<br>Excision of contralateral nodes identified on imaging *(fhSPECT or SPECT/CT*) during routine examination under anaesthetic. Serial sectioning of excised (sentinel) nodes to identify micrometastasis. | Procedure: Surgical procedure<br>* Excision of contralateral nodes identified on imaging *(fhSPECT or SPECT/CT*) during routine examination under anaesthetic. Serial sectioning of excised (sentinel) nodes to identify micrometastasis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of contralateral drainage | Rate of contralateral drainage | 24 hours post injection | 
| Accuracy of detection of contralateral nodes by lymphoscintigraphy using fhSPECT compared to SPECT/CT | Accuracy of detection of contralateral nodes by lymphoscintigraphy using fhSPECT compared to SPECT/CT | 24 hours post injection | 
| Number of contralateral nodes on 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 | 24 hours post injection | 
| Number and location of contralateral nodes seen with lymphoscintigraphy performed by i) single injection ii) four peritumoural injections (standard practice) as assessed by paired SPECT/CT scans. | Number and location of contralateral nodes seen with lymphoscintigraphy performed by i) single injection ii) four peritumoural injections (standard practice) as assessed by paired SPECT/CT scans. | 24 hours post injection | 
| Acceptability to patients assessed by questionnaire. | Acceptability to patients assessed by questionnaire. | 24 hours post injection | 
| Occult metastastatic rate of contralateral nodes (positive sentinel node biopsy). | Occult metastastatic rate of contralateral nodes (positive sentinel node biopsy). | 24 hours post injection |