Feasibility of Sentinel Lymph Node Biopsy in Rectal Cancer

Study Overview
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Brief Summary
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This study will assess whether the Sienna+/Sentimag system, which involves a magnetic tracer, is effective in identifying the sentinel lymph node in rectal cancer and whether it is then feasible to remove this lymph node during surgery to locally excise early rectal cancer.

Detailed Description
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One issue in managing rectal cancer is identifying which patients will benefit from less radical surgery, which is much safer and better tolerated. However it does not remove lymph nodes where cancer cells may have spread. If lymph nodes containing cancer are left behind, the cancer may recur. So this surgery is only suitable in early rectal cancers not involving lymph nodes. Unfortunately, current investigations do not always accurately identify involved lymph nodes. Sentinel lymph node biopsy (SLNB) is a technique to surgically remove the first lymph node where cancer cells spread. If this lymph node contains cancer, radical surgery is needed to reduce the risk of recurrence. However if it is clear, less radical surgery should be sufficient. This is standard practice for breast cancer and avoids unnecessary major surgery in many patients. The investigators aim to assess whether SLNB is useful in rectal cancer. The investigators will determine whether the Sienna+/Sentimag system effectively identifies the sentinel lymph node, and whether the node can then be removed surgically. The investigators will recruit patients in Oxford hospitals about to undergo surgery for rectal cancer. Patients will receive an injection of magnetic tracer during endoscopy prior to surgery. Some patients will have an extra MRI scan. During or after surgery, depending on the type of operation planned, a magnetic probe will be used to locate the sentinel lymph node in the tissue around the rectum. The removed specimen will be examined by a pathologist. Funding to undertake this study has been granted by the National Institute for Health Research (NIHR). Endomagnetics, the manufacturer, will supply the magnetic tracer and probe for use in this study. If successful, the investigators will plan a larger clinical trial. This could have a major impact on improving outcomes for patients by allowing less radical surgery to be used where it is most appropriate.

Official Title
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Feasibility of Sentinel Lymph Node Biopsy in Rectal Cancer

Conditions
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Rectal Cancer

Intervention / Treatment
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* Drug: Sienna+ injection
* Other: MRI scan
* Procedure: Surgery to excise rectal cancer
* Device: Sentimag probe


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosed with operable rectal cancer case discussed at Oxford Colorectal Cancer multi-disciplinary team (MDT) meeting willing and able to give informed consent willing and able to comply with all trial requirements, in the investigator's opinion Exclusion Criteria: females who are pregnant or lactating known intolerance or hypersensitivity to iron, dextran compounds, magnetic tracers or superparamagnetic iron oxide particles (SPIO) cancer involvement of anal sphincter complex adults who are not able to give consent or are deemed vulnerable

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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: Ex-vivo<br>Patients with relatively advanced rectal cancer who are scheduled to undergo radical surgery to excise rectal tumour and mesorectum. They will receive endoscopic Sienna+ injection (magnetic tracer) 5 days before planned surgery. They will then undergo surgery to excise rectal cancer. The excised specimen will be examined using the Sentimag probe and by standard histology to assess for lymph nodes ex-vivo. | Drug: Sienna+ injection<br>* Endoscopic injection of magnetic tracer<br>Procedure: Surgery to excise rectal cancer<br>* Surgery as scheduled according to size and stage of rectal cancer. This will be either radical surgery or transanal endoscopic microsurgery (TEM)<br>Device: Sentimag probe<br>* Probe to detect the previously injected magnetic tracer (Sienna+)<br>|
| Experimental: In-vivo<br>Patients with early rectal cancer scheduled to undergo local excision of a rectal tumour by transanal endoscopic microsurgery (TEM). They will receive endoscopic Sienna+ injection (magnetic tracer) 5 days before planned surgery, and have an MRI scan to assess tracer spread. They will then undergo TEM surgery to excise the rectal cancer. During surgery the Sentimag probe will be used to locate the sentinel lymph node so it can be surgically removed. The excised specimen will be examined by standard histology. | Drug: Sienna+ injection<br>* Endoscopic injection of magnetic tracer<br>Other: MRI scan<br>* MRI scan of pelvis to detect spread of magnetic tracer<br>Procedure: Surgery to excise rectal cancer<br>* Surgery as scheduled according to size and stage of rectal cancer. This will be either radical surgery or transanal endoscopic microsurgery (TEM)<br>Device: Sentimag probe<br>* Probe to detect the previously injected magnetic tracer (Sienna+)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing of Adverse or Hypersensitivity Reaction | Assess frequency of any adverse of hypersensitivity reactions to tracer after endoscopic injection | 5 days after injection | 
| Number of Operations Where Effects of Tracer Injection Can be Detected by Surgeon During Surgery | Assess frequency of Sienna+ tracer being detectable at the tumour injection site and in the lymph nodes at the time of surgery | at time of surgery | 
| Number of Operations Where There Was Any Surgical Difficulty Due to Tracer Injection Based on Qualitative Assessment by Surgeon | Surgeon's qualitative assessment of any difficulties encountered during surgery which could be attributable to prior injection of the tracer, such as pigmentation or fibrosis making surgery more difficult than normal | at time of surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Mesorectal Specimens Which Demonstrated Correlation Between Histopathology and Sentimag Probe Findings for Lymph Node Number and Location | The histopathology findings of lymph node distribution in the excised mesorectal specimen correlated with the information provided by the Sentimag probe. | 5 days after surgery | 
| Number of Mesorectal Specimens Which Demonstrated Coincidence Between Histopathological and Sentimag Probe Identification of the 'Sentinel' Lymph Node | A pathologist will identify the sentinel lymph node histologically and record whether this matches the location identified by the Sentimag probe which has been previously marked with a suture | 5 days after surgery | 
| High Resolution MRI Composite Map of Drainage Pattern of Sienna+ Tracer in Mesorectum | Evaluation of individual variability in Sienna+ distribution after endoscopic injection on high resolution MRI scans to establish a baseline for individual variation | MRI scan done 2 hours after Sienna+ tracer injection | 
| Number of TEM Operations Where the Sentinel Lymph Node Can be Identified and Removed | Sentimag probe is used to localise the sentinel node during TEM (transanal endoscopic microsurgery) and then remove it if possible | at time of surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rectal cancer, Sentinel Lymph Node Biopsy