Rectal Cancer
Conditions
Keywords
Rectal cancer, Sentinel Lymph Node Biopsy
Brief summary
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
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.
Interventions
Endoscopic injection of magnetic tracer
OTHERMRI scan
MRI scan of pelvis to detect spread of magnetic tracer
PROCEDURESurgery to excise rectal cancer
Surgery as scheduled according to size and stage of rectal cancer. This will be either radical surgery or transanal endoscopic microsurgery (TEM)
DEVICESentimag probe
Probe to detect the previously injected magnetic tracer (Sienna+)
Sponsors
University of Leeds
Endomagnetics Ltd.
Oxford University Hospitals NHS Trust
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing of Adverse or Hypersensitivity Reaction | 5 days after injection | Assess frequency of any adverse of hypersensitivity reactions to tracer after endoscopic injection |
| Number of Operations Where Effects of Tracer Injection Can be Detected by Surgeon During Surgery | at time of surgery | Assess frequency of Sienna+ tracer being detectable at the tumour injection site and in the lymph nodes at the time of surgery |
| Number of Operations Where There Was Any Surgical Difficulty Due to Tracer Injection Based on Qualitative Assessment by Surgeon | at time of surgery | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of TEM Operations Where the Sentinel Lymph Node Can be Identified and Removed | at time of surgery | Sentimag probe is used to localise the sentinel node during TEM (transanal endoscopic microsurgery) and then remove it if possible |
| High Resolution MRI Composite Map of Drainage Pattern of Sienna+ Tracer in Mesorectum | MRI scan done 2 hours after Sienna+ tracer injection | Evaluation of individual variability in Sienna+ distribution after endoscopic injection on high resolution MRI scans to establish a baseline for individual variation |
| Number of Mesorectal Specimens Which Demonstrated Correlation Between Histopathology and Sentimag Probe Findings for Lymph Node Number and Location | 5 days after surgery | The histopathology findings of lymph node distribution in the excised mesorectal specimen correlated with the information provided by the Sentimag probe. |
| Number of Mesorectal Specimens Which Demonstrated Coincidence Between Histopathological and Sentimag Probe Identification of the 'Sentinel' Lymph Node | 5 days after surgery | 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 |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ex-vivo 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.
Sienna+ injection: Endoscopic injection of magnetic tracer
MRI scan: MRI scan of pelvis to detect spread of magnetic tracer
Surgery to excise rectal cancer: Surgery as scheduled according to size and stage of rectal cancer. This will be either radical surgery or transanal endoscopic microsurgery (TEM)
Sentimag probe: Probe to detect the previously injected magnetic tracer (Sienna+) | 13 |
| In-vivo 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.
Sienna+ injection: Endoscopic injection of magnetic tracer
MRI scan: MRI scan of pelvis to detect spread of magnetic tracer
Surgery to excise rectal cancer: Surgery as scheduled according to size and stage of rectal cancer. This will be either radical surgery or transanal endoscopic microsurgery (TEM)
Sentimag probe: Probe to detect the previously injected magnetic tracer (Sienna+) | 2 |
| Total | 15 |
Baseline characteristics
| Characteristic | In-vivo | Ex-vivo | Total |
|---|---|---|---|
| Age, Customized Age category < 50 years | 1 Participants | 2 Participants | 3 Participants |
| Age, Customized Age category 51-60 years | 0 Participants | 5 Participants | 5 Participants |
| Age, Customized Age category 61-70 years | 0 Participants | 6 Participants | 6 Participants |
| Age, Customized Age category > 70 years | 1 Participants | 0 Participants | 1 Participants |
| Pre-operative N stage mrN0 - no lymph nodes invaded by cancer cells | 2 Participants | 10 Participants | 12 Participants |
| Pre-operative N stage mrN1 - up to 3 nearby lymph nodes contain cancer cells | 0 Participants | 2 Participants | 2 Participants |
| Pre-operative N stage mrN2 - more than 3 lymph nodes contain cancer cells | 0 Participants | 1 Participants | 1 Participants |
| Pre-operative tumour T stage mrT1 - tumour confined to inner bowel wall | 1 Participants | 3 Participants | 4 Participants |
| Pre-operative tumour T stage mrT2 - tumour extending into muscle layer of the bowel wall | 1 Participants | 5 Participants | 6 Participants |
| Pre-operative tumour T stage mrT3 - tumour has grown into the outer lining of the bowel wall | 0 Participants | 5 Participants | 5 Participants |
| Prior treatment Chemoradiation | 0 Participants | 3 Participants | 3 Participants |
| Prior treatment Local excision | 0 Participants | 3 Participants | 3 Participants |
| Prior treatment Nil | 2 Participants | 7 Participants | 9 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment United Kingdom | 2 participants | 13 participants | 15 participants |
| Sex: Female, Male Female | 0 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Male | 2 Participants | 10 Participants | 12 Participants |
| Tumour diameter | 2.8 centimeter | 3.0 centimeter | 3.0 centimeter |
| Tumour height above anal margin | 11 centimeter | 7 centimeter | 8 centimeter |
| Tumour location anterior | 1 Participants | 4 Participants | 5 Participants |
| Tumour location lateral | 0 Participants | 4 Participants | 4 Participants |
| Tumour location posterior | 1 Participants | 5 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 2 |
| other Total, other adverse events | 0 / 13 | 0 / 2 |
| serious Total, serious adverse events | 4 / 13 | 0 / 2 |
Outcome results
Primary
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
Time frame: at time of surgery
Population: Only patients who underwent surgery were analysed. Two patients in the ex-vivo group who were planned to have surgery did not proceed to surgery; instead they moved to a 'watch and wait' pathway after chemoradiation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ex-vivo | Number of Operations Where Effects of Tracer Injection Can be Detected by Surgeon During Surgery | 11 operations |
| In-vivo | Number of Operations Where Effects of Tracer Injection Can be Detected by Surgeon During Surgery | 2 operations |
Primary
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
Time frame: at time of surgery
Population: Only patients who underwent surgery were analysed. Two patients in the ex-vivo group who were planned to have surgery did not proceed to surgery; instead they moved to a 'watch and wait' pathway after chemoradiation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ex-vivo | Number of Operations Where There Was Any Surgical Difficulty Due to Tracer Injection Based on Qualitative Assessment by Surgeon | 0 operations |
| In-vivo | Number of Operations Where There Was Any Surgical Difficulty Due to Tracer Injection Based on Qualitative Assessment by Surgeon | 0 operations |
Primary
Number of Participants Experiencing of Adverse or Hypersensitivity Reaction
Assess frequency of any adverse of hypersensitivity reactions to tracer after endoscopic injection
Time frame: 5 days after injection
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ex-vivo | Number of Participants Experiencing of Adverse or Hypersensitivity Reaction | 0 Participants |
| In-vivo | Number of Participants Experiencing of Adverse or Hypersensitivity Reaction | 0 Participants |
Secondary
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
Time frame: MRI scan done 2 hours after Sienna+ tracer injection
Population: Only patients who had MRI scans done following tracer injection were included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ex-vivo | High Resolution MRI Composite Map of Drainage Pattern of Sienna+ Tracer in Mesorectum | tracer uptake by tumour | 6 MRI scans |
| Ex-vivo | High Resolution MRI Composite Map of Drainage Pattern of Sienna+ Tracer in Mesorectum | extraneous mucosal tracer uptake | 2 MRI scans |
| Ex-vivo | High Resolution MRI Composite Map of Drainage Pattern of Sienna+ Tracer in Mesorectum | tracer uptake by mesorectal nodes | 7 MRI scans |
| Ex-vivo | High Resolution MRI Composite Map of Drainage Pattern of Sienna+ Tracer in Mesorectum | Suspicious nodes on MRI after tracer injection | 3 MRI scans |
| In-vivo | High Resolution MRI Composite Map of Drainage Pattern of Sienna+ Tracer in Mesorectum | Suspicious nodes on MRI after tracer injection | 1 MRI scans |
| In-vivo | High Resolution MRI Composite Map of Drainage Pattern of Sienna+ Tracer in Mesorectum | tracer uptake by tumour | 1 MRI scans |
| In-vivo | High Resolution MRI Composite Map of Drainage Pattern of Sienna+ Tracer in Mesorectum | tracer uptake by mesorectal nodes | 2 MRI scans |
| In-vivo | High Resolution MRI Composite Map of Drainage Pattern of Sienna+ Tracer in Mesorectum | extraneous mucosal tracer uptake | 1 MRI scans |
Secondary
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
Time frame: 5 days after surgery
Population: Only patients who underwent radical surgery involving Total mesorectal excisison were included. The surgical specimens were analysed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ex-vivo | Number of Mesorectal Specimens Which Demonstrated Coincidence Between Histopathological and Sentimag Probe Identification of the 'Sentinel' Lymph Node | 2 surgical mesorectal specimen |
| In-vivo | Number of Mesorectal Specimens Which Demonstrated Coincidence Between Histopathological and Sentimag Probe Identification of the 'Sentinel' Lymph Node | 0 surgical mesorectal specimen |
Secondary
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.
Time frame: 5 days after surgery
Population: Only patients who underwent radical surgery involving Total mesorectal excisison were included. The surgical specimens were analysed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ex-vivo | Number of Mesorectal Specimens Which Demonstrated Correlation Between Histopathology and Sentimag Probe Findings for Lymph Node Number and Location | 2 surgical mesorectal specimen |
| In-vivo | Number of Mesorectal Specimens Which Demonstrated Correlation Between Histopathology and Sentimag Probe Findings for Lymph Node Number and Location | 0 surgical mesorectal specimen |
Secondary
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
Time frame: at time of surgery
Population: This measure only applies to the In-vivo group. Ex-vivo group did not undergo TEM surgery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| In-vivo | Number of TEM Operations Where the Sentinel Lymph Node Can be Identified and Removed | 0 TEM operations |