Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02635737 |
| Other study ID # |
2016BR005 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
July 6, 2016 |
| Est. completion date |
May 3, 2017 |
Study information
| Verified date |
January 2021 |
| Source |
Manchester University NHS Foundation Trust |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This is a single site, single arm, unblinded safety and feasibility cohort study
investigating the use of magnetic marker seeds to localise breast tumours.
Description:
Background and Rationale Breast Cancer Breast cancer is a heterogeneous disease, with great
diversity in the site, size and progression of tumours. Some are palpable and discovered by
the patient, though many are first detected during mammogram screening. For such cancers,
localisation is necessary prior to surgery, to guide surgeons to the target excision site.
Wire Guided Localisation Traditionally, localisation involves radiographic-guided insertion
of a wire into the breast, with positioning of the wire tip at the centre of the lesion.
However, this procedure carries several logistical limitations , stemming from the fact that
wire localisation must be performed on the day of surgery. This is to minimise risk of wire
migration or dislodgement , a significant possibility due to the external section of wire
left protruding from the breast. Same-day appointments demand excellent coordination between
radiological departments and operating theatres to ensure that disruption to procedure
scheduling is minimised. Delays may result from technically difficult procedures , leading to
over-running radiology appointments that have a knock on effect on operating lists.
Additionally, cancelled operations can result in preceding wire guidance procedures becoming
unnecessary, resulting in wasted staff hours.
Another limitation of wire guidance occurs because the wire directs surgeons along a linear
route. Lesions are found at a point along the wire, though it can be difficult to determine
how far along they are found. For this reason, surgeons making initial incisions may be
dictated by the visual trajectory of the wire, rather than the location of the lesion. This
can lead to excessive dissection and sub optimal cosmetic results.
Radioactive Seed Localisation Radioactive seed localisation (RSL) is a localisation technique
that is less commonly used in the United Kingdom (UK). A radioactive seed can be inserted up
to 5 days before surgery, thus eliminating the requirement for radiology appointments on the
same day as the patient's operation. The seed is detected in theatre using a handheld gamma
probe. The gamma probe directs the surgeon to a single specific point via the shortest route,
whereas, wires often transect the breast, meaning that surgeons commonly end up dissecting
across normal tissue to locate the tip of the wire. In addition, with RSL, there is no
distraction from external projections of wire, so the surgeon is guided purely by the audible
response to the seed. It is hypothesised that the advantages of RSL will lead to improved
surgical techniques and reduce pressures on theatre scheduling.
However, up to now, there is little evidence demonstrating clear superiority in surgical
outcome of one localisation technique. Several studies have found lower positive margin rates
in patients undergoing RSL versus wire guidance , , . This means that edges of excised
tissues less commonly involves cancerous tissue, suggesting that RSL more accurately
localises cancerous lesions. Conversely, many more studies, including one of the largest
trials to date, conclude there is no variability in surgical outcome.
Regardless of stance on surgical outcome, all studies noted that RSL offers significant
improvements in scheduling of appointments and patient convenience.
However, radioactive techniques are not without limitations. Several studies have evaluated
the use of standard radioisotope and blue dye injections for sentinel node biopsy. Each study
commented on the complex legislation regulating use of radioisotopes, particularly with
regards to operator training and correct disposal and handling. In addition, radioisotope use
increases patient and healthcare worker radiation exposure which, though minimal, would be
preferable to avoid.
Iron Oxide Use in Breast Surgery Several studies have investigated the use of liquid
injections of iron oxide rather than traditional radioisotope and blue dye injections, in
sentinel node identification. Following iron oxide injections, a handheld magnetometer was
used to detect the location of iron oxide in the lymph nodes. All studies concluded that iron
oxide particles performed equally as well as standard radioisotope & blue dye injections in
sentinel node identification, demonstrating potential for more widespread use of the
technique.
In addition, Ahmed et al tested localisation of cancerous lesions using a magnetic tracer
injection. The tracer successfully localised all tumours and resulted in appropriate
excisional margins, without excess tissue excision; thus demonstrating the feasibility of
magnetic tracer localisation of tumours.
Sentimark Magnetic Localisation The localisation method with which this project is concerned
has similar principles to RSL. However, instead of radioactive seeds, a soft magnetic seed
called Sentimark, is placed into the breast. The seed is similar to a biopsy clip and can be
detected using a handheld magnetometer called Sentimag. The Sentimag probe emits an
alternating magnetic field that detects the magnetic response of the Sentimark seed. The
magnetometer produces an audible response when held close to the Sentimark seed and can be
used by surgeons to locate target excision sites. Sentimark is inserted about a week before
operation, ideally during a biopsy appointment, for patient convenience.
This study will be the first to investigate magnetic seed localisation of tumours. It is
hypothesised that using magnetic seeds rather than injections with a magnetic tracer will
allow more accurate detection and localisation using the Sentimag probe. This is because the
probe is detecting the magnetic field produced by a single discrete object, rather than a
collection of iron oxide-containing liquid which may disperse throughout the breast.
Summary of Localisation Techniques The coordination and scheduling difficulties encountered
in wire guided localisation, alongside the logistical and safety issues of radioisotope
usage, highlight a requirement for further innovation and acquisition of new technologies in
the field of localisation. It is hoped that magnetic seed localisation can act as a feasible
alternative to existing technologies. Use of magnetism in localisation techniques offers a
potential alternative to wire guidance and RSL.
An important consideration with the deployment of the new seed is whether the size and shape
of the seed are sufficiently similar to previous designs to show similar migration patterns,
as movement of the seed prior to surgery can cause incomplete lesion excision with en-suing
requirements for re-operation or an increased risk of recurrence.
The migration performance of Sentimark in an implantation trial in goats, mean migration of
1.1mm with a range 0 to 3.6mm (N=10), was very similar to that observed by Alderliesten, et
al. who report a mean migration of 0.8mm, range 0 to 2.8mm (N=10) for RSL seeds which was
considered "clinically negligible" in RSL of human breast lesions. However, confirmation is
required that the magnetic marker performs as expected in the clinic.
The study will test a soft magnetic seed (Sentimark) and its accompanying handheld magnetic
probe (Sentimag) with particular consideration for its safety and performance once placed
into human breast tissue.
Device The device to be studied is a small (5mm x 0.9mm) metal magnetic marker (seed) that
has soft magnetic properties. This means that when exposed to a magnetic field it becomes
magnetic. The magnetism can then be detected using a magnetometer and probe which gives an
audible and visual signal of the strength of response from the seed and as it is directional
this can accurately guide the user to the site of the magnetic seed. The magnetometer is a CE
(Conformite Europeene) approved device and is used worldwide for detecting iron oxide in
sentinel lymph node biopsy procedures, and is proven in clinical practice. The seed itself
will be deployed by a radiologist into the centre of the tumour site using a similar
technique to that used to currently place a wire into the breast. The seed itself is
cylindrical and in in vivo studies in goats have shown similar migration performance to that
seen with radioactive seeds in human breast tissue.
The seed has also been tested in animal tissue models by (University Hospital of South
Manchester) UHSM radiologists and surgeons, and in these models it can be safely deployed by
the radiologists using existing techniques. The device was detected and surgical resection
was performed with 100% accuracy on all specimens. There is no radiation exposure from this
device.
Study Population Adult women with capacity to consent who have a proven breast cancer
requiring breast removing mastectomy surgery.
Potential Risks to Patients The device itself is a small piece of metal and in itself does
not offer a likely safety risk.
- Migration of the seed - the seed is cylindrical and therefore once placed in the breast
it has the potential to migrate along the path of the needle that was used to deploy it.
When deployed into mammary soft tissue in animal models the device has not migrated.
This study will involve placing the device in women having mastectomy so even if the
device migrates it will not affect patients cancer care (as the whole breast will be
removed along with the device no matter where it is located in the breast);
- Failure to detect the seed - the seed is small and the magnetic field generated is
proportional to the size of the seed. This study aims to assess whether the seed can be
detected in all sizes of breast as in some cases it may be possible that the seed lies
too deep in the breast to be detected using the magnetometer. To ensure safe resection
of the cancer, each patient in this study will be under-going a planned mastectomy, to
ensure that the device is fully removed even if detection should fail;
- Tissue acceptance - the seed is produced from a single material and has demonstrated
biocompatibility through ISO-10993 biocompatibility evaluation including demonstration
of tissue acceptance in mammary tissue of goats (28-day implantation period). Bone wax
is used as a terminal plug for Sentimark device. Bone wax is commonly used for the same
purpose in brachytherapy and RSL needles. Some reaction to bone wax may occur, such as
an allergic reaction or foreign body reactions (e.g. granulomas), as bone wax is a
minimally resorbable implantable substance.
Potential Benefits The study will be carried out in patients requiring a mastectomy. In this
population, the full cycle of marker (seed) deployment and removal can be evaluated, but as
the breast is being removed as part of the planned cancer treatment, patient treatment will
be unaffected should the magnetic seed not perform as intended. However, there will be no
direct benefit for patients taking part in the study and the potential benefits of this study
are limited to the advancement of medical knowledge. If the study confirms that the magnetic
marker (seed) is safe and the method is feasible, the device has the potential to be used for
localisation of breast cancers for lumpectomy surgery.
