Magnetic Seed Localisation of Breast Cancers
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Interventional

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.
    

Detailed 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.
    

Intervention name(s): Sentimark
Intervention type(s): Device
Intervention description(s): Placement of a metallic clip with paramagnetic properties for tumour localisation
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment