Magtrace and Sentimag system for locating sentinel lymph nodes for breast cancer

The committee noted that the clinical evidence showed Magtrace and Sentimag to be as effective as the dual technique for detecting sentinel lymph nodes, including malignant nodes. Other clinically relevant outcome measures such as the number of nodes retrieved per procedure and pain scores were deemed to be equivalent when compared with standard care. The committee considered the non-inferiority studies to be well conducted. The evidence base includes studies that have been done in a UK and NHS context. The committee concluded that the clinical evidence supports non-inferiority of Magtrace and Sentimag compared with current standard care.

The committee was advised that although Magtrace can be injected in the theatre 20 minutes before the start of a sentinel lymph node biopsy procedure, injection is more commonly done at a standard clinical appointment up to 30 days before surgery to give a better detection signal. The clinical experts highlighted the advantages of earlier injection in terms of improved theatre scheduling and convenience. An ongoing study is exploring the earliest appropriate time point for Magtrace injection before sentinel lymph node biopsy. The committee accepted the maximum time period for injecting Magtrace of 30 days as stated in the manufacturer's information for use and concluded that Magtrace allows for significantly earlier injection than the radioisotope used in standard practice.

The committee acknowledged that future MRI of the breast could be affected by residual Magtrace that remains in the body after a sentinel lymph node biopsy procedure. The EAC explained that the clinical evidence shows that follow-up MRI can be impaired for as long as 5 years after the procedure. There is 1 study that shows that a mammography was also affected after an injection of Magtrace. The clinical experts highlighted that follow-up MRI studies are becoming more common, particularly in the following groups: young people under the age of 40, people with occult cancers and people with dense breasts. Consensus from clinical experts is that Magtrace would not be advised for people who are likely to need MRI within 3 months after sentinel lymph node biopsy. Contrast-enhanced digital mammography or gadolinium-enhanced MRI could be used as alternative imaging techniques for these people, but they are associated with higher radiation or higher costs. The committee queried whether residual Magtrace would remain localised in lymph nodes in the breasts or whether it would spread throughout the body over time and affect imaging of other areas. The company clarified that this would remain residually in the breast tissue and that any particles outside of this would be engulfed by macrophages and excreted. The clinical experts stated that issues with mammography had not been identified after 3 years of using Magtrace. The committee concluded that future imaging is an important issue for clinicians to consider, so Magtrace should be carefully considered for people who are likely to need follow-up MRI studies after having a sentinel lymph node biopsy procedure.

The committee noted that the clinical evidence identified skin staining as the most common adverse event associated with Magtrace. The patient expert commented that skin staining was not a key issue, and that people find the brown staining is preferable to the blue staining associated with blue dye. The company provided data on patient experience, stating that 90% of people did not worry about skin staining caused by Magtrace. The clinical experts commented that from their experience, the size of the breasts and method of injection affects the rate of staining. A deeper peritumoral breast injection causes less staining, and this has been adopted by clinicians in practice. The committee concluded that skin staining is also an issue with the dual technique comparator and is not a significant concern for people having the injection.

The patient expert explained that people can be quite worried before having a sentinel lymph node biopsy procedure because of the need for radioactive material to be injected into the body and the risk of anaphylaxis associated with blue dye. The patient expert highlighted that these risks do not exist with Magtrace, but there are other considerations which are important for people having the procedure. Some people with breast cancer will have yearly follow-up imaging, and these could be affected by artefacts because of residual Magtrace. People may also experience skin staining and pass darker coloured urine after having Magtrace injected. Therefore, the patient expert suggested that people would prefer to have information before having sentinel lymph node biopsy with Magtrace and Sentimag. The committee agreed with the patient expert and concluded that it is important for people to be appropriately informed of the adverse events associated with the technology before the procedure.

The committee considered that the EAC base-case model was appropriate for decision making. They agreed with the parameters included in the model but were uncertain about whether the opportunity costs associated with additional sentinel lymph node biopsy procedures would be realised in practice. Opportunity costs were identified as the key cost driver for Magtrace and Sentimag. In the EAC's base-case analysis, Magtrace and Sentimag is cost saving by £78.90 per procedure, but cost incurring by £58.16 per procedure when opportunity costs are excluded from the model.

The EAC highlighted that there are currently 3 scenarios to consider when looking at the different hospitals in which sentinel lymph node biopsies are done. The differentiating factor is whether radiopharmacy and nuclear medicine facilities exist on the same site as where the sentinel lymph node biopsy is being done. Some hospitals can produce the radioisotope injection on the same site as the procedure, whereas other hospitals need the radioisotope to be transported to their site for injection before the procedures. The third scenario needs people to travel to 1 site for the radioisotope injection, then a different site where the biopsy is done. Clinical experts work at centres with and without access to radiopharmacy and explained there was general agreement that hospitals with limited or no access to radiopharmacy and nuclear medicine would be most likely to realise the opportunity costs which make Magtrace and Sentimag cost saving. The EAC highlighted that 55.9% of centres performing sentinel lymph node biopsy procedures have radiopharmacy and nuclear medicine facilities on site or are already using Magtrace and Sentimag, and would therefore be less likely to realise the opportunity costs included in the economic model. The committee concluded that hospitals without access to on-site radiopharmacy and nuclear medicine are likely to benefit from Magtrace because of the efficiency gains related to theatre scheduling and reduced supply chain issues. The committee acknowledged that Magtrace and Sentimag could also be an option for some hospitals with on-site radiopharmacy which still have challenges with theatre scheduling or experience delays.

The company explained that the Sentimag probe has a 5‑year lifespan and is supplied with a calibration cap which is used to calibrate the device each day before starting surgery. This takes about 20 seconds and is logged. During the procedure, the probe also needs to be reset each time it is moved out of the operation field, which takes around 3 seconds. In the event of an issue with the Sentimag probe, there is a contact procedure in place to report this to the company. The committee was advised that the gamma probes used in current practice need similar calibration. The lifespan of a gamma probe is around 2 years. The clinical experts did not consider calibration of the Sentimag probe to cause any inconvenience to clinicians. They also noted that the gamma probe was smaller and had a softer feel than the Sentimag probe. The committee concluded that the Sentimag probe is broadly similar to the gamma probes used in current practice.

One clinical study (Pinero-Madrona et al. 2015) mentioned the possible interference of surgical instruments when using Magtrace and Sentimag. The manufacturer's information for use states that the Sentimag probe head should be at least 0.5 metres away from any metal or magnetic objects. Clinical experts explained that metal and magnetic materials affect the signal detection on the Sentimag system, so plastic surgical instruments (for example, single-use disposable forceps and retractors) may need to be used. The committee was told that this can potentially make operating more difficult and time consuming, although it was also told that with more experience the need for alternative instruments can be avoided. The company explained that plastic instruments are provided with the technology at no extra charge and that titanium instruments can also be used. The committee concluded that some surgeons may need to use alternative surgical instruments with Magtrace and Sentimag. They acknowledged that this may take some time to get used to, but with experience it does not add any significant time to the procedure and using such instruments can potentially be avoided altogether.

The company commented that a minimum of 5 procedures were needed to build familiarity with Magtrace and Sentimag. The company suggested that representatives from the manufacturer are usually present for the first few procedures to support clinicians. Online resources and surgical footage are also available, as well as an annual retraining session for sites which regularly use the technology. The clinical experts stated it takes around 50 procedures or 2 years to be fully competent with Magtrace. The committee concluded that a learning curve is associated with using Magtrace and Sentimag, and the company has processes in place to support clinicians during this time.

The committee stated that further data collection was needed to monitor the difference in the number of sentinel lymph node biopsies being done in each hospital once Magtrace and Sentimag have been adopted into clinical practice. The realisation of the efficiency gains and opportunity costs is defined as being able to do additional procedures each week with Magtrace. Adverse events should also be reported. More evidence is needed on the impact of Magtrace on future MRI of the breast.