NICE Publishes Technology Appraisal Guidance About Intrabeam Radiotherapy System for Adjuvant Treatment of Early Breast Cancer

It is not recommended for routine commissioning during breast-conserving surgery

On 31 January 2018, NICE released Technology appraisal guidance [TA501] about Intrabeam radiotherapy system for adjuvant treatment of early breast cancer. It is not recommended for routine commissioning for adjuvant treatment of early invasive breast cancer during breast-conserving surgical removal of the tumour. Use of the Intrabeam radiotherapy system is recommended only using machines that are already available and in conjunction with NHS England specified clinical governance, data collection and submission arrangements.

The procedure should only be carried out by clinicians with specific training in the use of the Intrabeam radiotherapy system.

Patient selection for Intrabeam radiotherapy should be done by a multidisciplinary team experienced in the management of early invasive breast cancer, which includes both breast surgeons and clinical oncologists.

Clinicians wishing to undertake Intrabeam radiotherapy should take the following actions:

  • Inform the clinical governance leads in their NHS trusts.
  • Ensure that patients understand the uncertainties about the procedure and inform them about alternative treatment options.
  • Provide patients with NICE's written information on the evidence of the risks and benefits of the range of treatment options available as an aid to shared decision-making.

The Intrabeam radiotherapy system (Carl Zeiss UK) is a mobile irradiation system. It is designed to deliver a single dose of targeted low-energy radiation (X‑rays) directly to the tumour bed, while limiting the exposure of healthy tissue to radiation. Because it delivers low energy radiation, it can be used in an ordinary operating theatre at the time of surgery. The Intrabeam radiotherapy system provides a source of 50 kV energy from a spherical applicator of between 1.5 cm and 5.0 cm diameter. The applicator is sutured to the tumour bed so that breast tissue at risk of local recurrence receives the prescribed dose while skin and deeper structures are protected. Radiation is delivered over 20 to 30 minutes.

The Intrabeam radiotherapy system was granted a CE (Conformité Européene) mark in 1999 for use in radiotherapy.

Intrabeam can be used as an intraoperative radiotherapy system given as the sole treatment or as a boost treatment followed by external beam radiotherapy (EBRT). When intraoperative radiotherapy is given as a boost treatment with Intrabeam and followed by EBRT, there is no need for further external boost treatment. Six NHS centres in the UK have used Intrabeam for adjuvant treatment of early breast cancer.

Adverse reactions are mostly related to wound-related complications and radiotherapy-related complications.

The surface of the tumour bed typically receives a single fraction of 20 Gy, which attenuates to 5 Gy to 7 Gy at a depth of 1 cm.

The cost of the Intrabeam radiotherapy system (including the spherical applicators) is 435,000 GBP (excluding VAT, Carl Zeiss UK personal notification). The company estimates that device maintenance and servicing costs are about 35,000 GBP per year. Costs may vary in different settings because of negotiated procurement discounts.

Evidence for clinical effectiveness came from a randomised trial comparing Intrabeam with EBRT (TARGIT‑A). It was a non-inferiority trial and the primary endpoint was local recurrence in the conserved breast.

Length of follow-up in the trial was too short to reliably show the clinical effectiveness of Intrabeam compared with EBRT for the incidence of local recurrence.

The appraisal committee noted that the clinical evidence for Intrabeam was immature and associated with considerable uncertainty. It acknowledged that Intrabeam had not been proven to be non-inferior to EBRT and could be associated with a higher risk of local recurrence.

In TARGIT‑A, EBRT was delivered in an average of 23 fractions, longer than the 15 fractions delivered in established clinical practice in the NHS. The radiation doses administered with EBRT also ranged from 40 Gy to 56 Gy in TARGIT‑A, whereas established clinical practice in the NHS is a dose of 40 Gy. Comments from professional groups highlighted that quality control of EBRT was not reported in some centres, and there may have been considerable variation internationally. The appraisal committee concluded that some doubt remained about the generalisability of the trial data to NHS clinical practice.

The appraisal committee noted that the clinical evidence for Intrabeam was immature and associated with considerable uncertainty. It acknowledged that Intrabeam had not been proven to be non-inferior to EBRT and could be associated with a higher risk of local recurrence.

It was not possible to confirm that there is an overall survival benefit with Intrabeam compared with EBRT.

TARGIT‑A included a pre-pathology group (treatment with Intrabeam was delivered at the same time as surgical removal of the tumour) and a post-pathology group (treatment with Intrabeam was delayed and provided after a second surgical procedure to re-open the wound). The rate of local recurrence in the post-pathology group was higher than in the pre-pathology group, and the company stated that non-inferiority for local recurrence had not been established in the post-pathology group. The appraisal committee concluded that it was reasonable to consider treatment with Intrabeam only at the time of primary surgical removal of the tumour.

The appraisal committee considered the low rates of local recurrence that had so far been shown in both arms of the trial: 1.1% for EBRT and 2.1% for Intrabeam in the pre-pathology group. It noted that the pre-specified non-inferiority margin at 5 years for the absolute difference of local recurrence between treatment groups was 2.5%. The clinical experts stated that this was based on an estimated rate of a 5‑year local recurrence of 6% in the EBRT group. The appraisal committee considered that the difference in Kaplan–Meier estimates of local recurrence was 1% and the 95% CI was −0.68 to 2.68.

The results from both the company's and the assessment group's models estimated that the QALY difference between Intrabeam and EBRT was very small. The appraisal committee considered that, based on the high degree of uncertainty in the cost-effectiveness analysis, it was not possible to state the most plausible incremental cost-effectiveness ratio for Intrabeam compared with EBRT. It concluded that Intrabeam was associated with slightly lower costs and fewer QALYs than EBRT.