IART (Intra-Operative Avidination for Radionuclide Therapy) for accelerated radiotherapy in breast cancer patients. Technical aspects and preliminary results of a phase II study with 90Y-labelled biotin

Abstract

Background: Breast conserving surgery (BCS) plus external beam radiotherapy (EBRT) is considered the standard treatment for early breast cancer. We have investigated the possibility of irradiating the residual gland, using an innovative nuclear medicine approach named IART(®) (Intra-operative Avidination for Radionuclide Therapy).

Aim: The objective of this study was to determine the optimal dose of avidin with a fixed activity (3.7 GBq) of (90)Y-biotin, in order to provide a boost of 20 Gy, followed by EBRT to the whole breast (WB) at the reduced dose of 40 Gy. Local and systemic toxicity, patient's quality of life, including the cosmetic results after the combined treatment with IART(®) and EBRT, were assessed.

Methods: After tumour excision, the surgeon injected native avidin diluted in 30 ml of saline solution into and around the tumour bed (see video). Patients received one of three avidin dose levels: 50 mg (10 pts), 100 mg (15 pts) and 150 mg (10 pts). Between 12 to 24 h after surgery, 3.7 GBq (90)Y-biotin spiked with 185 MBq (111)In-biotin was administered intravenously (i.v.). Whole body scans and SPECT images were performed up to 30 h post-injection for dosimetric purposes. WB-EBRT was administered four weeks after the IART(®) boost. Local toxicity and quality of life were evaluated.

Results: Thirty-five patients were evaluated. No side effects were observed after avidin administration and (90)Y-biotin infusion. An avidin dose level of 100 mg resulted the most appropriate in order to deliver the required radiation dose (19.5 ± 4.0 Gy) to the surgical bed. At the end of IART(®), no local toxicity occurred and the overall cosmetic result was good. The tolerance to the reduced EBRT was also good. The highest grade of transient local toxicity was G3, which occurred in 3/32 pts following the completion of WB-EBRT. The combination of IART(®)+EBRT was well accepted by the patients, without any changes to their quality of life.

Conclusions: These preliminary results support the hypothesis that IART(®) may represent a valid approach to accelerated WB irradiation after BCS. We hope that this nuclear medicine technique will contribute to a better management of breast cancer patients.

To view this video click here: http://www.ecancermedicalscience.com/view-article.asp?doi=10.3332/ecancer.2010.166

Figure: 1

a: SPECT/CT fused images showing a hot region in the operated left breast. b: The hot region was divided into three different areas: high-uptake area (uptake higher than 50% of the maximum—isorois 50%); medium-uptake area (between 50% and 30% isorois) and low-uptake area (between 30% and 10% isorois).

Figure: 1

a: SPECT/CT fused images showing a hot region in the operated left breast. b: The hot region was divided into three different areas: high-uptake area (uptake higher than 50% of the maximum—isorois 50%); medium-uptake area (between 50% and 30% isorois) and low-uptake area (between 30% and 10% isorois).

Figure 2:

Whole body scans (anterior projection) acquired at 1, 3, 15 and 24 h post-injection of ⁹⁰Y-biotin in a patient operated in the right breast.

Figure 3:

Good cosmetic results and normal wound healing in a patient who received IART^® alone.

Figure 4:

Patient who received IART^® plus EBRT. a: No local toxicity was observed four weeks after IART^®; b: mild local toxicity after delivery of 20 Gy by EBRT; c: local toxicity (classified as G1) month after completion of EBRT; d: no local toxicity present six months after EBRT. Cosmetic outcome was judged good.

Figure 5:

a: A multi-hole needle conceived in order to deliver avidin at different depths into the breast parenchyma at each injection site. b: A screw syringe designed to deliver an equal volume (0.7 ml) of avidin in the surgical bed.

Figure 5:

a: A multi-hole needle conceived in order to deliver avidin at different depths into the breast parenchyma at each injection site. b: A screw syringe designed to deliver an equal volume (0.7 ml) of avidin in the surgical bed.