Bauke Anninga

Magnetic sentinel node and occult lesion localization in breast cancer (MagSNOLL Trial)

Non‐palpable breast cancers require localization‐guided surgery and axillary staging using sentinel lymph node biopsy (SLNB). This study investigated the novel technique of magnetic‐guided lesion localization and concurrent SLNB, which avoids the need for wire‐guided localization and radioisotopes.

Comparison of three magnetic nanoparticle tracers for sentinel lymph node biopsy in an in vivo porcine model

Introduction Breast cancer staging with sentinel lymph node biopsy relies on the use of radioisotopes, which limits the availability of the procedure worldwide. The use of a magnetic nanoparticle tracer and a handheld magnetometer provides a radiation-free alternative, which was recently evaluated in two clinical trials. The hydrodynamic particle size of the used magnetic tracer differs substantially from the radioisotope tracer and could therefore benefit from optimization. The aim of this study was to assess the performance of three different-sized magnetic nanoparticle tracers for sentinel lymph node biopsy within an in vivo porcine model. Materials and methods Sentinel lymph node biopsy was performed within a validated porcine model using three magnetic nanoparticle tracers, approved for use in humans (ferumoxytol, with hydrodynamic diameter dH =32 nm; Sienna+®, dH =59 nm; and ferumoxide, dH =111 nm), and a handheld magnetometer. Magnetometer counts (transcutaneous and ex vivo), iron quantification (vibrating sample magnetometry), and histopathological assessments were performed on all ex vivo nodes. Results Transcutaneous “hotspots” were present in 12/12 cases within 30 minutes of injection for the 59 nm tracer, compared to 7/12 for the 32 nm tracer and 8/12 for the 111 nm tracer, at the same time point. Ex vivo magnetometer counts were significantly greater for the 59 nm tracer than for the other tracers. Significantly more nodes per basin were excised for the 32 nm tracer compared to other tracers, indicating poor retention of the 32 nm tracer. Using the 59 nm tracer resulted in a significantly higher iron accumulation compared to the 32 nm tracer. Conclusion The 59 nm tracer demonstrated rapid lymphatic uptake, retention in the first nodes reached, and accumulation in high concentration, making it the most suitable tracer for intraoperative sentinel lymph node localization.

Intraoperative radiotherapy in early breast cancer.

Intraoperative radiotherapy (IORT) constitutes a paradigm shift from the conventional 3–5 weeks of whole‐breast external beam radiotherapy (EBRT). IORT enables delivery of radiation at the time of excision of the breast tumour, targeting the area at highest risk of recurrence, while minimizing excessive radiation exposure to healthy breast tissue. The rationale for IORT is based on the observation that over 90 per cent of local recurrences after breast‐conserving surgery occur at or near the original operation site.

Reduction of contrast medium volume in abdominal aorta CTA: Multiphasic injection technique versus a test bolus volume

OBJECTIVE The purpose of this study is to reduce the administered contrast medium volume in abdominal CTA by using a test bolus injection, with the preservation of adequate quantitative and qualitative vessel enhancement. STUDY DESIGN For this technical efficacy study 30 patients, who were referred for a CTA examination of the abdominal aorta, were included. Randomly 15 patients were assigned to undergo a multiphasic injection protocol and received 89 mL of contrast medium (Optiray 350) (protocol I). Fifteen patients were assigned to the test bolus injection protocol (protocol II), which implies injection of a 10 mL test bolus of Optiray 350 prior to performing CTA with a 40 mL of contrast medium. Quantitative assessment of vascular enhancement was performed by measuring the amount of Hounsfield Units in the aorta at 30 positions from the celiac trunk to the iliac arteries in both groups. Qualitative assessment was performed by three radiologists who scored the images at a 5-point scale. RESULTS Quantitative assessment showed that there was no significant difference in vascular enhancement for patients between the two protocols, with mean attenuation values of 280.9 ± 50.84 HU and 258.60 ± 39.28 HU, respectively. The image quality of protocol I was rated 4.31 (range: 3.67/5.00) and of protocol II 4.11 (range: 2.67/5.00). These differences were not statistically significant. CONCLUSION This study showed that by using a test bolus injection and the administration of 50 mL of contrast medium overall, CTA of the abdominal aorta can reliably be performed, with regard to quantitative and qualitative adequate vessel enhancement.

Reduced contrast medium in abdominal aorta CTA using a multiphasic injection technique

PURPOSE The purpose of this study was to determine if with a multiphasic injection technique the administered amount of contrast medium for abdominal computerized tomographic angiography (CTA) can be decreased, whilst improving CT image quality. MATERIALS AND METHODS In 30 patients a multiphasic injection method was compared to the standard uniphasic contrast medium injection protocol. Fifteen patients underwent abdominal CTA with a standard uniphasic injection protocol (protocol I) receiving 100mL of a non-ionic radiopaque contrast agent (Ioversol). The second group of 15 patients underwent CTA with a multiphasic injection protocol (protocol II) receiving a total of 89 mL Ioversol. Vascular contrast enhancement and difference in enhancement uniformity were assessed quantitatively and image quality was assessed by three independent radiologists. RESULTS Quantitative assessment of the vascular contrast enhancement showed that there was no significant difference in enhancement uniformity for patients between the protocols. The image quality was rated as being good to excellent in 81.8% and 88.0% of the scans, for protocol I and protocol II, respectively. However these differences were not statistically significant. CONCLUSION By using a multiphasic injection technique with CTA of the abdominal aorta a reduction of 11 percent of contrast medium can be realized. Enhancement patterns are quantitatively as well as qualitatively comparable to the standard contrast medium injection protocol.

Meta‐analysis of sentinel lymph node biopsy in breast cancer using the magnetic technique

The standard for sentinel lymph node biopsy (SLNB), the dual technique (radiolabelled tracer and blue dye), has several drawbacks. A novel magnetic technique without these drawbacks has been evaluated in a number of clinical trials. It uses a magnetic tracer and a handheld magnetometer to identify and excise sentinel lymph nodes. A systematic review and meta‐analysis was performed to assess the performance and utility of the magnetic in comparison to the standard technique.

Blue dye for identification of sentinel nodes in breast cancer and malignant melanoma: a systematic review and meta-analysis

The combined technique (radioisotope and blue dye) is the gold standard for sentinel lymph node biopsy (SLNB) and there is wide variation in techniques and blue dyes used. We performed a systematic review and meta-analysis to assess the need for radioisotope and the optimal blue dye for SLNB. A total of 21 studies were included. The SLNB identification rates are high with all the commonly used blue dyes. Furthermore, methylene blue is superior to iso-sulfan blue and Patent Blue V with respect to false-negative rates. The combined technique remains the most accurate and effective technique for SLNB. In order to standardize the SLNB technique, comparative trials to determine the most effective blue dye and national guidelines are required.

Magnetic guidance for cancer surgery

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Is IORT ready for roll-out?

Two large randomised controlled trials of intraoperative radiotherapy (IORT) in breast-conserving surgery (TARGIT-A and ELIOT) have been published 14 years after their launch. Neither the TARGIT-A trial nor the ELIOT trial results have changed the current clinical practice for the use of IORT. The in-breast local recurrence rate (LRR) after IORT met the pre-specified non-inferiority margins in both trials and was 3.3% in TARGIT-A and 4.4% in the ELIOT trial. In both trials, the pre-specified estimates for local recurrence (LR) with external beam radiation therapy (EBRT) significantly overestimated actual LRR. In the TARGIT-A trial, LR with EBRT was estimated at the outset to be 6%, and in the ELIOT trial, it was estimated to be 3%. Surprisingly, LRR in the EBRT groups has been found to be significantly lower, 1.3% in the EBRT arm of the TARGIT-A and 0.4% in the EBRT arm of the ELIOT trial, respectively. Median follow-up was 2.4 years for the TARGIT-A trial and 5.8 years for the ELIOT trial. However, the initial cohort of patients in the TARGIT-A trial (reported in 2010) now have a median follow-up of 3.8 years and data on LR were available at 5 years follow-up on 35% of patients (18% who received IORT). Although further follow-up will increase confidence with the data, it will also further delay clinical implementation. By carefully weighing the risks and benefits of a single-fraction radiation treatment with patients, IORT should be offered within agreed and strict protocols. Patients deemed at low risk of LR or those deemed suitable for partial breast irradiation, according to the GEC-ESTRO and ASTRO recommendations, could be considered as candidates for IORT. These guidelines apply to all partial breast irradiation techniques, and more specific guidelines for IORT would assist clinicians.

Magnetic Advances in Cancer Surgery

Sentinel lymph node biopsy (SLNB) provides prognostic information in the management of solid tumours. Currently, the ‘combined technique’ using radioisotope and blue dye is considered the ‘gold standard’. This technique has drawbacks due to radioisotope dependence and adverse reactions to blue dye. Novel alternatives have been developed, but the established ‘gold standard’ method for SLNB has not changed. This chapter covers the clinical experience with the magnetic technique, which was developed as an alternative to radioisotope dependence for SLNB in breast cancer. It also discusses its application to other cancers and assesses the published literature for current and potential future work. The magnetic technique has been proven to be non-inferior to the combined technique for SLNB in breast cancer and has consequently been extended to concurrent breast lesion localisation and SLNB in melanoma. Superparamagnetic iron oxide (SPIO)-enhanced MRI has proven applications in axillary staging of breast cancer and could prove a viable, non-invasive alternative to SLNB. The magnetic technique has demonstrated promising results when applied to cancer surgery. Further assessment within well-constructed randomised controlled trials is now necessary to bring this innovative application into routine clinical practice.