Optimising magnetic sentinel lymph node biopsy in an in vivo porcine model

The magnetic technique for sentinel lymph node biopsy (SLNB) has been evaluated in several clinical trials. An in vivo porcine model was developed to optimise the magnetic technique by evaluating the effect of differing volume, concentration and time of injection of magnetic tracer. A total of 60 sentinel node procedures were undertaken. There was a significant correlation between magnetometer counts and iron content of excised sentinel lymph nodes (SLNs) (r = 0.82; P < 0.001). Total number of SLNs increased with increasing volumes of magnetic tracer (P < 0.001). Transcutaneous magnetometer counts increased with increasing time from injection of magnetic tracer (P < 0.0001), plateauing within 60 min. Increasing concentration resulted in higher iron content of SLNs (P = 0.006). Increasing magnetic tracer volume and injecting prior to surgery improve transcutaneous ‘hotspot’ identification but very high volumes, increase the number of nodes excised. From the Clinical Editor Sentinel lymph node biopsy (SLNB) is the standard of care for axillary staging of breast cancer patients. Although the current gold standard technique is the combined injection of technetium-labelled nanocolloid and blue dye into the breast, the magnetic technique, using superparamagnetic carboxydextran-coated iron oxide (SPIO), has also been demonstrated as a feasible alternative. In this article, the authors set up to study factors in order to optimize the magnetic tracers. Graphical abstract Variable volumes and concentrations of a magnetic tracer were injected into the third inguinal mammary gland bilaterally in an in vivo porcine model (1) allowing the performance of magnetic sentinel lymph node biopsy of draining inguinal nodes (2). The harvested nodes were ‘darkly stained’ for iron uptake and ‘hot’ for magnetometer counts (3). The iron was deposited within the cortex and subcapsular space – visible as blue using PERL’s staining – on histopathology (4) and was quantified using quantitative magnetometry and a validated iron-grading scale

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

BACKGROUND: 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. METHODS: An ultrasound‐guided intratumoral injection of magnetic tracer (0·5 ml) was performed in a protocol‐driven predefined minimum of ten patients with palpable breast cancer to assess the ability of the magnetic tracer safely to localize the tumour at the site of injection and concurrently drain to the lymphatics. Once successful lesion localization had been confirmed (peak magnetometer count retained at the centre of the tumour), the technique was undertaken in a further 20 patients with non‐palpable breast cancers awaiting wide local excision and SLNB. All patients underwent SLNB with both the magnetic and standard dual (radioisotope and Patent Blue V dye) techniques. RESULTS: Thirty‐two patients were recruited, of whom 12 (1 with bilateral disease) presented with palpable and 20 with non‐palpable breast cancer. Peak magnetometer counts were retained at the tumour centre in all palpable (13) and non‐palpable (20) breast cancers. Re‐excisions for involved margins were necessary in two patients with non‐palpable breast cancers. The sentinel lymph node identification rates were 28 of 33 procedures for the magnetic technique alone, 32 of 33 for the magnetic technique combined with blue dye, and 32 of 33 for the standard dual technique. CONCLUSION: Magnetic lesion localization is feasible, with intratumoral magnetic tracer injection combined with a periareolar injection of blue dye for subsequent SNLB

Intraoperative radiotherapy in early breast cancer

Abstract Background 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. Methods This article reviews trials of IORT delivered with different techniques and devices. Results IORT is a very attractive option for delivering radiotherapy, reducing the traditional fractionated treatment to a single fraction administered at the time of surgery. IORT has been shown to be associated with reduced toxicity and has several potential benefits over EBRT. Only two randomized clinical trials have been published to date. The TARGIT-A and ELIOT trials have demonstrated that IORT is associated with a low rate of local recurrence, although higher than that after EBRT (TARGIT-A: 3·3 versus 1·3 per cent respectively, P = 0·042; ELIOT: 4·4 versus 0·4 per cent, P &amp;lt; 0·001). However, the local recurrence rate for IORT fell within the predefined 2·5 per cent non-inferiority margin in TARGIT-A, and the 7·5 per cent equivalence margin in ELIOT. Conclusion Longer follow-up data from existing trials, optimization of patient criteria and cost-effectiveness analyses are needed. Based on the current evidence, IORT can be offered as an alternative to EBRT to selected patients within agreed protocols, and outcomes should be monitored within national registries. </jats:sec

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

Joost J Pouw,1,* Muneer Ahmed,2,* Bauke Anninga,2 Kimberley Schuurman,1 Sarah E Pinder,2 Mieke Van Hemelrijck,3 Quentin A Pankhurst,4,5 Michael Douek,2 Bennie ten Haken1 1MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, the Netherlands; 2Research Oncology, Division of Cancer Studies, King&rsquo;s College London, Guy&rsquo;s Hospital, London, UK; 3Cancer Epidemiology Group, Division of Cancer Studies, King&rsquo;s College London, London, UK; 4Healthcare Biomagnetics Laboratory, University College London, London, UK; 5Institute of Biomedical Engineering, University College London, London, UK *These authors contributed equally to&nbsp;this work 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&nbsp;nm; Sienna+&reg;, dH =59&nbsp;nm; and ferumoxide, dH =111&nbsp;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 &ldquo;hotspots&rdquo; were present in 12/12 cases within 30&nbsp;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. Keywords: superparamagnetic iron oxide, breast cancer, magnetic tracer, ferumoxytol, ferumoxide, Sienna+&reg

Magnetic sentinel lymph node biopsy and localization properties of a magnetic tracer in an in vivo porcine model

The standard for the treatment of early non-palpable breast cancers is wide local excision directed by wire-guided localization and sentinel lymph node biopsy (SLNB). This has drawbacks technically and due to reliance upon radioisotopes. We evaluated the use of a magnetic tracer for its localization capabilities and concurrent performance of SLNB using a handheld magnetometer in a porcine model as a novel alternative to the current standard. Ethical approval by the IRCAD Ethics Review Board, Strasbourg (France) was received. A magnetic tracer was injected in varying volumes (0.1-5 mL) subcutaneously into the areolar of the left and right 3rd inguinal mammary glands in 16 mini-pigs. After 4 h magnetometer counts were taken at the injection sites and in the groins. The magnetometer was used to localize any in vivo signal from the draining inguinal lymph nodes. Magnetic SLNB followed by excision of the injection site was performed. The iron content of sentinel lymph nodes (SLNs) were graded and quantified. All excised specimens were weighed and volumes were calculated. Univariate analyses were performed to evaluate correlation. Magnetic SLNB was successful in all mini-pigs. There was a significant correlation (r = 0.86; p < 0.01) between magnetometer counts and iron content of SLNs. Grading of SLNs on both H&E and Perl's staining correlated significantly with the iron content (p = 0.001; p = 0.003) and magnetometer counts (p < 0.001; p = 0.004). The peak counts corresponded to the original magnetic tracer injection sites 4 h after injection in all cases. The mean volume and weight of excised injection site specimens was 2.9 cm(3) (SD 0.81) and 3.1 g (SD 0.85), respectively. Injection of ≥0.5 mL magnetic tracer was associated with significantly greater volume (p = 0.05) and weight of excision specimens (p = 0.01). SLNB and localization can be performed in vivo using a magnetic tracer. This could provide a viable alternative for lesion localization and concurrent SLNB in the treatment of non-palpable breast cancer

Health-Related Quality of Life After Completion of Successful Treatment for Childhood Cancer

Background. Previous studies have assessed health-related quality of life (HRQOL) during several treatment stages in children with cancer, but there is limited knowledge about HRQOL shortly after completing therapy. This study determined HRQOL of children with cancer shortly after the end of successful treatment compared with normative values. Procedure. Several age-specific HRQOL questionnaires were administered: the ITQOL (generic, proxy-report, 0-4 years), CHQ PF 50 (generic, proxy-report, 5-7 years), Kidscreen (generic, self-report, 8-18 years) and Disabkids (chronic generic, self-report, 8-18 years). Results. Children with cancer (N =191, mean age 9.25, SD 5.06, 47.1% female) participated. Physical well-being was affected for all ages. Compared to normative values 0- to 7-year-olds were rated significantly lower on the majority of the scales. In addition, 12- to 18-year-olds had significantly better HRQOL than the norm on social scales. Compared to chronically ill norms, 8- to 18-year-olds demonstrated no differences, except for 12- to 18-year-olds who experienced significantly more physical limitations. Additionally, we found that HRQOL of parents of 0- to 7-year-olds was poorer than the norm. Conclusion. HRQOL in children with cancer and their parents can be impaired compared with the norm. Therefore, HRQOL should be monitored in clinical practice to make paediatric oncologists aware of these problems. For young children, we recommend checking whether certain HRQOL problems can be explained by parental worries. For older children and adolescents, paediatric oncologists need to consider social desirability and the child's adaptive style. Pediatr Blood Cancer 2011;56:646-653. (C) 2010 Wiley-Liss, In

Optimising magnetic sentinel lymph node biopsy in an in vivo porcine model

The magnetic technique for sentinel lymph node biopsy (SLNB) has been evaluated in several clinical trials. An in vivo porcine model was developed to optimise the magnetic technique by evaluating the effect of differing volume, concentration and time of injection of magnetic tracer. A total of 60 sentinel node procedures were undertaken. There was a significant correlation between magnetometer counts and iron content of excised sentinel lymph nodes (SLNs) (r = 0.82; P < 0.001). Total number of SLNs increased with increasing volumes of magnetic tracer (P < 0.001). Transcutaneous magnetometer counts increased with increasing time from injection of magnetic tracer (P < 0.0001), plateauing within 60 min. Increasing concentration resulted in higher iron content of SLNs (P = 0.006). Increasing magnetic tracer volume and injecting prior to surgery improve transcutaneous ‘hotspot’ identification but very high volumes, increase the number of nodes excise