Muneer Ahmed

Novel techniques for sentinel lymph node biopsy in breast cancer: a systematic review

The existing standard for axillary lymph node staging in breast cancer patients with a clinically and radiologically normal axilla is sentinel lymph node biopsy with a radioisotope and blue dye (dual technique). The dependence on radioisotopes means that uptake of the procedure is limited to only about 60% of eligible patients in developed countries and is negligible elsewhere. We did a systematic review to assess three techniques for sentinel lymph node biopsy that are not radioisotope dependent or that refine the existing method: indocyanine green fluorescence, contrast-enhanced ultrasound using microbubbles, and superparamagnetic iron oxide nanoparticles. Our systematic review suggested that these new methods for sentinel lymph node biopsy have clinical potential but give high levels of false-negative results. We could not identify any technique that challenged the existing standard procedure. Further assessment of these techniques against the standard dual technique in randomised trials is needed.

Radioactive seed localisation (RSL) in the treatment of non-palpable breast cancers: Systematic review and meta-analysis

INTRODUCTION This systematic review compares the outcomes of radioactive seed localisation (RSL) versus standard wire-guided localisation (WGL) in the management of non-palpable breast cancers. METHODS We performed a literature search of PubMed, EMBASE and the Cochrane database to identify clinical studies using RSL. Included studies examined invasive breast cancer and reported objective pathological outcome measurements. Quantitative data analyses were performed. RESULTS 197 papers were identified with eight being clinically relevant to our study. From these eight studies there was only one identified as being a randomised controlled trial (RCT) and four as cohort studies having a control WGL group and included in the quantitative analysis. This provided an overall combined odds ratio (OR) 0.51 (95% CI, 0.36-0.72; z = 3.88; p = 0.0001) for involved surgical margin status; OR, 0.47 (95% CI, 0.33-0.69; z = 3.96; p < 0.0001) for re-operation rates and mean difference (MD) -1.32 (95% CI, -2.32, -0.32; z = 2.58; p = 0.01) for operative time favouring RSL over WGL. In the case of volume of specimens excised, MD 1.46; (95% CI, -22.35, 25.26; z = 0.12; p = 0.90) showing no statistical significance for volume of tissue excised in specimens between the two groups. CONCLUSIONS The results of this systematic review demonstrate a statistically significant benefit of RSL over the gold standard of WGL in terms of involved margin status, re-operation rates and reduced operative time but no statistically significant difference with WGL in terms of volume of tissue excised in the treatment of non-palpable breast cancers. Adequately powered, multicentre RCTs are needed to validate these results.

Systematic review of high-intensity focused ultrasound ablation in the treatment of breast cancer

A systematic review was undertaken to assess the clinical efficacy of non‐invasive high‐intensity focused ultrasound (HIFU) ablation in the treatment of breast cancer.

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.

The Role of Magnetic Nanoparticles in the Localization and Treatment of Breast Cancer

The role of magnetic nanoparticles (MNPs) in medical applications is rapidly developing. Advances in nanotechnology are bringing us closer to the development of dual and multifunctional nanoparticles that are challenging the traditional distinction between diagnostic and treatment agents. The current use of MNPs in breast cancer falls into four main groups: (1) imaging of primary and metastatic disease, (2) sentinel lymph node biopsy (SLNB), (3) drug delivery systems, and (4) magnetic hyperthermia. The current evidence for the use of MNPs in these fields is mounting, and potential cutting-edge clinical applications, particularly with relevance to the fields of breast oncological surgery, are emerging.

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.

Preclinical studies of the role of iron oxide magnetic nanoparticles for nonpalpable lesion localization in breast cancer

BACKGROUND One-third of all breast cancers are present as clinically nonpalpable lesions. The current gold standard treatment is surgical excision by wire-guided localization. This technique has patient, technical, and scheduling drawbacks. Alternatives exist but depend on radioisotopes with their legislative and waste management issues. Magnetic nanoparticles (MNPs) have already been successfully used for sentinel lymph node biopsy in breast cancer. We therefore aimed to determine the feasibility of using iron oxide MNPs and a handheld magnetometer for the localization of nonpalpable breast cancers using a preclinical model. METHODS We constructed phantom models to assess the relationship between the handheld magnetometer peak readings and the variation in volume of iron oxide MNPs and their depth of injection in a series of porcine and avian tissue models. We also radiolabeled the MNPs with (99m)Tc and alendronate to create the conjugate (99m)Tc-dipicolylamine-alendronate-MNP and used nano-single-photon emission computed tomography-computed tomography to perform imaging to demonstrate localization properties. RESULTS The handheld magnetometer readings follow a linear relationship with variations in volume of magnetic tracer and a logarithmic relationship with variations in depth of injection of the magnetic tracer at a fixed volume. The application of derived quadratic equations from the R(2) curves of handheld magnetometer signal versus depth allowed calculation of the depth of injection of iron oxide MNPs from the handheld magnetometer readings and demonstrated the predictable behavior of the iron oxide MNPs and the handheld magnetometer. Satisfactory localization characteristics were confirmed in the phantoms and imaged using nano-single-photon emission computed tomography and computed tomography. CONCLUSIONS Iron oxide MNPs demonstrate positive localization characteristics in phantom models with predictable behavior patterns. We suggest that the use of MNPs provides a potential technique for the localization of nonpalpable breast lesions and deserves further exploration in animal and human feasibility studies.

Why should breast surgeons use ultrasound

Portable ultrasound is now used in a variety of clinical settings by specialties outside of radiology. Despite increased accessibility to ultrasound, the overall performance of ultrasound by breast surgeons is consistently low. We discuss the reasons why this is unacceptable for future patient care and answer the question, ‘Why should breast surgeons use ultrasound?’ We reviewed the literature for evidence assessing the outcomes of breast surgeon-performed ultrasound both intra-operatively and in the outpatient department. Intra-operative ultrasound performed by surgeons reduces re-excision rates in breast-conserving surgery. Outpatient-based ultrasound performed by surgeons frees up the resources of radiology departments, allowing them to focus upon patients requiring more complex diagnostic and interventional procedures. For surgeons to competently perform intra-operative and outpatient-based ultrasound, a period of formal ultrasound training is necessary to acquire knowledge of ultrasound skills and techniques. This should be followed by a period of mentorship and supervised training with an experienced breast radiologist. Breast surgeon-performed ultrasound is beneficial to the multi-disciplinary care of breast cancer patients. To further improve multidisciplinary care, breast surgeons and radiologists should work more collaboratively to optimise imaging applications both in the operating theatre and outpatient department. Current advances in therapeutic percutaneous techniques are of interest to both surgeons and radiologists. In future, a hybrid specialisation should be considered to incorporate accreditation in both specialties for breast interventional procedures.

What is the future of axillary surgery for breast cancer

The Z11 trial demonstrated a subgroup of patients with low axillary burden who do not benefit from axillary lymph node dissection (ALND) at short-term follow-up when treated with adjuvant whole-breast radiotherapy and systemic therapy. We consider the role of sentinel lymph node biopsy (SLNB) and look at and beyond the Z11 trial to consider further imaging studies, which may offer truly minimally invasive management of the axilla and relegate SLNB to the realms of history. Regional lymph node status provides information regarding staging, local control, and prognostic outcomes in all cancers. This information was provided in breast cancer by axillary lymph node dissection (ALND). This changed with the development of sentinel lymph node biopsy (SLNB) [1, 2]. Sentinel lymph nodes (SLNs) are defined as the first lymph nodes receiving lymphatic drainage from the primary tumour and therefore the most likely to harbour metastatic cancer via lymphatic spread. SLNB is now the standard of care in patients with a clinically and radiologically clear axilla in early-stage breast cancer.

ROLL versus RSL: toss of a coin?

The safety and benefits of radio-guided localization (RGL) versus wire-guided localization (WGL) surgery in the treatment of non-palpable breast cancers have been confirmed through several meta-analyses. RGL has become the standard of care in several institutions, although overall uptake has been slow. In view of this evidence supporting RGL, we believe that the future discussion is not of RGL versus WGL, but rather of what form of RGL will constitute best practice of care going forward. We therefore discuss the case for radio-guided occult lesion localization versus radioactive seed localization in the treatment of non-palpable breast cancers, is it really a toss of a coin?