Localization Techniques for Non-Palpable Breast Lesions: Current Status, Knowledge Gaps, and Rationale for the MELODY Study (EUBREAST-4/iBRA-NET, NCT 05559411).

BACKGROUND: Surgical excision of a non-palpable breast lesion requires a localization step. Among available techniques, wire-guided localization (WGL) is most commonly used. Other techniques (radioactive, magnetic, radar or radiofrequency-based, and intraoperative ultrasound) have been developed in the last two decades with the aim of improving outcomes and logistics. METHODS: We performed a systematic review on localization techniques for non-palpable breast cancer. RESULTS: For most techniques, oncological outcomes such as lesion identification and clear margin rate seem either comparable with or better than for WGL, but evidence is limited to small cohort studies for some of the devices. Intraoperative ultrasound is associated with significantly higher negative margin rates in meta-analyses of randomized clinical trials (RCTs). Radioactive techniques were studied in several RCTs and are non-inferior to WGL. Smaller studies show higher patient preference towards wire-free localization, but little is known about surgeons' and radiologists' attitudes towards these techniques. CONCLUSIONS: Large studies with an additional focus on patient, surgeon, and radiologist preference are necessary. This review aims to present the rationale for the MELODY (NCT05559411) study and to enable standardization of outcome measures for future studies.

Preoperative non-palpable breast lesion localization, innovative techniques and clinical outcomes in surgical practice: A systematic review and meta-analysis.

Pre-operative localization of non-palpable breast lesions with non-wired non-ionizing (NWNI) techniques may improve clinical outcomes as reoperation rate, cosmetic outcome and contribute to organizational aspects improvement in breast-conserving surgery (BCS). However only limited literature is available and clinical studies involving these forefront devices are often small and non-randomized. Furthermore, there is a lack of consensus on free margins and cosmetic outcomes definitions. The objective of the present meta-analysis was to determine the crude clinical outcomes reported for the NWNI techniques on BCS. A literature search was performed of PubMed, Embase and Scopus databases up to February 2021 in order to select all prospective or retrospective clinical trials on pre-operative breast lesion localization done with NWNI devices. All studies were assessed following the PRISMA recommendations. Continuous outcomes were described in averages corrected for sample size, while binomial outcomes were described using the weighted average proportion. Twenty-seven studies with a total of 2103 procedures were identified. The technique is consolidated, showing for both reflectors' positioning and localization nearly the 100% rate of success. The re-excision and clear margins rates were 14% (95% CI, 11-17%) and 87% (80-92%), respectively. Overall, positive margins rates were 12% (8-17%). In studies that compared NWNI and wire localization techniques, positive margin rate is lower for the first techniques (12%, 6-22% vs 17%, 12-23%) and re-excision rate is slightly higher using the latter (13%, 9-19% vs 16%, 13-18%). Pre-operative NWNI techniques are effective in the localization of non-palpable breast lesions and are promising in obtaining clear (or negative) margins minimizing the need for re-excision and improving the cosmetic outcomes. Randomized trials are needed to confirm these findings.

Radioactive seed localisation of non-palpable lymph nodes - A feasibility study.

BACKGROUND: Radioactive seed localisation (RSL) is a preoperative localisation method using a small titanium seed containing iodine-125. The method is increasingly applied for localising non-palpable lesions in the treatment of breast cancer. We believe that RSL has the potential to be used in various surgical specialties. The aim of this feasibility study was to test RSL as a preoperative localisation of non-palpable lymph nodes. METHODS: Between November 24, 2015 and October 26, 2016, 15 patients with suspicious lymph nodes on imaging were included in the study. The lymph nodes were located in the axillary region (n = 9), the head and neck region (n = 5) and the inguinal region (n = 1). The seeds were placed in the centre of the lymph node, in the capsule or just outside the capsule guided by ultrasound. During surgery, incision and localisation of the lymph nodes were performed based on the auditory signal of the gamma probe. After excision, lymph nodes including iodine seeds were sent for pathologic examination and the seeds were returned to the Department of Nuclear Medicine. RESULTS: The non-palpable lymph nodes were all successfully marked using ultrasound. The lymph nodes were successfully localised and excised during surgery, and the procedure was performed without complications in the majority of the cases. CONCLUSION: Localisation of suspicious non-palpable lymph nodes using RSL is feasible. RSL may ease the surgical procedure, minimise trauma to the surrounding tissue and ultimately benefit the patient. Future prospective studies are necessary to determine the further use of RSL within different surgical specialties.

Localización radioguiada de lesiones no palpables y ganglio centinela en estadios iniciales de Cáncer de Mama (snoll). Primera experiencia en el Hospital Italiano de Buenos Aires / Radioguided non-palpable lesion localization and sentinel lymph node mapping (snoll) at early breast carcinoma. First experience at Hospital Italiano de Buenos Aires

Introducción Actualmente, entre un 25 y un 35% de los cánceres de mama se diagnostican como lesiones no palpables. La detección de lesiones cada vez más pequeñas exige el desarrollo de nuevas técnicas prequirúrgicas de marcación y localización. Presentamos la experiencia del Hospital Italiano de Buenos Aires con la técnica de localización radioguiada de lesiones no palpables y ganglio centinela (snoll). Objetivos El objetivo de este trabajo es describir las características clínico-patológicas de las pacientes sometidas a dicha técnica y las ventajas, desventajas, complicaciones y resultados en términos de márgenes libres, tasa de retumorectomías, volumen tumoral resecado y tiempo quirúrgico. Material y método Se trata de un estudio observacional, retrospectivo. Se incluyeron todas las pacientes con carcinomas no palpables en quienes se llevó a cabo la técnica de snoll entre el 1 de agosto de 2016 y el 4 de mayo de 2017. Resultados Se incluyó un total de 25 pacientes, todas con diagnóstico previo de carcinoma de mama invasor a través de una punción histológica. Utilizando la técnica snoll, se logró identificar la lesión de mama en el 96% de las pacientes. En el 100% de las pacientes, los márgenes quirúrgicos estaban libres de lesión, por lo que no se realizaron retumorectomías. Se identificó el 100% de los ganglios centinelas, 76% mediante la técnica snoll y 24% mediante la inyección previa del colorante Azul Patente. Conclusiones La técnica snoll demostró ser una técnica sencilla, que mejora el confort de la paciente y que presenta resultados comparables con las técnicas tradicionales. Si bien se trata de una primera experiencia, son alentadores los resultados en términos de márgenes libres, tiempo quirúrgico y volumen resecados.

Introduction Currently, about 25 to 35% of all breast tumors are diagnosed at a nonpalpable stage. The increasing ability to detect small lesions consequently demands the development of novel technology for preoperative lesion identification and intraoperative localization. In this study, we present our initial experience using Sentinel Node Occult Lesion Localization (snoll) at the Hospital Italiano de Buenos Aires. Objectives The objective of this study is to describe clinical and pathological characteristics of patients who were submitted to snoll technique and the advantages and disadvantages, complications and results in terms of tumor-free margins, subsequent surgery rate, total specimen volume and surgical time. Materials and method This is a retrospective, observational study. We included all patients with non-palpable breast cancer who were submitted to surgery and snoll technique between August 1st, 2016 and March 14th, 2017. Results A total of 25 patients were included in this study. All patients had previous diagnosis of invasive breast cancer by core needle biopsy. The breast lesion was correctly identified in 96% of patients through snoll. Surgical margins were tumor-free in all patients. No patients required subsequent surgery. All sentinel nodes were correctly identified. In 76% of cases, snoll was sufficient and in 24% additional injection of patent blue was required. Conclusions In our experience, snoll has proven to be a simple technique that improves patient comfort and shows comparable results when compared to traditional identification methods. Although these are our initial results, we believe our findings to be promising in terms of adequacy of margins, surgical time and total specimen volume.

Biópsia excisional por agulhamento de lesões mamárias não palpáveis: indicações, técnica e resultados / Excisonal biopsy with wirw localization of non palpable breast lesions: indicators, technique and results

Com o aumento do rastreamento mamográfico, identificam-se cada vez mais lesões menores e não palpáveis, surgindo a necessidade de localiza-las tanto para diagnóstico como para tratamento. Neste trabalho, descreveram-se a técnica e suas indicações e apresentaram-se os resultados dos casos de agulhamento do Serviço de Mastologia e Radiologia do Hospital de Clínicas de Porto Alegre (HCPA). Métodos: Avaliaram-se, retrospectivamente, 586 casos de agulhamento operados no período de 1995 a 2004. As indicações para o procedimento foram as alterações mamográficas de lesões não palpáveis, classificadas de acordo o sistema BIRADS. Resultados: A principal indicação cirúrgica foram as microcalcificações, num total de 373 casos (63,7%), seguidas de nódulos em 37,2%. A idade média das pacientes foi de 53 anos (23 a 82). O valor preditivo positivo (VPP) geral para malignidade foi de 0,30 (177/586 casos). As alterações funcionais benignas da mama (AFBMs) corresponderam ao diagnóstico mais comum (34,1%). Noventa e quatro por cento dos casos de carcinoma ductal in situ (CDIS) foram diagnosticados mamograficamente como microcalcificações. Conclusões: Considerando os dados apresentados e a experiência do serviço, a biópsia por agulhamento continua sendo o principal procedimento para diagnóstico e tratamento de lesões não palpáveis. Trata-se de um método seguro, porém não isento de riscos.

With the increasing use of mammography, more and smaller non- palpable lesions are found, bringing the need of localize them for diagnostic and even therapeutic purposes. We describe the surgical technique, indications and results with the well-known standard procedure of excision after wire localization. Method: We retrospectively evaluated the result of 586 wire localizations between 1995 and 2004. The indications for the procedure were non-palpable mammographic abnormalities classified according to BIRADS system. Results: The main indication for this procedure were microcalcifications in 63.7% of the cases (n=373), followed by lumps 37.2%. The mean age of these patients was 53 years (range 23- 82 years). We observed an overall positive predictive value (PPV) for malignancy of 0.30 (177/586 cases). Benign fybrocistic changes was found as the most common pathological diagnosis (34.1%). Ninety-four per cent of the ductal carcinoma in situ were detected mammographically as microcalcifications. Conclusions: The authors call attention for the use of a very careful and delicate surgical technique in order to achieve the best results. Our experience confirm that the wire-guided excision of non-palpable breast lesions is a safe and reliable diagnostic/therapeutic procedure.

Abordagem simultânea das lesões não palpáveis da mama e do linfonodo sentinela (SNOLL) / Simultaneous management of non-palpable breast lesion and sentinel lymph node (SNOLL)

As técnicas conjuntas da mastologia com auxílio da medicina nuclear representam um importante papel na atualidade. A investigação das lesões não palpáveis da mama por meio das cirurgias radioguiadas (ROLL), e a possibilidade da cirurgia conservadora da axila, por meio da análise do linfonodo sentinela (LS), são avanços tecnológicos disponíveis e cada vez mais utilizados na prática clínica. A utilização dessas duas técnicas conjugadas (SNOLL) procura associar as facilidades de ROLL com os benefícios do linfonodo sentinela, uma vez que o amplo uso dos métodos invasivos para diagnóstico do câncer de mama, tais como PAAF, core biopsy e mamotomia, permite o planejamento cirúrgico definitivo e simultâneo do tumor e da axila.

The multidiciplinary approach plays an important role in the evaluation and treatment of breast cancer. It included nuclear medicine in the last years.The radioguided ocult localization (ROLL) and the conservative surgery of the axilla (sentinel lymph node) are pratice of choice for managemente of many patients with breast cancer. The simultaneous use of both procedures (SNOLL) associates the facilities of the radioguided localization of the breast lesion and sentinel lymph node at the same surgery; it shows some benefits once the widespread use of interventional image techniques provide histologic diagnoses and makes possible the definitive surgical management of malignant lesions of the breast.