Magnetic Seed vs Guidewire Breast Cancer Localization With Magnetic Lymph Node Detection: A Randomized Clinical Trial.

Importance: Guidewires have been the standard for breast lesion localization but pose operative and logistic challenges. Paramagnetic seeds have shown promising results, but to the authors' knowledge, no randomized comparison has been performed. Objective: To determine whether the combination of a paramagnetic seed and superparamagnetic iron oxide (SPIO) is equivalent to guidewire and SPIO for breast cancer localization and sentinel lymph node detection (SLND). Design, Setting, and Participants: This was a phase 3, pragmatic, equivalence, 2-arm, open-label, randomized clinical trial conducted at 3 university and/or community hospitals in Sweden from May 2018 to May 2022. Included in the study were patients with early breast cancer planned for breast conservation and SLND. Study data were analyzed July to November 2022. Interventions: Participants were randomly assigned 1:1 to a paramagnetic seed or a guidewire. All patients underwent SLND with SPIO. Main Outcomes and Measures: Re-excision rate and resection ratio (defined as actual resection volume / optimal resection volume). Results: A total of 426 women (median [IQR] age, 65 [56-71] years; median [IQR] tumor size, 11 [8-15] mm) were included in the study. The re-excision rate was 2.90% (95% CI, 1.60%-4.80%), and the median (IQR) resection ratio was 1.96 (1.15-3.44). No differences were found between the guidewire and the seed in re-excisions (6 of 211 [2.84%] vs 6 of 209 [2.87%]; difference, -0.03%; 95% CI, -3.20% to 3.20%; P = .99) or resection ratio (median, 1.93; IQR, 1.18-3.43 vs median, 2.01; IQR, 1.11-3.47; P = .70). Overall SLN detection was 98.6% (95% CI, 97.1%-99.4%) with no differences between arms (203 of 207 [98.1%] vs 204 of 206 [99.0%]; difference, -0.9%; 95% CI, -3.6% to 1.8%; P = .72). More failed localizations occurred with the guidewire (21 of 208 [10.1%] vs 4 of 215 [1.9%]; difference, 8.2%; 95% CI, 3.3%-13.2%; P < .001). Median (IQR) time to specimen excision was shorter for the seed (15 [10-22] minutes vs 18 [12-30] minutes; P = .01), as was the total operative time (69 [56-86] minutes vs 75.5 [59-101] minutes; P = .03). The experience of surgeons, radiologists, and surgical coordinators was better with the seed. Conclusions and Relevance: The combination of SPIO and a paramagnetic seed performed comparably with SPIO and guidewire for breast cancer conserving surgery and resulted in more successful localizations, shorter operative times, and better experience. Trial Registration: ISRCTN.org Identifier: ISRCTN11914537.

Magnetic-Guided Axillary UltraSound (MagUS) Sentinel Lymph Node Biopsy and Mapping in Patients with Early Breast Cancer. A Phase 2, Single-Arm Prospective Clinical Trial.

Lymph Node Dissection (SLND) is standard of care for diagnosing sentinel lymph node (SLN) status in patients with early breast cancer. Study aim was to determine whether the combination of Superparamagnetic iron oxide nanoparticles (SPIO) MRI-lymphography (MRI-LG) and a Magnetic-guided Axillary UltraSound (MagUS) with biopsy can allow for minimally invasive, axillary evaluation to de-escalate surgery. Patients were injected with 2 mL of SPIO and underwent MRI-LG for SN mapping. Thereafter MagUS and core needle biopsy (CNB) were performed. Patients planned for neoadjuvant treatment, the SLN was clipped and SLND was performed after neoadjuvant with the addition of isotope. During surgery, SLNs were controlled for signs of previous biopsy or clip. The primary endpoint was MagUS SLN detection rate, defined as successful SLN detection of at least one SLN of those retrieved in SLND. In 79 patients, 48 underwent upfront surgery, 12 received neoadjuvant and 19 had recurrent cancer. MagUS traced the SLN in all upfront and neoadjuvant cases, detecting all patients with macrometastases (n = 10). MagUS missed only one micrometastasis, outperforming baseline axillary ultrasound AUS (AUC: 0.950 vs. 0.508, p < 0.001) and showing no discordance to SLND (p = 1.000). MagUS provides the niche for minimally invasive axillary mapping that can reduce diagnostic surgery.

Long-Term Outcome After Retro-Areolar Versus Peri-Tumoral Injection of Superparamagnetic Iron Oxide Nanoparticles (SPIO) for Sentinel Lymph Node Detection in Breast Cancer Surgery.

BACKGROUND/OBJECTIVE: SPIO is effective in sentinel node (SN) detection. No nuclear medicine department is needed, and no allergic reactions have occurred. This study aimed to compare retro-areolar and peri-tumoral SPIO injections regarding skin staining, detection rates and number of SNs. METHODS: Data on staining size, intensity and cosmetic outcome (0-5; 0 = no problem) were collected by telephone interviews with 258 women undergoing breast conservation. SN detection and the number of SNs were prospectively registered in 332 women. RESULTS: After retro-areolar and peri-tumoral injections, 67.3% and 37.8% (p < 0.001) developed skin staining, with remaining staining in 46.2 vs. 9.4% after 36 months (p < 0.001). Initial mean size was 16.3 vs. 6.8 cm (p < 0.001) and after 36 months, 6.6 vs. 1.8 cm2 (p < 0.001). At 75.1% of 738 interviews, staining was reported paler. After retro-areolar injections, cosmetic outcome scored worse for 2 years. The mean (median) scores were 1.3(0) vs. 0.5(0) points, and 0.2(0) vs. 0.1(0) points, at 12 and 36 months, respectively. Overall detection rates were 98.3% and 97.4% (p = 0.43) and the number of SNs 1.35 vs. 1.57 (p = 0.02) after retro-areolar and peri-tumoral injections. Injection, regardless of type, 1-27 days before surgery increased detection rates with SPIO, 98.0% vs. 94.2% (p = 0.06) ,and SN numbers, 1.56 vs. 1.27 (p = 0.003). CONCLUSION: SPIO is effective and facilitates planning for surgery. Peri-tumoral injection reduced staining with a similar detection rate. Staining was not considered a cosmetic problem among most women. Injecting SPIO 1-27 days before surgery increased the detection rate by 3.8% and increased the number of SNs by 0.3.

A combined, totally magnetic technique with a magnetic marker for non-palpable tumour localization and superparamagnetic iron oxide nanoparticles for sentinel lymph node detection in breast cancer surgery.

BACKGROUND: Surgery for non-palpable breast cancer may often be a challenging procedure. Recently, a magnetic seed (Magseed®) used for tumour localization has been developed. Superparamagnetic iron oxide nanoparticles (SPIO) for sentinel lymph node (SN) detection is a novel tracer that may be injected up to four weeks preoperatively. This study is the first combining the magnetic seed and SPIO. MATERIAL AND METHODS: Patients planned for breast conserving surgery and SN-biopsy (SNB) were recruited from two units in Sweden. Patients underwent lesion localization with Magseed® and SPIO injection (Magtrace™) by the breast radiologist in the preoperative period. Feasibility of successful lesion localization and excision together with a successful SNB detection was evaluated. Seed migration, number of SNs, specimen volume and calculated resection ratio (CRR) were reported.A survey of the physicians' experience was conducted. RESULTS: Localization was performed at a median of three days before surgery (range 0-25). All 32 patients underwent microscopically radical resection with a CRR of 1.49. No seed migration was noticed. SNB was successful in all patients. A median of two SNs was retrieved. Radiologists and surgeons reported the procedure easy to learn and outperformed guidewire localization in terms of localization and excision time. They thought the technique facilitated planning localization and surgery. CONCLUSIONS: The combined magnetic technique provided accuracy in tumour localization and SN detection without excess tissue excision and with promising results for flexibility in delivery of care. Larger studies are needed to confirm these findings.

Ductal Breast Carcinoma In Situ: Mammographic Features and Its Relation to Prognosis and Tumour Biology in a Population Based Cohort.

Casting-type calcifications and a histopathological picture with cancer-filled duct-like structures have been presented as breast cancer with neoductgenesis. We correlated mammographic features and histopathological neoductgenesis with prognosis in a DCIS cohort with long follow-up. Mammographic features were classified into seven groups according to Tabár. Histopathological neoductgenesis was defined by concentration of ducts, lymphocyte infiltration, and periductal fibrosis. Endpoints were ipsilateral (IBE) in situ and invasive events. Casting-type calcifications and neoductgenesis were both related to high nuclear grade, ER- and PR-negativity, and HER2 overexpression but not to each other. Casting-type calcifications and neoductgenesis were both related to a nonsignificant lower risk of invasive IBE, HR 0.38 (0.13-1.08) and 0.82 (0.29-2.27), respectively, and the HR of an in situ IBE was 0.90 (0.41-1.95) and 1.60 (0.75-3.39), respectively. Casting-type calcifications could not be related to a worse prognosis in DCIS. We cannot explain why a more aggressive phenotype of DCIS did not correspond to a worse prognosis. Further studies on how the progression from in situ to invasive carcinoma is driven are needed.

Breast cancer with neoductgenesis: histopathological criteria and its correlation with mammographic and tumour features.

Introduction. Breast cancer with mammographic casting type calcifications, high grade DCIS with an abnormal number of ducts, periductal desmoplastic reaction, lymphocyte infiltration, and tenascin-C (TN-C) overexpression has been proposed to represent a more aggressive form of breast cancer and has been denominated as breast cancer with neoductgenesis. We developed histopathological criteria for neoductgenesis in order to study reproducibility and correlation with other tumour markers. Methods. 74 cases of grades 2 and 3 DCIS, with or without an invasive component, were selected. A combined score of the degree(s) of concentration of ducts, lymphocyte infiltration, and periductal fibrosis was used to classify cases as showing neoductgenesis, or not. Diagnostic reproducibility, correlation with tumour markers, and mammographic features were studied. Results. Twenty-three of 74 cases were diagnosed with neoductgenesis. The kappa value between pathologists showed moderate reproducibility (0.50) (95% CI; 0.41-0.60). Neoductgenesis correlated significantly with malignant type microcalcifications and TN-C expression (P = 0.008 and 0.04) and with ER, PR, and HER2 status (P < 0.00001 for all three markers). Conclusions. We developed histological criteria for breast cancer with neoductgenesis. Neoductgenesis, by our applied histopathological definition was related to more aggressive tumour biology and malignant mammographic calcifications.

Non-echo planar diffusion-weighted MRI increases follow-up accuracy after one-step step canal wall-down obliteration surgery for cholesteatoma.

CONCLUSION: Non-echo planar (non-EPI) diffusion-weighted (DW) magnetic resonance imaging (MRI) increases the number of detected cholesteatoma after one-step canal wall-down (CWD) obliteration surgery for cholesteatoma compared with clinical evaluation alone. OBJECTIVE: To evaluate the use of DW-MRI for detection of cholesteatoma after surgical treatment using a CWD obliteration technique. METHODS: Thirty-eight adult patients (41 ears) treated with an identical one-step CWD obliteration surgical technique were included in a prospective and blinded study. All patients were investigated with non-EPI and EPI DW-MRI 1-9 months after the clinical examination. Follow-up time after primary surgery varied between 10 and 234 months. DW-MRI was assessed by two neuroradiologists and compared with clinical results. Inter-rater agreement was calculated. Positive non-EPI DW-MRI cases underwent revision surgery within 18-159 days after imaging. RESULTS: Seven of 41 cases were evaluated as positive for cholesteatoma on non-EPI DW-MRI. Since one patient refused surgery six of these seven cases underwent surgical revision and all were verified. There was agreement between clinical and non-EPI findings in five of eight cases. EPI findings correlated poorly with non-EPI and clinical findings. Inter-rater agreement (Cohen's kappa) was 0.91 for non-EPI DW-MRI (p < 0.001) and -0.062 for EPI DW-MRI (p = 0.43).

Effectiveness of population-based service screening with mammography for women ages 40 to 49 years: evaluation of the Swedish Mammography Screening in Young Women (SCRY) cohort.

BACKGROUND: The effectiveness of mammography screening for women ages 40 to 49 years still is questioned, and few studies of the effectiveness of service screening for this age group have been conducted. METHODS: Breast cancer mortality was compared between women who were invited to service screening at ages 40 to 49 years (study group) and women in the same age group who were not invited during 1986 to 2005 (control group). Together, these women comprise the Mammography Screening of Young Women (SCRY) cohort, which includes all Swedish counties. A prescreening period was defined to facilitate a comparison of mortality in the absence of screening. The outcome measure was refined mortality, ie, breast cancer death for women who were diagnosed during follow-up at ages 40 to 49 years. Relative risks (RRs) with 95% confidence intervals (CIs) were estimated. RESULTS: There was no significant difference in breast cancer mortality during the prescreening period. During the study period, there were 803 breast cancer deaths in the study group (7.3 million person-years) and 1238 breast cancer deaths in the control group (8.8 million person-years). The average follow-up was 16 years. The estimated RR for women who were invited to screening was 0.74 (95% CI, 0.66-0.83), and the RR for women who attended screening was 0.71 (95% CI, 0.62-0.80). CONCLUSIONS: In this comprehensive study, mammography screening for women ages 40 to 49 years was efficient for reducing breast cancer mortality.