Efficacy and safety of onasemnogene abeparvovec for the treatment of patients with spinal muscular atrophy type 1: A systematic review with meta-analysis.

BACKGROUND: Onasemnogene abeparvovec has been approved for the treatment of spinal muscular atrophy 5q type 1 in several countries, which calls for an independent assessment of the evidence regarding efficacy and safety. OBJECTIVE: Conduct a meta-analysis to assess the efficacy and safety of onasemnogene abeparvovec in patients diagnosed with SMA type 1, based on the available evidence. METHODS: This article results from searches conducted on databases up to November 2022. Outcomes of interest were global survival and event-free survival, improvement in motor function and treatment-related adverse events. Risk of bias assessment and certainty of evidence were performed for each outcome. Proportional meta-analysis models were performed when applicable. RESULTS: Four reports of three open-label, non-comparative clinical trials covering 67 patients were included. Meta-analyses of data available in a 12-month follow-up estimate a global survival of 97.56% (95%CI: 92.55 to 99.86, I2 = 0%, n = 67), an event-free survival of 96.5% (95%CI: 90.76 to 99.54, I2 = 32%, n = 66) and a CHOP-INTEND score ≥ 40 points proportion of 87.28% (95%CI: 69.81 to 97.83, I2 = 69%, n = 67). Proportion of 52.64% (95%CI: 27.11 to 77.45, I2 = 78%, n = 67) of treatment-related adverse events was estimated. CONCLUSION: The results indicate a potential change in the natural history of type 1 SMA, but the methodological limitations of the studies make the real extent of the technology's long-term benefits uncertain.

Cost-Effectiveness of Onasemnogene Abeparvovec Compared With Nusinersen and Risdiplam in Patients With Spinal Muscular Atrophy Type 1 in Brazil: Custo-Efetividade do Onasemnogeno Abeparvoveque (AVXS-101) em Comparação ao Nusinersena e Risdiplam em Pacientes com Atrofia Muscular Espinhal Tipo 1 no Brasil.

OBJECTIVES: This study aimed to evaluate the cost-effectiveness of the onasemnogene abeparvovec in relation to nusinersen and risdiplam in the treatment of spinal muscular atrophy type 1 from the perspective of the Brazilian Unified Health System. METHODS: A Markov model was built on a lifetime horizon. Short-term data were obtained from clinical trials of the technologies and from published cohort survival curves (long term). Costs were measured in current 2022 local currency (R$) values and benefits in quality-adjusted life-years (QALYs). Utility values were derived from type 1 spinal muscular atrophy literature, whereas costs related to technologies and maintenance care in each health state were obtained from official sources of reimbursement in Brazil. Deterministic and probabilistic, as well as scenario, sensitivity analyses were performed. RESULTS: Compared with the less costly strategy (nusinersen), the use of onasemnogene abeparvovec resulted in an incremental cost of R$2.468.448,06 ($975 671.169 - purchasing power parity [PPP]) and a 3-QALY increment and incremental cost-effectiveness ratio of R$742.890,92 ($293 632.774 - PPP)/QALY. Risdiplam had an extended dominance from other strategies, resulting in an incremental cost-effectiveness ratio of R$926.586,22 ($366 239.612 - PPP)/QALY compared with nusinersen. Sensitivity analysis showed a significant impact of the follow-up time of the cohort and the cost of acquiring onasemnogene abeparvovec. CONCLUSIONS: Over a lifetime horizon, onasemnogene abeparvovec seems to be a potentially more effective option than nusinersen and risdiplam, albeit with an incremental cost. Such a trade-off should be weighed in efficiency criteria during decision making and outcome monitoring from the perspective of the Brazilian Unified Health System.

Image-defined risk factors in localized thoracic neuroblastoma and ganglioneuroma.

BACKGROUND: The pretreatment International Neuroblastoma Risk Group Staging System (INRGSS) discriminates localized tumors L1/L2 depending on the absence/presence of image-defined risk factors (IDRFs) at diagnosis. Referring to this new staging system, we assessed initial imaging of localized thoracic neuroblastoma (NB) and ganglioneuroma (GN) and the extent of initial tumor resection. METHODS: Patients with localized thoracic NB/GN from the German clinical trials NB97 and NB2004 were included. Imaging at diagnosis and operative reports were reviewed retrospectively. IDRFs were assessed centrally and correlated to International Neuroblastoma Staging System (INSS) stage and extent of tumor resection. Additionally, we analyzed data on surgery-related complications. RESULTS: Imaging series of 88 patients were available for central review. In 18 children, no IDRF was present, 28 exhibited one IDRF, 42 two or more IDRFs, resulting in 70 patients with L2 disease. The most frequently observed IDRF was encasement of any vessel (n = 38). Initial surgical resection was aimed for in 45 patients (L1: n = 11; L2: n = 34). Complete and gross total resection rates were higher children with L2 NB (n = 8/25 L1, n = 17/25 L2 vs. n = 2/15 L1, n = 13/15 L2, respectively). The proportion of surgical complications was very similar between INRGSS L1 and L2 (n = 4/11 vs. n = 17/34). All complications were manageable, and no surgery-related deaths were observed. CONCLUSION: In this retrospective cohort, the extent of resection and the rate of surgical complications did not differ substantially between patients classified as L1/L2, indicating that INRGSS L2 does not equate unresectability. It appeared that individual IDRFs differ in value. Larger studies are needed to assess the significance and therapeutic/prognostic impact of such findings.

Disparity in the use of Alzheimer's disease treatment in Southern Brazil.

Alzheimer's disease (AD) treatment is freely available in the Brazilian public health system. However, the prescription pattern and its associated factors have been poorly studied in our country. We reviewed all granted requests for AD treatment in the public health system in October 2021 in the Rio Grande do Sul (RS) state, Southern Brazil. We performed a spatial autocorrelation analysis with the population-adjusted patients receiving any AD medication as the outcome and correlated it with several socioeconomic variables. 2382 patients with AD were being treated during the period analyzed. The distribution of the outcome variable was not random (Moran's I 0.17562, P <.0001), with the most developed regions having a higher number of patients/100,000 receiving any AD medication. We show that although AD medications are available through the public health system, there is a clear disparity between regions of RS state. Factors related to socioeconomic development partly explain this finding.

Introduction of a breast apparent diffusion coefficient category system (ADC-B) derived from a large multicenter MRI database.

OBJECTIVES: To develop an intuitive and generally applicable system for the reporting, assessment, and documentation of ADC to complement standard BI-RADS criteria. METHODS: This was a multicentric, retrospective analysis of 11 independently conducted institutional review board-approved studies from seven institutions performed between 2007 and 2019. Breast Apparent Diffusion coefficient (ADC-B) categories comprised ADC-B0 (ADC non-diagnostic), ADC-B1 (no enhancing lesion), and ADC-B2-5. The latter was defined by plotting ADC versus cumulative malignancy rates. Statistics comprised ANOVA with post hoc testing and ROC analysis. p values ≤ 0.05 were considered statistically significant. RESULTS: A total of 1625 patients (age: 55.9 years (± 13.8)) with 1736 pathologically verified breast lesions were included. The mean ADC (× 10-3 mm2/s) differed significantly between benign (1.45, SD .40) and malignant lesions (.95, SD .39), and between invasive (.92, SD .22) and in situ carcinomas (1.18, SD .30) (p < .001). The following ADC-B categories were identified: ADC-B0-ADC cannot be assessed; ADC-B1-no contrast-enhancing lesion; ADC-B2-ADC ≥ 1.9 (cumulative malignancy rate < 0.1%); ADC-B3-ADC 1.5 to < 1.9 (0.1-1.7%); ADC-B4-ADC 1.0 to < 1.5 (10-24.5%); and ADC-B5-ADC < 1.0 (> 24.5%). At the latter threshold, a positive predictive value of 95.8% (95% CI 0.94-0.97) for invasive versus non-invasive breast carcinomas was reached. CONCLUSIONS: The breast apparent diffusion coefficient system (ADC-B) provides a simple and widely applicable categorization scheme for assessment, documentation, and reporting of apparent diffusion coefficient values in contrast-enhancing breast lesions on MRI. CLINICAL RELEVANCE STATEMENT: The ADC-B system, based on diverse MRI examinations, is clinically relevant for stratifying breast cancer risk via apparent diffusion coefficient measurements, and complements BI-RADS for improved clinical decision-making and patient outcomes. KEY POINTS: • The breast apparent diffusion coefficient category system (ADC-B) is a simple tool for the assessment, documentation, and reporting of ADC values in contrast-enhancing breast lesions on MRI. • The categories comprise ADC-B0 for non-diagnostic examinations, ADC-B1 for examinations without an enhancing lesion, and ADC-B2-5 for enhancing lesions with an increasing malignancy rate. • The breast apparent diffusion coefficient category system may be used to complement BI-RADS in clinical decision-making.

Improving Breast Conserving Surgery Using the Faxitron® OR Specimen Radiography System - A Complication Analysis, Cost Evaluation and Literature Review.

BACKGROUND/AIM: The combination of pre-surgical clip placement and hook-wire guided surgery is considered the gold standard for adequately locating non-palpable lesions during breast conserving surgery. After surgical removal of the segment, radiography is required to confirm clip removal, increasing surgical time, post-surgical complication rates, and cost. PATIENTS AND METHODS: We performed a retrospective analysis, using the Faxitron® in-theater specimen radiography system, of the following primary endpoints: surgical time and complication rates. The secondary endpoints were cost effectiveness and clip-location rates. The Control cohort included breast conserving surgery patients prior to May 2019 (n=150) and the Validation cohort included breast conserving surgery patients after May 2019 (n=53). RESULTS: The analysis showed an improvement in surgical time when using the Faxitron® system, which is directly linked to a benefit in cost effectiveness. A numerical benefit in complication rates was also shown. A subgroup analysis showed a significant advantage in surgical time for breast conserving surgery plus sentinel node biopsy and open breast biopsies. CONCLUSION: Use of the Faxitron® system significantly reduces surgical time, which increases cost efficiency while maintaining a low complication rate.

Correlation analysis of resected breast tissue and implant volume after mastectomy and its association with breast density.

BACKGROUND: The current methods for calculating the ideal implant volume for breast reconstruction are based on pre- or intraoperative volume measurements of the existing breast volume and do not take into account the individual breast density of the woman. This study aims is to identify objective parameters that can help to improve the optimal implant selection. MATERIALS AND METHODS: This retrospective analysis includes 198 breast cancer patients who underwent mastectomy. Breast densities (ACR) measured in mammography and MRI were compared with the removed breast tissue weight and volume of the implants used. In addition, the resected weight was compared directly with the implant volume to calculate a mathematical function. RESULTS: There was no significant correlation between the ACR values and the resected weights [correlation coefficient: mammography:- 0.117 (p = 0.176), MRI - 0.033 (p = 0.756)]. A negative correlation between the implant volumes and both imaging methods could be demonstrated [correlation coefficient: mammography - 0.268; p = 0.002; MRI was - 0.200 (p = 0.055)]. A highly significant correlation between the resected weights and the implant volumes (correlation coefficient 0.744; p < 0.001) was observed. This correlation corresponds to a power function (y = 34.71 x0.39), in which any resected weight can be used for the variable x to calculate the implant volume. CONCLUSION: We were able to show that there is a significant correlation between the resected breast tissue and the implant volume. With our novel potency function, the appropriate implant volume can be calculated for any resected weight making it easier for the surgeon to choose a fitting implant in a simple and more objective manner.

Efficacy and Safety of Taliglucerase Alfa for the Treatment of Gaucher Disease: A 9-Year Experience

Abstract Gaucher disease (GD) is one of the most common lysosomal disorders, occurring in approximately 1 in 40,000 live births worldwide. Since 2014 enzyme replacement therapy (ERT) with taliglucerase alfa has been the treatment of choice for adult patients with GD in Brazil. The aim of this study was to evaluate the long-term efficacy and safety of taliglucerase alfa in a cohort of Brazilian patients treated at a referral center for inborn errors of metabolism. All patients who received at least one infusion of the enzyme at the study center were considered eligible to participate. Patients were followed for adverse reactions and events throughout the study period. Platelets, hemoglobin, chitotriosidase activity, bone marrow burden (BMB) score, bone mineral density, and the severity score index (SSI) were analyzed. For patients who were switched to taliglucerase alfa from imiglucerase, the same variables were compared before and after the switch. At 9-year follow-up, all parameters of interest had remained stable or improved. The overall rate of adverse events was lower than in other studies that evaluated long-term ERT with taliglucerase, and no serious adverse events were considered related to treatment. Based on our findings, ERT with taliglucerase alfa is an effective and safe approach for treatment of patients with GD.

A Systematic Review and Meta-Analysis of Enzyme Replacement Therapy in Late-Onset Pompe Disease.

Pompe disease (PD) is a glycogen storage disorder caused by deficient activity of acid alpha-glucosidase (GAA). We sought to review the latest available evidence on the safety and efficacy of recombinant human GAA enzyme replacement therapy (ERT) for late-onset PD (LOPD). METHODS: We systematically searched the MEDLINE (via PubMed), Embase, and Cochrane databases for prospective clinical studies evaluating ERT for LOPD on pre-specified outcomes. A meta-analysis was also performed. RESULTS: Of 1601 articles identified, 22 were included. Studies were heterogeneous and with very low certainty of evidence for most outcomes. The following outcomes showed improvements associated with GAA ERT, over a mean follow-up of 32.5 months: distance walked in the 6-min walking test (6MWT) (mean change 35.7 m (95% confidence interval [CI] 7.78, 63.75)), physical domain of the SF-36 quality of life (QOL) questionnaire (mean change 1.96 (95% CI 0.33, 3.59)), and time on ventilation (TOV) (mean change -2.64 h (95% CI -5.28, 0.00)). There were no differences between the pre- and post-ERT period for functional vital capacity (FVC), Walton and Gardner-Medwin Scale score, upper-limb strength, or total SF-36 QOL score. Adverse events (AEs) after ERT were mild in most cases. CONCLUSION: Considering the limitations imposed by the rarity of PD, our data suggest that GAA ERT improves 6MWT, physical QOL, and TOV in LOPD patients. ERT was safe in the studied population. PROSPERO register: 135102.

Hypoglycemia frequency and treatment satisfaction in patients receiving insulin analogues for treatment of type 1 diabetes mellitus.

OBJECTIVE: The aim of this study was to evaluate the frequency of hypoglycemia and the treatment satisfaction in patients with type 1 diabetes (T1D) using insulin analogues. METHODS: This observational retrospective study included 516 adult patients with T1D from 38 cities in Southern Brazil. Demographics and clinical data were collected using a self-report questionnaire. Hypoglycemia was defined as an event based on either symptoms or self-monitored blood glucose < 70 mg/dL. Treatment satisfaction was evaluated using the Diabetes Treatment Satisfaction Questionnaire status version (DTSQs) and with a specific question with scores ranging from 0-10. Common mental disorders were assessed using the General Health Questionnaire (GHQ-12). RESULTS: Overall, the mean age was 38 ± 14 years and 52% of the participants were women. The median diabetes duration was 18 years. The scores for insulin analogue treatment satisfaction were higher than those for previous treatments. DTSQ scores had a median value of 32 (interquartile range 29-35) and remained unchanged over time. The percentage of patients with hypoglycemia (including severe and nocturnal) was comparable across groups divided according to duration of use of insulin analogues. Most patients (n=395, 77%) screened positive for common mental disorders. CONCLUSION: Patient satisfaction with insulin analogue treatment was high and remained unchanged with time. Episodes of hypoglycemia also remained unchanged over time among patients using insulin analogues.

Hypoglycemia frequency and treatment satisfaction in patients receiving insulin analogues for treatment of type 1 diabetes mellitus

ABSTRACT Objective: The aim of this study was to evaluate the frequency of hypoglycemia and the treatment satisfaction in patients with type 1 diabetes (T1D) using insulin analogues. Subjects and methods: This observational retrospective study included 516 adult patients with T1D from 38 cities in Southern Brazil. Demographics and clinical data were collected using a self-report questionnaire. Hypoglycemia was defined as an event based on either symptoms or self-monitored blood glucose < 70 mg/dL. Treatment satisfaction was evaluated using the Diabetes Treatment Satisfaction Questionnaire status version (DTSQs) and with a specific question with scores ranging from 0-10. Common mental disorders were assessed using the General Health Questionnaire (GHQ-12). Results: Overall, the mean age was 38 ± 14 years and 52% of the participants were women. The median diabetes duration was 18 years. The scores for insulin analogue treatment satisfaction were higher than those for previous treatments. DTSQ scores had a median value of 32 (interquartile range 29-35) and remained unchanged over time. The percentage of patients with hypoglycemia (including severe and nocturnal) was comparable across groups divided according to duration of use of insulin analogues. Most patients (n=395, 77%) screened positive for common mental disorders. Conclusions: Patient satisfaction with insulin analogue treatment was high and remained unchanged with time. Episodes of hypoglycemia also remained unchanged over time among patients using insulin analogues.

Evaluation of severe hypoglycemia and common mental disorders in patients receiving insulin analogues for treatment of type 1 diabetes

ABSTRACT This is a retrospective report of the frequency of severe hypoglycemia and the association between common mental disorders and type 1 diabetes mellitus treated with insulin analogues. Patients with severe hypoglycemia compared with those without this complication had a higher prevalence of positive screening for common mental disorders (88% vs.77%, respectively, p = 0.03).

Diffusion-weighted Imaging Allows for Downgrading MR BI-RADS 4 Lesions in Contrast-enhanced MRI of the Breast to Avoid Unnecessary Biopsy.

PURPOSE: Diffusion-weighted imaging with the calculation of an apparent diffusion coefficient (ADC) has been proposed as a quantitative biomarker on contrast-enhanced MRI (CE-MRI) of the breast. There is a need to approve a generalizable ADC cutoff. The purpose of this study was to evaluate whether a predefined ADC cutoff allows downgrading of BI-RADS 4 lesions on CE-MRI, avoiding unnecessary biopsies. EXPERIMENTAL DESIGN: This was a retrospective, multicentric, cross-sectional study. Data from five centers were pooled on the individual lesion level. Eligible patients had a BI-RADS 4 rating on CE-MRI. For each center, two breast radiologists evaluated the images. Data on lesion morphology (mass, non-mass), size, and ADC were collected. Histology was the standard of reference. A previously suggested ADC cutoff (≥1.5 × 10-3 mm2/second) was applied. A negative likelihood ratio of 0.1 or lower was considered as a rule-out criterion for breast cancer. Diagnostic performance indices were calculated by ROC analysis. RESULTS: There were 657 female patients (mean age, 42; SD, 14.1) with 696 BI-RADS 4 lesions included. Disease prevalence was 59.5% (414/696). The area under the ROC curve was 0.784. Applying the investigated ADC cutoff, sensitivity was 96.6% (400/414). The potential reduction of unnecessary biopsies was 32.6% (92/282). CONCLUSIONS: An ADC cutoff of ≥1.5 × 10-3 mm2/second allows downgrading of lesions classified as BI-RADS 4 on breast CE-MRI. One-third of unnecessary biopsies could thus be avoided.

Evaluation of severe hypoglycemia and common mental disorders in patients receiving insulin analogues for treatment of type 1 diabetes.

This is a retrospective report of the frequency of severe hypoglycemia and the association between common mental disorders and type 1 diabetes mellitus treated with insulin analogues. Patients with severe hypoglycemia compared with those without this complication had a higher prevalence of positive screening for common mental disorders (88% vs. 77%, respectively, p = 0.03).

A Multicentric Comparison of Apparent Diffusion Coefficient Mapping and the Kaiser Score in the Assessment of Breast Lesions.

MATERIALS AND METHODS: In this multicentric study, individual patient data from 3 different centers were analyzed. Consecutive patients receiving standardized multiparametric breast magnetic resonance imaging for standard nonscreening indications were included. At each center, 2 experienced radiologists with more than 5 years of experience retrospectively interpreted the examinations in consensus and applied the KS to every histologically verified lesion. The corresponding mean ADC of each lesion was measured using a Wielema type 4 region of interest. According to established methods, the KS and ADC were combined, yielding the KS+ score. Diagnostic accuracy was evaluated by the area under the receiver operating characteristics curve (AUROC) and compared between the KS, ADC, and KS+ (DeLong test). Likewise, the potential to help avoid unnecessary biopsies was compared between the KS, ADC, and KS+ based on established high sensitivity thresholds (McNemar test). RESULTS: A total of 450 lesions in 414 patients (mean age, 51.5 years; interquartile range, 42-60.8 years) were included, with 219 lesions being malignant (48.7%; 95% confidence interval [CI], 44%-53.4%). The performance of the KS (AUROC, 0.915; CI, 0.886-0.939) was significantly better than that of the ADC (AUROC, 0.848; CI, 0.811-0.880; P < 0.001). The largest difference between these parameters was observed when assessing subcentimeter lesions (AUROC, 0.909 for KS; CI, 0.849-0.950 vs 0.811 for ADC; CI, 0.737-0.871; P = 0.02).The use of the KS+ (AUROC, 0.918; CI, 0.889-0.942) improved the performance slightly, but without any significant difference relative to a single KS or ADC reading (P = 0.64).When applying high sensitivity thresholds for avoiding unnecessary biopsies, the KS and ADC achieved equal sensitivity (97.7% for both; cutoff values, >4 for KS and ≤1.4 × 10-3 mm2/s for ADC). However, the rate of potentially avoidable biopsies was higher when using the KS (specificity: 65.4% for KS vs 32.9% for ADC; P < 0.0001). The KS was superior to the KS+ in avoiding unnecessary biopsies. CONCLUSIONS: Both the KS and ADC may be used to distinguish benign from malignant breast lesions. However, KS proved superior in this task including, most of all, when assessing small lesions less than 1 cm. Using the KS may avoid twice as many unnecessary biopsies, and the combination of both the KS and ADS does not improve diagnostic performance.

Evaluation of 3.0-T MRI Brain Signal after Exposure to Gadoterate Meglumine in Women with High Breast Cancer Risk and Screening Breast MRI.

Background Otherwise healthy women at high risk for breast cancer undergo annual contrast agent-enhanced breast MRI screening examinations, resulting in high cumulative doses of gadolinium-based contrast agents (GBCAs). Whereas the majority of studies showed no T1 signal ratio increase in deep brain nuclei after more than six doses of macrocyclic GBCA, this has not been explored in a healthy study population. Purpose To assess whether women who are administered large cumulative doses of macrocyclic GBCA with breast MRI at high-risk breast cancer screening exhibit T1 alterations in deep brain nuclei. Materials and Methods In this prospective study from November 2017 to March 2018, healthy women who were either exposed (because of high-risk breast cancer screening) or unexposed to only gadoterate meglumine underwent 3.0-T brain MRI with a dedicated head coil, including T1 mapping and magnetization-prepared rapid gradient-echo sequences. T1 times and T1 signal intensities were measured in the dentate nucleus (DN), globus pallidus (GP), crus anterior of capsula interna (CA), and pons. Ratios of DN to pons and GP to CA were calculated, and univariable Pearson correlation coefficients were calculated. Multivariable analysis included partial regression analysis. Results This study evaluated 25 women (mean age, 51 years ± 11 [standard deviation]) who were exposed to a mean GBCA dose of 129 mL (median 112 mL; range, 70-302 mL) and 16 women (mean age, 37 years ± 10) who were never exposed to any GBCA. Infratentorially, no correlation between cumulative GBCA dose and T1 times or signal intensity ratios was detected (P = .66 and .55, respectively). In partial correlation analysis by considering age as a confounder, there was a moderate negative correlation between GP-to-CA ratio and GBCA dose (r = -0.40; P = .01) but not for GP T1 times (r = 0.19; P = .24). Conclusion After administration of relatively large cumulative doses of gadoterate dimeglumine, healthy women at high risk for breast cancer who underwent annual contrast-enhanced breast MRI screening did not exhibit T1 signal increase in deep brain nuclei at 3.0-T MRI. © RSNA, 2019.

First Reported Use of the Faxitron LOCalizer™ Radiofrequency Identification (RFID) System in Europe - A Feasibility Trial, Surgical Guide and Review for Non-palpable Breast Lesions.

BACKGROUND/AIM: The problem of adequately marking any given lesion within a breast surgical site is commonly solved by introducing a titanium clip. However, clip dislocation and/or stereotactic hook-wire dislocation are common problems. An ideal solution would be a clip that can be easily found without the use of stereotactic intervention. This work reviews the available data on radiofrequency identification devices (RFID) in breast surgery, reports initial experience data in Europe and discusses surgical pitfalls, advantages and disadvantages. PATIENTS AND METHODS: This study represents a single center, consecutively recruited, initiation trial with subsequent surgeon questionnaire for the first institution in Europe to report Faxitron LOCalizer™ chip data. Four patients with non-palpable tumors were marked with the system and were correlated via mammography, pre- and intra-operative ultrasound and pathology. Data were then compared to available literature and a literature review was added. RESULTS: The four patients marked with this RFID system, displayed a 100% success location rate at a 0% complication rate. Surgeons evaluated the new system as being safe to use and only slightly more difficult to place compared to a standard clip. A significant improvement in ultrasound localization and intraoperative localization was also reported for the LOCalizer™ system when compared to a standard titanium clip. CONCLUSION: This trial added a small number of consecutively recruited patients to an existing number of available data, resulting in a total of 121 evaluated and reviewed Faxitron LOCalizer™ marked non-palpable in-breast lesions worldwide.

Residual glandular tissue (RGT) in BRCA1/2 germline mutation carriers with unilateral and bilateral prophylactic mastectomies.

BACKGROUND: Prophylactic mastectomy (PME) is increasingly performed in women carrying deleterious BRCA1 and BRCA2 germline mutations. The oncologic risk resulting from residual fibroglandular tissue (RGT) is unknown. METHODS: All women who had received a mastectomy and at least one postoperative breast MRI, between 2006 and 2016 were extracted from the register of the Center for Hereditary Breast and Ovarian Cancer Cologne (CHBOC). The index MRI was evaluated in terms of basic clinical data and the morphological criteria of RGT. The RGT volume was measured in diameter and was semi-automatically evaluated using software. RESULTS: We identified 169 women carrying BRCA1/2 mutations who underwent prophylactic and curative mastectomy: a total of 338 breasts. RGT was found in 128 of the 338 breasts (37.9%). 68 of the 128 breasts (53.1%) were related to bilateral PME, 37 (28.9%) to unilateral PME and 23 (18.0%) to curative mastectomy. RGT was predominantly unifocal and located in the retroareolar breast region. RGT was observed more often after bilateral PME (p < 0.0001). In this subgroup, the nipple-sparing mastectomy dominated (108 of 136, 79.4%), in contrast to 23 standard mastectomies (23 of 94, 24.5%) in the subgroup of curative mastectomy (23%). There was a trend towards higher amounts of RGT in surgical units with fewer mastectomies performed. During follow-up, two breast cancers were detected after bilateral and unilateral PME, respectively. CONCLUSIONS: Our results suggest that the indication for surgery and in particular the selected surgical procedure affect the surgical outcome with respect to RGT. Oncological safety should not be neglected, especially in the high-risk group of BRCA1/2 mutation carriers.

High-risk breast cancer surveillance with MRI: 10-year experience from the German consortium for hereditary breast and ovarian cancer.

PURPOSE: To report on 10 years of high-risk service screening with annual MRI in the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC). METHODS: A cohort of 4,573 high-risk, previously unaffected women (954 BRCA1 carriers, 598 BRCA2 carriers, 3021 BRCA1/2 non-carriers) participating in the GC-HBOC surveillance program was prospectively followed. Screening outcomes for 14,142 screening rounds with MRI between 2006 and 2015 were analyzed and stratified by risk group, type of screening round, and age. RESULTS: A total of 221 primary breast cancers (185 invasive, 36 in situ) were diagnosed within 12 months of an annual screening round with MRI. Of all cancers, 84.5% (174/206, 15 unknown) were stage 0 or I. In BRCA1 carriers, 16.9% (10/59, 5 unknown) of all incident cancers (screen-detected and interval cancers combined) and in BRCA2 carriers 12.5% (3/24, 4 unknown) were stage IIA or higher, compared to only 4.8% (2/42, 2 unknown) in high-risk BRCA1/2 non-carriers. Program sensitivity was 89.6% (95% CI 84.9-93.0) with no significant differences in sensitivity between risk groups or by age. Specificity was significantly lower in the first screening round (84.6%, 95% CI 83.6-85.7) than in subsequent screening rounds (91.1%, 95% CI 90.6-91.7), p < 0.001. Cancer detection rates (CDRs) and as a result positive predictive values were strongly dependent on type of screening round, risk group and patient age. CDRs ranged from 43.5‰ (95% CI 29.8-62.9) for the first screening round in BRCA2 carriers to 2.9‰ (95% CI 1.3-6.3) for subsequent screening rounds in high-risk non-carriers in the age group 30 to 39 years. CONCLUSIONS: High-risk screening with MRI was successfully implemented in the GC-HBOC with high sensitivity and specificity. Risk prediction and inclusion criteria in high-risk non-carriers need to be adjusted to improve CDRs and thus screening efficacy in these patients.