Several methods for tumor delineation are used in literature on breast diffusion weighted imaging (DWI) to measure the apparent diffusion coefficient (ADC). However, in the process of reaching ...consensus on breast DWI scanning protocol, image analysis and interpretation, still no standardized optimal breast tumor tissue selection (BTTS) method exists. Therefore, the purpose of this study is to assess the impact of BTTS methods on ADC in the discrimination of benign from malignant breast lesions in DWI in terms of sensitivity, specificity and area under the curve (AUC).
In this systematic review and meta-analysis, adhering to the PRISMA statement, 61 studies, with 65 study subsets, in females with benign or malignant primary breast lesions (6291 lesions) were assessed. Studies on DWI, quantified by ADC, scanned on 1.5 and 3.0 Tesla and using b-values 0/50 and ≥ 800 s/mm2 were included. PubMed and EMBASE were searched for studies up to 23-10-2019 (n = 2897). Data were pooled based on four BTTS methods (by definition of measured region of interest, ROI): BTTS1: whole breast tumor tissue selection, BTTS2: subtracted whole breast tumor tissue selection, BTTS3: circular breast tumor tissue selection and BTTS4: lowest diffusion breast tumor tissue selection. BTTS methods 2 and 3 excluded necrotic, cystic and hemorrhagic areas. Pooled sensitivity, specificity and AUC of the BTTS methods were calculated. Heterogeneity was explored using the inconsistency index (I2) and considering covariables: field strength, lowest b-value, image of BTTS selection, pre-or post-contrast DWI, slice thickness and ADC threshold. Pooled sensitivity, specificity and AUC were: 0.82 (0.72-0.89), 0.79 (0.65-0.89), 0.88 (0.85-0.90) for BTTS1; 0.91 (0.89-0.93), 0.84 (0.80-0.87), 0.94 (0.91-0.96) for BTTS2; 0.89 (0.86-0.92), 0.90 (0.85-0.93), 0.95 (0.93-0.96) for BTTS3 and 0.90 (0.86-0.93), 0.84 (0.81-0.87), 0.86 (0.82-0.88) for BTTS4, respectively. Significant heterogeneity was found between studies (I2 = 95).
None of the breast tissue selection (BTTS) methodologies outperformed in differentiating benign from malignant breast lesions. The high heterogeneity of ADC data acquisition demands further standardization, such as DWI acquisition parameters and tumor tissue selection to substantially increase the reliability of DWI of the breast.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In breast diffusion weighted imaging (DWI) protocol standardization, it is recently shown that no breast tumor tissue selection (BTTS) method outperformed the others. The purpose of this study is to ...analyze the feasibility of three fixed-size breast tumor tissue selection (BTTS) methods based on the reproducibility, accuracy and time-measurement in comparison to the largest oval and manual delineation in breast diffusion weighted imaging data.
This study is performed with a consecutive dataset of 116 breast lesions (98 malignant) of at least 1.0 cm, scanned in accordance with the EUSOBI breast DWI working group recommendations. Reproducibility of the maximum size manual (BTTS1) and of the maximal size round/oval (BTTS2) methods were compared with three smaller fixed-size circular BTTS methods in the middle of each lesion (BTTS3, 0.12 cm3 volume) and at lowest apparent diffusion coefficient (ADC) (BTTS4, 0.12 cm3; BTTS5, 0.24 cm3). Mean ADC values, intraclass-correlation-coefficients (ICCs), area under the curve (AUC) and measurement times (sec) of the 5 BTTS methods were assessed by two observers.
Excellent inter- and intra-observer agreement was found for any BTTS (with ICC 0.88-0.92 and 0.92-0.94, respectively). Significant difference in ADCmean between any pair of BTTS methods was shown (p = <0.001-0.009), except for BTTS2 vs. BTTS3 for observer 1 (p = 0.10). AUCs were comparable between BTTS methods, with highest AUC for BTTS2 (0.89-0.91) and lowest for BTTS4 (0.76-0.85). However, as an indicator of clinical feasibility, BTTS2-3 showed shortest measurement times (10-15 sec) compared to BTTS1, 4-5 (19-39 sec).
The performance of fixed-size BTTS methods, as a potential tool for clinical decision making, shows equal AUC but shorter ADC measurement time compared to manual or oval whole lesion measurements. The advantage of a fixed size BTTS method is the excellent reproducibility. A central fixed breast tumor tissue volume of 0.12 cm3 is the most feasible method for use in clinical practice.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To evaluate whether immunomodulation can eliminate high sustained antibody levels, and thereby improve clinical outcome in classic infantile Pompe patients receiving enzyme replacement therapy (ERT) ...with recombinant human alpha-glucosidase (rhGAA).
Three patients (two cross-reactive immunologic material (CRIM) negative) with high sustained antibodies received a three-week treatment protocol with Rituximab and Bortezomib, followed by daily Rapamycin and monthly IVIG. Patients received 40 mg/kg/week rhGAA. Antibody titers were measured using ELISA. Neutralizing effects on cellular uptake were determined. Clinical efficacy was measured in terms of (ventilator-free) survival, reduction in left ventricular mass index (LVMI) and improvement in motor function.
Before immunomodulation anti-rhGAA antibody titers ranged from 1:156,250 to 1:781,250 and at last assessment from 1:31,250 to 1:156,250. Neutralizing effects of anti-rhGAA antibody titers (observed in two patients) disappeared. Infusion-associated reactions were no longer present. Immunomodulation resulted in substantial increases of aspartate transaminase, alanine transaminase, and creatine kinase levels. The two CRIM-negative patients who could walk at start of immunomodulation maintained their ability to walk; the patient who had lost this ability did not regain it.
To some extent, the immunomodulation protocol used in our study reduced antibody titers, but it did not eliminate them. Overall, there have been few reports on secondary immunomodulation, and various protocols have been applied. Future research should seek to identify the most successful immunomodulation protocol in patients with high sustained titers.
Purpose
Although adjuvant systemic therapy (AST) helps increase breast cancer-specific survival (BCSS), there is a growing concern for overtreatment. By estimating the expected BCSS of AST using ...PREDICT, this study aims to quantify the number of patients treated with AST without benefit to provide estimates of overtreatment.
Methods
Data of all non-metastatic unilateral breast cancer patients diagnosed in 2015 were retrieved from cancer registries from The Netherlands and the USA. The PREDICT tool was used to estimate AST survival benefit. Overtreatment was defined as the proportion of patients that would have survived regardless of or died despite AST within 10 years. Three scenarios were evaluated: actual treatment, and recommendations by the Dutch or USA guidelines.
Results
59.5% of Dutch patients were treated with AST. 6.4% (interquartile interval IQI = 2.5, 8.2%) was expected to survive at least 10 years due to AST, leaving 93.6% (IQI = 91.8, 97.5%) without AST benefit (overtreatment). The lowest expected amount of overtreatment was in the targeted and chemotherapy subgroup, with 86.5% (IQI = 83.4, 89.6%) overtreatment, and highest in the only endocrine treatment subgroup, with 96.7% (IQI = 96.0, 98.1%) overtreatment. Similar results were obtained using data from the USA, and guideline recommendations.
Conclusion
Based on PREDICT, AST prevents 10-year breast cancer death in 6.4% of the patients treated with AST. Consequently, AST yields no survival benefit to many treated patients. Especially improved personalization of endocrine therapy is relevant, as this therapy is widely used and is associated with the highest amount of overtreatment.
To determine the willingness of women with extremely dense breasts to undergo breast cancer screening with magnetic resonance imaging (MRI) in a research setting, and to examine reasons for women to ...participate or not.
Between 2011 and 2015, 8,061 women (50–75 years) were invited for supplemental MRI as part of the Dense Tissue and Early Breast Neoplasm Screening (DENSE) trial (ClinicalTrials.gov Identifier: NCT01315015), after a negative screening mammography in the national population-based mammography screening programme. Demographics of participants and non-participants were compared. All invitees were asked to report reasons for (non)participation. Ethical approval was obtained. Participants provided written informed consent.
Of the 8,061 invitees, 66% answered that they were interested, and 59% eventually participated. Participants were on average 54-years old (interquartile range: 51–59 years), comparable to women with extremely dense breasts in the population-based screening programme (55 years). Women with higher socio-economic status (SES) were more often interested in participation than women with lower SES (68% versus 59%, p<0.001). The most frequently stated reasons for non-participation were “MRI-related inconveniences and/or self-reported contraindications to MRI” (27%) and “anxiety regarding the result of supplemental screening” (21%). “Expected personal health benefit” (68%) and “contribution to science” (43%) were the most frequent reasons for participation.
Of women invited for MRI because of extremely dense breasts, 59% participated. Common reasons for non-participation were “MRI-related inconveniences” and “anxiety regarding the result of supplemental screening”. In case of future implementation, availability of precise evidence on benefits and harms might reduce this anxiety.
•59% of women with extremely dense breasts participate in supplemental MRI screening.•Most common reasons for non-participation were ‘MRI-related inconveniences’.•Anxiety for the extra screening result was also a common non-participation reason.•Addressing this anxiety might improve participation in supplemental screening.
Abstract Background New insights show that an axillary lymph node dissection (ALND) may not always be indicated for metastases detected by ultrasound (pathologically proven). This study investigated ...whether axillary ultrasound accurately predicts pN0, pN1 and pN2–pN3 status. Methods Data were retrospectively collected from all consecutive patients with invasive breast cancer who underwent (primary) surgery between 2008 and 2012. False negative percentages and negative predictive values (NPVs) for sonographic nodal staging were calculated for all patients and again for cT1–2 patients treated by breast conserving therapy (BCT). Results A total of 577 axillary ultrasounds were included. After negative ultrasound findings (cN0), pathology showed pN2–pN3 disease in 4.4% of these cases, with an NPV of 95.5% (93.4–97.1%). When cN1 (1–3 suspicious nodes) was predicted, pathology showed pN2–pN3 disease in 41.2%, with an NPV of 58.5% (44.2–71.5%). In the subgroup of patients with cT1–2 breast cancer that were treated by BCT, pathology showed pN2–pN3 disease in 2.3% after negative ultrasound findings (cN0), with an NPV of 97.7% (94.9–99.0%). When cN1 was predicted ( n = 12), pathology showed pN2–pN3 disease in 50.0%, with an NPV of 50.0% (22.3–77.9%). A direct ALND was performed in these 12 cN1 cases; pathology showed six patients with pN1 (three patients with one and three with two macrometastases) and six with pN2–pN3 disease (4, 5, 11, 13, 16 or 22 macrometastases, respectively). Conclusion In conclusion, a negative axillary ultrasound generally excludes the presence of pN2–pN3 disease. An axillary ultrasound cannot accurately differentiate between pN1 and pN2–pN3. It could be argued that the standard performance of an axillary ultrasound in breast cancer patients is questionable; multidisciplinary discussion could guide decisions on the use of axillary ultrasound for the individual patient.
In this randomized trial, women with extremely dense breast tissue were invited to undergo MRI screening or received only mammography during a 2-year screening period. There was a 50% lower rate of ...interval cancers among the women invited for MRI screening. Among those who underwent MRI-directed biopsies, 26% had breast cancer.
In the Dutch breast cancer screening program, women recalled with a BI-RADS 0 score are referred for additional imaging, while those with BI-RADS 4/5 scores are also directed to an outpatient breast ...clinic. Approximately six out of ten women are recalled without being diagnosed with a malignancy. However, these recalls require additional imaging and doctor visits, which result in patient anxiety and increased health care costs. Conventional types of imaging used for additional imaging are full-field digital mammography and tomosynthesis. Contrast-enhanced spectral mammography has proved to have higher sensitivity and specificity than conventional imaging in women recalled from screening. Therefore, the aim is to study if CESM instead of conventional imaging is a more accurate, patient-friendly, and cost-effective strategy in the work-up of women recalled from breast cancer screening.
This prospective, multicenter, randomized controlled trial will be conducted at four centers and will include 528 patients recalled for suspicious breast lesions from the Dutch breast cancer screening program. Participants are randomized in two groups: (1) standard care using conventional breast imaging techniques as initial imaging after recall versus (2) work-up primarily based on CESM. Written informed consent will be collected prior to study inclusion. The primary outcome is the diagnostic accuracy for detection of breast cancer. Secondary outcomes are numbers of additional diagnostic exams, days until final diagnosis, health care costs, and experienced patient anxiety.
Based on previously published retrospective studies, we expect to demonstrate in this prospective multicenter randomized controlled trial, that using CESM as a primary work-up tool in women recalled from breast cancer screening is a more accurate, cost-effective, and patient-friendly strategy.
Netherlands Trial Register, NL6413/NTR6589. Registered on 6 July, 2017.
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