The addition of breast magnetic resonance imaging (MRI) to screening mammography for women with BRCA mutations significantly increases sensitivity, but there is little data on clinical outcomes. We ...report screening performance, cancer stage, distant recurrence rate, and breast cancer-specific mortality in our screening study.
From 1997 to 2009, 496 women aged 25 to 65 years with a known BRCA1/2 mutation, of whom 380 had no previous cancer history, were enrolled in a prospective screening trial that included annual MRI and mammography.
In 1847 screening rounds, 57 cancers were identified (53 screen-detected, 1 interval, and 3 incidental at prophylactic mastectomy), of which 37 (65%) were invasive. Sensitivity of MRI vs mammography was 86% vs 19% over the entire study period (P<0.0001), but was 74% vs 35% from 1997 to 2002 (P=0.02) and 94% vs 9% from 2003 to 2009 (P<0.0001), respectively. The relative sensitivities of MRI and mammography did not differ by mutation, age, or invasive vs non-invasive disease. Of the incident cancers, 97% were Stage 0 or 1. Of 28 previously unaffected women diagnosed with invasive cancer, 1 BRCA1 mutation carrier died following relapse of a 3 cm, node-positive breast cancer diagnosed on her first screen at age 48 (annual breast cancer mortality rate=0.5%). Three patients died of other causes. None of the 24 survivors has had a distant recurrence at a median follow-up of 8.4 years since diagnosis.
Magnetic resonance imaging surveillance of women with BRCA1/2 mutations will detect the majority of breast cancers at a very early stage. The absence of distant recurrences of incident cancers to date is encouraging. However, longer follow-up is needed to confirm the safety of breast surveillance.
Current recommendations for women who have a BRCA1 or BRCA2 mutation are to undergo breast surveillance from age 25 years onward with mammography annually and clinical breast examination (CBE) every ...6 months; however, many tumors are detected at a relatively advanced stage. Magnetic resonance imaging (MRI) and ultrasound may improve the ability to detect breast cancer at an early stage.
To compare the sensitivity and specificity of 4 methods of breast cancer surveillance (mammography, ultrasound, MRI, and CBE) in women with hereditary susceptibility to breast cancer due to a BRCA1 or BRCA2 mutation.
A surveillance study of 236 Canadian women aged 25 to 65 years with BRCA1 or BRCA2 mutations who underwent 1 to 3 annual screening examinations, consisting of MRI, mammography, and ultrasound at a single tertiary care teaching hospital between November 3, 1997, and March 31, 2003. On the day of imaging and at 6-month intervals, CBE was performed.
Sensitivity and specificity of each of the 4 surveillance modalities, and sensitivity of all 4 screening modalities vs mammography and CBE.
Each imaging modality was read independently by a radiologist and scored on a 5-point Breast Imaging Reporting and Data System scale. All lesions with a score of 4 or 5 (suspicious or highly suspicious for malignancy) were biopsied. There were 22 cancers detected (16 invasive and 6 ductal carcinoma in situ). Of these, 17 (77%) were detected by MRI vs 8 (36%) by mammography, 7 (33%) by ultrasound, and 2 (9.1%) by CBE. The sensitivity and specificity (based on biopsy rates) were 77% and 95.4% for MRI, 36% and 99.8% for mammography, 33% and 96% for ultrasound, and 9.1% and 99.3% for CBE, respectively. There was 1 interval cancer. All 4 screening modalities combined had a sensitivity of 95% vs 45% for mammography and CBE combined.
In BRCA1 and BRCA2 mutation carriers, MRI is more sensitive for detecting breast cancers than mammography, ultrasound, or CBE alone. Whether surveillance regimens that include MRI will reduce mortality from breast cancer in high-risk women requires further investigation.
Aim To evaluate the sensitivity and specificity of magnetic resonance imaging (MRI) computer-aided detection (CAD) for breast MRI screen-detected lesions recommended for biopsy in a high-risk ...population. Material and methods Fifty-six consecutive Breast Imaging Reporting and Data System (BI-RADS) 3–5 lesions with histopathological correlation nine invasive cancers, 13 ductal carcinoma in situ (DCIS) and 34 benign were retrospectively evaluated using a breast MRI CAD prototype (CAD-Gaea). CAD evaluation was performed separately and in consensus by two radiologists specializing in breast imaging, blinded to the histopathology. Thresholds of 50, 80, and 100% and delayed enhancement were independently assessed with CAD. Lesions were rated as malignant or benign according to threshold and delayed enhancement only and in combination. Sensitivities, specificities, and negative predictive values (NPV) were determined for CAD assessments versus pathology. Initial MRI BI-RADS interpretation without CAD versus CAD assessments were compared using paired binary diagnostic tests. Results Threshold levels for lesion enhancement were: 50% to include all malignant (and all benign) lesions; and 100% for all invasive cancer and high-grade DCIS. Combined use of threshold and enhancement patterns for CAD assessment was best (73% sensitivity, 56% specificity and 76% NPV for all cancer). Sensitivities and NPV were better for invasive cancer (100%/100%) than for all malignancies (54%/76%). Radiologists' MRI interpretation was more sensitive than CAD ( p = 0.05), but less specific ( p = 0.001) for cancer detection. Conclusion The breast MRI CAD system used could not improve the radiologists' accuracy for distinguishing all malignant from benign lesions, due to the poor sensitivity for DCIS detection.
The ability to make accurate judgments and execute effective skilled movements under severe temporal constraints are fundamental to elite performance in a number of domains including sport, military ...combat, law enforcement, and medicine. In two experiments, we examine the effect of stimulus strength on response time and accuracy in a temporally constrained, real‐world, decision‐making task. Specifically, we examine the effect of low stimulus intensity (black) and high stimulus intensity (sequin) uniform designs, worn by teammates, to determine the effect of stimulus strength on the ability of soccer players to make rapid and accurate responses. In both field‐ and laboratory‐based scenarios, professional soccer players viewed developing patterns of play and were required to make a penetrative pass to an attacking player. Significant differences in response accuracy between uniform designs were reported in laboratory‐ and field‐based experiments. Response accuracy was significantly higher in the sequin compared with the black uniform condition. Response times only differed between uniform designs in the laboratory‐based experiment. These findings extend the literature into a real‐world environment and have significant implications for the design of clothing wear in a number of domains.
To compare the clinical results of percutaneous sclerotherapy of venous vascular malformations (VVMs) with the authors' proposed magnetic resonance (MR) imaging classification.
MR findings and ...clinical results of percutaneous alcohol sclerotherapy in 59 pediatric patients with VVMs were retrospectively reviewed. Before treatment, lesions were graded with MR imaging on the basis of margins and size, respectively: grade 1, well defined, less than or equal to 5 cm; grade 2A, well defined, greater than 5 cm; grade 2B, ill defined, less than or equal to 5 cm; and grade 3, ill defined, greater than 5 cm. Regression models were used to test trends in therapy across the MR classification grades, including the repeat sclerotherapies, volumes of ethanol and metrizamide administered for each lesion, and number of access sites. Clinical response to sclerotherapy, which was evaluated with consensus by a multidisciplinary team, was graded as poor, good, or excellent. Association between MR imaging grade and clinical assessment was tested with the Fisher exact test.
There were 14 grade 1 lesions, nine grade 2A, 15 grade 2B, and 21 grade 3. Twenty-four patients had a poor response to sclerotherapy; 19, good; and 16, excellent. Ten of 14 (71%) grade 1 lesions had an excellent response; none, a poor response. Twelve of 21 (57%) grade 3 lesions had a poor response; none, an excellent result. Grade 2 lesions were relatively equally distributed among the three categories, with the exception of nine of 15 (60%) grade 2B lesions that had a poor response (P <.001). There was a trend with increasing lesion grade for increasing numbers of sclerotherapy sessions, volumes of ethanol and metrizamide for each lesion, and numbers of access sites.
There is a strong association between this proposed MR imaging classification and the results of percutaneous sclerotherapy.
Like the Dutch study, Martin Leach and colleagues found that despite the clear superiority of MRI for detecting invasive cancer, mammography was more sensitive than MRI for ductal carcinoma in situ ...(DCIS). This was also our experience in the first years of our study. However, since becoming more adept at diagnosing the subtle signs of DCIS on MRI, we have found MRI to be much more sensitive than mammography, with a differential similar to what we see with invasive cancer. This might also explain the reduced benefit of MRI observed in the UK study once the BRCA1 mutation carriers were excluded from the analysis, since BRCA2 mutation carriers and non-carriers are much more likely to present with DCIS. The relatively large size of some of the incident cancers in both the Dutch and UK studies compared with ours might reflect either inexperience of reading MRI, or the unavailability of MRI-guided biopsy which is necessary to diagnose cancers visible only on MRI, and thus to achieve the full potential of this modality. This technology was unavailable early in the UK study and its availability in the Dutch study was not stated. A younger patient population with more rapidly proliferating tumours could be an additional explanation for the larger tumours.
This study tested the hypothesis that the increases in salivary and plasma NO
after dietary NO
supplementation would be greater when oral temperature and pH were independently elevated, and ...increased further when oral temperature and pH were elevated concurrently. Seven healthy males (mean ± SD, age 23 ± 4 years) ingested 70 mL of beetroot juice concentrate (BR, which provided ~6.2 mmol NO
) during six separate laboratory visits. In a randomised crossover experimental design, salivary and plasma NO
and NO
were assessed at a neutral oral pH with a low (T
-pH
), intermediate (T
-pH
), and high (T
-pH
) oral temperature, and when the oral pH was increased at a low (T
-pH
), intermediate (T
-pH
), and high (T
-pH
) oral temperature. Compared with the T
-pH
condition (976 ± 388 µM), the mean salivary NO
1-3 h post BR ingestion was higher in the T
-pH
(1855 ± 423 µM), T
-pH
(1371 ± 653 µM), T
-pH
(1792 ± 741 µM), T
-pH
(1495 ± 502 µM), and T
-pH
(2013 ± 662 µM) conditions, with salivary NO
also higher at a given oral temperature when the oral pH was increased (
< 0.05). Plasma NO
was higher 3 h post BR ingestion in the T
-pH
, T
-pH
, and T
-pH
conditions, but not the T
-pH
and T
-pH
conditions, compared with T
-pH
(
< 0.05). Therefore, despite ingesting the same NO
dose, the increases in salivary NO
varied depending on the temperature and pH of the oral cavity, while the plasma NO
increased independently of oral temperature, but to a greater extent at a higher oral pH.
Oxidative stress may play an important role in the pathophysiology of cystic fibrosis (CF). This review aimed to quantify CF-related redox imbalances.
Systematic searches of the Medline, CINAHL, ...CENTRAL and PsycINFO databases were conducted. Mean content of blood biomarkers from people with clinically-stable CF and non-CF controls were used to calculate the standardized mean difference (SMD) and 95% confidence intervals (95% CI).
Forty-nine studies were eligible for this review including a total of 1792 people with CF and 1675 controls. Meta-analysis revealed that protein carbonyls (SMD: 1.13, 95% CI: 0.48 to 1.77), total F2-isoprostane 8-iso-prostaglandin F2α (SMD: 0.64, 95% CI: 0.23 to 1.05) and malondialdehyde (SMD: 1.34, 95% CI: 0.30 to 2.39) were significantly higher, and vitamins A (SMD: −0.66, 95% CI -1.14 to −0.17) and E (SMD: −0.74, 95% CI: −1.28 to −0.20), β-carotene (SMD: −1.80, 95% CI: −2.92 to −0.67), lutein (SMD: −1.52, 95% CI: −1.83 to −1.20) and albumin (SMD: −0.98, 95% CI: −1.68 to −0.27) were significantly lower in the plasma or serum of people with CF versus controls.
This systematic review and meta-analysis found good evidence for reduced antioxidant capacity and elevated oxidative stress in people with clinically-stable CF.
Display omitted
•Blood biomarkers of oxidative stress were elevated in stable CF vs non-CF controls.•Lipid peroxidation was positively correlated with age and immune cell count in CF.•Antioxidants vitamins A & E, β-carotene, lutein and albumin were lower in stable CF.•Antioxidants were positively correlated with body mass index and lung function in CF.
Sexually transmitted and genital infections in pregnancy are associated with adverse pregnancy and birth outcomes. Point-of-care tests for these infections facilitate testing and treatment in a ...single antenatal clinic visit and may reduce the risk of adverse outcomes. Successful implementation and scale-up depends on understanding comparative effectiveness of such programmes and their comparative costs and cost effectiveness. This systematic review synthesises and appraises evidence from economic evaluations of point-of-care testing and treatment for sexually transmitted and genital infections among pregnant women in low- and middle-income countries.
Medline, Embase and Web of Science databases were comprehensively searched using pre-determined criteria. Additional literature was identified by searching Google Scholar and the bibliographies of all included studies. Economic evaluations were eligible if they were set in low- and middle-income countries and assessed antenatal point-of-care testing and treatment for syphilis, chlamydia, gonorrhoea, trichomoniasis, and/or bacterial vaginosis. Studies were analysed using narrative synthesis. Methodological and reporting standards were assessed using two published checklists.
Sixteen economic evaluations were included in this review; ten based in Africa, three in Latin and South America and three were cross-continent comparisons. Fifteen studies assessed point-of-care testing and treatment for syphilis, while one evaluated chlamydia. Key drivers of cost and cost-effectiveness included disease prevalence; test, treatment, and staff costs; test sensitivity and specificity; and screening and treatment coverage. All studies met 75% or more of the criteria of the Drummond Checklist and 60% of the Consolidated Health Economics Evaluation Reporting Standards.
Generally, point-of-care testing and treatment was cost-effective compared to no screening, syndromic management, and laboratory-based testing. Future economic evaluations should consider other common infections, and their lifetime impact on mothers and babies. Complementary affordability and equity analyses would strengthen the case for greater investment in antenatal point-of-care testing and treatment for sexually transmitted and genital infections.
Purpose:
The pursuit of real-time image guided radiotherapy using optimal tissue contrast has seen the development of several hybrid magnetic resonance imaging (MRI)-treatment systems, high field and ...low field, and inline and perpendicular configurations. As part of a new MRI-linac program, an MRI scanner was integrated with a linear accelerator to enable investigations of a coupled inline MRI-linac system. This work describes results from a prototype experimental system to demonstrate the feasibility of a high field inline MR-linac.
Methods:
The magnet is a 1.5 T MRI system (Sonata, Siemens Healthcare) was located in a purpose built radiofrequency (RF) cage enabling shielding from and close proximity to a linear accelerator with inline (and future perpendicular) orientation. A portable linear accelerator (Linatron, Varian) was installed together with a multileaf collimator (Millennium, Varian) to provide dynamic field collimation and the whole assembly built onto a stainless-steel rail system. A series of MRI-linac experiments was performed to investigate (1) image quality with beam on measured using a macropodine (kangaroo) ex vivo phantom; (2) the noise as a function of beam state measured using a 6-channel surface coil array; and (3) electron contamination effects measured using Gafchromic film and an electronic portal imaging device (EPID).
Results:
(1) Image quality was unaffected by the radiation beam with the macropodine phantom image with the beam on being almost identical to the image with the beam off. (2) Noise measured with a surface RF coil produced a 25% elevation of background intensity when the radiation beam was on. (3) Film and EPID measurements demonstrated electron focusing occurring along the centerline of the magnet axis.
Conclusions:
A proof-of-concept high-field MRI-linac has been built and experimentally characterized. This system has allowed us to establish the efficacy of a high field inline MRI-linac and study a number of the technical challenges and solutions.
PDF
