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BACKGROUND: Due to the superficial location, suspicious findings of the nipple-areolar complex (NAC) are not amenable to stereotactic or MRI-guided sampling and have historically necessitated surgical biopsy or skin-punch biopsy. There are limited reports of US-guided core biopsy of the nipple (US-CBN). OBJECTIVE: We report our nearly 3-year pilot experience with US-CBN at an academic breast imaging center. METHODS: An institutional review board-exempt and HIPAA-compliant retrospective review was performed. We assessed patient demographics, breast imaging characteristics, procedural data, pathology, and outcomes. RESULTS: Nine female patients aged 27 to 64 underwent US-CBN from January 2021 to October 2023. Initial imaging abnormalities included abnormal MRI enhancement, mammographic calcifications, and sonographic masses. After initial or second-look US, all imaging findings had sonographic correlates for biopsy specimens, the majority of which were sonographic masses (8/9). US-CBN was performed by 6 breast radiologists using a variety of devices. All biopsy specimen results were concordant with sonographic abnormalities, although 1 was considered discordant from the initial abnormality seen on MRI. There were no complications, and discomfort during the procedure was well-treated. Two patients (22%, 2/9) were diagnosed with malignancy. CONCLUSION: This pilot study demonstrated that US-CBN can be performed by a breast radiologist for definitive diagnosis of suspicious nipple abnormalities seen on breast imaging, avoiding surgery, and maintaining nipple integrity. In our population, 22% (2/9) of US-CBNs revealed malignancy.
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Background: Allostatic load (AL) is the accumulation of physiological dysregulation attributed to repeated activation of the stress response over a lifetime. We assessed the utility of AL as a prognostic measure for high-risk benign breast biopsy pathology results. Method: Eligible patients were women 18 years or older, with a false-positive outpatient breast biopsy between January and December 2022 at a tertiary academic health center. AL was calculated using 12 variables representing four physiological systems: cardiovascular (pulse rate, systolic and diastolic blood pressures, total cholesterol, high-density lipoprotein, and low-density lipoprotein); metabolic (body mass index, albumin, and hemoglobin A1C); renal (creatinine and estimated glomerular filtration rate); and immune (white blood cell count). Multivariable logistic regression was used to assess the association between AL before biopsy and breast biopsy outcomes controlling for patients' sociodemographics. Results: In total, 170 women were included (mean age, 54.1 ± 12.9 years): 89.4% had benign and 10.6% had high-risk pathologies (radial scar/complex sclerosing lesion, atypical ductal or lobular hyperplasia, flat epithelial atypia, intraductal papilloma, or lobular carcinoma in-situ). A total of 56.5% were White, 24.7% Asian, and 17.1% other races. A total of 32.5% identified as Hispanic. The mean breast cancer risk score using the Tyrer-Cuzick model was 11.9 ± 7.0. In multivariable analysis, with every one unit increase in AL, the probability of high-risk pathology increased by 37% (odds ratio, 1.37; 95% confidence interval, 1.03, 1.81; p = 0.03). No significant association was seen between high-risk pathology and age, ethnicity, breast cancer risk, or area deprivation index. Conclusion: Our findings support that increased AL, a biological marker of stress, is associated with high-risk pathology among patients with false-positive breast biopsy results.
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As the proportion of women diagnosed with invasive breast cancer increases, the role of imaging for staging and surveillance purposes should be determined based on evidence-based guidelines. It is important to understand the indications for extent of disease evaluation and staging, as unnecessary imaging can delay care and even result in adverse outcomes. In asymptomatic patients that received treatment for curative intent, there is no role for imaging to screen for distant recurrence. Routine surveillance with an annual 2-D mammogram and/or tomosynthesis is recommended to detect an in-breast recurrence or a new primary breast cancer in women with a history of breast cancer, and MRI is increasingly used as an additional screening tool in this population, especially in women with dense breasts. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.
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Neoplasias de la Mama , Medicina Basada en la Evidencia , Invasividad Neoplásica , Sociedades Médicas , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Humanos , Femenino , Estados Unidos , Invasividad Neoplásica/diagnóstico por imagen , Estadificación de Neoplasias , Mamografía/normas , Imagen por Resonancia Magnética/métodosRESUMEN
BACKGROUND. Abbreviated breast MRI (AB-MRI) achieves a higher cancer detection rate (CDR) than digital breast tomosynthesis when applied for baseline (i.e., first-round) supplemental screening of individuals with dense breasts. Limited literature has evaluated subsequent (i.e., sequential) AB-MRI screening rounds. OBJECTIVE. This study aimed to compare outcomes between baseline and subsequent rounds of screening AB-MRI in individuals with dense breasts who otherwise had an average risk for breast cancer. METHODS. This retrospective study included patients with dense breasts who otherwise had an average risk for breast cancer and underwent AB-MRI for supplemental screening between December 20, 2016, and May 10, 2023. The clinical interpretations and results of recommended biopsies for AB-MRI examinations were extracted from the EMR. Baseline and subsequent-round AB-MRI examinations were compared. RESULTS. The final sample included 2585 AB-MRI examinations (2007 baseline and 578 subsequent-round examinations) performed for supplemental screening of 2007 women (mean age, 57.1 years old) with dense breasts. Of 2007 baseline examinations, 1658 (82.6%) were assessed as BI-RADS category 1 or 2, 171 (8.5%) as BI-RADS category 3, and 178 (8.9%) as BI-RADS category 4 or 5. Of 578 subsequent-round examinations, 533 (92.2%) were assessed as BI-RADS category 1 or 2, 20 (3.5%) as BI-RADS category 3, and 25 (4.3%) as BI-RADS category 4 or 5 (p < .001). The abnormal interpretation rate (AIR) was 17.4% (349/2007) for baseline examinations versus 7.8% (45/578) for subsequent-round examinations (p < .001). For baseline examinations, PPV2 was 21.3% (38/178), PPV3 was 26.6% (38/143), and the CDR was 18.9 cancers per 1000 examinations (38/2007). For subsequent-round examinations, PPV2 was 28.0% (7/25) (p = .45), PPV3 was 29.2% (7/24) (p = .81), and the CDR was 12.1 cancers per 1000 examinations (7/578) (p = .37). All 45 cancers diagnosed by baseline or subsequent-round AB-MRI were stage 0 or 1. Seven cancers diagnosed by subsequent-round AB-MRI had a mean interval of 872 ± 373 (SD) days since prior AB-MRI and node-negative status at surgical axillary evaluation; six had an invasive component, all measuring 1.2 cm or less. CONCLUSION. Subsequent rounds of AB-MRI screening of individuals with dense breasts had lower AIR than baseline examinations while maintaining a high CDR. All cancers detected by subsequent-round examinations were early-stage node-negative cancers. CLINICAL IMPACT. The findings support sequential AB-MRI for supplemental screening in individuals with dense breasts. Further investigations are warranted to optimize the screening interval.
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Densidad de la Mama , Neoplasias de la Mama , Imagen por Resonancia Magnética , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Persona de Mediana Edad , Imagen por Resonancia Magnética/métodos , Estudios Retrospectivos , Detección Precoz del Cáncer/métodos , Anciano , Adulto , Mama/diagnóstico por imagen , Mama/patologíaRESUMEN
Many novel PET radiotracers have demonstrated potential use in breast cancer. Although not currently approved for clinical use in the breast cancer population, these innovative imaging agents may one day play a role in the diagnosis, staging, management, and even treatment of breast cancer.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Radiofármacos , Tomografía de Emisión de Positrones/métodos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodosRESUMEN
BACKGROUND: Early changes in breast intratumor heterogeneity during neoadjuvant chemotherapy may reflect the tumor's ability to adapt and evade treatment. We investigated the combination of precision medicine predictors of genomic and MRI data towards improved prediction of recurrence free survival (RFS). METHODS: A total of 100 women from the ACRIN 6657/I-SPY 1 trial were retrospectively analyzed. We estimated MammaPrint, PAM50 ROR-S, and p53 mutation scores from publicly available gene expression data and generated four, voxel-wise 3-D radiomic kinetic maps from DCE-MR images at both pre- and early-treatment time points. Within the primary lesion from each kinetic map, features of change in radiomic heterogeneity were summarized into 6 principal components. RESULTS: We identify two imaging phenotypes of change in intratumor heterogeneity (p < 0.01) demonstrating significant Kaplan-Meier curve separation (p < 0.001). Adding phenotypes to established prognostic factors, functional tumor volume (FTV), MammaPrint, PAM50, and p53 scores in a Cox regression model improves the concordance statistic for predicting RFS from 0.73 to 0.79 (p = 0.002). CONCLUSIONS: These results demonstrate an important step in combining personalized molecular signatures and longitudinal imaging data towards improved prognosis.
Early changes in tumor properties during treatment may tell us whether or not a patient's tumor is responding to treatment. Such changes may be seen on imaging. Here, changes in breast cancer properties are identified on imaging and are used in combination with gene markers to investigate whether response to treatment can be predicted using mathematical models. We demonstrate that tumor properties seen on imaging early on in treatment can help to predict patient outcomes. Our approach may allow clinicians to better inform patients about their prognosis and choose appropriate and effective therapies.
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The sea urchin embryo development toxicity test was used to investigate toxicity of the benthic substrate in Biscayne National Park (BISC). Twenty-five sites were selected based upon a high potential for anthropogenic stressor input (e. g., hydrocarbons, personal care products, nutrients, etc.) or proximity to coral reef habitats. We found that sediment interstitial water (porewater) was toxic to urchin embryos at 22 of 25 sites. Healthy sites included two coral reefs (Anniversary Reef and Marker 14 Reef) and Turkey Point Channel. Discrete areas of BISC have highly toxic sediments and the presence of sediment contaminants could negatively impact reproduction, growth and population density of benthic invertebrates, such as corals. Results of the sea urchin embryo development toxicity test can be used as a baseline assessment for monitoring improvements or degradation in ecosystem health and could be a valuable tool to investigate the suitability of degraded habitats for future reef restoration. Since the last comprehensive environmental assessment of BISC was performed in 1999, further investigation into the sources of toxicity at BISC is needed.
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Lytechinus , Parques Recreativos , Animales , Ecosistema , Estado de Salud , TurquíaRESUMEN
Breast cancer is one of the most pervasive forms of cancer and its inherent intra- and inter-tumor heterogeneity contributes towards its poor prognosis. Multiple studies have reported results from either private institutional data or publicly available datasets. However, current public datasets are limited in terms of having consistency in: a) data quality, b) quality of expert annotation of pathology, and c) availability of baseline results from computational algorithms. To address these limitations, here we propose the enhancement of the I-SPY1 data collection, with uniformly curated data, tumor annotations, and quantitative imaging features. Specifically, the proposed dataset includes a) uniformly processed scans that are harmonized to match intensity and spatial characteristics, facilitating immediate use in computational studies, b) computationally-generated and manually-revised expert annotations of tumor regions, as well as c) a comprehensive set of quantitative imaging (also known as radiomic) features corresponding to the tumor regions. This collection describes our contribution towards repeatable, reproducible, and comparative quantitative studies leading to new predictive, prognostic, and diagnostic assessments.
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Neoplasias de la Mama , Algoritmos , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Femenino , Humanos , Imagen por Resonancia MagnéticaRESUMEN
Underconsumption of dietary fiber and the milieu of chemicals with which it is associated is a health concern linked to the increasing global burden of chronic diseases. The benefits of fiber are partially attributed to modulation of the gut microbiota, whose composition and function depend on the amount and quality of microbiota-accessible substrates in the diet. However, not all types of fiber are equally accessible to the gut microbiota. Phaseolus vulgaris L., or common bean, is a food type rich in fiber as well as other prebiotics posing a great potential to positively impact diet-microbiota-host interactions. To elucidate the magnitude of bean's effects on the gut microbiota, increasing doses of common bean were administered in macronutrient-matched diet formulations. The microbial communities in the ceca of female and male mice were evaluated via 16S rRNA gene sequencing. As the bean dose increased, the Bacillota:Bacteroidota ratio (formerly referred to as the Firmicutes:Bacteroidetes ratio) was reduced and α-diversity decreased, whereas the community composition was distinctly different between the diet groups according to ß-diversity. These effects were more pronounced in female mice compared to male mice. Compositional analyses identified a dose-responsive bean-induced shift in microbial composition. With an increasing bean dose, Rikenellaceae, Bacteroides, and RF39, which are associated with health benefits, were enhanced. More taxa, however, were suppressed, among which were Allobaculum, Oscillospira, Dorea, and Ruminococcus, which are predominantly associated with chronic disease risk. Investigation of the origins of the dose dependent and biological sex differences in response to common bean consumption may provide insights into bean-gut microbiota-host interactions important to developing food-based precision approaches to chronic disease prevention and control.
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Neoadjuvant immunotherapy with anti-cytotoxic T lymphocyte-associated protein 4 (CTLA4) + anti-programmed cell death protein 1 (PD1) monoclonal antibodies has demonstrated remarkable pathological responses and relapse-free survival in ~80% of patients with clinically detectable stage III melanoma. However, about 20% of the treated patients do not respond. In pretreatment biopsies of patients with melanoma, we found that resistance to neoadjuvant CTLA4 + PD1 blockade was associated with a low CD4/interleukin-2 (IL-2) gene signature. Ex vivo, addition of IL-2 to CTLA4 + PD1 blockade induced T cell activation and deep immunological responses in anti-CTLA4 + anti-PD1-resistant human tumor specimens. In the 4T1.2 breast cancer mouse model of neoadjuvant immunotherapy, triple combination of anti-CTLA4 + anti-PD1 + IL-2 cured almost twice as many mice as compared with dual checkpoint inhibitor therapy. This improved efficacy was due to the expansion of tumor-specific CD8+ T cells and improved proinflammatory cytokine polyfunctionality of both CD4+ and CD8+ T effector cells and regulatory T cells. Depletion studies suggested that CD4+ T cells were critical for priming of CD8+ T cell immunity against 4T1.2 and helped in the expansion of tumor-specific CD8+ T cells early after neoadjuvant triple immunotherapy. Our results suggest that the addition of IL-2 can overcome resistance to neoadjuvant anti-CTLA4 + anti-PD1, providing the rationale for testing this combination as a neoadjuvant therapy in patients with early-stage cancer.
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Antígeno CTLA-4 , Interleucina-2 , Melanoma , Animales , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/inmunología , Antígeno CTLA-4/antagonistas & inhibidores , Antígeno CTLA-4/inmunología , Humanos , Interleucina-2/farmacología , Melanoma/tratamiento farmacológico , Melanoma/inmunología , Melanoma/patología , Ratones , Terapia Neoadyuvante , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunologíaRESUMEN
Fluorine 18 (18F) fluorthanatrace (18F-FTT) is a PET radiotracer for imaging poly (adenosine diphosphate-ribose) polymerase-1 (PARP-1), an important target for a class of drugs known as PARP inhibitors, or PARPi. This article describes the stepwise development of this radiotracer from its design and preclinical evaluation to the first-in-human imaging studies and the initial validation of 18F-FTT as an imaging-based biomarker for measuring PARP-1 expression levels in patients with breast and ovarian cancer. A detailed discussion on the preparation and submission of an exploratory investigational new drug application to the Food and Drug Administration is also provided. Additionally, this review highlights the need and future plans for identifying a commercialization strategy to overcome the major financial barriers that exist when conducting the multicenter clinical trials needed for approval in the new drug application process. The goal of this article is to provide a road map that scientists and clinicians can follow for the successful clinical translation of a PET radiotracer developed in an academic setting. Keywords: Molecular Imaging-Cancer, PET, Breast, Genital/Reproductive, Chemistry, Radiotracer Development, PARPi, 18F-FTT, Investigational New Drug © RSNA, 2022.
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Neoplasias Ováricas , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Femenino , Humanos , Estudios Multicéntricos como Asunto , Poli(ADP-Ribosa) Polimerasa-1/metabolismo , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Poli(ADP-Ribosa) Polimerasas/metabolismo , Tomografía de Emisión de Positrones/métodos , Estados UnidosRESUMEN
BACKGROUND: Orthopaedic surgeons must consider their postoperative pain management strategies to minimize harm from prescription opioid use. Patients often reference their pain threshold to predict how they will tolerate surgical pain and the need for postoperative analgesia, but the direct relationship between these factors has not yet been studied. The purpose of this study was to determine the relationship between patients' self-reported pain tolerance and prescription opioid usage after foot and ankle surgery. METHODS: This is a retrospective follow-up of a prospective cohort study of adult patients who underwent outpatient foot and ankle surgeries. Patient and procedural demographics, opioid pills dispensed, and opioid pills consumed by the first postoperative visit were obtained. Patients were contacted at a mean of 13.1 ± 4.0 months postoperatively and asked to respond to the qualitative statement "Pain doesn't bother me as much as it does most people." Patients were also asked their quantitative pain threshold (0-100), with 0 being "very pain intolerant" and 100 being a "very high pain tolerance," as well other questions regarding past surgical and narcotic consumption history. RESULTS: Of the 700 survey respondents, the average age was 50.9 years and 34.7% were male. Bivariate analysis determined that predictors of lower postoperative opioid consumption included higher quantitative (P = .047) and qualitative (P = .005) pain tolerance scores. Multivariate analysis for the entire cohort demonstrated that higher qualitative pain threshold was associated with lower postoperative opioid consumption (P = .005) but this did not meet statistical significance as an independent predictor of the top quartile of pill consumers. CONCLUSION: Assessment of both qualitative and quantitative score of patients' pain threshold prior to surgery may assist the surgeon in tailoring postoperative pain control. Additionally, asking this question can create an opportunity for educating patients regarding responsible utilization of narcotic medication. LEVELS OF EVIDENCE: Level III.
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Analgésicos Opioides , Dolor Postoperatorio , Adulto , Analgésicos Opioides/uso terapéutico , Tobillo/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Narcóticos/uso terapéutico , Umbral del Dolor , Dolor Postoperatorio/tratamiento farmacológico , Estudios Prospectivos , Estudios Retrospectivos , AutoinformeRESUMEN
OBJECTIVE: To assess the frequency, management, and early outcomes of COVID-19 vaccine-related adenopathy on breast MRI. METHODS: This IRB-exempt retrospective study reviewed patients who underwent breast MRI following COVID-19 vaccine approval in the U.S. from December 14, 2020, to April 11, 2021 (N = 1912) and compared patients who underwent breast MRI the year prior to the pandemic, March 13, 2019, to March 12, 2020 (N = 5342). Study indication, patient age, date of study, date and type of vaccination(s), time difference between study and vaccinations, lymph node-specific and overall management recommendations, and outcomes of additional examinations were recorded. Differences in the final assessment categories between the subjects scanned pre-pandemic and post-vaccine were compared using the Fisher exact test. RESULTS: Vaccine-related adenopathy was mentioned in 67 breast MRI reports; only 1 in the pre-pandemic group. There were no clinically relevant differences in patient demographics between groups. There was a statistically significant increase in BI-RADS 0 assessments between the pre-pandemic and post-vaccine approval groups-0.8% (45/5342) versus 1.8% (34/1912) (P = 0.001) and BI-RADS 3 assessments-6.5% (348/5342) versus 9.2% (176/1912) (P < 0.0001). Of the 29 patients who underwent additional imaging (range, 2-94 days following MRI) and the 2 patients who underwent biopsy, 47% (31/66), none were found to have malignant adenopathy. CONCLUSION: COVID-19 vaccination is associated with transient axillary adenopathy of variable duration. This leads to additional imaging in women undergoing breast MRI, so far with benign outcomes, and this may affect audits of outcomes of MRI.
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To understand the contribution of mononuclear phagocytes (MNP), which include monocyte-derived intestinal macrophages, to the pathogenesis of inflammatory bowel disease (IBD), it is necessary to identify functionally-different MNP populations. We aimed to characterise intestinal macrophage populations in patients with IBD. We developed 12-parameter flow cytometry protocols to identify and human intestinal MNPs. We used these protocols to purify and characterize colonic macrophages from colonic tissue from patients with Crohn's disease (CD), ulcerative colitis (UC), or non-inflamed controls, in a cross-sectional study. We identify macrophage populations (CD45+CD64+ HLA-DR+) and describe two distinct subsets, differentiated by their expression of the mannose receptor, CD206. CD206+ macrophages expressed markers consistent with a mature phenotype: high levels of CD68 and CD163, higher transcription of IL-10 and lower expression of TREM1. CD206- macrophages appear to be less mature, with features more similar to their monocytic precursors. We identified and purified macrophage populations from human colon. These appear to be derived from a monocytic precursor with high CCR2 and low CD206 expression. As these cells mature, they acquire expression of IL-10, CD206, CD63, and CD168. Targeting the newly recruited monocyte-derived cells may represent a fruitful avenue to ameliorate chronic inflammation in IBD.
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Susceptibilidad a Enfermedades , Enfermedades Inflamatorias del Intestino/etiología , Enfermedades Inflamatorias del Intestino/metabolismo , Macrófagos/inmunología , Macrófagos/metabolismo , Glicoproteínas de Membrana/metabolismo , Receptores Inmunológicos/metabolismo , Biomarcadores , Susceptibilidad a Enfermedades/inmunología , Perfilación de la Expresión Génica , Humanos , Inmunidad Innata , Inmunidad Mucosa , Inmunofenotipificación , Enfermedades Inflamatorias del Intestino/patología , Interleucina-10/genética , Interleucina-10/metabolismo , Mucosa Intestinal/inmunología , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Glicoproteínas de Membrana/genética , Receptores Inmunológicos/genética , TranscriptomaRESUMEN
Background Suppression of background parenchymal enhancement (BPE) is commonly observed after neoadjuvant chemotherapy (NAC) at contrast-enhanced breast MRI. It was hypothesized that nonsuppressed BPE may be associated with inferior response to NAC. Purpose To investigate the relationship between lack of BPE suppression and pathologic response. Materials and Methods A retrospective review was performed for women with menopausal status data who were treated for breast cancer by one of 10 drug arms (standard NAC with or without experimental agents) between May 2010 and November 2016 in the Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis 2, or I-SPY 2 TRIAL (NCT01042379). Patients underwent MRI at four points: before treatment (T0), early treatment (T1), interregimen (T2), and before surgery (T3). BPE was quantitatively measured by using automated fibroglandular tissue segmentation. To test the hypothesis effectively, a subset of examinations with BPE with high-quality segmentation was selected. BPE change from T0 was defined as suppressed or nonsuppressed for each point. The Fisher exact test and the Z tests of proportions with Yates continuity correction were used to examine the relationship between BPE suppression and pathologic complete response (pCR) in hormone receptor (HR)-positive and HR-negative cohorts. Results A total of 3528 MRI scans from 882 patients (mean age, 48 years ± 10 [standard deviation]) were reviewed and the subset of patients with high-quality BPE segmentation was determined (T1, 433 patients; T2, 396 patients; T3, 380 patients). In the HR-positive cohort, an association between lack of BPE suppression and lower pCR rate was detected at T2 (nonsuppressed vs suppressed, 11.8% [six of 51] vs 28.9% [50 of 173]; difference, 17.1% [95% CI: 4.7, 29.5]; P = .02) and T3 (nonsuppressed vs suppressed, 5.3% [two of 38] vs 27.4% [48 of 175]; difference, 22.2% [95% CI: 10.9, 33.5]; P = .003). In the HR-negative cohort, patients with nonsuppressed BPE had lower estimated pCR rate at all points, but the P values for the association were all greater than .05. Conclusions In hormone receptor-positive breast cancer, lack of background parenchymal enhancement suppression may indicate inferior treatment response. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Philpotts in this issue.
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Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante/métodos , Medios de Contraste , Aumento de la Imagen/métodos , Imagen por Resonancia Magnética/métodos , Terapia Neoadyuvante/métodos , Adulto , Anciano , Mama/diagnóstico por imagen , Estudios de Cohortes , Femenino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND[18F]FluorThanatrace ([18F]FTT) is a radiolabeled poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi) that enables noninvasive quantification of PARP with potential to serve as a biomarker for patient selection for PARPi therapy. Here we report for the first time to our knowledge noninvasive in vivo visualization of drug-target engagement during PARPi treatment.METHODSTwo single-arm, prospective, nonrandomized clinical trials were conducted at the University of Pennsylvania from May 2017 to March 2020. PARP expression in breast cancer was assessed in vivo via [18F]FTT PET before and after initiation of PARPi treatment and in vitro via [125I]KX1 (an analog of [18F]FTT) binding to surgically removed breast cancer.RESULTSThirteen patients had baseline [18F]FTT PET. Nine of these then had resection and in vitro evaluation of [18F]FTT uptake with an analog and uptake was blocked with PARPi. Of the other 4 patients, 3 had [18F]FTT PET uptake, and all had uptake blocked with treatment with a therapeutic PARPi. Initial in vivo [18F]FTT tumor uptake ranged from undetectable to robust. Following initiation of PARPi therapy, [18F]FTT uptake was not detectable above background in all cases. In vitro tumor treatment with a PARPi resulted in 82% reduction in [125I]KX1 binding.CONCLUSION[18F]FTT noninvasively quantifies PARP-1 expression. Early results indicate ability to visualize PARPi drug-target engagement in vivo and suggest the utility of further study to test [18F]FTT PET as a predictive and pharmacodynamic biomarker.TRIAL REGISTRATIONClinicalTrials.gov identifiers NCT03083288 and NCT03846167.FUNDINGMetavivor Translational Research Award, Susan G. Komen for the Cure (CCR 16376362), Department of Defense BC190315, and Abramson Cancer Center Breakthrough Bike Challenge.
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Neoplasias de la Mama/diagnóstico por imagen , Neoplasias Hepáticas/diagnóstico por imagen , Ganglios Linfáticos/diagnóstico por imagen , Poli(ADP-Ribosa) Polimerasa-1/metabolismo , Inhibidores de Poli(ADP-Ribosa) Polimerasas/metabolismo , Radiofármacos , Neoplasias de la Columna Vertebral/diagnóstico por imagen , Adulto , Anciano , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Femenino , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundario , Ganglios Linfáticos/metabolismo , Persona de Mediana Edad , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Columna Vertebral/tratamiento farmacológico , Neoplasias de la Columna Vertebral/metabolismo , Neoplasias de la Columna Vertebral/secundarioRESUMEN
Breast MRI is the most sensitive modality for the detection of breast cancer. However, false-negative cases may occur, in which the cancer is not visualized at MRI and is instead diagnosed with another imaging modality. The authors describe the causes of false-negative breast MRI results, which can be categorized broadly as secondary to perceptual errors or cognitive errors, or nonvisualization secondary to nonenhancement of the tumor. Tips and strategies to avoid these errors are discussed. Perceptual errors occur when an abnormality is not prospectively identified, yet the examination is technically adequate. Careful development of thorough search patterns is critical to avoid these errors. Cognitive errors occur when an abnormality is identified but misinterpreted or mischaracterized as benign. The radiologist may avoid these errors by utilizing all available prior examinations for comparison, viewing images in all planes to better assess the margins and shapes of abnormalities, and appropriately integrating all available information from the contrast-enhanced, T2-weighted, and T1-weighted images as well as the clinical history. Despite this, false-negative cases are inevitable, as certain subtypes of breast cancer, including ductal carcinoma in situ, invasive lobular carcinoma, and certain well-differentiated invasive cancers, may demonstrate little to no enhancement at MRI, owing to differences in angiogenesis and neovascularity. MRI is a valuable diagnostic tool in breast imaging. However, MRI should continue to be used as a complementary modality, with mammography and US, in the detection of breast cancer. ©RSNA, 2021.
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Neoplasias de la Mama , Carcinoma Ductal de Mama , Mama , Neoplasias de la Mama/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Mamografía , Sensibilidad y EspecificidadRESUMEN
OBJECTIVE: The A6702 multisite trial confirmed that apparent diffusion coefficient (ADC) measures can improve breast MRI accuracy and reduce unnecessary biopsies, but also found that technical issues rendered many lesions non-evaluable on diffusion-weighted imaging (DWI). This secondary analysis investigated factors affecting lesion evaluability and impact on diagnostic performance. METHODS: The A6702 protocol was IRB-approved at 10 institutions; participants provided informed consent. In total, 103 women with 142 MRI-detected breast lesions (BI-RADS assessment category 3, 4, or 5) completed the study. DWI was acquired at 1.5T and 3T using a four b-value, echo-planar imaging sequence. Scans were reviewed for multiple quality factors (artifacts, signal-to-noise, misregistration, and fat suppression); lesions were considered non-evaluable if there was low confidence in ADC measurement. Associations of lesion evaluability with imaging and lesion characteristics were determined. Areas under the receiver operating characteristic curves (AUCs) were compared using bootstrapping. RESULTS: Thirty percent (42/142) of lesions were non-evaluable on DWI; 23% (32/142) with image quality issues, 7% (10/142) with conspicuity and/or localization issues. Misregistration was the only factor associated with non-evaluability (P = 0.001). Smaller (≤10 mm) lesions were more commonly non-evaluable than larger lesions (p <0.03), though not significant after multiplicity correction. The AUC for differentiating benign and malignant lesions increased after excluding non-evaluable lesions, from 0.61 (95% CI: 0.50-0.71) to 0.75 (95% CI: 0.65-0.84). CONCLUSION: Image quality remains a technical challenge in breast DWI, particularly for smaller lesions. Protocol optimization and advanced acquisition and post-processing techniques would help to improve clinical utility.