Newly Diagnosed Breast Cancer: Comparison of Contrast-enhanced Spectral Mammography and Breast MR Imaging in the Evaluation of Extent of Disease.

Purpose To compare the diagnostic performances of contrast material-enhanced spectral mammography and breast magnetic resonance (MR) imaging in the detection of index and secondary cancers in women with newly diagnosed breast cancer by using histologic or imaging follow-up as the standard of reference. Materials and Methods This institutional review board-approved, HIPAA-compliant, retrospective study included 52 women who underwent breast MR imaging and contrast-enhanced spectral mammography for newly diagnosed unilateral breast cancer between March 2014 and October 2015. Of those 52 patients, 46 were referred for contrast-enhanced spectral mammography and targeted ultrasonography because they had additional suspicious lesions at MR imaging. In six of the 52 patients, breast cancer had been diagnosed at an outside institution. These patients were referred for contrast-enhanced spectral mammography and targeted US as part of diagnostic imaging. Images from contrast-enhanced spectral mammography were analyzed by two fellowship-trained breast imagers with 2.5 years of experience with contrast-enhanced spectral mammography. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value were calculated for both imaging modalities and compared by using the Bennett statistic. Results Fifty-two women with 120 breast lesions were included for analysis (mean age, 50 years; range, 29-73 years). Contrast-enhanced spectral mammography had similar sensitivity to MR imaging (94% [66 of 70 lesions] vs 99% [69 of 70 lesions]), a significantly higher PPV than MR imaging (93% [66 of 71 lesions] vs 60% [69 of 115 lesions]), and fewer false-positive findings than MR imaging (five vs 45) (P < .001 for all results). In addition, contrast-enhanced spectral mammography depicted 11 of the 11 secondary cancers (100%) and MR imaging depicted 10 (91%). Conclusion Contrast-enhanced spectral mammography is potentially as sensitive as MR imaging in the evaluation of extent of disease in newly diagnosed breast cancer, with a higher PPV. © RSNA, 2017.

Understanding the needs of people aging with type 1 diabetes: a user-focused research study with prototype diabetes advance directive and setting the stage for future research.

Purpose: People living with Type 1 diabetes (T1D) are living longer than ever and facing the new "luxury" of the challenges of aging. While research is slowly expanding and addressing T1D physiology with regards to aging, there is little research addressing specific challenges and barriers to optimal care by those aging with T1D. To address this gap, this study employed human-centered design research to explore the gaps and barriers to care faced by people aging with T1D. Methods: Researchers employed human-centered design methods of needfinding and user interviews and facilitated participatory workshops. In total, 27 people with T1D (PWT1D), 5 loved ones (partners of PWT1D), and 7 healthcare providers (HCPs) were engaged. Results: Design artifacts were developed, including user personas that help visually articulate the different experiences of PWT1D and their unique needs as they age, as well as a prototype diabetes-specific advance directive that could be further refined to specifically aid those with Type 1 diabetes who are aging and requiring more interactions with the healthcare system. Initial user testing with people with T1D as well as healthcare providers demonstrated the need for such a diabetes advance directive tool or document. Conclusion: This work supports the conclusion that additional focus and scientific enquiry should be given to the needs of people aging with Type 1 diabetes, with a goal of improving the experience of all people with T1D when interacting with their care providers or with the healthcare system as a whole.

Quantitative Analysis of Contrast-enhanced Mammography for Risk Stratification of Benign Versus Malignant Disease and Molecular Subtype.

OBJECTIVE: To assess quantitative enhancement of benign, high-risk, and malignant lesions and differences in molecular subtype and grade of malignant lesions on contrast-enhanced mammography (CEM). METHODS: This IRB-approved retrospective study included women who underwent CEM for diagnostic work-up of a breast lesion between 2014 and 2020. Inclusion criteria were women who had diagnostic work-up with CEM and had BI-RADS 1 or 2 with one year follow-up, BI-RADS 3 with tissue diagnosis or stability for 2 years, or BI-RADS 4 or 5 with tissue diagnosis. An enhancement ratio was calculated for all lesions. This was obtained by drawing a region of interest within the lesion and a second region of interest in the nonenhancing background tissue using a program developed with MATLAB. Descriptive statistics were evaluated using chi-squared tests, Fisher exact tests, and analysis of variance. A logistic regression model was used to predict cancer outcome using the enhancement ratio. Statistical significance was defined as P < 0.05. RESULTS: There were 332 lesions in 210 women that met study criteria. Of the 332 lesions, 50.9% (169/332) were malignant, 5.7% (19/332) were high-risk, and 43.4% (144/332) were benign. Enhancement intensity of malignant lesions was higher than benign lesions. Odds ratio for quantitative enhancement of malignant lesions was 30.15 (P < 0.0001). Enhancement ratio above 1.49 had an 84.0% sensitivity and 84.0% specificity for malignancy. HER2-enriched breast cancers had significantly higher mean enhancement ratios (P = 0.0062). CONCLUSION: Quantitative enhancement on CEM demonstrated that malignant breast lesions had higher mean enhancement intensity than benign lesions.

Monitoring Patient Response to Pembrolizumab With Peripheral Blood Exhaustion Marker Profiles.

Exhausted T cells are effector T cells that are silenced due to continuous T cell receptor (TCR) stimulation from persistent antigens. Characteristics of exhaustion include the increased expression of multiple inhibitory receptors such as programme death-1[PD-1], lymphocyte activation gene 3 [LAG-3], T cell Ig and mucin domain [TIM-3], the loss of effector cytokine secretion and altered transcriptional profile. The PD-1/PD-L1 interaction induces functional exhaustion of tumor-reactive cytotoxic T cells and interferes with anti-tumor T cell immunity. T cell exhaustion has been observed in metastatic melanoma patients where the exhaustion of tumor specific T cells suggests that tumor clearance has been impeded and contributed to tumor immune escape. Checkpoint immunotherapies are antibodies designed to block the interaction between the inhibitory receptors expressed on T cells and their respective ligands. Therapies such as anti-PD-1 (Pembrolizumab and Nivolumab) block these inhibitory receptors and are associated with a significant improvement in overall survival and progression free survival. However, only 20-40% of metastatic melanoma patients experience long-term benefit. In a cohort of 16 metastatic melanoma patients receiving pembrolizumab, blood was serially collected before each infusion (mean 8.3; range 1-12 cycles). The presence of inhibitory markers LAG-3, TIM-3, and PD-1 on the surface of T cells was examined and assessed in relation to patient response to identify if inhibitory markers can be used to differentiate responders from non-responders for Pembrolizumab. We confirmed that across a range of cycles (range 1-26) of pembrolizumab, PD-1 expression was significantly higher on CD4+ T cells from non-responders compared to responders and TIM-3 expressed on the surface of CD8+ T cells was significantly higher in non-responders compared to responders. This longitudinal data confirms previous studies that assessed single timepoints. This study provides preliminary evidence that PD-1 and TIM-3 may be predictive of non-responders when assessed over multiple treatment cycles.

Biomarkers of platinum resistance in ovarian cancer: what can we use to improve treatment.

Ovarian cancer has poor survival rates due to a combination of diagnosis at advanced disease stages and disease recurrence as a result of platinum chemotherapy resistance. High-grade serous ovarian cancer (HGSOC), the most common ovarian cancer subtype, is conventionally treated with surgery and paclitaxel/carboplatin combination chemotherapy. Initial response rates are 60-80%, but eventually the majority of patients become platinum-resistant with subsequent relapses. Extensive research on individual biomarkers of platinum resistance has revealed many potential targets for the development new treatments. While this is ongoing, there are also epigenetic, DNA repair, genome and immune changes characterised in platinum-resistant HGSOC that can be targeted with current therapies. This review discusses biomarkers of platinum chemotherapy resistance in ovarian cancer with a focus on biomarkers that are targetable with alternative treatment combinations to those currently used. After decades of research focused on elucidating the biological cause of platinum resistance, future research needs to focus on using this knowledge to overcome resistance for patients with ovarian cancer.

Diabetic Mastopathy: Adjunctive Use of Ultrasound and Utility of Core Biopsy in Diagnosis.

Diabetic mastopathy is uncommon but occurs in long-term insulin-dependent diabetic patients who develop hard palpable breast masses which mimic breast cancer and are occult mammographically. Ultrasound evaluation is useful to analyze the masses. There is a spectrum of ultrasound findings from marked acoustic shadowing to a vague hypoechoic area without shadowing. Ultrasound-guided core biopsy (CB) is recommended for a definitive diagnosis since fine needle aspiration biopsy (FNAB) yields insufficient material for diagnosis secondary to extensive fibrosis. Four of the 11 patients in our series had FNAB, which was reported as insufficient material for diagnosis. However, 10 of 11 patients with diabetic mastopathy were successfully diagnosed by ultrasound-guided CB, helping to avoid an unnecessary surgical excisional biopsy.

The research pendulum: multiple roles and responsibilities as a researcher.

Qualitative research on sexual identities has highlighted the use of oral narratives to understand the lives of lesbians and gay men. Feminist ethnographers, sociologists and queer theorists have further posed methodological inquiries to the issues of insider/outsider, the possibilities of an erotic subject and the matter of representation. Using interview data with Hong Kong lesbians, this paper discusses a researcher's multiple positionalities and its effects on both the researched and the researcher. Being self-reflexive requires a researcher to test her or his own boundaries and to take up social responsibilities as the interpreter of texts. This paper calls for further dialogue between a researcher's subject positions, research processes and the final presentation of findings. doi:10.1300/J155v10n03_02.