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Our rationale was to investigate whether 18 F-FDG PET/MRI in addition to (guideline-recommended) conventional staging leads to changes in therapeutic management in patients with newly diagnosed breast cancer and compare the diagnostic accuracy of 18 F-FDG PET/MRI with that of conventional staging for determining the Union for International Cancer Control (UICC) stage. Methods: In this prospective, double-center study, 208 women with newly diagnosed, therapy-naïve invasive breast cancer were enrolled in accordance with the inclusion criteria. All patients underwent guideline-recommended conventional staging and whole-body 18 F-FDG PET/MRI with a dedicated breast examination. A multidisciplinary tumor board served to determine 2 different therapy recommendations for each patient, one based on conventional staging alone and another based on combined assessment of conventional staging and 18 F-FDG PET/MRI examinations. Major changes in therapy recommendations and differences between the conventional staging algorithm and 18 F-FDG PET/MRI for determining the correct UICC stage were reported and evaluated. Results: Major changes in therapeutic management based on combined assessment of conventional staging and 18 F-FDG PET/MRI were detected in 5 of 208 patients, amounting to changes in therapeutic management in 2.4% (95% CI, 0.78%-5.2%) of the study population. In determining the UICC stage, the guideline-based staging algorithm and 18 F-FDG PET/MRI were concordant in 135 of 208 (64.9%; 95% CI, 58%-71.4%) patients. The conventional guideline algorithm correctly determined the UICC stage in 130 of 208 (62.5%; 95% CI, 55.5%-69.1%) patients, and 18 F-FDG PET/MRI correctly determined the UICC stage in 170 of 208 (81.9%; 95% CI, 75.8%-86.7%) patients. Conclusion: Despite the diagnostic superiority of 18 F-FDG PET/MRI over conventional staging in determining the correct UICC stage, the current (guideline-recommended) conventional staging algorithm is sufficient for adequate therapeutic management of patients with newly diagnosed breast cancer, and 18 F-FDG PET/MRI does not have an impact on patient management., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: We determined over-the-counter magnifier usage rates by patients who newly presented for vision rehabilitation services, and sought to elucidate whether patients' ratings of over-the-counter magnifiers were associated with vision rehabilitation management strategies., Methods: Retrospective records reviews of 274 new vision rehabilitation patients seen between 2021-2023 were completed by three optometric providers at an ophthalmic academic center, college of optometry, and private practice., Results: Over half (58%) of patients tried an over-the-counter magnifier. Older age was significantly associated with trying over-the-counter magnifiers (OR:1.04; p  < 0.001). Patients who tried an over-the-counter magnifier had significantly greater odds of the provider recommending and/or dispensing a prescribed hand-held optical illuminated magnifier ( P < =0.04) or recommending a CCTV electronic magnifier ( p  = 0.049). The majority indicated over-the-counter magnifiers were somewhat (46%) or not helpful (38%). There was a significantly greater odds of rating the over-the-counter magnifier as not helpful when the provider subsequently recommended a CCTV (OR:4.8; p  = 0.01) or higher spectacle-based near add power (OR: 2.0; p  = 0.02)., Conclusions: Since most new patients were unsatisfied with over-the-counter magnifiers, it is encouraging that previous over-the-counter magnifier use often led to upgrades with hand-held optical illuminated magnifiers prescribed by vision rehabilitation providers, or patients were transitioned to CCTV electronic magnifiers or spectacle-based high add powers for near reading. These findings support that older adults who have previously experienced that over-the-counter magnifiers were either helpful or unhelpful are ideal candidates to receive vision rehabilitation by optometric providers who can transition them to a prescribed magnification device to better support their visual functioning needs for near reading.

Significance: Future work should develop and evaluate interventional strategies to help overcome visual and health-related barriers to travel in visually impaired seniors and mitigate adverse impacts of loneliness for those who do not leave town., Purpose: Life space refers to the area in which a person travels within a given time period. We explored whether demographics, vision, and/or health characteristics were related to restrictions in self-reported life space for visually impaired seniors., Methods: Visually impaired (n = 114) clinical trial participants aged ≥55 years learned visual assistive iPhone apps and completed the following baseline questionnaires: Life Space, 36-Item Short-Form Health Survey, University of California, Los Angeles Loneliness Scale, and New-General Self-efficacy Scale. Multiple logistic regressions evaluated associations between life space and patient factors after accounting for their distance to the next county or state., Results: During 2021 to 2023, 17%, 43%, and 70% of participants had not left their town, county, or state, respectively, in the past 3 months, or planned to in the next 3 months. Those with reduced distance best-corrected visual acuity had greater odds of not leaving the county in these time frames (odds ratio [OR] = 3.5; p=0.04). Minority race was associated with greater odds of not leaving town or the county in the past 2 weeks or future 3 months (OR = 4.3 to 6.4; p=0.009 to 0.049). Increased self-efficacy was associated with reduced odds of not leaving the state in the past 3 months, next 3 months, or past and/or future 3 months (OR = 0.54 to 0.55; p=0.02 to 0.03). Better physical function was associated with reduced odds of not leaving the state in the past 2 weeks or 3 months (OR = 0.96 to 0.98; p=0.01 to 0.04). Increased loneliness was related to greater odds of not leaving town in the past and/or future 3 months (OR = 1.8 to 2.0; p=0.007 to 0.009)., Conclusions: Minority race, reduced vision, self-efficacy, and physical health were related to life space restrictions in this cohort of visually impaired seniors, whereas loneliness was greater among those who were not leaving town., Competing Interests: Conflict of Interest Disclosure: There are no relevant financial conflicts of interest for any author. The sponsor provided funding but was not involved in the study design, conduct, analysis, or manuscript preparation. The authors had access to and control of the data in this study. The authors were responsible for preparation of this manuscript and the decision to submit this article for publication. Each of the authors had full access to the study data and take full responsibility for their presentation in this article., (Copyright © 2024 American Academy of Optometry.)

Significance: A majority of visually impaired older adults were able to learn to proficiently use visual-assistive iPhone applications (apps) following a median 1 hour and/or multiple training sessions, which should be considered when planning vision rehabilitation service delivery, including the option for remote telerehabilitation for those who prefer that modality., Purpose: Older adults with low vision are increasingly using technology to improve their visual functioning. We examined whether age-related comorbidities were potential barriers to success in learning to use visual-assistive apps on a smartphone., Methods: A clinical trial assessed visual-assistive apps in 116 older adults aged 55+ years (mean [standard deviation], 72 [10] years). Subjects were randomized to use an app (SuperVision+, Seeing AI, or Aira) preloaded to a loaner iPhone and completed one-on-one training. App proficiency was measured by the participant's ability to use the iPhone/app without cueing at the end of training sessions. Training time was recorded for the initial session and totaled after subsequent sessions. Multiple regression models explored significant factors associated with training time and proficiency., Results: Median initial and total training times were 45 and 60 minutes, respectively. Increased initial and total training times were both significantly related to increased age (p<0.001), legal blindness (p<0.007), Seeing AI versus SuperVision+ app (p<0.03), and participants from New England versus California (p<0.001). Most (71%) achieved proficiency after the initial training session; those odds were significantly greater among younger participants (p=0.04), those who opted for telerehabilitation (p=0.03), those who had higher cognitive scores (p=0.04), or those who were from New England (p=0.04). The majority (90%) was ultimately proficient with the app; those odds were significantly greater among participants who already had an optical magnifier (p=0.008), but were unrelated to other factors including study site., Conclusions: Following multiple, extensive training sessions, age, mild cognitive loss, or level of visual impairment did not preclude gaining proficiency with visual-assistive apps by visually impaired seniors, but those factors were associated with longer training times. Telerehabilitation can be a viable option to provide app training remotely for visually impaired seniors who choose that modality., Competing Interests: Conflict of Interest Disclosure: None of the authors have reported a financial conflict of interest., (Copyright © 2024 American Academy of Optometry.)

Background: Leucine-rich α-2 glycoprotein 1 (LRG-1) is a secreted glycoprotein that is mainly produced in the liver. Elevated levels of LRG-1 are found in a multitude of pathological conditions including eye diseases, diabetes, infections, autoimmune diseases, and cancer. In patients with early breast cancer (BC), high intratumoral LRG-1 protein expression levels are associated with reduced survival. In this study, we assessed serum levels of LRG-1 in patients with early BC and investigated its correlation with the presence of disseminated tumor cells (DTCs) in the bone marrow and survival outcomes., Methods: Serum LRG-1 levels of 509 BC patients were determined using ELISA and DTCs were assessed by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3. We stratified LRG-1 levels according to selected clinical parameters. Using the log-rank (Mantel-Cox) test and multivariate Cox regression analysis, Kaplan-Meier survival curves and prognostic relevance were assessed., Results: Mean serum levels of LRG-1 were 29.70 ± 8.67 µg/ml. Age was positively correlated with LRG-1 expression (r = 0.19; p < 0.0001) and significantly higher LRG-1 levels were found in patients over 60 years compared to younger ones (30.49 ± 8.63 µg/ml vs. 28.85 ± 8.63 µg/ml; p = 0.011) and in postmenopausal patients compared to premenopausal patients (30.15 ± 8.34 µg/ml vs. 26.936.94 µg/ml; p = 0.002). Patients with no DTCs showed significantly elevated LRG-1 levels compared to the DTC-positive group (30.51 ± 8.69 µg/ml vs. 28.51 ± 8.54 µg/ml; p = 0.004). Overall and BC-specific survival was significantly lower in patients with high serum LRG-1 levels (above a cut-off of 33.63 µg/ml) compared to patients with lower LRG-1 levels during a mean follow-up of 8.5 years (24.8% vs. 11.1% BC-specific death; p = 0.0003; odds ratio 2.63, 95%CI: 1.56-4.36). Multivariate analyses revealed that LRG-1 is an independent prognostic marker for BC-specific survival (p = 0.001; hazard ratio 2.61)., Conclusions: This study highlights the potential of LRG-1 as an independent prognostic biomarker in patients with early BC., (© 2024. The Author(s).)

Purpose: To evaluate if a machine learning prediction model based on clinical and easily assessable imaging features derived from baseline breast [ 18 F]FDG-PET/MRI staging can predict pathologic complete response (pCR) in patients with newly diagnosed breast cancer prior to neoadjuvant system therapy (NAST)., Methods: Altogether 143 women with newly diagnosed breast cancer (54 ± 12 years) were retrospectively enrolled. All women underwent a breast [ 18 F]FDG-PET/MRI, a histopathological workup of their breast cancer lesions and evaluation of clinical data. Fifty-six features derived from positron emission tomography (PET), magnetic resonance imaging (MRI), sociodemographic / anthropometric, histopathologic as well as clinical data were generated and used as input for an extreme Gradient Boosting model (XGBoost) to predict pCR. The model was evaluated in a five-fold nested-cross-validation incorporating independent hyper-parameter tuning within the inner loops to reduce the risk of overoptimistic estimations. Diagnostic model-performance was assessed by determining the area under the curve of the receiver operating characteristics curve (ROC-AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy. Furthermore, feature importances of the XGBoost model were evaluated to assess which features contributed most to distinguish between pCR and non-pCR., Results: Nested-cross-validation yielded a mean ROC-AUC of 80.4 ± 6.0% for prediction of pCR. Mean sensitivity, specificity, PPV, and NPV of 54.5 ± 21.3%, 83.6 ± 4.2%, 63.6 ± 8.5%, and 77.6 ± 8.1% could be achieved. Histopathological data were the most important features for classification of the XGBoost model followed by PET, MRI, and sociodemographic/anthropometric features., Conclusion: The evaluated multi-source XGBoost model shows promising results for reliably predicting pathological complete response in breast cancer patients prior to NAST. However, yielded performance is yet insufficient to be implemented in the clinical decision-making process., (© 2023. The Author(s).)

Purpose: An evidence basis is lacking but needed to compare reading ability outcomes after magnification device training remotely via telerehabilitation versus in office., Methods: A multicenter randomized controlled trial at academic centers and vision rehabilitation private practices randomized 61 visually impaired adults to telerehabilitation or in-office training 1 to 4 months after dispensing new portable electronic, hand-held, or stand optical magnifiers. Telerehabilitation included loaner equipment for Zoom videoconferencing with remote control access software. Using a multilevel regression model, changes in Activity Inventory responses using Rasch analysis estimated reading ability in dimensionless log odds units (logits) (0.14-logit change corresponds with ability change expected from a one-line change in visual acuity)., Results: Across 47 participants who completed the trial, reading ability with new magnifiers improved significantly by 0.61 logits on average (95% confidence interval [CI], 0.36-0.86; P < 0.001) from baseline to 1 month, and by an additional 0.44 logits on average (95% CI, 0.19-0.69; P < 0.001) from 1 to 4months (i.e., after magnifier training), with very similar significant findings for both telerehabilitation (n = 29; mean improvement = 0.44 logits; 95% CI, 0.08-0.80; P = 0.018) and in-office training (n = 18; mean improvement = 0.43 logits; 95% CI, 0.15-0.71; P = .003), and no significant difference between randomized groups across both follow-ups (95% CI, -0.43 to 0.61; P = .73). Vision, demographics, and health factors were nonsignificantly related to reading ability changes from 1 to 4 months., Conclusions: Reading ability improved after the provision of newly dispensed magnifiers, with further improvements following additional magnifier training via either telerehabilitation or in-office usual care., Translational Relevance: These findings provide support for the use of telerehabilitation to enhance reading ability with newly prescribed magnifiers as an alternative modality of care delivery.

Background: Compared to standard neuro-diagnostic techniques, retinal biomarkers provide a probable low-cost and non-invasive alternative for early Alzheimer's disease (AD) risk screening. We have previously quantified the periarteriole and perivenule capillary free zones (mid-peripheral CFZs) in cognitively unimpaired (CU) young and older adults as novel metrics of retinal tissue oxygenation. There is a breakdown of the inner retinal blood barrier, pericyte loss, and capillary non-perfusion or dropout in AD leading to potential enlargement of the mid-peripheral CFZs. We hypothesized the mid-peripheral CFZs will be enlarged in CU older adults at high risk for AD compared to low-risk individuals., Methods: 20 × 20° optical coherence tomography angiography images consisting of 512 b-scans, 512 A-scans per b-scan, 12-µm spacing between b-scans, and 5 frames averaged per each b-scan location of the central fovea and of paired major arterioles and venules with their surrounding capillaries inferior to the fovea of 57 eyes of 37 CU low-risk (mean age: 66 years) and 50 eyes of 38 CU high-risk older adults (mean age: 64 years; p = 0.24) were involved in this study. High-risk participants were defined as having at least one APOE e4 allele and a positive first-degree family history of AD while low-risk participants had neither of the two criteria. All participants had Montreal Cognitive Assessment scores ≥ 26. The mid-peripheral CFZs were computed in MATLAB and compared between the two groups., Results: The periarteriole CFZ of the high-risk group (75.8 ± 9.19 µm) was significantly larger than that of the low-risk group (71.3 ± 7.07 µm), p = 0.005, Cohen's d = 0.55. The perivenule CFZ of the high-risk group (60.4 ± 8.55 µm) was also significantly larger than that of the low-risk group (57.3 ± 6.40 µm), p = 0.034, Cohen's d = 0.42. There were no significant differences in foveal avascular zone (FAZ) size, FAZ effective diameter, and vessel density between the two groups, all p > 0.05., Conclusions: Our results show larger mid-peripheral CFZs in CU older adults at high risk for AD, with the potential for the periarteriole CFZ to serve as a novel retinal vascular biomarker for early AD risk detection., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: To investigate the diagnostic feasibility of a shortened breast PET/MRI protocol in breast cancer patients., Methods: Altogether 90 women with newly diagnosed T1 tumor-staged (T1 ts ) and T2 tumor-staged (T2 ts ) breast cancer were included in this retrospective study. All underwent a dedicated comprehensive breast [ 18 F]FDG-PET/MRI. List-mode PET data were retrospectively reconstructed with 20, 15, 10, and 5 min for each patient to simulate the effect of reduced PET acquisition times. The SUV max/mean of all malign breast lesions was measured. Furthermore, breast PET data reconstructions were analyzed regarding image quality, lesion detectability, signal-to-noise ratio (SNR), and image noise (IN). The simultaneously acquired comprehensive MRI protocol was then shortened by retrospectively removing sequences from the protocol. Differences in malignant breast lesion detectability between the original and the fast breast MRI protocol were evaluated lesion-based. The 20-min PET reconstructions and the original MRI protocol served as reference., Results: In all PET reconstructions, 127 congruent breast lesions could be detected. Group comparison and T1 ts vs. T2 ts subgroup comparison revealed no significant difference of subjective image quality between 20, 15, 10, and 5 min acquisition times. SNR of qualitative image evaluation revealed no significant difference between different PET acquisition times. A slight but significant increase of IN with decreasing PET acquisition times could be detected. Lesion SUV max group comparison between all PET acquisition times revealed no significant differences. Lesion-based evaluation revealed no significant difference in breast lesion detectability between original and fast breast MRI protocols., Conclusions: Breast [ 18 F]FDG-PET/MRI protocols can be shortened from 20 to below 10 min without losing essential diagnostic information., Key Points: • A highly accurate breast cancer evaluation is possible by the shortened breast [ 18 F]FDG-PET/MRI examination protocol. • Significant time saving at breast [ 18 F]FDG-PET/MRI protocol could increase patient satisfaction and patient throughput for breast cancer patients at PET/MRI., (© 2023. The Author(s).)

Background: This study compares the diagnostic potential of conventional staging (computed tomography (CT), axillary sonography and bone scintigraphy), whole-body magnetic resonance imaging (MRI) and whole-body 18 F-fluorodeoxyglucose positron emission tomography ( 18 F-FDG PET/)MRI for N and M staging in newly diagnosed breast cancer. Methods: A total of 208 patients with newly diagnosed breast cancer were prospectively included in this study and underwent contrast-enhanced thoracoabdominal CT, bone scintigraphy and axillary sonography as well as contrast-enhanced whole-body 18 F-FDG PET/MRI. The datasets were analyzed with respect to lesion localization and characterization. Histopathology and follow-up imaging served as the reference standard. A McNemar test was used to compare the diagnostic performance of conventional staging, MRI and 18 F-FDG PET/MRI and a Wilcoxon test was used to compare differences in true positive findings for nodal staging. Results: Conventional staging determined the N stage with a sensitivity of 80.9%, a specificity of 99.2%, a PPV (positive predictive value) of 98.6% and a NPV (negative predictive value) of 87.4%. The corresponding results for MRI were 79.6%, 100%, 100% and 87.0%, and were 86.5%, 94.1%, 91.7% and 90.3% for 18 F-FDG PET/MRI. 18 F-FDG PET/MRI was significantly more sensitive in determining malignant lymph nodes than conventional imaging and MRI ( p < 0.0001 and p = 0.0005). Furthermore, 18 F-FDG PET/MRI accurately estimated the clinical lymph node stage in significantly more cases than conventional imaging and MRI (each p < 0.05). Sensitivity, specificity, PPV and NPV for the M stage in conventional staging were 83.3%, 98.5%, 76.9% and 98.9%, respectively. The corresponding results for both MRI and 18 F-FDG PET/MRI were 100.0%, 98.5%, 80.0% and 100.0%. No significant differences between the imaging modalities were seen for the staging of distant metastases. Conclusions: 18 F-FDG PET/MRI detects lymph node metastases in significantly more patients and estimates clinical lymph node stage more accurately than conventional imaging and MRI. No significant differences were found between imaging modalities with respect to the detection of distant metastases.

Introduction: When optimal lighting is applied to hard-copy materials for visually impaired individuals, laboratory-based reading performance can improve significantly. However, it is not known whether their lighting preferences are related to ocular factors or if laboratory-based reading improvements will translate to home-based environments., Methods: Preferences for brightness (lux) and colour temperature (degrees Kelvin; K) with the LuxIQ/2 for 'most comfort' while reading at near were evaluated in-clinic for 71 adults with ocular disease affecting the outer (n = 37; 52%), inner or all retinal layers (n = 34; 48%). Twenty participants received either an OttLite Cobra lamp or a generic gooseneck lamp with a bulb resembling LuxIQ/2 parameters for their preferred reading light, and then completed home-based telephone evaluations using the sustained silent reading test., Results: Participants with outer retinal disease preferred significantly brighter light intensity by an average of 838 lux versus those with inner retinal disease (95% CI: 331, 1344; p = 0.002). No participants opted for a coloured tint for reading based on the LuxIQ/2 measurements since they preferred white light only; most preferred the OttLite Cobra lamp. At home, reading speed improved significantly by an average of 37 words per minute with the new lamp (95% CI: 12, 62; p = 0.005)., Conclusions: Patients with outer retinal disease prefered brighter light intensity for reading. Clinic-based lighting preferences yielded improvements in reading speed when using a new task light at home., (© 2023 College of Optometrists.)

Introduction: Triple negative breast cancer (TNBC) shows an aggressive growing and spreading behavior and has limited treatment options, often leading to inferior disease outcome. Therefore, surrogate markers are urgently needed to identify patients at high risk of recurrence and more importantly, to identify additional therapeutic targets enabling further treatment options. Based on the key role of the non-classical human leukocyte antigen G (HLA-G) and its related receptor immunoglobulin-like transcript receptor-2 (ILT-2) in immune evasion mechanisms of tumors, members of this ligand-receptor axis appear to be promising tool for both, defining risk groups and potential therapeutic targets., Materials and Methods: To follow this, sHLA-G levels before and after chemotherapy (CT), HLA-G 3' UTR haplotypes, and allele variations rs10416697 at the distal gene promoter region of ILT-2 were defined in healthy female controls and early TNBC patients. The results obtained were associated with clinical status, presence of circulating tumor cell (CTC) subtypes, and disease outcome of patients in terms of progression-free or overall survival., Results: sHLA-G plasma levels were increased in TNBC patients post-CT compared to levels of patients pre-CT or controls. High post-CT sHLA-G levels were associated with the development of distant metastases, the presence of ERCC1 or PIK3CA-CTC subtypes post-CT, and poorer disease outcome in uni- or multivariate analysis. HLA-G 3' UTR genotypes did not influence disease outcome but ILT-2 rs10416697C allele was associated with AURKA-positive CTC and with adverse disease outcome by uni- and multivariate analysis. The prognostic value of the combined risk factors (high sHLA-G levels post-CT and ILT-2 rs10416697C allele carrier status) was an even better independent indicator for disease outcome in TNBC than the lymph nodal status pre-CT. This combination allowed the identification of patients with high risk of early progression/death with positive nodal status pre-CT or with non-pathological complete therapy response., Conclusion: The results of this study highlight for the first time that the combination of high levels of sHLA-G post-CT with ILT-2 rs10416697C allele receptor status is a promising tool for the risk assessment of TNBC patients and support the concept to use HLA-G/ILT-2 ligand-receptor axis as therapeutic targets., Competing Interests: Author SK-B is a consultant for Qiagen. Author A-KB: Presentations, advisory boards, funding congresses etc. for/by Fa. Amgen, Astra Zeneca, Daiichi Sankyo, Gilead, Hexal, Novartis und Pfizer. Author OH: Presentations, advisory boards, funding congresses etc. for/by Fa. Riemser, Roche, Astra Zeneca, Amgen, Pfizer, Eisai, Gilead, Hexal, MSD, Novartis, Seagen und Daiichi Sankyo. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hoffmann, Wormland, Bittner, Hölzenbein, Schwich, Schramm, Rohn, Horn, Kimmig, Kasimir-Bauer and Rebmann.)

Significance: Vision rehabilitation providers tend to recommend handheld, illuminated optical magnifiers for short-duration spot reading tasks, but this study indicates that they are also a viable option to improve sustained, continuous text reading (e.g., books or magazines), especially for visually impaired adults who read slowly with only spectacle-based near correction., Purpose: The utility of handheld optical magnifiers for sustained silent reading tasks involving normal-sized continuous text could be a valuable indication that is not recognized by vision rehabilitation providers and patients., Methods: Handheld, illuminated optical magnifiers were dispensed to 29 visually impaired adults who completed the sustained silent reading test by phone at baseline without the new magnifier and 1 month after using the magnifier. Reading speed in words per minute (wpm) was calculated from the time to read each page and then averaged across up to 10 pages or determined for the fastest read page (maximum)., Results: From baseline without the magnifier to 1 month with the magnifier, there was a significant improvement in mean reading speed by 14 wpm (95% confidence interval [CI], 2.6 to 24; P = .02) and for maximum reading speed by 18 wpm (95% CI, 5.4 to 30; P = .005) on average across participants. Participants who had slower baseline reading speeds without the magnifier demonstrated significantly greater improvements in mean and maximum reading speeds on average with the magnifier (95% CI, 8 to 32 [ P = .003]; 95% CI, 4 to 36 [ P = .02]). A significantly greater number of pages were read with the new magnifier than without it (Wilcoxon z = -2.5; P = .01). A significantly greater number of pages were read with the magnifier by participants who read fewer pages at baseline (95% CI, 0.57 to 5.6; P = .02) or had greater improvements in mean reading speed (95% CI, 0.57 to 5.6; P = .007)., Conclusions: Many visually impaired adults read more quickly and/or read a greater number of pages after using a new magnifier for a month than compared to without it. The largest gains occurred among those with more difficulty at baseline, indicating the potential to improve reading rates with magnifiers for those with greater deficits., Competing Interests: Conflict of Interest Disclosure: None of the authors have reported a financial conflict of interest., (Copyright © 2023 American Academy of Optometry.)

Purpose: Evaluate the diagnostic potential of [ 18 F]FDG-PET/MRI data compared with invasive acquired biomarkers in newly diagnosed early breast cancer (BC)., Methods: Altogether 169 women with newly diagnosed BC were included. All underwent a breast- and whole-body [ 18 F]FDG-PET/MRI for initial staging. A tumor-adapted volume of interest was placed in the primaries and defined bone regions on each standard uptake value (SUV)/apparent diffusion coefficient (ADC) dataset. Immunohistochemical markers, molecular subtype, tumor grading, and disseminated tumor cells (DTCs) of each patient were assessed after ultrasound-guided biopsy of the primaries and bone marrow (BM) aspiration. Correlation analysis and group comparisons were assessed., Results: A significant inverse correlation of estrogen-receptor (ER) expression and progesterone-receptor (PR) expression towards SUV max was found (ER: r = 0.27, p < 0.01; PR: r = 0.19, p < 0.05). HER2-receptor expression showed no significant correlation towards SUV and ADC values. A significant positive correlation between Ki67 and SUVmax and SUV mean ( r = 0.42 p < 0.01; r = 0.19 p < 0.05) was shown. Tumor grading significantly correlated with SUV max and SUV mean (ρ = 0.36 and ρ = 0.39, both p 's < 0.01). There were no group differences between SUV/ADC values of DTC-positive/-negative patients., Conclusions: [ 18 F]FDG-PET/MRI may give a first impression of BC-receptor status and BC-tumor biology during initial staging by measuring glucose metabolism but cannot distinguish between DTC-positive/-negative patients and replace biopsy.

Purpose: Based on the tumor-promoting features of extracellular vesicles (EV) and PD-L1/2-bearing EV subpopulations (PD-L1/2 EV ), we evaluated their potential as surrogate markers for disease progression or eligibility criteria for PD-1 immune checkpoint inhibition (ICI) approaches in early triple-negative breast cancer (TNBC)., Methods: After enrichment of EV from plasma samples of 56 patients before and 50 after chemotherapy (CT), we determined levels of EV particle number and PD-L1/2 EV by nanoparticle tracking analysis or ELISA and associated the results with clinical status/outcome and the presence of distinct circulating tumor cells (CTC) subpopulations., Results: Compared to healthy controls, patients had a tenfold higher EV concentration and significantly elevated PD L2 EV but not PD L1 EV levels. The most important clinical implications were found for PD-L2 EV . High PD-L2 EV levels were associated with a significantly reduced 3-year progression-free and overall survival (PFS and OS). A loss of PD-L2 EV after CT was significantly more prominent in patients achieving pathological complete response (pCR). Increased pre-CT PD-L2 EV levels were found in patients having NOTCH1-positive or ERBB3-positive CTC. The presence of ERBB3-positive CTC combined with high pre-CT PD-L2 EV resulted in a shorter PFS., Conclusion: This study highlights PD L2 EV as a promising biomarker for risk assessment of TNBC patients and represents the basic for additional studies introducing PD-L2 EV as an eligibility criterion for PD-1 ICI approaches., (© 2022. The Author(s).)

In addition to its high prognostic value, the involvement of axillary lymph nodes in breast cancer patients also plays an important role in therapy planning. Therefore, an imaging modality that can determine nodal status with high accuracy in patients with primary breast cancer is desirable. Our purpose was to investigate whether, in newly diagnosed breast cancer patients, machine-learning prediction models based on simple assessable imaging features on MRI or PET/MRI are able to determine nodal status with performance comparable to that of experienced radiologists; whether such models can be adjusted to achieve low rates of false-negatives such that invasive procedures might potentially be omitted; and whether a clinical framework for decision support based on simple imaging features can be derived from these models. Methods: Between August 2017 and September 2020, 303 participants from 3 centers prospectively underwent dedicated whole-body 18 F-FDG PET/MRI. Imaging datasets were evaluated for axillary lymph node metastases based on morphologic and metabolic features. Predictive models were developed for MRI and PET/MRI separately using random forest classifiers on data from 2 centers and were tested on data from the third center. Results: The diagnostic accuracy for MRI features was 87.5% both for radiologists and for the machine-learning algorithm. For PET/MRI, the diagnostic accuracy was 89.3% for the radiologists and 91.2% for the machine-learning algorithm, with no significant differences in diagnostic performance between radiologists and the machine-learning algorithm for MRI ( P = 0.671) or PET/MRI ( P = 0.683). The most important lymph node feature was tracer uptake, followed by lymph node size. With an adjusted threshold, a sensitivity of 96.2% was achieved by the random forest classifier, whereas specificity, positive predictive value, negative predictive value, and accuracy were 68.2%, 78.1%, 93.8%, and 83.3%, respectively. A decision tree based on 3 simple imaging features could be established for MRI and PET/MRI. Conclusion: Applying a high-sensitivity threshold to the random forest results might potentially avoid invasive procedures such as sentinel lymph node biopsy in 68.2% of the patients., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Low vision affects over 300 million people worldwide and can compromise both activities of daily living and quality of life. Rehabilitative training and vision assistive equipment (VAE) may help, but some visually impaired people have limited resources to attend in-person visits to rehabilitation clinics to be trained to learn to use VAE. These people may be able to overcome barriers to care through access to remote, internet-based consultation (telerehabilitation)., Objectives: To compare the effects of telerehabilitation with face-to-face (e.g. in-office or inpatient) vision rehabilitation services for improving vision-related quality of life and near reading ability in people with visual function loss due to any ocular condition. Secondary objectives were to evaluate compliance with scheduled rehabilitation sessions, abandonment rates for VAE devices, and patient satisfaction ratings., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Eyes and Vision Trials Register) (2021, Issue 9); Ovid MEDLINE; Embase.com; PubMed; ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any language restriction or study design filter in the electronic searches; however, we restricted the searches from 1980 onwards because the internet was not introduced to the public until 1982. We last searched CENTRAL, MEDLINE Ovid, Embase, and PubMed on 14 September 2021, and the trial registries on 16 March 2022., Selection Criteria: We included randomized controlled trials (RCTs) or controlled clinical trials (CCTs) in which participants diagnosed with low vision had received vision rehabilitation services remotely from a human provider using internet, web-based technology compared with an approach involving in-person consultations., Data Collection and Analysis: Two review authors independently screened titles and abstracts retrieved by the searches of the electronic databases and then full-text articles for eligible studies. Two review authors independently abstracted data from the included studies. Any discrepancies were resolved by discussion., Main Results: We identified one RCT/CCT that indirectly met our inclusion criteria, and two ongoing trials that met our inclusion criteria. The included trial had an overall high risk of bias. We did not conduct a quantitative analysis since multiple controlled trials were not identified.  The single included trial of 57 participants utilized a parallel-group design. It compared 30 hours of either personalized low vision training through telerehabilitation with a low vision therapist (the experimental group) with the self-training standard provided by eSight using the eSkills User Guide that was self-administered by the participants at home for one hour per day for 30 days (the comparison group). The trial investigators found a similar direction of effects for both groups for vision-related quality of life and satisfaction at two weeks, three months, and six months. A greater proportion of participants in the comparison group had abandoned or discontinued use of the eSight Eyewear at two weeks than those in the telerehabilitation group, but discontinuance rates were similar between groups at one month and three months. We rated the certainty of the evidence for all outcomes as very low due to high risk of bias in randomization processes and missing outcome data and imprecision.   AUTHORS' CONCLUSIONS: The included trial found similar efficacy between telerehabilitation with a therapist and an active control intervention of self-guided training in mostly younger to middle-aged adults with low vision who received a new wearable electronic aid. Given the disease burden and the growing interest in telemedicine, the two ongoing studies, when completed, may provide further evidence of the potential for telerehabilitation as a platform for providing services to people with low vision., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Significance: This pilot study provides some insight about the potential benefits of telerehabilitation training to improve the reading ability of adults with low vision using magnifiers, to spur future work with larger groups. Telerehabilitation services can be implemented clinically to facilitate access to follow-up care for low vision., Purpose: A recent Cochrane systematic review revealed that there are no published visual function outcomes for telerehabilitation with handheld magnification devices for low vision; thus, this study aimed to provide evidence for its preliminary efficacy., Methods: One to 4 months after receiving a new magnification device (i.e., handheld or stand optical magnifier or portable electronic magnifier), 14 adult low vision patients (with any visual acuity level or ocular diagnosis) received two training sessions at home via telerehabilitation with their vision rehabilitation provider located remotely in-office. Telerehabilitation included a loaner smartphone for Zoom videoconferencing with remote control access software. The Minnesota Low-Vision Reading Test was administered during each of the telerehabilitation sessions to assess near reading (acuity and speed) with the new magnifier., Results: Mean reading acuity with the magnifier was 0.17 logMAR across subjects before training at telerehabilitation session 1, which significantly improved to 0.09 on average a few weeks later at telerehabilitation session 2 (95%confidence interval, -0.001 to -0.16; P = .047). Logarithm reading speed with the magnifier for the reading acuity level at session 1 improved significantly by 0.18 log words per minute on average for the same text size at session 2 (95% confidence interval, 0.06 to 0.29; P = .002). With the magnifier at session 2, 71% of participants gained at least 0.1 log unit in reading acuity, and half improved by >0.01 in log reading speed; all participants with increased reading speed also improved in reading acuity ( P = .02)., Conclusions: These preliminary data support that telerehabilitation can enhance reading ability and efficiency with newly prescribed magnifiers as an alternative option to in-office vision rehabilitation., Competing Interests: Conflict of Interest Disclosure: None of the authors have reported a financial conflict of interest., (Copyright © 2022 American Academy of Optometry.)

PET/MRI has been available since 2010, representing the newest of the hybrid imaging modalities. It combines functional as well as morphologic high-resolution MRI data with metabolic information from PET, providing image data sets with complementary information. Especially in the field of oncology, PET/MRI is a promising imaging modality with diverse applications. Since its introduction there has already been a large quantity of studies indicating a high diagnostic value of PET/MRI for whole-body cancer staging. The simultaneous acquisition of metabolic PET and MRI data is expected to have a major impact in the assessment of breast cancer due to the superior resolution of MRI in breast tissue compared to CT. While there is an ongoing debate if the added value of breast 18 F-FDG PET/MRI in the primary diagnosis of breast cancer has clinical impact compared to breast MRI, a large number of studies have proven that 18 F-FDG PET/MRI is extremely valuable for whole-body breast cancer staging and especially for treatment monitoring. Besides molecular markers, distant metastases and axillary lymph node involvement are the most important predictors for overall survival and recurrence in breast cancer patients. Due to the high soft tissue contrast, functional imaging from MRI and metabolic information from PET, distant metastases in organs and in particular in the bones are detected better compared to the conventional staging algorithm with CT and bone scan and can significantly influence the therapy regime. Instead of mastectomy and extensive axillary dissection being performed in many patients, the improved imaging and diagnostic confidence also has helped that local therapy control can be achieved with reduced invasiveness. A future role of 18 F-FDG PET/MRI could therefore become treatment response evaluation under neoadjuvant treatment before or instead of operative therapy. In addition to reduced radiation exposure compared to conventional staging examinations, hybrid 18 F-FDG PET/MRI might serve as a comprehensive "all-in-one" breast cancer staging tool, providing precise local and whole-body staging including MRI of the head in one procedure, which save patients a diagnostic marathon., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: C-reactive protein (CRP) is an acute phase reactant influenced by inflammation and tissue damage. Elevated CRP levels have been associated with poor outcome of various cancers including breast cancer. However, evidence regarding a potential impact of CRP levels on outcome of neoadjuvant chemotherapy (NACT) in patients with early breast cancer (EBC) is insufficient., Methods: Patients who had received NACT for EBC and had available data regarding CRP levels before therapy, pathologic complete remission (pCR), and follow-up were included. The association between CRP at baseline and outcome parameters was analyzed., Results: 152 women were included in this analysis; median follow-up was 5.8 years. No association between CRP at baseline and pCR rates could be detected. 6.6% of the patients developed a local recurrence, 10.5% developed a distant recurrence, and 5.2% died from breast cancer. A negative correlation (Spearman-Rho) between CRP at baseline and overall survival (OS) (correlation coefficient (CC) -0.255; p = 0.45), disease-free survival (DFS) (CC -0.348; p = 0.075), local recurrence-free survival (LRFS) (CC -0.245; p = 0.327), and distant DFS (DDFS) (CC -0.422; p = 0.057) was not statistically significant, although especially in DFS and DDFS a strong trend was detected. The probability of death from breast cancer was 2% if the CRP was <0.08 mg/dL and 40% if the CRP was >2.08 mg/dL; this association was highly statistically significant (χ 2 ; p < 0.001). These results were independent from age, estrogen and progesterone receptor status, HER2 status, nodal status, and grading. The hazard ratio for OS was 5.75 ( p = 0.004) for CRP <0.08 mg/dL versus CRP >2.08 mg/dL., Discussion/conclusion: CRP at baseline is not predictive for pCR in EBC after NACT in our patient dataset. However, an association of parameters of long-term prognosis with CRP could be demonstrated. Although the correlations of higher CRP levels at baseline and shorter OS, DFS, LRFS, and DDFS were not significant, a strong trend could be detected that was reproduced in the analysis of different groups of CRP levels and the probability of breast cancer mortality. Higher CRP levels are indicating a worse prognosis in EBC after NACT in this retrospective analysis. These results justify further investigation of CRP not as a predictive parameter for pCR but as a biomarker of long-term prognosis in EBC in prospective trials and may lead to therapeutic approaches with the aim of lowering CRP levels., Competing Interests: H.C.K. received honoraria and travel support from AstraZeneca, Pfizer, Roche, Daiichi Sankyo, Tesaro, MSD, onkowissen, Eli Lilly, SurgVision, Exact Sciences, und Genomic Health and holds stock of Theraclion und Phaon scientific. C.K.L. received honoraria from Roche, Novartis, Pfizer, Amgen, Astra Zeneca, onkowissen, Gilead Sciences, SeaGen, Sanofi-Genzyme, and MSD and research funding from Gilead Sciences. A.K.B. received honoraria and travel support from Amgen, AstraZeneca, Daiichi Sankyo, Hexal, Novartis, Pfizer, Roche, MSD, and SeaGen. O.H. received honoraria and travel support from Amgen, AstraZeneca, Daiichi Sankyo, Hexal, Novartis, Pfizer, Roche, MSD, Riemser, SeaGen, Gilead, and Eisai. A.E., S.W., M.S., and M.S. have nothing to disclose., (Copyright © 2022 by S. Karger AG, Basel.)

Purpose: We examined different methods to reduce the burden of accessing technology for videoconferencing during telerehabilitation for magnification devices for the visually impaired., Methods: During telerehabilitation studies over the past 5 years, vision rehabilitation providers assessed and gave training to visually impaired participants with newly dispensed magnification devices at home who connected to Zoom videoconferencing via loaner tablets or smartphones with assistance from (phase 1; n = 10) investigators by phone, (phase 2; n = 11) local Lions Club volunteers in participants' homes, or (phase 3; n = 24) remote access control software in a randomized controlled trial with 13 usual care controls who received in-office training. All participants completed the same post-telerehabilitation phone survey., Results: A significantly greater proportion of phase 3 subjects indicated they strongly or mostly agreed that the technology did not interfere with the session (96%) compared to phase 1 (60%; 95% confidence interval [CI], 1.2-12.5; P = 0.03) or phase 2 (55%; 95% CI, 1.8-188; P = 0.01). The majority indicated telerehabilitation was as accurate as in person (68%), they were comfortable with telerehabilitation (91%) and interested in a future session (83%), and their magnifier use improved (79%), with no significant differences in these responses between phases (all P > 0.10), including comparisons of participants randomized to telerehabilitation or in-office training in phase 3 who reported similar overall satisfaction levels (P = 0.84)., Conclusions: Participants across all phases reported high levels of acceptance for telerehabilitation, with least interference from technology using remote access control in phase 3., Translational Relevance: With accommodations for accessibility to videoconferencing technology, telerehabilitation for magnification devices can be a feasible, acceptable, and valuable option in countries with resources to support the technology.

Purpose: The evaluation of the clinical relevance of missed lung nodules at initial staging of breast cancer patients in [ 18 F]FDG-PET/MRI compared with CT., Methods: A total of 152 patients underwent an initial whole-body [ 18 F]FDG-PET/MRI and a thoracoabdominal CT for staging. Presence, size, shape and location for each lung nodule in [ 18 F]FDG-PET/MRI was noted. The reference standard was established by taking initial CT and follow-up imaging into account (a two-step approach) to identify clinically-relevant lung nodules. Patient-based and lesion-based data analysis was performed., Results: No patient with clinically-relevant lung nodules was missed on a patient-based analysis with MRI VIBE, while 1/84 females was missed with MRI HASTE (1%). Lesion-based analysis revealed 4/96 (4%, VIBE) and 8/138 (6%, HASTE) missed clinically-relevant lung nodules. The average size of missed lung nodules was 3.2 mm ± 1.2 mm (VIBE) and 3.6 mm ± 1.4 mm (HASTE) and the predominant location was in the left lower quadrant and close to the hilum., Conclusion: All patients with newly-diagnosed breast cancer and clinically-relevant lung nodules were detected at initial [ 18 F]FDG-PET/MRI staging. However, due to the lower sensitivity in detecting lung nodules, a small proportion of clinically-relevant lung nodules were missed. Thus, supplemental low-dose chest CT after neoadjuvant therapy should be considered for backup.

Background: To achieve long-term improvement in health care of transgender women, it is necessary to analyze all aspects of gender-confirming surgery, especially the relation of risks and benefits occurring in these procedures. While there are many studies presenting data on the urologic part of the surgery, there are just few data about complications and satisfaction with breast augmentation., Methods: This is a retrospective study using parts of the BREAST-Q Augmentation Questionnaire and additional questions for symptoms of capsular contracture and re-operations and analyzing archived patient records of all transwomen which were operated at University Hospital Essen from 2007 to 2020., Results: 99 of these 159 patients (62%) completed the questionnaire after a median time of 4 years after surgery. Breast augmentation led to re-operations due to complications in 5%. The rate of capsular contracture (Baker Grad III-IV) in this population was 3%. Most patients (75%) rated high scores of satisfaction with outcome (more than 70 points) and denied to have restrictions due to their implants in their everyday life. All patients reported an improvement in their quality of life owing to breast augmentation., Conclusion: Breast augmentation by inserting silicon implants is a safe surgical procedure which takes an important part in reducing gender dysphoria., (© 2022. The Author(s).)

Background: The aim of this study was to assess whether multiparametric 18 F-FDG PET/MRI-based radiomics analysis is able to predict pathological complete response in breast cancer patients and hence potentially enhance pretherapeutic patient stratification., Methods: A total of 73 female patients (mean age 49 years; range 27-77 years) with newly diagnosed, therapy-naive breast cancer underwent simultaneous 18 F-FDG PET/MRI and were included in this retrospective study. All PET/MRI datasets were imported to dedicated software (ITK-SNAP v. 3.6.0) for lesion annotation using a semi-automated method. Pretreatment biopsy specimens were used to determine tumor histology, tumor and nuclear grades, and immunohistochemical status. Histopathological results from surgical tumor specimens were used as the reference standard to distinguish between complete pathological response (pCR) and noncomplete pathological response. An elastic net was employed to select the most important radiomic features prior to model development. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for each model., Results: The best results in terms of AUCs and NPV for predicting complete pathological response in the entire cohort were obtained by the combination of all MR sequences and PET (0.8 and 79.5%, respectively), and no significant differences from the other models were observed. In further subgroup analyses, combining all MR and PET data, the best AUC (0.94) for predicting complete pathologic response was obtained in the HR+/HER2- group. No difference between results with/without the inclusion of PET characteristics was observed in the TN/HER2+ group, each leading to an AUC of 0.92 for all MR and all MR + PET datasets., Conclusion: 18 F-FDG PET/MRI enables comprehensive high-quality radiomics analysis for the prediction of pCR in breast cancer patients, especially in those with HR+/HER2- receptor status.

Purpose: Advanced driver assistance systems (ADAS) have been reported to improve the safety of elderly and normally sighted drivers. The purpose of this study was to assess exposure to, perceived safety of, comfort level with, and interest in using ADAS among drivers with age-related macular degeneration (AMD)., Methods: Current drivers aged 60+ years were recruited at four US sites to complete a survey about ADAS and driving habits. Frequency of use and/or perceptions of eight ADAS were investigated. An avoidance score was generated using questions about difficult driving situations., Results: The survey was completed by 166 participants (80 with AMD vs. 86 without). Participants with AMD had worse self-rated vision than those without (34% vs. 2% poor or fair rating), and drove fewer weekly miles (median [interquartile range [IQR] 30 [15 to 75] vs. 60 [30 to 121] miles, P = 0.002). Participants with AMD reported more avoidance of difficult driving situations (P < 0.001). There was no difference in the number of ADAS used by AMD status (median [IQR for AMD = 2.5 [1 to 5] vs. 3 [2 to 4] without, P = 0.87). Greater reported number of ADAS used was associated with less avoidance of difficult situations (P = 0.02). The majority perceived improved safety with most ADAS., Conclusions: Many drivers with AMD utilize common ADAS, which subjectively improve their road safety and may help to reduce self-imposed restrictions for difficult situations and mileage., Translational Relevance: Drivers with AMD are adopting readily available ADAS, for which they reported potential benefits, such as safety and less restrictive driving.

Background: The free-breathing T1-weighted 3D Stack of Stars GRE (StarVIBE) MR sequence potentially reduces artifacts in chest MRI. The purpose of this study was to evaluate StarVIBE for the detection of pulmonary nodules in 18 F-FDG PET/MRI., Material and Methods: In this retrospective analysis, conducted on a prospective clinical trial cohort, 88 consecutive women with newly diagnosed breast cancer underwent both contrast-enhanced whole-body 18 F-FDG PET/MRI and computed tomography (CT). Patients' chests were examined on CT as well as on StarVIBE and conventional T1-weighted VIBE and T2-weighted HASTE MR sequences, with CT serving as the reference standard. Presence, size, and location of all detectable lung nodules were assessed. Wilcoxon test was applied to compare nodule features and Pearson's, and Spearman's correlation coefficients were calculated., Results: Out of 65 lung nodules detected in 36 patients with CT (3.7 ± 1.4 mm), StarVIBE was able to detect 31 (47.7%), VIBE 26 (40%) and HASTE 11 (16.8%), respectively. Overall, CT showed a significantly higher detectability than all MRI sequences combined (65 vs. 36, difference 44.6%, p < 0.001). The VIBE showed a significantly better detection rate than the HASTE (23.1%, p = 0.001). Detection rates between StarVIBE and VIBE did not significantly differ (7.7%, p = 0.27), but the StarVIBE showed a significant advantage detecting centrally located pulmonary nodules (66.7% vs. 16.7%, p = 0.031). There was a strong correlation in nodule size between CT and MRI sequences (HASTE: ρ = 0.80, p = 0.003; VIBE: ρ = 0.77, p < 0.001; StarVIBE: ρ = 0.78, p < 0.001). Mean image quality was rated as good to excellent for CT and MRI sequences., Conclusion: The overall lung nodule detection rate of StarVIBE was slightly, but not significantly, higher than conventional T1w VIBE and significantly higher than T2w HASTE. Detectability of centrally located nodules is better with StarVIBE than with VIBE. Nevertheless, all MRI analyses demonstrated considerably lower detection rates for small lung nodules, when compared to CT., (© 2022. The Author(s).)

Purpose: To compare CT, MRI, and [ 18 F]-fluorodeoxyglucose positron emission tomography ([ 18 F]-FDG PET/MRI) for nodal status, regarding quantity and location of metastatic locoregional lymph nodes in patients with newly diagnosed breast cancer., Materials and Methods: One hundred eighty-two patients (mean age 52.7 ± 11.9 years) were included in this prospective double-center study. Patients underwent dedicated contrast-enhanced chest/abdomen/pelvis computed tomography (CT) and whole-body ([ 18 F]-FDG PET/) magnet resonance imaging (MRI). Thoracal datasets were evaluated separately regarding quantity, lymph node station (axillary levels I-III, supraclavicular, internal mammary chain), and lesion character (benign vs. malign). Histopathology served as reference standard for patient-based analysis. Patient-based and lesion-based analyses were compared by a McNemar test. Sensitivity, specificity, positive and negative predictive values, and accuracy were assessed for all three imaging modalities., Results: On a patient-based analysis, PET/MRI correctly detected significantly more nodal positive patients than MRI (p < 0.0001) and CT (p < 0.0001). No statistically significant difference was seen between CT and MRI. PET/MRI detected 193 lesions in 75 patients (41.2%), while MRI detected 123 lesions in 56 patients (30.8%) and CT detected 104 lesions in 50 patients, respectively. Differences were statistically significant on a lesion-based analysis (PET/MRI vs. MRI, p < 0.0001; PET/MRI vs. CT, p < 0.0001; MRI vs. CT, p = 0.015). Subgroup analysis for different lymph node stations showed that PET/MRI detected significantly more lymph node metastases than MRI and CT in each location (axillary levels I-III, supraclavicular, mammary internal chain). MRI was superior to CT only in axillary level I (p = 0.0291)., Conclusion: [ 18 F]-FDG PET/MRI outperforms CT or MRI in detecting nodal involvement on a patient-based analysis and on a lesion-based analysis. Furthermore, PET/MRI was superior to CT or MRI in detecting lymph node metastases in all lymph node stations. Of all the tested imaging modalities, PET/MRI showed the highest sensitivity, whereas CT showed the lowest sensitivity, but was most specific., (© 2021. The Author(s).)

Despite major improvements in diagnostics and therapy in early as well as in locally advanced breast cancer (LABC), metastatic relapse occurs in about 20% of patients, often explained by early micro-metastatic spread into bone marrow by disseminated tumor cells (DTC). Although neoadjuvant chemotherapy (NACT) has been a successful tool to improve overall survival (OS), there is growing evidence that various environmental factors like the non-classical human leukocyte antigen-G (HLA-G) promotes cancer invasiveness and metastatic progression. HLA-G expression is associated with regulatory elements targeting certain single-nucleotide polymorphisms (SNP) in the HLA-G 3' untranslated region (UTR), which arrange as haplotypes. Here, we systematically evaluated the impact of HLA-G 3'UTR polymorphisms on disease status, on the presence of DTC, on soluble HLA-G levels, and on therapy and disease outcome in non-metastatic LABC patients. Although haplotype frequencies were similar in patients ( n  = 142) and controls ( n = 204), univariate analysis revealed that the UTR-7 haplotype was related to patients with low tumor burden, whereas UTR-4 was associated with tumor sizes >T1. Furthermore, UTR-4 was associated with the presence of DTC, but UTR-3 and UTR-7 were related to absence of DTC. Additionally, increased levels of soluble HLA-G molecules were found in patients carrying UTR-7. Regarding therapy and disease outcome, univariate and multivariate analysis highlighted UTR-1 or UTR-2 as a prognostic parameter indicative for a beneficial course of disease in terms of complete response towards NACT or progression-free survival (PFS). At variance, UTR-4 was an independent risk factor for a reduced OS besides already known parameters. Taken into account the most common HLA-G 3'UTR haplotypes (UTR-1-UTR-7, UTR-18), deduction of the UTR-1/2/4 haplotypes to specific SNPs revealed that the +3003C variant, unique for UTR-4, seemed to favor a detrimental disease outcome, while the +3187G and +3196G variants, unique for UTR-1 or UTR-2, were prognostic parameters for a beneficial course of disease. In conclusion, these data suggest that the HLA-G 3'UTR variants +3003C, +3187G, and +3196G are promising candidates for the prediction of therapy and disease outcome in LABC patients., Competing Interests: Author SK-B is a consultant for Qiagen. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rebmann, Schwich, Michita, Grüntkemeier, Bittner, Rohn, Horn, Hoffmann, Kimmig and Kasimir-Bauer.)

Objectives: To compare the diagnostic accuracy of contrast-enhanced thoraco-abdominal computed tomography and whole-body 18F-FDG PET/MRI in N and M staging in newly diagnosed, histopathological proven breast cancer., Material and Methods: A total of 80 consecutive women with newly diagnosed and histopathologically confirmed breast cancer were enrolled in this prospective study. Following inclusion criteria had to be fulfilled: (1) newly diagnosed, treatment-naive T2-tumor or higher T-stage or (2) newly diagnosed, treatment-naive triple-negative tumor of every size or (3) newly diagnosed, treatment-naive tumor with molecular high risk (T1c, Ki67 >14%, HER2neu over-expression, G3). All patients underwent a thoraco-abdominal ceCT and a whole-body 18F-FDG PET/MRI. All datasets were evaluated by two experienced radiologists in hybrid imaging regarding suspect lesion count, localization, categorization and diagnostic confidence. Images were interpreted in random order with a reading gap of at least 4 weeks to avoid recognition bias. Histopathological results as well as follow-up imaging served as reference standard. Differences in staging accuracy were assessed using Mc Nemars chi2 test., Results: CT rated the N stage correctly in 64 of 80 (80%, 95% CI:70.0-87.3) patients with a sensitivity of 61.5% (CI:45.9-75.1), a specificity of 97.6% (CI:87.4-99.6), a PPV of 96% (CI:80.5-99.3), and a NPV of 72.7% (CI:59.8-82.7). Compared to this, 18F-FDG PET/MRI determined the N stage correctly in 71 of 80 (88.75%, CI:80.0-94.0) patients with a sensitivity of 82.1% (CI:67.3-91.0), a specificity of 95.1% (CI:83.9-98.7), a PPV of 94.1% (CI:80.9-98.4) and a NPV of 84.8% (CI:71.8-92.4). Differences in sensitivities were statistically significant (difference 20.6%, CI:-0.02-40.9; p = 0.008). Distant metastases were present in 7/80 patients (8.75%). 18 F-FDG PET/MRI detected all of the histopathological proven metastases without any false-positive findings, while 3 patients with bone metastases were missed in CT (sensitivity 57.1%, specificity 95.9%). Additionally, CT presented false-positive findings in 3 patients., Conclusion: 18F-FDG PET/MRI has a high diagnostic potential and outperforms CT in assessing the N and M stage in patients with primary breast cancer., Competing Interests: The authors have declared that no competing interests exist.

Objectives: To compare the diagnostic performance of [ 18 F]FDG PET/MRI, MRI, CT, and bone scintigraphy for the detection of bone metastases in the initial staging of primary breast cancer patients., Material and Methods: A cohort of 154 therapy-naive patients with newly diagnosed, histopathologically proven breast cancer was enrolled in this study prospectively. All patients underwent a whole-body [ 18 F]FDG PET/MRI, computed tomography (CT) scan, and a bone scintigraphy prior to therapy. All datasets were evaluated regarding the presence of bone metastases. McNemar χ 2 test was performed to compare sensitivity and specificity between the modalities., Results: Forty-one bone metastases were present in 7/154 patients (4.5%). Both [ 18 F]FDG PET/MRI and MRI alone were able to detect all of the patients with histopathologically proven bone metastases (sensitivity 100%; specificity 100%) and did not miss any of the 41 malignant lesions (sensitivity 100%). CT detected 5/7 patients (sensitivity 71.4%; specificity 98.6%) and 23/41 lesions (sensitivity 56.1%). Bone scintigraphy detected only 2/7 patients (sensitivity 28.6%) and 15/41 lesions (sensitivity 36.6%). Furthermore, CT and scintigraphy led to false-positive findings of bone metastases in 2 patients and in 1 patient, respectively. The sensitivity of PET/MRI and MRI alone was significantly better compared with CT (p < 0.01, difference 43.9%) and bone scintigraphy (p < 0.01, difference 63.4%)., Conclusion: [ 18 F]FDG PET/MRI and MRI are significantly better than CT or bone scintigraphy for the detection of bone metastases in patients with newly diagnosed breast cancer. Both CT and bone scintigraphy show a substantially limited sensitivity in detection of bone metastases., Key Points: • [ 18 F]FDG PET/MRI and MRI alone are significantly superior to CT and bone scintigraphy for the detection of bone metastases in patients with newly diagnosed breast cancer. • Radiation-free whole-body MRI might serve as modality of choice in detection of bone metastases in breast cancer patients., (© 2021. The Author(s).)

We explored the feasibility of using Bluetooth low energy (BLE) beacon sensors to determine when individuals with low vision (LV) use handheld magnifiers at home. Knowing the frequency and duration of magnifier use would be helpful to document increased magnifier use after successful rehabilitation training, or conversely, to know when someone has abandoned a magnifier and requires assistance. Estimote Sticker BLE beacon sensors were attached to the handles of optical handheld magnifiers and dispensed to eight LV subjects to use at home. Temperature and motion data from the BLE beacon sensors were collected every second by a custom mobile application on a nearby smartphone and transmitted to a secure database server. Subjects noted the date and start/end times of their magnifier use in a diary log. Each of the 99 diary-logged self-reports of magnifier use across subjects was associated with BLE beacon sensor recordings of motion (mean 407 instances; SD 365) and increased temperature (mean 0.20 °C per minute; SD 0.16 °C) (mean total magnitude 5.4 °C; SD 2.6 °C). Diary-logged duration of magnifier use (mean 42 min; SD 24) was significantly correlated with instances of motion ( p < 0.001) and rate of temperature increase ( p < 0.001) recorded by the BLE beacon sensors. The BLE beacon sensors reliably detected meaningfully increased temperature, coupled with numerous instances of motion, when magnifiers were used for typical reading tasks at home by people with LV.

Purpose: Binocular summation refers to better visual performance with two eyes than with one eye. Little is known about the mechanism underlying binocular contrast summation in patients with common eye diseases who often exhibit binocularly asymmetric vision loss and structural changes along the visual pathway. Here we asked whether the mechanism of binocular contrast summation remains preserved in eye disease., Methods: This study included 1035 subjects with normal ocular health, cataract, age-related macular degeneration, glaucoma, and retinitis pigmentosa. Monocular and binocular contrast sensitivity were measured by the Pelli-Robson contrast sensitivity chart. Interocular ratio (IOR) was quantified as the ratio between the poorer and better eye contrast sensitivity. Binocular summation ratio (BSR) was quantified as the ratio between binocular and better eye contrast sensitivity., Results: All groups showed statistically significant binocular summation, with the BSR ranging from 1.25 [1.20, 1.30] in the glaucoma group to 1.31 [1.27, 1.36] in the normal vision group. There was no significant group difference in the BSR, after accounting for IOR. By fitting a binocular summation model Binocular = (Leftm + Rightm)1/m to the contrast sensitivity data, we found that the same binocular summation rule, reflected by the parameter m, applies across the five groups., Conclusions: Cortical binocular contrast summation appears to be preserved in spite of eye diseases that can affect the two eyes differently. This finding supports the importance of assessing both monocular and binocular functions, rather than relying on a monocular assessment in the better eye as a potentially inaccurate surrogate measure.

Purpose: Presence of disseminated tumour cells (DTCs) in the bone marrow (BM) has been described as a surrogate of residual disease in patients with early breast cancer (EBC). PADDY (Pooled Analysis of DTC Detection in Early Breast Cancer) is a large international analysis of pooled data that aimed to assess the prognostic impact of DTCs in patients with EBC., Experimental Design: Individual patient data were collected from 11 centres. Patients with EBC and available follow-up data in whom BM sampling was performed at the time of primary diagnosis before receiving any anticancer treatment were eligible. DTCs were identified by antibody staining against epithelial cytokeratins. Multivariate Cox regression was used to compare the survival of DTC-positive versus DTC-negative patients., Results: In total, 10,307 patients were included. Of these, 2814 (27.3%) were DTC-positive. DTC detection was associated with higher tumour grade, larger tumour size, nodal positivity, oestrogen receptor and progesterone receptor negativity, and HER2 positivity (all p < 0.001). Multivariate analyses showed that DTC detection was an independent prognostic marker for overall survival, disease-free survival and distant disease-free survival with hazard ratios (HR) and 95% confidence intervals (CI) of 1.23 (95% CI: 1.06-1.43, p = 0.006), 1.30 (95% CI: 1.12-1.52, p < 0.001) and 1.30 (95% CI: 1.08-1.56, p = 0.006), respectively. There was no association between locoregional relapse-free survival and DTC detection (HR 1.21; 95% CI 0.68-2.16; p = 0.512)., Conclusions: DTCs in the BM represent an independent prognostic marker in patients with EBC. The heterogeneous metastasis-initiating potential of DTCs is consistent with the concept of cancer dormancy., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ADH, FAT and SYB report a grant from Exact Sciences. TNF received personal fees from AstraZeneca, Novartis, Roche, Pfizer, Esai, Tesaro, Teva, Celgene, Daichi Sankyo, MSD, Menarini. PAF reports grants from Cepheid, Novartis and Biontech, personal fees from Novartis, Roche, Pfizer, Celgene, Daiichi-Sankyo, TEVA, Astra Zeneca, Merck Sharp & Dohme, Myelo Therapeutics, Macrogenics, Eisai, Puma and Lilly. CAK is a member of the SAB of HiberCell, New York. All other authors declare no potential conflicts of interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Neuropilin-1 (NRP-1) is a transmembrane protein that acts as a multifunctional non-tyrosine kinase receptor with an established role in development and immunity. NRP-1 also regulates tumor biology, and high expression levels of tissue NRP-1 have been associated with a poor prognosis. Recently, ELISA-based quantification of soluble NRP-1 (sNRP-1) has become available, but little is known about the prognostic value of sNRP-1 in malignancies., Materials and Methods: We measured sNRP-1 in the serum of 509 patients with primary early breast cancer (BC) at the time of diagnosis using ELISA., Results: Mean serum values of sNRP-1 were 1.88 ± 0.52 nmol/l (= 130.83 ± 36.24 ng/ml). SNRP-1 levels weakly correlated with age, and were higher in peri- and postmenopausal patients compared to premenopausal patients, respectively (p < 0.0001). Low levels of sNRP-1 were associated with a significant survival benefit compared to high sNRP-1 levels at baseline (p = 0.005; HR 1.94; 95%CI 1.23-3.06). These findings remained significant after adjustment for tumor stage including lymph node involvement, grading, hormone receptor, HER2 status, and age (p = 0.022; HR 1.78; 95%CI 1.09-2.91)., Conclusion: Our findings warrant further investigations into the prognostic and therapeutic potential of sNRP-1 in BC.

Background: This study investigated the performance of simultaneous 18 F-FDG PET/MRI of the breast as a platform for comprehensive radiomics analysis for breast cancer subtype analysis, hormone receptor status, proliferation rate and lymphonodular and distant metastatic spread., Methods: One hundred and twenty-four patients underwent simultaneous 18 F-FDG PET/MRI. Breast tumors were segmented and radiomic features were extracted utilizing CERR software following the IBSI guidelines. LASSO regression was employed to select the most important radiomics features prior to model development. Five-fold cross validation was then utilized alongside support vector machines, resulting in predictive models for various combinations of imaging data series., Results: The highest AUC and accuracy for differentiation between luminal A and B was achieved by all MR sequences (AUC 0.98; accuracy 97.3). The best results in AUC for prediction of hormone receptor status and proliferation rate were found based on all MR and PET data (ER AUC 0.87, PR AUC 0.88, Ki-67 AUC 0.997). PET provided the best determination of grading (AUC 0.71), while all MR and PET analyses yielded the best results for lymphonodular and distant metastatic spread (0.81 and 0.99, respectively)., Conclusion: 18 F-FDG PET/MRI enables comprehensive high-quality radiomics analysis for breast cancer phenotyping and tumor decoding, utilizing the perks of simultaneously acquired morphologic, functional and metabolic data.

Purpose: To compare breast magnetic resonance imaging (MRI), thoracal MRI, thoracal 18 F-fluorodeoxyglucose positron emission tomography ( 18 F-FDG PET)/MRI and axillary sonography for the detection of axillary lymph node metastases in women with newly diagnosed breast cancer. Materials and Methods: This prospective double-center study included patients with newly diagnosed breast cancer between March 2018 and December 2019. Patients underwent thoracal ( 18 F-FDG PET/)MRI, axillary sonography, and dedicated prone breast MRI. Datasets were evaluated separately regarding nodal status (nodal+ vs. nodal-). Histopathology served as reference standard in all patients. The diagnostic performance of breast MRI, thoracal MRI, thoracal PET/MRI and axillary sonography in detecting nodal positive patients was tested by creating receiver-operating-characteristic curves (ROC) with a calculated area under the curve (AUC). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for all four modalities. A McNemar test was used to assess differences. Results: 112 female patients (mean age 53.04 ± 12.6 years) were evaluated. Thoracal PET/MRI showed the highest ROC-AUC with a value of 0.892. The AUC for breast MRI, thoracal MRI and sonography were 0.782, 0.814 and 0.834, respectively. Differences between thoracal PET/MRI and axillary sonography, thoracal MRI and breast MRI were statistically significant (PET/MRI vs. axillary sonography, P = 0.01; PET/MRI vs. thoracal MRI, P = 0.02; PET/MRI vs. breast MRI, P = 0.03). PET/MRI showed the highest sensitivity (81.8%, 36/44) (95%-CI: 67.29-91.81%) while axillary sonography had the highest specificity (98.5%, 65/66), 95%-CI: 91.84-99.96%). Conclusion: 18 F-FDG PET/MRI outperforms axillary sonography, breast MRI and thoracal MRI in determining the axillary lymph node status. In a clinical setting, the combination of 18 F-FDG PET/MRI and axillary sonography might be considered to provide even more accuracy in diagnosis., (Copyright © 2021 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Purpose: The aim of this study was to correlate prognostically relevant immunohistochemical parameters of breast cancer with simultaneously acquired SUVs and apparent diffusion coefficient (ADC) values derived from hybrid breast PET/MRI., Patients and Methods: Fifty-six women with newly diagnosed, therapy-naive, histologically proven breast cancer (mean age, 54.1 ± 12.0 years) underwent dedicated prone 18F-FDG breast PET/MRI. Diffusion-weighted imaging (b-values: 0, 500, 1000 s/mm2) was performed simultaneously with the PET acquisition. A region of interest encompassing the entire primary tumor on each patient's PET/MRI scan was used to determine the glucose metabolism represented by maximum and mean SUV as well as into corresponding ADC maps to assess tumor cellularity represented by mean and minimum ADC values. Histopathological tumor grading and prognostically relevant immunohistochemical markers, that is, Ki67, progesterone receptor, estrogen receptor, and human epidermal growth factor receptor 2 (HER2), were assessed. Pearson correlation coefficients were calculated to compare SUV and ADC values as well as the immunohistochemically markers and molecular subtype. For the comparison with the tumor grading, a Wilcoxon test was used., Results: A significant inverse correlation between SUV and ADC values derived from breast PET/MRI (r = -0.49 for SUVmean vs ADCmean; r = -0.43 for SUVmax vs ADCmin; both P's < 0.001) was found. Tumor grading and Ki67 both showed a positive correlation with SUVmean from breast PET/MRI (r = 0.37 and r = 0.32, P < 0.01). For immunohistochemical markers, HER2 showed an inverse correlation with ADC values from breast PET/MRI (r = -0.35, P < 0.01). Molecular subtypes significantly correlate with SUVmax and SUVmean (r = 0.52 and r = 0.42, both P's < 0.05). In addition, estrogen receptor expression showed an inverse correlation with SUVmax and SUVmean from breast PET/MRI (r = -0.45 and r = -0.42, P < 0.001)., Conclusions: The present data show a correlation between increased glucose metabolism, cellularity, tumor grading, estrogen and HER2 expression, as well as molecular subtype of breast cancer primaries. Hence, simultaneous 18F-FDG PET and diffusion-weighted imaging from hybrid breast PET/MRI may serve as a predictive tool for identifying high-risk breast cancer patients in initial staging and guide-targeted therapy., Competing Interests: Conflicts of interest and sources of funding: The authors declare no conflict of interest. The study is funded by Deutsche Forschungsgemeinschaft, a German research foundation (BU3075/2-1). The funding foundation was not involved in the trial design, patient recruitment, data collection, analysis, interpretation or presentation, writing or editing of the reports, or the decision to submit for publication. The corresponding author had full access to all data in the study and had all the responsibility for the decision to submit for publication., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Impairment of visual function is one of the major symptoms of people with multiple sclerosis (pwMS). A multitude of disease effects including inflammation and neurodegeneration lead to structural impairment in the visual system. However, the gold standard of disability quantification, the expanded disability status scale (EDSS), relies on visual assessment charts. A more comprehensive assessment of visual function is the full contrast sensitivity function (CSF), but most tools are time consuming and not feasible in clinical routine. The quantitative CSF (qCSF) test is a computerized test to assess the full CSF. We have already shown a better correlation with visual quality of life (QoL) than for classical high and low contrast charts in multiple sclerosis (MS)., Objective: To study the precision, test duration, and repeatability of the qCSF in pwMS. In order to evaluate the discrimination ability, we compared the data of pwMS to healthy controls., Methods: We recruited two independent cohorts of MS patients. Within the precision cohort ( n = 54), we analyzed the benefit of running 50 instead of 25 qCSF trials. The repeatability cohort ( n = 44) was assessed by high contrast vision charts and qCSF assessments twice and we computed repeatability metrics. For the discrimination ability we used the data from all pwMS without any previous optic neuritis and compared the area under the log CSF (AULCSF) to an age-matched healthy control data set., Results: We identified 25 trials of the qCSF algorithm as a sufficient amount for a precise estimate of the CSF. The median test duration for one eye was 185 s (range 129-373 s). The AULCSF had better test-retest repeatability (Mean Average Precision, MAP) than visual acuity measured by standard high contrast visual acuity charts or CSF acuity measured with the qCSF (0.18 vs. 0.11 and 0.17, respectively). Even better repeatability (MAP = 0.19) was demonstrated by a CSF-derived feature that was inspired by low-contrast acuity charts, i.e., the highest spatial frequency at 25% contrast. When compared to healthy controls, the MS patients showed reduced CSF (average AULCSF 1.21 vs. 1.42, p < 0.01)., Conclusion: High precision, usability, repeatability, and discrimination support the qCSF as a tool to assess contrast vision in pwMS., Competing Interests: MD holds equity in and employment by Adaptive Sensory Technology and holds patents related to the qCSF. The qCSF device was provided to INIMS free of charge; no further compensation was granted. HZ received research grants from Novartis and speaking honoraria from Bayer Healthcare, unrelated to this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Rosenkranz, Kaulen, Zimmermann, Bittner, Dorr and Stellmann.)

Purpose: We evaluated whether omitting (censoring) points in more severely damaged visual field areas can reduce test-retest variability of static automated perimetry (SAP) in retinitis pigmentosa (RP), as variability creates a significant challenge when monitoring for changes., Methods: Cohort 1 included 27 eyes in 16 RP subjects with visual acuity (VA) ranging from 20/20 to 20/70 who completed Humphrey 10-2 size III SAP, once per visit at three visits. Cohort 2 included 15 eyes in nine RP subjects with VA ≤ 20/60 who completed Humphrey 30-2 size V SAP, twice per visit at three visits. Variability was assessed using 95% coefficient of repeatability (CR) calculations for uncensored (all threshold values and data points included) and censored data., Results: In cohort 1, the uncensored between-visit 95% CR was 11.6 decibels (dB); censoring locations with threshold values of <8 to 20 dB resulted in 31% to 53% reductions in the 95% CR. For cohort 2, uncensored 95% CRs were 8.7 and 8.0 dB for within- and between-visit variability, respectively; censoring <8 to 17 dB resulted in 15% to 41% and 15% to 43% reductions in within-visit and between-visit 95% CRs, respectively. For both cohorts, censoring at higher values yielded slightly less variability, at the expense of discarding data from a greater number of eyes and test locations., Conclusions: For 20/20 to 20/70 VA tested with size III stimuli, censoring lower sensitivity values results in substantially lower test-retest variability, which may help detect true changes for locations without severe baseline loss., Translational Relevance: A rule of thumb for clinical practices using SAP to monitor RP is that longitudinal losses of >9 dB for individual test locations with initial values ≥ 9 dB are likely to be real and meaningful, as they exceed typical variability., Competing Interests: Disclosure: A.K. Bittner, None; A. Mistry, None; L. Nehmad, None; R. Khan, None; G. Dagnelie, None, (Copyright 2020 The Authors.)

Objectives: To evaluate and compare the diagnostic potential of whole-body MRI and whole-body 18 F-FDG PET/MRI for N and M staging in newly diagnosed, histopathologically proven breast cancer., Material and Methods: A total of 104 patients (age 53.4 ± 12.5) with newly diagnosed, histopathologically proven breast cancer were enrolled in this study prospectively. All patients underwent a whole-body 18 F-FDG PET/MRI. MRI and 18 F-FDG PET/MRI datasets were evaluated separately regarding lesion count, lesion localization, and lesion characterization (malignant/benign) as well as the diagnostic confidence (5-point ordinal scale, 1-5). The N and M stages were assessed according to the eighth edition of the American Joint Committee on Cancer staging manual in MRI datasets alone and in 18 F-FDG PET/MRI datasets, respectively. In the majority of lesions histopathology served as the reference standard. The remaining lesions were followed-up by imaging and clinical examination. Separately for nodal-positive and nodal-negative women, a McNemar chi 2 test was performed to compare sensitivity and specificity of the N and M stages between 18 F-FDG PET/MRI and MRI. Differences in diagnostic confidence scores were assessed by Wilcoxon signed rank test., Results: MRI determined the N stage correctly in 78 of 104 (75%) patients with a sensitivity of 62.3% (95% CI: 0.48-0.75), a specificity of 88.2% (95% CI: 0.76-0.96), a PPV (positive predictive value) of 84.6% % (95% CI: 69.5-0.94), and a NPV (negative predictive value) of 69.2% (95% CI: 0.57-0.8). Corresponding results for 18 F-FDG PET/MRI were 87/104 (83.7%), 75.5% (95% CI: 0.62-0.86), 92.2% (0.81-0.98), 90% (0.78-0.97), and 78.3% (0.66-0.88), showing a significantly better sensitivity of 18 F-FDG PET/MRI determining malignant lymph nodes (p = 0.008). The M stage was identified correctly in MRI and 18 F-FDG PET/MRI in 100 of 104 patients (96.2%). Both modalities correctly staged all 7 patients with distant metastases, leading to false-positive findings in 4 patients in each modality (3.8%). In a lesion-based analysis, 18 F-FDG PET/MRI showed a significantly better performance in correctly determining malignant lesions (85.8% vs. 67.1%, difference 18.7% (95% CI: 0.13-0.26), p < 0.0001) and offered a superior diagnostic confidence compared with MRI alone (4.1 ± 0.7 vs. 3.4 ± 0.7, p < 0.0001)., Conclusion: 18 F-FDG PET/MRI has a better diagnostic accuracy for N staging in primary breast cancer patients and provides a significantly higher diagnostic confidence in lesion characterization than MRI alone. But both modalities bear the risk to overestimate the M stage.

Background: We analyzed mRNA profiles of prostate cancer related genes in circulating tumor cells (CTCs) of primary, non-metastatic triple-negative breast cancer (TNBC) patients (pts) before and after neoadjuvant chemotherapy to elucidate the potential of prostate cancer targets in this BC subgroup. Method: Blood from 41 TNBC pts ( n = 41 before / 26 after therapy) was analyzed for CTCs applying the AdnaTest EMT-2/Stem Cell Select. Multimarker RT-qPCR allowed the detection of the prostate specific antigen PSA , the prostate specific membrane antigen PSMA , full-length androgen receptor ( AR-FL ), and AR splice-variant seven ( AR-V7 ). Results: Before therapy, at least one prostate cancer related gene was detected in 15/41 pts (37%). Notably, in 73% of AR-FL positive cases, AR-V7 was co-expressed. After therapy, CTCs of only one patient harbored prostate cancer related genes. AR-V7 + and PSMA + CTCs significantly correlated with early relapse ( p = 0.041; p = 0.00039) whereas PSMA + CTCs also associated with a reduced OS ( p = 0.0059). This correlation was confirmed for PSMA + CTCs in univariate (PFS p = 0.002; OS p = 0.015), but not multivariate analysis. Conclusion: Although CTCs that expressed prostate cancer related genes were eliminated by the given therapy, PSMA + CTCs significantly identified pts at high risk for relapse. Furthermore, AR inhibition, often discussed for this BC subgroup, might not be successful in the primary setting of the disease since we identified AR-FL + CTCs together with AR-V7 + CTCs, associated with therapeutic failure., (Copyright © 2020 Kasimir-Bauer, Keup, Hoffmann, Hauch, Kimmig and Bittner.)