INTRODUCTION This study leverages a large, diverse cohort to characterize ethnoracial differences in amyloid positron emission tomography (PET) positivity and identify social determinants of health (SDOHs) contributing to these differences.METHODS We assessed differences in amyloid PET positivity by ethnoracial group (Black, Latinx, or all other races/ethnicities [AORE]) among Medicare beneficiaries with cognitive impairment. Secondary analyses associated various SDOHs with amyloid PET positivity. RESULTS Among 5757 participants (21.7% Black, 20.3% Latinx, 58.1% AORE), we found lower odds of amyloid positivity in Black (odds ratio [OR]: 0.72, 95% confidence interval [CI]: 0.62-0.83) and Latinx (OR: 0.78, 95% CI: 0.67-0.91) compared to AORE. Individuals in the comfortable (OR: 1.22, 95% CI: 1.05-1.42) and distressed (OR: 1.40, 95% CI: 1.08-1.82) Area Deprivation Index (ADI) groups had greater odds of amyloid positivity than individuals in the prosperous group. DISCUSSION Amyloid PET positivity rates were lower among Black and Latinx individuals and higher among individuals in more deprived ADI categories. This has potential implications for anti-amyloid therapies.

INTRODUCTION:Relationships between Alzheimer's disease neuropathology, residential neighborhood, and cognitive impairment remain incompletely understood. METHODS:We examined whether residence within a disadvantaged neighborhood was associated with amyloid positron emission tomography (PET) positivity. We used data from the observational, multisite, Imaging Dementia-Evidence for Amyloid Scanning study that included cognitively impaired Medicare beneficiaries. Our secondary analysis examined multivariable-adjusted associations between neighborhood disadvantage (measured by Area Deprivation Index [ADI] deciles 1-90 vs. 91-100 representing greatest disadvantage) and amyloid PET positivity. RESULTS:Among 15,346 White, 829 Latino, 637 Black/African American, and 321 Asian individuals, 51% were female, mean age was 75.7 years, 535 (3.8%) resided in ADI 91 to 100 decile, and 61.6% were amyloid PET positive. The ADI 91-100 decile was associated with lower odds of PET positivity by visual interpretation (odds ratio [OR] 0.80, 95% confidence interval [CI] 0.67-0.96, p ≤ .001) but not PET Centiloid value ≥ 40 versus ≤ 10 (OR 0.81, 95% CI 0.66-1.01, p = 0.060). CONCLUSION:Residence in the most disadvantaged neighborhoods may be associated with lower amyloid pathology in cognitively impaired individuals.

BACKGROUND. Digital breast tomosynthesis (DBT) has shown improved screening performance compared with digital mammography (DM), although the modality is less well-studied in women 40-44 years old and 75 years and older. OBJECTIVE. The purpose of this study was to compare screening performance between DM and DBT in Tomosynthesis Mammographic Imaging Screening Trial (TMIST) Lead-In trial (A4705) participants who were ineligible for transition to the full TMIST trial (EA1151) due to age at trial entry (40-44 or ≥ 75 years). METHODS. A4705, a prospective trial recruiting women 40 years old and older at four Canadian sites from October 2014 to July 2017, randomized participants to undergo multiple screening rounds by DM or DBT. Final EA1151 eligibility incorporated a narrower age range of 45-74 years. This unplanned analysis included a subset of A4705 participants ineligible for transition to EA1151 due to age at entry (40-44 or ≥ 75 years old). Examination-level screening performance metrics were calculated. The reference standard was determined by 1-year follow-up after participants' last screening round. RESULTS. The study included 271 A4705 participants (mean age, 54 ± 17 [SD] years) who were age-ineligible for EA1151; 181 were 40-44 years old (76 and 105 randomized to DM and DBT, respectively), and 90 were 75 years old or older (46 and 44 randomized to DM and DBT, respectively). Participants in the DM and DBT arms underwent 389 and 482 screening examinations, respectively (mean, 3.2 screening rounds per participant in each arm). Eight cancers were diagnosed (seven screen-detected [one by DM; six by DBT]; one interval cancer in the DBT arm). In participants 40-44 years old, DM, compared with DBT, exhibited a recall rate of 13.2% versus 12.0%, a cancer detection rate (CDR) per 1000 examinations of 0.0 versus 14.6, a PPV1 of 0.0% versus 12.2%, and a PPV3 of 0.0% versus 83.3%, respectively. In participants 75 years old and older, DM, compared with DBT, exhibited a recall rate of 10.1% versus 3.6%, a CDR per 1000 examinations of 7.2 versus 7.1, a PPV1 of 7.1% versus 20.0%, and a PPV3 of 50.0% in both arms. CONCLUSION. Screening performance metrics were overall more favorable for DBT than for DM in women 40-44 years old and 75 years old and older. CLINICAL IMPACT. DBT may mitigate limitations of DM and improve screening performance in the evaluated age groups.

Amyloid PET use has been associated with change in clinical management among cognitively impaired older adults but various ethnoracial groups were underrepresented in prior studies. New IDEAS examined whether this association exists among cognitively impaired ethnoracially diverse Medicare beneficiaries and beneficiaries presenting with clinically “atypical” (non-memory predominant) presentations of Alzheimer's disease (AD). New IDEAS was a national, multi-site, prospective, longitudinal study that enrolled Medicare beneficiaries with mild cognitive impairment (MCI) or dementia who underwent amyloid PET scan as recommended by their treating dementia specialists at “real-world” clinics. The study examined association between amyloid PET and subsequent change in clinical management within 90 days of PET. Primary endpoint was change in management between pre- and post-PET visits defined as a composite inclusive of change in AD and non-AD drugs and change in counseling about safety and future planning. Proportions of change in management between pre- and post-PET visit by group are reported as well as logistic regression examining association between composite change in management and multiple factors. Median age of 4363 participants is 75 (range 35-98) years and 55.4% are female, 63.8% having MCI and 65.4% (95% CI 64.0, 66.8) amyloid PET positive. The sample includes 938 (21.5%) Black/African American, 707 (16.2%) Hispanic/Latino, and 2718 (62.3%) other individuals with 1330 (30.5%) participants with atypical presentations of AD (Table 1). Overall change in management occurred in 54.7% (95% CI 51.5, 57.9) of Black/African American, 53.7% (50.1, 57.4) of Hispanic/Latino, and 60.2% (58.3, 62.0) of other individuals. By clinical presentation, 44.1% (40.7, 47.6) of atypical clinical MCI, 52.6% (48.4, 56.7) of atypical dementia, 63.9% (61.8, 66.0) of typical MCI, and 59.9% (56.8, 62.8) of typical dementia participants had an overall change in management (Table 2). Logistic regression demonstrated significant interactions between Black/African American identity and positive amyloid PET scan (OR 1.64, 95% CI 1.14, 2.36; p 0.008) (Table 3). New IDEAS demonstrated that amyloid PET use among ethnoracially diverse Medicare beneficiaries and those with atypical and typical clinical presentations of AD leads to changes in clinical management, highlighting the value of this biomarker in a real-world clinical care setting.

Ductal carcinoma in situ (DCIS) is a non-lethal, pre-invasive breast cancer that is diagnosed in approximately 50,000 women annually in the United States. While only 10 - 30% of cases upstage to invasive cancer at surgery, the majority of DCIS cases are treated with surgery and subsequent radiation therapy, potentially overtreating some lower risk DCIS that may never progress to invasive cancer. Imaging biomarkers quantifying texture, shape, and signal intensities have been linked to tumor aggressiveness and cancer progression. These biomarkers are computed through high-throughput radiomic analysis using radiologist-provided lesion segmentations and publicly available software; however, the lesion segmentation step is manually taxing and prone to inter-reader variability. Here, we propose a promptless deep-learning pipeline to segment DCIS from the first post-contrast MRI, using the MA-SAM architecture with 5-slice volumes fed into the model, leveraging 3D features and a pre-trained Segment Anything Model (SAM) ViT heavy backbone. After 10-fold cross validation on a cohort of 297 patients from the ECOG-ACRIN E4112 trial, we achieved a median dice score of 0.53 against an expert radiologist. On a similar breast tumor MRI segmentation task, 4 expert readers achieved a comparable median dice of 0.60. The MA-SAM scores also far exceed nnUNet implementations with dice scores below 0.40. Radiomic features are derived using the CaPTk platform and summarized through principal component analysis (PCA). Despite a moderate dice score, we show that the features derived from the AI segmentation significantly (p = 0.013) improve the prediction of disease progression (AUC 0.72 to 0.78) compared to the clinical and magnetic resonance features alone. This improvement is similar to that of radiologist-generated features (AUC 0.76, p=0.0047) published in 2025 on the same cohort. This new AI-based segmentation method holds potential to accelerate radiomic analyses, increase clinical access, and identify low-risk DCIS thereby reducing overtreatment.

BACKGROUND:Socioeconomic vulnerabilities and healthcare environment contribute to disparities in dementia assessment. Whether these affect dementia management, however, remains unclear. We used Imaging Dementia - Evidence for Amyloid Scanning (IDEAS) study data to compare the impact of amyloid PET on pharmacological management across social factors, patient comorbidities, and physician practice settings. METHODS:We analyzed rates of pharmacological change in IDEAS participants with visually interpretable amyloid PET, completed pre- and post-PET case reports, social determinants (racioethnic identity of Asian, Black, Hispanic, or White, area deprivation index (ADI), living arrangement, education) and medical history. Outcomes included any change between pre-PET and post-PET visits in prescription of Alzheimer's disease (AD) drugs, and of non-AD drugs treating dementia risk factors or affecting cognition/mood/behavior. We used multilevel logistic regression with a random site intercept to test whether the probability of change in management associated with social determinants, race/ADI interactions with amyloid-positivity, comorbidities, and clinical setting, adjusting for demographics. RESULTS:Among 10,904 cognitively impaired participants (Table 1), 90% were White, with 4.8% Hispanic, 3.1% Black, and 1.8% Asian representation. 10% resided in highly disadvantaged neighborhoods (ADI 9-10), 83% lived with ≥1 person, and 68% were educated past high school. Pre-FDR correction (adjusted P-values: Table 1), AD drug management change was associated with dyslipidemia (OR [95% CI]=0.88 [0.80-0.97], Punadj=.007), depression (0.87 [0.77, 0.97], Punadj=.014), and tobacco use (0.87 [0.77, 0.99], Punadj=.028). Non-AD drug management change was associated with depression (1.73 [1.51, 1.97], Punadj<.001), group practice (0.72 [0.56, 0.93], Punadj=.012) and ADI in amyloid-positive participants (0.68 [0.47, 0.98], Punadj=.04). Change rates were also associated with amyloid-PET status, impairment level, and etiology. Figure 1 summarizes change rates across social factors. CONCLUSIONS:These results suggest amyloid status, cognitive impairment level, dementia etiology, and comorbidities may inform pharmacological decision-making. Clarifying dementia etiology with amyloid PET may, for instance, help clinicians optimize treatment plans to address undermanaged depression in cognitively impaired older adults. Further, socioeconomic disadvantage may limit clinical response to amyloid-positivity. Replication in New IDEAS and examination of Medicare claims will help elucidate whether disparities in pre-PET management and management changes are primarily driven by access barriers to assessment and healthcare.

Breast ductal carcinoma in situ (DCIS) requires personalized treatment given its variable natural history. This study reports the first prospective oncologic outcomes of radiotherapy decisions as guided by 12-gene molecular assay, the DCIS score (DS). To assess surgical outcomes following preoperative breast magnetic resonance imaging (MRI) in women with DCIS and estimate 5-year and 10-year ipsilateral breast event (IBE) rates in participants given DS-based postoperative radiotherapy recommendations after local excision (WLE). Women with screen-detected DCIS who were eligible for WLE were enrolled to a single-arm, multicenter trial conducted at 75 institutions within the Eastern Cooperative Oncology Group–American College of Radiology Imaging Network (March 2015 to April 2016) and received a preoperative breast MRI-guided surgical treatment. Those who underwent successful WLE were advised to omit radiotherapy for low DS (<39) and receive radiotherapy for intermediate/high DS (≥39). Those achieving WLE as final treatment and successful DS assay (n = 171) were included in a prespecified analysis. Participants were followed up every 6 months for DCIS or invasive IBE, and 5-year IBE rates were analyzed from July to November 2023. DS-based postoperative radiotherapy recommendations. Five-year IBE rates, with 95% CIs. Among the 339 participants, the mean (SD) age was 59.1 (10.1) years. A total of 171 women (50.4%) received WLE for pure DCIS with free surgical margins and had DS data available. A total of 159 (93.0%) adhered to DS-based radiotherapy recommendations; 7 of 82 patients (8.5%) with a low DS underwent radiotherapy, and 5 of 89 patients (5.6%) with an intermediate/high DS declined radiotherapy. Over median (range) follow-up of 5 (0.5-5.0) years, 8 of 171 women experienced IBEs (4.8%; 95% CI, 2.4%-9.4%). IBE rates were similar for participants with a low DS(5.1%; 95% CI, 1.9%-12.9%) and participants with an intermediate/high DS (4.5%; 95% CI, 1.7%-11.7%). Among the 159 women who had adhered to DS-based radiotherapy recommendations, IBE rates were similar for participants with a low DS (5.5%; 95% CI, 2.1%-14.1%) and intermediate/high DS (4.8%; 95% CI, 1.8%-12.3%). The findings of this prespecified analysis of a clinical trial suggest that DS-guided radiotherapy post-WLE for DCIS shows markedly lower 5-year IBE rates (approximately 5%) for intermediate/high DS than previously reported data following WLE alone. Despite a limited sample size, these data potentially provide support for radiotherapy use in patients with intermediate/high DS, and omission when DS is low, although confirmatory studies are needed. ClinicalTrials.gov Identifier: NCT02352883

INTRODUCTION:We examined sex effects on amyloid positron emission tomography (PET) in a large cohort of patients evaluated for cognitive complaints in a "real-world" specialty setting. METHODS:We analyzed 10,361 amyloid PET scans (51% females) from the Imaging Dementia-Evidence for Amyloid Scanning Study. Amyloid positivity was defined by either local visual read or central PET processing and quantification (≥ 24.4 Centiloids). Sex differences were examined using multilinear regression and logistic regression adjusted for age, comorbidities, and other demographic and clinical covariates. RESULTS:Females had higher rates of positive amyloid PET visual reads (63% vs. 59%, P < 0.001) and higher Centiloids (CLs; median 48.7 vs. 36.8, p < 0.001). On logistic regression, females had higher odds ratios (ORs) for positive amyloid PET (visual read OR 1.20, 95% confidence interval [CI]: 1.11-1.31; CL threshold-based OR 1.37, 95% CI: 1.26-1.49; both p < 0.001). DISCUSSION:Females with cognitive impairment showed higher amyloid PET positivity and greater amyloid burden. Further research is needed to explore mechanisms and treatment implications. HIGHLIGHTS:Females exhibited higher rates of amyloid positron emission tomography (PET) positivity and higher amyloid burden than males. These sex effects were found in patients with both mild cognitive impairment (MCI) and dementia. Females also had higher rates of dementia and amnestic MCI, while males had higher rates of non-amnestic MCI and more cholinesterase inhibitor use.

Models using clinical and MRI-based radiomic features identified from ductal carcinoma in situ lesions improved prediction of disease upstaging at surgery compared with standard clinical information alone.

Importance:Limited longitudinal data exist regarding health-related quality of life (HRQL) following surgery for ductal carcinoma in situ (DCIS) breast cancer. Objective:To assess individual- and neighborhood-level factors associated with longitudinal trajectories of mental and physical HRQL among individuals with DCIS eligible for breast conservation surgery. Design, Setting, and Participants:This cohort study was an ancillary to a prospective, nonrandomized clinical trial of women with DCIS breast cancer between March 2015 and April 2016 at 75 US institutions, community practices, and academic centers coordinated by the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) Cancer Research Group (E4112). Eligible participants were recently diagnosed with unilateral DCIS who were eligible for wide local excision (WLE) and had a diagnostic mammogram within 3 months of study registration. Patient-reported outcome (PRO) questionnaires were administered to participants at the time of registration, after surgeon consultation but presurgery, at the first postoperative visit, 12 months postsurgery, and 24 months postsurgery. Self-reported social determinants of health (SDOH) and clinical history and surgery received were also collected. Data were analyzed from June 2024 to November 2024. Main Outcomes and Measures:PRO measures assessing patient knowledge of DCIS and perception of being informed; HRQL, measured using the 10-item Patient-Reported Outcomes Measurement Information System with mental and physical health subscales. Results:Among the 296 women, the median age at enrollment was 60 years (range, 34-87 years) (11 Asian [4%], 41 Black [14%], 229 White [77%]); 147 participants (50%) reported at least 1 family member with breast cancer. The majority of participants had non-Hispanic ethnicity (280 [95%]), had private insurance (227 [77%]), resided in areas of low-to-moderate deprivation (ADI median, 44 [range, 1-99]), and received a single WLE (185 [63%]). Participants exhibited good knowledge of DCIS (median, 80 [range, 20-100]) and a high perception of being informed (median, 10 [range, 3-10]). Being American Indian or Alaska Native, Asian, Black, multiracial, or not reporting race (χ2 = 6.8 [df, 2]; P = .03), having insurance other than private (χ2 = 14.3 [df, 2]; P < .001), and having more than 1 surgery (χ2 = 12.3 [df, 4]; P = .02) were associated with decreases in mental health at 24 months compared with baseline. Having private insurance and a low perception of being informed of one's treatment were associated with increases in physical health at 2 years. Conclusions and Relevance:In this cohort study of women with DCIS, in the 24 months following diagnosis, nonprivate insurance, minoritized race, and number of surgeries received were associated with reduced mental HRQL. Nonprivate insurance was also associated with reduced physical HRQL. Trial Registration:ClinicalTrials.gov Identifier: NCT02352883.

Importance:Breast ductal carcinoma in situ (DCIS) requires personalized treatment given its variable natural history. This study reports the first prospective oncologic outcomes of radiotherapy decisions as guided by 12-gene molecular assay, the DCIS score (DS). Objective:To assess surgical outcomes following preoperative breast magnetic resonance imaging (MRI) in women with DCIS and estimate 5-year and 10-year ipsilateral breast event (IBE) rates in participants given DS-based postoperative radiotherapy recommendations after local excision (WLE). Design, Setting, and Participants:Women with screen-detected DCIS who were eligible for WLE were enrolled to a single-arm, multicenter trial conducted at 75 institutions within the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (March 2015 to April 2016) and received a preoperative breast MRI-guided surgical treatment. Those who underwent successful WLE were advised to omit radiotherapy for low DS (<39) and receive radiotherapy for intermediate/high DS (≥39). Those achieving WLE as final treatment and successful DS assay (n = 171) were included in a prespecified analysis. Participants were followed up every 6 months for DCIS or invasive IBE, and 5-year IBE rates were analyzed from July to November 2023. Intervention:DS-based postoperative radiotherapy recommendations. Main Outcomes and Measures:Five-year IBE rates, with 95% CIs. Results:Among the 339 participants, the mean (SD) age was 59.1 (10.1) years. A total of 171 women (50.4%) received WLE for pure DCIS with free surgical margins and had DS data available. A total of 159 (93.0%) adhered to DS-based radiotherapy recommendations; 7 of 82 patients (8.5%) with a low DS underwent radiotherapy, and 5 of 89 patients (5.6%) with an intermediate/high DS declined radiotherapy. Over median (range) follow-up of 5 (0.5-5.0) years, 8 of 171 women experienced IBEs (4.8%; 95% CI, 2.4%-9.4%). IBE rates were similar for participants with a low DS(5.1%; 95% CI, 1.9%-12.9%) and participants with an intermediate/high DS (4.5%; 95% CI, 1.7%-11.7%). Among the 159 women who had adhered to DS-based radiotherapy recommendations, IBE rates were similar for participants with a low DS (5.5%; 95% CI, 2.1%-14.1%) and intermediate/high DS (4.8%; 95% CI, 1.8%-12.3%). Conclusions and Relevance:The findings of this prespecified analysis of a clinical trial suggest that DS-guided radiotherapy post-WLE for DCIS shows markedly lower 5-year IBE rates (approximately 5%) for intermediate/high DS than previously reported data following WLE alone. Despite a limited sample size, these data potentially provide support for radiotherapy use in patients with intermediate/high DS, and omission when DS is low, although confirmatory studies are needed. Trial Registration:ClinicalTrials.gov Identifier: NCT02352883.

The Imaging Dementia-Evidence for Amyloid Scanning (IDEAS) Study collected over 15,000 community-acquired amyloid-PET scans, without structural MRI and with different acquisition times, tracers and scanners. Here we describe and validate rPOP (robust PET-Only Processing), a pipeline for 18 F-Florbetapir (FBP), 18 F-Florbetaben (FBB) and 18 F-Flutemetamol (FLUTE) scans collected in IDEAS. Each image undergoes automatic origin reset to center of mass, spatial normalization based on weighted PET templates (with SPM12) and data-driven differential smoothing (with AFNI). We received n=740 (514 FBP, 182 FBB, 44 FLUTE) amyloid-PET scans from the IDEAS–Brain Health Registry substudy (IDEAS-BHR), with amyloid-PET local visual reads available for N=663 scans. We performed semi-quantification via rPOP and estimated neocortical Centiloids after tracer-specific calibrations using the GAAIN VOIs with whole cerebellum reference. Centiloids were calculated for clinical groups (MCI or dementia), to compare rPOP-based amyloid-status (centiloids≥24.4) with visual reads. The pipeline was validated with n=1518 ADNI scans (n=1249 FBP, n=269 FBB), using MRI-based amyloid-status as a reference and testing the associations between rPOP- and MRI-based centiloids. rPOP successfully processed N=2233/2258 (98.9%) scans in the first pass, with N=24/25 warping-related failures rescued with a manual reorientation and origin reset prior to warping. In IDEAS-BHR, we observed the expected centiloids distribution (Figure 1A-B) both according to visual reads and also stratifying by clinical stage amyloid-negative, i.e. mean±sd Centiloids MCI/Dementia: 2±23/-5±27; amyloid-positive: MCI/Dementia: 65±42/80±37. There was high concordance (Table 1) between rPOP-based amyloid status and both local visual reads (IDEAS-BHR, Cohen’s k=0.72 [0.7-0.74], ∼86% concordance). Very high concordance was also observed in the ADNI dataset (k=0.88 [0.87-0.89], ∼94% concordance), with rPOP- and MRI-based Centiloids being strongly linearly associated (R 2 :0.95, p<0.001), with a tighter relationship in images with better resolution (β= -0.016, p<0.001). With rPOP, we successfully derived Centiloids quantification from heterogeneous IDEAS amyloid-PET scans and validated the pipeline with ADNI scans acquired in a research setting. These data show that community-acquired amyloid-PET scans can be successfully analyzed, enabling joint efforts by clinical sites and research centers.