Purpose To determine the interval cancer rate (ICR) after negative screening contrast-enhanced mammography (CEM) and compare the characteristics of interval cancers (ICs) with those of CEM screen-detected cancers. Materials and Methods This retrospective, single-institution study included consecutive screening CEM examinations performed from January 2015 through December 2021. ICs diagnosed within 1 year of a negative screening CEM and all CEM screen-detected cancers were identified. Two breast radiologists independently reviewed prior negative CEM examinations to classify ICs as missed, misinterpreted, or occult. Patient- and lesion-level characteristics were compared between ICs and screen-detected cancers using the Wilcoxon rank sum test for continuous variables and the Fisher exact or χ2 tests for categorical variables. Results The study included 6911 screening CEM examinations in 2756 female patients (median age, 53 years; IQR, 47-60 years). Among 6120 negative screening examinations, 14 ICs were diagnosed in 14 patients. The overall ICR was 2.29 cancers per 1000 examinations, and the symptomatic ICR was 0.82 per 1000 examinations (five of 6120). ICs accounted for 13% (14 of 106) of all cancers diagnosed (interval and screen detected). Invasive ICs occurred more frequently in the setting of moderate or marked background parenchymal enhancement than screen-detected cancers (six of eight, 75% vs 17 of 57, 30%; P = .02). Most ICs (10 of 14, 71%) were occult on prior screening CEM. Conclusion The ICR after CEM was 2.29 cancers per 1000 examinations, representing 13% of all cancers diagnosed. Most ICs were occult at prior CEM, and invasive ICs were more frequently associated with moderate or marked background parenchymal enhancement when compared with CEM screen-detected cancers. Keywords: Mammography, Breast, Interval Cancers Supplemental material is available for this article. © RSNA, 2026.

IMPORTANCE: The use of audiovisual aids in the consent process may improve comprehension and willingness to participate in research. However, data supporting this hypothesis are lacking.
OBJECTIVE: To determine the impact of audiovisual augmentation of the consent process on willingness to participate in research and on consent comprehension.
DESIGN, SETTING, AND PARTICIPANTS: The Personalizing Cardiovascular Health: A Population Approach to Promoting Cardiovascular Disease Resistance and Resilience Among Individuals With Obesity (RESILIENCE) nonrandomized cohort study embedded this multiarm randomized clinical trial to test different participant consent modalities. RESILIENCE recruited participants between September 2019 and March 2022, with the analysis for this randomized substudy conducted from July to December 2025. No follow-up was undertaken for this study. This component of the study was conducted exclusively virtually and completed online within a single large US academic health system.
INTERVENTIONS: Potential participants were randomized for this trial in a 1:1:1:1 allocation to receive consent information via (1) text-only (2) text and physician-featured video, (3) text and patient-featured video, or (4) text and animated video.
MAIN OUTCOMES AND MEASURES: The primary outcome was provision of consent to participate in the cohort clinical study. The secondary outcome was consent comprehension, based on a score of at least 5 of 7 on a follow-up comprehension survey. Robust log-linear Poisson regression was used to determine the relative risks (RRs) of outcomes in comparison with the text-only arm. Analyses were conducted with the evaluable population.
RESULTS: Of 1535 participants (968 [63.1%] female; 658 [42.9%] ≥60 years of age; 380 randomized to text-only, 386 to text and physician-featured video, 383 to text and patient-featured video, and 386 to text and animated video) who began the consent process, 888 (57.9%) overall gave consent to participate in the study. Patient consent rates were similar across the 4 consent delivery strategies (text only [comparator], 221 of 380 [58.2%]; text and physician video, 241 of 386 [62.4%]; RR, 1.07 [96% CI, 0.95-1.21]; text and patient video, 203 of 383 [53.0%]; RR, 0.91 [96% CI, 0.8-1.04]; and text and animated video, 223 of 386 [57.8%]; RR, 0.99 [96% CI, 0.88-1.13]). Among 884 individuals who consented and completed the consent comprehension survey, the rate of comprehension of the consent process was high 86.4% (n = 764) and did not vary among the intervention delivery strategies (text only, 193 of 221 [87.3%]; text and physician video, 207 of 241 [85.9%]; text and patient video, 177 of 203 [87.2%]; and text and animated video, 187 of 223 [83.9%]). Compared with the text-only arm, the RRs of consent comprehension were not different for the text and physician-featured video arm (RR, 1.00; [95% CI, 0.93-1.07]), the text and patient-featured video arm (RR, 1.00 [95% CI, 0.93-1.07]) and the text and animated video arm (RR, 0.96 [95% CI, 0.89-1.04]).
CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of virtual consent delivery, the rates of patient consent and consent comprehension were similar regardless of whether they were delivered by text only or text augmented by physician, patient, or animated videos. Further evaluation of these consent delivery processes across different study types and patient populations is suggested to optimize the recruitment of diverse, informed populations.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04551872.

Oligometastatic cancer is characterised by a low volume of metastases to a small number of anatomical sites. However, evaluating the impact of metastases-directed therapies (MDTs) on overall survival or quality of life is often challenging. Current clinical trials use a wide range of primary endpoints that might not be validated or suited to MDT. To address this issue, we did a systematic review of international trial registries, alongside a Delphi consensus process involving 30 experts and five patient representatives. The aim was to identify preferred primary endpoints for MDT trials in oligometastatic disease, regardless of tumour type. Overall survival and progression-free survival were the most frequently used endpoints across the 121 comparative trials reviewed. Over four Delphi consensus rounds, overall survival had the highest level of agreement, although its limitations as a sole endpoint were emphasised. In addition to the widely used progression-free survival endpoint, polymetastatic progression-free survival and start-or-switch of systemic therapy-free survival also reached consensus, particularly for trials integrating systemic therapies. Both polymetastatic progression-free survival and systemic therapy-free survival permit repeat MDT without classifying it as treatment failure. Patient representatives highlighted the importance of time-to-deterioration of quality of life. This consensus supports overall survival as a primary endpoint and, in addition to progression-free survival, recommends polymetastatic progression-free survival and systemic therapy-free survival, especially in combination with systemic therapies. Adopting these endpoints will make MDT trials more relevant, comparable, and patient-centred, thereby empowering future clinical and policy decisions.

BACKGROUND: CDK4/6 inhibitors have shown clinical benefits in patients with hormone receptor-positive, HER2-negative advanced breast cancer. This meta-analysis aims to evaluate their effect on survival outcomes across clinically relevant subgroups.
METHODS: For this reconstructed individual patient-level meta-analysis, we searched PubMed, Web of Science, the Cochrane Library, and Scopus on June 2, 2025, for phase 3 trials that compared CDK4/6 inhibitors plus endocrine therapy with endocrine monotherapy in patients with hormone receptor-positive, HER2-negative advanced breast cancer. Kaplan-Meier curves were reconstructed with the use of a time-to-event algorithm to retrieve survival data for individual patients. A series of pooled analyses for the reconstructed individual patient data were conducted with the use of a stratified Cox regression model. A pairwise random-effects meta-analysis was also conducted. Patients were stratified by endocrine sensitivity into endocrine-sensitive and endocrine-resistant, as well as by age, ethnicity, progesterone receptor status, menopausal status, Eastern Cooperative Oncology Group performance status, bone-only disease, and visceral metastasis. Primary outcomes analysed were progression-free survival and overall survival. The protocol is registered in PROSPERO (CRD420251073444).
FINDINGS: 11 phase 3 trials, including 6035 patients and four agents-abemaciclib, ribociclib, palbociclib, and dalpiciclib-were included. CDK4/6 inhibitors plus endocrine therapy significantly improved progression-free survival in both endocrine-sensitive (HR 0·57, 95% CI 0·52-0·63; p<0·0001) and endocrine-resistant cancers (0·51, 0·45-0·57; p<0·0001). Overall survival was also improved with CDK4/6 inhibitors plus endocrine therapy in both subgroups: endocrine-sensitive (0·83; 0·74-0·92; p=0·0005) and endocrine-resistant (0·77; 0·67-0·89; p=0·0003). All individual agents, when combined with endocrine therapy showed progression-free survival benefits: abemaciclib (HR 0·53, 95% CI 0·46-0·61; p<0·0001), ribociclib (0·60, 0·52-0·68; p<0·0001), palbociclib (0·56, 0·49-0·65; p<0·0001), and dalpiciclib (0·49, 0·40-0·61; p<0·0001). However, only abemaciclib (0·79, 0·67-0·92; p=0·0031) and ribociclib (0·73, 0·64-0·84; p<0·0001) showed significant overall survival benefits; palbociclib did not reach statistical significance (0·89, 0·77-1·02; p=0·0920), and data for dalpiciclib remain immature. Other clinically relevant subgroups, stratified by age, ethnicity, progesterone receptor status, menopausal status, Eastern Cooperative Oncology Group performance status, bone-only disease, and visceral metastasis, showed progression-free survival and overall survival benefits in patients with endocrine-sensitive and endocrine-resistant tumours.
INTERPRETATION: CDK4/6 inhibitors plus endocrine therapy significantly improved survival in hormone receptor-positive, HER2-negative advanced breast cancer. Benefits in progression-free survival and overall survival were consistent across major clinical subgroups. Although all agents improved progression-free survival, only ribociclib and abemaciclib showed statistically significant overall survival benefits, whereas palbociclib did not, and data for dalpiciclib remain immature. Further head-to-head comparisons and assessments of toxicity profiles, as well as patient-reported outcomes, are needed.
FUNDING: None.

BACKGROUND: PI3K/AKT pathway activation is implicated in CDK4/6 inhibitor resistance. The use of AKT inhibition with continued CDK4/6 blockade after CDK4/6 inhibitor resistance remains unexplored. We evaluated the safety of ipatasertib and an antioestrogen with or without palbociclib in patients with treatment refractory HR+/HER2- metastatic breast cancer.
METHODS: This single-centre, open-label, phase 1b trial was conducted at the Massachusetts General Hospital (Boston, MA, USA). Eligible patients were women older than 18 years with biopsy proven HR+/HER2- locally advanced, unresectable, or metastatic breast cancer; an Eastern Cooperative Oncology Group performance status of 0-2; disease progression on at least one previous therapy for metastatic disease; and measurable disease or bone lesions. Patients received 400 mg oral ipatasertib with standard 500 mg intramuscular fulvestrant dosing (ipatasertib and fulvestrant group) or with an aromatase inhibitor (oral anastrozole 1 mg per day, exemestane 25 mg per day, or letrozole 2·5 mg per day; ipatasertib and aromatase inhibitor group) on days 1-28 of each cycle. The ipatasertib and fulvestrant plus palbociclib group included a dose-escalation phase with patients assigned sequentially to escalating doses of ipatasertib and palbociclib using a standard 3 + 3 design starting at the recommended dose of palbociclib (125 mg on days 1-21) and the lowest dose of ipatasertib (200 mg on days 1-21). The primary endpoint was safety and progression-free survival was a key secondary endpoint. Safety was analysed in all patients who received at least one dose of ipatasertib and progression-free survival was assessed in all enrolled participants. This study is registered with ClinicalTrials.gov, NCT03959891 (active, not recruiting).
FINDINGS: Between June 5, 2019, and Feb 16, 2022, 77 patients were enrolled (19 assigned to ipatasertib and fulvestrant, 16 to ipatasertib and aromatase inhibitor, and 42 to ipatasertib and fulvestrant plus palbociclib). All patients were female (77 [100%]); 75 were White (97%) and two (3%) were Asian. The median age was 62 years (range 32-88) and 66 (86%) of 77 patients received previous CDK4/6 inhibitor (median number of previous lines was 3 [range 1-13]). The median follow-up was 12·5 months (IQR 7·6-19·7). The recommended phase 2 dose was established at 400 mg ipatasertib on days 1-21 with 100 mg palbociclib on days 8-28 and standard fulvestrant 500 mg. Median progression-free survival was 5·5 months (95% CI 3·8-7·4). Serious adverse events related to study treatment occurred in seven (17%) patients in the ipatasertib and fulvestrant plus palbociclib group and one (5%) in the ipatasertib and fulvestrant group, which were related to neutropenia, leukopenia, thrombocytopenia, and hyperglycaemia. Common grade 3-4 adverse events related to study treatment (occurring in >5% of patients) were neutropenia (30 [39%] of 77), leukopenia (15 [19%]), diarrhoea (14 [18%]), rash (seven [9%]), lymphopenia (three [4%]), and anaemia (four [5%]). Four deaths occurred during the study (one possibly treatment-related due to grade 5 hyperglycaemia in the ipatasertib and fulvestrant group and two due to infectious issues and one due to pulmonary complications in the ipatasertib and fulvestrant plus palbociclib group), deemed unrelated to study treatment.
INTERPRETATION: The combination of fulvestrant, ipatasertib, and palbociclib showed preliminary signs of clinical activity and showed expected adverse events in heavily pretreated patients with HR+/HER2- metastatic breast cancer, warranting further evaluation in those with CDK4/6 inhibitor-refractory disease.
FUNDING: Genentech, Howard Hughes Medical Institute, National Foundation for Cancer Research, and Breast Cancer Research Foundation.

The AIXA Osteo model architecture (X1AI-Osteo) has undergone internal validation in Taiwan, demonstrating its capability to evaluate osteoporosis and predict T-scores reliably. Nonetheless, its efficacy in alternative clinical environments has not been confirmed yet. This study uses real-world data from a Japanese clinical environment to externally evaluate the AIXA Osteo model and improves upon common image capture discrepancies in cross-domain applications and diagnostic variability arising from disparate reference databases. We used a structure-preserving CycleGAN and a large-mask inpainting model to enhance the quality of radiographs and restored regions with missing areas. Additionally, the T-scores between NHANES III and Asian standards were reconciled through a feature fusion module. In a validation set of 300 participants, preprocessing improved the area under the curve of the model from 92.9% to 97.2%, sensitivity from 88.6% to 95.7%, and the positive predictive value from 80.5% to 90.5%. With respect to the T-score prediction performance, the consistency correlation coefficient between model and dual-energy X-ray absorptiometry measurements improved from 0.956 to 0.994. These findings indicate that the proposed framework for image preprocessing and the feature fusion module support the application of X-ray-based artificial intelligence for osteoporosis screening in heterogeneous clinical environments.

There is a growing awareness that body CT scans contain rich cardiometabolic information that can be leveraged for additional patient benefits. However, the clinical implementation of opportunistic CT screening in routine practice has been hindered by valuable yet onerous manual measurements and subjective assessments. Explainable artificial intelligence (AI) algorithms are now poised to change this. The potential impact of opportunistic screening is further enhanced by the large volume of CT scans being obtained. In this “How I Do It” installment, the authors briefly outline some current approaches that can be obtained “on the fly,” while focusing more on emerging automated solutions. Detecting unsuspected or presymptomatic conditions, such as osteoporosis, cardiovascular disease, sarcopenia, and hepatic steatosis, could lead to preventive interventions, regardless of the original indication for imaging. Composite models that combine multiple cardiometabolic CT biomarkers can be applied to survival prediction and assessment of biologic aging, frailty, cancer cachexia, metabolic syndrome, and fracture risk, among other factors. For clinical reporting, a range of logistical, actuarial, and ethical issues must be carefully considered. However, if executed properly, we believe that opportunistic CT screening can add substantial value, be cost saving, and provide a new level of personalized precision medicine befitting the dawning AI information era.