Citations

Importance Lichen planus is a chronic, highly pruritic, inflammatory disease that affects the skin and other tissues. Objective To evaluate the efficacy and safety of ruxolitinib, 1.5%, cream in patients with cutaneous lichen planus. Design, Setting, and Participants This phase 2, 16-week, randomized, double-blind, vehicle-controlled trial with a 16-week open-label extension was conducted from November 2022 to February 2024. Patients were enrolled from 19 sites in the US and Canada. The trial included adults with predominantly cutaneous lichen planus, an Investigator’s Global Assessment (IGA) score of 3 or 4, an Itch Numerical Rating Scale score of 4 or greater, and an affected body surface area of 20% or less were enrolled. Data were analyzed from February to August 2024. Interventions Patients were randomized 1:1 to ruxolitinib, 1.5%, twice daily cream or vehicle cream for 16 weeks, after which eligible patients applied ruxolitinib cream twice daily as needed in a 16-week, open-label extension. Main Outcomes and Measures The primary end point was IGA treatment success (IGA score of 0 or 1 [clear/almost clear skin] with a ≥2-grade improvement from baseline) at week 16. Results Among 64 randomized patients, 46 (72%) were female, 18 (28%) were male, 18 (28%) were African American/Black, 4 (6%) were Asian, 40 (63%) were White, and the median (range) age was 57.0 (18-78) years. Significantly more patients who applied ruxolitinib, 1.5%, cream vs vehicle achieved IGA treatment success (50.0% [95% CI, 31.9%-68.1%] vs 21.9% [95% CI, 9.3%-40.0%], respectively; response rate difference, 29.4% [95% CI, 7.6%-51.3%]; P = .01; primary end point) at week 16, with further improvement to week 32. Similar results were observed in the proportion of patients who achieved a 4 or greater–point improvement from baseline in Itch Numerical Rating Scale score (week 16, 48.4% [95% CI, 30.2%-66.9%] vs 16.1% [95% CI, 5.5%-33.7%]; response rate difference, 33.5%; 95% CI, 12.2%-54.9%; P = .004; secondary end point). No serious treatment-emergent adverse events or discontinuations due to an adverse event were observed with ruxolitinib cream. Conclusions and Relevance The results of this randomized clinical trial suggest that ruxolitinib cream significantly reduced lesions and itch in patients with lichen planus. Therefore, ruxolitinib cream represents a potential treatment option for patients with cutaneous lichen planus. Trial Registration ClinicalTrials.gov Identifier: NCT05593432

Abstract Background While the radiation dose to left anterior descending (LAD) artery is associated with overall survival (OS) in NSCLC patients, manual segmentation is labor‐intensive. Several auto‐segmentation models were developed on average 4DCT with promising geometric agreement, yet their feasibility in clinical outcome analysis on lung CT remains unclear. Purpose This study evaluates whether automated LAD segmentation can reproduce, at the group level, the established dose‐survival association in a multi‐institutional clinical trial dataset. Methods Three deep learning‐based auto‐segmentation (DLAS) models for automatic segmentation of the LAD coronary artery were applied to 460 patients from the NRG Oncology/RTOG 0617 dataset. Kaplan–Meier curves and Cox proportional hazard ratio (HR) were calculated using each model's segmentation. The LAD V15 Gy was used to stratify patients into high‐and low‐risk groups, and the cut‐off values were determined by minimizing mean absolute error (MAE) between DLAS‐derived and manual OS curves. Results All three models demonstrated significantly different OS curves between the high risk and low risk groups ( p < 0.05). The HR was 1.40 (95% CI: 1.02–1.93; p = 0.0381; MAE = 7.1%), 1.32 (95% CI: 1.03–1.68; p = 0.0258; MAE = 9.6%), and 1.37 (95% CI: 1.03–1.84; p = 0.0331; MAE = 7.9%) for the three models using a common V15 Gy ≥ 10% cut‐off. After optimizing the cut‐off, one model aligned well with what was derived from manual segmentation (MAE = 4.3%). Conclusion Among the evaluated models, one DL model showed the strongest performance of survival groups separation and achieved group‐level overall survival stratification comparable to that previously reported using manual contours in the multi‐institutional cohort. Further validation with paired manual contours and pre‐specified cutoffs is warranted.

Vascular stents are crucial devices in the treatment of cardiovascular diseases, and their structural design and function critically affect therapeutic efficacy and patient prognosis. Conventional stents can effectively restore vascular patency by providing mechanical support to blood vessels. However, they still face significant challenges including restenosis, thrombosis, and limited adaptability to complex patient-specific lesion characteristics. To address these limitations, drug delivery offers an important strategy to modulate the pathological microenvironment, enhance long-term vascular healing, and reduce systemic side effects. Meanwhile, advances in computational simulations have provided powerful tools for optimizing stent design through structural mechanics, hemodynamics, and drug release modeling. Computational approaches enable the rational design of stent architectures with improved mechanical stability, vascular compatibility, and therapeutic regulation. Consequently, the development of vascular stents is evolving toward the synergistic integration of drug delivery, structural optimization, and intelligent design. This review summarizes the latest advances in functional vascular stents, clinical applications and computational design. This work aims to provide valuable insights for the engineering of efficient, precise, and intelligent vascular stents for cardiovascular therapies.

ABSTRACT We examined the prognostic value of routine NGS data in newly diagnosed acute myeloid leukemia (AML) treated with intensive (7 + 3 backbone) induction, specified by AML subtype. A contemporary (2015–2025) series of 545 Mayo Clinic patients (median age 56 years, females 44%) was considered. Median follow‐up was 49 months with 341 (63%) allogeneic hematopoietic stem cell transplantations (AHSCT) recorded. AML subtypes included core‐binding factor (CBF; N = 72; 13%), primary non‐CBF ( N = 403; 74%), post‐myelodysplastic syndromes (MDS) or post‐myelodysplastic/myeloproliferative neoplasms (post‐MDS‐MDS/MPN; N = 28; 5%), post‐MPN ( N = 15; 3%), and therapy‐related (t‐AML; N = 27; 5%). Corresponding complete remission rates, with/without count recovery (CR/CRi), were 89%, 76%, 64%, 27%, and 78% ( p < 0.01) and 5‐year transplant‐censored survival rates 68%, 57%, 21%, 0%, and 55% ( p < 0.01). In multivariable analyses, the prognostic value of specific mutations was mostly limited to primary non‐CBF AML where adverse karyotype (OR 1.9; p = 0.04) predicted inferior and FLT3 ‐ITD (OR 0.4; p < 0.01) or NPM1 MUT / FLT3 WT (OR 0.1; p < 0.01) superior CR/CRi while KRAS MUT (HR 8.8; p < 0.01), TP53 MUT (HR 5.4; p < 0.01), and TET2 MUT (HR 2.3; p = 0.01) predicted inferior and NPM1 MUT / FLT3 WT (HR 0.3; p = 0.01) superior survival. Prognostication in intensively‐treated AML should start with subtype specification and recognition of the limited value of NGS in non‐primary AML. Post‐MPN AML is particularly associated with dismal outcomes and should be prognostically distinguished from post‐MDS‐MDS/MPN AML. In primary non‐CBF AML, in addition to previously established risk factors, the favorable impact of FLT3 ‐ITD on achieving CR/CRi and the unfavorable impact of KRAS MUT and TET2 MUT on transplant‐censored survival were noted and require confirmation from additional studies.

Abstract Background The left anterior descending (LAD) coronary artery is a critical organ‐at‐risk in thoracic radiotherapy. In thoracic stereotactic body radiation therapy (SBRT), sharp dose gradients and poor LAD contrast on 4DCT scans introduce uncertainty in LAD dose assessment. Methods We evaluated the performance of an AI‐generated LAD region structure as a surrogate for manual LAD contours in early‐stage NSCLC. We used deep inspiration breath hold (DIBH) scans from 49 patients with manually delineated LADs; planning risk volume contours were expanded by 3 mm. Then, 96 lung SBRT dose maps were registered by matching the left anterior portion of the heart contours. Dice similarity coefficient (DSC), inclusion ratios (IR), dose–volume histogram (DVH) metrics, linear regression, and linear mixed models were used to compare the structures. The correlation of the AI LAD region and LAD dose to mean heart dose (MHD) was assessed. Results The AI LAD region showed strong correlation with manual LAD contours for maximum dose (D1%, R 2 = 0.93) and volume receiving ≥10 Gy (V10Gy, R 2 = 0.81). The planning risk volume also demonstrated high correlation to the AI LAD region. MHD was a poor predictor of LAD dose ( R 2 ≈0.4). Additional dose metric correlations were assessed. Discussion To investigate dose volume effects to the LAD during radiotherapy for stage I NSCLC, a robust segmentation paradigm must be established. It must be easily implementable on typical imaging acquired during treatment, with an emphasis on clinical translatability. Our model has shown that the AI LAD region has a strong correlation with LAD dose under typical lung SBRT doses and supports its use for further investigation into LAD dose volume constraints during lung SBRT. Conclusion AI LAD region provides a clinically feasible and scalable alternative to manual LAD contouring for dose estimation in lung SBRT. Its strong correlation with key dose metrics validates its use in large‐scale retrospective and prospective studies.

Background: Integrating machine learning (ML) with population pharmacokinetic (PPK) modeling may improve therapeutic drug monitoring predictions. Methods: Tacrolimus trough concentrations from lung transplant patients were split into a training data set (1151 concentrations in 80 patients) and a testing data set (224 concentrations in 20 patients). A PPK model was developed using NONMEM, followed by the development of 10 ML models to fit individual pharmacokinetic parameters from the PPK model with Bayesian forecasting. The best performing ML model was selected as the final model. Both the final PPK and ML models were compared for prediction performance. A web-based dashboard was established with R-shiny to recommend dosing regimens based on patient data. Results: In the PPK model, postoperative days, hematocrit, aspartate aminotransferase, tacrolimus daily dose, coadministered voriconazole or posaconazole, and the CYP3A5*3 genotype were identified significant covariates on the clearance. The Cubist ML model outperformed the PPK model, showing lower root mean squared error for tacrolimus concentrations in the testing data set. An online web-based precision dosing dashboard was created, accessible at (https://tac-dose-ml.shinyapps.io/shiny/). Conclusions: Integrating ML with PPK modeling could yield superior tacrolimus concentration predictions for lung transplant patients, offering an efficient alternative to Bayesian forecasting. The online dashboard provides rapid, individualized dosing recommendations.

TPS6138 Background: Patients with early-stage oral cavity cancer (OCC; T1-2N0M0; AJCC 8th edition) have a 20-30% risk of occult nodal metastases despite clinical and radiographic evaluations. Standard-of-care treatment for most patients includes elective neck dissection (END), which requires surgical removal of the regional cervical lymph nodes, even though 70-80% of these necks are disease-free. Sentinel lymph node biopsy (SLN Bx), a less invasive procedure, could assess the first echelon lymph nodes as an alternative to END, potentially reducing morbidity and costs. A pivotal clinical trial comparing SLN Bx to END (NCT#04333537) is underway to inform efforts to establish optimal disease management for early-stage OCC. Methods: To assess the efficacy of SLN Bx in this population, we activated an international, multi-institutional, prospective phase II/III trial in July 2020, randomizing patients to two surgical arms: SLN Bx and END. A node-negative 18 F-FDG PET/CT imaging biomarker study with centralized read was required before randomization. OCC patients with a positive PET/CT remained in a registry to compare imaging findings with final neck pathology. Given the current evidence on morbidity for SLN Bx versus END, the phase II was designed to determine whether the change in patient-reported neck and shoulder function and related quality of life (QOL) from baseline to 6 months after surgery, using the Neck Dissection Impairment Index (NDII), showed a signal of superiority of SLN Bx compared to END (minimum important difference ³ 7.5; one-sided a = 0.10; 90% power). As of December 2024, 261 patients had been randomized and 203 were analyzed for the “Go/No-Go” decision to move forward into phase III. The phase III portion is a non-inferiority (NI) trial with disease-free survival (DFS) as the primary endpoint (NI margin hazard ratio 1.34 based on a 5% absolute difference in 2-year DFS; one-sided a = 0.05; 80% power, and two interim looks). The change in NDII from baseline to 6 months after surgery is a hierarchical co-primary endpoint for phase III. Phase III opened in October 2025 upon receiving a “Go” signal from phase II. Target accrual for phase III is 686 node-negative PET/CT patients, including those randomized in phase II (425 additional patients). In addition to sites requiring radiotherapy and imaging credentialing, quality assurance will include central pathology review of all negative SLN Bx cases and surgeon credentialing through an education course with SLN Bx and END case review by the surgical co-chairs. A surgical quality assurance working group will review all trial SLN Bx and END procedures. As of 01/12/26, 351 patients have been screened, and 273 of the planned 686 have been randomized. Clinical trial information: NCT#04333537 .

6588 Background: TET2 is the most frequently mutated gene in chronic myelomonocytic leukemia (CMML) and has been associated with favorable outcome, with recent studies suggesting a more pronounced prognostic impact in the presence of ≥2 TET2 mutations ( Csizmar et al. leukemia 2025;39:2030; Kynning et al. Br J Haematol. 2025 Nov 25. doi: 10.1111/bjh.70264 ). We sought to determine if this particular observation extended to patients with ≥3 TET2 mutations ( TET2 MUT ) and also held true in the context of recently reiterated genetic risk factors. Methods: The current study was conducted under institutional review board approved minimum risk protocols allowing retrospective patient data collection and analysis. Diagnostic criteria were according to the International Consensus Classification (Arber et al. Blood 2022. 140:1200). All statistical analyses were conducted using JMP 18 software. Results: 536 CMML patients who underwent CLIA-approved NGS testing were stratified according to the number of TET2 MUT : 221 (41%) wild-type, 148 (28%) with one, 153 (29%) 2, and 14 (2%) ≥3 TET2 MUT . Co-mutation frequencies with significant differences between one vs. two TET2 MUT included ASXL1 (46% vs. 29%; p<0.01), KRAS (7% vs. 14%; p=0.02) and SETBP1 (5% vs. 0.6%; p=0.02). Phenotypic comparisons revealed preponderance of prognostically favorable traits associated with wild-type TET2 but no significant differences between one vs. two TET2 MUT . In age-adjusted univariate analysis, transplant-censored overall survival (TCOS), calculated from the time of mutation detection, was superior in patients with one (p<0.01; HR 0.7) or 2 (p<0.01; HR 0.4) but not ≥3 (p=0.4) TET2 MUT , vs. those with wild-type TET2 . TCOS was also superior with 2 vs. 1 (p=0.02; HR 0.7) but not with ≥3 vs. 1 (p=0.7) TET2 MUT ; the results were similar when TCOS was calculated from the time of diagnosis. Multivariable analysis confirmed the survival advantage of exactly two TET2 MUT vs. wild-type TET2 (p<0.01; HR 0.5), one TET2 MUT (p<0.01; HR 0.6), or ≥3 TET2 MUT (p<0.01; HR 0.4), after adjusting for age, sex, anemia, circulating blasts ≥2%, and leukocyte count ≥13×10⁹/L. The favorable impact of exactly two TET2 MUT persisted in CMML-MD and CMML-MP and remained independent of TET2 VAF, mutation type, karyotype, and other prognostically relevant mutations. This association was sustained in the BLAST (p<0.01; HR 0.5) and CPSS-mol (p=0.02; HR 0.7) models, but not in BLAST-mol model (p=0.12). Conclusions: Mechanistic explanation for this novel observation includes the possibility that TET2 mutational categories based on mutation count reflect distinct biological states rather than having a simple linear effect. The persistence of this signal despite adjustment for established molecular and genetic risk factors supports its consideration in the development of future CMML prognostic models.