Browse Articles

Real-world treatment patterns and clinical characteristics of patients with t(11;14)-positive multiple myeloma.

e23437 Background: Multiple myeloma (MM) patients harboring the t(11;14) translocation represent a distinct subtype with unique biological and clinical characteristics. While t(11;14)+ patients are increasingly being targeted in clinical studies, there is limited data on how they present in the community oncology setting. Here, we aimed to characterize renal function and treatment of t(11;14)+ patients using a large, geographically diverse real-world data platform. Methods: This retrospective cohort study leveraged deidentified electronic health records (EHRs) from the OMNY Health real-world data platform (2017-2025). Contributing health systems covered the Upper Midwest, Mid-Atlantic, and Southeast regions of the United States. Patients with cytogenetic evidence of t(11;14) translocation were selected and indexed at their first MM diagnosis. Estimated glomerular filtration rate (eGFR) in mL/min/1.73 m2 was calculated as the mean within 60 days (+/- 30 days) of the index date. Normal kidney function was defined as an eGFR > 90 mL/min/1.73 m². Mild and moderate kidney dysfunction were characterized by an eGFR threshold of < 90 and < 60 mL/min/1.73 m², respectively. Start of first-line (1L) therapy was assessed by reporting the administration patterns of Bortezomib, Lenalidomide, Daratumumab and Dexamethasone within 30 days following the index date. Results: A total of 52,984 encounters (102 unique patients) with a MM diagnosis and cytogenetic evidence of t(11;14) translocation were selected. Patients were predominately White (67.6%) and male (58.8%) with mean age of 64.9 (males) and 66.5 (females) years. Mean (standard deviation) eGFR among 48 evaluable patients was 57.1 (29.2) mL/min/1.73 m². 93.7% of patients had indication of kidney dysfunction (47.9% mild, 45.8% moderate) at diagnosis while 6.3% presented as normal. Among 45 patients receiving 1L therapy within 30 days of diagnosis, regimens were categorized as singlet (33.3%), doublet (40.0%) or triplet (26.7%). Mean time to regimen adjustment was longest for singlets (218.3 ± 312.6 days), followed by doublets (147.6 ± 392.4 days) and triplets (27.2 ± 46.3 days). Conclusions: We found a high rate of renal impairment in t(11;14)+ patients at the time of their first MM diagnosis and an inverse relationship between regimen intensity and time to adjustment. Together, these results lay a critical foundation for better understanding how t(11;14)+ patients are managed in routine clinical practice. Further research is needed to understand whether sociodemographic factors or other clinical characteristics are associated with initial treatment selection and time to regimen adjustment.

Real-world characteristics, homologous recombination repair mutation (HRRm) testing, treatment patterns, and outcomes of patients with metastatic castration-sensitive prostate cancer (mCSPC) in the US community oncology setting.

5080 Background: Homologous recombination repair mutation (HRRm) testing is recommended by NCCN guidelines for metastatic castration-sensitive prostate cancer (mCSPC). The real-world CAPTURE study is one of the first to associate HRRm carriers with worse outcomes. However, real-world data to quantify prognostic and predictive value of HRRm in mCSPC are limited and heterogeneous, especially for patients treated within US community oncology settings. Methods: This was a retrospective observational cohort study of patients with documentation of HRRm testing who initiated systemic therapy for mCSPC (index) between 1/1/2019-3/31/2024 in The US Oncology Network or non-Network practices. Stratified random samples of 150 patients with HRRm and 150 patients without HRRm were selected for chart abstraction to collect patient characteristics within 60 days prior to index and prostate cancer treatments (androgen deprivation therapy, ADT; androgen receptor pathway inhibitors, ARPi; docetaxel, DOC) through the end of follow-up (3/31/2025). Somatic and/or germline testing results for a 12-gene HRRm panel (ATM, ATR, BRCA1, BRCA2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, RAD51C) were recorded from all available records. Descriptive Kaplan-Meier analyses of overall survival (OS) and real-world progression-free survival (rwPFS) were assessed per HRRm, de novo metastatic and high-volume disease (HVD) status. Results: Overall, 300 patients were selected with median (IQR) age of 69 (63-77) years and median (IQR) follow-up of 25 (15-36) months. Among patients with available data at baseline, most were Gleason ≥8 (79% of 181) and PSA >4 ng/mL (85% of 274). In the HRRm cohort (N=150), 70 (47%) patients were BRCAm and 80 (53%) patients had non-BRCAm HRRm mutations. De novo mCSPC was identified in 97 (65%) patients with HRRm and 100 (67%) patients without HRRm. HVD was observed in 85 (57%) patients with HRRm and 96 (64%) without HRRm. Frontline (index) systemic therapies for mCSPC in the HRRm/non-HRRm subgroups included ADT (28%/22%), ADT+ARPi (39%/47%), ADT+DOC (15%/15%) and ADT+ARPi+DOC (15%/15%). Outcomes are summarized below. Conclusions: Patients with HRRm mCSPC experienced numerically shorter OS and rwPFS than non-HRRm patients. This highlights an important need for early HRRm testing and targeted treatment strategies within earlier disease settings. Outcome, median (95% CI), months HRRm (N=150) No HRRm(N=150) OS, overall 44.0 (36.8-55.2) 48.5 (40.2-NR) rwPFS, overall 17.5 (14.4-22.1) 22.6 (17.9-33.4) N (%), de novo 97 (65) 100 (67) OS, de novo 41.7 (30.6-44.9) 48.5 (33.4-69.4) rwPFS, de novo 15.4 (13.0-23.1) 22.0 (17.2-32.3) N (%), HVD 85 (57) 96 (64) OS, HVD 44.4 (36.8-55.2) 42.5 (33.4-69.4) rwPFS, HVD 17.7 (12.0-27.3) 19.2 (16.3-30.3)

Outcome of neoadjuvant immunotherapy for patients with resectable stage III/IV cutaneous melanoma: A Swedish nationwide population-based study (NEO-MEL).

9565 Background: Randomized trials have shown that neoadjuvant immune checkpoint inhibitor (ICI) improves outcomes compared with adjuvant therapy alone in patients with resectable stage III–IV cutaneous melanoma. Furthermore, pathological response was a strong predictor for relapse-free survival (RFS). The translationability to routine real-world patients is unknown. Methods: This population-based cohort study included all patients with macroscopic, resectable cutaneous melanoma treated with neoadjuvant immune checkpoint inhibitor(s) across all academic melanoma centers in Sweden between January 1, 2022 and December 30, 2025. Clinical and pathological data were extracted from medical records. Results: A total of 279 patients initiated neoadjuvant ICI and received a median of two treatment cycles, 94% received PD1-inhibitor monotherapy, 91% underwent surgery as planned and 251 had evaluable pathological assessment. Among all patients who started treatment, 37% had a complete pathological response (pCR), 6% near pCR, 15% a partial pathological response (pPR) and 32% no pathological response (pNR). At a median follow-up time of 20 months, the estimated 24-month event-free survival was 69% (95% CI, 62-76), distant metastasis-free survival (DMFS) 75% (95% CI, 69-82) and overall survival (OS) 87% (95% CI, 82-92). Among those who underwent surgery and had an evaluable pathological assessment, RFS, DMFS and OS stratified by pathological response are shown in the table. Conclusions: Early nationwide implementation of neoadjuvant ICI in patients with resectable cutaneous melanoma resulted in favourable outcomes that closely mirror those reported in randomized clinical trials. Pathological response N RFS at 24 months% (95% CI) DMFS at 24 months% (95% CI) OS at 24 months% (95% CI) pCR 103 92 (85-100) 93 (86-100) 94 (87-100) near pCR 17 76 (56-100) 83 (64-100) 90 (73-100) pPR 41 83 (71-97) 85 (74-98) 92 (81-100) pNR 90 48 (36-63) 63 (52-78) 81 (70-92)

Multimodal diffusion on low-rank approximation radiomic phenotypes with deep learning survival model for prediction of survival in post-operative GBM patients.

e14005 Background: Glioblastoma (GBM) exhibits substantial biological and imaging heterogeneity, resulting in variable postoperative outcomes that are inadequately captured by conventional prognostic factors. Although multimodal radiomics enables quantitative tumor characterization, its high dimensionality limits clinical robustness and translation. This study aimed to develop a clinically translatable multimodal diffusion model for personalized survival prediction in patients with postoperative GBM. Methods: A retrospective cohort of 450 patients with de novo glioblastoma from the University of Pennsylvania, each with standard preoperative multimodal MRI (T1, T2, FLAIR, and contrast-enhanced T1), was analyzed. From each modality, 354 radiomic features were extracted and subsequently compressed into a stable 11-dimensional latent representation using density-based Isomap (PR-Isomap), with dimensionality determined by an isometry-driven gap statistic. These low-rank radiomic phenotypes were integrated through a multimodal diffusion framework to generate clinically actionable imaging embeddings. Survival risk was modeled using a deep survival model, optimizing the log-hazard function via a negative log-likelihood loss for individualized outcome prediction. Results: The optimized survival modeling framework demonstrated reliable prognostic performance, yielding a binary classification accuracy of 72.7% through an ensemble consensus of machine learning classifiers evaluated under 10-fold cross-validation, alongside a concordance index of 0.60. Using MRI-derived latent embeddings (hidden dimension = 128; learning rate = 1×10⁻⁴; dropout = 0.2), risk stratification based on hazard-score quartiles produced well-separated Kaplan–Meier survival curves, providing clear evidence that the learned imaging representations capture clinically meaningful differences in patient survival trajectories. In the final model, risk stratification based on hazard-score quartiles identified well-balanced high- and low-risk cohorts (n = 113 each), with clear separation between patients below the first quartile (Q1 = 0.0812) and above the third quartile (Q3 = 0.0820), further supporting the robustness of the proposed survival risk grouping. Conclusions: The integration of deep learning–driven multimodal diffusion modeling with radiomic embedding approximation establishes a clinically robust and objective framework for prognostic stratification in GBM. By capturing complementary imaging-derived phenotypes, this approach enables individualized post-operative risk assessment and supports precision neuro-oncology through data-informed optimization of adjuvant therapeutic strategies.

Effect of FDG-PET–based bone marrow assessment on prognostic accuracy compared to conventional histologic evaluation in patients with follicular lymphoma: A subanalysis of the FIL FOLL12 trial.

7074 Background: Bone marrow biopsy (BMB) is an invasive staging procedure for follicular lymphoma (FL) and its results are needed to calculate FLIPI2 and PRIMA-PI scores. Beyond conventional biopsy bone marrow can also be assessed through FDG-PET bone staging (PETb). We report preliminary data on a comparison of BMB and PETb in assessing BM involvement among FL patients enrolled in the FIL-FOLL12 trial. Methods: Untreated stage II–IV FL patients requiring therapy were included. Patients were balanced according to treatment received and arm. BMBs were assessed by morphology and immunohistochemistry. PET/CT scans were reviewed by two expert nuclear medicine physicians. Pathological bone uptake (PETb+) was defined as mono- or multifocal, or diffuse FDG uptake in bone segments higher than liver activity (SUVmax). Results: This analysis included 179 patients; no significant differences in disease characteristics were observed between the revised cohort and the remaining patients enrolled in the FOLL12 trial. High-risk FLIPI2 was noted in 35.4%, and β2-microglobulin was increased in 53% of patients. BMB involvement was present in 58.5% (median infiltration 30%, range 0.5–95%). PETb was positive in 38 cases (21%), including 14% with focal or multifocal involvement and 7% with diffuse increased uptake. Concordant results between BMB and PETb were observed in 53.6%: among 103 BMB+ patients, 30 were PETb+ (29%). PETb identified BM involvement in 8 cases missed by BMB. While BMB+ was not associated with a different risk of PFS compared to BMB-, we observed a significant impact of PETb+ on PFS: PETb+ had 41% 5-year PFS (CI 25-72, p=0.003), while BMB+/PETb- showed 74% (CI 62-83, p=0.27) and BMB-/PETb- 66%(CI 52-72, reference).We then calculated FLIPI2 and PRIMA-PI using either conventional BMB or PETb to define BM involvement. The agreement between BMB and PETb scores was 87% for FLIPI2 and 67% for PRIMA-PI and the main disagreement was due to reallocation to lower risk groups; FLIPI2 0-2 patients raised from 65% to 74.3% according to FLIPI2-PET. FLIPI2 was confirmed prognostic for PFS and its c-Harrel increased from 0.582 to 0.602 when BMB was substituted with PETb (Table 1), with a 52% (CI 39-64) 5-Year PFS for conventional high risk FLIPI2 shifting to 41% (CI26-56) for high risk FLIPI2-PET. Conclusions: Although BMB detects marrow involvement in most patients, this does not uniformly translate into adverse prognosis. PETb, while less sensitive, identifies metabolically active and prognostically relevant bone disease. A FDG-PET-based assessment of bone involvement could refine risk stratification in FL and spare BMB in most patients Score HR for High risk CI c-Harrell FLIPI2 2.03 1.25-3.31 0.582 FLIPI2-PET 2.58 1.57-4.26 0.602 PRIMA-PI 1.23 0.67-2.23 0.537 PRIMA-PI-PET 1.47 0.85-2.54 0.550

Longer durations of piperacillin/tazobactam treatment cause more prolonged alteration of colonization resistance in mice

Broad-spectrum antibiotics that are excreted into the intestinal tract disrupt microbiota that provide colonization resistance against healthcare-associated pathogens. Minimizing the duration of treatment is a core element of efforts to reduce the adverse effects of antibiotics, but limited information is available on whether this approach preserves colonization resistance. Here, we used a mouse model to examine the impact of 1, 3, 6, and 10-days of treatment with the broad-spectrum antibiotic piperacillin/tazobactam on colonization resistance against vancomycin-resistant Enterococcus faecium (VRE) and carbapenemase-producing Klebsiella pneumoniae at 6-, 10-, and 24-days post-treatment; colonization resistance against Clostridioides difficile was tested at 6 days post-treatment. Colonization resistance was not altered at these time points by 1 day of treatment, whereas 3, 6, and 10 days of treatment caused more prolonged microbiota disruption and altered colonization resistance extending to 6, 10, and 24 days, respectively. In contrast, 5 or 10 days of treatment with aztreonam, a narrow-spectrum antibiotic with no activity against anaerobes, did not alter colonization resistance. These findings provide support for efforts to minimize the duration of antibiotic therapy as longer durations of piperacillin/tazobactam treatment caused greater and more prolonged alteration of colonization resistance. Our results also highlight the potential for short courses of broad-spectrum antibiotics to alter colonization resistance and suggest that selection of antibiotics that cause less disruption of anaerobes may be useful to preserve colonization resistance.

Niosomes in drug delivery: A comprehensive review and therapeutic perspectives

Bioinspired Enzyme‐Like Mechanism Enables Adaptive Local Charge Modulation for Blue Energy Harvesting

ABSTRACT Enhancing the performance of ion‐selective membranes is critical for achieving efficient osmotic energy conversion. However, existing charge‐regulation strategies struggle to adapt to dynamically changing ion‐transport environments. Inspired by natural cytochrome c oxidase (C c O), this work demonstrates that atomically precise heteronuclear FeCo dual‐atom nanozymes (FeCo‐DACs) can dynamically modulate the local charge distribution at active sites via an oxidase‐like mechanism, thereby enhancing osmotic energy conversion. By tailoring the coordination environments of heteronuclear and homonuclear dual‐atom sites, enzyme‐like activity and ion selectivity are optimized. The bioinspired composite membrane incorporating Fe─Co bonded nanozymes directly into bacterial cellulose (BC/FeCo‐DACs) achieves a power density of 15.4 W m −2 during the mixing of natural river water and seawater, without external stimuli. Combined experimental and theoretical analyses reveal that the heteronuclear FeCo configuration, with an optimal metal–metal bond length, balances oxygen adsorption/desorption while establishing the most energetically favorable proton‐consumption pathway, enabling spontaneous dynamic local charge regulation and improved osmotic energy conversion performance.

Effect of Muller maneuver on upper airway characteristics and surrounding structures in patients with obstructive sleep apnea: a cone-beam computed tomography study

A proximity-labeling map of PI5P4K phosphoinositide kinases interaction networks

Large language model-guided extraction of explainable clinical decision trees from longitudinal meningioma clinical notes.

e14004 Background: Meningiomas are the most common primary brain tumors, requiring longitudinal integration of clinical observations, imaging, histopathology, and multimodal treatment responses documented in narrative clinical notes. This unstructured knowledge remains largely inaccessible for systematic decision support, comparative practice analysis, and collaborative learning across institutions. We therefore developed a novel LLM-guided framework that extracts structured, explainable clinical decision trees (CDTs) from longitudinal meningioma notes while enabling privacy-preserving aggregation of real-world care pathways. Methods: We used a structured LLM workflow to convert longitudinal meningioma clinical notes into explainable CDTs. First, a guideline-aligned generic meningioma decision tree and ontology were defined based on NCCN management domains. For each patient, the LLM extracted meningioma-relevant clinical events directly supported by note text, including relative timing, NCCN domain classification, uncertainty labeling, and verbatim evidence quotes, with safeguards to prevent inference or hallucination. Extracted events were assembled into patient-specific directed graphs representing observed temporal transitions. Events were then mapped to a predefined canonical state vocabulary to generate patient-level state sequences, enabling aggregation of individual graphs into a cohort-level CDT with empirically derived node frequencies and transition probabilities. All outputs used de-identified data and relative time to ensure privacy. Results: The pipeline successfully generated patient-specific state sequences and aggregated CDTs capturing diverse meningioma management patterns across diagnostic evaluation, surgical resection, radiation therapy, and surveillance strategies. Stakeholder input from seven multidisciplinary clinicians (neuro-oncologists, oncologists) at Massachusetts General Hospital demonstrated 100% agreement that CDTs improve treatment planning confidence (compared to a black-box LLM), 75% preference for CDTs over free-text notes for knowledge assimilation, and 80% preference for adaptive complexity (simple trees for routine cases, higher complexity for rare presentations). Conclusions: LLM-guided extraction of explainable clinical decision trees from longitudinal clinical notes is feasible, clinically interpretable, and supports privacy-preserving aggregation of real-world care pathways. This approach provides a scalable foundation for evidence-based decision support, practice pattern analysis, and quality improvement initiatives in meningioma care and other conditions requiring complex longitudinal management.

Retrospective assessment of Duffy-Null associated neutrophil counts (DANC) status and impact on treatment among patients with and without cancer in an urban academic medical center.

1642 Background: Duffy-Null Associated Neutrophil Count (DANC) is a non-pathologic state characterized by a low absolute neutrophil count (ANC) without increased risk of infections. Despite this, cancer patients (pts) with DANC have often been excluded from clinical trials due to low ANC and may receive inappropriate dose delays or reductions of standard anticancer therapy. Testing for Duffy-null phenotype is readily available, but no standard of care exists for management of chemotherapy dosing in cancer pts with DANC. In preparation for a prospective study evaluating chemotherapy dose modifications in cancer pts with DANC, we examined characteristics of pts, both with and without cancer, who underwent Duffy antigen testing at our institution, as well as whether results of testing in cancer pts impacted cancer management. Methods: Pts who received Duffy antigen testing from 05/02/2024-05/01/2025 were identified from the Montefiore Health System pt registry. Baseline characteristics including white blood cell count (WBC), ANC, demographics, and cancer status were obtained and correlated with Duffy status. Reviewed documentation for Duffy-status impact on chemotherapeutic management. Results: 523 pts [283 (54.1%) Non-Hispanic Black (NHB), 168 (32.1%) Hispanic (H), 18 (3.4%) Non-Hispanic White (NHW), and 54 (10.3%) Other] were identified. Median age was 56 yrs. Indication for testing was neutropenia in 518 pts (99.0%). 407 (77.8%) pts were found to have DANC and 116 (22.2%) were Duffy-antigen positive. Duffy-null phenotype was seen in 265 (93.6%) pts; 103 (61.3%) H pts, and 4 (22.2%) NHW pts. Race/ethnicity was strongly correlated with Duffy-status (p < 0.001). Median baseline WBC and ANC were lower in pts with DANC than in pts without [WBC 3.4 vs 4,4 (p < 0.001); ANC 1.1 vs 1.8 (p < 0.001)]. 32 (6.4%) pts of the total cohort had cancer [23 (71.9%) NHB, 7 (21.9) H, 2 (6.3%) other], of which 26 pts (22 NHB, 4 H) had DANC. 13 (40.6%) ordering providers were adult solid tumor oncologists [8 Breast, 4 GYN, 1 GU], 5 (15.4%) pediatric hematologist-oncologists, 6 (18.8%) classical hematologists, 6 (18.8%) hematology/oncology providers, and 2 (6.3%) family medicine providers. Knowledge of Duffy antigen status impacted management in 26 (81.3%) pts with cancer, leading to fewer dose delays and reductions in cancer pts with DANC, while in 6 (18.8%) pts testing did not (p = 0.31). Conclusions: In our diverse cohort of pts undergoing Duffy antigen testing, predominantly as part of evaluation for neutropenia, almost all NHB pts were found to have Duffy-null phenotype. DANC was also seen in over half of H pts, and in 22% of NHW pts. Among cancer pts, testing for DANC is underutilized, but frequently impacts chemotherapy management, emphasizing the need for prospective evaluation of the utility of Duffy antigen testing in cancer pts receiving chemotherapy.

Global context matters: Vision transformer–based dermoscopic classification of skin tumors.

e13680 Background: Skin cancer is the most common malignancy worldwide, encompassing a spectrum from benign nevi to aggressive melanoma and nonmelanoma skin cancers. Dermoscopy improves diagnostic accuracy but remains operator dependent, with substantial interobserver variability, particularly for atypical or early lesions. Convolutional neural networks (CNNs) have demonstrated expert-level performance in skin lesion classification; however, their reliance on localized receptive fields may limit modeling of global lesion symmetry, border irregularity, and spatial color patterns central to dermoscopic diagnosis. Vision Transformers (ViTs) introduce an alternative paradigm using self-attention to capture long-range contextual relationships across entire images. We evaluated a ViT-B/16 model for automated diagnosis and classification of skin tumors from dermoscopic images. Methods: We analyzed anonymized publicly available dermoscopy datasets derived from established skin cancer imaging repositories, including the ISIC Archive, comprising malignant melanoma, basal cell carcinoma, squamous cell carcinoma, and benign melanocytic lesions, with ground truth established by histopathology or expert consensus. Images were standardized, augmented, and split into training and validation cohorts using stratified sampling. A Vision Transformer B/16 model pretrained on ImageNet was fine-tuned for multi-class skin tumor classification. Input images (224×224) were partitioned into non-overlapping 16×16 patches and embedded into a token sequence with positional encodings and a learnable class token. The architecture employed 12 transformer encoder blocks with multi-head self-attention and feed-forward networks. Performance was evaluated using accuracy, sensitivity, specificity, F1 score, and area under the receiver operating characteristic curve (AUROC). Results: The Vision Transformer achieved strong diagnostic performance across skin tumor classes, with overall accuracy exceeding 96% and AUROC greater than 0.96. Attention-based global modeling improved discrimination of lesions with irregular borders, heterogeneous pigmentation, and asymmetric morphology—features critical for melanoma detection. Performance remained stable across lesion subtypes and imaging conditions, supporting robustness and generalizability comparable to state-of-the-art CNN approaches. Conclusions: Vision Transformer–based modeling enables accurate and interpretable classification of skin tumors by capturing global dermoscopic context beyond localized feature extraction. Although computationally more intensive than conventional CNNs, ViT architectures offer complementary strengths in modeling complex lesion morphology and warrant further prospective evaluation for integration into clinical skin cancer screening and diagnostic workflows.

Association between gut microbiome and treatment outcomes in metastatic pancreatic cancer patients: A pilot study.

e16381 Background: Pancreatic ductal adenocarcinoma (PDAC) remains a leading cause of cancer mortality in Japan, currently ranking fourth. While gemcitabine plus nab-paclitaxel is a standard first-line regimen for metastatic PDAC, substantial inter-patient variability in treatment response is observed. Emerging evidence suggests that the gut microbiome may modulate chemotherapy efficacy. This pilot study aimed to explore the association between gut microbiome profiles and clinical outcomes in Japanese patients with metastatic PDAC. Methods: This retrospective pilot study enrolled patients with metastatic PDAC treated with first-line palliative chemotherapy between July 2021 and August 2023 (N = 19). Baseline fecal samples were collected prior to treatment initiation. Microbial DNA was extracted and 16S rRNA sequencing was performed. Bioinformatic analysis was conducted using QIIME2. Alpha diversity indices and taxonomic composition were analyzed. Clinical response was assessed according to RECIST v1.1. Exploratory analyses were performed to examine associations between microbial metrics and outcomes, including response rate and overall survival (OS), using Wilcoxon rank-sum test, Fisher’s exact test, and Kaplan–Meier analysis. Results: Of the 19 patients, 10 were classified as responders (PR or SD) and 9 as non-responders (PD). No statistically significant differences were observed in alpha diversity between responders and non-responders (e.g. Chao1, p = 0.624; Shannon index, p = 0.838; Faith’s PD, p = 0.437). Descriptive taxonomic analysis showed a relative enrichment of Streptococcus in non-responders. Median OS did not differ significantly between high vs. low Chao1 groups (12.2 vs. 15.7 months, p = 0.164) nor high Shannon vs. low Shannon groups (12.2 vs. 15.5 months, p = 0.219). Exploratory univariate analyses suggested potential associations between clinical factors such as diabetes status and baseline CA19-9 levels with outcomes, although these findings were not statistically robust. Conclusions: This pilot study did not identify a clear association between baseline gut microbiome diversity and chemotherapy outcomes in Japanese patients with metastatic PDAC. A descriptive trend toward increased Streptococcus abundance in non-responders was observed, consistent with prior observational studies linking this genus to adverse outcomes in gastrointestinal malignancies. However, given the limited sample size, this study was statistically underpowered to detect subtle microbial effects. Larger, prospective longitudinal studies are required to validate these microbial associations in PDAC.

Long term survival outcomes of immune checkpoint inhibitors in metastatic melanoma: Later relapse and long-term outcomes beyond 5 years.

9556 Background: Immune checkpoint inhibitors (ICI) have improved survival outcomes in patients with metastatic melanoma, with a subset achieving durable long term survival outcomes. However, the incidence of late relapse and outcomes among patients who are alive but not progression-free at 5 years remain unknown. Methods: This is a multi-institutional retrospective study of patients with metastatic melanoma treated with either single agent anti-PD1 therapy or a combination of anti-PD1/CTLA-4 who started treatment prior to January 1, 2016. We analyzed the following outcomes: progression free survival at 5 years, late relapses (defined as progression > 5 years after ICI initiation), sites of late relapse, and long-term overall survival. Results: 206 patients with metastatic melanoma were included; 65% (n = 135) were male. Most patients 86% (n = 177) had cutaneous melanoma and 29% (n = 59) had BRAF V600E/K mutations. In this cohort, 56% (n = 115) received a single agent anti-PD1, while the remaining 44% (n = 91) of patients received a combination of Ipilimumab (IPI) plus anti-PD1. The median follow-up from treatment initiation was 9.1 years. At 5 years, 68% (n = 140) of patients were progression-free. Late relapse, occurring > 5 years after ICI treatment initiation, was seen in 6% (n = 12) of patients, at a median of 8.2 years from ICI treatment initiation. Among 12 patients with melanoma relapses, site of relapses was most commonly at nodal metastases (50%), followed by visceral (17%), brain (17%), and bone/spine (17%), soft tissue (8%), and unspecified sites (8%). Overall, 50% of patients had oligo progression, 33% had metastasis at multiple sites, and 17% unspecified. Following late relapse, 83% (n = 10) were rechallenged with ICI; 50% were rechallenged with the same ICI, 17% switched from IPI plus anti-PD1 to single agent anti-PD1, 17% unspecified, and the other 17% were not rechallenged with ICI. The disease control rate was 75% among patients rechallenged with anti-PD1, 100% among those rechallenged with IPI plus anti-PD1, and 100% among patients who switched from IPI plus anti-PD1 to single agent anti-PD1. At last follow-up, 75% (n = 9) of patients with late relapse were alive. Additional analyses, including Kaplan Meier estimates of progression-free and overall survival and incidence of long term sequalae from immune related adverse events will be reported. Conclusions: In this multi-institutional cohort of long-term survivors with metastatic melanoma, late relapse occurred uncommonly. And the outcomes following late relapses were generally favorable, with many patients still experiencing ongoing survival. The findings in our study support continued long-term surveillance beyond 5 years and provide clear expectations in daily clinical practice regarding cure and survivorship following anti-PD1 based therapy in metastatic melanoma

Developing early endpoints in neoadjuvant breast cancer to support accelerated approval.

e12755 Background: Pathologic complete response (pCR) is an early endpoint in neoadjuvant breast cancer considered in accelerated approval decisions by the FDA. However trial-level odds ratios of pCR and mature hazard ratios of disease free survival are only weakly associated in meta-analyses, resulting in approvals being delayed until survival evidence becomes available. We used data from the I-SPY 2 trial to develop early endpoints with better trial level correlations to support accelerated approvals. Methods: The I-SPY 2 trial treated 2117 patients with early stage high-risk breast cancer across 26 regimens between 2010 and 2022. When we separate the regimens into groups by subtype, there were 47 total experimental groups (19 HR+HER2-, 19 HR-HER2- and 9 HER2+). Each group is matched to concurrent control group enrolled within 90 days of the enrollment period, forming a experimental/control comparison. Treatment groups with less than 10 patients or insufficient follow-up were excluded, leaving 27 comparisons across 1577 patients. Hazard ratios for event free survival and negative log odds ratios for various early endpoints (e,g, pCR, RCB Class 0 or1) are computed for each experimental/control comparison. Novel early endpoints, including a binary subtype-specific RCB cutoffs, were developed on a training subset, with 5 comparisons held out for validation. The weighted trial-level correlation (R) was calculated overall and in HRHER2 subgroups. Subtype specific RCB cutoffs were chosen to optimize the overall and within subgroup weighted correlation, while maintaining C indices > .70 for individual survival association. More sophisticated models with RCB index as a continuous variable that incorporated baseline T stage, nodal status and response predictive subtypes were also explored. Results: Overall weighted correlations (R) for PCR, RCB 0/1 and Subtype Specific RCB cutoffs are shown in Table 1. Optimal cutoffs of RCB of 1.1 for HER2+, 1.7 for HR-HER2-, and 2.6 for HR+HER2- were identified giving a correlation of .70 overall in the training set and .54 in training and validation combined. The C index (C) was greater than 0.8 for all endpoints indicating good individual association. Preliminary results using more sophisticated models will be presented. Conclusions: Subtype-specific RCB cutoffs show a modest but clear improvement as an early endpoint over RCB-0/1 and pCR while maintaining a strong patient-level association with survival. External validation efforts are underway. Integrative approaches using continuous RCB improve trial level correlation and will be presented. Trial-level weighted correlation and individual C indices across all 3 subtypes and within each HRHER2 subtype separately. Measure OverallR,C HER2+R,C HR+HER2-R,C HR-HER2-R,C PCR .23, .84 .31, .80 .13, .84 .18, .87 RCB 0-1 .31, .83 .37, .80 .38, .85 .16, .85 Subtype Specific Cutpoint .54, .80 .37, .77 .40, .75 .54, .87 R = correlation; C = C index.

AI-driven H&E plasma cell to predict pathological complete response in IO-treated triple-negative breast cancer (Yale; NCT02489448).

1122 Background: Pathological complete response (pCR) remains difficult to predict in triple-negative breast cancer (TNBC) patients treated with immune checkpoint inhibitors due to limited validated biomarkers. While tumor-infiltrating lymphocytes (TILs) are prognostic in TNBC, they are commonly treated as a composite population. Plasma cells are central to humoral immunity and can influence antitumor response through antibody production, antigen presentation, and T-cell modulation. However, the independent and cooperative prognostic role of plasma cells, either alone or in spatial interaction with other immune cells has not been systematically evaluated, particularly in TNBC. Here, we evaluated the value of plasma cells to predict pathological complete response using AI-based analysis of routine H&E slides. Methods: We analyzed 239 stage I–III TNBC patients across four cohorts. Models were trained on KEYNOTE-522 regimen treated patients (D1, N=130) and validated in both the Yale TNBC immunotherapy trial cohort (D2, N=65; NCT02489448) treated with durvalumab (anti-PD-L1 antibody) and University Hospital cohort (D3, N=25) treated with pembrolizumab. Plasma cells and lymphocytes were automatically detected on whole-slide H&E images using deep learning–based nuclear segmentation and tumor region classification. Quantified metrics included immune cell density, tumor-infiltrating plasma cell (TIP) ratios, and spatial features capturing plasma cell clustering and interaction with lymphocytes. Density-based classifiers were trained on D1 and evaluated for pCR prediction. Results: Plasma cell density alone predicted pCR with higher accuracy than lymphocyte density across both validation cohorts. In D2), plasma cell density achieved an AUC of 73.2 compared with 62.9 for lymphocyte density. Similarly, in the external institutional cohort (D3), plasma cell density outperformed lymphocyte density (AUC 69.2 vs 60.8, respectively; Table 1). These findings demonstrate the superior predictive value of plasma cell density over conventional lymphocyte-based measures for pCR in immunotherapy-treated TNBC. Conclusions: Plasma cells demonstrate independent and cooperative predictive value in immunotherapy-treated TNBC. AI-derived plasma cell density and spatial interaction features improve pCR prediction and survival stratification beyond conventional lymphocyte-based metrics. Comparison of plasma cell performance compared to lymphocytes on holdout set D2 (Yale TNBC clinical trial NCT02489448) and D3. Holdout 1 Holdout 2 Yale NCT02489448 (N=64), D2 UH Hospital (N=25), D3 M plasma 73.2 69.2 M lymph 62.9 60.8

Camrelizumab (C) plus rivoceranib (R) with transarterial chemoembolization (TACE) vs TACE alone in unresectable hepatocellular carcinoma (uHCC): A randomized, phase 3 trial.

4001 Background: The combination of C (anti–PD-1 antibody) + R (VEGFR2 tyrosine kinase inhibitor) significantly improved progression-free survival (PFS) and overall survival (OS) vs sorafenib as first-line treatment for advanced HCC, and improved event-free survival vs surgery alone as perioperative treatment for resectable HCC. We conducted a phase 3 trial evaluating C+R with TACE in intermediate-stage HCC and here present data from the protocol-specified PFS interim analysis (IA). Methods: In this multicenter, open-label, phase 3 trial, patients (pts) with TACE-eligible uHCC, Child-Pugh A, ECOG performance status (PS) 0–1 and no extrahepatic spread were randomized 1:1 to receive C (200 mg, iv, Q3W) + R (250 mg, po, QD) + TACE or TACE alone. TACE (cTACE or DEB-TACE) was administered at the investigator (INV)’s discretion; C+R continued until loss of clinical benefits, unacceptable toxicities, or other protocol-specified criteria. The primary endpoint was PFS by BIRC per mRECIST. As of Sep.13, 2025, 214 PFS events occurred and a preplanned IA was performed. Results: 423 pts (ECOG PS 1, 22.9%; AFP ≥400 ng/mL, 26.7%; portal vein invasion [vp1/2], 9.7%) were randomized to C+R+TACE (n=214) or TACE (n=209). As of data cutoff, median follow-up was 16.4 mo. Median PFS by BICR per mRECIST was significantly longer with C+R+TACE vs. TACE (11.1 vs. 8.3 mo; HR 0.73 [95% CI 0.56–0.96]; 1-sided p=0.0127). PFS by BICR per RECIST v1.1 (13.9 vs 9.5 mo; HR 0.67 [95% CI 0.50–0.91]) and by INV per mRECIST (13.8 vs 7.0 mo; HR 0.61 [95% CI 0.47–0.81]) and per REIST v1.1 (15.7 vs 8.4 mo; HR 0.61 [95% CI 0.45–0.81]) showed consistent findings (Table 1). PFS benefits with addition of C+R persisted across most prespecified subgroups. OS was not mature, with an early trend favoring C+R+TACE (HR 0.76 [95% CI 0.46–1.24]); OS was 91.4% vs 85.5% at 12 mo, and 82.0% vs 73.3% at 24 mo. Among treated pts, grade ≥3 TRAEs occurred in 73.7% (157/213) in C+R+TACE arm vs. 28.7% (60/209) in TACE arm; of them, the most common in C+R+TACE arm were increased AST (20.7% vs 12.9%), hypertension (19.7% vs 4.3%), increased ALT (17.8% vs 9.6%), and decreased platelet count (11.3% vs 2.9%). Conclusions: C+R+TACE provided statistically significant and clinically meaningful improvement in PFS vs TACE, with manageable safety, supporting this regimen as a potential new treatment option for TACE-eligible uHCC. Follow-up for OS is ongoing. Clinical trial information: NCT05320692 . PFS outcomes (ITT set). BIRC INV C+R+TACE (n=214) TACE (n=209) C+R+TACE (n=214) TACE (n=209) Per mRECIST Median (95% CI), mo 11.1 (7.8–14.0) 8.3 (6.9–9.5) 13.8 (8.5–17.3) 7.0 (5.7–9.5) HR (95% CI)* 0.73 (0.56–0.96); 1-sided p=0.0127 † 0.61 (0.47–0.81) Per RECIST v1.1 Median (95% CI), mo 13.9 (10.9–19.4) 9.5 (8.1–11.1) 15.7 (10.3–19.6) 8.4 (6.9–10.8) HR (95% CI)* 0.67 (0.50–0.91) 0.61 (0.45–0.81) *Stratified Cox proportional hazard model. †Stratified Log-Rank test.

Chemotherapy use among women < 50 years with hormone receptor–positive breast cancer with low (≤15) Oncotype DX 21-gene recurrence score: A National Cancer Database (NCDB) analysis.

544 Background: RxPONDER demonstrated a benefit to chemotherapy (CT) in premenopausal women with hormone receptor-positive (HR+) breast cancer (BC) with 1-3 pathological positive lymph nodes (pN1) regardless of Oncotype DX RS. Whether the benefit is due to the cytotoxic effects of CT itself or potentially from the CT-induced ovarian suppression remains to be determined. In the absence of large prospective data evaluating the predictive ability of RS in this population, including pN1mi, we sought to examine adjuvant CT use patterns among premenopausal women and low RS. Methods: This retrospective analysis queries the NCDB from 2018-2022 for patients (pts) with BC <50 years old (surrogate for premenopausal status) and clinically node negative disease at the time of diagnosis. Pts with stage I-III HR+ HER2-negative BC who underwent upfront curative breast surgery and had pathologically confirmed lymph node status (pN) were included. Oncotype DX RS was categorized as low if RS ≤15. Multivariable binary logistic regression was used to examine associations between clinical-pathological factors and the receipt of adjuvant CT. Results: 6040 pts with Oncotype DX RS ≤15 met inclusion criteria. Most pts, 5090 (84.3%), had invasive ductal carcinoma, and high (>51%) ER and PR expression (>93% of patients). Among all low RS, 5081 (84.4%) had pN0 and 939 (15.5%) had pN1 or higher disease, 704 pts (76.6%) having 1 LN involved, of which 317 pts were pN1mi; 148 (16.1%) had 2 LN and 67 (7.3%) had 3+ LN. Accounting for all pts, 265 (4.4%) received CT: 64 (24.2%) were pN0, while 201 (75.8%) were pN1+. Among pts with pN1 BC, older age was associated with lower odds of receiving adjuvant CT (aOR 0.96, 95%CI 0.93-1.00, p=0.03). Other factors including higher pathologic tumor stage (pT3/T4 vs pT1/T2; aOR 4.46, 95% CI 2.34–8.51), higher pN involvement, specifically 2 LN (aOR 2.45, 95% CI 1.60–3.75) and ≥3 LN (aOR 4.65, 95% CI 2.54–8.51) compared to 1 positive regional LN, and poorly (vs well) differentiated tumor (aOR 2.36, 95% CI 1.14–4.88) had higher odds of receiving CT. Similarly, pts with pN0 and low RS that had pT3/T4 tumors (aOR 3.99, 95% 1.16-13.72) and higher grade (moderately and poorly differentiated tumors) had higher odds of receiving CT (aOR 1.84 95% CI 1.03-3.27 and 6.11 95% CI 2.58-14.44, respectively). Conclusions: Among women <50 years with low RS (≤15), CT receipt was strongly associated with clinicopathologic risk factors, including higher tumor stage, poorly differentiated grade and higher regional nodal involvement. These findings indicate that despite a low RS, young age and node positivity are associated with adjuvant CT recommendation. These results highlight the importance of ongoing trials such as OFSET, which aims to better answer the appropriateness of CT among premenopausal women.

Clinical features, management, and outcomes of adolescents and young adults with myeloproliferative neoplasms.

6580 Background: Myeloproliferative neoplasms (MPNs)—polycythemia vera (PV), essential thrombocythemia (ET), myelofibrosis (MF)—are chronic myeloid malignancies mainly occurring in older adults. However, up to 20% of pts are diagnosed as adolescents and young adults (AYA; ages 13–39). Thus, treatment guidelines and outcome data primarily apply to older subjects, leaving clinical features, outcomes, and management of younger pts poorly defined. We describe the characteristics, risk stratification, and treatment of AYA pts at a tertiary academic center. Methods: We conducted a retrospective study of AYA pts with MPN treated at Mass General Brigham between 2007–2025. Pts diagnosed at ages 13–39 and meeting 2022 WHO criteria for MPN were included. Data abstracted from the electronic medical record included demographics, diagnostics, cardiovascular (CV) risk factors, thrombotic and bleeding events, risk stratification, and management. Descriptive statistics were applied. Results: 90 AYA pts with MPN were identified. Median age at diagnosis was 27 years (range 16–39), 53 (58.9%) were female and 64 (71.1%) were White. ET was the most frequent (65.6%), followed by PV (22.2%), MF (6.7%), and MPN-unclassified (5.6%). Most pts (73.3%) were diagnosed incidentally with abnormal blood counts. At least one CV risk factor—HTN, HL, DM, BMI >25, tobacco use—was present in 53 pts (58.9%). JAK2 mutation was present in 55 pts (61.1%), CALR in 26 (28.9%), MPL in 3 (3.3%), and triple-negative in 7 (7.8%). Across 18 (20.0%) pts, 23 thrombotic events occurred; arterial (n= 9) and venous (n= 14);13 in the year prior to diagnosis and 10 after; 3 pts (3.3%) experienced events in both time periods and 4 (4.4%) pts experienced more than one event. Seven (7.8%) experienced major bleeding in the year prior to diagnosis or any time after, defined by ISTH criteria. Of the 23 pts with thrombotic and/or bleeding events, 19 were subsequently cytoreduced, most often with interferon (ropeginterferon n=10; peginterferon n=3). One pt received ruxolitinib and 12 hydroxyurea. Of 71 pts classified as low-risk, 34 (47.9%) received cytoreduction. Indications included extreme thrombocytosis (32.4%), inadequate control with phlebotomy (23.5%), symptom burden (23.5%), bleeding risk/history (17.6%), and disease modification (14.7%). Median follow-up was 3.6 years (IQR 1.9-7.6), 4 (4.4%) pts progressed to MF, and 1 (1.1%) to accelerated phase MPN. Two (2.2%) of these pts have undergone allogeneic stem cell transplantation. One (1.1%) death was reported during follow-up. Conclusions: In this AYA MPN cohort, > 20% were high-risk due to thrombotic events. CV comorbidities were common despite young age. Nearly half of low-risk pts received cytoreductive therapy, highlighting potential limitations of standard risk stratification in young pts. These findings support the need for age-specific guidelines for AYA pts with MPN.