Browse Articles

Benchmarking survival outcomes of quemliclustat in first-line metastatic pancreatic ductal adenocarcinoma: Insights from ARC-8 and implications for PRISM-1.

e16396 Background: Outcomes in first-line metastatic pancreatic ductal adenocarcinoma (mPDAC) remain poor, with gemcitabine plus nab-paclitaxel (GnP) yielding median overall survival (OS) < 11 months in contemporary trials. ARC-8, a phase I/Ib randomized study, evaluated the CD73 inhibitor quemliclustat combined with GnP ± the PD-1 inhibitor zimberelimab and demonstrated encouraging survival outcomes. We conducted a trial-in-context benchmark analysis to assess whether the ARC-8 OS signal exceeds contemporary first-line expectations after accounting for cross-trial differences. Methods: Published ARC-8 efficacy data were synthesized for treatment-naïve mPDAC patients receiving 100-mg quemliclustat-based regimens (quemliclustat + GnP or quemliclustat + zimberelimab + GnP). As ARC-8 lacked a control arm, a matched synthetic control arm (SCA) was derived from historical GnP-treated patients using key baseline characteristics. Contemporary phase III GnP benchmarks from MPACT and NAPOLI-3 control arms were included. Cross-trial differences in OS, progression-free survival (PFS), and overall response rate (ORR) were qualitatively assessed for potential directional bias. Results: Across benchmarking approaches, pooled ARC-8 quemliclustat-based regimens were associated with a median OS of 15.7 months, exceeding contemporary first-line GnP benchmarks. In the matched SCA comparison, OS remained improved (HR for death 0.63), despite baseline characteristics expected to bias against ARC-8. PFS and ORR were broadly similar to GnP benchmarks. No new safety signals or toxicity were observed. Conclusions: In a trial-in-context benchmark analysis, quemliclustat-based regimens in ARC-8 were associated with a consistent OS advantage compared with contemporary GnP benchmarks despite similar PFS and ORR, suggesting a clinically meaningful survival signal and supporting the clinical and biologic rationale for the ongoing phase III PRISM-1 trial. OS, PFS and ORR for ARC-8 Quemliclustat regimens v/s GnP benchmarks. Population/ comparator Median OS, months (95% CI) 12-moOS (%) Median PFS, months ORR (%) ARC-8 Q100 ± Z + GnP (n=122) 15.7 (12.7 63 6.3 (5.4-7.7) 39 Synthetic control GnP (matched, n=515) 9.5 (8.8-10.5) 39.7 5.6 37.3 Contemporary phase III GnP benchmarks 9.2 (8.3-10.6) 40 5.6 (5.3-5.8) 36 Q=quemliclustat; Z=zimberelimab; GnP=gemcitabine+nab-paclitaxel.

Promoting acral melanoma awareness among nail salon technicians and cosmetology educators in California: A theoretically grounded qualitative needs assessment.

e22567 Background: A growing body of literature has explored the role of cosmetology professionals in promoting early community detection of skin cancer. However, no research efforts have explored this topic through a qualitative methods lens, and no theoretical framework has been proposed, gaps we aimed to address. Methods: We conducted 26 semi-structured interviews with nail salon technicians and cosmetology educators in California, which encompasses over 20% of the licensed workforce nationwide, exploring barriers and facilitators to promoting acral melanoma (AM) awareness in the nail salon. Transcripts were independently coded using hybrid deductive-inductive thematic analysis, with a-priori codes informed by situated learning theory, and themes organized using the socioecological framework. Results: Themes emerged across four socioecological levels. At the individual level, participants demonstrated strong understanding of scope-of-practice boundaries, and disposition for recognition and communicating skin and nail abnormalities. Experience strongly correlated with self-efficacy for health communication with clients. At the interpersonal level, the face-to-face nature of nail services and repeat clientele facilitated trust building and longitudinal observation. Client receptivity varied based on technicians' perceived education level. Language discordance was highlighted as a key barrier. At the organizational level, salon culture varied from health-focused environments that empowered difficult conversations, to high-volume settings that discouraged them. Existing digital training infrastructure from the two main cosmetology curriculum providers was identified as an opportunity to broadly disseminate acral melanoma training. At the healthcare systems level, lack of access to care among patients was noted. Additionally, a key barrier identified by participants is the limited understanding of the appropriate healthcare follow up pathways. Conclusions: Grounded in situated learning and landscape of practice (LoP) theoretical frameworks, nail technicians and other cosmetology professionals can be viewed as a distinct community of practice (CoP) occupying a unique position in the landscape of practice (LoP) relevant to melanoma detection. Their work creates a boundary zone with the healthcare professionals CoP which, if developed, can support early detection of AM. LoP framework posits that boundary zones can be strengthened through development of 1) boundary objects (visual recognition guides, healthcare communication scripts, documentation tools), 2) boundary practices (standardizing follow up recommendations, establishing feedback mechanisms), and 3) creating productive boundary encounters (continuing education events, collaborative training development).

Intelligence-driven data extraction for the breast cancer multidisciplinary team meeting case preparation: Results from a prospective external validation.

e13669 Background: Cancer Multi-Disciplinary Team Meetings (MDTMs) are central to UK Cancer Pathways irrespective of patient case complexities. A major bottleneck for the MDT is time-consuming, laborious manual review of clinical summaries and investigation reports to prepare MDTM cases. Large Language Models (LLMs) can extract critical, structured information from this vast, complex unstructured text reservoir. After a multiple LLM benchmark testing model in an internal sandbox environment as part of an Oncology Intelligence Platform, the most optimal LLM (maximal accuracy, minimal hallucinations and Graphics Processing Unit usage) was deployed for a Data Extraction task to prepare cases for the Breast Cancer MDTM. This was a prospective, external validation experience to highlight LLM performance. Methods: A retrospective dataset consisting of structured and unstructured radiology investigation text reports of confirmed breast cancer patients from the Barts Health NHS Trust Data Platform was obtained from 2018 to 2024. These reports were multisource including regional (Mammogram, Ultrasound and MRI Breast) and systemic scans (Staging/Response Assessment CT Chest Abdomen Pelvis and Bone Scans). An Artificial Intelligence (AI) powered Cancer MDTM CoPilot software platform (OncoflowTM) was used on this data to perform strategic extraction to a set of defined objective parameters, including clinical TNM (tumour-node-metastasis) classification points. Results: 165 aforementioned reports of varying disease stages (I to IV) were prospectively processed by OncoFlow’s fine tuned, cancer data extraction task specific LLM. This LLM was an open source, domain-specific, multilingual, instruction-tuned (having undergone distillation and reinforcement learning), autoregressive transformer model. There were 21 extraction features. These were divided into 3 Tiers based on data types - T1a (continuous numeric), T1b (discrete ordinal), T2 (categorical with intrinsic order), T3 (free text) comprising 2, 4, 3, 12 parameters respectively. Performance metrics for T1 features used Mean Absolute Error (MAE), which ranged from 96 to 99% for T1a and 74 to 93% for T1b. T2 being multi-class, used F1 scores, i.e., Micro-F1 (model performance on whole dataset/all classes) ranging 0.8 - 0.9 and Macro-F1 (average model performance across each class) ranging 0.6 - 0.8. Token-level F1 score, measuring precision and recall, was used in model performance for T3 parameters. This ranged from 78 to 95%. Exact match accuracy for the aforesaid was 62 to 93%. Conclusions: The LLM achieved robust, clinically relevant accuracy scores across all data tiers. The reliable scores showcase the model’s readiness to streamline and standardise MDTM case preparations.

Efficacy and safety of a short-course (12-week) de-escalated neoadjuvant regimen (weekly paclitaxel/trastuzumab/pertuzumab) in early HER2-positive breast cancer: Interim analysis of a prospective study.

599 Background: Standard neoadjuvant regimens for HER2-positive early breast cancer (EBC), such as 6 cycles of TCHP, achieve high pathological complete response (pCR) rates but carry significant toxicity risks. De-escalation strategies aiming to reduce treatment intensity and duration without compromising efficacy are clinically relevant. We present the interim analysis of a prospective study evaluating a shortened (12-week), carboplatin-free and anthracycline-free regimen (THP). Methods: We enrolled patients (pts) with histologically confirmed HER2-positive (IHC 3+ or ISH+) EBC, clinical stages T0-1N1M0 or T2-3N0-1M0. Pts received a de-escalated regimen consisting of 12 weekly infusions of paclitaxel (80 mg/m²) combined with trastuzumab and pertuzumab administered every 3 weeks for 4 cycles (12 weeks total). The primary endpoint was pCR rate (ypT0/is ypN0). Secondary endpoints included safety and treatment adherence. This interim analysis reports data from the first 70 pts who completed surgery. Results: Median age was 50 years. The cohort included 69% stage IIA and 31% stage IIB pts; 57% were cN0. 60% had HR-positive and 40% had HR-negative disease. Treatment compliance was excellent: 100% of pts completed the full 12-week course. The overall pCR rate was 60.0% (42/70). Efficacy was strongly associated with hormonal status: the pCR rate reached 82.1% (23/28) in the HR-negative subgroup, compared to 45.2% (19/42) in the HR-positive subgroup. The safety profile was exceptionally favorable compared to historical TCHP data. Grade ≥3 neutropenia occurred in only 4% of pts. No cases of febrile neutropenia or symptomatic cardiotoxicity were observed. Grade ≥3 non-hematological toxicity (diarrhea/rash) was limited to 8%. Peripheral neuropathy was predominantly grade 1, with occasional grade 2 events; no grade ≥3 neuropathy occurred. Conclusions: The short-course (12-week) de-escalated THP regimen demonstrated high efficacy, particularly in HR-negative/HER2-positive pts (pCR 82.1%), comparable to longer, more toxic multi-agent regimens. With a 0% rate of febrile neutropenia and 100% completion rate, this regimen represents a promising "chemo-light" option for selected patients, potentially guiding future de-escalation strategies in personalized oncology. Baseline characteristics and clinical outcomes (N=70). Characteristic / Endpoint N (%) or Median (Range) Median Age, years 50 (29–75) Node-positive disease (cN+) 30 (43%) HR-negative / HER2-positive 28 (40%) Completed full 12-week NACT 70 (100%) Breast-conserving surgery 34 (49%) Pathological Complete Response (Total) 42 (60.0%) pCR in HR-negative subgroup 23/28 (82.1%) pCR in HR-positive subgroup 19/42 (45.2%) Grade 3-4 Neutropenia 3 (4%) Febrile Neutropenia 0 (0%)

Association between breast cancer located in the upper outer quadrant (UOQ) and axillary lymph node metastasis (N1 disease): Clinical implications and prognostic significance.

e12764 Background: While tumor location influences lymphatic drainage patterns, its prognostic value in node-positive disease is unknown. We evaluated whether upper outer quadrant (UOQ) tumor location is associated with distinct survival outcomes in patients with N1 breast cancer. Methods: We conducted a retrospective cohort study of 1,914 breast cancer patients with N1 disease treated at Seoul National University Hospital between January 2000 and December 2020. N1 disease was defined as biopsy-confirmed clinical N1 in neoadjuvant chemotherapy recipients or pathologic N1 in upfront surgery patients. Tumor location was determined by preoperative imaging (ultrasonography and MRI). Distant metastasis-free survival (DMFS) and overall survival (OS) were analyzed using Kaplan-Meier and Cox proportional hazards models. Results: Among enrolled patients, 938 (49.0%) had UOQ tumors and 976 (51.0%) had non-UOQ tumors. While UOQ patients were older (median 49 vs 47, p-value 0.004) and received breast-conserving surgery and radiotherapy more frequently (58.6% vs 44.8, p-value < 0.001), tumor stage, molecular subtype, histologic grade, and systemic treatment were comparable between groups. In this node-positive cohort, UOQ location was associated with significantly superior 5-year DMFS (86.3% vs 75.3%, p < 0.001) and OS (93.4% vs 87.9%, p < 0.001). On multivariate analysis, UOQ location remained a significant independent favorable prognostic factor, reducing the risk of distant metastasis by 50% (HR 0.50, 95% CI 0.42–0.60, p < 0.001) and death by 47% (HR 0.53, 95% CI 0.42–0.66, p < 0.001) after adjusting for tumor stage, molecular subtype, histologic grade. Conclusions: Among patients with node-positive breast cancer, UOQ tumor location confers a substantial survival advantage independent of conventional prognostic factors. This finding suggests that nodal positivity has a less adverse prognostic impact when the primary tumor is located in the UOQ, potentially reflecting distinct patterns of lymphatic spread. Tumor location might be incorporated into risk stratification for N1 breast cancer patients.

MOMENTUM: A phase 2, open-label, single-arm, multicenter study to evaluate the efficacy of cemsidomide + dexamethasone in subjects with relapsed/refractory multiple myeloma (RRMM).

TPS7579 Background: Cemsidomide is a novel, highly potent, cereblon-based, IKZF1/3 MonoDAC degrader, having a similar mechanism of action as BMS’s IMiD or CELMoD degraders for MM. Cemsidomide displays catalytic activity enabling rapid and deep target degradation with high binding affinity to overcome resistance due to low cereblon levels. Cemsidomide binds to cereblon to facilitate the recruitment and ubiquitination of IKZF1/3 leading to the proteasomal degradation of both proteins. IKZF1/3 degradation induces multiple myeloma cell death, activation of fully differentiated T-cells which prevents T-cell exhaustion and promotes secretion of key immune stimulating cytokines. In a Phase 1 study, cemsidomide, given orally QD over 14 days with a 14 day “off” period (14/14) in combination with weekly dexamethasone in a heavily pre-treated patient population (7 median prior lines), was well tolerated and demonstrated durable anti-myeloma activity at increasing dose levels. A 53% ORR was observed as the highest dose of 100 µg QD 14/14, with a 36% ORR observed across all dose levels (Dhakal IMS 2025). Methods: MOMENTUM (NCT07284758) is a Phase 2 multi-center, open-label, single-arm, global study to further evaluate the anti-myeloma activity as well as safety, tolerability, and PK/PD of cemsidomide. The study will enroll ~100 patients. The patient population eligible for this study include those who have received at least 3 prior antimyeloma regimens, which must have included an IKZF1/3 degrader other than cemsidomide, a proteasome inhibitor, an anti-CD38 antibody, and a TCE or CAR-T therapy (unless not indicated). Prior TCE or CAR-T therapy may be one or more targets including but not limited to: BCMA, GPRC5D, FcRH5, and CD38. Patients must have an ECOG score of ≤2, and adequate organ function prior to dosing. Patients will receive cemsidomide 100 µg QD 14/14 and dexamethasone in a 28-day cycle until progressive disease, AE requiring treatment discontinuation, or withdrawal of consent. The primary endpoint of this study is ORR per IMWG response Criteria (IMS 2025) assessed by an Independent Review Committee (IRC). Secondary endpoints include assessment of DOR, PFS, and OS. Exploratory objectives include antimyeloma activity assessed by investigator, degradation of IKF1/3, quantification of protein expression, and patient QoL assessments. Exposure-response relationships between cemsidomide and relevant markers of safety and efficacy will also be analyzed. A safety review committee and an IRC will be established to oversee safety and efficacy throughout the trial. The study is open to enrollment as of December 2025. Clinical trial information: NCT07284758 .

A phase II clinical study of stereotactic radiotherapy (SRT) combined with chemotherapy and tislelizumab for the treatment of metastatic nasopharyngeal carcinoma.

e18020 Background: In general, immune checkpoint inhibitors combined with chemotherapy can benefit patients with metastatic nasopharyngeal cancer (mNPC), but immunotherapy is still ineffective in some patients. Previously, studies have verified the safety and efficacy of local radiotherapy in newly diagnosed mNPC patients. In addition, radiotherapy can also enhance immune responses by changing the tumor microenvironment. This study preliminarily explores the efficacy and safety of stereotactic radiotherapy (SRT) combined with chemotherapy and tislelizumab (PD-1 inhibitor) in mNPC. Methods: A prospective, single-arm, single-center phase II study, thirty-seven cases were enrolled with pathological diagnosis of mNPC. The metastatic lesions received SRT (adjusted individually based on the size, location of the metastatic lesions, and the distance to adjacent critical organs) along with 4-6 cycles of chemotherapy combined with immunotherapy. For newly diagnosed metastatic patients, nasopharyngeal and metastatic lymph node GTV irradiation was performed after 4-6 cycles of chemotherapy and immunotherapy, followed by immunotherapy maintenance therapy until disease progression or for up to 2 years. The primary endpoint was progression-free survival (PFS) within the radiation field, and the secondary endpoints were objective response rate (ORR) and safety. Results: From October 2022 to June 2025, a total of 38 eligible patients were screened, which 30 patients underwent metastatic radiotherapy and 8 patients did not undergo metastatic radiotherapy due to personal reasons. Among the 38 patients, the mean age was 56 years and predominantly male (84.2%), meanwhile 65.8% patients were newly diagnosis with metastases. The median follow-up time for the 30 patients was 21.4 months, and the median PFS in target lesions has not yet been reached. 12 -month PFS rate in target lesions is 96% [89%-100%, 95% CI] and 24 -month PFS rate in target lesions is 78% [61%-100%, 95% CI]. After SRT for metastatic lesions, the efficacy could be evaluated in 27 patients, including 17 (63%, 95%CI 42%-80%) patients with CR, 9 patients with PR (33%, 95%CI 17%-54%), and 1(4%, 95%CI 0.19%-21%) patient with SD. The most common TEAEs are still chemotherapy related. Immune-related adverse reactions are mainly dermatitis, pneumonia, hepatitis, and hypothyroidism, all of which are mild. Conclusions: For patients with mNPC, receiving SRT for metastatic lesions along with chemotherapy and immunotherapy holds excellent prospects for local disease control. Clinical trial information: NCT05652192 .

Historical redlining and oral squamous cell carcinoma staging at diagnosis.

e22598 Background: Previous research has shown that residents in historically redlined zones, areas defined from the discriminatory housing policy in 1935-1940, are more prone to being diagnosed with later-stage cancer for breast cancer, cervical cancer, lung cancer, colorectal cancer, and prostate cancer. However, little was known about this relationship for oral squamous cell carcinoma, which lacks general screening guidelines at primary care settings and general practice incorporating oral cancer screening during routine dental care. Methods: We used cancer registry data from a single tertiary medical center mainly from year 2016-2025 to identify patients diagnosed with primary oral squamous cell carcinoma. Main exposure is whether the patient resided in historically redlining zone, defined as Homeowners’ Loan Corporation (HOLC) grades C and D. Main outcome of interest is the stage of oral squamous cell carcinoma, which is grouped as the binary outcome (late stages [stage III, IV] vs early stages [stages I, II]). Logistic regression is used to study the association between redlining and being diagnosed with late-stage oral squamous cell carcinoma. The data was visualized by a map incorporating the redlining zone and stages of oral squamous cell carcinoma at diagnosis. R version 4.2.3 is used for statistical analysis. Results: Among 566 patients diagnosed with primary oral squamous cell carcinoma, 232 (41%) are female, 105 (19%) are black/African American, and 39 lived in the historically redlining zone. The median age at diagnosis was younger among patients from redlined zones (median [IQR]: 59.81 [52.01, 63.84] ) compared to those from non-redlined zones (median [IQR]: 65.7 [57.94, 74.28] (p = 0.001). The unadjusted odds of a late-stage diagnosis were higher for patients in historically redlined zones (OR = 2.51, 95% CI = [1.18, 5.59]). Findings were similar after adjusting for sex, age, and smoking status(OR = 2.38, 95% CI = [1.11, 5.71]). Conclusions: The findings suggest that patients living in historically redlining zones are more likely to receive a late-stage diagnosis of oral squamous cell carcinoma and to be diagnosed at a relatively younger age. Findings indicate a need to increase resources, including increased dental care, in these areas to help identify cancers at an earlier stage and reduce disparities in oral squamous cell carcinoma outcomes. Further research and potential policy and/or public health initiatives targeting these populations for risk reduction and screening are warranted. Association between residing in historical redlining zone and odds of being stage III/IV oral squamous cell carcinoma at diagnosis. OR (95% CI ) Model 1: Unadjusted 2.51 [1.18, 5.95] Model 2: Adjusted for age 2.49 [1.17, 5.94] Model 3: Adjusted for age, sex 2.49 [1.17, 5.95] Model 4: Adjusted for age, sex, smoking status 2.38 [1.11, 5.71] OR = odds ratio; CI = confidence interval.

Impact of disseminated intravascular coagulation on in-hospital outcomes in patients with multiple myeloma: A nationwide analysis.

e19557 Background: Disseminated intravascular coagulation (DIC) is an uncommon but severe hematologic complication in multiple myeloma (MM). Its impact on in-hospital mortality, clinical complications, and resource utilization remains poorly characterized at a national level. Thus, we aimed to compare outcomes of hospitalized MM patients with and without DIC using a National Inpatient Sample (NIS) database. Methods: We conducted a cross-sectional study using the NIS database to identify adult hospitalizations with a diagnosis of MM from 2018 to 2021. Patients were stratified by the presence or absence of DIC. Primary outcomes included in-hospital mortality, length of stay (LOS), and total hospital charges (THC). Secondary outcomes included multiple in-hospital complications. Survey-weighted univariable and multivariable regression models were used to calculate adjusted odds ratios (aOR) and beta coefficients (β), adjusting for demographics and clinical covariates. Results: We identified a cohort of 467,530 adult MM hospitalizations from 2018 to 2021. Among these, 1,945 (0.4%) were complicated by DIC. In-hospital mortality was substantially higher with DIC than without DIC (49.0% vs 5.1%, p < 0.001); after multivariable adjustment, DIC remained an independent factor for increased odds of mortality (aOR 9.63 [7.53, 12.3], p < 0.001). Similarly, LOS was longer with DIC both before (median 9 vs 5 days, p < 0.001) and after adjusted analysis (β +5.4 days, p < 0.001). Inflation-adjusted THC were higher with DIC (median $158,749 vs $53,790, p < 0.001), with higher adjusted charges (β +$166,793, p < 0.001). The DIC group also had a significantly increased likelihood of non-home discharge (aOR 5.64, p < 0.001). A detailed comparison of in-hospital complications showed DIC group had higher rates of acute kidney injury (73% vs 35%; aOR 4.13 [3.24, 5.28]), renal replacement therapy need (28% vs 8.7%; aOR 3.76 [2.71, 5.22]), respiratory failure (57% vs 18%; aOR 4.25 [3.34, 5.41]), need for mechanical ventilation (42% vs 4.2%; aOR 7.70 [5.96, 9.94]), acute hepatic failure (21% vs 1.2%; aOR 13.7 [9.80, 19.3]), septic shock (40% vs 4.2%; aOR 4.79 [3.54, 6.48]), and cardiac arrest (9.8% vs 1.1%; aOR 4.41 [3.00–6.49]) (all p < 0.001). Additionally, patients with DIC also had higher odds of ischemic stroke (4.9% vs 1.7%; aOR 2.92 [1.81, 4.71]), hemorrhagic stroke (3.3% vs 0.8%; aOR 3.54 [0.81, 1.11]), and major bleeding (19% vs 5.0%; aOR 3.32 [2.50, 4.40]) (all p < 0.001). Pulmonary embolism and deep vein thrombosis were numerically higher but not statistically significant. Conclusions: MM patients with DIC experienced markedly worse inpatient outcomes and significantly greater resource utilization compared with those without DIC, highlighting DIC as a critical prognostic marker in MM hospitalizations and underscoring the need for early recognition and aggressive multidisciplinary management.

Association of PCSK9 inhibitors with clinical outcomes in patients with cancer receiving immune checkpoint inhibitors: A real-world analysis.

2657 Background: Although developed as lipid-lowering agents, PCSK9 inhibitors (PCSK9i) have shown preclinical potential to synergize with immune checkpoint inhibitors (ICIs) by increasing tumor antigen presentation and overcoming ICI resistance. However, there is limited evidence describing their use and associated outcomes in real-world oncology practice. We aimed to explore the clinical outcomes in relation to PCSK9i use in patients with cancer receiving ICIs. Methods: This propensity score-matched (PSM) cohort study utilized the TriNetX research network, encompassing real-time electronic health records from > 70 U.S. healthcare organizations. The study population included adults (aged ≥18 years) diagnosed with non-small cell lung cancer, melanoma, renal cell carcinoma, or breast cancer, who underwent concurrent ICI therapy (e.g., pembrolizumab, nivolumab, atezolizumab, durvalumab) plus PCSK9i (e.g., evolocumab, alirocumab; with or without statins) or high-intensity statins alone (atorvastatin ≥ 40 mg, or rosuvastatin ≥ 20 mg) between 01/01/2011 (the earliest year of ICI approval) and 01/01/2025 for hyperlipidemia. The primary outcome was overall survival (OS). Secondary outcomes included emergency room (ER) visits, all-cause hospitalization, ICU admission, and 4-point (acute myocardial infarction, heart failure, stroke, and unstable angina) major adverse cardiovascular event (MACE). A 1:1 PSM was applied to balance potential confounders, including demographics, socioeconomic status, cancer site, Charlson-Comorbidity-Index comorbidities, and laboratory parameters [Albumin, LDL, AST/ALT, and BMI]. Time-to-event analyses were performed using Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), with log-rank test for significant survival differences. Follow-up began at the initiation of concurrent ICI plus PCSK9i or statin and continued until 01/05/2025, or until the occurrence of the study outcomes. Results: A total of 254 patients in PCSK9i cohort were matched to 254 patients from the statin-only cohort (n = 13734). Patients receiving PCSK9i demonstrated significantly improved OS compared with those receiving statins alone (HR 0.67, 95% CI 0.52-0.88) and associated with lower risk of ER visits (HR 0.64, 95% CI 0.49-0.83), hospitalization (HR 0.68, 95% CI 0.54-0.85), and ICU admission (HR 0.69, 95% CI 0.50-0.95; all p<0.01). No significant difference was observed for MACE outcomes (HR 0.79, 95% CI 0.59-1.07, p=0.13). Conclusions: In this large, real-world analysis, the use of PCSK9i in patients with cancer and hyperlipidemia treated with ICIs was associated with improved overall survival and reduced healthcare utilization. These findings support ongoing prospective clinical trials evaluating the potential synergistic effects of PCSK9 inhibition with ICI therapy.

An automated, EHR-integrated intervention system for patient-reported insomnia symptoms.

12058 Background: Insomnia affects >20% of patients on cancer therapy. It is consistently reported to be one of the most burdensome sequelae. Systematic screening for insomnia in cancer patients is uncommon. Without identification, patients cannot access care. Unfortunately, even if insomnia is identified, most cancer centers lack on-site sleep specialists. To address both the screening and treatment gaps, we leveraged our institution's EHR-based patient-reported outcomes (PRO) data collection system to develop a fully automated solution to identify patients with insomnia, and share an evidence-based psychoeducational video intervention with them. Methods: Prior to established outpatient appointments at our hospital, all patients are asked to complete eSyM, an electronic PRO-CTCAE symptom assessment. Two insomnia items (symptom severity and interference) are combined to generate an insomnia score (0-3; higher is worse, with present analyses for those reporting a score ≥2). Patients with an elevated insomnia score were sent a patient portal message explaining they were identified as having insomnia, and offered an educational video with strategies to improve their sleep. We tracked patient engagement, as well as report of insomnia symptoms via eSyM response at the patient’s subsequent appointment closest to 60 days post-Baseline (±30 days). Data was analyzed from patients who reported completed eSyM insomnia questions at both timepoints between 02/25 to 09/25. Results: Patients with insomnia (N=307) were an average of 63 years old, predominantly female (63%), White (84%), married (63%), and possessed a college degree or higher (57%). They were diagnosed with a broad range of cancers (breast = 20%, GI = 15%, thoracic = 10%). The vast majority (92%) opened the patient portal message with the video link, with the video watched in entirety 498 times. Overall, insomnia scores significantly decreased from baseline (x̄ = 2.3) to follow-up (x̄ = 1.9; p <.001), with 42% reporting symptomatic improvement at follow-up (48% no change and 9% worse). Specifically, 41% reported either Severe or Very Severe insomnia symptoms at baseline, improving to 30% at follow-up; 37% reported insomnia interfered with their life Quite a Bit or Very Much at baseline, improving to 23% at follow-up. Multivariate analyses revealed sociodemographic characteristics (Black, Medicare, and disabled) associated with less insomnia improvement. Conclusions: We developed a fully automated system that leverages electronic PRO data and our EHR to identify symptomatic cancer patients with insomnia and intervene. Our findings demonstrate that we can successfully connect with patients reporting insomnia and potentially improve outcomes with a low-intensity intervention. This framework can readily be deployed to identify and address other common side effects of cancer treatment (e.g., fatigue, pain) that impair recovery and quality-of-life.

NeoIRENIE: A phase 2 randomized trial of intensified neoadjuvant therapy for melanoma patients with multi-omic biomarker or clinically predicted poor response to standard immune checkpoint inhibitor (ICI) therapy.

TPS9610 Background: Neoadjuvant immunotherapy (NAT) with immune checkpoint inhibitors (ICI) has emerged as superior treatment for stage III melanoma, demonstrating improved outcomes compared to adjuvant therapy. The SWOG-1801 trial showed 23% EFS benefit at 2 years for NAT versus adjuvant PEMBRO (72% vs 49%, P=0.004), while the NADINA trial confirmed superiority of NAT IPI/NIVO over adjuvant NIVO (2-year RFS 83.7% vs 57.2%, HR 0.32). Pathological response, particularly major pathological response (MPR; ≤10% viable tumor), strongly correlates with improved outcomes, with the International Neoadjuvant Melanoma Consortium pooled analysis (N=610 ICI patients) demonstrating 3-year RFS of 93% for MPR patients versus 41% for those with no pathological response. However, standard NAT with IPI (1mg/kg) and NIVO (3mg/kg) achieves MPR in only ~60% of patients. Multi-omic biomarkers can predict poor response to anti-PD-1 therapy, identifying patients who may benefit from intensified ICI therapy. The NeoIRENIE trial evaluates whether intensified ICI regimens improve pathological response in poor prognosis patients identified by biomarker prediction, treatment failure, or mucosal histology. Methods: Phase 2, non-comparative, multicenter, randomized trial with 3 cohorts (N=493, Table 1). All pts undergo therapeutic lymph node dissection/completion surgery at week 6 with path response evaluation per INMC criteria. Cohorts 1a, 2 and 3 pts without MPR receive adjuvant NIVO 480mg Q4W for 11 doses. CT, MRI brain and FDG PET/CT performed at baseline, pre-surgery and during 10-year follow-up. Tumor, blood and stool samples collected at baseline, wk 3, surgery and recurrence. Primary endpoint: path response rate in each INMC response category. Secondary endpoints: event-free survival, RECIST response rate, metabolic response rate, overall survival, safety/tolerability, surgical outcomes and quality of life. Exploratory endpoints: biomarker analyses and validation of multi-omic predictive model. Clinical trial information: NCT06999980 . Cohort N Resectable Melanoma Patient Population *Arms(Randomization) 1a 168 Stage IIIB/C/D cutaneous; biomarker-predicted poor responders; treatment-naïve A-D(1:1:1:1) 1b 154 Stage IIIB/C/D cutaneous; biomarker-predicted high responders; treatment-naïve E-F(1:1) 2 111 Stage IIIB/C/D cutaneous; recurrence within 6 months of adjuvant or NAT ICI therapy A-C(1:1:1) 3 60 Any stage mucosal melanoma; treatment-naïve A-B(1:1) * Arms: A=IPI 3mg/kg + NIVO 1mg/kg Q3W x2. B=NIVO 480mg + RELA 160mg + IPI 1mg/kg Q4W x2. C=NIVO 480mg + RELA 160mg Q4W x2. D=IPI 1mg/kg + NIVO 3mg/kg Q3W x2. E=IPI 1mg/kg + NIVO 3mg/kg Q3W x2. F=PEMBRO 200mg Q3W x2.

A phase 2, open-label, multi-center, single-arm study of atezolizumab and bevacizumab in the treatment of second line and beyond, recurrent/metastatic endometrial cancer.

2576 Background: The treatment paradigm for advanced/recurrent endometrial cancer (EC) is undergoing rapid transformation. Currently, use of immune checkpoint inhibitors (ICI) is standard of care for deficient mismatch repair (dMMR) tumors in the front line setting and ICI “can” be used in proficient MMR (pMMR). The purpose for this study is to evaluate an alternative ICI and anti-angiogenic regimen, atezolizumab plus bevacizumab in pts with recurrent EC with no prior ICI use and to identify blood-based correlates of non-responders early in treatment. Methods: This multicenter, single-arm, open label phase 2 trial (NCT03526432) enrolled pts with recurrent EC who had relapsed following platinum based chemotherapy. No prior ICI was allowed. Treatment consisted of atezolizumab 1,200 mg plus bevacizumab 15 mg/kg iv on day 1 every 21 days until progression or toxicity. The primary endpoint was objective response rate (ORR). Peripheral whole blood was collected at baseline and after 2 cycles of therapy, and high-dimensional immune profiling was performed. Results: Sixty-five pts were enrolled and received at least one dose of trial treatment. Fifty-six pts were response-evaluable (45 with pMMR tumors, 7 with dMMR tumors and 4 with unknown MMR status). Median age was 65 years. All pts had received at least one prior chemotherapy and 22 pts (39.3%) received prior radiation therapy. The ORR was 33.9%; 95% CI, 21.8 to 47.8; (19/56 patients), which include 5 complete and 14 partial responses; median duration of response (DOR) was 16 months. In addition, 63% of pts survived progression-free for at least 6 months. The median PFS was 8.8 months (95% CI, 5.5 to 12.0). The median OS was 41.55 months (95% CI, 27.0 – 57.5). The most common grade 3 or 4 adverse events were hypertension (21.5%), fatigue (7.7%) and diarrhea (7.7%). In peripheral blood analysis, non-responders demonstrated expansion of a suppressive myeloid population characterized by PD-L1⁺CD16+ monocytes. There was an increase of ICOS⁺ Tregs consistent with an immunosuppressive phenotype. Within the effector T cell compartment, central memory CD8⁺ T cells expressing Fas and CD27 expanded in non-responders. Conclusions: The combination of atezolizumab and bevacizumab in patients with recurrent EC and post cytotoxic chemotherapy has efficacy in both dMMR and pMMR populations and a toxicity profile that appears more favorable than other treatments. This data suggests atezolizumab and bevacizumab could be considered as an alternative regimen in the recurrent, metastatic setting among pts who are ICI naïve and for whom there are concerns regarding the adverse events of treatment. Peripheral whole blood analysis of non-responders correlated with immune angiogenic escape mechanism with higher levels of ICOS+Tregs, Fas+CD27+ CD8T cells, and PDL1+ CD16+ monocytes. Clinical trial information: NCT3526432 .

Risk of non-Hodgkin lymphoma in sarcoidosis patients with salivary gland involvement: A retrospective cohort study.

e19060 Background: Sarcoidosis is an inflammatory disease characterized by non-caseating granulomas that most commonly affect the lungs and intrathoracic lymph nodes but may virtually involve any organ system. Salivary gland sarcoidosis is a rare manifestation of systemic sarcoidosis and may clinically mimic Sjogren's syndrome. While salivary gland disease is a well-established risk factor for non-Hodgkin lymphoma (NHL) in Sjogren's syndrome, its association with NHL in sarcoidosis remains poorly characterized. This study aims to assess whether salivary gland involvement in sarcoidosis is associated with an increased risk of NHL and other hematological malignancies. Methods: We conducted a retrospective cohort study using TriNetX, a multi-institutional, de-identified EHR database. The study population included adult patients (≥18 years) with sarcoidosis. The exposure cohort was comprised of patients with salivary gland involvement while the control group was comprised of patients without salivary gland involvement. Patients with Sjogren's syndrome and prior hematological malignancies were excluded. One-to-one propensity score matching was performed based on age, sex, race, and medication exposures to glucocorticoids and antineoplastics. The primary outcome was defined as the development of NHL. The secondary outcome was defined as the development of any hematological malignancy. Results: After matching, 2,093 patients were included per cohort. NHL occurred in 25 patients in the exposure cohort and 11 patients in the control cohort with a risk ratio of 2.27 (95% CI 1.12-4.61) and an odds ratio of 2.29 (95% CI 1.12- 4.66). Overall hematological malignancies occurred in 47 patients in the exposure cohort and 18 patients in the control cohort with a risk ratio of 2.61 (95% CI 1.52-4.48) and an odds ratio of 2.65 (95% CI 1.53- 4.58). Conclusions: Salivary gland involvement in sarcoidosis is associated with a 2.3-fold increased risk of NHL and a 2.6-fold increased risk of overall hematological malignancies, although the absolute risk remains low at 1.19% and 2.25% respectively. These results suggest chronic salivary gland inflammation in sarcoidosis may drive carcinogenesis through persistent B-cell activation as is well described in Sjogren’s syndrome. Collectively, the findings highlight salivary gland involvement as a clinically meaningful risk marker in sarcoidosis patients, supporting targeted surveillance and lower biopsy thresholds in this population.

Potent and broad-spectrum anti-Candida activity of 6α-(3’-methoxy-4’-hydroxybenzoyl)-lup-20(29)-ene-3-one, a triterpenoid from Paullinia pinnata

Vulvovaginal candidiasis is a common infection that affects women of reproductive age, with a high prevalence among pregnant women. When left untreated, it can lead to pregnancy complications including miscarriage. The study evaluated the activity of the ethyl acetate (EtOAc) extract of Paullinia pinnata and its isolated compound 6α-(3’-methoxy-4’-hydroxybenzoyl)-lup-20(29)-ene-3-one against drug-resistant strains and clinical isolates of Candida albicans , Candida glabrata , Candida krusei , Candida parapsilosis and Candida tropicalis . Furthermore, the effects of the combinations of 6α-(3’-methoxy-4’-hydroxybenzoyl)-lup-20(29)-ene-3-one with voriconazole, nystatin or caspofungin on the Candida strains and isolates as well as its antibiofilm activity against the drug-resistant strains are reported in this study. The EtOAc leaves extract of P. pinnata demonstrated considerable activity against the drug-resistant Candida strains and clinical isolates with minimum inhibitory concentrations (MICs) of 31.25 to 500 µg/mL when assessed for anti- Candida activity using the microbroth dilution method. The extract was column fractionated to obtain five bulk fractions, and from the most active bulk fraction, BF4 (MIC = 3.91–31.25 µg/mL), 6α-(3’-methoxy-4’-hydroxybenzoyl)-lup-20(29)-ene-3-one was isolated. This study is the first reported biological activity of the compound. 6α-(3’-methoxy-4’-hydroxybenzoyl)-lup-20(29)-ene-3-one exhibited strong activity against the panel of drug-resistant Candida species with MIC ranging from 0.5 to 16 µg/mL (0.85–27.10 µM). This activity was within similar range to that of ketoconazole (MIC = 1–8 µg/mL) and amphotericin B (MIC = 0.5–2 µg/mL). When combined with voriconazole, nystatin or caspofungin using the checkerboard assay, 6α-(3’-methoxy-4’-hydroxybenzoyl)-lup-20(29)-ene-3-one recorded synergism of 33.33% to 83.33% with the antifungals, with majority of the synergistic interactions observed against C. albicans and C. glabrata strains and isolates. 6α-(3’-methoxy-4’-hydroxybenzoyl)-lup-20(29)-ene-3-one also demonstrated anti-biofilm activity. Its IC 50 values against the formation of biofilms and preformed biofilms of the Candida species were 15.30–46.40 μg/mL (25.91–78.60 μM) and 25.40–90.84 μg/mL (43.02–153.86 μM), respectively. In conclusion, P. pinnata possesses strong anti- Candida activity and its isolated compound, 6α-(3’-methoxy-4’-hydroxybenzoyl)-lup-20(29)-ene-3-one displayed potent anti- Candida and anti-biofilm action. These findings identify 6α-(3’-methoxy-4’-hydroxybenzoyl)-lup-20(29)-ene-3-one as a promising anti- Candida compound warranting further investigation, including cytotoxicity in mammalian cells, before its therapeutic potential can be fully assessed.

All biogenic phosphors: Albumen, chlorophylls, silk fibroin toward biohybrid white light-emitting diodes

White light-emitting diodes (WLEDs) integrating natural luminophores into hybrid architectures provide promising strategies for sustainable and stable lighting solutions. However, their fundamental emission mechanisms remain insufficiently explored. In this work, we successfully fabricated biohybrid WLEDs (BioHWLEDs) via layer-by-layer (LbL) assembly of biophosphor heterostructures composed of chlorophyll, albumen, and silk fibroin. Steady-state photoluminescence (PL) profile revealed enhanced and broadened chlorophyll emission with albumen incorporation. The albumen-chlorophyll LbL (Alb/Chl LbL) films exhibited strong PL-absorption spectral overlap indicative of the Förster-type resonant energy transfer (FRET). This mechanism was corroborated by time-resolved PL studies, obtaining an improved and quantified FRET efficiency of 52.96%. The resulting BioHWLEDs demonstrated an electrically tunable color output and further achieved near-pure white chromaticity coordinates (0.33, 0.30) after silk fibroin addition, alongside excellent operational stability. This study highlights the potential of structured biomaterials as eco-friendly phosphors for advancing tunable and solid-state lighting technologies.

Phycologically synthesized ZnO nanoparticles: Enhancing growth, nutrition, biochemical efficiency, and silk quality in the Bombyx mori L.

An experimental study on the effects of different strength training methods on smash performance and scoring in adolescent badminton players

An artificial intelligence optimized hepatic differentiation unveils NR5A2 and AP-1 transcriptional regulation in hepatic maturation

Liver transplantation (LT) in liver limited metastatic colorectal cancer (CRC): Insights and opportunities.

3608 Background: Liver transplantation (LT) for liver limited metastatic colorectal cancer (LL-mCRC) remains underutilized. Reasons for transplant ineligibility are not well described and the acceptance of this procedure for mCRC remains limited. Herein, we describe our initial experience with LT in patients with LL-mCRC. We characterize patient outcomes, characterize the pattern of failure for patients undergoing LT evaluation, and describe the prognostic implication of lymphadenectomy in LT evaluation. Methods: Patients with LL-mCRC potentially eligible for LT were identified, discussed in multidisciplinary tumor boards and liver transplantation clinics, and managed. The Weill Cornell Liver Transplant institutional database was queried to identify patients evaluated for LT, those who were transplanted, and those who were not. Demographic, surgical data, and clinical outcomes abstracted from medical record. Results: Between 7/2020 and 3/2025, 20 patients with LL-mCRC were evaluated for LT. Median age (range) 55 years (29-63); N=10 (50%) white; N=18 (90%) male. All had adenocarcinoma histology with N=14 (70%) left sided primary disease. At diagnosis, N=11 (55%) had ≥1 liver lesion >5.5cm and median CEA (range) was 200 (4.8-6945). The most common mutations were APC (60%), KRAS (55%), TP53 (45%), and PIK3CA (35%). N=6 (30%) had a LT with a median time from diagnosis to transplant of 23.7 months (mo) (range 16-42). The median overall survival (OS) from LT is 64.5 mo (range 22-87). N=5 (83%) are alive with a median follow up of 67 mo (range 22-87). N=3 patients had recurrent disease with a median time to recurrence of 3 mo (range 2-9), 2 in lungs, and 1 retrocrural lymph nodes. At this time, N=4 (67%) patients have no evidence of disease, and one with retrocrural lymph node disease is responding to treatment. The single patient who underwent LT and died was portal lymph node positive at the time of transplant and had an early recurrence (at 2 mo post-transplant). For the 14 patients who were evaluated for transplant, but did not undergo transplant, their mOS is 28 mo (range 13-44). Reasons why these patients did not undergo LT are shown in Table 1. The majority failed transplant evaluation due to progressive disease (lung 43%, liver 21%, abdomen 14%). Positive portal lymphadenectomy was a poor prognostic characteristic, with all 3 patients deceased. Conclusions: LT is a treatment option that confers durable remission and improved OS in LL-mCRC. Recurrent disease after transplant is generally controllable with local treatment modalities. Patient selection is critical in identifying appropriate LT candidates. Portal lymphadenectomy is prognostic and should be considered in all transplant evaluations. Not Transplanted N=14 New lung metastases 6 (43) Progression in liver 3 (21) Worsening liver function 2 (14) Progression in lymph nodes 1 (7) Peritoneal metastases at surgery 1 (7) Patient preference 1 (7)