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Listening, explaining, caring: Patient experience in an oncology primary care clinic background.

e13790 Background: Cancer survivors experience a range of late effects and long-term comorbid conditions due to shared risk factors and secondary effects of cancer treatment. An oncology primary care clinic at the University of Cincinnati Cancer Center was established in 2020 to address these unique needs of the survivorship population. The clinic's goal is to provide full-scope primary care services with special attention to addressing treatment-related effects, managing comorbid conditions, and screening for second primary malignancies. Methods: Patient experience data was collected using seven questions from the Consumer Assessment of Healthcare Providers and Systems (CHAPS) Clinician and Group Survey. Data reflects evaluation of three physicians and one nurse practitioner from April 2025-December 2025. The CHAPS is electronically sent to randomly selected patients seen in clinic, once every 90 days, and completion is optional with response options: Yes, definitely; Yes, somewhat; and No. Patients’ quotes were taken from the open response comments section. Among 175 patients responding, the average scores of patients who responded Yes, definitely are reported. Results: Patient experience scores were consistently high across most domains. Nearly all respondents reported positive interactions and felt providers explained in a way they could understand (98.85%), listened carefully (98.29%), gave easy-to-understand instructions (97.06%), knew important medical history (97.14%), showed respect (98.85%), and spent enough time in appointments (98.27%). Additionally, 99.43% indicated that providers had access to their medical records, especially important in the oncology primary care setting. However, office follow-up with test results (76.52%) was rated lower, highlighting an area for improvement. Patient qualitative feedback highlights exceptionally positive experiences with providers, emphasizing qualities such as compassion, thoroughness, attentiveness, and strong communication skills. Patients consistently describe feeling heard, respected, and well cared for, with providers taking time to listen, explain, and address concerns comprehensively. Providers are praised for managing complex conditions and fostering trust through clear communication and advocacy. Conclusions: Results reflect strong provider-patient relationships and exceptional quality of care. Feedback reflects high patient satisfaction and strong provider-patient relationships, essential components for optimal primary care of a complex patient population.

Expression of Concern: Unraveling candidate genomic regions responsible for delayed leaf senescence in rice

Biomedical and insecticidal efficacy of green synthesized nanoparticles from underexplored Tanzanian medicinal plants: A comparative study using Pueraria montana, Vernonia amygdalina, and Tephrosia vogelii

A Colloidal Quantum Dot Thermistor and Bolometer

ABSTRACT Bolometric detection offers a compelling route to room‐temperature mid‐ and long‐wave infrared (MWIR/LWIR) photodetection by measuring temperature‐induced conductivity changes in a thermistor element thermally coupled to an absorber. However, conventional thermistor materials such as vanadium oxide (VO x ) and amorphous silicon (a‐Si) exhibit moderate temperature coefficient of resistance (TCR) values (−2 to −3%/K). Higher TCRs have been achieved using SiGe/Si quantum wells (∼−5%/K), yet these require costly epitaxial growth and further improvements are hindered by lattice mismatch‐induced defects. Here, we report a novel thermistor platform based on colloidal quantum dots (CQDs) that circumvents these limitations by exploiting their lattice‐mismatch‐free nature. By tuning the size and surface chemistry of lead chalcogenide CQDs, we engineer the energetic potential landscape to modulate thermal activation energy, achieving TCR values of up to −9%/K. We further integrate this CQD thermistor with a plasmonic metamaterial absorber (PMA), enabling room‐temperature wavelength‐selective photodetection across the mid‐ to long‐wave infrared (MWIR/LWIR) spectrum. The bolometer detectors exhibited LWIR response with a time constant of ∼8 ms and room‐temperature detectivity approaching 10 6 Jones at 9 µm, without using microelectromechanical systems (MEMS) technology.

Circulating ACE2 levels and ACE I/D polymorphism in severe aortic stenosis

Structural basis for HIV-1 Rev recognition by the histone chaperone human Nap1

Spatial fractionated radiotherapy (SCART) remodeling of the tumor immune microenvironment and changes to ablative effects in murine models: Spatial transcriptomic and histopathologic evidence.

e15100 Background: Spatially fractionated radiotherapy (SFRT) delivers heterogeneous dose distributions to improve the therapeutic ratio. SCART (Spatially Compressed Ablative Radiotherapy), an advanced SFRT modality, offers physical advantages, but its immunobiological mechanisms remain poorly defined. This study evaluated SCART's effects on intratumoral immune architecture and ablative efficacy in a murine hepatocellular carcinoma model. Methods: Subcutaneous H22 tumors were established in BALB/c mice and treated when the short axis ≥10 mm and volume ≥700 mm³. Groups: SCART (21 Gy × 3 fractions; heterogeneous plan with central peak 21 Gy and peripheral valley 5 Gy), SBRT (uniform 21 Gy × 3), and single-fraction (21 Gy × 1). Tumors were collected 72 hours after treatment initiation. Histology (H&E) assessed necrosis and gross immune infiltration. High-definition spatial transcriptomics (0.5 μm resolution) profiled gene expression and cellular spatial organization. Analyses comprised differential expression, KEGG/GO enrichment, and spatial multimodal integration. CD45⁺/PTPRC⁺ immune populations were extracted, clustered by unsupervised machine learning, and annotated using SingleR plus AI-assisted marker- and literature-guided refinement to map immune cell distributions. Results: Baseline immune barrier: Spatial transcriptomics identified a native immune barrier at the tumor margin in untreated tumors, with fewer CD45⁺ cells at the periphery versus core—an effect not evident on H&E. Post-irradiation recruitment: SCART substantially increased peripheral immune-cell infiltration, especially at dose-gradient interfaces, exceeding the effect observed with SBRT. SCART versus SBRT: SCART elicited broader immune-activation gene programs and higher immune-cell infiltration density while reducing dose to adjacent normal tissues. The central high-dose SCART region produced effects comparable to SBRT; the intermediate- and low-dose regions of SCART represent critical intratumoral zones for immune responses. Fractionation benefit: The 21 Gy × 3 SCART regimen yielded superior 3D conformality relative to single-fraction irradiation. Conclusions: SCART remodels the spatial immune microenvironment by breaching peripheral immune barriers and promoting immune-cell recruitment, demonstrating superior immunomodulatory and ablative effects versus conventional SBRT. Fractionated SCART (21 Gy × 3) enhances conformality and central necrosis, indicating potential for reduced radiation energy requirements. These findings furnish combined immunological and dosimetric evidence to support the clinical translation of SCART.

Circulating HPV DNA for early detection of minimal residual disease after definitive therapy in oropharyngeal cancer: A phase II biomarker-driven study.

6069 Background: Persistent detection of circulating HPV DNA (cfHPVDNA) in plasma following definitive therapy for HPV-positive oropharyngeal squamous cell carcinoma (HPV+OPSCC) is strongly associated with inferior outcomes, including increased risk of relapse and distant metastasis, and defines a high-risk patient population. Immune checkpoint blockade targeting the PD-1 pathway has demonstrated clinically meaningful activity in both curative and palliative settings. We hypothesize that balstilimab, an anti–PD-1 antibody, can induce cfHPVDNA clearance in patients (pts) with persistent ctHPVDNA after definitive treatment and improve long-term disease control. Methods: Eligible pts had HPV+OPSCC, stage I–III per AJCC 8th edition (excluding T1–2N0 and T1–2N1 with lymph nodes <3 cm), and baseline ctHPVDNA (>20 copies/ml) per our institution digital droplet PCR assay. After completion of definitive standard-of-care therapy, ctHPVDNA was assessed at 3- and 6-months. Pts with positive ctHPVDNA test in the absence of radiographic evidence of disease were eligible to receive balstilimab (AGEN2034) at 3 mg/kg intravenously every 2 weeks for 6 months. The primary endpoint was cfHPVDNA clearance rate. Secondary endpoints included time to cfHPV DNA clearance, recurrence-free survival, overall survival, and safety. The study was designed to enroll up to 20 pts using a Bayesian optimal phase II design considering an expected clearance rate of 30%. In order to treat 20 pts, 140 pts would needed to be pre-screened with a baseline positive ctHPVDNA (15% of expected minimal residual disease). Results: A total of 168 pts were pre-screened, of whom 139 were eligible to proceed; disease stage was I, II, and III in 46% (N=64), 28% (N=39), and 26% (N=36) of pts, respectively. The median baseline ctHPVDNA level was 614 copies/mL (range, 26–239,111). A total of 130 of 139 pts had the 3-month ctHPVDNA assessment, as nine have been excluded (loss of follow-up or withdraw consent). Five had a positive ctHPVDNA result, all of whom had radiographic evidence of disease recurrence (3 local, 1 distant, and 1 both local and distant). Among the remaining 125 pts, 100 have completed the 6-month ctHPVDNA assessment. One pt had a positive ctHPVDNA result with radiographic evidence of local recurrence. One patient had a qualitative positive test (<20 copies/ml) without evidence of disease, but the following test prior to trial enrollment was negative. To date, no pts has been allocated to receive balstilimab. Conclusions: Persistent ctHPV DNA positivity without radiographic evidence of disease has not been observed following definitive therapy. These findings suggest that cfHPVDNA surveillance may have limited utility for early detection of minimal residual disease in this setting, thereby challenging the feasibility of ctHPVDNA–guided post-definitive intervention strategies. Clinical trial information: NCT05363709 .

Young-onset prostate cancer in the real world: A single-institution cohort of 126 patients diagnosed before age 55.

e17136 Background: Prostate cancer diagnosed before the age of 55 years is considered early-onset disease and represents a distinct clinical subgroup with limited real-world evidence. We report clinical characteristics, treatments, and outcomes of a large cohort of young patients treated at Instituto Oncológico Henry Moore (IOHM). Methods: All patients in the IOHM database with biopsy-confirmed prostate cancer diagnosed before age 55 between October 1, 2012, and October 1, 2025, were identified. Patients were followed in person or by telephone until death or January 2026. Clinical, pathological, treatment, and outcome data were analyzed. Results: Median age at biopsy was 51 years (range: 42-54). Diagnosis occurred through screening in 70 patients (55%) and due to symptoms in 56 (45%). Gleason scores were 6 (n = 51), 7 (n = 39), 8 (n = 14), 9 (n = 19), and 10 (n = 3). Disease stage at diagnosis was stage I in 48 patients, stage II in 39, stage III in 12, and stage IV in 27 patients (21%). A first-degree family history of prostate or breast cancer was present in 20 patients (15%). Fifty-two percent were current or former smokers, 30% had hypertension, and 31% were obese (BMI > 30). Three patients with stage I Gleason 6 disease opted for active surveillance. Radical prostatectomy was performed in 63 patients and radiotherapy in 25 patients. All patients received systemic therapy (hormonal therapy with or without chemotherapy) according to ASCO and NCCN guidelines. Median follow-up was 64 months (range: 2-169). Median time to progression and overall survival decreased with advancing stage, with stage IV patients showing 29 and 38 months, respectively. Recurrence after radical prostatectomy occurred in 21 of 63 patients (33%). Overall survival did not differ by mode of detection or initial local treatment. Table 1 shows the evolution of patient population by stage. Conclusions: 1. This represents the largest single-institution cohort of young patients with prostate cancer reported in Argentina. 2. Twenty of 126 patients (15%) had a first-degree family history of prostate or breast cancer. 3. In 70 patients (55%), the tumor was detected through screening. 4. Sixty-three of 99 patients with early-stage tumors (63%) were treated surgically. 5. Only 3 of 32 patients with stage I, Gleason 6 disease opted for active surveillance. 6. Time to progression and estimated survival in young patients with advanced tumors treated according to current recommendations are very short, highlighting the need for more effective therapeutic strategies for this patient population. Patient population evolution by stage. Characteristic Stage I Stage II Stage III Stage IV Total patients 48 39 12 27 Pt with disease progression 8 16 4 20 Deaths 4 3 3 19 Estimated time to progression (months), Kaplan-Meier 146 113 108 29 Estimated overall survival (months), Kaplan-Meier 169 150 120 38

Management of chemotherapy-induced adverse events in patients with metastatic pancreatic ductal adenocarcinoma: A US-based modified Delphi consensus.

e16400 Background: Metastatic pancreatic ductal adenocarcinoma (mPDAC) is an aggressive malignancy with poor prognosis. Chemotherapy (CTX) regimens, including irinotecan-based combinations, are the mainstay for patients with mPDAC; however, these are linked with adverse events (AEs) that may compromise clinical outcomes. Although management strategies for CTX-induced AEs are available, their application in US clinical practice is inconsistent. To address this gap, a modified Delphi consensus process was undertaken. Methods: A US-based modified Delphi consensus process was conducted to develop evidence-based guidance statements for managing and mitigating CTX-induced AEs in patients with mPDAC. The process included 25 experts (gastrointestinal oncologists and oncology nurses), organized into a 21-member Delphi panel and 4-member steering committee (SC). All had ≥ 3 years of experience in pancreatic cancer care; SC members also had ≥ 3 years of experience in liposomal irinotecan-based regimens. Draft statements, informed by published evidence and expert insight, were anonymously refined and approved by the SC, then voted on anonymously by the Delphi panel for up to three rounds. At each round, panellists indicated their level of agreement for each statement via a 5-point Likert scale, and could provide feedback for any they disagreed with. Consensus was defined a priori as any statement achieving ≥ 50% response and ≥ 80% agreement within a voting round. Non-consensus statements were anonymously revised by the SC based on panellist feedback and reintroduced in the next round. Results: Consensus was reached for all 25 draft statements that entered the first voting round (participation rate: 85.7%; agreement range: 82.4–100.0%), eliminating the need for further rounds. These statements, covering 7 thematic areas, include recommendations on pre-treatment assessment, patient and caregiver education, proactive management of diarrhea, nausea and vomiting, neutropenia, and neuropathy, as well as individualized approaches for higher-risk groups. For example, one diarrhea-specific statement recommends that patients with mPDAC and their caregivers receive at-home antidiarrheals with clear usage instructions, report the first loose stool, track symptoms for review, and follow reinforced dietary guidance. The statements also identify evidence gaps and priorities for future research, including the need to address disparities in AE recognition, reporting, and management. Conclusions: These statements, developed by a multidisciplinary panel of experts, provide practical guidance to optimize care for patients with mPDAC by improving consistency in managing CTX-induced AEs. Although US-based, these recommendations may be relevant to other regions.

Trends and disparities in pancreatic carcinoma mortality among adults with type 2 diabetes mellitus in the United States: A CDC-based retrospective analysis (2000-2023).

e16418 Background: Type 2 Diabetes Mellitus is a potent risk factor for pancreatic cancer, which remains the leading cause of mortality in the United States (US). In type 2 diabetes mellitus, insulin resistance and elevated circulating insulin levels fuel tumor growth. Despite development in preventive measures and strategies, a substantial proportion of U.S. adults is diabetic. These conditions contribute to pancreatic carcinoma. This study aims to evaluate mortality trends associated with pancreatic carcinoma in type 2 diabetic patients in the United States (US) and to identify the affected population. Methods: Data for this study were obtained from the CDC WONDER database, which provides detailed information on causes of death across the United States. Mortality data related to pancreatic carcinoma in individuals with type 2 diabetes were analysed. Age-adjusted mortality rates (AAMRs) were estimated, and mortality trends were analysed using JoinPoint regression to determine the annual percent change (APC). Results: From 2000 to 2023, a total of 26007 deaths were linked to pancreatic carcinoma with type 2 diabetes as a contributing factor. The AAMRs increased from 2.39 in 2000 to 7.97 in 2023, showing a 3.3-fold increase in mortality. A pronounced rise was observed during the COVID-19 pandemic, with the AAMR reaching 6.77 and an APC of 8.07. Males experienced higher mortality rates compared to females (9.9 vs 6.37 in 2023). Among racial and ethnic groups, Non-Hispanic (NH) Black or African American individuals had the highest average AAMR, followed by Hispanic individuals, NH White individuals and lastly NH other populations. Geographically, the West, among census regions, had the highest AAMR, and rural areas had higher mortality rates compared to urban areas. Conclusions: This study reveals an alarming 3.3-fold increase in type 2 diabetes-related pancreatic cancer mortality in the United States from 2000 to 2023. Significant disparities were observed, with higher mortality rates among males, Non-Hispanic Black or African American populations, West residents, and rural communities. These findings highlight the urgent need for targeted public health strategies, enhanced diabetes awareness and equitable access to cancer screening and preventive care to reduce rising pancreatic cancer mortality.

Baseline corticosteroid use and outcomes in non–small cell lung cancer patients receiving immune checkpoint inhibitors, stratified by indication.

11184 Background: Baseline systemic corticosteroids are often prescribed to patients with non-small cell lung cancer (NSCLC) initiating immune checkpoint inhibitors (ICIs). Prior studies associating steroids with reduced ICI efficacy have largely treated steroid exposure as binary without accounting for indication. We evaluated outcomes following baseline steroid use by indication. Methods: We conducted a retrospective cohort study using TriNetX, a federated research network of de-identified electronic medical records. Using approximately 7,000-12,000 patients per stratum, NSCLC patients initiating ICIs were stratified by presence of systemic steroid prescriptions within 30 days prior to ICI initiation by indication: brain metastases (BM), pulmonary disease (PD), autoimmune disease (AI), and palliative indications (PI). In each stratum, steroid-exposed patients were compared with propensity-matched steroid-naive controls adjusting for demographics, non-brain metastases, comorbidities, substance use, and prior cancer treatments. Outcomes included mortality, ICU admission, and infection at 1 month. Results: Baseline steroid use was associated with worse 1 month outcomes in an indication dependent manner. Among patients receiving steroids for BM, mortality was higher compared with controls (8.75% vs 5.46%; HR 1.62, 95% CI 1.44-1.82; p < 0.001), as were ICU admission (5.06% vs 2.80%; RR 1.81, 95% CI 1.53-2.14; p < 0.001) and infection (6.81% vs 4.20%; RR 1.62, 95% CI 1.40-1.88; p < 0.001). Similarly, among patients receiving steroids for PI, steroid use was associated with increased mortality (9.68% vs 5.29%; HR 1.87, 95% CI 1.69-2.06; p < 0.001), ICU admission (4.83% vs 2.65%; RR 1.82, 95% CI 1.57-2.12; p < 0.001), and infection (7.50% vs 4.21%; RR 1.78, 95% CI 1.56-2.03; p < 0.001). In contrast, steroid use for PD or AI was not associated with increased mortality. PD was associated with higher ICU admission (3.35% vs 2.61%; RR 1.29, 95% CI 1.10-1.51; p = 0.0027) and infection (6.31% vs 4.23%; RR 1.49, 95% CI 1.31-1.70; p < 0.001), while AI was associated with increased ICU admission (3.63% vs 2.68%; RR 1.36, 95% CI 1.11-1.65; p = 0.0039) but not increased infection risk. These survival patterns persisted at longer follow-up, with higher mortality among patients with BM and PI at 6 months (BM HR 1.40, 95% CI 1.32-1.48; p < 0.001; PI HR 1.40, 95% CI 1.33-1.47; p < 0.001), 1 year (BM HR 1.40, 95% CI 1.33-1.47; p < 0.001; PI HR 1.36, 95% CI 1.31-1.42; p < 0.001), and 5 years (BM HR 1.30, 95% CI 1.24-1.35; p < 0.001; PI HR 1.32, 95% CI 1.27-1.37; p < 0.001), while no long-term survival decrement was observed for PD or AI. Conclusions: Baseline steroid use prior to ICI initiation is associated with increased early and long-term mortality in NSCLC in BM and PI but not PD and AI. Accounting for clinical indication is important to understand real-world ICI outcomes of patients using steroids.

Trends in biosimilar bevacizumab adoption and Medicare spending by socioeconomic deprivation and rurality, 2019-2023.

1529 Background: Biosimilar bevacizumab has the potential to reduce oncology drug spending, but the equity of its real-world adoption across socioeconomic and geographic contexts remains uncertain. Methods: We analyzed Medicare Part B provider-year claims from 2019-2023 for bevacizumab administrations. Biosimilar adoption was defined as the proportion of total bevacizumab services delivered as biosimilars. Neighborhood socioeconomic deprivation was measured using Area Deprivation Index (ADI) quintiles (Q1=least deprived; Q5=most deprived). Rurality was classified using provider-level Rural-Urban Commuting Area (RUCA) codes available in Medicare Part B, with urban defined as RUCA 1-3 and non-urban as RUCA ≥4. Adoption patterns were compared using chi-square tests for categorical outcomes and independent t-tests for spending measures. Temporal trends in adoption by ADI quintile were compared using logistic regression with Year × ADI interaction terms to test whether adoption trajectories diverged over time. Statistical significance was defined as p<0.05. Results: The study included 11,803 provider-year observations. Biosimilar market share increased from 0.5% of services in 2019 to 61.3% in 2023. In 2023, biosimilar adoption differed significantly by ADI quintile (p=0.0004), ranging from 55.7% in ADI Q4 to 81.3% in the most deprived quintile (Q5), patterns that may reflect institutional purchasing or practice-level factors rather than patient-level access alone. Adoption was higher in urban compared with non-urban areas (62.0% vs 33.6%, p=0.002), despite no baseline differences in 2019. Biosimilars were less expensive than originator bevacizumab in all years (all p<0.001). Mean per-administration savings increased from $8.03 (10.3%) in 2019 to $36.4 (52.2%) in 2023 (p=0.001). Originator prices did not differ by ADI in 2023 (p=0.58). Conclusions: Biosimilar bevacizumab adoption expanded rapidly and generated increasing Medicare savings, but uptake varied by socioeconomic deprivation and rurality. Differences in adoption, rather than pricing, appear to drive inequities in realized savings. Targeted policy strategies may be needed to promote equitable biosimilar diffusion in oncology care. Biosimilar bevacizumab adoption in 2023 by socioeconomic deprivation and rurality. Category Biosimilar share of services (%) ADI Q1 (least deprived) 58.1 ADI Q2 61.1 ADI Q3 61.7 ADI Q4 55.7 ADI Q5 (most deprived) 81.3 Urban 62.0 Non-urban 33.6

Young breast cancer patients and molecular reclassification using RNA-sequencing.

e12591 Background: Choice of breast cancer (BC) treatment is to a large extent based on immunohistochemistry (IHC) subtyping. Often genomically driven, young BC patients have a large proportion of non-luminal subtypes and unfavorable clinicopathologic profiles. In addition, a higher discordance between IHC and molecular BC subtyping has been shown in young BC patients. RNA-based classifiers may more accurately characterize the tumor biology. This study was conducted in Ethiopia, a Low-Income Country (LIC) in Eastern Africa. Here, almost all of the biomarker decision is based on histopathology and IHC. The aim of the study was to compare histopathology and IHC with RNA based classification of breast cancer in Ethiopia. Methods: This is a cross-sectional prospective cohort of 50 BC patients between the age of 18 and 39 enrolled between February 2021 and September 2023 at Tikur Anbessa Specialized Hospital (TASH), Ethiopia. Fresh frozen tissue samples were used for RNA extraction and RNA-sequencing. BC intrinsic subtypes were classified as Luminal A, Luminal B, HER2-enriched, and Basal using the SCAN-B, and as Luminal A-like, Luminal B-like, HER2-positive, and triple negative BC (TNBC), based on IHC method, which was available for 43 samples. The results between the two approaches were compared. Results: RNA based classification revealed a high-grade tumor in 84% while only 36% of the patients were classified as high-grade using histologic diagnosis. A higher proportion of HER2-enriched tumors were found (36%) using RNA-sequencing compared to the IHC (11.6%). Moreover, there was a high discordance in Luminal B classification between RNA classification (28%) and the IHC (53.5%) technique. Many of the tumors classified as Luminal B-like by IHC were molecularly HER2-enriched, accounting for 40% of the classification difference. Conclusions: In this cohort of young BC patients, we found a significant discordance between IHC and molecular subtyping. RNA-sequencing revealed a substantially higher proportion of biologically aggressive tumor than the conventional histopathology and IHC classification. High-grade tumors were markedly underestimated by histopathology and IHC compared with RNA-sequencing. The discordance was mainly observed for Luminal B and HER2-enriched BC. The differences seen in the study may be explained by several factors, including the young age of the patients, tissue type, preanalytical issues affecting IHC, and an obvious fundamental methodological difference between the two approaches, that might have a potential clinical implication. In LIC, where IHC plays a vital role in BC management and where a high proportion of patients are young, reliance on IHC classification may miss a considerable proportion of biologically aggressive diseases. Therefore, RNA-based molecular diagnostic approaches may offer an added value for a portion of selected BC patients in LMICs like Ethiopia.

MicroRNAs as surrogate biomarkers of future endometrial malignancy in women with endometrial hyperplasia without atypia and an open-label randomized trial of metformin, weight control, and exercise intervention.

5622 Background: Endometrial hyperplasia (EH) is regarded as an endometrial cancer (EC) precursor. The severity of atypia reflects risk of future EC. According to Kurman et al., the risk of progression to EC was < 1% in simple hyperplasia (SH) and 3% in complex hyperplasia (CH) without atypia (non-A). Our group previously identified 4 MicroRNAs (MiRs) and PTEN by immunohistochemistry stain are significant risk biomarkers of future endometrial malignancy. Methods: This prospective open-label randomized controlled study enrolled a total of 60 patients SH/CH non-A. All participants were randomized 1:1 to with or without metformin intervention and received education for exercise and weight control. A stratification of body mass index was performed, but not for HbA1C. PTEN immunohistochemistry stain and MiR profiles of the endometrial tissue were analyzed. Results: 57 participants were eligible for analysis. After all the participants had been followed up for 3 years, an analysis was performed in which 3 with progression to atypical hyperplasia and 6 with recurrent SH/CH non-A were observed. Exercise intensity was inversely correlated with use of metformin or not (p = 0.028). The predicting progression/recurrence by any of the 4 miRs (miR30a-3p, miR141, miR-200a, and miR200b) were all significant (p < 0.05). PTEN expression, metformin, exercise, or body weight control intervention did not alter the risk of EH recurrence/EC progression. Metformin group has a trend of decreased risk of progression/recurrence yet not significant (p = 0.291). The decreased impact of metformin may be partly related to their lower intensity of exercise as compared to no-metformin group. Impact of interventions may need longer observation. Conclusions: Presence of any of the 4 miRs (miR30a-3p, miR141, miR-200a, and miR200b) seem related to risk of recurrence/progression of SH/CH non-A, while PTEN expression, metformin, exercise, and weight control are not, in our prospective cohort. Clinical trial information: NCT05292573 .

Long term follow-up results and prognosis analysis of TPF regimen chrono-chemotherapy combined with cisplatin concurrent chemoradiotherapy for the treatment of distant nasopharyngeal carcinoma.

e18034 Background: To research whether TPF (Docetaxel plus Fluorouracil plus Cisplatin) chrono-chemotherapy combined with cisplatin concurrent chemoradiotherapy can reduce long-term toxicity without affecting the survival of patients with de novo metastatic nasopharyngeal carcinoma (mNPC) compared with conventional chemotherapy combined with cisplatin concurrent chemoradiotherapy. Methods: A retrospective analysis of the clinical data of 121 de novo mNPC patients who treated with TPF chemotherapy at our hospital from January 1, 2012, to December 31, 2018. Among them, 79 patients were treated with chrono-chemotherapy and 42 patients were treated with conventional chemotherapy. The specific chemotherapy regimen for chrono-chemotherapy group:TPF induction chemotherapy for 2-4 cycles, docetaxel: 75mg/m2, ivgtt, d1; Cisplatin: 75mg/m2, civ, d1-5, 60h (10Am—10Pm); 5-Fluorouracil: 750mg/m2/d, civ, administered by intravenous infusion of electronic chemotherapy automatic injection pump d1-5, 60 hours (10 Pm-10 Am), 21 days/cycle. The evaluation of therapeutic efficacy after induction should involve intensity-modulated radiotherapy for at least patients with stable disease, during which concurrent cisplatin chemotherapy is administered. Two cycles of adjuvant chemotherapy were administered 1 month after radiotherapy with the same regimen as induction chemotherapy. The total chemotherapy cycle was 4-6 cycles. The Kaplan-Meier method and log-rank test were used to estimate overall survival (OS) and progression-free survival (PFS), while the COX proportional hazards model was employed for multivariate analysis. Long-term toxic side effects between the two groups were assessed using the chi-square test or Mann-Whitney U test. Propensity score matching was utilized to address confounding factors. Results: At a median follow-up of 104 months, 69.6% of patients died in the chrono-chemotherapy group and 73.8% in the conventional chemotherapy group, and the median OS and PFS in the chrono-chemotherapy group and conventional chemotherapy group were 40 vs 32 months (P=0.636) and 30 vs 19 months, respectively (P=0. 975), there were no statistically significant differences in OS rates and PFS rates at 3, 5, and 7 years between the two groups before and after matching. The incidence of xerostomia, dysphagia, and trismus in the chrono-chemotherapy group matched for timing was significantly lower than that in the conventional chemotherapy group, with a statistically significant difference. (P<0.05). Conclusions: The TPF chrono-chemotherapy combined with cisplatin concurrent chemoradiotherapy reduces the incidence of toxic side effects while ensuring survival, which can benefit patients.

Real-world analysis of the association between new-onset depression and outcomes in metastatic breast cancer.

1117 Background: Depression is prevalent in patients with advanced cancers and it may influence the disease course and treatment. While depression is associated with worse survival in solid tumors, real-world data quantifying its impact on mortality and healthcare utilization patterns in metastatic breast cancer (MBC) are limited. We utilized a global de-identified database to evaluate the association of new-onset depression with overall survival (OS) and care utilization. Methods: We conducted a retrospective cohort study using the TriNetX global network. We identified adult women with MBC and survival greater than 6 months from diagnosis. Two cohorts were defined: (1) patients with first instance of depression 1-month to 3-years after MBC diagnosis, and (2) patients without depression before or during this period. Propensity score matching was performed (1:1) to balance baseline demographics, comorbidities, tumor receptor status, and previous cancer therapies. Outcomes included OS, palliative care utilization, ED visits, and Inpatient Hospitalizations over follow-up of 5 years. Results: We matched 2,753 patients per cohort with well-balanced baseline characteristics (mean age 60.1 ± 13.2 years). Depression was associated with shorter median OS (1,703 days vs not reached; HR 1.28, 95% CI 1.17–1.40, p<0.001) and 6.7% absolute increase in mortality risk (38.1% vs 31.4%). Patients with depression demonstrated significantly higher care utilization: with increased hospitalization (HR 1.52, CI 1.39–1.67), increased ED Visits (HR 1.41, 95% CI 1.30–1.52), and increased use of palliative care visits (HR 1.65, 95% CI 1.49–1.83). Subgroup analysis showed that those treated with common anti-depressants had lower median OS and higher care utilization, with a larger effect size and more statistical significance for SSRIs than SNRIs. Conclusions: In this large real-world cohort, new-onset depression in women with MBC was associated with significantly worse survival and increased emergency department, inpatient, and palliative care utilization. This finding may suggest a higher symptom burden or earlier recognition of complex needs. Exposure to common antidepressants was associated with lower OS and higher healthcare utilization, which may suggest residual confounding in the form of depression severity or MBC disease burden. Prospective studies are needed to further understand this relationship. These findings underscore the critical need for integrated psychosocial oncology screening.

Galeterone and gemcitabine in advanced pancreatic ductal adenocarcinoma.

e16433 Background: Advanced pancreatic cancer (PC) has limited chemotherapeutic options and a dismal prognosis. Mutant KRAS, present in 90% of cases, activates the MAPK and PI3K pathways, driving chemoresistance and metastatic spread (PMID 40829181). In pre-clinical work, galeterone (GAL), a novel steroidal anti-androgen, alone or combined with gemcitabine (GEM) depleted pan-KRAS and critical mediators of the eukaryotic translational initiation complex, and inhibited MiaPaca-2 xenograft growth (PMID 28881737). In a phase 2 multi-arm trial in patients with advanced PC, GAL monotherapy was tolerable but minimally effective. We herein report results from the GAL plus GEM arm. Methods: Patients with locally advanced or metastatic PC who progressed after at least 1 prior line of systemic therapy were eligible. Galeterone was administered orally at 2550mg daily and gemcitabine intravenously at 1000mg/m2 weekly for 3 weeks on 28-day cycle. The primary endpoint was radiographic response rate per RECIST v1.1, and secondary endpoints included progression-free survival, overall survival (OS) and adverse events (AEs). We used a Simon’s optimal two-stage design with a null hypothesis of P 0 = 0.05 and one-sided alternative of P 1 = 0.20 with an early stopping rule for futility. The study closed after enrollment of 9 patients due to sponsor withdrawal of funding. Results: The median age of enrolled patients was 66 (range 48-69). Six were male and 3 were female. Four patients were White, 2 were Black, 1 Asian, and 2 with unknown race. Eight identified as non-Hispanic and 1 as Hispanic. Five out of 9 patients withdrew before the 1 st radiographic assessment; 2 transitioned to hospice due to progressive PC, 1 died due to PC, 1 withdrew after treatment-unrelated stroke, and 1 withdrew due to nausea possibly related to treatment. Most (8/9) received 2 prior lines of therapy. For the 4 evaluable patients, 3 had stable disease at the 1 st 8-week assessment and 1 patient had partial response. Stable disease duration ranged from 2.3 to 7.7 months. The partial response lasted 9.2 months. Median time on treatment for all enrolled patients was 1.2 months, and median OS was 3.3 months (range 0.6 – 14.2). Treatment-related AEs (TRAEs) for GAL were mostly grade 1-2 and included fatigue, nausea, vomiting and dizziness; 2 patients experienced grade 3 fatigue. There were no new or unexpected safety signals with gemcitabine. Five patients required dose-reduction of gemcitabine due to hematologic toxicity. Conclusions: GAL plus GEM was overall well-tolerated but with limited efficacy in an all-comer population. Two participants however with prior progression on GEM had prolonged disease control with this regimen suggesting a signal of efficacy in a subset of patients. Future work aims to evaluate more potent GAL analogues and develop predictive biomarkers for response with a focus on its ability to inhibit RAS signaling and the translational initiation complex. Clinical trial information: NCT04098081 .

Frailty phenotypes and acute care escalation in hospitalized patients with solid tumors: A National Inpatient Sample analysis, 2016–2023.

e23202 Background: Frailty-aware oncology is increasingly emphasized, yet inpatient frailty is inconsistently captured and often reduced to single markers. Whether cumulative multi-domain frailty burden predicts inpatient outcomes among hospitalized patients with solid tumors remains unclear. Methods: A survey-weighted analysis of the National Inpatient Sample (NIS), 2016–2023, was performed. Adult hospitalizations with solid tumor malignancies (ICD-10-CM C00–C80) were included. Hematologic malignancies (C81–C96) and palliative care encounters (Z51.5) were excluded. Frailty proxies included malnutrition (E43/E44/E46), cachexia or weight loss (R64), sarcopenia (M62.84), dysphagia (R13*), and pressure ulcer (L89*). Frailty burden was categorized as 0, 1, 2, or ≥3 domains. The primary outcome was in-hospital mortality. Secondary outcomes included any airway escalation (mechanical ventilation or tracheostomy), shock (R57*), length of stay (LOS), and hospitalization cost. Survey-weighted multivariable logistic regression estimated adjusted odds ratios (aORs) with 95% confidence intervals (CIs). LOS and cost were modeled using survey-weighted linear and gamma regression. Results: Among 3,046,500 unweighted solid tumor hospitalizations (weighted subpopulation size 15,232,496), frailty burden distribution was: 0 domains 79.46% (95% CI 79.32–79.61), 1 domain 16.46% (95% CI 16.34–16.57), 2 domains 3.61% (95% CI 3.57–3.65), and ≥3 domains 0.48%(95% CI 0.47–0.49). Unadjusted mortality increased stepwise with frailty burden from 2.02% (95% CI 1.99–2.05) to 9.81% (95% CI 9.31–10.33), and airway escalation from 2.60% (95% CI 2.57–2.63) to 11.50% (95% CI 10.98–12.05). LOS increased from 5.00 days (95% CI 4.99–5.02)to 11.52 days (95% CI 11.29–11.75), and mean cost from $20,943.82 (95% CI $20,532.55–$21,355.09) to $35,440.96 (95% CI $34,009.64–$36,872.28). After adjustment, frailty burden remained strongly associated with mortality (1 domain aOR 2.08, 95% CI 2.04–2.12; 2 domains aOR 3.14, 95% CI 3.04–3.25; ≥3 domains aOR 4.18, 95% CI 3.91–4.47) and airway escalation (1 domain aOR 2.58, 95% CI 2.53–2.63; 2 domains aOR 3.77, 95% CI 3.66–3.88; ≥3 domains aOR 4.69, 95% CI 4.41–4.98). In phenotype-specific models, malnutrition (aOR 1.86, 95% CI 1.82–1.90) and pressure ulcer (aOR 2.25, 95% CI 2.17–2.34) were the strongest predictors of mortality, while dysphagia was most strongly associated with airway escalation (aOR 2.98, 95% CI 2.91–3.06). Conclusions: In nationally representative solid tumor hospitalizations, cumulative multi-domain frailty burden identifies stepwise risk for inpatient mortality, acute care escalation, LOS, and cost. Frailty phenotyping using routinely coded inpatient markers may support earlier multidisciplinary assessment and inform risk-adjusted inpatient oncology care pathways.

Efficacy and safety of pralsetinib in advanced or metastatic <i>RET</i> -altered thyroid cancer (TC): Final analysis of the phase 1/2 ARROW study.

6028 Background: RET alterations are targetable oncogenic drivers in multiple solid tumors and TCs. Pralsetinib is an oral, potent, selective RET inhibitor granted accelerated approval by the FDA for adults and children aged ≥12 y with advanced/metastatic RET fusion-positive TC who require systemic therapy and are radioactive iodine-refractory, based on ARROW trial (NCT03037385) results. Accelerated approval for medullary TC (MTC) was withdrawn by the sponsor in 2023 due to recruitment challenges in the confirmatory trial. We report final efficacy and safety in ARROW patients with RET -altered TC and MTC. Methods: Phase 2 ARROW patients were enrolled from 84 sites in 13 countries. Primary end points were overall response rate (ORR; per RECIST v1.1) and safety. Progression-free survival (PFS), overall survival (OS), and safety were assessed in patients with advanced/metastatic TC and MTC who received ≥1 dose of pralsetinib (Efficacy Population [EP]). ORR and duration of response (DOR) were assessed in the Measurable Disease Population (MDP). Results: At the May 20, 2024, data lock, 28 patients with RET -altered TC and prior systemic treatment and 145 patients with RET -altered MTC received pralsetinib 400 mg/d (median treatment duration: 24.7 mo [TC]; and 35.4 mo [MTC]). In the TC and MTC groups, median age was 58 and 57 y; 39% and 64% were male; median (range) prior lines of treatment was 2 (1, 9) and 1 (1, 6). 53.8% of MTC patients had prior systemic treatment. In TC and MTC patients, ORRs (95% CI) were 91.7% (73.0, 99.0) and 68.2% (59.5, 76.0) (Table). Treatment-related adverse events (TRAEs) occurred in 27 (96%) TC and 142 (98%) MTC patients; 68% and 67% had grade ≥3. TRAEs in ≥35% of TC and MTC patients were increased AST (50% and 38%) and ALT (43% and 30%), decreased white blood cell count (39% and 30%), and anemia (39% each). Death due to a TRAE occurred in 1 TC patient (liver injury) and 1 MTC patient (pneumonia). Safety was consistent with prior reports. Conclusions: The final analysis of ARROW confirms that pralsetinib yields clinically meaningful and durable responses in patients with RET -altered TC and MTC with a manageable safety profile consistent with prior reports. Clinical trial information: NCT03037385 . Efficacy summary. All MTC MTCPrior Cabozantinib/Vandetanib MTC Treatment-Naïve TCPrior Systemic Treatment MDP, n 132 60 62 24 ORR, % (95% CI) 68.2(59.5, 76.0) 56.7(43.2, 69.4) 79.0(66.8, 88.3) 91.7(73.0, 99.0) Complete response, n (%) 12 (9.1) 2 (3.3) 7 (11.3) 4 (16.7) Partial response, n (%) 78 (59.1) 32 (53.3) 42 (67.7) 18 (75.0) DOR, median, mo (95% CI) 39.6(29.4, NE) 21.7(15.1, 34.8) NR(36.8, NE) NR(16.0, NE) DOR follow-up, median, mo (95% CI) 45.7(41.0, 48.4) 48.9(36.9, 58.7) 45.1(40.4, 47.8) 35.4(26.9, 40.0) EP, n 145 67 67 28 OS, median, mo (95% CI) NR(54.6, NE) 42.2(31.2, NE) NR(NE, NE) NR(25.4, NE) PFS, median, mo (95% CI) 37.2(27.5, 55.5) 24.9(19.9, 35.0) 55.3(36.8, NE) NR(14.7, NE) NE, not evaluable; NR, not reached.