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Overcoming resolution constraints in automated colony counting via a high-performance deep learning framework using SAHI

Soft Ionic and Electronic Triboelectric Nanogenerators: Toward Attachable and Implantable Biomedical Applications

ABSTRACT The growing societal demand for convenient and personalized healthcare solutions has driven significant progress in human‐interactive technologies. Soft electronics, with their extrinsic deformability, have sparked innovations in the design of stretchable and highly adaptable biomedical devices that enhance wearability. Despite these advancements, portable power sources remain a key limitation, constrained by short operating times and the inconvenience of frequent recharging or battery replacement. To overcome this hurdle, triboelectric nanogenerators (TENGs), which convert mechanical energy into electricity, have emerged as promising sustainable power sources, offering high efficiency, lightweight design, and self‐sustaining operation. Recent developments in integrating TENGs with ionic materials have enabled their use on or beneath the skin, allowing the harvesting of biomechanical energy that would otherwise be wasted to power healthcare devices. This review provides a comprehensive overview of attachable and implantable TENGs, classified by electronic and ionic materials, and examines their material choices, device structures, and operational mechanisms. This review further explores various sustainable biomedical applications, assessing the performance of these devices in both sustainable power sources and self‐powered physiological signal sensing. Finally, key future research directions are outlined, including sweat tolerance, skin compliance, AI‐enabled TENG biointerfaces, acoustic transparency, minimally invasive implantation strategies, and regulatory considerations for clinical translation.

Binding of RbFox proteins at weak 5’splice site of A2 induces its alternative splicing in non-muscle myosin heavy-chain IIA mRNA

Risk of venous thromboembolism in resectable non-small cell lung cancer treated with neoadjuvant and adjuvant immunotherapy: A self-controlled case series.

e20100 Background: In October 2021, atezolizumab was approved for adjuvant treatment of non–small cell lung cancer (NSCLC) with PD-L1 expression ≥1%. Since then, pembrolizumab and nivolumab have also been approved for neoadjuvant and adjuvant treatment in resectable NSCLC. The approval of immunotherapy (IO) to treat NSCLC has increased survival and improved outcomes in this population. However, the relationship between IO and VTE risk remains incompletely characterized. Here, we studied the risk of VTE in patients with resectable NSCLC receiving PD-1 or PD-L1 inhibitors in the neoadjuvant and adjuvant settings. Methods: We conducted a retrospective study at an urban academic center that included patients with resectable NSCLC who received neoadjuvant or adjuvant PD-1 or PD-L1 inhibitors between January 2022 and December 2025. Statistical analyses were performed using GraphPad Prism (10.6.1) and IBM SPSS Statistics (30.0.0). Fisher’s Exact and t-test analyses were conducted as indicated. This study utilized a self-controlled case series design in which each patient served as their own control to minimize confounding factors. A control window of one year prior to IO initiation was compared with a risk window of the year following initiation. Results: Twenty-six patients were included who received PD-1 or PD-L1 inhibitors in the neoadjuvant or adjuvant setting. VTE occurred in 11.5% of patients after IO initiation. Incidence of VTE following IO had an incidence rate ratio of 1.5, with incidence rate of 7.69 per 100 person-years prior to IO and 11.54 per 100 person-years following start of IO. The mean time to VTE was 267 (SD = 64.26) days. Though not reaching statistical significance, patients with neoadjuvant IO exposure had higher odds of VTE development compared to those with adjuvant exposure (OR = 9.50; 95% CI [0.83, 142.60]; p = 0.123). Average Khorana score (KS) in those without VTE development was 1.48 (SD = 0.67) while average KS in those who developed VTE was 2.33 (SD = 1.53). Conclusions: This study is novel in its exploration of VTE incidence in NSCLC treated with neoadjuvant or adjuvant IO. The rate of VTE development in this study was consistent with previously reported real-world VTE incidence (between 6% to 13%) in NSCLC patients with platinum-based doublet chemotherapy, but higher than reported VTE rate in major phase 3 clinical trials (between 2% to 4%). These results suggest a signal between neoadjuvant IO use and increased VTE risk which warrants further investigation in a larger prospective study. Additionally, the results demonstrate that utilization of KS could assist in identification of patients at higher risk for VTE development in this population. Future studies are needed to assess whether those at highest risk for VTE development may benefit from thromboprophylaxis prior to IO initiation.

Net costs associated with inpatient (IP) administration of step-up dosing (SUD) of bispecific antibodies (bsAbs) among Medicare patients (pts) with relapsed/refractory multiple myeloma (MM).

e19504 Background: Initiation of bsAbs requires SUD with close monitoring, typically in IP settings, to mitigate early toxicities. As bsAb use expands, it is crucial to understand the financial viability for administering bsAbs, particularly non–PPS-exempt hospitals paid via a capitated, DRG-based method where costs may exceed payout. We compared net costs and payments for Medicare pts initiating bsAbs in the IP setting at non-PPS-exempt hospitals and explored cost variations for hospital characteristics and adverse events (AEs). Methods: Using Medicare FFS Parts A/B claims (10/25/21–10/20/24), pts ≥65 years with MM, IP bsAb initiation, and 12 mos continuous pre-index coverage were identified. Pts receiving other MM therapies <30 days post-index or treated in PPS-exempt hospitals were excluded. Hospital costs were estimated by applying revenue center–specific Medicare cost–charge ratios from CMS Hospital Cost Reports to IP facility charges. Outpatient (OP) bsAb costs were estimated using ASP/unit administered/wasted at the time of the claim. Costs for other OP services were estimated using revenue center–specific cost–charge ratios. Medicare payments were defined as total allowed amounts on IP and OP claims, and net cost as payments minus estimated costs. IP resource use and net cost recovery by academic vs nonacademic hospital, length of stay (LOS), and AEs were analyzed. Results: Of 3074 pts with a bsAb claim, 1129 met inclusion criteria. Mean IP LOS was 9 days (range 1–68). Hospital mean estimated IP cost/day for index hospitalization was $3963. Mean estimated costs for index hospitalization were $36964 per pt for IP SUD and $28366 for mean Medicare payments with a mean loss of $8598 per pt (median −$5616). Payments exceeded estimated costs on average by $2764–8149 for 1–4-day hospitalizations and roughly equal costs for hospitalizations at 5 days. For pts with LOS of 6–9 days and ≥10 days, payments were lower than costs by $6735 and $16659, respectively, suggesting a loss. For pts with subsequent OP administrations (74%) observable in this sample, cumulative payments and costs were assessed following the index hospitalization, mean cumulative longitudinal payments were ≥ cumulative costs within 2–3 mos. IP stay net losses were higher among pts with infection (−$6406 vs no infection), neutropenia (−$7006), and febrile neutropenia (−$10018). Payment patterns and estimated costs were similar across hospital types. Conclusions: Results suggest a large financial burden on non-PPS-exempt hospitals for IP-administered bsAb SUD. While shorter LOS for IP SUD generally did not result in financial losses, longer LOS was associated with disproportionately higher costs relative to payments. Care models (e.g. OP SUD) are key to manage initiation costs and ensure delivery of care for bsAbs remains financially sustainable.

Profiling patients with <i>MET</i> exon 14 ( <i>MET</i> ex14) skipping NSCLC with a sustained clinical benefit to tepotinib in VISION.

8612 Background: Tepotinib is a highly selective MET inhibitor with clinical activity in patients with MET ex14 skipping NSCLC. We previously reported long-term efficacy and safety outcomes of tepotinib from VISION in patients with ≥3-years follow-up (data cut-off: May 20, 2024; Mazieres et al. ELCC 2025 [Poster 81P]). Here, we provide a subset analysis of patients from VISION who achieved long-term responses to tepotinib to identify clinical characteristics associated with durable benefit. Methods: Patients with advanced MET ex14 skipping NSCLC detected by liquid (L+) and/or tissue (T+) biopsy received tepotinib 500 mg (450 mg active moiety) once daily. The primary endpoint was objective response by independent review using RECIST v1.1. Secondary endpoints included duration of response and safety. Exploratory analyses of baseline and on-treatment liquid biopsy biomarkers were carried out for potential prognostic, predictive, or pharmacodynamic relevance. For this subset analysis, patients with a long-term response were defined as those with a duration of response (DOR) to tepotinib of &gt;36 months. Results: Of 313 patients enrolled, 26 patients had a DOR &gt;36 months (range: 36.6–78.9). In these patients, median age was 67.7 years (range: 52–84), 53.8% were male, 50.0% were White and 34.6% were Asian, 92.3% had adenocarcinoma, 53.8% had a history of smoking, and 53.8% were L+ and 65.4% were T+. Median duration of treatment was 50.7 months (range: 15.9–83.1). Seventeen patients received tepotinib as first-line and nine as second-or-later line therapy. Twenty-four patients achieved &gt;50% decrease, while six patients achieved &gt;80% decrease in the sum of longest diameters from baseline. Eighteen patients’ cancer had not progressed at the data cut-off of May 20, 2024, and 14 patients were still receiving treatment. In 12 patients who discontinued treatment, reasons for discontinuation were: adverse events (5 patients [peripheral edema in 2 patients]), disease progression per investigator (3 patients), non-compliance (1 patient), consent withdrawal (1 patient), and other reasons (2 patients). Among patients with long-term responses who stopped treatment early due to adverse events (prior to disease progression), continued responses were observed for up to 52 months after tepotinib discontinuation without any further subsequent anticancer treatment. Of nine patients who received treatment prior to tepotinib, four patients received immunotherapy alone, and eight patients received chemotherapy without immunotherapy. Baseline and on-treatment biomarker data will be presented. Conclusions: Patients who achieved long-term responses to tepotinib in VISION had similar clinical characteristics and safety outcomes to the overall population of patients from VISION (Mazieres et al. ELCC 2025 [Poster 81P]); ongoing biomarker analyses may help to further characterize these patients. Clinical trial information: NCT02864992 .

Combination synergy of spliceosome modulator ADC with a K-Ras inhibitor in <i>K-Ras</i> –mutated pancreatic cancers.

e16427 Background: AKTX-101 is a TROP2 ADC containing the spliceosome modulator payload, PH1(1). PH1 can target oncogenic driver splice variants such as AR-v7 and WT Androgen Receptor in prostate cancer. Alternative splicing of K-Ras results in two isoforms, 4A and 4B. When K-Ras WT carcinoma cells were treated with PH1, exon skipping of KRAS RNA was altered in a region common to both isoforms (2). AKTX-101 exhibited single digit nM potency in NCI-H441 lung cancer model with a K-Ras G12V driver mutation. Methods: To investigate the potential efficacy of AKTX-101 in pancreatic cancer, in vitro cytotoxicity assays were performed using 4 cell lines with oncogenic K-Ras G12C or G12D mutations. Here we tested AKTX-101 vs 3 TROP2 ADCs bearing topoisomerase I-payloads, alone, and in combination with adagrasib. In the combination experiments, ADCs were fixed at their IC50 concentrations, or at 20nM if IC50 was not reached, and adagrasib was varied from a top concentration of 100µM with nine 4-fold serial dilutions. The mean for the Bliss Independence scores was used to determine combination index: Bliss scores of &gt; 5 indicated synergy and &lt; -5 reflected antagonism. Results: In KRAS G12C and G12D mutant pancreatic cancer cell lines, the combination of AKTX-101 and adagrasib exhibited synergistic cell killing not seen with the other TROP2 ADC/adagrasib combinations. Mean Bliss scores were &gt; 10 for the AKTX-101+ adagrasib combination, vs. primarily negative Bliss scores for the competitor TROP2 ADCs/adagrasib combinations, suggesting synergy may be due to novel biology of PH1 targeting splicing. Conclusions: The TROP2 ADC, AKTX-101 exhibited synergistic efficacy with adagrasib in K-Ras G12C and G12D mutated pancreatic cancer cell lines. This synergy may be linked to PH1-specific effects on K-Ras splicing and may have contributed to improved adagrasib efficacy in G12D-mutated pancreatic cancer, where currently adagrasib is not approved. References Mitra SK, Monteith W, Do M, Tuffy G, Savage S, Kang J, Abuhay M, Losic T, Ghone S, Haskins WE, Jammalamadaka V, Satyal S. Cancer Res. 2023;83(7_Supplement):6297. Mitra SK, Jammalamadaka V, Kang J, Losic T, Tuffy G, Liang TW, Tipton K, Lopez A, Savage S, Monteith W, Haskins WE, Jurica MS, Satyal S, Do M. Development of a splicing modulator-based ADC payload class with immune stimulatory properties for cancer therapy. Cancer Res . 2021;81(13_Supplement):1832. In vitro combinations of Trop2 ADCs with adagrasib. K-Ras mutation Cell line AKTX-101 IC50 (nM) Adagrasib (Ada) IC50 (nM) Bliss Mean AKTX-101 + Ada Bliss Mean SG + Ada Bliss Mean Dato-DXd + Ada Bliss Mean Sac-TMT + Ada G12C PA1266 &gt;20.0 2288.5 15.95 -6.18 -3.87 -5.22 G12D HPAF-II &gt;20.0 3346.7 17.55 -13.73 -11.63 -12.16 G12D Panc 10.05 &gt;20.0 4387.7 17.51 -5.87 8.23 -3.29 G12D SW-1990 &gt;20.0 2529.5 6.78 -5.20 -4.74 -7.66 Where SG= Sacituzumab govetican, Dato-DXd= Datopotamab deruxtecan, Sac-TMT= Sacituzumab tirumotecan.

Can GLP-1 receptor agonists mitigate cancer progression? A propensity-matched analysis across seven solid tumors.

3143 Background: GLP-1 receptor agonists (GLP-1RAs) are pleiotropic medications, initially developed for diabetes, yet with beneficial effects on obesity and cardiovascular disease. Given the rapidly expanding therapeutic use of these agents and emerging preclinical data suggesting immunomodulatory effects, we examined whether GLP-1RA exposure following cancer diagnosis was associated with altered risk of progression to metastatic disease. Methods: Utilizing the TriNetX Global Health Research Network, we identified 10,225 patients with stage I-III cancer who initiated GLP-1RA therapy after diagnosis. GLP-1RA-exposed patients were propensity-matched 1:1 to DPP-4 inhibitor controls across seven cancers: breast adenocarcinoma, prostate adenocarcinoma, NSCLC, colorectal adenocarcinoma (CRC), hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), and pancreatic adenocarcinoma. Matching included demographics, BMI, glycemic factors, smoking, comorbidities, screening frequency, oncologic treatments, and concurrent medications. Primary outcome was progression to stage IV disease. Additionally, we used The Cancer Genome Atlas (TCGA) data to assess whether GLP-1R expression correlated with overall survival. Results: GLP-1RA exposure demonstrated reduced metastatic progression across 6/7 malignancies, with statistically significant reductions in four cancer types: NSCLC, breast, CRC, and HCC (Table 1). No significant safety signals or increased adverse events were observed in GLP-1RA-exposed patients compared to controls. Additionally, high tumor GLP-1R expression correlated with improved survival across the seven tumors (HR=0.67, 95% CI 0.54-0.83, p&lt;0.001), most notably in breast cancer (HR=0.55, 95% CI 0.35-0.87, p=0.011). Conclusions: In this large propensity-matched cohort, GLP-1RA initiation after cancer diagnosis was associated with dramatically reduced metastatic progression across multiple solid tumors. Corroborating these clinical findings, elevated GLP-1R expression independently predicted improved overall survival. These findings warrant validation in prospective randomized controlled trials and mechanistic investigation of potential antineoplastic pathways driven by GLP-1RAs. Effect of GLP1-1RA exposure compared to DPP-4i exposure on progression of stage I-III cancer to stage IV cancer. Cancer Type Matched Pairs (n) Events GLP-1RA/DPP-4i Cumulative Incidence (%) Hazard Ratio (95% CI) P-value NSCLC 2,157 215/482 10.0 vs 22.3 0.50 (0.43-0.59) &lt;0.001 Breast 1,187 121/239 10.2 vs 20.1 0.57 (0.46-0.71) &lt;0.001 Colorectal 784 105/174 13.4 vs 22.2 0.69 (0.54-0.88) 0.003 HCC 275 52/78 18.9 vs 28.4 0.62 (0.44-0.89) 0.009 Prostate 1,010 83/137 8.2 vs 13.6 0.79 (0.60-1.04) 0.09 RCC 523 75/99 14.3 vs 18.9 0.95 (0.71-1.29) 0.76 Pancreatic 120 28/37 23.3 vs 30.8 0.69 (0.42-1.13) 0.14

A silent but rising threat: Increasing small intestinal cancer mortality among older adults in the United States.

e16482 Background: Small intestinal cancer is a rare but increasingly diagnosed malignancy that presents unique management challenges in the geriatric population due to age-related physiological changes. This study evaluates small intestine mortality trends among the older population in the United States from 1999 to 2023, stratified by demographic and geographic factors. Methods: The mortality data from the CDC WONDER multiple cause of death files for adults aged ≥65 years were used to analyze age-adjusted and crude mortality rates (AAMRs and CMRs) per 100,000 through ICD-10 Codes: C17, stratified by year, gender, race/ethnicity, and geography. Joinpoint regression was used to estimate average annual percent change (AAPC) and annual percent change (APC) with 95% confidence intervals (CIs). Statistical significance was defined as p &lt; 0.05. Results: From 1999 to 2023, a total of 42,200 deaths were reported among older adults with small intestinal cancer, with most occurring at Decedent's home. The overall AAMR increased from 7.43 in 1999 to 9.28 in 2023 (AAPC: 1.41; 95% CI: 1.06 to 1.75; p &lt; 0.001), with the most significant increase between 2011 and 2023 (APC: 3.18; 95% CI: 2.72 to 3.65). Adults aged 85 years and older exhibited the highest CMR with an annual increase of 2.22% (p &lt; 0.001). Women consistently showed higher annual increases in mortality compared with men (1.47 vs. 1.19). The highest AAMRs were observed among NH Blacks, while the lowest were noted among Hispanics or Latinos. Geographic disparities were evident, with the South experiencing the greatest rise and the Northeast the least. Metropolitan areas showed a steeper increase than non-metropolitan areas (AAPC: 1.39 vs. 0.82). Mississippi and Oklahoma ranked highest, falling within the top 90th percentile. Conclusions: Mortality from small cancer among older adults has increased over the past two decades in the U.S., with disproportionate burden in women, NH Blacks, the population of metropolitan areas, and Southern regions and some central states, underscoring the need for targeted interventions and equitable healthcare access while addressing geographic and age-related inequities. Average Annual Percentage Changes (AAPC) per 100,000 for trends related to small intestinal cancer mortality among older adults from 1999 to 2023. Variable AAPC (95%CI) P-Value Overall 1.41(1.06 to 1.75) 0.000001 Male 1.19(0.76 t 1.62) 0.000001 Female 1.47(0.82 to 2.12) 0.000001 NH Blacks 1.86 (1.26 to 2.47) 0.000001 Hispanic or Latinos 1.18 -0.46 to 2.84) 0.159478 South 1.59 (0.98 to 2.20) 0.000001 Northeast 0.23 (-1.33 to 1.82) 0.772880 Non-metropolitan areas 0.82 (-0.17 to 1.84) 0.104715 Metropolitan areas 1.39 (0.94 to 1.84) &lt; 0.000001

Second-line TKI therapy following first-line immune checkpoint inhibitor combinations in metastatic RCC: A systematic review and meta-analysis of safety outcomes.

e16561 Background: Sequential tyrosine kinase inhibitor (TKI) therapy following immune checkpoint inhibitor (ICI)-based first-line treatment is standard practice in metastatic renal cell carcinoma (mRCC), yet the cumulative toxicity burden remains poorly characterized. We conducted the first meta-analysis to quantify toxicity with second-line TKIs following first-line ICI-based combinations. Methods: A systematic search of PubMed, EMBASE, the Cochrane Library, and MEDLINE through January 2026 identified studies reporting toxicity outcomes (Grade ≥3 adverse events per CTCAE, serious adverse events, treatment discontinuation) of second-line TKIs in mRCC patients previously treated with ICI-based combinations. A single-arm meta-analysis used the Freeman-Tukey double arcsine transformation with the DerSimonian-Laird random-effects model. Subgroup analyses by TKI type and prior ICI regimen, sensitivity analysis restricted to prospective studies, and publication bias assessment using funnel plots and Egger's regression test were performed. Results: Ten studies (1,093 patients; 2 phase 3 RCTs, 2 phase 2 trials, 6 retrospective cohorts) were included. The pooled incidence of Grade ≥3 adverse events was 45.4% (95% CI: 35.2%-55.8%; I² = 87.3%; 7 studies, n = 832), serious adverse events 30.0% (95% CI: 23.1%-37.3%; I² = 62.5%; 4 studies, n = 523), and treatment discontinuation 12.9% (95% CI: 2.5%-29.8%; I² = 93.9%; 5 studies, n = 486). Subgroup analysis by TKI type showed Grade ≥3 AE rates of 48% for cabozantinib (3 studies, n = 368), 60% for tivozanib (1 study, n = 171), 63% for axitinib (1 study, n = 40), and 30% for various TKIs (5 studies, n = 443), with substantial between-subgroup heterogeneity (I² = 95.2%, p0.0001). By prior ICI regimen, Grade ≥3 AE rates were approximately 40% following IO-IO, 45% following IO-TKI, and 48% following mixed regimens. Sensitivity analysis restricted to prospective studies confirmed robustness (pooled 45.1%; 95% CI: 40.0%-50.2%; I² = 44.6%, p = 0.165). Egger's test showed no significant publication bias for Grade ≥3 AEs (p = 0.893) or discontinuation (p = 0.652), with marginal asymmetry for SAEs (p = 0.087). Conclusions: Approximately 45% of mRCC patients receiving second-line TKI after first-line ICI-based combinations experience Grade ≥3 adverse events. Toxicity varies by TKI agent (cabozantinib ~48%, tivozanib ~60%, axitinib ~63%), while prior ICI regimen has modest impact. Despite substantial toxicity, low discontinuation rates (~13%) suggest most patients tolerate therapy with appropriate management. These findings support individualized TKI selection and proactive toxicity monitoring post-ICI. Future prospective studies with standardized reporting and head-to-head comparisons are needed to optimize sequencing and develop predictive toxicity biomarkers.

Sequencing of PARP inhibitors and taxane chemotherapy in HRR-altered metastatic castration-resistant prostate cancer: A real-world VA analysis.

5072 Background: Taxane-based chemotherapy (taxane) and poly(ADP-ribose) polymerase inhibitors (PARPi) are established life-prolonging therapies for patients with homologous recombination repair (HRR)–altered metastatic castration-resistant prostate cancer (mCRPC), particularly tumors with BRCA1/2 alterations. However, data informing the optimal sequencing of PARPi and taxane chemotherapy in this patient population is limited, especially because subsequent treatments may not be captured in reports of clinical trials. Real-world evidence may help describe treatment sequencing patterns and outcomes. Methods: We conducted a retrospective cohort study using the nationwide Veterans Affairs (VA) healthcare system. Patients with mCRPC and HRR alterations treated with either PARPi or taxanes for mCRPC were included. HRR mutation status was ascertained from genomic results captured within the VA database and included different platform/assays. Baseline characteristics were assessed at mCRPC treatment initiation. The primary endpoint was overall survival (OS) from the initiation of PARPi or taxane. Secondary analyses included OS comparisons by initial treatment class and OS from initiation of second-line therapy among patients who received both PARPi and taxane chemotherapy. Survival was estimated using Kaplan–Meier methods and compared using Cox proportional hazards models with inverse probability of treatment weighting (IPTW) to adjust for baseline differences. Results: Between Jan 2014 - May 2025, a total of 418 patients (26.8% non-Hispanic Black, median age 74.5 years), with HRR-altered mCRPC (31.3% BRCA2, 26.8% ATM, 21.1% CDK12, 13.4% CHEK2) were included in the final analysis. Metastatic involvement included bone metastases in 80.9% of patients, and visceral metastases in 11.2%. Median PSA was 30.2 ng/mL. Prior to mCRPC, 58.6% of patients had received ARPIs and 14.1% had received taxane chemotherapy. With a median follow-up of 14.1 months, patients received PARPi (N=211) or taxane (N=207), and 30.1% received both treatments for mCRPC. OS was similar between patients initially treated with PARPi versus taxane for mCRPC (HR 1.09, 95% CI 0.84-1.41). Among patients who received both therapies, OS did not differ based on treatment sequence (PARPi→taxane vs taxane→PARPi; HR 0.90, 95% CI 0.41-1.85). Conclusions: In this real-world VA cohort of HRR-altered mCRPC, overall survival was similar whether PARP inhibitors or taxanes were used as initial therapy and did not differ by subsequent treatment sequence. Treatment crossover was observed in routine clinical practice.

Circulating tumor DNA (ctDNA) clearance after immune checkpoint inhibition (ICI) with radiotherapy (RT) as a prognostic indicator for patients with advanced melanoma.

9533 Background: ctDNA is becoming a useful biomarker for ICI treatment response assessment in advanced melanoma. RT is capable of producing an abscopal effect, potentially enhancing ICI efficacy. The utility of ctDNA monitoring with concurrent ICI and RT remains incompletely explored. Here, we describe the clinical characteristics and survival outcomes of patients with advanced stage melanoma treated with ICI and palliative RT based on ctDNA dynamics. Methods: In this multicenter, retrospective study, patients with unresectable stage III/IV melanoma treated with ICI and palliative RT were identified. Patients had prospectively collected, tumor-informed, exome-based, ctDNA monitoring (Natera). Within 3 months prior to RT, patients had a baseline ctDNA level. Patients were separated into 3 cohorts based on nadir ctDNA dynamics within 3 months after RT. Those with undetectable ctDNA were categorized as “ctDNA cleared.” Patients with a positive fold ctDNA change were “increasing ctDNA” and negative fold change were “decreasing ctDNA.” Hazard ratios for overall survival (OS) probability were determined via log-rank tests and multivariate analysis (MVA) used cox proportional hazard models. Results: 50 patients treated with ICI and palliative RT were analyzed. Median follow up was 8.0 months from RT start. Median age was 65 (24-86) and median baseline ctDNA level was 8.9 MTM/mL (0-11390 MTM/mL). Melanoma primaries included: 82% (41) cutaneous, 10% (5) mucosal, 8% (4) unknown primary. ICI regimens included 70% (35) ipilimumab/nivolumab, 16% (8) nivolumab/relatlimab, 2% (1) anti-PD-1/investigational ICI, 12% (n=6) anti-PD-1 monotherapy. 20 patients had ctDNA clearance, 12 patients had decreasing ctDNA, and 18 patients had increasing ctDNA following RT with ICI. The most common RT sites were the CNS (50%, n=25) and skin/soft tissue (24%, n=12), followed by lymph nodes and bone (each 14%, n=7), and lung and liver (each 6%, n=3). Patients with ctDNA clearance had longer OS (p=0.001) compared to those with increasing or decreasing and detectable ctDNA following RT. One year OS was 85.9% with ctDNA clearance, 30.6% with decreasing ctDNA, 22.0% for increasing ctDNA. In a MVA adjusting for age, M substage, radiation site, and melanoma subtype, both decreasing and increasing ctDNA were associated with worse OS compared with ctDNA clearance (HR 5.08 [95% CI, 1.26–20.48, p=0.022] and HR 9.83 [95% CI, 2.69–35.94, p&lt;0.001], respectively). Conclusions: Among patients with advanced melanoma treated with ICI and palliative RT, ctDNA clearance is associated with significantly improved OS compared to patients with detectable ctDNA within 3 months following RT. Ongoing prospective studies are needed to understand the long-term clinical impact of RT on ICI-treated patients with melanoma, and better define the role of ctDNA monitoring for this population.

GLIX1: A first-in-class oral molecule targeting the DNA damage response by restoring TET2 activity.

e14072 Background: The Ten-Eleven Translocation methylcytosine dioxygenase 2 (TET2) initiates the DNA demethylation by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine and 5-carboxycytosine. The later two oxidized species are processed by base excision repair (BER) generating single-stranded DNA breaks that are well tolerated in normal cells. In cancer, DNA hypermethylation is common and TET2 activity is inhibited, giving rise to increased DNA methylation in close genomic proximity. Restoration of TET2 activity in cancer cells leads to excessive BER, resulting in numerous single-strand DNA breaks in close proximity, which ultimately converge to form lethal double-strand DNA breaks overwhelming DNA repair capacity, resulting in cell death. This mechanism is applicable to hematological and solid tumors and is particularly pronounced in glioblastoma (GBM). GLIX1 is a small molecule administered orally, targeting the DNA damage response by enhancing TET2 activity. Methods: Mechanistic studies evaluated the effect of GLIX1 on TET2 activity and 5hmC generation using biochemical assays, in vitro cellular systems, and in vivo models. Brain penetration of GLIX1 was assessed in rodents following oral administration with determination of brain-to-plasma exposure ratios. Antitumor activity was evaluated in multiple subcutaneous and orthotopic GBM xenograft models (U87-MG and SNB-19). Safety was evaluated in repeat-dose toxicology studies in rats and dogs. Results: GLIX1 increased TET2-dependent 5hmC generation in biochemical assays, in vitro, and in vivo systems. High potency of GLIX1 was observed in vitro in a broad range of cancer cell lines. GLIX1 demonstrated robust brain penetration, with brain exposure corresponding to 68–85% of plasma levels in mice following oral dosing. In GBM xenograft models, GLIX1 showed pronounced antitumor activity following oral administration. Toxicology studies demonstrated that GLIX1 is safe and well tolerated, up to the highest feasible doses tested (2000 mg/kg rats and 1000 mg/kg dogs). Conclusions: GLIX1 targets the DNA damage response by enhancing TET2 activity. Its unique mechanism is applicable to a broad range of cancers. GLIX1 crosses the blood brain barrier and has shown significant activity in various in vitro and in vivo GBM and glioma tumor models. These data, together with the fact that high grade gliomas are characterized by markedly reduced genomic levels of 5hmC compared with normal tissue, reflecting impaired TET2 activity and a potential therapeutic vulnerability, support clinical evaluation of GLIX1 in GBM as the first indication. A first-in-human Phase I clinical trial with GLIX1 in Adults with Recurrent or Progressive High-Grade Glioma is planned to initiate in Q1 2026.

Dual pathology, amplified risk? Understanding outcomes in TLS with concurrent heart failure.

e18618 Background: Tumor lysis syndrome (TLS) is a life-threatening oncological emergency that is associated with end-organ dysfunction and high mortality. Co-existing heart failure (HF) may further worsen the clinical outcome, particularly given the central role of aggressive fluid resuscitation in TLS management. There is a paucity of population-level data comparing outcomes in TLS patients with and without concomitant HF, and this study aims to address that gap. Methods: We retrospectively analysed adult hospitalizations (≥18 years) in the National Inpatient Sample (NIS) from 2018-2021using ICD-10 codes to identify TLS (ICD-10: E88.3) and HF (ICD-10: I50). Baseline characteristics and clinical outcomes – including mortality, length of stay (LOS), and inflation-adjusted charges – were extracted. Adjusted odds ratios (aORs) and beta coefficients (βs) were calculated for different outcomes using multivariable regression analyses that accounted for demographic, clinical, and hospital-level factors. Results: Among 61,705 hospitalizations for TLS, 11,780 patients had co-exsisting HF. Patients who had HF were older (Median age 71 vs. 65 years, p&lt;0.001), with similar sex distribution (38% vs. 37% females). Compared with those without HF, the HF group had lower burden of solid tumors (49% vs. 56%) and acute myeloid leukemia (2.9% vs. 7.2%) but higher burden of acute lymphoblastic leukemia (18% vs 14%), chronic lymphocytic Lymphocytic leukemia (7 4% vs. 5.2%), and multiple myeloma (7.8% vs. 5.5%). Chronic myeloid leukemia burden was similar in both groups (3.0% vs. 3.1%). Admitted patients for TLS with HF (vs without HF) had worse outcomes in terms of mortality (29% vs. 23%; aOR: 1.40 [1.23, 1.58]), acute kidney injury (81% vs. 68%; aOR 1.44 [1.27, 1.63]), need for renal replacement therapy (18% vs. 13%; aOR 1.35 [1.15, 1.57]), sepsis (33% vs. 27%; aOR 1.42 [1.26, 1.60]), respiratory failure (50% vs. 30%; aOR 2.24 [2.01, 2.49]), need for mechanical ventilation (19% vs. 15%; aOR 1.43 [1.23, 1.65]), and cardiac arrythmias (47% vs. 19%; aOR 2.90 [2.57, 3.27]). TLS patients with HF had longer LOS (β = +2.6 days [1.8, 3.3], p&lt;0.001), higher healthcare costs (β = +64,972$, p&lt;0.001), and increased non-home discharges (aOR 1.43 [1.28, 1.60]), when compared to those without HF. Conclusions: Among patients hospitalized with TLS, concomitant HF had worse clinical outcomes in patients, including mortality, sepsis, respiratory failure, need for mechanical ventilation, acute kidney injury, renal replacement therapy, and cardiac arrhythmias. These patients experienced longer LOS, higher healthcare costs, and more non-home discharges. A multidisciplinary approach is needed to manage these high risk patients for optimal care and to prevent adverse in-hospital outcomes.

Spatial mapping of fibroblast subtypes in primary colorectal cancer.

e15665 Background: Colorectal cancer (CRC) is the third leading cause of cancer related death. CRC arises from colon stem cells, the equilibrium of colon stem cell maintenance and differentiation is heavily dependent on fibroblast signals along the crypt-villous axis. Such fibroblast cues may be important determinants of CRC cell states and progression as well. Hence, in this study, we phenotyped fibroblast subtypes and analyzed their spatial mapping in primary CRC. Methods: We performed Xenium spatial transcriptomics of 38 primary CRC samples from 35 CRC cases (8 with metastatic disease at diagnosis), with varying depths of tumor invasion. Data was analyzed using R Seurat package. Results: There were 5 major fibroblast subtypes with distinct spatial arrangement – WNT5A+BMP+, WNT5A+hypoxic, ADAMDEC1+stromal, matrix-cancer associated fibroblasts (mCAFs) and Inflammatory-CAFs (iCAFs). The key markers of the WNT5A+ BMP+ fibroblasts were WNT5A, WNT5B, NRG1, BMP5 and corresponded to normal epithelial crypt niche fibroblasts. mCAFs showed higher expression of POSTN, SULF1, and FN1 and iCAFs had higher expression of C3. The WNT5A+hypoxic fibroblasts had overlapping gene expression with WNT5A+BMP+ and mCAFs and over-expressed hypoxia markers ( VEGFA, NDRG1 ). They may represent a transitional state between WNT5A+BMP+ and mCAFs based on trajectory analysis. Spatially, the WNT5A+BMP+ and ADAMDEC1+stromal fibroblasts were predominantly located in the adjacent normal appearing colon tissue. The WNT5A+BMP+ fibroblasts, which lines normal intestinal epithelium, was also detected along the lining of tumor regions in mucosa and submucosa including at deep stromal invaginations into tumor nests. The presence of normal intestinal WNT5A+BMP+ fibroblasts lining tumor nests in submucosa is interesting, temporal data is necessary to understand if tumor cells induce this transcriptional state in neighboring fibroblasts or if fibroblasts migrate with tumor cells as they invade. Several markers of the WNT5A+BMP+ fibroblasts (NRG1, WNT5A, BMPs) are involved in epithelial differentiation and intestinal injury repair and may maintain epithelial identity in CRC tumor cells. Notably, higher NRG1 and WNT5A expression in primary CRC bulk RNA sequencing data was associated with better overall survival (log rank p = 0.04 and p = 0.01 respectively) in The Cancer Genome Atlas (TCGA). The WNT5A+hypoxic was the most abundant fibroblast subset lining tumor nests throughout the colon, they were absent farther away from the tumor nests. mCAFs are the predominant population throughout the tumor stroma and their proportion at the lining of tumor nests increased in deeper layers of the colon. Conclusions: Taken together, we describe key fibroblast populations and their spatial distributions in primary CRC, their impact on tumor cell phenotype through paracrine signaling needs further investigation.

Anti-CD38 treatment patterns in multiple myeloma patients with Medicare/Medicaid versus private insurance.

e19575 Background: Multiple myeloma (MM) is one of the most common hematological malignancies, and the incidence of MM continues to increase around the world. MM survival has increased dramatically over the past 10 years, partially due to the introduction of anti-CD38 antibodies in different stages of MM therapy. MM patients with Medicaid/Medicaid are at higher risk of morbidity and mortality likely related to their access to different treatment modalities. We explored anti-CD38 treatment patterns in patients with private insurance versus Medicare/Medicaid. Methods: Data were extracted from Altopros Evidence Network from 1/1/2020-10/3/2025. The Altopros Evidence Network was searched for patients 18 years or older with MM. We then separated the MM cohort into patients with private insurance versus Medicare/Medicaid, and examined use of anti-CD38 antibodies at 30 days from diagnosis and within 6 year. We identified 5176 patients in the Medicare/Medicaid group and 11715 patients in the private insurance group. Results were powered to p&lt;0.001. Results: The Medicare/Medicaid cohort was older than the private insurance group (the median age was 73.6 years and 65.8 years, respectfully) and had a higher percentage of peripheral vascular disease (38.3% vs 23.7%) and cerebrovascular disease (29.1% vs 18.1%). After propensity score matching, the use of CD38 directed therapy within 30 days was not statistically significantly higher in the private insurance group than the Medicare/Medicaid group (IRR 0.987, 95% CI 0.818-1.19, p=0.89). The use of CD38 directed therapy within 6 years was also not significantly higher in the private insurance group (IRR 0.934, 95% CI 0.843-1.03, p=0.187). Conclusions: Patients with private insurance did not have a statistically higher chance of being placed on anti-CD38 directed therapy within both 30 days and 6 years after diagnosis than those with Medicare/Medicaid. This suggests that access to anti-CD38 antibodies may not be related to increased morbidity/mortality experienced in patients with Medicare/Medicaid with MM.

Long-term outcomes of laparoscopic versus open gastrectomy for far-advanced gastric cancer after preoperative chemotherapy.

e16072 Background: Evidence supporting the implementation of laparoscopic gastrectomy (LG) for far-advanced gastric cancer (GC) including T4b, bulky lymph nodes and limited metastasis after preoperative chemotherapy remains inadequate. This study aimed to compare the long-term outcomes of laparoscopic versus open gastrectomy (OG) in patients with far-advanced GC after preoperative chemotherapy. Methods: This retrospective cohort study was conducted using data from patients with far-advanced GC who underwent either LG or OG and lymphadenectomy after preoperative chemotherapy between January 2018 and June 2024 at the Gastro-intestinal Surgical Department of the University Medical Center, a tertiary hospital in Ho Chi Minh City, Vietnam. Surgical outcomes, postoperative complications, and long-term oncologic outcomes, including overall survival (OS) and progession-free survival (PFS) were compared between the two groups. Results: A total of 70 patients were included in the study, of whom 33 patients underwent LG and other 65 patients underwent OG. There were no significant differences between the two groups in terms of operating time, blood loss, the length of proximal and distal resected margin, the number of retrieved lymph nodes, curability, and overall and major postoperative complications. Most postoperative complications were classified as minor according to the Clavien-Dindo classification. Time to the first flatus, time to tolerance of oral intake, and the length of postoperative hospital stay were also similar between groups. The 3- and 5-year OS rates were comparable between the two groups (51% and 32% vs. 42% and 32% in the LG and OG groups, respectively). The 3- and 5-year PFS rates were also equivalent between the two groups (41% and 38% vs. 41% and 38%, respectively). Conclusions: LG demonstrated comparable long-term oncologic outcomes to OG in patients with far-advanced GC after preoperative chemotherapy. LG may be considered a safe, effective alternative for selected patients.

Prognostic value of serum tumor markers in phase I immunotherapy trials: A single-institution retrospective analysis.

e14534 Background: Serum tumor markers are routinely monitored in patients with advanced solid tumors, but their utility in the phase I immunotherapy setting is not well established. We investigated whether baseline and best overall response (BOR) levels of these markers, and their changes during treatment, correlate with response and survival outcomes in patients on phase I immunotherapy trials across multiple tumor types. Methods: We retrospectively analyzed patients enrolled on phase I immunotherapy trials at our center between April 2017 and May 2023, with paired tumor marker assessments at baseline (within 30 days cycle 1 day 1 [C1D1]) and at BOR (within 21 days of BOR date, during which time patients received only study treatment). Markers analyzed included CA15-3 (breast), CA125 (ovarian), CA19-9 (pancreatic, cholangiocarcinoma, gastric/gastroesophageal junction [GEJ]), and CEA (colorectal, pancreatic, gastric/GEJ). In pancreatic cancer, CA19-9 was the primary analysis and CEA was exploratory. Associations between marker levels and BOR were assessed using Fisher's exact and Kruskal-Wallis tests. Spearman correlation evaluated relationships between marker percent change and radiographic response. Univariate Cox regression assessed associations with overall survival (OS), time to progression (TTP), and progression-free survival (PFS). Results: 106 patients with paired baseline and BOR marker data were included: colorectal (n = 35), pancreatic (n = 30), breast (n = 15), ovarian (n = 15), cholangiocarcinoma (n = 6), and gastric/GEJ (n = 5). Median age was 59 years; 61.3% were female; 74.5% received combination immunotherapy. In pancreatic cancer, CA19-9 levels at BOR were significantly higher in patients with progressive disease (PD) compared to stable disease (SD) or partial response (PR) (median 9,500 vs 535.4 vs 173.5 U/mL; p = 0.026). CA19-9 percent change from baseline to BOR positively correlated with radiographic response change (ρ = 0.44, p = 0.02). On Cox regression, CA19-9 percent change was associated with worse OS (HR 1.02 per 10% increase, 95% CI 1.00-1.04; p = 0.014), TTP (HR 1.02, p = 0.029), and PFS (HR 1.02, p = 0.029). In colorectal cancer, elevated CEA at BOR ( &gt; 3.8 ng/mL) was associated with worse OS (HR 4.65, 95% CI 1.10-19.71; p = 0.037). Greater radiographic tumor burden change was associated with worse OS (HR 1.23 per 10% increase, p = 0.038), TTP (HR 1.34, p = 0.003), and PFS (HR 1.33, p = 0.003). Conclusions: Changes in tumor marker levels—particularly CA19-9 in pancreatic cancer and CEA in colorectal cancer—provide prognostic information in phase I immunotherapy trials, though concordance with radiographic change was modest. Given the challenges of early response assessment with immunotherapy, tumor markers may serve as a practical adjunct to imaging for longitudinal monitoring. Prospective validation and longitudinal trajectory analysis are warranted.

BXQ-350 in combination with FOLFOX7 and bevacizumab: Evaluation of effect on oxaliplatin-induced CIPN and neutropenia—A phase 1b/2a trial to assess the efficacy and safety of BXQ-350, a first-in-class sphingolipid metabolism modulator, in newly diagnosed metastatic colorectal carcinoma.

12080 Background: Chemotherapy-induced peripheral neuropathy (CIPN) and Neutropenia are significant side effects associated with many cancer drugs and are highly prevalent in mCRC patients receiving oxaliplatin-based regimens. CIPN can severely impact quality of life (QoL) and may require dose vacation, reduction or interruption. CIPN pathology is complex and not completely understood; preclinical and clinical data have shown inflammatory (IL-6, Il-8, IL-10) and immune involvement as well as elevated levels of sphingolipids, a class of bioactive signaling molecules. Neutropenia can also be a potentially severe side effect and may occur in up to 40% of mCRC patients receiving FOLFOX. BXQ-350 is a nanovesicle formulation of Saposin C, an allosteric activator of sphingolipid metabolism that normalizes dysregulated sphingolipid metabolism by lowering S1P, GM3 and GluCer levels while it increases ceramide level, promoting a return to homeostasis. Methods: BXQ-350 is being investigated in a Phase 1b/2 study in combination with mFOLFOX7 and Bevacizumab (SoC) in newly diagnosed mCRC patients (NCT05322590). Primary objectives are to assess safety and preliminary efficacy of this combination, and to determine cumulative oxaliplatin dose. Secondary objectives include intensity, frequency and time to onset of CIPN. Results: The Phase Ib trial enrolled 33 oxaliplatin dosing evaluable patients; all patients completed the primary treatment period (6 months of SoC treatment plus BXQ-350). Amongst the 33 patients, 19 completed the full 12 Cycles of oxaliplatin dosing, 28 completed at least 8 Cycles with only 2 patients having dosing halted before Cycle 8 due to CIPN. There were no reported Grade 4 and only 3 reported Grade 3 CIPN AEs, all occurred after Cycle 12. Analysis of Neurofibrillary Light Chain (NfL) biomarkers suggests concordance with physician and patient reported outcomes. Grade 3 or higher Neutropenia was meaningfully reduced to 5% in mCRC patients receiving FOLFOX plus Bevacizumab. Conclusions: Results show that BXQ-350 was safe and well tolerated in the combination. Data suggest that BXQ-350 may provide additional clinical benefits and may reduce intensity or delay onset of CIPN while meaningfully reducing Grade 3 or higher Neutropenia, allowing for increased cumulative dosing of oxaliplatin and relative dose intensity in 1L mCRC. Clinical trial information: NCT05322590 .

The efficacy and safety of calmangafodipir in preventing chemotherapy-induced peripheral neuropathy: A systematic review and meta-analysis.

e24208 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent, dose-limiting toxicity of oxaliplatin-based chemotherapy with significant impact on quality of life and treatment delivery. Calmangafodipir (CaM), a manganese-containing superoxide dismutase mimetic, has been investigated as a potential neuroprotective agent to prevent CIPN. This study is being done to assess the efficacy and safety of Calmangafodipir in preventing chemotherapy-induced peripheral neuropathy. Methods: A systematic search of Cochrane Central, PubMed, ScienceDirect, Scopus, and Google Scholar from inception to January 2026 identified randomized controlled trials evaluating CaM versus placebo in patients receiving chemotherapy. Eligible studies enrolled human subjects undergoing chemotherapy, compared CaM with placebo, and reported CIPN outcomes and/or adverse events. Data were pooled using random-effects models; risk ratios (RR) or odds ratios (OR) with 95% confidence intervals (CI) were calculated, and heterogeneity was assessed with the I 2 statistic. Results: Of 238 records screened, 4 RCTs met inclusion criteria. At 9 months, CaM was associated with a significantly higher risk of CIPN compared with placebo (RR 1.37, 95% CI 1.10–1.70, p = 0.004; I 2 = 0). At 4 months, there was no significant difference in CIPN risk between CaM and placebo (HR 0.60, 95% CI 0.34–1.05, p = 0.07; I 2 = 0). There was no statistically significant difference in overall adverse events for CaM 2 versus placebo (OR 0.61, 95% CI 0.17–2.11, p = 0.43; I 2 = 0) or treatment-emergent serious adverse events for CaM 5 versus placebo (OR 1.91, 95% CI 0.36–10.20, p = 0.45; I 2 = 78%). Conclusions: In this meta-analysis of randomized trials, calmangafodipir did not prevent chemotherapy-induced peripheral neuropathy and was associated with a higher long-term CIPN risk at 9 months compared with placebo. While overall toxicity and serious adverse events were not significantly different between groups, these findings do not support the use of calmangafodipir as a preventive strategy for CIPN and highlight the need for alternative neuroprotective approaches.