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Perioperative chemotherapy plus disitamab vedotin (RC48) and toripalimab in HER2-overexpressed locally advanced gastric or gastroesophageal junction cancer (PERISCOPE-02): An open-label, single-arm, phase 2 trial.

4080 Background: The use of Disitamab vedotin (RC48) and programmed death-1 (PD-1) inhibitor is effective in patients with HER2-expressing advanced gastric or gastroesophageal junction (G/GEJ) cancer. However, their use has not been investigated in patients with localized disease. This trial evaluated the safety and anti-tumor activity of perioperative chemotherapy combined with RC48 and toripalimab in the treatment of locally advanced HER2-overexpressed (defined as IHC 2+ or 3+) G/GEJ cancer. Methods: This study was an investigator-initiated, open-label, single-arm, phase 2 trial was conducted at Sun Yat-sen University Cancer Center. Eligible patients with HER2-overexpressed locally advanced G/GEJ cancer received 3-4 cycles of neoadjuvant XELOX plus RC48 and toripalimab, followed by surgery. The primary endpoint was TRG 0/1 after neoadjuvant treatment. This study is registered at Chinese Clinical Trial Registry (ChiCTR2400081677). Results: Between July 11, 2024, and July 11, 2025, of 26 patients screened for eligibility, 25 patients were enrolled, all patients had no distant metastasis confirmed by laparoscopic exploration and ascitic fluid cytology, 20 (80%) patients had clinical stage III disease and 5(20%) with stage II. Of these 25 patients, the median age was 58 (IQR, 37-74) years. Tumors were located in the stomach in 21(84%) patients and in the gastroesophageal junction in 4 (16%) patients. The patients with HER2 IHC expression of 2+ and 3+ was 21 (84%) and 4 (16%) respectively. 15 (60%) patients had the PD-L1 CPS of 1 or more, 24 (96%) patients were pMMR. The primary endpoint of TRG 0/1 was met in 16 (64%) patients, 9 (36%) patients achieved pCR (ypT0N0), and 24 (96%) were ypN0. 10 (40%) patients experienced grade 3 treatment-related adverse events, the most common treatment-related adverse events were increased ALT or AST (5 [20%] patients) and neutropenia (3 [12%] patients), no grade 4 treatment-related adverse events. Surgical morbidity (Clavien-Dindo II/III) occurred in 2 of 25 (8%) patients, with no 30-day surgical mortality. Conclusions: Our findings suggested that perioperative chemotherapy plus RC48 and toripalimab had controllable safety and showed encouraging efficacy in patients with HER2-overexpressed G/GEJ cancer. Clinical trial information: ChiCTR2400081677.

Treatment duration with avutometinib/defactinib in recurrent low-grade serous ovarian carcinoma by KRAS mutation status.

5561 Background: Low grade serous ovarian carcinoma (LGSOC) is characterized by MAPK pathway alterations (most commonly KRAS , which occurs in 1/3 of tumors) and poor chemosensitivity. Avutometinib (MEK/RAF clamp) in combination with defactinib (FAK inhibitor) has shown durable responses in patients with recurrent LGSOC harboring a KRAS mutation and was recently FDA approved for this indication. However, data is lacking regarding the activity of avutometinib + defactinib (A+D) vs single agent MEK inhibitors for treatment of women with recurrent LGSOC. Here we examine patients who were treated with A+D. We also examine the duration of treatment in patients who received a single agent MEK inhibitor followed by A+D. Methods: In this single-institution retrospective cohort study, patients with recurrent LGSOC treated with A+D between 2021 – 2025 were included and stratified by tumor KRAS mutation status. The primary outcome was median duration of treatment on A+D, compared using Wilcoxon-Rank sum test. Pair-wise comparison of treatment duration in patients who were treated with single agent MEK inhibitors and A+D was performed. Results: 26 patients were included in the final analysis. Median age at diagnosis was 49 years (range 20-85). Patients had a median of 4 (range 1-9) prior lines of therapy, including hormonal (92%, n=24), bevacizumab (38%, n=10), and MEK inhibitors trametinib and binimetinib (35%, n=8). Eight (31%) patients harbored a tumor KRAS mutation. Among these 26 patients, median duration of treatment with A+D was 16.8 months in the KRAS -mutant and 5.5 months in the KRAS -wild type cohorts, respectively (p=0.037). Nine patients were treated with both A+D and a MEK inhibitor, three of whom had KRAS -mutant tumors. All nine patients received the single agent MEK inhibitor prior to treatment with A+D, with a median of 7 (range 4-8) prior lines of therapy before treatment with A+D. Among the three patients with KRAS -mutant tumors, median duration of treatment with single agent MEK inhibitor was 4.4 months (range 0.4-24.2) while with A+D, it was 17.6 months (range 6.1-23.4). Conclusions: In this single-institution retrospective cohort, treatment with A+D was associated with a significantly longer median duration of therapy in patients with KRAS -mutant recurrent LGSOC compared with KRAS -wild type disease. Among patients who received both regimens, A+D appeared to provide longer treatment duration than prior single agent MEK inhibitors in the KRAS -mutant subset, though this is limited by small sample size. These findings support improved activity of A+D in KRAS -mutant LGSOC and warrant confirmation in larger prospective studies.

Impact on overall survival after adjusting for treatment crossover in first-line metastatic NSCLC trials for pembrolizumab plus chemotherapy.

8596 Background: High crossover rates were observed in the chemotherapy alone arm in KEYNOTE(KN)-189 and KEYNOTE-407, attributable to protocol-permitted crossover to pembrolizumab monotherapy and subsequent anti-PD1/PD-L1 therapies per clinical practice. The objective was to assess the impact on overall survival (OS) by adjusting for treatment crossover. Methods: The analysis used pooled data from KN-189 global (NCT02578680; cut-off date: 08MAR2022) and Japan extension (NCT03950674; cut-off date: 07FEB2023), and pooled data from KN-407 global (NCT02775435; cut-off date: 23FEB2022) and China extension (NCT03875092; cut-off date: 10FEB2023). The survival time of participants (pts) in the chemotherapy alone arm who crossed over to pembrolizumab or subsequent anti-PD1/PD-L1 therapy was adjusted using a Two-Stage Estimation model (TSE) and Rank-Preserving Structural Failure Time model (RPSFT). Subsequently, a stratified Cox regression model was used to estimate the treatment effect of pembrolizumab+chemotherapy (P+C) relative to chemotherapy. Results: Overall, 646 and 669 patients were included in the analysis for KN-189 & KN-407 with a median follow-up of 64.6 months (range, 59.3-82.8) and 56.7 months (range, 50.1-69.3), respectively. In KN-189, adjusting OS for 56.3% pts who crossed over from the chemotherapy arm resulted in a larger treatment effect estimate for P+C relative to chemotherapy than observed in the unadjusted Intention-to-Treat (ITT) analysis. Similarly, for KN-407, after adjusting OS for 53.7% pts who crossed over, compared with chemotherapy alone, P+C showed more pronounced benefit than in the unadjusted ITT approach. The greater treatment effect for P+C was consistently demonstrated in both studies regardless of the PD-L1 TPS cutoff values. Conclusions: After adjusting for treatment crossover, pembrolizumab + chemotherapy demonstrated greater magnitude of OS benefit versus chemotherapy alone in both trials. TSE and RPSFT analyses support the robustness of these findings showing similar direction and magnitude of treatment effects across PD-L1 TPS cut-offs. Clinical trial information: NCT02578680 ; NCT03950674 ; NCT02775435 ; NCT03875092 . KN-189 KN-407 Population N Unadjusted ITT TSE RPSFT N Unadjusted ITT TSE RPSFT All comers 431 vs 215 0.60 (0.50; 0.72) 0.44 (0.33, 0.58) 0.46 (0.35, 0.61) 332 vs 337 0.65 (0.55, 0.76) 0.47 (0.35, 0.63) 0.52 (0.40, 0.67) TPS <1% 140 vs 66 0.51 (0.37, 0.70) 0.41 (0.27, 0.63) 0.42 (0.28, 0.63) 115 vs 121 0.75 (0.56, 0.99) 0.59 (0.35, 0.98) 0.64 (0.42, 0.98) TPS ≥1% 267 vs 132 0.65 (0.52, 0.82) 0.48 (0.32, 0.71) 0.50 (0.34, 0.73) 207 vs 209 0.60 (0.48, 0.74) 0.40 (0.28, 0.59) 0.45 (0.32, 0.63) TPS 1-49% 132 vs 61 0.66 (0.47, 0.92) 0.48 (0.27, 0.86) 0.54 (0.33, 0.88) 114 vs 124 0.59 (0.45, 0.79) 0.38 (0.22, 0.64) 0.45 (0.30, 0.70) TPS ≥ 50% 135 vs 71 0.66 (0.47, 0.93) 0.48 (0.26, 0.87) 0.48 (0.26, 0.87) 93 vs 85 0.63 (0.45, 0.88) 0.44 (0.24, 0.79) 0.46 (0.26, 0.81)

Afatinib versus chemotherapy in advanced NSCLC with uncommon <i>EGFR</i> mutations: A pooled individual patient–level survival analysis of ACHILLES/TORG1834 and LUX-Lung 2/3/6.

e20736 Background: Uncommon EGFR mutations represent a biologically and clinically heterogeneous subset of non–small cell lung cancer (NSCLC), for which optimal first-line treatment remains uncertain due to limited randomized evidence. While afatinib has shown activity in post hoc analyses of the LUX-Lung program, prospective comparative data have been scarce until the recent ACHILLES/TORG1834 randomized trial. We conducted a pooled individual patient–level analysis to comprehensively quantify the progression-free survival (PFS) benefit of afatinib versus chemotherapy in advanced NSCLC harboring uncommon EGFR mutations. Methods: Individual patient data were pooled from ACHILLES/TORG1834 and the prospective LUX Lung 2, 3, and 6 studies. Eligible patients had advanced NSCLC with uncommon EGFR mutations treated with afatinib or platinum-based chemotherapy. Exon 20 insertions and de novo T790M mutations were excluded. The primary endpoint was PFS. Treatment effects were estimated using Cox proportional hazards models with likelihood ratio testing. Kaplan–Meier methods were used to estimate median PFS and landmark PFS rates. Results: Among 170 patients included, 101 PFS events occurred. Afatinib significantly reduced the risk of disease progression or death compared with chemotherapy (HR 0.54; 95% CI, 0.36–0.84; p = 0.005), supported by a significant likelihood ratio test (p = 0.007). Median PFS was 10.8 months (95% CI, 8.4–13.0) with afatinib versus 6.0 months (95% CI, 5.2–8.3) with chemotherapy. Landmark PFS rates consistently favored afatinib at 6 months (75.3% vs 48.9%), 12 months (41.1% vs 17.9%), 18 months (27.9% vs 13.5%), and 24 months (19.8% vs 4.5%), demonstrating durable disease control. Conclusions: This pooled individual patient–level analysis demonstrates that afatinib confers a statistically significant and clinically meaningful improvement in PFS compared with chemotherapy in patients with advanced NSCLC harboring sensitizing uncommon EGFR mutations. The consistency of benefit across randomized and prospective trials, together with sustained landmark PFS advantages, supports afatinib as a preferred treatment option for this heterogeneous molecular subgroup and provides robust evidence to inform clinical decision-making and guideline development. Progression-Free survival by treatment in patients with uncommon EGFR-Mutant NSCLC. Treatment Median PFS (months) 95% CI HR (95% CI) vs Chemo p-value 6-mo PFS 12-mo PFS 18-mo PFS 24-mo PFS Chemotherapy 5.97 5.18–8.28 Reference – 48.90% 17.90% 13.50% 4.50% Afatinib 10.79 8.38–13.03 0.54 (0.36–0.84) 0.005 75.30% 41.10% 27.90% 19.80%

Mortality trends of lymphoid and hematopoietic malignancies among US adults: A CDC WONDER– based demographic and regional analysis, 1999–2020.

e19101 Background: Malignant neoplasms of lymphoid and hematopoietic tissues are a major cause of oncology-related morbidity and mortality. The diverse pathological subtypes and intricate clinical progression of these malignancies can impact therapeutic management and long-term prognosis. This study analyzes long-term mortality trends and sociodemographic patterns of lymphoid and hematopoietic malignancies in U.S. adults. Methods: Mortality data (1999–2020) for adults ≥25 years with malignant neoplasms of lymphoid and hematopoietic tissues (C81–C96) were obtained from the CDC WONDER database. Crude and age-adjusted mortality rates (per 100,000) were calculated using the 2000 U.S. standard population. Trends were analyzed using Joinpoint regression (APC with 95% confidence intervals, p≤0.05), stratified by demographic and geographic categories. Results: Between 1999 and 2020, 1,217,470 deaths were reported, and the age-adjusted mortality rate declined significantly over the study period (AAPC: −1.8%; 95% CI: −2.0 to −1.6; p&lt; 0.000001). This decline was characterized by a steady decrease from 1999 to 2008 (APC:− 1.9%; p &lt; 0.001), a slower reduction from 2008-2012 (APC: −1.0%; p &lt; 0.001), and then a pronounced decrease from 2012–2020 (APC: −2.1%; p &lt; 0.001). The AAMR was significantly higher in males than in females (33.3 vs 20.05). The highest AAMR was observed among non-Hispanic whites (26.17), followed by non-Hispanic blacks (25.6). Crude mortality rates rose with age and were highest for those 65 and older (100.12), followed by those 45–64 (14.25) and those aged 25–44 (2.51). The AAMR increased significantly in the Midwest (27.61) and nonmetropolitan areas (26.87). AAMR varied considerably by state, ranging from 20.01 in Hawaii to 28.30 in West Virginia. Conclusions: Mortality due to lymphoid and hematopoietic malignancies showed a significant decrease over a period of twenty years. Particularly among males, the Midwest, NH White individuals, older adults, and non-metropolitan areas, indicating a higher burden of malignancy-related complications over time relative to other demographics. These results imply that specific interventions taken into consideration age-related risk factors and regional disparities are necessary to lower the burden of blood-related cancers. Mortality trends of lymphoid and hematopoietic malignancies among U.S. adults. Key Subgroup AAPC (%) 95% CI P-value Overall -1.83 -2.01 to -1.64 &lt;0.000001 Male -1.70 -1.94 to -1.45 &lt;0.000001 Female -2.13 -2.39 to -1.87 &lt;0.000001 Age ≥85 years 4.25 4.01 to 4.48 &lt;0.000001 Non- metropolitan areas -1.56 -1.64 to -1.48 &lt;0.000001 Black or African American -1.59 -1.70 to -1.47 &lt;0.000001 Asian or Pacific Islander -1.68 -2.27 to -1.09 &lt;0.000001 Midwest Census Region -1.70 -1.79 to -1.61 &lt;0.000001

Pulmonary hypertension-associated mortality among patients with lung cancer: A CDC WONDER analysis (2003-2023).

e20775 Background: Lung cancer remains a leading cause of cancer-related mortality globally. In advanced stages, tumor-driven vascular remodeling can predispose patients to secondary Pulmonary Hypertension (PH), contributing to significant cardiopulmonary morbidity. Despite recognition of cancer-associated PH, its epidemiology in lung cancer is poorly characterized. Methods: In this retrospective cohort study, we analyzed mortality records from the CDC WONDER database (2003–2023) for decedents aged ≥45 years with both lung cancer (ICD-10: C34) and secondary PH (ICD-10: I27.2) listed as contributing or underlying causes of death. Analyses adhered to STROBE guidelines for observational studies. Age-adjusted mortality rates (AAMRs) per 100,000 population, annual percent changes (APCs), and average annual percent changes (AAPCs) were estimated using Joinpoint regression, stratified by age, sex, US census region, urbanization, state, and place of death. Results: We identified 8,428 deaths over 21 years. Overall AAMR increased from 0.15 in 2003 to 0.52 per 100,000 in 2023 (AAPC 6.31%, 95% CI 5.54–7.09). Adults aged ≥65 years experienced the largest increases, with a rapid rise from 2003–2011 (APC 10.08%, 95% CI 7.82–12.37), plateau 2011–2014, and further increase 2014–2023 (APC 8.07%, 95% CI 6.89–9.24; AAPC 7.15%, 95% CI 4.81–9.52). Males exhibited consistently higher AAMRs than females (AAPC 6.66%, 95% CI 3.68–9.74). Regional variation was notable, with the West showing the highest AAPC (8.12%, 95% CI 7.32–8.92), followed by Midwest, South, and Northeast. Mortality increased significantly in metropolitan areas from 2003–2020 (APC 5.87%, 95% CI 4.84–6.91) and in non-metropolitan areas after 2005 (APC 6.41%, 95% CI 5.06–7.78). Most deaths occurred in inpatient facilities (3,431), followed by home (2,846). States with the greatest mortality burden included California, Florida, Texas, Ohio, Pennsylvania, and Colorado. Conclusions: A three-fold rise in AAMR over two decades highlights secondary PH as an under-recognized contributor to morbidity among lung cancer patients, particularly older males in Western metropolitan regions. These findings underscore the need for enhanced screening, early recognition, and further research into tumor-mediated mechanisms driving PH in lung cancer.

Measurement of cross-correlated charge noise spectrum from transport currents through series-coupled silicon quantum dots

Cross-correlated charge noise in silicon quantum dots has emerged as an important issue for fault-tolerant quantum computation, as it has been suggested to both limit quantum error correction performance and reveal unique information about noise sources. We develop a method to characterize charge noise cross-correlations in a semiconductor qubit device based solely on quantum-dot transport current. By dynamically switching the site-selective sensitivity of transport current through a double quantum dot to charge noise, we extract potential fluctuations at individual dots without requiring additional sensing devices or spin operations. Based on the obtained power spectral densities, we discuss the coupling of a dominant two-level fluctuator to individual dots. We furthermore verify the consistency of the measurement protocol by applying artificial noise via gate electrodes and investigate the temperature dependence of charge noise correlations. The method offers a convenient and versatile alternative approach that substantially facilitates the assessment of charge noise correlations in diverse semiconductor qubit devices.

Unveiling the Hall effect and electrical transport properties of chlorophyll-polypyrrole films deposited on ITO substrate for optoelectronic applications

Efficient Dynamic Potential Stabilization via a Bioinspired Ion Pump Prevents Sensing Signals Drift

ABSTRACT Artificial ion‐sensing systems rely on external power to sustain interfacial potentials, facing persistent stability challenges. During continuous operation, progressive energy depletion results in potential decay, manifesting as signal drift and eventual system failure. This problem stems from the absence of an efficient active regulation mechanism analogous to biological ion pumps, which harness ATP hydrolysis to actively transport ions against electrochemical gradients, dynamically compensating for potential dissipation. Inspired by this mechanism, we developed an oxygen‐driven bioinspired ion pump that exploits oxygen‐sensitive O─Zn bonds within NH 4 + ‐intercalated V 2 O 5 to achieve efficient Zn 2+ extraction and reverse pumping in oxygen‐rich environments, successfully emulating biological active transport. This design enables sustained electrode potential stability through dynamic ion pumping while significantly enhancing the ion‐storage capacity of V 2 O 5 . Theoretical simulations elucidated the mechanism linking O─Zn bond dissociation to adsorption site energy states under oxygen enrichment, alongside the resulting Zn 2+ pumping process. The constructed self‐powered respiration sensor demonstrated stable operation for 480 h in ambient air without external power, exhibiting a minimal performance degradation rate of only 0.2% (compared to 13.9% in oxygen‐free environments). This work proposes an oxygen‐driven bioinspired ion‐pumping strategy, offering a novel pathway to overcome persistent energy supply challenges in potentiometric sensors.

Small RNA ASpks2 promotes Mycobacterium tuberculosis survival in macrophages via targeting polyketide synthase 2

Preoperative endocrine treatment response in primary postmenopausal endometrial cancer.

5619 Background: While preoperative endocrine therapy with letrozole has become an established approach for treatment decisions in estrogen receptor (ER) positive breast cancer, this concept has not been transferred to endometrial cancer so far. We hypothesized that preoperative endocrine treatment response to letrozole, assessed by changes in Ki67 expression between baseline and surgery as a marker for cellular proliferation, can be evaluated in primary endometrial cancer as a predictive, patient-specific biomarker. Methods: Postmenopausal patients with first diagnosis of endometrial cancer planned to undergo definitive surgical management with hysterectomy were prospectively included in this single-arm biomarker analysis. Letrozole was administered orally at a daily dose of 2.5mg for a period of 2 to 4 weeks until surgery. Eligibility criteria included all molecular subtypes and histologies and no prior treatment for endometrial cancer was allowed. Ki67 expression was assessed immunohistochemically by two independent pathologists as the percentage of positive tumour nuclei. Relative change in Ki67 (%) from pre-treatment biopsy to post-treatment specimen was assessed using the Wilcoxon signed-rank test, substantial response was defined as relative reduction of Ki67 expression ≥50%. Results: A total of 23 patients were prospectively enrolled with median age of 70 years (range 52-88) and median BMI of 32 kg/m² (range 20-48). 22 patients had endometrioid histology (22/23, 95.7%), of those 86.4% (19/22) low-grade and three high-grade (13.6%). One patient had a high-grade serous tumor. 17 of the 23 patients (73.9%) were classified as NSMP (no specific molecular profile), 14 of them ER positive (82.3%). 5 of 23 patients were classified as dMMR (mismatch repair deficient, 21.7%) and one as p53mut (p53 mutant). Median pre-treatment Ki67 expression was 50% (range 10-85) compared to 15% (range 1-80) post-treatment (p&lt;0.0002). Following preoperative letrozole treatment, 16 of 23 patients (69.6%) had a relative reduction of more than 50% in Ki67 expression, 13 of these (81.3%) were of NSMP, three (18.8%) of dMMR molecular subtype. Regarding ER expression in these responders, all dMMR and 11/13 NSMP tumors (84.6%) were ER positive. Two NSMP tumors (14.5%) showed a response to endocrine treatment despite being ER negative. Conclusions: Short-term preoperative letrozole treatment enables identification of patients with substantial endocrine treatment response in primary endometrial cancer. Using this preoperative window-of opportunity, dynamic Ki67 evaluation might serve as an easily accessible predictive biomarker to tailor patient-specific treatment decisions.

Integrating static and dynamic modulation: An evaluation of RapidArc Dynamic for left-sided chest wall irradiation.

e12511 Background: Left-sided breast cancer radiotherapy poses a significant challenge in balancing target coverage with the sparing of critical cardiac substructures. RapidArc Dynamic (RAD) is a novel hybrid technique that integrates the continuous arc delivery of volumetric modulated arc therapy (VMAT) with the fixed-beam modulation of intensity modulated radiotherapy (IMRT) through strategic gantry pauses and dynamic collimator rotation. This study aims to evaluate the dosimetric performance of RAD, benchmarking it against IMRT and VMAT, with a specific focus on cardiac substructure sparing and normal tissue complication probability (NTCP). Methods: Twenty patients with left-sided breast cancer treated with post-mastectomy adjuvant radiotherapy were retrospectively enrolled. For each patient, RAD (2 partial arcs with 6 gantry pauses), IMRT (9 fields), and VMAT (5 partial arcs) plans were generated with a prescription of 50 Gy in 25 fractions. Dosimetric metrics, plan complexity, and conformity index were analyzed, and NTCP values were calculated using the Lyman-Kutcher-Burman (LKB) model for multiple endpoints. Results: RAD demonstrated significantly lower (P &lt; 0.05) doses to the heart, left lung, and spinal cord compared to both IMRT and VMAT. Specifically, RAD achieved superior sparing of the left anterior descending coronary artery (LAD) and left ventricle (LV), reducing mean and maximum doses significantly compared to competing modalities. While VMAT resulted in a higher low-dose bath to the contralateral breast, RAD successfully mitigated this issue, delivering significantly lower contralateral doses. Furthermore, RAD yielded significantly lower predicted NTCPs for cardiac perfusion defects, LA major adverse cardiac events, and pulmonary pneumonitis compared to IMRT and VMAT. Conclusions: RAD offers a feasible and effective alternative for left-sided chest radiotherapy, providing an optimal balance between high dose conformity and superior ipsilateral organ sparing. By significantly reducing doses to critical cardiac substructures and minimizing predicted complications, RAD may reduce the risk of late toxicity in breast cancer survivors.

Deconstructing implementation of reflex biomarker testing in non–small cell lung cancer (NSCLC): Diverse strategies to overcome barriers.

e13542 Background: Comprehensive tumor biomarker testing (CBT) is critical and time sensitive for newly diagnosed advanced NSCLC and increasingly for earlier stages. To avoid delays and variability in ordering at the point of oncology visit, reflex CBT (requested by pathology at diagnosis) is recommended (Gosney ESMO Open 2023). However, implementation is challenging due to delays in staging and uncertainty in reimbursement policy, such as CMS 14-day rule and pathologist ordering authority. Literature on reflex CBT mostly describes practices of single large academic institutions. To inform a broad range of institutions, we examined reflex CBT practices and strategies to address challenges across diverse settings. Methods: We interviewed 6 diverse centers (Table) that implemented reflex CBT and achieved ≥80% of reflex CBT for advanced stage patients with results returned ≤ 21 days of diagnosis. Results: Four centers use a 2-step CBT order process with diagnosing pathologists initiating the process and a centralized function placing the order (Table). Two centers use 1-step ordering by diagnosing pathologist or centralized oncology function. To authorize orders, centers proactively identify a treating physician, or use stand-in oncologist or physician ordering biopsy. Three centers test all stages due to economy of scale, expanding indications and patient assistance programs if tested externally. Others use proxy staging based on initial imaging and clinical data. Inpatient orders are delayed at 3 centers due to 14-day rule. Conclusions: Our findings enable reflex CBT implementation in diverse settings by flexibly mixing and matching practices to tailor to institutional operational contexts. Barriers are addressable and should not impede adoption. CENTER CHARACTERISTICS C1 C2 C3 C4 C5 C6 # cases a year ≥500 100 300 250 500 ≥500 # hospitals served 7 1 3 1 3 1 Academic No Yes No No Yes No Where CBT done Send out Send out Send out Send out Inhouse Inhouse CBT ORDER PROCESS Who initiates order process Diagnosing pathologist Diagnosing pathologist Diagnosing pathologist No initiation step No initiation step Diagnosing pathologist Who places order Central function in oncology Central function in oncology Central function in pathology Central function in oncology Diagnosing pathologist Central function in oncology Physician on order Treating or stand-in physician Treating physician Treating physician Treating physician Physician on biopsy Stand-in physician NSCLC stages tested All All Proxy stage III, IV Proxy stage IB, II resectable, III, IV All Proxy stage III, IV Who determines proxy stage N/A N/A Diagnosing pathologist Central function N/A Central function Does 14-day rule Impact inpatient CBT No, ordered same as outpatient Ordered for stage III, IV, others delayed No, ordered same as outpatient Orders delayed No, ordered same as outpatient Orders delayed C1-6, Center 1-6.

Comparative burden of tumor lysis syndrome: ALL vs AML using a national U.S. dataset.

e18529 Background: Tumor lysis syndrome (TLS) is a life-threatening metabolic emergency caused by rapid tumor cell breakdown, resulting in hyperuricemia, hyperkalemia, hyperphosphatemia, and secondary hypocalcemia. These metabolic derangements increase the risk of acute kidney injury, multiorgan failure, and death, particularly in patients with hematologic malignancies. Thus, we aimed to compare in-hospital outcomes among patients with TLS and acute lymphoblastic leukemia (ALL) vs. acute myeloid leukemia (AML) using the National Inpatient Sample (NIS) database. Methods: We conducted a cross-sectional study using the NIS database to identify adult patients hospitalized with TLS (ICD 10:E88.3) and a diagnosis of ALL (ICD 10: C92.0) and AML (ICD 10: C91.0) between 2018-21. Patients were stratified by leukemia subtype (ALL vs. AML). Primary outcomes included in-hospital mortality, length of stay (LOS), and inflation-adjusted total hospital charges, while secondary outcomes included acute kidney injury (AKI), renal replacement therapy (RRT), respiratory failure (RF), mechanical ventilation, sepsis, and non-home discharge. Survey-weighted univariable and multivariable regression models were used to estimate adjusted odds ratios (aORs) and beta coefficients (β), adjusting for demographic and clinical covariates. Results: We identified a cohort of 14,105 patients hospitalized with TLS, including 9,740 (69%) with ALL and 4,365 (31%) with AML. Patients with ALL were significantly older than the AML group (Median age 70 vs. 50 years), but had similar gender distribution (Males 64% vs. 62%). In-hospital mortality was significantly higher among patients with ALL compared with AML (28% vs 13%, p&lt;0.001). After multivariable adjustment, ALL group had almost 85% increased mortality risk (aOR 1.85 [1.43–2.39]) compared to AML group. Additional independent predictors of mortality included weekend admission (aOR 1.39; p=0.004), liver disease (aOR 3.54; p&lt;0.001), and coagulopathy (aOR 2.04; p&lt;0.001). Hospital LOS was significantly longer in patients with ALL after multivariable adjustment (β +2.7 days [1.0–4.4]; p = 0.002), accompanied by non-significantly higher inflation-adjusted total hospital charges (β + $22,275; p=0.3). ALL group (compared to AML) had a higher risk of in-hospital complications, including AKI (70% vs. 49%; aOR 1.37; p = 0.002), need for RRT (11% vs. 6.5%; aOR 1.73; p = 0.006), RF (40% vs. 21%; aOR 1.84; p &lt; 0.001), mechanical ventilation need (17% vs. 11%; aOR 1.75; p &lt; 0.001), sepsis (32% vs. 25%; aOR 1.62; p &lt; 0.001), and non-home discharge (45% vs. 27%; aOR 1.54; p &lt; 0.001). Conclusions: Compared to AML, the ALL group had higher mortality and complication burden among patients with TLS, reinforcing the need for intensified prophylaxis, vigilant monitoring, and early aggressive management in this high-risk population.

Age-stratified outcomes of immune checkpoint inhibitors in geriatric patients with melanoma: A real-world cohort study.

e13779 Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of melanoma and are used across multiple disease stages. Geriatric patients comprise a rapidly growing proportion of patients with melanoma but remain underrepresented in clinical trials, limiting real-world age-stratified data on ICI outcomes in the geriatric population. Methods: We conducted a multicenter retrospective cohort study using the TriNetX platform to compare ICI outcomes in patients aged 65-74 years versus ≥75 years. Patients with Melanoma who had received pembrolizumab, nivolumab, atezolizumab, cemiplimab, durvalumab, and/or ipilimumab were included. We excluded patients receiving concurrent chemotherapy, those with carcinoid tumors, neuroendocrine tumors and hematologic/lymphoid malignancies. Patients with ulcerative colitis, microscopic colitis, Crohn’s disease and history of organ transplant were also excluded to minimize confounding due to chronic immunosuppressive therapy. The index date was first ICI administration. After 1:1 propensity score matching on demographic variables, cohort 1 (age 65-74 years) and cohort 2 (age ≥75 years) included 6223 patients each. The measure of association analysis was used to calculate the proportion of patients with outcomes and survival was analyzed using Kaplan-Meier analysis. The primary outcome was all-cause mortality. Secondary outcomes included ICU admission, systemic corticosteroid initiation, pneumonitis, gastrointestinal colitis/enterocolitis, hepatitis, myocarditis and the use of ICD-10 code for adverse effects of ICIs (T45.AX5 A/D/S). Results: All-cause mortality was significantly lower among patients with melanoma aged 65–74 compared with those aged ≥75 years receiving ICI (27.6% vs 39.1%). The risk difference was −11.4% (95% CI -0.131 to -0.098; p &lt; 0.001), with an odds ratio of 0.596 (95% CI 0.553 to 0.643). No significant age-based differences were observed in ICU admission, myocarditis, or pneumonitis. However, incidence of hepatitis (20.9% vs 16.2% p &lt; 0.001), gastrointestinal colitis/enterocolitis (13.9% vs 10.7% p &lt; 0.001), systemic corticosteroid use (79.8% vs 74.3% p &lt; 0.001) and use of ICD-10 code for adverse effects of ICIs (1.7% vs 1.1% p = 0.005) was more frequent among patients aged 65–74 years. Conclusions: Among patients with melanoma treated with ICIs, those aged ≥75 years had higher all-cause mortality, but had lower rates of ICI-related complications. In contrast, patients aged 64-75 years had lower all-cause mortality but higher incidences of hepatitis, colitis/enterocolitis and systemic steroid use. These findings highlight clinically meaningful differences within the geriatric population, potentially influenced by age-related immune dysregulation, immunosenescence, and co-morbidity burden, and underscore the need for more age-stratified research in geriatric oncology.

Real-world survival outcomes of patients with cholangiocarcinoma receiving chemotherapy versus chemo-immunotherapy: A TriNetX database analysis.

e16305 Background: Cholangiocarcinoma is an aggressive malignancy with poor prognosis, with median overall survival under 12 months in advanced disease. Following the TOPAZ-1 and KEYNOTE-966 trials, chemo-immunotherapy has become standard of care; however, real-world survival data across diverse populations are limited. We evaluated overall survival and safety outcomes of chemo-immunotherapy versus chemotherapy alone using a large international database. Methods: We performed a retrospective international cohort study using the TriNetX Global Collaborative Network. Adults with intrahepatic or extrahepatic cholangiocarcinoma treated between January 1, 2000, and December 31, 2024 were included, excluding those with prior malignancies or pre-index treatment. Chemo-immunotherapy (platinum-based chemotherapy plus durvalumab or pembrolizumab) was compared with chemotherapy alone. The primary outcome was overall survival at 6 months, 1 year, and 2 years; secondary outcomes included hospitalization, sepsis, hematologic toxicity, and immune-related adverse events. Kaplan–Meier and Cox proportional hazards analyses were performed after propensity score matching. Results: After propensity score matching, 1,362 patients were included per cohort with balanced baseline characteristics. At 1 year, chemo-immunotherapy improved overall survival (56.2% vs 50.4%; HR 0.84, 95% CI 0.74–0.94; p = 0.004), consistent with TOPAZ-1 and KEYNOTE-966. This benefit persisted at 2 years, with longer median overall survival (443 vs 370 days; HR 0.88, 95% CI 0.79–0.99; p = 0.019) and sustained Kaplan–Meier separation, though 2-year survival rates were similar. Hospitalization, sepsis, and palliative care rates were comparable however non-significant. Hematologic toxicity was modestly higher with chemo-immunotherapy, while immune-related adverse events remained infrequent, supporting an acceptable real-world safety profile. Conclusions: In this large real-world cohort, chemo-immunotherapy significantly improved 1- and 2-year overall survival versus chemotherapy, with manageable hematologic toxicity and low immune-related adverse events, supporting its use as first-line therapy and validating trial results in diverse patients. Clinical outcomes: chemo-immunotherapy vs chemotherapy alone. Outcome Time Point Chemo-Immunotherapy Chemotherapy Alone Effect Estimate Overall Survival (%) 6 months 73.78 69.97 HR 0.84 (CI 0.72–0.98) 1 year 56.2 50.4 HR 0.84 (0.74–0.94) 2 years 33 32.5 HR 0.88 (0.79–0.99) Hospitalization (Risk) 2 years 0.37 0.32 RR 0.83 (0.70–1.03) Sepsis 2 years 0.18 0.15 RR 1.15 (0.90–1.13) Palliative care 2 years 0.15 0.16 RR 0.91 (0.76–1.10) Hematologic toxicity 2 years 0.17 0.14 RR:1.17 (0.8-0.9) Pneumonitis 2 years 0.08 0.07 RR 1.15 (0.8-1.5) Colitis 2 years 0.06 0.05 RR 1.11 (0.8–1.5)

Neoadjuvant tislelizumab plus chemotherapy in MSS/pMMR high-risk locally advanced colon cancer: Updated analysis results from a phase 2 trial.

3638 Background: Patients with locally advanced colon cancer (LACC) have a poor prognosis, and those with N+ or T4 staging are prone to developing metastases. Only about 5% pathological complete response rates were observed in neoadjuvant chemotherapy. We conducted a single-arm, phase II trial to evaluate the efficacy and safety of immunotherapy combined with chemotherapy in locally advanced colon cancer. Methods: LACC patients clinically staged as T4 or N2 with histologically confirmed microsatellite stable/mismatch repair proficient (MSS/pMMR) type untreated colon adenocarcinoma are eligible for enrollment. Participants received 2-6 cycles of neoadjuvant therapy consisting of capecitabine and oxaliplatin (CAPOX) plus tislelizumab, followed by complete mesocolic excision. The primary endpoint was the pathological complete response (pCR) rate. This study was registered at ClinicalTrials.gov (NCT06124378). Results: A total of 61 patients were enrolled with a median age of 54 years (IQR 43–62). 35 (57%) of the recruited patients had a cT4 tumor and 47 (77%) of the patients had N2. All patients received neoadjuvant CAPOX plus tislelizumab, while three patients were excluded from activity analyses due to adverse events and the patient decision. Among the remaining 58 patients, 16 (28%) patients received 2 cycles, 39 (67%) patients completed 4 cycles, and 3 patients (5%) received 6 cycles prior to surgery. 14% patients achieved clinical complete response and the overall response rate was 91% based on clinical efficacy, with no cases of progressive disease observed. The regimen achieved a pathological complete response (pCR) rate of 41.4%, with all patients undergoing R0 resection. The major pathological response rate was 51.7% (95% CI 38.6 to 64.6). In subgroup analyses, patients with right-sided tumors exhibited higher pCR rates (16 [47%, 95% CI 30–65] of 34, compared to 8 [33%, 95% CI 17–54] of 24 for left-sided cases. However, no statistically significant differences were observed between the subgroups. Treatment-related adverse events of any grade occurred in 52 (85.2%) of 61 patients. The most common adverse events were peripheral sensory neurotoxicity (37 [61%] of 61) and decreased appetite (31 [51%]). Grade 3 drug-related serious adverse events occurred in 8 (13%) patients while no grade 4–5 adverse events occurred. Conclusions: This prospective trial demonstrates that neoadjuvant tislelizumab plus CAPOX provides a promising treatment strategy with encouraging antitumor activity and a manageable safety profile for MSS/pMMR locally advanced colon cancer. Clinical trial information: NCT06124378 .

Eiu-104101: A first-in-human phase 1a/1b study of EVOLVE104, a trispecific CD3×CD2×ULBP2/5/6 T-cell engager, in advanced urothelial and squamous cell carcinomas.

TPS2682 Background: EVOLVE T cell engagers (TCEs) bind to a tumor antigen and to both CD3 and CD2 on T cells, thereby providing integrated costimulation via CD2 binding. EVOLVE TCEs demonstrate superior T cell activation and tumor cell killing compared to first generation TCEs, without excess cytokine release or tonic T cell activation, and may offer clinical benefits such as enhanced potency and duration of activity. UL16 binding proteins 2, 5 and 6 (ULBP2/5/6) belong to a family of cell surface proteins that are ligands for the NKG2D receptor. We have previously reported that cell-surface ULBP2/5/6 is not present in vital organs and found in some mucosal epithelia. Cell surface ULBP2/5/6 is found in urothelial carcinomas and squamous cell carcinomas (SCCs). With high expression on malignant cells and limited normal tissue expression, ULBP2/5/6 are intriguing targets for cancer immunotherapy. EVOLVE104 is a trispecific TCE that binds ULBP2/5/6 and both CD3 and CD2 on T cells. Preclinical studies with EVOLVE104 demonstrated enhanced T cell activation and killing of ULBP2/5/6-positive tumor cells compared to bispecific TCEs, and no safety concerns were identified in preclinical toxicity studies. With this encouraging preclinical profile, EVOLVE104 represents a novel approach to redirected T cell therapy in solid tumors. Methods: EIU-104101 is a first-in-human phase 1a/1b study evaluating EVOLVE104 monotherapy in adults with advanced solid tumors. Eligible tumor types include urothelial carcinoma of the bladder and SCCs of the bladder, lung, esophagus, tongue, skin, and anogenital region (penis, anus, vagina, vulva, cervix, and urethra). Subjects must have locally advanced or metastatic disease that has relapsed from, or is refractory to, standard-of-care therapies. Study objectives include assessing the safety, efficacy, pharmacokinetics and pharmacodynamics of EVOLVE104 and identifying the recommended phase 2 dose (RP2D). The phase 1a portion of the study will enroll up to 80 subjects using a Bayesian optimal interval (BOIN) dose-escalation scheme including backfill at dose levels deemed safe, with a key objective to identify one or more recommended doses for expansion (RDEs). Phase 1b includes two expansion cohorts: Cohort A, which will be a dose optimization cohort in a single indication (to be determined based on the phase 1a observations) in which 40 subjects will be randomized 1:1 to two RDEs to determine the RP2D; and Cohort B, which will enroll up to 40 subjects in other relevant indications. The study opened in October 2025 and is actively enrolling at US sites. ClinicalTrials.gov Identifier: NCT07217171. Clinical trial information: NCT07217171 .

First-line odronextamab (Odro) plus chemotherapy (CHOP) in diffuse large B-cell lymphoma (DLBCL): OLYMPIA-3 Part 1B results.

7009 Background: Approximately 25% of patients (pts) treated with rituximab + CHOP do not have a complete response (CR), and those with refractory/relapsed disease or high-risk features have poor outcomes. To address this unmet need, bispecific antibody combinations are being evaluated. In Part 1A (dose escalation) of the Phase 3 OLYMPIA-3 study (NCT06091865), odronextamab (Odro)-CHOP demonstrated generally manageable safety (most common treatment-emergent adverse events [TEAE] were neutropenia [81.8%] and cytokine release syndrome [CRS; 54.5%]) and encouraging preliminary efficacy in pts with previously untreated DLBCL, with CR rates of 100% on PET/CT (160 mg dose level, selected for Part 1B dose optimization). Here, we report Part 1B results. Methods: Part 1B included pts aged ≥18 years with untreated CD20+ DLBCL not otherwise specified or high-grade B-cell lymphoma with at least 1 high-risk feature. Odro-CHOP was administered in 6 × 21-day cycles, with Odro 0.7/4/20 mg step-up dosing from Cycle 1 Day 8. Pts were randomized 1:1 to receive Odro 160 mg QW/320 mg Q2W (Regimen [R] 1) or Odro 160 mg QW/160 mg Q3W (R2) with CHOP. Primary endpoint was safety. Secondary endpoints included investigator-assessed objective response rate (ORR) and CR rate per 2014 Lugano criteria. Results: At data cut-off (August 19, 2025), 40 pts were enrolled in Part 1B (20 per regimen). Median age was 67.5 years, 60.0% of pts were male, and 75.0% had an IPI score of 3–5. Median duration of treatment exposure was 18.1 weeks (R1) and 16.6 weeks (R2); 67.5% of pts completed 6 treatment cycles. Median relative dose intensity ranged from 90.1 to 100% for Odro and 92.7 to 100% for CHOP. The safety profile of Odro-CHOP was similar across regimens. TEAEs led to dose interruption/delay in 70.0% vs 50.0% of pts and to CHOP dose reduction in 10.0% vs 5.0% of pts with R1 vs R2, respectively. No TEAEs led to Odro dose reduction and 1 led to treatment discontinuation (Grade 4 neutropenic sepsis, R2). The most common TEAEs were neutropenia (57.5%), CRS (55.0%), and anemia (42.5%). CRS rates were consistent with Part 1A, predominantly Grade 1 (42.5% of pts). ICANS occurred in 3 pts (all Grade 1) and resolved completely. All enrolled pts were analyzed including 3 pts who discontinued treatment prior to tumor imaging assessment. With a median follow-up of 2.3 months in both regimens, ORRs were 95.0% (R1) and 90.0% (R2), and CR rates were 85.0% (both regimens). Conclusions: In Part 1B of OLYMPIA-3, the safety profile of Odro-CHOP was generally manageable and preliminary efficacy was encouraging with no meaningful differences between regimens, and combination with Odro did not impact the delivery of CHOP. Given these results, the less frequent Odro dosing regimen (R2) with CHOP was selected as the recommended Phase 3 dose for Part 2 (randomized controlled trial). Biomarker data will be presented. Clinical trial information: NCT06091865 .

Minimally invasive versus open esophagectomy for resectable esophageal cancer: Systematic review and meta-analysis of randomized controlled trials.

e16117 Background: Minimally invasive esophagectomy (MIE; thoracoscopic/robotic/hybrid) is on the rise for resectable esophageal cancer, but the impact on long-term survival and key postoperative outcomes between MIE and open transthoracic esophagectomy remains clinically important. We aim to compare MIE versus open transthoracic esophagectomy in terms of efficacy and safety. Methods: PubMed, Embase, Cochrane Library and ClinicalTrials.gov were searched for randomized controlled trials comparing MIE (including hybrid and robotic-assisted approaches) with open transthoracic esophagectomy. The primary endpoint was overall survival (OS). Secondary endpoints were pulmonary complications and major morbidity; anastomotic leak and short-term mortality were further included in the analysis. Outcomes were pooled as hazard ratios (HRs), and binary outcomes as risk ratios (RRs), using a DerSimonian and Laird random-effects model; heterogeneity was assessed with I². Results: Six RCTs were included for perioperative endpoints (data summarized in Table.1). MIE was associated with improved OS HR 0.75 (95% CI 0.57-0.99; I² = 0%). Pulmonary complications were significantly reduced with MIE RR 0.65 (95% CI 0.47-0.90; I² = 51.0%). There was a non-significant reduction in major morbidity RR 0.81 (95% CI 0.64-1.02; I² = 62.6%). Anastomotic leak was non-significantly higher with MIE RR 1.36 (95% CI 0.97-1.91; I² = 0%). Short-term mortality did not differ between approaches RR 0.97 (95% CI 0.43-2.22; I² = 0%). Conclusions: MIE is associated with improved OS and fewer pulmonary complications versus open transthoracic esophagectomy, with no clear difference in short-term mortality. Anastomotic leak was non-significantly higher with MIE, which signals the importance of continued optimization of anastomotic technique as MIE becomes more widely adopted. Data summery table with event counts for each outcome. Trial Pulmonary Events Major Morbidity Anastomotic Leak Short-term Mortality Biere et al, 2012 7/59 vs 19/56 - 7/59 vs 4/56 1/59 vs 0/56 Paireder et al, 2018 3/14 vs 3/12 6/14 vs 4/12 3/14 vs 2/12 0/14 vs 1/12 Mariette et al, 2019 18/102 vs 31/103 37/103 vs 67/104 11/102 vs 7/103 1/103 vs 2/104 Van der Sluis et al, 2019 17/54 vs 32/55 32/54 vs 44/55 13/54 vs 11/55 1/54 vs 0/55 ROMIO Study Group 2024 85/258 vs 91/261 82/258 vs 88/261 21/258 vs 21/261 4/259 vs 6/261 Takeuchi et al, 2025 12/150 vs 18/150 63/150 vs 65/150 17/150 vs 7/150 4/150 vs 2/150 Total 142/637 vs 194/637 220/579 vs 268/582 72/637 vs 52/637 11/639 vs 11/638