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A hybrid CNN-DNN model for battery remaining useful life RUL prediction

Regulation of chromatin dynamics by a calcium-dependent nucleoskeleton

Effect of smoking status on risk of mortality for patients with lung cancer treated with immunotherapy.

e20648 Background: Immune checkpoint inhibitors have become a mainstay of treatment for lung cancer. However, their effectiveness varies, and is strongly influenced by patient characteristics. Smoking is the most important etiologic factor for lung cancer, and is expected to be associated with a high tumor mutational burden, which may in turn influence immunotherapy response. However, the extent to which smoking status modifies the benefit of immunotherapy in real-world populations is not well established. Methods: We identified 43,437 cases of invasive lung cancer with documentation of smoking status from the California Cancer Registry 2010-2021. Immunotherapy was documented as given or not given. Smoking status was defined as never, current or former. Cox regression was used to assess the unadjusted risk of mortality associated with immunotherapy and after adjusting for age, sex, race/ethnicity, stage, socio-economic status (SES), Charlson Comorbidity Index and insurance status. Analyses were conducted separately for current and former and never smokers. Results: Smoking status was documented for 43,347 cases (never = 15.887, current = 27,056, and former = 404). There were 4,014 cases treated with immunotherapy. The unadjusted risk of mortality for patients treated with immunotherapy was increased in non-smokers whereas immunotherapy reduced the risk of mortality in current and former smokers. After adjustment, all patients had a reduced risk of mortality, but current and former smokers had a higher risk reduction than non-smokers. Conclusions: Smoking modifies the effect of immunotherapy in patients with lung cancer, and our data suggests patients who currently or formerly smoked may derive a greater benefit from immunotherapy. This will need careful patient messaging as we continue public efforts towards smoking cessation. Unadjusted and adjusted* hazard ratios and 95% confidence intervals for immunotherapy. Unadjusted Adjusted* HR (95%CI) HR (95%CI) Never smokers 1.35 (1.26, 1.45) 0.76 (0.70, 0.82) Current or former smoker 0.86 (0.82, 0.91) 0.52 (0.49, 0.55) *Adjusting for age, sex, race/ethnicity, stage, SES, Charlson Comorbidity Index and insurance status.

Mortality involving breast cancer and chronic lower respiratory diseases among postmenopausal women in the United States: A CDC WONDER analysis (1999–2020).

e13785 Background: Breast cancer and chronic lower respiratory diseases (CLRD) are leading causes of mortality among postmenopausal women in the United States and frequently coexist due to shared risk factors such as aging and multimorbidity. Despite being leading causes of mortality, national trends and population-level disparities in deaths involving both conditions remain underexplored. Methods: We analyzed CDC WONDER data from 1999 to 2020 to assess mortality among postmenopausal women (≥55 years) with breast cancer and CLRD listed as multiple causes of death. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated using the 2000 U.S. standard population. Trends were stratified by age, race/ethnicity, census region, state, and urbanization status, and evaluated using Joinpoint regression to estimate annual percent change (APC) with 95% confidence intervals. Results: From 1999 to 2020, a total of 51,726 deaths involved co-listed breast cancer and CLRD. Overall AAMRs declined from 1999 to 2017 (APC: −0.80; p < 0.001) but rose sharply from 2017 to 2020 (APC: 4.41; p < 0.001). Non-Hispanic Black women experienced a sustained increase (APC: 1.40; p = 0.0004), while Non-Hispanic White women showed declines until 2018, followed by a reversal. Women aged ≥75 years had the highest mortality and largest recent increase. Regionally, the South showed a consistent upward trend post-2017, with state-level AAMRs ranging from highest in West Virginia to lowest in Utah. Metropolitan areas accounted for higher absolute deaths, whereas non-metropolitan areas exhibited persistently rising rates over time. Conclusions: Breast cancer and CLRD mortality rates among postmenopausal women declined for nearly two decades rising after 2017, with significant disparities by race, geography, urbanization and age. Higher mortality persisted among Non-Hispanic Black women, older adults, and rural populations emphasizes structural inequities and vulnerability to healthcare disruptions. Focused public health interventions addressing multimorbidity and access to care are essential to reduce mortality in high risk populations. Joinpoint APC in age-adjusted mortality, US subgroups (1999–2020). Variable Duration APC Lower 95% CI Upper 95% CI p-value Overall 1999–2017 -0.8 -1.02 -0.58 <0.01 Northeast 1999–2018 -1.52 -2.19 -1.13 0.01 Midwest 1999–2018 -1.04 -3.06 -0.23 0.04 South 2017–2020 6.45 1.12 12.32 <0.01 West 1999–2018 -1.49 -4.87 3.67 0.07 Age 55–74 1999–2017 -1.47 -1.98 -1.2 <0.01 Age 75+ 2006–2017 -1 -3.72 -0.57 <0.01 Metropolitan 1999–2017 -1.03 -1.23 -0.83 <0.01 Black or African American 1999–2020 1.4 0.76 2.25 <0.01 White 1999–2018 -0.53 -0.8 -0.32 <0.01

Allogeneic hematopoietic cell transplantation following chimeric antigen receptor T-cell (CAR-T) therapy in B-cell acute lymphoblastic leukemia (B-ALL): A systematic review and meta-analysis.

e18577 Background: Chimeric antigen receptor T-cell (CAR-T) therapy induces high initial response rates in B-cell acute lymphoblastic leukemia (B-ALL); however, relapse remains frequent. The impact of allogeneic hematopoietic cell transplantation (allo-HCT) following CAR-T therapy on long-term outcomes remains uncertain. We performed a meta-analysis to evaluate survival and relapse outcomes associated with allo-HCT after CAR-T therapy in B-ALL. Methods: Eligible comparative studies evaluating allo-HCT after CAR-T therapy versus no transplant were identified through a systematic search following PRISMA guidelines. Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted for overall survival (OS), leukemia-free survival (LFS), and relapse. Pooled estimates were calculated using inverse-variance methods. Fixed-effects models were applied when heterogeneity was minimal (I²<50%); random-effects models were used otherwise. Heterogeneity was assessed using Cochran’s Q and I² statistics. Publication bias was assessed qualitatively using funnel plots. Results: Five retrospective studies encompassing 127 patients were included. Cohorts included pediatric, adolescent/young adult, and adult patients with relapsed/refractory B-ALL (median ages of 11-44 years across studies; male predominance, when reported). Most patients achieved complete remission (CR) with minimal residual disease (MRD) negativity post-CAR-T (MRD-negative pre-HCT in 78–93% of reported cases). Donors were unrelated in 39%, matched siblings in 31%, and haploidentical in 30% of reported cases (n=93 donors); conditioning regimens included cyclophosphamide/fludarabine or TBI-based myeloablative approaches. The median interval from CAR-T infusion to allo-HCT was approximately 3 months (range 2–10 months). Three studies contributed to the OS analysis and five to the LFS analysis. Allo-HCT after CAR-T was associated with improved OS (pooled HR 0.49; 95% CI, 0.33–0.72; p=0.0004; I²=0%). LFS was also improved (HR 0.30; 95% CI: 0.16–0.55; p=0.0001; I²=80.9%). Relapse risk was markedly lower with allo-HCT (HR 0.16; 95% CI: 0.10–0.23; p<0.001; I²=0%; two studies). Transplant-related mortality ranged 3-29% across reports, with notable acute/chronic graft-versus-host disease and infections. Conclusions: Allo-HCT following CAR-T therapy was associated with improved survival in selected patients with B-ALL, driven primarily by reduced relapse risk. These findings support further prospective evaluation of allo-HCT after CAR-T therapy.

Prognostic impact of actionable driver alterations and efficacy of targeted therapy in lung squamous cell carcinoma: A large-scale nationwide genomic screening (LC-SCRUM-Asia).

8631 Background: Precision medicine based on multi-gene analysis improves prognosis and has established multigene analysis as the standard of care in lung adenocarcinoma.However, the clinical utility of multi-gene analysis in lung squamous cell carcinoma (LUSC) remains controversial due to the rarity of actionable driver alterations and the uncertain therapeutic benefits of targeted therapy. This study aimed to elucidate the prognostic value of driver alterations and the efficacy of targeted therapy in LUSC. Methods: We have prospectively analyzed patients with non-small cell lung cancer (NSCLC) enrolled in a nationwide genomic screening project in Japan (LC-SCRUM-Asia) using NGS (Oncomine Comprehensive/Precision Assay). We evaluated clinical outcomes in patients with LUSC, comparing overall survival (OS) according to the presence of actionable driver alterations and receipt of targeted therapy. Results: From March 2015 to October 2025, 19,357 patients were enrolled, of whom 2,917 had LUSC. Among these LUSC patients, actionable driver alterations were identified in 180 patients (6.2%) cases, including EGFR mutations (n = 78), KRAS G12C (n = 33), MET exon 14 skipping (n = 28), ALK fusions (n = 18), EGFR exon 20 insertions (n = 7), RET fusions (n = 6), ROS1 fusions (n = 5), BRAF V600E (n = 4), and HER2 exon 20 insertions (n = 1).In the survival analysis of 2,017 patients with advanced/recurrent disease, median OS was significantly longer in patients with actionable driver alterations compared to those without (18.2 vs. 15.0 months; HR 0.79, p = 0.02). However, among patients with actionable driver alterations, there was no significant difference in median OS between patients who received targeted therapies (n = 97) and those who did not (n = 45) (18.3 vs. 17.0 months, p = 0.94). The efficacy of targeted therapies was notably limited; median progression-free survival was 12.4 months for ALK tyrosine kinase inhibitors (TKIs) (n = 17), 8.4 months for EGFR TKIs (n = 46), 4.5 months for KRAS G12C inhibitors (n = 10), 3.6 months for MET TKIs (n = 15), and 3.4 months for ROS1 TKIs (n = 5). Collectively, these outcomes were consistently inferior to those reported in pivotal clinical trials. Conclusions: Although actionable driver alterations were identified in approximately 6% of LUSC and were associated with a favorable prognosis, targeted therapy demonstrated limited efficacy and failed to extend overall survival compared to non-targeted approaches. These findings indicate that the clinical utility of multi-gene analysis in LUSC is currently limited, highlighting the need for the development of novel therapeutic strategies specific to this histology.

Age-stratified evaluation of subsequent primary malignancy risk in patients with primary Lynch syndrome–spectrum cancers.

10620 Background: Lynch syndrome spectrum cancers (LSSC) include several of the most common cancers in both men and women. Patients with LS are advised to undergo intensive cancer screening and genetic evaluation. However, most at-risk individuals are not assessed by a cancer geneticist, especially those in middle or older age, despite these cancers often appearing late in life. This study evaluates the incidence and timing of LS-related and non-LS–related subsequent primary malignancy (SPMs) in patients diagnosed with LSSCs. Methods: We used SEER data (1992–2021) to identify patients with LSSC — colorectal (CRC), endometrial (EC), gastric, Bladder/GU tract (GUC), Small bowel, ovarian, pancreatic, sebaceous, and brain (BC) by using histology and site code. Demographics, survival data, and SPMs details were extracted. Patient were stratified by age < 40 years, 40-60 years, and > 60 years. We calculated the mortality-related competitive risk-adjusted cumulative incidence (CI) of SPMs at 5 and 10 years for both LSSCs and all cancers. Median follow up were calculated by reverse KM method. We calculated the time to the development of 1 st SPM after the index cancer diagnosis. Proportions were compared using chi-square test. Results: We identified 774955 patients with LSSC (50.4% Female, mean age 66.2 (SD 13.3) with a median follow-up of 149 months. 74331 (9.6%) patients developed a subsequent malignancy, with 30666 (41.3%) of all SPM had at least 1 LSSC. In < 40 year, 40-60-year, and > 60 years groups, 4.5%, 8.1%, and 10.5 % of total patients with LSSCs had a SPM of which 68.2%, and 43.3%, and 39.9 % patient had at least 1 LSSCs (p < 0.001). Median time to cancers and adjusted CI is given in the table. There was significant difference in distribution of primary (p-value < 0.01) and subsequent (p-value < 0.01) LSSC. CRC was the most common primary LSSC across age group, with Brain, and EC, and GU Cancers were the 2 nd most common cancer in < 40, 40-60, and > 60-year age group respectively representing 19.3%, 16.7%, and 22.9% cancers of respective LSSCs. Among SPM, CRC was the most common across all age group (42.8% of LSS SPM) whereas EC was 2 nd most common LSS SPM in < 40 years, and GU cancers in both 40-60 (35%), and > 60 (31.8%) years group. Conclusions: For LSSC patient, likelihood of developing SPM increased with longer survival, and older patients demonstrated the highest SPM burden for both LSSC and non-LSSCs. These findings suggest that cancer genetics evaluation and robust LS-directed surveillance should be extended beyond younger populations, as older patients remain at significant risk for LS-related SPMs. Age group 18-40 Years 41-60 Years >60 Years Median follow up (months) 131 141 155 Median time to any SPM 40 52 28 Median time to subsequent LSSC 22 28 22 Any SPM 5-year CI % 2.8 4.7 7.8 10-year CI % 3.7 7.1 10.6 Subsequent LSSC 5-year CI % 2.3 2.4 3.3 10-year CI % 2.8 3.2 4.3

Real-world efficacy and safety of neoadjuvant TCHP in HER2-positive non-metastatic breast cancer in a government tertiary care center in India.

e12643 Background: Randomized trials support Docetaxel, Carboplatin, Trastuzumab, and Pertuzumab (TCHP) in HER2-positive breast cancer; however, real-world evidence from low- and middle-income countries and public-sector hospitals remains limited. Following the introduction of generic Trastuzumab and Pertuzumab in India, access to dual HER2 blockade has expanded in government healthcare systems. This study presents the first Indian government-sector real-world evaluation of neoadjuvant TCHP. Methods: We conducted a retrospective cohort study of 53 patients with non-metastatic HER2-positive breast cancer treated with neoadjuvant TCHP at a tertiary government hospital between 2019 and 2025. The primary endpoint was pathological complete response (pCR; ypT0/is ypN0). Toxicity was graded using CTCAE v5.0. Exact 95% confidence intervals (CI) were calculated using the Clopper–Pearson method, and Fisher’s exact test compared pCR rates between hormone receptor (HR) subgroups. Results: Of 53 patients, 24 (45.3%) were HR-positive and 29 (54.7%) HR-negative. Stage distribution was 2 (3.8%) stage I, 14 (26.4%) stage II, and 38 (71.7%) stage III. The overall pCR rate was 58.5% (31/53; 95% CI, 44.1–71.9%).pCR rates were consistent across subgroups. By HR status, pCR occurred in 54.2% (13/24; 95% CI, 32.8–74.4%) of HR-positive and 62.1% (18/29; 95% CI, 42.3–79.3%) of HR-negative tumors (p = 0.587). By clinical stage, pCR was achieved in 50.0% (1/2; 95% CI, 1.3–98.7%) of stage I, 57.1% (8/14; 95% CI, 28.9–82.3%) of stage II, and 57.9% (22/38; 95% CI, 40.8–73.7%) of stage III patients, demonstrating preserved efficacy despite advanced disease.Treatment adherence was 96.2% (51/53). Grade 3 diarrhea occurred in 7.5% and Grade 2 neutropenia in 5.7%. No Grade 4 toxicities or treatment-related deaths occurred. Conclusions: This first Indian government-sector real-world study demonstrates that neoadjuvant TCHP in the post-generic HER2-therapy era achieves high and consistent pCR across HR and stage subgroups, including a cohort predominantly composed of stage III disease. Outcomes were comparable to pivotal international trials, with high treatment completion and acceptable toxicity. These findings support scalable implementation of dual HER2-targeted neoadjuvant therapy in public healthcare systems, with relevance for resource-constrained oncology settings globally.

National real-world adoption of 5-fraction breast radiotherapy in the United States (2020–2023).

590 Background: The landmark FAST-Forward trial demonstrated that ultra-hypofractionated whole-breast irradiation with 26 Gy in 5 fractions over 1 week was non-inferior to 40 Gy in 15 fractions for local control (HR 0.67, 95% CI 0.38–1.16), with similar normal tissue effects at 5 years. In response, major international guidelines incorporated 26 Gy in 5 fractions as a standard approach or recommended option for selected patients. Despite robust randomized evidence and guideline endorsement, U.S. real-world adoption patterns and equity of uptake across patient populations remain incompletely characterized. This study evaluated national trends in 5-fraction breast radiotherapy and sociodemographic differences from 2020 to 2023. Methods: The National Cancer Database radiotherapy fractionation fields were used to identify radiotherapy (RT) courses with evaluable fraction counts, and a binary indicator for 5-fraction RT (yes/no) was created. Temporal trends by diagnosis year (2020–2023) were assessed, and associations between 5-fraction RT and sociodemographic factors (primary insurance, urban or rural status, neighborhood income quartile, and race) were examined using chi-square testing. Results: Among 536,783 RT courses with complete data from 2020 to 2023, use of 5-fraction RT increased substantially over time: 4.3% in 2020, 8.1% in 2021, 12.7% in 2022, and 17.4% in 2023, resulting in an overall adoption rate of 10.7% (p < 0.001). In the subset eligible for fractionation (5, 15–16, 25–28 fractions; N = 31,448), 5-fraction RT accounted for 11.7% and differed significantly by insurance type (p < 0.001): Medicare 17.4%, Private 7.6%, Medicaid 5.9%, and Uninsured 6.9%. Geographic variation was notable (p < 0.001), ranging from 7.3% in mid-size metropolitan areas (250,000–1 million population) to 17.7%–18.1% in more remote or non-adjacent areas; large metropolitan areas (≥1 million) had 12.8% uptake. Neighborhood income showed a gradient (p < 0.001): 10.1% in the lowest quartile compared to 12.5% in the highest. Race was also associated with uptake (p < 0.001), with lower use among Black patients compared to White patients (9.4% vs 12.2%). Conclusions: In routine U.S. practice, adoption of 5-fraction breast RT increased rapidly from 2020 to 2023, with the most pronounced growth after 2021, reflecting the swift translation of trial evidence into clinical practice. However, uptake varies by insurance, geography, income, and race, indicating that diffusion is not uniform. Given the potential benefits of ultra-hypofractionation in reducing treatment burden and supporting timely completion, targeted implementation strategies, such as provider education, reimbursement alignment, and facility-level operational support, may be necessary to ensure equitable access as 5-fraction regimens become more widely adopted and potentially become the standard of care.

Spevatamig (PT886), a claudin 18.2 (CLDN18.2)/CD47 bispecific antibody, in combination with gemcitabine plus nab-paclitaxel (GnP) in frontline (1L) treatment of metastatic pancreatic ductal adenocarcinoma (mPDAC).

4192 Background: Spevatamig is an IgG1-based bispecific antibody targeting CLDN18.2 and CD47 with an optimized anti-CD47 arm designed to bind to CD47 more highly on cancer cells than on human red blood cells. We have previously described its monotherapy safety data and preliminary combination efficacy data in 1L mPDAC (Saeed et al., J Clin Oncol. 2026). Herein, we provide updated data from patients in the 1L mPDAC cohort, including additional efficacy data from the 2 mg/kg QW spevatamig + GnP dose level and new safety data from the 3 mg/kg QW spevatamig + GnP dose level. Methods: TWINPEAK is a multi-cohort Phase 1/2 dose escalation and expansion study (US: NCT05482893; China: CTR20252758) of spevatamig as monotherapy or combination therapy (with chemotherapy and/or an immune-checkpoint inhibitor) in patients with select gastrointestinal (GI) cancers. Here we report data from the Phase 2 cohort of spevatamig + GnP in 1L mPDAC at 2 dose levels: 2 mg/kg QW (N=22) and 3 mg/kg QW (N=22). Key endpoints include safety and tolerability, objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS) and median overall survival (mOS). Results: As of January 15, 2026, 151 patients have been treated with spevatamig collectively in monotherapy and combination settings. In the 2 mg/kg QW spevatamig + GnP dose level (N=22), spevatamig continues to demonstrate tolerability when combined with chemotherapy, with cytopenia rates not exceeding those anticipated with GnP and no grade ≥ 3 nausea or vomiting events. The ORR is 48%, DCR is 90%, mPFS is 7.3 months (95% confidence interval: 5.6 months - not yet reached) and mOS is > 13 months (still maturing), with a median follow-up duration of 8.9 months. Antitumor activity was demonstrated irrespective of tumor CLDN18.2 expression levels and RAS mutational status. In the 3 mg/kg QW spevatamig + GnP dose level (N=22), no significant additive toxicity was noted when compared to the adverse event profile anticipated with GnP alone among patients with available safety data. No grade ≥ 3 nausea or vomiting events occurred. Updated safety data will be provided at the meeting for patients in this dose level. Conclusions: Overall, spevatamig 2 mg/kg QW or 3 mg/kg QW + GnP is well tolerated, with no significant additive toxicity compared to the adverse event profile anticipated with GnP alone. The additional efficacy data from patients treated at the 2 mg/kg QW spevatamig + GnP dose level continues to demonstrate promise when compared to pivotal trials of GnP in 1L mPDAC; enrollment into the 3 mg/kg QW spevatamig + GnP dose level is ongoing with maturing efficacy data. These two dose levels exhibit good combinability with chemotherapy and can be assessed in future combination studies with novel targeted therapies such as KRAS inhibitors. Clinical trial information: NCT05482893 .

Phase 2 sequential treatment of percutaneous hepatic perfusion with melphalan/hepatic delivery system followed by tebentafusp in the treatment of metastatic uveal melanoma.

TPS9605 Background: Metastatic uveal melanoma (mUM) typically has a poor prognosis with limited treatment options. Tebentafusp (TEBE) is the only approved systemic agent for HLA-A*02:01 positive mUM, and percutaneous hepatic perfusion (PHP) is FDA approved for patients with mUM in the liver (solely or predominantly). Combining PHP with nivolumab plus ipilimumab in the randomized phase 2 CHOPIN trial significantly improved overall response (ORR), progression-free survival (PFS) and overall survival (OS) compared to PHP alone, but with significantly higher grade 3 or greater adverse events. In the phase 3 TEBE clinical trial there was a modest ORR of 11%, and improved OS compared to investigator choice therapy. We hypothesize that PHP causes antigen release and changes in the hepatic tumor microenvironment that may enhance response to TEBE. In this investigator-initiated trial, we aim to explore the combination of sequential regional and systemic therapy in HLA-A*02:01 positive mUM patients. Methods: This is a single institution phase 2 clinical trial combining PHP using the melphalan hepatic delivery system for 2 cycles followed sequentially by intravenous TEBE at approved dosage for up to 1 year of therapy. For patients with unequivocal progression on TEBE, up to 4 additional cycles of PHP will be considered if they continue to meet standard eligibility for PHP. The primary objective is to assess the PFS in uveal melanoma patients who have isolated or liver dominant metastases with landmark analyses at 6 months, 12 months and 24 months. Secondary objectives include (1) toxicity, (2) objective response and duration of response, (3) hepatic and extra-hepatic PFS, (4) OS, (5) biomarker discovery, RNA sequencing and spatial immunofluorescence analysis of the tumor microenvironment through core biopsies performed pre-PHP, after PHP number 2, and post-TEBE treatment. Blood samples for immune panel analysis will be collected at these timepoints. Response assessments are undertaken with standard cross-sectional imaging every 12 weeks for 36 months. Planned accrual is 18 patients with an interim futility analysis after 10 patients are treated to assess the 6-month PFS for the cohort. Primary analysis will be performed using the Kaplan-Meier method. Salient eligibility criteria include: (1) age ≥18 years, (2) histologically confirmed metastatic UM, HLA-A*02:01 positive, (3) measurable disease per RECIST v1.1, (4) ECOG performance status of ≤1, (5) adequate marrow, renal and hepatic function; (6) no more than 50% of liver involvement by tumor. Limited extrahepatic disease is allowed. This study opened for enrollment in November 2025, and two patients have been treated to date (NCT07276386). This study is supported by Delcath Systems, Inc. Clinical trial information: NCT07276386 .

Reducing ED utilization for oncologic neutropenic and non-neutropenic fever through an urgent care pathway: A quality improvement project.

e23282 Background: Emergency department (ED) utilization by oncology patients is high and wait times can be long, potentially increasing risk of pathogen exposure. Several cancer centers have piloted pathways for oncology patients to be evaluated and treated in urgent cares (UCs), however, they are commonly underutilized for initial evaluation of acute, low risk, oncology related chief concerns. This quality improvement (QI) study aims to increase UC utilization for low risk, adult, solid oncology patients presenting with neutropenic or non-neutropenic fever at the University of California, Los Angeles Jonsson Comprehensive Cancer Center (UCLA). Methods: To evaluate the need for a clinical pathway for neutropenic and non-neutropenic fever in adult solid oncology patients, a retrospective chart review of patients seen in the UCLA ED from February to August 2024 was performed to determine the number of patients that would meet criteria for the proposed UC pathway. These criteria were based on the Multinational Association for Supportive Care in Cancer (MASCC) score for neutropenic patients, and oncology physician clinical judgement based on severity of illness and discharge or admission status for non-neutropenic patients. Demographic information, rate of preventable ED visits, time spent in ED, time to intravenous (IV) antibiotics, and time to IV fluids were also collected. These findings supported the development of a QI project, with an upcoming intervention—the oncologic fever UC management pathway. This pathway will refer eligible patients to a “Next Day Clinic” for outpatient management of non-neutropenic or neutropenic fever. Results: 40 eligible patients were evaluated during the study period. Median age was 62 years. 23/40 (57.5 %) were female. 7/40 (17.5%) were neutropenic. Based on our pre-determined criteria, 2/7 neutropenic patients would be eligible for the proposed UC pathway. Of non-neutropenic patients, 6/33 (18.2%) were discharged from the ED and also deemed eligible for the pathway. 34/40 (85%) were admitted with a median hospital length of stay of 3 days. Median time to antibiotics was 126 minutes. Median time to IV fluids was 147 minutes. Median time spent in the ED prior to admission or discharge orders was 235 minutes. 3/40 (7.5%) received a Granulocyte Colony-Stimulating Factor (G-CSF) product within 10 days preceding the ED encounter. 7/40 (17.5%) received G-CSF during the inpatient admission. 0/40 patients were evaluated in UC prior to the ED encounter. Conclusions: Baseline data from this retrospective study revealed long ED wait times, several potentially preventable ED visits, and that UCLA UC clinics are severely underutilized for initial evaluation of oncologic fever. These findings support the upcoming launch of the UC oncologic fever pathway as part of a QI project that aims to optimize high quality, patient-centered, oncologic care.

Clinical characterization of patients with molecular glioblastoma.

e14074 Background: Glioblastoma (GBM) represents a highly aggressive type of WHO grade 4 intracranial tumor with a median survival of 12-15 months, ranging from 10-24 months. Our understanding of the molecular features of these tumors and their impact on treatment response and overall survival (OS) has been evolving. Here, we describe the clinical characterization of molecular glioblastoma (mol-GBM), a newly described subset of IDH-wildtype and H3-wildtype gliomas that harbor at least one diagnostic molecular alteration (EGFR amplification, pTERT mutation, +7/-10 chromosomal alterations) in the absence of WHO grade 4 histological features (necrosis and/or microvascular proliferation). Methods: A retrospective chart review of patients diagnosed with GBM seen at MedStar Georgetown University Hospital between 2021 and 2025 was conducted. Clinical and diagnostic data were reviewed. OS was determined. Results: Of the 347 charts reviewed, 281 met WHO 2021 GBM criteria. 19 patients (7%; 6 male/13 female) fit criteria for mol-GBM, with average age at diagnosis of 66 years (range 43-80). Thirteen patients had supratentorial involvement affecting ≥ 2 lobes, 3 patients had brainstem lesions, and 3 patients had unilobar tumors. MRI showed non-enhancing (15/19) or minimally enhancing lesions (4/19), with infiltrative homogenous FLAIR hyperintensity and mass effect in 13/19 cases. Thirteen patients underwent biopsy; 6 had resection. Histopathology revealed diffusely infiltrating astrocytic neoplasms of variable cellularity and without grade 4 histologic features. Ki-67 proliferation index ranged from 1-30%. Molecular features diagnostic of mol-GBM were pTERT (17/19), EGFR amplification (2/19), and +7/-10 chromosomal alteration (8/19). Mol-GBM diagnosis was further supported in 4 cases by DNA methylation profiling. Common additional mutations included PTEN (10/19), EGFR (6/19) and NF1 (5/19). No tumors harbored PIK3R1 alterations. Three patients had tumors with PIK3CA pathogenic mutations. Thirteen of 15 patients had unmethylated MGMT. Ten patients started concomitant chemoradiation, 2 discontinued due to side effects. Average time from symptom onset to diagnosis was 4.3 months, and from surgery to start of radiation was 30.9 weeks. Median OS of 14 patients was 15.6 months; mean OS: 18.3 months; range: 1-78 months. Six patients are still alive. Conclusions: Our cohort showed no meaningful difference in OS between patients with mol-GBM and histologically diagnosed GBM. We found that our mol-GBM cases uniformly lacked the typical high-gradeMRI characteristics and had histopathologic features suggestive of low-grade glioma, despite aggressive clinical behavior and poor prognosis, emphasizing the importance of recognizing this diagnostic consideration. Additional research is needed to further define this intriguing GBM subset and to determine the appropriate management of patients with this disease.

Trends in hypofractionation, stereotactic body radiotherapy, metastatic radiotherapy utilization, and plan pricing at a tertiary cancer center: A plan-level analysis (2018–2024).

e23210 Background: Hypofractionation radiotherapy is supported by robust evidence across multiple disease sites, yet real- world adoption patterns, economic implications, and the extent to which changes reflect sustained practice evolution rather than transient responses to the COVID-19 pandemic remain incompletely characterized, particularly in low-middle-income settings. Methods: We conducted a retrospective analysis of all curative and/or ablative external beam radiotherapy courses delivered at a tertiary cancer center between January 2018 and December 2024. Temporal trends in fractionation, metastasis-directed radiotherapy utilization, and radiotherapy plan pricing were evaluated using Spearman correlation, linear regression, generalized additive models, and data- driven change-point analysis. An approximate standardized plan price was derived from institutionally adopted pricing schedules to enable longitudinal comparisons. Results: A total of 10,527 radiotherapy plans delivered to 9,285 patients were analyzed. The mean number of fractions per treatment course declined from 23.4 in 2018 to 17.2 in 2024 (Spearman ρ = −0.93, p = 0.003). Statistically significant reductions were observed for breast, prostate, and colorectal cancers, with disease-specific change-points occurring in 2019–2021. The overall cohort change-point occurred in early 2022, with confidence intervals, excluding March 2020, suggesting that adoption was not temporally driven by COVID-19. The proportion of metastatic radiotherapy plans increased from 8.2% to 19.7% over the study period (ρ = 0.93, p = 0.0025). Among plans with pricing data, the mean radiotherapy plan price declined from approximately 7,299 ± 1,755 USD in 2018 to 6,933 ± 1,976 USD in 2024, corresponding to an average decrease of 83 USD per plan per year (p = 0.015). Pricing for metastatic plans remained stable over time. Conclusions: Hypofractionation and Stereotactic Body Radiotherapy adoption at this high-volume center reflects a sustained, evidence-based evolution in practice across multiple disease sites. This shift was accompanied by increased use of radiotherapy for metastatic disease and a reduction in average plan pricing for high-volume primary cancers, underscoring the role of hypofractionation and Stereotactic Body Radiotherapy in improving treatment efficiency and health- system value in resource-constrained settings.

Morphological features of melanoma destruction under the influence of EGFR inhibitors: Gefitinib and a novel pyrimidine derivative.

e21539 Background: The global rise in cutaneous melanoma incidence necessitates the search for new therapeutic targets. The EGFR signaling pathway is associated with proliferation, tumor cell survival, and the development of resistance to targeted and immunotherapy, making it an attractive target for further study. The aim of this work was to investigate the effect of the EGFR inhibitor gefitinib and a novel 2-styryl derivative of 4-oxo-1,4-dihydropyrimidine (6MPSoVn), which possesses affinity for the internal domain of EGFR, on tumor morphology in the B16/F10 melanoma model. Methods: C57Bl/6 mice with transplanted B16/F10 melanoma were divided into three groups: group 1 (n=20) received oral gefitinib, group 2 (n=20) – i.p. 6MPSoVn and the control group (n=20) – i.p. vehicle. Treatment started on the day of tumor transplantation according to the schedule: 5 days of administration followed by a 2-day break; the total duration of the course was 14 days. On day 14, animals were euthanized, followed by morphological examination of the tumor tissue. Sections 5–7 μm thick were stained with hematoxylin and eosin. Microscopy was performed using a Leica DMLS2 microscope equipped with an Olympus digital camera and an image analysis system. Results: The mean tumor volume in the control group was 3.7±0.6 cm³ (M±m), while in the gefitinib and 6MPSoVn groups it was 2.3±0.5 cm³ and 2.4±0.6 cm³, respectively. In the control group, the tumor structure was characterized by a dense arrangement of cells with large polymorphic nuclei and numerous melanin granules in the cytoplasm. In the gefitinib group, the tumor structure was partially preserved; however tumor cell shrinkage due to cytoplasmic condensation without loss of plasma membrane integrity was observed. Nuclear fragmentation was accompanied by the formation of apoptotic bodies and melanin aggregation in areas of cell death. These changes are characteristic of apoptosis. In the 6MPSoVn group, extensive areas of tumor necrosis were revealed (more than 60% of the section area). Tumor cells showed signs of dystrophy and degeneration: karyopyknosis, vacuolization, cytoplasmic lysis, loss of plasma membrane integrity, and release of melanin granules into the extracellular space. Foci of destruction exhibited pronounced lymphocytic infiltration. Loose fibrous connective tissue with a histiocytic component formed at the tumor periphery. These morphological features may also indicate necroptosis, which requires further investigation using IHC methods. Conclusions: Thus, EGFR inhibitors are capable of causing irreversible damage to melanoma cells in vivo . Cell death induced by gefitinib occurs via the mechanism of apoptosis, whereas the novel compound 6MPSoVn induces B16/F10 melanoma cell death predominantly via the necrosis pathway, accompanied by connective tissue proliferation and signs of immune activation.

The effectiveness of a multidisciplinary pain program in improving adherence to the use of aromatase inhibitors in breast cancer survivors.

12122 Background: Aromatase Inhibitors (AI) have become the standard of care to reduce breast cancer recurrence in hormone receptor-positive (HR+) breast cancer patients. AIs have been shown to be effective in reducing the risk of breast cancer recurrence by 47%. However, up to 52% of patients prematurely discontinue their use due to AI-associated musculoskeletal pain symptoms called Aromatase Inhibitor-associated musculoskeletal pain syndrome (AIMSS). No effective treatment exists to treat AIMSS. The present study examined the effectiveness of a multicomponent pain treatment program in reducing symptoms of AIMSS with the goal of improving adherence to AI medication. Methods: This trial enrolled breast cancer survivors with AIMSS in an intensive multicomponent pain treatment program. Pain, impact on functioning, fatigue, and mood were assessed with the Brief Pain Inventory, Center for Epidemiologic Studies of Depression- Revised Questionnaire, Pain Catastrophizing Scale, Symptom Impact Questionnaire Revised, and Fatigue Questionnaire at baseline, 3-month, 6-month, 9-month, and 12-month intervals. Adherence to AI medication was obtained from patients’ self-reports. The treatment program consisted of a two-day structured intervention focused on Cognitive-Behavioral skills to address strategies to improve pain control, fatigue, sleep disturbance, and stress while educating patients on the efficacy of Aromatase Inhibitors in prolonging cancer-free survival. Results: A total of 73 patients were enrolled, with a median age of 63 years (range 31-79). Participants were primarily white, married, and highly educated. The measures showed elevated levels of pain, fatigue, and psychological distress at baseline with decrements in self-reported levels of functioning. Significant improvements across all measures were observed at the 3-month follow-up after participation in the multicomponent pain treatment program. Significant improvements in painrelated outcomes were observed at 3 months (WPI Δ −1.6; SS Δ −4.0; both p < 0.001), with sustained reductions in symptom severity through 6-month, 9-month, and 12-month follow-up. Self-report of AI medication adherence at one year showed that 77.9% of patients were still taking their prescribed medication. Conclusions: Patients with AIMSS experienced substantial emotional distress, pain, fatigue, and functional impairment at baseline. Following the intervention, significant improvements were observed across pain, physical functioning, fatigue, and psychological distress, with benefits sustained at one year. Importantly, the intervention was associated with high long-term adherence at one-year follow-up, highlighting its potential to improve both quality of life and treatment persistence.

A phase 1b study of xaluritamig (a STEAP1 x CD3 T-cell engager) in pediatric, adolescent, and adult patients with relapsed/refractory (R/R) Ewing sarcoma.

TPS10057 Background: Ewing sarcoma (EWS) is an aggressive tumor of the bone and soft tissue primarily affecting adolescents and young adults. For patients with recurrent disease, outcomes remain poor with 5-year survival rates of 10%–15%, highlighting the need for novel approaches. STEAP1 is highly expressed in EWS cell lines, xenograft models, and patient tumor samples 1 and is transcriptionally regulated by EWSR1::FLI1 , the main oncogenic driver in EWS. Xaluritamig, a humanized bispecific XmAb 2+1 T-cell engager targeting STEAP1 and CD3, has demonstrated potent, antigen-dependent T-cell–mediated lysis of STEAP1-expressing EWS cell lines 1 and induced robust in vivo antitumor activity in EWS xenograft models with concomitant CD8+ T-cell activation. In metastatic castration-resistant prostate cancer, another STEAP1-expressing solid malignancy, xaluritamig has shown meaningful antitumor activity and a manageable safety profile 2 supporting its clinical evaluation in R/R EWS. Methods: This ongoing, phase 1b, single-arm, open-label, two-part, multicenter study (NCT07297979) is evaluating xaluritamig in pediatric, adolescent, and adult patients with a histologic diagnosis of EWS and an EWSR1 :: ETS fusion gene locally confirmed by next-generation sequencing. Patients must have R/R EWS following ≥1 line of systemic therapy and Karnofsky or Lansky performance status ≥70. Part 1 (dose confirmation) consists of cohort 1 (age ≥12 years) and cohort 2 (age ≥2 to <12 years), and part 2 (dose expansion) includes patients aged ≥2 years with no upper age limit at enrollment. This study includes a 21-day screening period, a treatment period, a safety follow-up period, and a long-term follow-up period. Patients receive xaluritamig every 2 weeks once reaching the target dose until radiographic disease progression per RECIST v1.1, clinical disease progression, unacceptable toxicity, initiation of other anticancer therapy not permitted per protocol, withdrawal of consent, death, or end of study as determined by the sponsor, whichever is earlier. Primary endpoints are safety, tolerability, and determination of recommended dose(s) for expansion. Secondary endpoints are pharmacokinetics, preliminary antitumor activity, and immunogenicity. Biomarker evaluation as an exploratory endpoint includes assessment of serum cytokines, other pro-inflammatory markers, immune-cell subsets, circulating tumor DNA, STEAP1 protein expression, and tumor genomic profile and their association with safety and efficacy. CRS mitigation plan includes step-up dosing, steroid premedication, and administration of interleukin-6 inhibitors as needed. Site activation commenced in January 2026 and enrollment is ongoing. 1. Nolan-Stevaux O. Cancer Res. 2020;80(16_Suppl):DDT02–03. 2. Kelly WK, Danila DC, Lin CC, et al. Cancer Discov . 2024;14(1):76-89. Clinical trial information: NCT07297979 .

Associations between circulating immunologic markers and HCC in individuals with chronic HCV infection.

e16271 Background: Although immunologic proteins have been associated with hepatocellular carcinoma (HCC) development, little is known about whether these associations are with HCC or underlying fibrosis/cirrhosis. Methods: We sampled 92 HCC cases and 184 controls from The Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) prospective study. All participants were chronically infected with hepatitis C virus (HCV) and presented with advanced fibrosis or cirrhosis. Conditional logistic regression was used to compare baseline plasma levels for 248 markers in individuals who developed HCC vs. controls. We also evaluated the association between immune markers and cirrhosis (Ishak 5-6) vs. fibrosis (Ishak 3-4) among controls. We assessed biological pathways associated with HCC development compared to controls. P-values for individual markers and pathways were corrected for multiple testing; p-value < 0.05 was used to determine significance among a-priori markers. Results: After multivariable adjustment, three a-priori markers: ICAM-1 (Q 4v1 OR: 8.1; 95%CI: 2.8-23.4), HGF (Q 4v1 OR: 3.1; 95%CI: 1.2-8.0), SCF (Q 4v1 OR: 0.4; 95%CI: 0.2-0.9) and seven novel markers: ACE2 (Q 4v1 OR: 5.2; 95%CI: 1.8-15.2), CDH1 (Q 4v1 OR: 3.2; 95%CI: 1.3-7.5), CD244 (Q 4v1 OR: 4.6; 95%CI: 1.8-12.0), OPG (Q 4v1 OR: 6.1; 95%CI: 2.1-17.4), TNFRSF10A (Q 4v1 OR: 3.3; 95%CI: 1.4-8.1), NOTCH1 (Q 4v1 OR: 2.8; 95%CI: 1.2-6.5), and HAOX1 (Q 4v1 OR: 3.4; 95%CI: 1.3-8.7) were significantly associated with HCC development. All three a-priori markers, as well as ACE2, CDH1, and CD244, were shown to be significantly associated with cirrhosis vs. fibrosis. Biological pathways related to apoptotic process, cellular response to cytokine stimulus, extracellular matrix organization and inflammatory response were associated with HCC development. Conclusions: We confirmed the association of ICAM-1, HGF, and SCF and identified 7 additional proteins associated with HCV-related HCC in the context of underlying fibrosis/cirrhosis.

Immune-related adverse event severity and clinical outcomes with immune checkpoint inhibitor immunotherapy in participants with non–small cell lung cancer: Analysis of the lung MAP sub-studies S1400A, S1400I, S1400F, and S1800A.

8572 Background: Immune checkpoint inhibitors (ICIs) have advanced the treatment paradigm for non-small cell lung cancer (NSCLC), but ICIs are associated with risk of immune-related adverse events (irAEs). There is an unmet need to better understand how the severity of irAE impacts the clinical outcome of NSCLC treated with ICIs. We hypothesized that participants (pts) with lower grade irAEs would have better outcomes than those with higher grade irAEs and those without irAEs. Methods: We evaluated outcomes in Lung-MAP pts with advanced NSCLC treated with ICIs in the 2L setting (S1400A [durvalumab vs docetaxel], S1400I [nivolumab +/- ipilimumab], S1400F [durvalumab + tremelimumab], and S1800A [pembrolizumab + ramucirumab vs standard-of-care]), using 6-, 12-, and 24-week landmark analyses of the relationship between irAE severity (Grade(G) 1 or 2 vs G3 or 4 and vs no irAE) and overall survival (OS) from the landmark timepoint. OS was compared between groups using Cox Proportional hazards model with separate analyses for ICI-naïve (S1400A and S1400I) and ICI-exposed (S1400F and S1800A). Results: Analyses included 315 ICI-naïve and 127 ICI-refractory pts. In the ICI- naïve cohort, no irAEs and G 3-4 irAEs were associated with inferior OS compared with G1-2 irAEs by 12 wks of treatment (no irAEs: HR 1.68, CI 1.28 – 2.22, p < 0.0005 G3-4: HR 2.28, CI 1.47 – 3.53; p < 0.0005). This difference in OS between the irAE groups was consistent at the 6 wk (p = 0.006) and 24 wk (p = 0.03) landmark timepoints. See table for outcomes in the ICI naïve cohort. In the ICI-exposed cohort, there was no difference in OS between the irAE groups at any landmark timepoint (6 weeks: p = 0.39; 24 weeks: p = 0.98). Conclusions: In the ICI-naïve cohort, G1-2 irAEs in were associated with better OS compared to no irAEs and G3-4 irAEs for all landmark times. This association was not observed in the ICI-exposed cohort. Additional analyses will incorporate molecular and immune features evaluating risk and severity of irAEs. Outcomes for ICI naïve cohort. Landmark Time irAE Group N mOS (95% CI) 6 weeks No irAE 160 9.0 (7.9-10.9) G 1-2 124 14.6 (10.1-19.0) G 3-4 20 5.9 (3.5-10.8) 12 weeks No irAE 124 8.2 (6.5-9.8) G 1-2 130 15.4 (11.5-9.8) G 3-4 29 5.3 (2.9 - 8.0) 24 weeks No irAE 77 7.0 (5.8-9.8) G 1-2 121 14.9 (10.9-18.5) G 3-4 34 5.9 (3.1-13.9)

Overall survival in patients with extensive stage small cell lung cancer treated with durvalumab instead of atezolizumab.

e20136 Background: Standard of care treatment for patients with extensive-stage small cell lung cancer (ES-SCLC) includes a combination of chemotherapy (cisplatin or carboplatin plus etoposide) and a programed death ligand 1 (PD-L1) targeted monoclonal antibody. The use of immunotherapy has significantly improved overall survival (OS) for ES-SCLC patients. However, no head-to-head trials have addressed which immunotherapy provides superior outcomes in this population. To our knowledge, this is the first large-scale study that compares OS for patients who received Durvalumab vs Atezolizumab in their treatment for ES-SCLC. Methods: A retrospective cohort study using the TriNetX Research Network, a federated platform of HIPAA-compliant patient records from 158 healthcare organizations (HCO) from the Global Collaborative Network was carried out. We compared first-line outcomes of atezolizumab vs durvalumab in patients with ES-SCLC. Cohorts were balanced for age and sex. Overall survival (OS) was assessed via Kaplan-Meier analysis. Tarlatamab was excluded from primary analysis and evaluated in a separate secondary query. Results: From January 2019 to December 2025, 6,750 patients were identified across 113 HCOs for each balanced cohort. Durvalumab demonstrated superior OS compared to Atezolizumab [p < 0.0001]. Durvalumab patients had a lower risk of brain metastasis (OR 0.348). Brain metastasis at the time of diagnosis showed that patients who received Durvalumab maintained superior OS [p < 0.0001]. Patients who received messenger ribonucleic acid (mRNA) COVID vaccines within 100 days of initiation of the treatment had better OS than those who didn’t, an effect observed in both Durvalumab [p = 0.0004] and Atezolizumab [p < 0.001]. In the vaccinated patients, Durvalumab demonstrated better OS. Survival probabilities for Durvalumab vs. Atezolizumab at 6, 12, and 24 months were 88% vs. 73%, 77% vs. 50%, and 64% vs. 33%, respectively. When patients received Tarlatamab, there was no longer a difference in OS regardless of the front-line treatment received. Conclusions: In ES-SCLC patients, Durvalumab had statistically superior OS compared to Atezolizumab. Although COVID mRNA vaccination improved overall outcomes, the survival advantage for Durvalumab remained. This benefit also persisted in patients with brain metastases. While PD-L1 inhibitors often show comparable effects across trials, this real-world database analysis revealed significant outcome differences warranting further investigation. Future analyses should evaluate the long-term effects of Tarlatamab as mature data becomes available, given its recent Food and Drug Administration approval. Although TriNetX relies on coding accuracy, survival exceeded those reported in pivotal trials, highlighting the need for prospective clinical trials to address this question for the treatment of ES-SCLC.