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Tumor-agnostic and cross-indication actionable alterations in <i>IDH</i> -wildtype glioma: Precision oncology opportunities in an aggressive disease.

e14060 Background: Gliomas have few approved targeted therapies. Given frequent blood-brain-barrier disruption in gliomas, molecular targets with FDA-approved therapies in other solid tumors represent relevant precision-oncology opportunity. Methods: A total of 235 glioma tumor tissue samples underwent targeted next-generation sequencing at Datar Cancer Genetics. Clinical actionability was assessed using ESCAT. Subgroup analyses were performed based on IDH status. Results: Of 235 samples, 6 were grade I (2.6%), 17 grade II (7.2%), 38 grade III (16.2%), and 159 grade IV (67.8%); grade was unavailable in 15 (6.4%). Overall, 43.8% (103/235) harbored ≥1 tumor-agnostic or cross-indication actionable alteration with an FDA-approved therapy in solid tumors. Tumor-agnostic biomarkers included TMB-H (11.6%; 16/138), dMMR (1.7%; 2/116), BRAF V600E (4.9%; 11/225), and NTRK fusions (0.6%; 1/178); HER2 amplifications and RET fusions were not detected. Canonical CNS alterations included IDH1/2 (24.0%; 54/225), TERT promoter (36.1%; 73/202), TP53 (42.4%; 95/224), H3F3A (3.8%; 7/185), ATRX (8.2%; 18/219), EGFR amplification (21.2%; 43/203), CDKN2A/2B loss (18.8%; 38/202), EGFRvIII (12.9%; 23/178), and EGFR mutations (10.7%; 24/225). Cross-indication alterations involved PI3K-AKT-mTOR ( PIK3CA 8.4% [19/225], PTEN 18.3% [41/224]) and FGFR (4.3%; 10/235); KIAA1549-BRAF and PTPRZ1-MET fusions were each detected in 1.1% (2/178). ESCAT Tier I alterations were present in 29% (69/235) and Tier II–III in 56% (132/235). Though incidence of tumor-agnostic biomarkers was similar in IDH -mutant and IDH -wildtype ( IDH -WT) gliomas (13.0% [7/54] vs 11.6% [21/181]), the cross-indication biomarkers were enriched in IDH -WT gliomas (40.9% [74/181] vs 20.4% [11/54]). In grade IV gliomas, cross-indication biomarkers were more frequent in IDH -WT than IDH -mutant tumors (45.3% [62/137] vs 18.2% [4/22]), with similar findings in combined grade III–IV gliomas (42.9% [66/154] vs 25.6% [11/43]). Conclusions: Despite poorer prognosis, IDH -WT gliomas are enriched for cross-indication actionable alterations, reflecting biological actionability without established clinical benefit, and supporting comprehensive molecular profiling to guide indication-expanded therapies, clinical trial enrolment, and prospective interventional basket trials. Tumor-agnostic and cross-indication actionable alterations in gliomas. Biomarker Overall % (n/N) IDH -WT (%) IDH -Mutant (%) Approved Indication PTEN mutations 18.3 (41/224) 21.8 7.4 Breast FGFR1/2/3 alterations 4.3 (10/235) 5.5 0.0 Multiple ERBB2 mutations 0.0 (0/179) 0.0 0.0 Multiple BRCA1/2 mutations 0.6 (1/156) 0.8 0.0 Multiple PIK3CA mutations 8.4 (19/225) 7.6 11.1 Breast TMB-H 11.6 (16/138) 8.9 23.1 Tumor-agnostic dMMR/MSI-H 1.7 (2/116) 2.0 0.0 Tumor-agnostic NTRK fusions 0.6 (1/178) 0.7 0.0 Tumor-agnostic

Phase 2 study of intratumoral oncolytic VV1 plus cemiplimab: Simon's stage 1 results from head and neck squamous cell carcinoma (HNSCC) cohort.

e18026 Background: Immune checkpoint inhibitor (ICI) therapy is part of standard of care first-line therapy for recurrent or metastatic (R/M) HNSCC. However, less than 20% of patients (CPS ≥1) have an objective response to ICI monotherapy, and most tumors progress within ~3 months. We sought to improve the proportion of patients who benefit from a chemotherapy-free regimen by combining intratumoral (IT) VV1 oncolytic virus (VSV-IFNβ-NIS) injections with the anti-PD-1 antibody, cemiplimab. We report a pre-planned analysis of Simon's stage 1 results. Methods: We activated a phase 2 study testing the efficacy of first line IT VV1 plus cemiplimab in 1 st line patients with R/M HNSCC. A Simon's two-stage design was employed whereby 10 patients would be accrued in stage 1, and if 3 or more responses were observed, 12 additional patients would be accrued for stage 2. The primary endpoint was objective response rate (ORR) per investigator (RECIST 1.1). Eligible patients had untreated R/M HNSCC from primary oropharynx, oral cavity, hypopharynx, or larynx sites with CPS ≥1. Patients had to have at least one measurable lesion amenable to IT injection. Treatment comprised of IT injections to 1-5 lesions of oncolytic VV-1 virus and IV cemiplimab 350 mg on day 1, repeated every 21 days. Each lesion could be injected 3 times; a 4th injection was allowed if a partial response (PR) was achieved after 3 injections. Cemiplimab could be continued for up to 2 years until progression or unacceptable toxicity. Results: Patient and tumor characteristics, as well as efficacy and toxicity are summarized in the table below. Ten patients were treated at the time of Stage 1 analysis, with 3 showing a confirmed PR for ORR of 30%. Responder CPS scores were 45, 12 and 20%. Two of the responders subsequently showed progression after 6.2 and 9.9 months, the third has maintained PR at 7.7 months to date. Eight of 10 patients showed decrease in the sum of target lesion size (mean decrease of 16%; range -57 to 77%). One grade 2 event of ICI nephritis resolved with corticosteroid treatment. Conclusions: Three patients showed confirmed PR by RECIST 1.1 in Simon's stage 1, meeting criteria to proceed to Simon's stage 2. A total of 22 patients in the HNSCC will be enrolled. VV1 plus cemiplimab shows promise in first line R/M HNSCC based on these initial results. Clinical trial information: NCT04291105 . Patient demographics. N (treated) 10 Sex 20% female Median age (y) 60 (54 – 76) Oropharynx 7 HPV+ 7 Oral cavity 3 PD-L1 CPS median (range) 7.5 (1-45%) Locoregional injection 3 Distant injection 6 Local and distant injection 1 Best response (RECIST 1.1) PR 3 SD 5 PD 2 Adverse Events #pts any VV1/cemiplimab-related G3 AE 4 Lymphopenia 3 Elevated ALK 1

OMAHA-004: Phase 3 trial of the steroidogenesis inhibitor opevesostat versus androgen receptor pathway inhibitor (ARPI) switch in participants with metastatic castration-resistant prostate cancer (mCRPC) after a prior ARPI.

TPS5135 Background: Opevesostat (MK-5684; ODM-208) is an oral, nonsteroidal inhibitor of cytochrome P450 11A1 (CYP11A1), a catalyst of the first and rate-limiting step of steroid biosynthesis. Opevesostat showed antitumor activity in participants with heavily pretreated mCRPC in the phase 1/2 CYPIDES trial. The randomized, open-label, phase 3 OMAHA-004 trial (NCT06136650) is designed to evaluate the efficacy and safety of opevesostat in participants with mCRPC after a prior ARPI. Methods: Eligible participants have mCRPC that progressed during androgen deprivation therapy ≤6 months before screening and on or after 1 ARPI for metastatic or nonmetastatic hormone-sensitive prostate cancer (HSPC) or CRPC for ≥8 weeks (≥14 weeks with bone progression). Prior ARPI plus docetaxel for HSPC is permitted if participants received no more than 6 cycles of docetaxel without radiographic disease progression. Approximately 1314 participants will be randomized 1:1 to opevesostat 5 mg orally twice-daily plus dexamethasone 1.5 mg and fludrocortisone 0.1 mg orally once daily or abiraterone acetate 1000 mg orally once daily plus prednisone 5 mg orally twice daily (if prior enzalutamide, darolutamide, or apalutamide) or enzalutamide 160 mg orally once-daily (if prior abiraterone). Stratification factors are metastatic site (bone only vs liver vs other), androgen receptor ligand binding mutation (AR-LBDm) status (positive vs negative), and prior docetaxel treatment for HSPC (yes vs no). Once the predefined enrollment threshold for participants with either mutation status (AR-LBDm-positive, ~400 participants or AR-LBDm-negative, ~914 participants) is met, no additional participants with that mutation status will be permitted to enroll. The protocol was amended to use radiographic progression-free survival per Prostate Cancer Working Group 3 (PCWG3)-modified RECIST v1.1 by blinded independent central review (BICR), analyzed separately in participants with AR-LBDm–positive and –negative disease, as the primary end point and overall survival as a key secondary end point. Other secondary end points include time to initiation of first subsequent anticancer therapy or death, objective response rate and duration of response per PCWG3-modified RECIST v1.1 by BICR, time to pain progression; time to prostate-specific antigen (PSA) progression, PSA response rate, time to first symptomatic skeletal-related event, and safety and tolerability. Enrollment is ongoing. Clinical trial information: NCT06136650 .

Closing the depression gap in community oncology: Real-world outcomes from collaborative care.

12088 Background: Depression is prevalent among patients with cancer, yet access to evidence-based care remains uneven. Community oncology clinics, where the majority of cancer care occurs, are less likely to offer integrated mental health services compared to comprehensive cancer centers, resulting in higher underdiagnosis, undertreatment, and persistent depressive symptoms. The Collaborative Care Model (CoCM) offers a potential strategy to address this disparity in community oncology. Methods: Community oncology patients with clinically significant symptoms of depression, as measured by a baseline PHQ-9 score ≥ 5, and receiving collaborative care, delivered primarily remotely, for at least 80 days were analyzed as part of this observational study. Patients had their PHQ-9 assessed after 90 (≥ 80 &amp; ≤ 100) days, including evidence of remission (PHQ-9 &lt; 5) and signs of response (decrease of PHQ-9 score by ≥ 50% or ≥ 5 points). Mean within-patient changes among all patients, stratified by baseline depression severity, were measured using paired t-tests. Results: Among 307 patients, mean PHQ-9 scores were observed to decline from 12.9 (SD 4.7) at baseline to 8.2 (SD 5.1) after 90 days of collaborative care (mean change -4.72, 95% CI -5.30 to -4.14, P&lt; 0.001); 26.7% were observed to have depressive symptoms in remission and 51.5% had a clinical response. Patients with severe depression (PHQ-9 &gt;=20) at baseline had the largest improvement (mean change -9.60, 95% CI -11.78 to -7.42, P &lt; 0.001). Conclusions: Community oncology patients with depressive symptoms receiving collaborative care experienced reductions in PHQ-9 scores after 90 days of care, with a substantial proportion experiencing clinical response and/or remission in this brief timeframe. Symptom changes were observed across the full spectrum of symptom severity. These real-world outcomes highlight meaningful decreases in depressive symptoms, underscoring the promise of CoCM as a scalable care model for community oncology clinics. Observed depression outcomes among community oncology patients engaged in Collaborative Care Model (CoCM) psychosocial care for 90 days, stratified by baseline PHQ-9 severity. PHQ-9 Score Category at Baseline N Mean PHQ-9 Score at Baseline (SD) Mean PHQ-9 Score at 90 Days (SD) N Observed in Remission at 90 Days (%) N Experiencing Response at 90 Days (%) Mean Total PHQ-9 Score Change(95% CI) All (5–27) 307 12.9 (4.7) 8.2 (5.1) 82 (26.7) 158 (51.5) -4.72*** (-5.30, -4.14) Mild (5-9) 81 7.2 (1.4) 5.4 (3.6) 36 (44.4) 26 (32.1) -1.86*** (-2.64, -1.08) Moderate (10-14) 113 11.9 (1.4) 7.8 (4.2) 28 (24.8) 55 (48.7) -4.08*** (-4.85, -3.31) Moderately Severe (15-19) 83 16.5 (1.4) 9.9 (5.5) 15 (18.1) 55 (66.3) -6.61*** (-7.85, -5.38) Severe (20-27) 30 21.9 (1.6) 12.3 (6.0) &lt;11 22 (73.3) -9.60*** (-11.78, -7.42) ***P&lt;0.001.

Support of academic non-clinical efforts for cancer investigator faculty at Association of American Cancer Institutes.

9005 Background: Academic non-clinical time (NCT) for physician scientists (PS) and clinical investigators (CI) is critical in advancing novel scientific findings from the laboratory to the community through clinical trials implemented to improve patient outcomes. CI are uniquely positioned to bridge these bench findings to bedside applications given their dual clinical and research training. However, CI face increasing competing pressures that threaten this career path. The Association of American Cancer Institutes (AACI) Physician Clinical Leadership Initiative (PCLI) conducted a national survey in 2018 to identify trends in academic NCT for the physician-trained researchers across US academic cancer centers involved in basic, translational, or clinical research. We recently reevaluated allocation of academic NCT to support faculty. Methods: In 2024, AACI PCLI electronically sent a 20-question descriptive survey to 95 academic cancer centers. Survey items assessed the time commitments of medical oncologists caring for patients with hematologic (including cellular therapy and stem cell transplantation) and solid tumor malignancies, as well as institutional academic NCT policies and incentive structures. Responses were summarized using descriptive statistics for quantitative items and qualitative review for open-ended responses. Results: Sixty centers (63%) participated. Clinical effort expectations and the amount of academic NCT varied widely by center and faculty role. The median expected effort was 30% (IQR 18%) clinical research and 50% (IQR 14%) direct patient care for CI, and 70% (IQR 20%) basic/clinical research and 20% (IQR 10%) direct patient care for PS. The most common duration of CI startup academic NCT support was 3 years, but this varied greatly across centers. Most centers required external funding to continue academic NCT (48% for CI and 72% for PS). PS were more likely than CI to receive more sustained support when some degree of extramural funding was obtained. Nearly 80% of CI academic NCT was supported by cancer center funds. Clinical trial accrual was the top priority for academic NCT for faculty engaged in clinical research, while mentoring and teaching ranked among the lowest. Incentive plans for clinically active faculty were common (85% of centers) and were largely work relative value unit (wRVU)-based, with limited incorporation of research or mentoring contributions. Conclusions: This survey highlights systemic failures in institutional support for CI, including inconsistent allocation of academic NCT, limited support duration, misaligned incentives, and lack of succession planning. These findings underscore the need for sustainable, multisource funding models, recalibrated incentive structures, and robust mentoring pathways to retain and advance CI for accelerating cancer research through advancing discoveries into the clinic.

Day-7 single-cell RNA sequencing of acute lung responses after 17-Gy whole-thorax irradiation in mice.

e24193 Background: Radiation pneumonitis (RP) is a clinically important toxicity of thoracic radiotherapy and can set the stage for later fibrotic remodeling. The early post-irradiation window is attractive for intervention, but the multicellular biology of acute RP is not well resolved. We used day-7 single-cell RNA sequencing (scRNA-seq) in a murine RP model to define actionable pathways and potential biomarkers relevant to radiation oncology. Methods: Ten-week-old male C57BL/6 mice received single-fraction 17 Gy whole-thorax irradiation (IR) or sham control (NC). Day-7 micro-CT confirmed pneumonitis-like opacities. Lungs were processed for 10x Genomics scRNA-seq (OeBio; IR n = 3, NC n = 3). After filtering doublets/low-quality cells, 7,587–9,040 cells per sample were retained (mean UMI/cell 6,082–6,916; mean genes/cell 2,099–2,107; mitochondrial UMI fraction 0.0262–0.0329). Integrated analysis yielded 17 clusters spanning T cells, neutrophils, monocytes, macrophage lineages (including alveolar macrophages, AMs), Dendritic cells (DCs), B cells, Natural killer (NK) cells and stromal/epithelial compartments. Differential expression with GO/KEGG enrichment was performed. Results: By day 7, IR shifted the lung toward innate inflammation: neutrophils and monocytes increased, while T/NK and B cells decreased; AMs were markedly reduced. Across myeloid subsets, enrichment converged on TNF/NF-κB, NOD-like receptor, IL-17 signaling, and oxidative-stress programs. Neutrophils showed a lipid-mediator shift (Alox5ap up; Ptgs2 and Acod1 down), and monocytes upregulated acute-phase and lipid-inflammatory genes (Saa3, Pla2g7). Tissue compartments demonstrated parallel injury responses: Type II alveolar epithelial (AT2) cells increased DNA damage/senescence markers (Cdkn1a) with inflammatory response modules, and endothelium showed leukocyte-recruitment and inflammatory/Type I IFN features (Icam1 up). Antigen processing/presentation programs were reduced in AMs and AT2 cells (Cd74/MHC-II down). In lymphoid subsets, γδT17/ILC signatures were enriched for stress-associated pathways, supporting an IL-17–linked inflammatory niche with weakened adaptive immune crosstalk. Conclusions: Acute RP at day 7 after 17 Gy whole-thorax irradiation is characterized by a coordinated IL-17/NOD–Type I IFN injury program, myeloid lipid-mediator rewiring, and early loss of antigen-presentation capacity in AMs and AT2 cells. These data highlight tractable mitigation directions (IL-23/IL-17 signaling, leukotriene-related pathways, and myeloid recruitment) and nominate translational candidates (SAA, PLA2G7, IL-17–associated mediators) for early risk stratification.

Safety and feasibility of outpatient administration of targeted alpha therapies: A systematic review and meta-analysis of radiation exposure and waste management.

e23183 Background: Targeted alpha therapies offer potent antitumor efficacy but are traditionally administered in specialized inpatient settings due to radiation safety concerns. Evaluating real-world radiation exposure, waste management, and regulatory compliance is essential to determine the feasibility of safely decentralizing these treatments to outpatient and community oncology centers. Methods: We systematically searched major databases for clinical trials and real-world studies evaluating outpatient administration of targeted alpha therapies. Pooled safety analyses were performed using Stata version 18.0, and risk of bias was assessed using the ROBINS-I tool. Results: A total of 11 studies were included, comprising 1,842 patients, of whom 614 received targeted alpha therapy and 307 served as controls; remaining studies were single-arm safety cohorts. The pooled mean post-discharge external dose rate was 0.04 µSv/h at 1 m (95% CI: 0.02–0.07) and 0.03 µSv/h at 2 m (95% CI: 0.01–0.05), with most measurements below detector thresholds. The pooled estimated annual caregiver/public exposure was 0.06 mSv (95% CI: 0.03–0.09), well below regulatory limits. The pooled proportion of patients meeting regulatory discharge criteria was 100% (95% CI: 98–100). Occupational whole-body exposure was minimal, with higher relative extremity exposure during administration that remained within safety limits. Conclusions: Outpatient targeted alpha therapy demonstrated negligible radiation exposure and full regulatory compliance, supporting safe delivery in community oncology settings.

Factors associated with delays in treatment initiation and interruptions in head and neck squamous cell carcinoma: A retrospective single-institution analysis.

e18115 Background: Timely initiation and uninterrupted delivery of curative-intent therapy are critical in head and neck squamous cell carcinoma (HNSCC). Despite guideline recommendations, real-world delays and treatment interruptions remain common and may adversely affect outcomes. We aimed to characterize treatment timelines, interruptions, and associated factors in patients with HNSCC at a safety-net hospital. Methods: We conducted a retrospective chart review of 58 patients with HNSCC treated with curative intent at University Health Truman Medical Center from 2019–2024. Demographic, clinical, insurance, and treatment timeline data were collected. Delayed treatment was defined as initiation &gt;45 days from diagnosis; treatment interruptions were any unplanned pause in therapy. Results: Mean age was 58.5 years (range 34–80); 75.9% were male. Most presented with stage III–IV disease (81.4%). Mean time from diagnosis to first oncology consultation was 18.5 days, and mean time to treatment initiation was 87.5 days. Delays &gt;45 days occurred in 62.1% of patients. Contributors included awaiting radiation consultation (17.2%), surgical coordination/metastatic work-up (13.8%), social barriers (housing insecurity, substance use; 8.6%), and insurance-related issues (6.9%). Treatment interruptions occurred in 32 patients (55.2%), median 1.5 interruptions among affected patients. Leading causes were treatment-related toxicity or hospitalization (59.4%), non-compliance (34.4%), insurance issues (15.6%), and social factors (substance use, housing insecurity; 9.4% each). Mean time to treatment initiation was shortest among privately insured patients (55.4 days) versus Medicaid/Medicare (93.0 days) and uninsured patients (87.4 days). Conclusions: Delays in treatment initiation and interruptions were common in this safety-net population. Insurance status, social determinants, and system-level coordination were key contributors. These findings highlight targets for interventions to improve timely and uninterrupted delivery of curative-intent therapy in patients with HNSCC.

HRS-5041, an androgen receptor degrader, in metastatic castration-resistant prostate cancer: A phase 1, multicenter, first-in-human study.

3112 Background: ADT plus NHA have been approved for PC of different stages. However, patients (pts) inevitably develop drug resistance, and AR mutations are a common cause of this resistance. HRS-5041 is a novel, oral, highly effective AR degrader that specifically targets the AR wild type (AR WT) and clinically relevant AR LBD mutants. We conducted a phase 1 trial to assess HRS-5041 in NHA-resistant mCRPC. Methods: Pts with mCRPC who had progressed on ≥1 NHA and ≥1 taxane chemo (unless refused or not indicated to chemo) were eligible. Pts orally received HRS-5041 at 30–540 mg QD or 240–300 mg BID during dose-escalation (DE), followed by dose or indication expansion at 180–360 mg QD or 240-300 mg BID. 240 mg BID and 360 mg QD were selected for dose optimization. The primary endpoints were DLT, MTD, and RP2D. Results: As of Dec. 12, 2025, 156 pts were enrolled, including 77 with AR-LBD mutation and 79 with AR-LBD WT. During DE, no DLT occurred. MTD was not reached. TRAEs were reported in 133 (85.3%) pts; the most common were anemia (38.5%), decreased appetite (25.6%), and diarrhea (24.4%). Grade ≥3 TRAEs and serious TRAEs occurred in 20 (12.8%) and 4 (2.6%) pts. No TRAEs led to death. Among all evaluable pts, rate of PSA reduction ≥50% was 0 for 1 pt at 30 mg QD, 0 for 4 pts at 90 mg QD, 17.4% for 23 pts at 180 mg QD, 32.1% for 53 pts at 360 mg QD, 40.0% for 5 pts at 540 mg QD, 35.7% for 56 pts at 240 mg BID, and 11.1% for 9 pts at 300 mg BID. Data by AR-LBD status for expanded doses are shown in table. Both 360mg QD and 240mg BID groups showed excellent PSA response rates and rPFSs, regardless of AR-LBD status. Among pts with AR-LBD mutations, the 240 mg BID group showed a superior rate of PSA reduction ≥50% and a higher 8-month rPFS rate than the 360 mg QD group. Notably, 2 patients in the 240 mg BID group achieved CR, including 1 with liver metastases. Conclusions: HRS-5041 showed tolerable safety and promising antitumor activity in pretreated mCRPC. A phase 3 study is currently underway in mCRPC pts with AR-LBD mutation, with a recommended dose of 240mg BID. Clinical trial information: NCT05942001 . Efficacy outcomes. Dose 180 mg QD 180 mg QD 360 mg QD 360 mg QD 240 mg BID 240 mg BID AR-LBD status AR-LBD mutation AR-LBD WT AR-LBD mutation AR-LBD WT AR-LBD mutation AR-LBD WT PSA reduction ≥30% * 5 (50.0) 1 (7.7) 15 (48.4) 8 (36.4) 17 (54.8) 7 (28.0) PSA reduction ≥50% * 3 (30.0) 1 (7.7) 10 (32.3) 7 (31.8) 15 (48.4) 5 (20.0) rPFS, mo † NR (2.2–NR) 5.8 (2.1–8.6) 11.0 (5.5–NR) 13.8 (8.2–NR) 11.0 (8.2–NR) NR (3.5–NR) 8-month rPFS rate † 53.3 (17.7–79.6) 32.6 (5.8–64.3) 58.1 (35.6–75.2) 82.9 (55.7–94.2) 85.3 (60.2–95.1) 71.2 (46.4–86.0) ORR # 2 (66.7) 0 0 0 3 (42.9) 1 (11.1) Data are n (%) or median (95% CI). * Assessed in pts who had at least one post-baseline PSA assessment or who discontinued treatment due to death/clinical progression without post-baseline PSA assessment; N was 10, 13, 31, 22, 31, and 25. † Assessed in full analysis set; N was 10, 14, 32, 23, 33, and 25. # Assessed in pts with baseline target lesions; N was 3, 4, 10, 5, 7, and 9.

Prior authorization utilization, administrative burden, and implications for timely care.

e23035 Background: U.S. payers widely use prior authorization (PA) to manage utilization of high-cost therapies. Although intended to promote evidence-based care, PAs are associated with delays and administrative burden. Data describing variation in PA practices and comparing potential reforms remain limited. Methods: This mixed-methods MBA health policy analysis incorporated publicly available administrative data, peer-reviewed literature, federal reports, and a cross-sectional stakeholder survey. Analyses focused on PA utilization, denial rates, administrative burden, and downstream effects across Medicare Advantage, Medicaid, and commercial insurance. The focus of the analysis was on 7 potential PA reforms proposed by Congress, including electronic processes, automatic approvals, standardized appeals, expanded gold card eligibility, PA time limits, public reporting of denials and appeals, and regulation of AI use in PA processing. The survey focused on PA perceptions and selecting the most and least feasible and impactful PA reforms. Descriptive statistics summarized findings. Results: PA use was extensive across payers. Medicare Advantage plans required PA for most covered services. Denial rates varied widely, ranging from 3.5 to 13%, with higher rates reported for specialty and time-sensitive services. Administrative costs related to PA were &gt; $90 billion annually, the bulk borne by providers and patients rather than payers. Prior studies identified associations between PA-related restrictions and delayed initiation of cancer care, and increased downstream acute care utilization. Survey respondents (n = 40) included patients, clinicians, and insurance administration with direct PA experience. Of respondents, almost all reported negative impressions, such as frustrating” or time-consuming. Respondents identified electronic processing and automatic approvals as the most feasible and impactful strategies to improve efficiency and access. After combining the scored and survey analyses, the weighted consensus was for Congress to mandate electronic processing of PAs. Conclusions: PA remains a prominent feature of oncology care delivery and is associated with substantial administrative burden and variability across payers. This analysis highlights the importance of PA reforms to ensure timely access while ensuring evidence-based cancer care. Respondent exposure to Prior Authorization (PA). Exposure to PA Percentage Yes, as a healthcare professional 65.0% Yes, as a patient 42.5% Yes, as an insurance/administrative worker 12.5% No, have not encountered PA directly 5.0%

Neoadjuvant versus adjuvant chemotherapy for resectable high-grade soft tissue sarcoma: A real-world propensity-matched survival analysis.

11585 Background: High-grade soft tissue sarcomas are aggressive malignancies for which complete surgical resection remains the cornerstone of curative-intent therapy. Current clinical guidelines recommend consideration of perioperative chemotherapy for selected high-risk patients; however, the optimal timing of systemic therapy remains uncertain. We performed a real-world analysis to compare survival outcomes between neoadjuvant and adjuvant chemotherapy in patients with resected high-grade soft tissue sarcoma. Methods: We conducted a retrospective cohort study using the TriNetX Database, identifying adults (≥18 years) with high-grade soft tissue sarcoma who underwent surgical resection and received combination chemotherapy with doxorubicin and ifosfamide either within 6 months before surgery or after surgery . The index date was defined as time of diagnosis. Propensity score matching (1:1) was performed to balance baseline demographics and various comorbidities. Overall survival (OS) was assessed using Kaplan–Meier methods and Cox proportional hazards models at fixed time points (1, 3, 5, and 10 years) and over the entire follow-up period. Results: A total of 714 patients were identified (479 adjuvant; 235 neoadjuvant). After propensity score matching, 229 patients were included in each cohort. At 1 year, overall survival was similar between adjuvant and neoadjuvant chemotherapy (53.1% vs 53.1%; risk ratio [RR] 1.06, 95% CI 0.81–1.37; log-rank p = 0.77). Additionally, analyses at 3, 5, and 10 years demonstrated no statistically significant differences in OS between cohorts, with overlapping Kaplan–Meier survival curves at all evaluated time points. Over the entire follow-up period, survival probabilities at the end of follow-up were 51.5% in the adjuvant cohort and 53.4% in the neoadjuvant cohort. There was no significant difference in overall survival (hazard ratio [HR] 1.04, 95% CI 0.75–1.44; p = 0.73). Conclusions: In this large, real-world, propensity-matched analysis of patients with resectable high-grade soft tissue sarcoma, survival outcomes were comparable across short-, intermediate-, and long-term follow-up intervals in both neo-adjuvant and adjuvant chemotherapy cohorts. Current guidelines recommend neo-adjuvant radiation treatment as category 1, and chemotherapy (neo-adjuvant or adjuvant) is a consideration. Neo-adjuvant chemotherapy has the potential to delay definitive treatment, however, this analysis suggests that the timing of chemotherapy does not adversely impact the outcomes in short or long term follow up. There are several limitations to our analysis (size of the tumors and grading was not available and timing of XRT could not be assessed, however, given that AIM chemo cohort was selected, it can be assumed that patients had higher grade, larger tumors and received XRT as standard of care.

Temporal trends in adherence to adjuvant endocrine therapy across age groups in hormone receptor–positive breast cancer.

634 Background: Adjuvant endocrine therapy (ET) reduces recurrence and mortality in hormone receptor–positive breast cancer, yet adherence remains suboptimal. Adherence varies by age, with younger patients at higher risk for non-adherence. Whether increased awareness has improved adherence over time is unclear. We evaluated temporal trends in ET adherence. Methods: We conducted a retrospective cohort study using the MarketScan claims database. Eligible patients were 18–100 years old with non-metastatic breast cancer (2009–2022), treated with surgery within 6 months of diagnosis, and began adjuvant ET (aromatase inhibitor [AI] or tamoxifen) within 1 year of diagnosis. The analysis included patients insured 1 year prior to and 1 year following ET initiation. ET was assessed using proportion of days covered (PDC) and defined as adherent (PDC ≥0.80) vs non-adherent for the year after ET initiation. Trends in adherence were evaluated using the Cochran–Armitage trend test and logistic regression with an age–calendar year interaction. Age was categorized as &lt;50 vs ≥50 years. Multivariable logistic regression was used to identify factors associated with ET adherence, reported as adjusted odds ratios (ORs). Results: Among 88,994 patients receiving ET (57,002 AI, 31,992 tamoxifen) from 2010–2022, the average adherence rate was 77.7% (79.3% AI, 74.9% tamoxifen). Adherence was lower in patients &lt;50 vs ≥50 years (74.1% vs 78.8%; OR 0.85, 95% CI 0.81–0.89). In patients &lt;50 on an AI, adherence increased over time from 66.6% in 2010 to 76.8% in 2022 (OR per year 1.07, 95% CI 1.05–1.09, p &lt; 0.001), whereas no increase in adherence over time was seen in young patients on tamoxifen or in any patients aged ≥50 years. In a multivariable analysis of the entire cohort (Table), younger age and polypharmacy (&gt;10 concurrent medications) were associated with lower odds of adherence, while receipt of 90-day prescription supplies, chemotherapy (neoadjuvant/adjuvant), and CDK4/6 inhibitors were associated with higher odds of adherence. Conclusions: Young women remain at high risk for ET non-adherence. While tamoxifen adherence did not improve over time, AI adherence increased over time in younger patients. This likely reflects heightened awareness, better supportive care, and clinician–patient discussions emphasizing AI adherence in young, high-risk populations. In contrast, despite similar increases in awareness, AI adherence has not improved in postmenopausal patients. These results highlight a persistent gap in ET adherence and the need for targeted interventions across age groups. Factors associated with adherence to adjuvant endocrine therapy. Covariate Adjusted OR 95% CI Age &lt;50 vs ≥50 years 0.85 0.81–0.89 Polypharmacy 0.80 0.78–0.84 90-day prescription supply 2.80 2.71–2.89 Neoadjuvant chemotherapy 1.30 1.19–1.43 Adjuvant chemotherapy 1.29 1.23–1.34 CDK4/6 inhibitor use 1.55 1.15–2.08

Dimeric Self‐Assembled Monolayer Materials for High‐Performance Perovskite and Perovskite/Organic Tandem Solar Cells

ABSTRACT While perovskite/organic tandem solar cells (POTSCs) hold great potential in terms of power conversion efficiencies (PCEs), achieving highly efficient POTSCs remains challenging. A primary bottleneck is the formation of unfavorable buried interfaces and energy level misalignment, often caused by inadequate self‐assembled monolayers (SAMs) on indium tin oxide/nickel oxide (ITO/NiO x ) substrates used for the front perovskite subcell. To address this critical issue, two dimeric SAM materials, named DTh‐4PACz and DPh‐4PACz, were synthesized using thiophene and benzene linkers, respectively, to connect two carbazole‐derived molecules. The DPh‐4PACz‐modified ITO/NiO x substrate exhibits an improved buried interface, leading to wide‐bandgap (WBG) perovskites with enhanced crystallinity and reduced defect density compared to the DTh‐4PACz‐based counterpart. Besides, DPh‐4PACz possesses enhanced conductivity and forms better energy level alignment with the WBG perovskites. Consequently, the best‐performing WBG perovskite solar cell (PSC) based on DPh‐4PACz achieves a higher PCE of 18.78%, compared to 16.77% for the DTh‐4PACz‐based PSC. By integrating the DPh‐4PACz‐based WBG PSC as the front subcell into POTSCs, the resulting device delivers an exceptional PCE of 26.63% (certified at 26.09%). Moreover, the DPh‐4PACz‐based POTSC shows enhanced thermal and light stability. This work provides an effective dimeric SAM material design strategy for efficient and stable PSCs and POTSCs.

Characterization of cadmium-doped nZVI residuals: Structure, morphology, and photoelectrochemical properties

Manipulating Carrier Recombination Dynamics Through Rational Dual‐Trap Engineering in Exciplex Heterojunction for High‐Performance OLEDs

ABSTRACT While trap states are traditionally considered as performance‐limiting defects in organic light‐emitting diodes (OLEDs), this work presents a dual‐trap exciplex heterojunction system that strategically engineers trap states to enhance device performance. The tailored electron (4CzTPNBu in p‐type host) and hole (PO‐01 in n‐type host) traps are employed for interfacial bidirectional carrier capture synergistically without compromising carrier transport in the exciplex heterojunction system. This innovative design converts interfacial traps into immediate radiative trap‐assisted recombination (TAR) centers with significant expansion of exciton recombination zone, simultaneously preventing carrier transport imbalance and charge accumulation. The yellow OLEDs demonstrate cutting‐edge 33.9% external quantum efficiency (EQE), and 453.6 h operational lifetime (LT 90 at 1000 cd m −2 ) representing a ninefold enhancement over conventional architectures. Through ideality factor analysis complemented by single‐carrier device and transient electroluminescence studies, the fundamental charge transport physics and trap‐mediated dynamics are unraveled. Implementation of dual‐trap in narrow‐band hyperfluorescent systems also enables EQEs surpassing 36% and mitigated efficiency roll‐off, along with prolonged LT 90 of 178.7 h. The dual‐trap methodology successfully merges the advantages for twin emitters and achieves a win‐win scenario for efficiency and lifetime, providing a promising paradigm for future high‐performance OLED development.

Electrolyte abnormalities and arrhythmia-associated inpatient deterioration in hospitalized cancer patients: National patterns in the National Inpatient Sample, 2018–2022.

e23162 Background: Electrolyte abnormalities are frequent during cancer hospitalizations, but their independent association with arrhythmias and downstream inpatient deterioration remains incompletely characterized at a national level. This study evaluated the relationship between common electrolyte disorders and arrhythmias, severity, organ support, mortality, and resource utilization during cancer hospitalizations. Methods: A retrospective serial cross-sectional analysis was conducted using adult hospitalizations with a principal diagnosis of malignancy in the 2018 to 2022 National Inpatient Sample with discharge-level survey weighting. Electrolyte disorders were identified using ICD-10-CM codes for hyponatremia (E87.1), hypokalemia (E87.6), hyperkalemia (E87.5), and hypocalcemia (E83.51). The primary outcome was any arrhythmia (I47 to I49). Secondary outcomes included extreme All Patient Refined Diagnosis Related Group severity, mechanical ventilation, in-hospital mortality, length of stay, and hospitalization cost. Survey-weighted multivariable models adjusted for demographics, payer, ZIP-code income quartile, admission type, cancer subtype, hospital characteristics, and year. Results: Among 961,848 unweighted cancer hospitalizations representing 4.81 million admissions nationally, 24.9% had at least one electrolyte disorder. Arrhythmias occurred in 14.2% overall and were more frequent with electrolyte disorders (18.0% vs 12.9%). After adjustment, any electrolyte disorder was independently associated with arrhythmia (adjusted odds ratio (aOR) 1.48, 95% CI 1.46 to 1.50), extreme severity (aOR 2.27, 95% CI 2.20 to 2.35), mechanical ventilation (aOR 2.60, 95% CI 2.53 to 2.68), and in-hospital mortality (aOR 2.53, 95% CI 2.42 to 2.64). Hyperkalemia demonstrated the strongest associations, including arrhythmia (aOR 1.77), mechanical ventilation (aOR 3.32), and mortality (aOR 4.12). Admissions with any electrolyte disorder had longer length of stay (9.8 vs 5.7 days) and higher costs ($29,013 vs $21,007). Conclusions: Electrolyte abnormalities are common during cancer hospitalizations and are independently associated with arrhythmias, severe illness, mechanical ventilation, mortality, and increased resource utilization. These findings highlight metabolic instability as a clinically actionable marker of high-acuity inpatient risk in oncology populations.

Neoadjuvant immunotherapy combined with radiochemotherapy vs chemotherapy alone in pMMR colon cancers: The TORCH-C randomized phase 2 clinical trial.

3634 Background: The prognosis for locally advanced colon cancer (LACC) with bulky nodal disease and/or clinically T4 stage remains poor, with high rates of recurrence and metastasis. Immunotherapy has become the standard treatment for deficient mismatch repair or microsatellite instability-high (dMMR/MSI-H) colon cancer. However, there has been little progress for the majority of cases, which was mismatch-repair proficient or microsatellite stable (pMMR/MSS). For locally advanced colon cancer with T4b stage or bulky lymph nodes, neoadjuvant chemotherapy is currently widely used. Whether combining it with immunotherapy and radiotherapy can improve efficacy is worthy of exploration. TORCH-C is the first study to evaluate this combination. Methods: TORCH-C is a prospective, multicenter, randomized phase 2 study that enrolled patients from April 3, 2023, through September 9, 2025. A total of 120 high-risk LACC (T4/bulky N+M0，pMMR/MSS) patients were 1:1 randomized to either an immunotherapy combined with SCRT and CAPOX chemotherapy group (group A) or a chemotherapy alone group (group B). Patients in the group B received 4 cycles of CAPOX (oxaliplatin 130 mg/m 2 intravenously day 1 and capecitabine 1000 mg/m 2 orally days 1-14). Patients in the group A received SCRT (25Gy in 5 fraction) and 4 cycles of the PD-1 inhibitor (serplulimab, 300mg intravenously day 1) combined with CAPOX. The radiotherapy target volume includes only the primary colon tumor and enlarged lymph nodes, without elective nodal irradiation. After neoadjuvant therapy, patients will be evaluated for radical colon resection. All patients will receive adjuvant chemotherapy of four cycles of CAPOX. The primary outcome was pathological complete response (pCR) rate. The secondary outcomes included tumor downstaging, R0 resection, 3-year disease free survival (DFS), 3-year overall survival (OS), 3-year local recurrence-free survival and treatment-related toxicity. Results: 120 patients have been enrolled and randomized. 107 patients were included in the mITT analysis (54 in group A and 53 in group B). 103 have received surgery (50 in the chemotherapy group, 53 in the radiotherapy group). The pCR rate was 10% (5/50) in chemotherapy group (group B) and 45.3% (24/53) in the radiotherapy group (group A) ( P &lt;0.05). The most common grade 3-4 adverse event (AE) among patients was thrombocytopenia, (22.2%, 12/54) in the group A and (18.9%, 10/53) in the group B. Conclusions: The combination of PD-1 inhibitor, SCRT, and chemotherapy shows promising efficacy and significantly improved pCR rates in patients with MSS/pMMR high-risk LACC. This regimen may provide a new therapeutic option to achieve R0 resection and improve long-term survival. Clinical trial information: NCT05732493 .

The influence of exercise on the mediational relationship between chemotherapy-induced sensory neuropathy and cancer-related fatigue: A nationwide phase II RCT in 111 patients receiving chemotherapy.

12151 Background: Cancer-related fatigue (CRF) and chemotherapy-induced sensory neuropathy (e.g., numbness, tingling, and pain) are common, sometimes debilitating toxicities that often co-occur in patients receiving neurotoxic chemotherapy. Both CRF and sensory neuropathy significantly diminish daily function and quality of life. Exercise is recommended for treating CRF and may also alleviate sensory neuropathy. Whether exercise-induced reductions in CRF are mediated by improvements in sensory neuropathy remains unknown. Methods: We conducted a nationwide phase II randomized controlled trial (RCT) through the University of Rochester Cancer Center NCI Community Oncology Research Program (URCC NCORP) Research Base. Patients who received neurotoxic chemotherapy in the past 9 months and developed moderate or severe (rated ≥4 on a 0-10 numerical scale) chemotherapy-induced sensory neuropathy (e.g., numbness, tingling, hot/burning or sharp/shooting pain in the hands and feet) in the past 2 weeks were randomized to virtually delivered Exercise for Cancer Patients (vEXCAP) or usual care (UC). vEXCAP is a 6-week, individually tailored, progressive walking and resistance band exercise intervention delivered virtually. CRF severity and sensory neuropathy were assessed via the Brief Fatigue Inventory severity score and the EORTC QLQ-CIPN20 sensory subscale (0-100 scale), respectively, at pre- and post-intervention. Causal mediation analyses were conducted to determine the extent to which exercise-induced improvements in CRF were mediated by changes in sensory neuropathy at post-intervention. Results: One hundred eleven patients (mean age 59.5 years; 76% female; 84% white; 37% breast cancer; 36% gastrointestinal cancer) were randomized and completed pre- and post-intervention assessments. vEXCAP participants, compared to UC participants, experienced significantly greater reductions in CRF (-0.95±0.33, p = 0.014) and clinically meaningful improvements in sensory neuropathy at post-intervention (-5.38±2.77 [MCID = 4.2], p = 0.055). Causal mediation analyses indicated that reductions in sensory neuropathy significantly mediate exercise-induced improvements in CRF severity (-0.18±0.13, p = 0.056), accounting for 19% (95% CI: 0% - 64%) of the exercise effect on CRF severity at post-intervention. Conclusions: vEXCAP reduces CRF severity and chemotherapy-induced sensory neuropathy among patients receiving neurotoxic chemotherapy. Approximately 19% of the exercise-induced improvements in CRF severity are mediated by reductions in chemotherapy-induced sensory neuropathy. Future Phase III RCTs are needed to confirm these findings and further explore the mediational role of chemotherapy-induced sensory neuropathy on CRF to help optimize the treatment of CRF using exercise. Clinical trial information: NCT04888988 .

Oncologic equivalence of brand-name vs generic imatinib in neoadjuvant <i>KIT</i> exon 11 GIST: A real-world international cohort study.

11535 Background: Neoadjuvant imatinib is routinely used to facilitate resection of localized gastrointestinal stromal tumors (GIST) with KIT exon 11 mutations. However, whether generic formulations achieve oncologic outcomes equivalent to the brand-name drug in curative-intent neoadjuvant therapy remains unknown. Methods: We performed a retrospective, international dual-institution cohort study of 131 patients with localized KIT exon 11–mutant GIST treated with neoadjuvant imatinib followed by surgical resection (2010–2025) at UC San Diego and Fondazione IRCCS Istituto Nazionale dei Tumori (Milan). Patients received either brand-name or generic imatinib based on institutional practice. The primary endpoint was tumor size reduction. Secondary endpoints included histopathologic response and overall survival. Multivariable regression and Kaplan–Meier analyses were performed. Results: Of 131 patients, 71 (54%) received brand-name and 60 (46%) received generic imatinib. Objective response (≥30% tumor reduction) occurred in 54% vs 37%, respectively (P=0.078). Median tumor size reduction was −33.3% with brand-name and −25.5% with generic imatinib (P=0.105). In multivariable analysis, longer neoadjuvant duration was independently associated with greater tumor reduction (β=−0.02 per day; 95% CI, −0.04 to −0.00; P=0.04), whereas imatinib formulation, dose, and treatment center were not. Pathologic outcomes, including viable tumor percentage (P=0.053), necrosis (P=0.777), and mitotic index (P=0.889), were similar between groups. Five-year overall survival was 87.2% with no difference by formulation (log-rank P=0.24). Conclusions: In this first international analysis of neoadjuvant therapy for KIT exon 11–mutant GIST, generic imatinib demonstrated oncologic equivalence to the brand-name formulation across tumor response, pathologic, and survival outcomes. As generic imatinib use has expanded globally following patent expiration, these findings reinforce its role as a clinically effective, cost-efficient, and accessible therapy. Demonstrating therapeutic equivalence in the neoadjuvant setting has direct implications for practice guidelines, formulary decisions, and equitable delivery of precision oncology worldwide. Tumor size reduction and objective response by imatinib formulation. Outcome Brand-name (n=71) Generic (n=60) P Value ≥30% tumor size reduction 38 (53.5%) 22 (36.7%) 0.078 Any tumor size reduction 59 (83.1%) 49 (81.7%) 1.0 ≥20% tumor size increase 5 (7.0%) 2 (3.3%) 0.452 Tumor size reduction, (median [IQR]) −33.3% (−45 to −18.4) −25.5% (−38.8 to −10.5) 0.11 Note: P values calculated using Fisher’s exact test for categorical outcomes and Mann–Whitney U test for continuous variables. Tumor size reduction reported as median (interquartile range, IQR).

Fatty acid degradation (FAD)–guided comprehensive therapy for unresectable hepatocellular carcinoma: A prospective phase II study (FAD-HCC-01).

TPS4256 Background: Hepatocellular carcinoma (HCC) exhibits marked molecular and metabolic heterogeneity, leading to variable therapeutic responses and limiting the effectiveness of current systemic treatments. Despite recent advances in immunotherapy and targeted agents, no validated biomarker is available to guide treatment selection in unresectable HCC. We previously established a fatty acid degradation (FAD) pathway-based molecular classification of HCC, revealing that FAD-associated transcriptional programs delineate biologically distinct HCC subtypes with heterogeneous immune microenvironments and differential responses to systemic and locoregional therapies. These findings suggest that FAD-based stratification may enable a more precise, biology-driven treatment strategy. However, the feasibility of implementing FAD-guided treatment allocation in a prospective clinical setting has not been established. FAD-HCC-01 is designed to evaluate the feasibility, safety, and preliminary efficacy of a FAD-guided comprehensive therapy in patients with unresectable HCC. Methods: FAD-HCC-01 is a prospective, multicenter, open-label phase II study enrolling patients with unresectable or non-curatively treatable HCC. Eligible patients have histologically or clinically confirmed HCC, BCLC stage B or C disease, Child–Pugh class A to B (≤7), ECOG performance status 0-1, and no prior systemic therapy. Tumors are classified into FAD subtypes (F1, F2, or F3) using transcriptomic profiling with ssGSEA-based FAD scoring; MRI-derived fat fraction may serve as a provisional surrogate when tumor tissue is unavailable. A total of 86 patients will be enrolled, with 43 patients planned for each treatment cohort. Patients are assigned to two parallel cohorts according to FAD subtype. Patients with F1 or F2 tumors receive camrelizumab (200 mg intravenously every 3 weeks) plus rivoceranib (250 mg orally once daily). Patients with F3 tumors receive transarterial chemoembolization (TACE) combined with camrelizumab and rivoceranib, with TACE performed per institutional standards and repeated as clinically indicated. Treatment continues until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint is objective response rate assessed by RECIST v1.1. Secondary endpoints include ORR by mRECIST, disease control rate, progression-free survival, overall survival, duration of response, conversion to curative treatment, and safety. Key feasibility objectives include successful FAD subtyping, adherence to FAD-guided treatment allocation, and integration of molecular or imaging-based classification into routine clinical workflows. Exploratory analyses will assess concordance between MRI fat fraction and FAD subtypes and explore molecular correlates of treatment response. Clinical trial information: NCT07314372 .