Browse Articles

Overall survival after intravenous iron use in patients with cancer and iron deficiency: A propensity-matched real-world study.

11128 Background: Iron deficiency affects up to two-thirds of patients with cancer and frequently coexists with anemia, with the highest prevalence in pancreatic, colorectal, and lung cancers. Functional iron deficiency driven by cancer-related inflammation predominates. Although intravenous (IV) iron is recommended to improve hematologic outcomes and reduce transfusion requirements, its impact on survival remains uncertain. We evaluated the association between IV iron use and overall survival (OS) in patients with advanced solid tumors using large real-world data. Methods: We conducted a retrospective cohort study using a TriNetX, a federated electronic health record network. Adults with solid malignancies and laboratory-defined iron deficiency (TSAT ≤ 20% and ferritin ≤ 500 ng/mL) were identified and categorized by IV iron exposure. Cohorts were matched 1:1 using propensity score matching for demographics, comorbidities, cancer site, iron indices (ferritin, transferrin saturation), hemoglobin, and treatment-related variables. OS was assessed using Kaplan–Meier analysis (5-year cap) and Cox proportional hazards modeling. Results: After propensity matching, 4,802 patients receiving IV iron were compared with 4,751 patients who did not receive IV iron, with a good balance across baseline characteristics. In Kaplan–Meier analysis (capped at 5 years), median overall survival (OS) was 875 days in the IV iron group and 858 days in the no IV iron group, with similar 5-year survival probabilities (38.6% vs 37.5%) and no significant difference by log-rank testing (p=0.53). On multivariable Cox proportional hazards modeling, IV iron exposure was not independently associated with mortality (HR 1.04, 95% CI 0.996–1.094; p=0.075). Male sex (HR 1.09, p<0.0001) and increasing age (HR 1.013 per year, p<0.0001) were associated with higher mortality. Iron indices demonstrated strong prognostic associations, with low transferrin saturation (<10%: HR 1.48; 10–20%: HR 1.24; both p<0.0001) and anemia diagnoses including iron deficiency anemia (HR 1.05, p=0.0048) and anemia of chronic disease (HR 1.23, p<0.0001) independently associated with increased mortality, while lower ferritin levels were associated with improved survival (<100 ng/mL: HR 0.53; 100–200 ng/mL: HR 0.78; both p<0.0001). Cancer site was also independently associated with OS, with higher mortality observed in digestive, respiratory, urinary tract, and central nervous system malignancies, and improved survival in breast and thyroid/endocrine cancers. Conclusions: In this large propensity-matched real-world cohort, IV iron was not associated with worse overall survival in patients with cancer and iron deficiency, supporting its survival safety while highlighting iron indices, anemia, and cancer type as key prognostic markers.

Determinants of trial completion, termination, and efficacy in solid tumor immunotherapy: Mapping IO clinical trial evolution from 2015-2022.

e23326 Background: Clinical trial success depends not only on scientific rationale but also on trial design and strategic planning. We performed a large-scale landscape analysis of IO trials to identify factors associated with trial termination, endpoint success, and strategic shifts over time, aiming to inform more predictive and efficient trial design. Methods: We analyzed interventional solid tumor IO trials from ClinicalTrials.gov finished from 2015–2022. Trials were categorized by investigational treatment, tumor type, disease stage, treatment setting, phase, sponsor type, year of initiation and termination reason. Among completed trials, primary endpoint success or failure was assessed when outcomes were available. Statistical analyses included chi-square or Fisher exact tests and logistic regression. Results: Among 1,430 trials, 960 (67.1%) were completed and 470 (32.9%) were terminated. Termination increased over time from 23.4% (2015–2017) to 36.3% (2018–2019) and 59.1% (2020–2022) (aOR 4.39, 95% CI 3.14–6.13) p < 0.001). Investigational treatment affected termination rate (p < 0.01): PD-(L)1 + chemotherapy and PD-(L)1 monotherapy had the lowest (17.4% and 19.7%), compared with PD-(L)1 + targeted combinations, bispecific antibodies (bsAb), cell- and vaccine-based therapies combined (43.2%; p < 0.001, aOR 3.81). Termination and its reasons were associated with sponsors, being lower in industry-led trials (p = 0.04). Recruitment-related termination was more common in non-industry (41.2% vs 24.6%), and business for industry trials (38.5% vs 21.9%). Recruitment was the dominant reason for all studies ( > 60%) except for PD-(L)1 + targeted, where futility and business-related factors predominated (57%). Phase 1-2 trials had higher rate of termination than phase 3 (32.5% vs 22.4%; p = 0.009). Termination was higher in locally advanced/metastatic than in locoregional disease (37% vs 25%; p = 0.02). IO strategy mix shifted over time (p = 0.01). PD-(L)1 monotherapy declined from 13.3% to 4.7%, while targeted, bsAb, and other combinations increased from 20.6% to 32.3%. BsAb trials were heavily industry-sponsored (90.7%), while RT-IO and PD-(L)1 mono- were entirely non-industry driven (97.7% & 69.7%; p < 0.001). Among assessable completed (49.1% 471/960) trials, primary endpoint was met in 56.1% varying by tumor type (p = 0.002) (higher success in upper GI cancers 75.0%, basket trials 69.8%, NSCLC 67.2%, melanoma 62.7%, lower in CRC 34.5%, and non-TNBC breast cancer 28.0%). Conclusions: Since 2015 IO trials have shifted from late line monotherapy to earlier settings combination strategies with clusters of success in select tumors. Termination increased over time, strongly influenced by recruitment issues, IO strategy and sponsor. We provide a quantitative base for developing predictive models to guide future IO trial design and improve efficiency.

A pilot study of a personalized cancer vaccine in combination with immune checkpoint inhibitor in advanced pancreatic cancer.

e16434 Background: Neoantigens, derived from somatic mutations, have emerged as a compelling therapeutic target. Vaccines targeting these neoantigens are designed to overcome current limitations in cancer therapy by activating tumor-specific T-cell responses. HRXG-K-1939 is a novel lipid nanoparticle (LNP)-encapsulated, mRNA-based personalized cancer vaccine (PCV). This investigator-initiated trial evaluated the safety, efficacy, and immunogenicity of HRXG-K-1939 in combination with immune checkpoint inhibitors (ICI) in patients with heavily pretreated advanced pancreatic cancer. Methods: Patients who had progressed after at least two lines of systemic therapy and had measurable disease (per RECIST v1.1) were enrolled and received up to 9 doses of HRXG-K-1939 (IM) combined with an ICI. Key endpoints were safety, clinical efficacy, immunogenicity assessed by ELISpot. Results: As of January 26, 2026, five eligible patients with advanced pancreatic cancer were enrolled: four had an ECOG performance status of 1, and one had a status of 0. In terms of prior therapies, four patients had received three lines of chemotherapy, and one had received two lines. All of them received at least one dose of PCV [0.14 mg (n = 3) and 0.4 mg (n = 2)] , shown a tolerable safety profile. All TRAEs were CTCAE grade 1-2, mainly including injection site reactions (100%) and fever (100%). No dose limiting toxicity was observed. Among the five patients, three experienced rapid disease progression following vaccination, while one achieved a partial response (PR) and one maintained stable disease (SD) resulting in an objective response rate (ORR) of 20%. Notably, both patients who achieved PR and SD completed the full course of nine vaccine doses. Patient-01, a 63-year-old male (0.14 mg cohort, post-3L treatment) maintained stable disease and remains alive with ongoing survival of 28.0 months since enrollment. Patient-02, a 33-year-old female (0.4 mg cohort, post-2L treatment) had a 31.7% reduction after nine doses vaccination, which enabled curative-intent surgery; she has been disease-free for > 5.4 months with an overall survival > 15 months since enrollment. Of note, immunogenicity analysis in these two patients revealed positive neoantigen-specific T-cell responses (ELISpot), with peptide response rates of 91.7% (11/12) and 100% (20/20). The responses emerged as early as cycle 3 and were sustained through cycle 9. Conclusions: HRXG-K-1939 combination with ICI demonstrated a manageable safety profile, along with encouraging signs of efficacy and immunogenicity in this study. These findings support the further development of personalized neoantigen vaccines in advanced pancreatic cancer. Clinical trial information: ChiCTR2300077339.

Prevalence of cardiovascular, kidney, and metabolic disease in breast and lung cancer patients in the United States.

e23081 Background: Cardiovascular, kidney, and metabolic (CKM) diseases impact cancer treatment tolerance and outcomes. We sought to detail CKM comorbidity burden at the time of breast cancer and lung cancer diagnosis among a representative sample of older adults in the United States. Methods: Using the SEER–Medicare linked database, we identified adults ≥ 65 years diagnosed with breast or lung cancer between 2010 and 2019 with Medicare A and B coverage in the year prior to cancer diagnosis. CKM conditions were identified using the CMS Chronic Conditions Data Warehouse, defined from ICD-9 and ICD-10 diagnosis codes from Medicare claims. CKM comorbidity burden was compared by age, sex, race, and Medicaid dual eligibility. Results: Among 129,047 lung cancer patients (mean age 74.7, 50.2% women, 10.2% black, 5.1% Asian), individual CKM conditions were highly prevalent, including ischemic heart disease (39.1%), heart failure (21.5%), diabetes (29.6%), and chronic kidney disease (23.2%). Among 279,418 breast cancer patients (mean age 73.2, 99.1% women, 11.3% black, 4.6% Asian), ischemic heart disease (27.4%), heart failure (14.7%), diabetes (26.1%), and chronic kidney disease (12.5%) were also common. Overall, CKM burden was greater in lung versus breast cancer, with higher prevalence of ≥1 (68.3% vs 61.2%), ≥2 (52.6% vs 42.0%), and ≥3 CKM comorbidities (38.1% vs 26.1%), and higher mean Charlson comorbidity index (2.03±2.04 vs 0.95±1.44). In both cancer types, CKM burden increased with age, with notable racial and socioeconomic differences. Among breast cancer patients, multi-comorbidity (≥3 CKM conditions) varied by self-identified race (21% of Asian, 35% of black, and 25% of white patients), with similar findings in lung cancer. Medicaid dual-eligible patients had a higher prevalence of ≥3 CKM comorbidities than non-dual-eligible patients in breast (43.7% vs 22.3%) and lung cancer (48.6% vs 35.0%). Conclusions: CKM comorbidity burden is highly prevalent among older adults with breast and lung cancer, with disparities by race and Medicaid dual-eligibility. Early targeted strategies addressing cardiometabolic disease alongside cancer care at diagnosis may help improve patient outcomes.

Gastroesophageal reflux symptoms and sleep quality among medical students at a private university in Lima, Peru: A cross-sectional study

Introduction Poor sleep quality is common among medical students and is associated with academic and health-related consequences. Gastroesophageal reflux disease (GERD) may contribute to sleep disturbances through biological and behavioral mechanisms, however, evidence in medical students is limited and previous studies have not adequately controlled for confounding. Objective To evaluate the association between GERD and sleep quality among medical students in Lima, Peru. Methods Cross-sectional analytical study conducted among medical students from a private university in Lima, Peru. Sleep quality was assessed using the Pittsburgh Sleep Quality Index, and GERD symptoms were measured with the Frequency Scale for the Symptoms of GERD. Poisson regression with robust variance was used to estimate adjusted prevalence ratios (aPR) with 95% confidence intervals (95% CI). Results A total of 171 students were analyzed (median age: 22 years; 64.9% female). The prevalence of GERD symptom burden was 76.6%, and poor sleep quality was observed in 84.8% of participants. Students with GERD symptom burden had a higher prevalence of poor sleep quality compared to those without GERD (aPR: 1.27; 95% CI: 1.03 to 1.58). Additionally, for each one-point increase in the GERD symptom score, the prevalence of poor sleep quality increased by 1.0% (aPR: 1.01; 95% CI: 1.003 to 1.018), demonstrating a dose–response relationship. Conclusion GERD symptoms were significantly associated with poor sleep quality among Peruvian medical students. This study provides context-specific adjusted evidence from an understudied Latin American medical student population. These findings support the need for screening strategies and early interventions targeting both conditions in this population.

Erratum: “Enhancement of spin-flop-induced magnetic hysteresis in van der Waals magnet (Fe1− <i>x</i> Co <i>x</i> )5GeTe2” [Appl. Phys. Lett. <b>122</b> , 152402 (2023)]

Banana peel waste valorization for a circular bioeconomy: A global analysis

Ceramic Papermaking: A Facile Route to Fire‐Strengthening, Multifunctional Ultralight SiC Fiber Mat

ABSTRACT High‐temperature thermal insulation properties of ultralight SiC materials make them highly promising for extreme environment applications. In this study, inspired by ancient paper‐making, we demonstrate the room‐temperature assembly of pre‐formed SiC fibers into an ultralight ceramic “paper” using an aqueous CTAB‐stabilized slurry. Under the baptism of 1600°C the “paper” does not burn and strengthens itself. Aerodynamic heat triggers surface oxidation, welding fiber crossings into stable junctions and boosting compressive strength from 49 to 206 kPa, while the skeleton retains its shape with only 1.23% mass loss. The resultant ultralight SiC fiber mat (SFM) carries an ultralow thermal conductivity of 42 mW m −1 K −1 and a density of 0.13 g cm −3 , yet survives 80% compression, 135° bending and 45° twisting without fracture. Repeated flame impingement, cyclic airflow scouring and ten‐cycle ablation leave the back‐face temperature below 400°C, evidencing reliable reusability. Because the “ceramic papermaking” route relies solely on gravity sedimentation and pH‐triggered structural assembly, meter‐scale or intricately patterned parts can be molded in hours, then dried at 80°C, avoiding complex sol‐gel chemistry or high‐temperature carbothermal synthesis. The same Seebeck‐principle network further endows SFM with real‐time temperature measurement (±10°C accuracy), integrating insulation and damage tolerance in one fire‐strengthened sheet.

Deceleration-phase restrengthening in compositionally zoned fault materials under transient slip

Abstract Moderate intraplate earthquakes often nucleate at depth and may not produce surface rupture. Yet the frictional response during fault slip deceleration remains poorly constrained, even though this stage may influence whether slip ceases locally or continues. Here, motivated by the 2024 Buan earthquake in South Korea (Mw 4.2), we combine low-velocity friction experiments that constrain nucleation-relevant behavior with high-velocity friction experiments that quantify frictional recovery during transient, decelerating slip. Low-velocity experiments on intact granite and granular wall-rock powder show near-neutral to weak velocity-weakening behavior and measurable healing, consistent with nucleation-relevant instability in crystalline basement. High-velocity pulse-like loading reveals a strong material contrast during deceleration: granular wall-rock powder restrengthens as slip rate decays, whereas clay-rich gouge remains persistently weak. These results show that, under prescribed transient slip histories, frictional evolution depends not only on dynamic weakening at peak slip rate, but also on composition-dependent frictional recovery during deceleration. This provides experimental constraints on how material contrasts may influence transient slip evolution in compositionally zoned fault materials.

Biosynthetic and genetic pathways related to sialic acid metabolism

Long-term outcomes with sustained minimal residual disease (MRD) negativity in belantamab mafodotin–treated patients (pts) with relapsed/refractory multiple myeloma (RRMM): An update from DREAMM-8.

7515 Background: B-cell maturation antigen (BCMA)–directed therapies have changed the RRMM treatment landscape. In the phase 3 DREAMM-8 trial (NCT04484623), BCMA-directed antibody-drug conjugate (ADC) belantamab mafodotin + pomalidomide and dexamethasone (BPd) demonstrated significant progression-free survival (PFS) benefit and higher rates of complete response (CR)–based MRD negativity vs triplet pomalidomide, bortezomib, dexamethasone (PVd) in pts with RRMM and ≥1 prior line of therapy (LOT). As MRD negativity predicts improved survival in MM, this long-term, postbaseline update describes clinical outcomes and characteristics of pts with sustained MRD negativity. Methods: Pts with ≥1 prior LOT including lenalidomide were randomized 1:1 to BPd or PVd. The primary endpoint was PFS (independent review committee assessed); PFS2 was investigator assessed. CR-based sustained MRD negativity (≥12 mo) was an exploratory endpoint. Pts with ≥ CR were tested for MRD negativity by next-generation sequencing (10 −5 sensitivity). Results: At data cutoff (7/7/2025), with median follow-up of 35.8 mo overall, the intention-to-treat population of BPd (n=155) vs PVd (n=147) was &gt;4× more likely to achieve ≥ CR + MRD negativity (27.7% vs 6.1%) and sustained MRD negativity (15.5% vs 2.7%). In pts with ≥ CR (BPd, n = 67; PVd, n = 25), rates of MRD negativity were also higher with BPd vs PVd (64.2% vs 36.0%), as were rates of sustained MRD negativity (55.8% vs 44.4%) among all ≥ CR + MRD negative pts. Pts with sustained MRD negativity had durable PFS in both arms; 1 of 24 and 0 of 4 pts experienced PFS events with BPd and PVd, respectively. In pts without sustained MRD negativity, median PFS was 21.1 mo with BPd (HR vs sustained MRD negative, 0.04; 95% CI, 0.01-0.32) and 10.2 mo with PVd (HR vs sustained MRD negative, not estimable [NE]). Sustained MRD negativity was also associated with durable PFS2 in both arms; 2 of 25 and 0 of 4 pts experienced PFS2 events with BPd and PVd, respectively. In pts without sustained MRD negativity, median PFS2 was 20.2 mo with BPd (HR vs sustained MRD negative, 0.08; 95% CI, 0.02-0.33) and 9.3 mo with PVd (HR vs sustained MRD negative, NE). Findings were similar in pts with vs without ≥ CR + MRD negativity. Of BPd-treated pts, those with MRD negativity (n=43) received 1-3 prior LOT, of which most (74.4%) had 1. MRD-positive pts (n=112) received up to 6 prior LOT, of which 44.6% received 1 and 17.0% received &gt;3. Almost 40% of pts with CR-based MRD negativity had high-risk cytogenetics. Conclusions: Pts receiving BPd vs PVd were &gt;4× more likely to achieve sustained MRD negativity, which was associated with improved PFS and PFS2. MRD negative vs positive pts in the BPd arm more often had 1 prior LOT. These findings further support BPd, a BCMA-directed ADC regimen, in earlier LOTs for RRMM, including in pts with high-risk cytogenetics. Clinical trial information: NCT04484623 .

Adjuvant nivolumab in addition to postoperative radiation therapy in locally advanced head and neck cancer: Results of the phase II NadiHN trial.

6092 Background: The benefit of adding immune checkpoint inhibition to standard postoperative adjuvant radiotherapy in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) with an intermediate risk of recurrence remains unclear. Methods: The phase II, open-label, randomized, multicenter national NadiHN trial (EudraCT 2016-004787-20) enrolled participants with resected locally advanced HNSCC (R0 resection with ≥5 mm margins; no extracapsular nodal extension). Patients were stratified by primary site (oropharyngeal vs non-oropharyngeal), p16 status (for oropharyngeal tumors), centrally assessed PD-L1 tumor cell (TC) score (≥1% vs &lt;1%), and center, and were randomized 1:1 to receive nivolumab before, during, and after postoperative radiotherapy (PORT) or PORT alone. Nivolumab (10 cycles of 240 mg q2w, followed by 10 cycles of 480 mg q4w) started 2 weeks prior to PORT. The primary endpoint was disease-free survival (DFS) in the intention-to-treat population. The planned sample size of 176 patients was designed to provide 80% power to detect a significant DFS improvement (log-rank test). Key secondary endpoints included overall survival (OS) and safety. Enrollment remained below target. During the trial, an adaptive interim analysis was implemented and led to early study termination upon Data Monitoring Committee recommendation due to futility. Results: Between 2017 and 2022, 84 participants were randomized (42 per arm). After a median follow-up of 37.3 months, median DFS was not reached in either group. The 2-year DFS rate was numerically higher with nivolumab + PORT (80%) than with PORT alone (69%), but the difference was not statistically significant (HR 0.934; 95% CI 0.408–2.140; p = 0.7301). Censoring deaths without documented recurrence yielded similar results. OS also did not differ significantly (HR 2.618; 95% CI 0.892–7.684; p = 0.0827). Grade ≥3 treatment-emergent adverse events occurred in 80.6% of patients in the nivolumab arm and 52.5% in the control arm. One treatment-related death occurred in the nivolumab + PORT arm. Conclusions: Interpretation of the trial is limited by early termination, small sample size, and fewer-than-expected DFS events. Adjuvant nivolumab added to standard PORT numerically—but not significantly—improved DFS in locally advanced HNSCC. Signals of potential benefit were observed in the PD-L1–positive subgroup (2y-DFS 82.4 vs. 76.2%) and lymph-node–positive subgroups (2y-DFS 84.2% vs. 70.7%). No new safety signals were identified. Funding: The trial was sponsored by the University Hospital Bonn with financial support from Bristol Myers Squibb. Clinical trial information: EudraCT 2016-004787-20.

Beyond rule-based matching: A locally deployable retrieval-augmented framework for clinical trial prescreening.

e13678 Background: Enrollment in clinical trials is critically hindered by the administrative burden of manually matching patient histories with unstructured eligibility criteria. resulting in the frequent overlooking of eligible patients, stagnating adult cancer patient enrollment at only 5–7%. Traditional keyword-based search fails to capture semantic nuance, and standard AI models are limited by their static training data. In this study, we validate the Retrieval-Augmented Generation (RAG) architecture that dynamically retrieves the clinical trial protocols relevant to a patient's case and integrates this external text into our locally deployed Cross-Encoder model for analysis. This allows the system to ground its eligibility assessments in a real-time review of trial criteria, ensuring decisions reflect current protocols rather than relying on the static, often outdated knowledge memorized during model training. Methods: We utilized the TREC Clinical Trials dataset (2021-22) of 375,581 trials, to validate the RAG architecture on a pooled oncology cohort of 57 patients. We implemented a four stage framework , which each level designed to resolve a specific barrier to automated matching: Semantic Retrieval (S-PubMedBert): Captures conceptual clinical meaning (e.g., linking "Lung Cancer" to "SCLC") independent of exact word overlap. Keyword Retrieval (BM25): Enforces strict matching for critical molecular identifiers (e.g., "HER2-positive") to prevent false positives. Reciprocal Rank Fusion: Synthesizes semantic and keyword signals to prioritize trials with high confidence from both methods. Cross-Encoder Reranking (BGE-Reranker-v2-M3): Performs a final assessment of top candidates to verify complex eligibility logic (e.g., exclusion criteria) akin to human chart reviews. Results: The framework achieved a retrieval Precision@10 of 0.47, representing a 67.8% relative improvement over a standard keyword search baseline (BM25) of 0.24, and Precision@3 of 0.50. While cloud-based LLMs may achieve marginally higher precision, they are deployable only in non-HIPAA environments; our system achieves comparable utility with zero Patient Health Information leakage. Conclusions: We conclude that a locally hosted lightweight Retrieval-Augmented architecture could serve as a superior alternative to standard keyword based trial matching, balancing specialist-level precision with data privacy. This framework effectively eliminates the manual screening bottleneck, establishing a scalable foundation for automated, real-time patient recruitment. Metric RAG BM25* Relative Improvement Precision@3* 0.50 0.33 +51.6% Precision@10* 0.47 0.28 +67.8% NDCG@10* 0.67 0.31 +116% Precision@k – Proportion of relevant trials identified within the top k results. NDCG@k – Normalized Discounted Cumulative Gain at k . BM25 – Best Matching 25 (Standard keyword search baseline).

Neoadjuvant systemic therapy for triple-negative breast cancer: A safety-net health system’s experience.

e13127 Background: Pembrolizumab-based neoadjuvant chemoimmunotherapy has become a standard of care for stage II–III triple-negative breast cancer (TNBC) based on randomized trial data showing significant improved pathologic complete response (pCR) and survival compared to chemotherapy alone. These associations have yet to be studied within our large safety-net health system. We evaluated pCR and survival outcomes of neoadjuvant and surgery-first approaches at a single institution. Methods: This retrospective study included patients diagnosed with stage II–III TNBC at JPS Health Network between 01/01/2019 and 12/31/2024. Patients were stratified by initial treatment strategy into neoadjuvant therapy (NAT) and surgery-first groups. Within the NAT group, patients received either chemotherapy alone or pembrolizumab-based chemoimmunotherapy. The study end points were pCR, overall survival (OS), and disease-free survival (DFS). Associations between treatment regimen and pCR were assessed using logistic regression, while OS and DFS were estimated using Kaplan–Meier methods and compared by log-rank testing. Results: A total of 110 patients were included, with 94 receiving NAT and 16 treated with upfront surgery. Patients in the NAT group had more advanced disease, including a higher proportion of stage III diagnoses (42%), whereas 75% of surgery-first patients were diagnosed with stage IIA disease. Among 87 NAT patients who underwent definitive surgery, pCR rates differed significantly by regimen. Pembrolizumab-based chemoimmunotherapy accounted for 74% of all pCRs (p = 0.001). Pembrolizumab-based therapy was also the only regimen independently associated with pCR when compared with other chemotherapy-only regimens (OR 3.40; p = 0.03). Among patients who achieved pCR, 89% remained disease-free compared with 56% of those with residual disease. Failure to achieve pCR was associated with increased mortality risk (HR 1.88; 95% CI 1.13–3.13; p = 0.014). No statistically significant differences in OS or DFS were observed between the two treatment strategies or across neoadjuvant regimens. Conclusions: Pembrolizumab-based neoadjuvant chemoimmunotherapy was associated with significantly higher rates of pCR compared with other neoadjuvant regimens, despite more advanced disease at presentation. Achievement of pCR was strongly prognostic and associated with a lower mortality risk. Although survival differences by treatment strategy were not observed, likely due to limited follow-up and sample size, these findings highlight pCR as a primary end point and support the use of pembrolizumab-based neoadjuvant therapy in this safety-net setting.

Beta-blocker use at immune checkpoint inhibitor initiation and survival in advanced solid tumors: A multi-institutional real-world cohort study.

e14544 Background: Preclinical data suggest that β-adrenergic signaling may impair antitumor immunity and modulate responses to immune checkpoint inhibitors (ICIs). Whether beta-blockers influence ICI effectiveness in routine practice remains uncertain. We investigated the association between beta-blocker use at ICI initiation and survival outcomes across advanced solid tumors. Methods: Adults (≥18 years) with advanced solid tumors initiating PD-1/PD-L1/CTLA-4 therapy (2014–2024) were identified from the TriNetX Research Network. Beta-blocker exposure was defined as prescription within −90 to +30 days of first ICI administration. Propensity score matching (1:1) balanced demographics, tumor type, comorbidity, and concomitant medications. Co-primary endpoints were overall survival (OS) at 1 and 5 years; secondary endpoints included time to next systemic therapy or death (TTNTD) and immune-related adverse events (irAEs) based on diagnostic codes. A 30-day landmark excluded early mortality bias. Kaplan–Meier and log-rank tests were used for comparisons. Results: Before matching, 20,612 patients received beta-blockers and 56,578 did not; after matching, 18,217 per group. At 5 years, OS was lower with beta-blockers (30% vs 32%, p &lt; 0.0001; median 17.1 vs 22.3 months) and 1-year OS was similarly reduced (57% vs 63%, p &lt; 0.0001). TTNTD was shorter (15.5 vs 20.2 months). The composite rate of irAEs was modestly higher with beta-blockers (44% vs 42%, p &lt; 0.0001) with earlier onset (median 19.3 vs 21.1 months). In the 30-day landmark analysis, OS differences persisted (5-year: 32% vs 33%, p &lt; 0.0001; median 20.0 vs 24.7 months; 1-year: 61% vs 66%, p &lt; 0.0001). TTNTD remained shorter (18.7 vs 22.6 months, p &lt; 0.0001), and irAE rates were similar (40.5% vs 39.6%, p = 0.061) with no difference in time to irAE. To our knowledge, this represents the largest real-world analysis to date evaluating beta-blocker exposure at ICI initiation across solid tumors. The direction of association contrasts with preclinical expectations and selected small clinical series reporting potential benefit, highlighting the importance of context and prospective validation. Conclusions: Beta-blocker exposure at ICI initiation was associated with inferior survival and reduced treatment durability. This suggests caution when extrapolating preclinical hypotheses regarding β blockade and reinforce the need for prospective subtype-specific evaluation of beta-blockers as immunomodulatory agents. Residual confounding and selection bias cannot be fully excluded given the retrospective real-world design. Key matched clinical outcomes comparing beta-blocker vs no beta-blocker exposure at ICI initiation. Outcome Beta-Blocker No Beta-Blocker p-value 1-yr OS 57% 63% &lt;0.0001 5-yr OS 30% 32% &lt;0.0001 Median OS 17.1 mo 22.3 mo — Median TTNTD 15.5 mo 20.2 mo — irAE composite 44% 42% &lt;0.0001

A phase 3 randomized trial comparing temozolomide with PCV as adjuvant chemotherapy in grade 2 and 3 diffuse gliomas in adults.

TPS2104 Background: Both Temozolomide (TMZ) and PCV are standard adjuvant chemotherapy regimens used in treatment of grade 2 gliomas with high risk features and grade 3 gliomas. The PCV regimen has a complex schedule, higher rate of adverse events (esp myelosuppression), and is difficult to administer, but has long-term data with an overall survival benefit. On the other hand,TMZ is an oral drug, with a simple dosing schedule, and fewer adverse events. Currently, there is lack of data directly comparing PCV to TMZ, there is emerging evidence to suggest that PCV may be the regimen of choice for oligodendrogliomas (ODGs). There is often debate on the choice of adjuvant chemotherapy. Hence we are conducting this study to compare TMZ with PCV in this setting. Methods: This is an ongoing phase 3, parallel-arm, non-inferiority trial. Adults with high-risk grade 2 (age ≥40 years and/or the presence of residual disease ≥1 cm after maximal safe resection) or grade 3 gliomas, are randomized 2:1 to receive TMZ or PCV after adjuvant radiation (RT). Patients receive adjuvant focal conformal radiation, with doses between 54 to 59.4 Gy at 1.8-2 Gy/fraction with conventional fractionation. In the TMZ arm, patients receive RT with concurrent TMZ 75 mg/m 2 /day (max. 49 days) followed by adjuvant TMZ 150-200 mg/m 2 for 5 of 28 days (max. 12 cycles). In the PCV arm, patients receive Procarbazine 60 mg/m 2 on days 8-21, CCNU 110 mg/m 2 on day 1 and Vincristine 1.4 mg/m 2 on days 8, 29 of a 56-day cycle (maximum 6 cycles). Adjuvant chemotherapy is started within 8 weeks of completing RT. Adverse events are recorded as per CTCAE v4.03. EORTC QLQ C-30 &amp; QLQ BN-20 is used for quality of life (QoL) assessment. Follow up evaluation will be conducted every 3 months in the 1 st year, every 4 months in the 2 nd year, and every 6 months from the 3 rd to 5 th year, then annually. The primary endpoint of the study is Progression-Free Survival (PFS). Secondary endpoints are Overall Survival (OS), safety,compliance &amp; QoL. Sample Size: Assuming a 3-year PFS of 70% in the PCV arm, with type 1 error of 5% (1- sided), type 2 error of 20%, with 2:1 ratio of accrual (in favor of the TMZ arm) for 10 years, with a study duration of 15 years, to show a non-inferiority by 12% for the upper limit of 95% confidence interval of the PFS with one interim analysis; the sample size estimated by group sequential design for time-to-event outcome was 216. Statistical analysis: Kaplan Meir analysis will be used to estimate the PFS &amp; OS and log rank test will be used for comparison between two arms.Cox proportional hazard model will be constructed for calculation of hazard ratio with its 95%CI. An interim analysis will be performed at 82 events of progression. If the log rank p value for the difference in the estimated PFS of the 2 arms is ≤ 0.006 then the trial will be terminated. Otherwise the trial will continue and undergo a final analysis at 163 events of progression. Clinical trial information: CTRI/2018/07/015056.

Prognostic significance of CD8+T lymphocytes and CD68+ macrophages in assessing pathologic response in pediatric soft tissue sarcomas.

10042 Background: The tumor immune microenvironment (TIME) plays a critical role in treatment response in pediatric oncology. Conventional clinical and demographic parameters often fail to accurately predict individual therapeutic outcomes. Increasing evidence suggests that the phenotype and spatial distribution of immune cells within the tumor may provide valuable prognostic information. This study evaluated the prognostic significance of immune markers (CD4, CD8, CD20, CD68) and their localization in predicting therapy-induced pathomorphologic response in pediatric soft tissue sarcomas (STS). Methods: A retrospective analysis was conducted in 98 pediatric patients with embryonal and alveolar STS. Immunohistochemical profiling was performed to assess the status, density, and spatial localization (intratumoral vs peritumoral) of CD4+, CD8+, CD20+, and CD68+ immune cells. Treatment response was evaluated based on the degree of therapy-induced pathomorphosis (grades I–IV) and standard imaging criteria. Statistical analysis included Spearman correlation and chi-square testing. Results: Intratumoral immune-cell infiltration demonstrated stronger prognostic value than demographic or clinical characteristics. A significant association was observed between CD8+ T-cell positivity and higher grades of pathomorphologic response (grades III–IV; p=0.001). CD68+ macrophage infiltration was also significantly correlated with tumor regression (p&lt;0.001). Intratumoral localization of CD8+ (p=0.002) and CD68+ (p=0.021) cells was significantly associated with improved therapeutic response compared with peritumoral localization. No significant associations were identified for age (p=0.771), sex (p=0.775), or histologic subtype (p=0.960). Conclusions: Intratumoral CD8+ T lymphocytes and CD68+ macrophages are key predictors of therapeutic response in pediatric STS. These findings support the integration of immunohistochemical profiling into routine clinical practice for response stratification. The results also provide a rationale for combining standard chemotherapy with immunomodulatory strategies to enhance intratumoral immune infiltration. Clinical trial information: B2023.2.DSc/Tib856.

Effect of elinzanetant on sleep disturbance and aspects of quality of life in women with breast cancer experiencing vasomotor symptoms: OASIS-4 subgroup analysis by type of endocrine therapy.

512 Background: In the Phase III OASIS-4 trial, elinzanetant (EZN), a dual neurokinin (NK)-targeted therapy (NK-1 and NK-3 receptor antagonist), significantly improved vasomotor symptoms (VMS), sleep disturbance and menopause-related quality of life (QoL) in women taking endocrine therapy (ET) for breast cancer. This post hoc analysis evaluated the effect of EZN on sleep disturbance and menopause-related QoL by ET type. Methods: Women aged 18–70 years with ≥35 moderate-to-severe ET-associated VMS/week were randomized 2:1 to EZN 120 mg daily for 52 weeks or placebo (PBO) for 12 weeks then EZN 120 mg for 40 weeks. Mean change from baseline (BL) to week 12 in Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form (PROMIS SD SF) 8b total T-score (range 28.9–76.5; &lt; 55 normal, 55– &lt; 60 mild, 60– &lt; 70 moderate, ≥70 severe) and Menopause-specific QoL questionnaire (MENQOL) total/domain scores (range 1–8; higher score indicates greater bother) were analyzed descriptively by ET type (tamoxifen [TAM], aromatase inhibitor [AI], ovarian function suppression [OFS], no OFS). Results: Mean BL PROMIS SD SF 8b total T-scores and MENQOL total scores were numerically similar across ET subgroups (Table), with some variability in MENQOL domain scores (ranges: vasomotor 6.6–6.9; psychosocial 3.3–4.2; physical 4.1–4.6; sexual 3.7–5.5). Greater numerical reductions with EZN vs PBO from BL to week 12 were observed across all subgroups for PROMIS SD SF 8b total T-score and MENQOL total score (Table), as well as MENQOL domain scores (ranges: vasomotor -2.6 to -2.9 vs -1.2 to -1.5; psychosocial -0.8 to -1.0 vs -0.4 to -0.6; physical -0.7 to -0.9 vs -0.3; sexual -0.5 to -0.9 vs -0.3 to 0.0). Conclusions: In this post hoc analysis, EZN consistently improved sleep disturbance and menopause-related QoL, including vasomotor, psychosocial, physical and sexual aspects, across all ET subgroups. Taken with previous data, findings suggest to support the efficacy of EZN in reducing VMS, sleep disturbance and improving menopause-related QoL independently of ET type. TAM AI OFS No OFS EZN (n=175) PBO (n=90) EZN (n=141) PBO (n=68) EZN (n=88) PBO (n=48) EZN (n=228) PBO (n=110) PROMIS SD SF 8b total T-score, mean (95% CI) BL 61.0 (60.1, 61.9) 60.5 (59.0, 62.0) 60.1 (59.0, 61.2) 61.1 (59.5, 62.7) 60.4 (59.0, 61.7) 61.6 (59.5, 63.7) 60.7 (59.9, 61.5) 60.4 (59.1, 61.7) Change from BL to Week 12 -11.0 (-12.3, -9.7) -4.3 (-5.9, -2.6) -10.0 (-11.4, -8.7) -3.8 (-5.5, -2.0) -10.4 (-12.1, -8.7) -6.5 (-8.7, -4.2) -10.6 (-11.8, -9.5) -3.1 (-4.5, -1.7) MENQOL total score, mean (95% CI) BL 4.7 (4.5, 4.9) 4.5 (4.2, 4.7) 5.0 (4.8, 5.2) 5.2 (4.9, 5.5) 4.9 (4.6, 5.1) 4.9 (4.5, 5.3) 4.8 (4.7, 5.0) 4.7 (4.5, 5.0) Change from BL to Week 12 -1.4 (-1.6, -1,2) -0.5 (-0.7, -0.3) -1.2 (-1.4, -1.0) -0.6 (-1.0, -0.3) -1.2 (-1.5, -1.0) -0.6 (-1.0, -0.3) -1.3 (-1.5, -1.2) -0.5 (-0.7, -0.3)

Outcomes by LymphoMAP archetypes in untreated diffuse large B-cell lymphoma from the POLARIX trial.

7017 Background: Single cell multiomics helped identify three tumor microenvironment archetypes: FMAC, high tumor-associated fibroblasts and macrophages; LN, high naive and memory T cells; TEX, high exhausted CD8 + T cells (Li, et al, Cancer Cell 2025) with FMAC associated with inferior outcomes with 1L R-CHOP. The POLARIX study showed sustained and significant 5-year PFS/DFS benefits favoring Pola-R-CHP (Morschhauser et al, JCO 2025) supporting use as a standard of care for pts with untreated intermediate/high-risk LBCL. In this post hoc exploratory analysis, we investigated the clinical outcomes of LymphoMAP subtypes in POLARIX. Methods: LymphoMAP subtypes were determined from global gene expression patterns (GEP) using the LymphoMapR classifier. Cell of origin (COO) status was determined by NanoString. Hazard ratios (HR) were adjusted for IPI score (2 vs 3–5), age (≤ 60 vs &gt; 60 years) and COO. All statistics are descriptive. Results: GEP data were available for 669 pts (Pola-R-CHP, n=331; R-CHOP, n=338; baseline characteristics comparable with ITT); among which 244 (33.5%), 229 (34.2%), 196 (29.3%) were FMAC, LN, and TEX respectively (Table). Balanced baseline clinical characteristics seen across subtypes, except lower proportion of LN with high IPI (3–5) and higher proportion of TEX as ABC-DLBCL (Table). With a median follow-up 61 months, the adjusted HRs for PFS favored Pola-R-CHP compared with R-CHOP in all subtypes and were 0.66 (95% CI: 0.43–1.01) for FMAC, 0.79 (95% CI: 0.51–1.23) for LN, and 0.81 (95% CI: 0.50–1.32) for TEX. The 5-yr PFS estimates (95% CI) were 66.0 (57.1–76.2)%, 64.6 (55.4–75.4)%, 68.8 (59.7–79.4)% for FMAC, LN, and TEX respectively in the Pola-R-CHP arm, and 56.9 (47.6-68.0)%, 61.2 (52.8–70.9)%, 56.6 (45.8–69.9)% for FMAC, LN, and TEX respectively in the R-CHOP arm. A similar trend of OS improvement was observed in the FMAC subtype with 5-yr OS estimates of 82.5 (76.3–89.3)% vs 72.0 (63.8–81.2)% with Pola-R-CHP vs R-CHOP (HR 0.64; 95% CI: 0.37–1.10). Trends of PFS and OS improvements of Pola-R-CHP over R-CHOP were observed in ABC-DLBCL pts across all LymphoMAP subtypes. For GCB-DLBCL pts, no benefit was observed with Pola-R-CHP vs R-CHOP in the TEX subtype. Conclusions: In this exploratory analysis, Pola-R-CHP demonstrated PFS/OS improvement trends over R-CHOP in all three LymphoMAP subtypes, especially for the FMAC subtype. Future prospective validation is required. FMAC (N = 244) LN (N = 229) TEX (N = 196) BEP (N = 669) Pola-R-CHPR-CHOP 134 (55%)110 (45%) 105 (46%)124 (54%) 92 (47%)104 (53%) 331 (50%)338 (50%) Age Median [Min, Max] 65 [22, 80] 66 [19, 80] 64 [22, 80] 65 [19, 80] IPI 3–5 157 (64%) 125 (55%) 133 (68%) 415 (62%) Bulky 109 (45%) 99 (43%) 87 (44%) 295 (44%) Extranodal 174 (71%) 146 (64%) 143 (73%) 463 (69%) COO ABC GCB Unclassified Unknown 68 (28%)138 (57%)20 (8%)18 (7%) 56 (24%)135 (59%)34 (15%)4 (2%) 90 (46%)65 (33%)38 (19%)3 (2%) 214 (32%)338 (50%)92 (14%)25 (4%)

A phase 2 study of androgen deprivation therapy and the androgen receptor ligand–directed degrader (BMS-986365) prior to radical prostatectomy in patients with high-risk localized prostate cancer.

TPS5152 Background: Although radical prostatectomy (RP) is a curative approach for patients (pts) with high-risk localized prostate cancer (PC), recurrence rates remain high. Neoadjuvant studies of androgen deprivation therapy (ADT) plus an androgen receptor pathway inhibitor (ARPI) suggest improvement in local disease control at the time of RP and may be associated with better long-term outcomes (McKay et al. PC Prostatic Dis. 2018; McKay et al. ASCO 2023: #5095). An ongoing phase 3 study is evaluating ADT plus apalutamide for 6 months prior to RP in pts with high-risk or locally advanced PC; co-primary endpoints are pathologic complete response (pCR) and metastasis-free survival (NCT03767244). BMS-986365 is an orally administered ligand-directed degrader targeting the androgen receptor (AR) via a first-in-class dual mechanism of 1) AR degradation and 2) AR antagonism. A phase 1 study showed that BMS-986365 was well tolerated with a manageable safety profile, with antitumor activity in pts with metastatic castration-resistant PC (mCRPC) regardless of AR gene alterations (Rathkopf et al. Ann Oncol. 2025), leading to an ongoing phase 3 study in mCRPC (rechARge: NCT06764485). Due to its dual mechanism and promising data in mCRPC, we hypothesize that neoadjuvant treatment with ADT plus BMS-986365 prior to RP will result in robust pathologic response rates. Methods: This is a single center, phase 2, single-arm trial testing the combination of ADT plus BMS-986365 for 6 months prior to RP in pts with high-risk localized PC. Eligible pts include those who are candidates for RP and meet ≥ 1 high-risk criteria: PSA ≥ 20 ng/mL, Gleason ≥ 8, or clinical stage ≥ cT3a (N1M0 disease allowed). Pts will receive degarelix SC once monthly (first dose 240mg, maintenance dose 80mg) and BMS-986365 at a dose of 300mg PO twice daily (liquid-filled capsule formulation) for 6 months; RP will occur 2 weeks after the last dose of BMS-986365. The dose of BMS-986365 was selected based on the phase 1 data and equivalent doses utilized in the ongoing phase 3 rechARge study. The primary endpoint is the rate of pCR and/or minimal residual disease (MRD, defined as tumor ≤ 5mm) at the time of RP. A two-stage design will evaluate if pCR and/or MRD rate exceeds 0.20, which is the rate observed in historical studies of ADT and ARPI prior to RP (McKay et al. J Urol. 2021) 10 pts will be enrolled in Stage 1; if ≥ 3/10 pts achieve a pCR and/or MRD, an additional 20 pts will be enrolled in Stage 2. If ≥ 10/30 pts achieve a pCR and/or MRD, the treatment will be declared sufficiently active (alpha = 0.05, power 0.80). Secondary endpoints include safety and time to biochemical recurrence. As part of exploratory analyses, cfDNA, pre-/post-treatment (prostatectomy) tissue, and pre-/post-treatment multiparametric MRI will be collected. The study opened to accrual in January 2026. Clinical trial information: NCT07335796 .