Browse Articles

Liquids as Reinforcements for Anisotropic and Tough Soft Matter Composites (Adv. Mater. 33/2026)

Programming Migration Energy Landscapes in Isoreticular Hydrogen‐Bonded Organic Framework Nanochannels for Kinetic Cs ⁺ /Sr ²⁺ Separation

ABSTRACT Precise separation of Cs + and Sr 2+ remains a critical challenge in nuclear waste remediation, where subtle variations in migration energetics under sub‐nanometer confinement limit separation fidelity. Here, we demonstrate migration energy‐landscape programming in an isoreticular series of hydrogen‐bonded organic framework (HOF) nanochannels to achieve kinetic Cs + /Sr 2+ separation. To overcome the intrinsic processability limitations of hydrogen‐bonded assemblies, we develop an interfacial chemical reaction‐mediated confined assembly strategy that suppresses stochastic nucleation and yields continuous, defect‐minimized crystalline HOF membranes. This isoreticular platform preserves identical channel geometry while enabling systematic modulation of pore‐wall nitrogen density as an independent chemical variable, effectively decoupling structural confinement from chemical regulation. Multiscale simulations and temperature‐dependent transport measurements reveal that nitrogen enrichment selectively amplifies the translocation energy barrier for Sr 2+ while maintaining low‐barrier hopping pathways for Cs + . The resulting migration‐barrier asymmetry transforms structurally equivalent nanochannels into precise kinetic discriminators. Under competitive and electrically assisted conditions, the optimized membrane achieves a record‐high Cs + /Sr 2+ selectivity of 155.5. This work establishes programmable migration energy landscapes in crystalline nanochannels as a general strategy for engineering kinetic ion separations beyond conventional size‐ or valence‐governed limits.

A Cryoprotectant‐Compatible Nanoporous Platform for Stable and Scalable Delivery of Biopharmaceuticals

ABSTRACT CRISPR‐Cas9 ribonucleoproteins (RNPs) represent a promising class of biopharmaceuticals for treating genetic and complex diseases. However, their clinical translation is limited by instability during storage and delivery. Lyophilization offers a potential solution, though conventional approaches often compromise structural integrity and bioactivity under non‐cryogenic conditions. Here, we have developed a nanostructured delivery platform, designated Nano Banker & Blowball (NB 2 ), which features a blowball‐like architecture and tunable nanoscale pores. These pores are designed to protect RNPs and enable controlled release. The freeze‐dried formulation (FNB 2 ) integrates optimized cryoprotectants and a surface‐engineered nanoparticle design, preserving morphology and function without excessive excipients. FNB 2 exhibits rapid rehydration and retains ∼70% of gene editing activity post‐lyophilization, enabling robust functional gene editing in vitro and in vivo. It also maintains long‐term stability and supports efficient cellular uptake, enabling administration via multiple routes. FNB 2 represents a scalable and robust platform for genetic therapeutics, vaccines, and biologics, particularly well‐suited for resource‐limited and emergency medical applications.

A cold manipulation of rainbow trout (Oncorhynchus mykiss) at eyed-stage has few impacts on hepatic lipid metabolism in juveniles

Where and how do mammalian cells shape autophagosomes?

Secondary genomic alterations and clinical outcomes in myxoid liposarcoma: A multi-institutional analysis.

11580 Background: Myxoid liposarcoma (MLS) is defined by DDIT3 rearrangements. The clinical and prognostic significance of secondary genomic alterations remains incompletely characterized. We retrospectively evaluated the clinical, pathological, and prognostic implications of commonly co-occurring mutations in patients with MLS. Methods: Patients with pathologically confirmed MLS treated at Memorial Sloan-Kettering Cancer Center (MSKCC) and MD Anderson Cancer Center (MDACC) who underwent next-generation sequencing (NGS) on the primary tumor (9/2010-5/2024) were included. To ensure the analysis represented de novo mutations rather than acquired alterations, patients with NGS performed only at the time of recurrent disease were excluded. The primary endpoint was disease-free survival (DFS) among surgically treated patients. Associations between genomic alterations and clinico-pathologic characteristics were assessed using univariable and multivariable analyses. Results: The cohort included 76 patients (67 MSKCC, 9 MDACC) with a median age of 39 years. At diagnosis, 83% of patients (n = 63) had localized disease and underwent definitive surgery, while 17% presented with de novo metastasis; 45% had high-grade disease (≥5% round cell component). Genomic analysis identified TERT promoter mutations in 68%, PIK3CA in 30%, and PTEN in 18%. Notably, PIK3CA and PTEN mutations were not mutually exclusive, with 10.5% of the total cohort harboring concurrent alterations in both genes. TERT promoter mutations were significantly associated with male sex (75% vs 33%, p < 0.001), older age (40 vs 33 years, p = 0.02), high-grade pathology (54% vs 25%, p = 0.026), and larger median tumor size (12.9 vs 7.5 cm, p = 0.002). PIK3CA mutations were associated with male sex (83% vs 53%, p = 0.02) and a trend toward larger median tumor size (13.6 vs 9.3 cm, p = 0.061) and de novo metastasis (30% vs 11%, p = 0.053). For the 63 patients with localized disease, the median DFS was not reached (95% CI: 55.7–NR) with a 24-month DFS rate of 75% (95% CI 61-84). In univariable analysis for DFS, significant predictors of recurrence included PIK3CA mutation (HR 4.61; p = 0.001), PTEN mutation (HR 5.15; p < 0.001), tumor size (HR 1.06 per cm; p = 0.012), high-grade pathology (HR 2.81; p = 0.024) and male sex (HR 2.79; p = 0.049). The presence of both PIK3CA and PTEN mutations conferred particularly poor prognosis (HR 16.34 compared to neither mutation; p < 0.001). In separate multivariable analyses adjusted for grade, both PIK3CA (HR 5.75, p < 0.001) and PTEN (HR 4.27, p = 0.002) remained independent predictors of DFS. Conclusions: Secondary genomic alterations in MLS are highly prevalent and connote distinct clinical phenotypes. While TERT promoter mutations correlate with aggressive pathologic features, PIK3CA and PTEN mutations are independent prognostic factors for DFS and may help risk-stratify patients for potential adjuvant therapies.

Efficacy and safety of tucatinib (TUC) vs placebo (PBO) combined with trastuzumab and pertuzumab (HP) as maintenance therapy for HER2+ metastatic breast cancer by stratified subgroups.

1005 Background: In the phase 3 HER2CLIMB-05 study (NCT05132582), TUC + maintenance HP demonstrated a statistically significant improvement in progression-free survival (PFS) vs control treatment (Tx) (hazard ratio: 0.641, P < 0.0001) in patients (pts) with HER2+ locally advanced or metastatic breast cancer (MBC). Here we report additional efficacy and safety outcomes by stratified subgroups. Methods: Pts with centrally confirmed HER2+ MBC without evidence of progression following chemotherapy-based induction Tx (taxane + HP) were randomly assigned 1:1 to TUC (300 mg) or PBO BID + HP. Randomization was stratified by diagnosis ( de novo /recurrent), hormone receptor (HR) status (positive/negative), and presence or history of brain metastases (BM; yes/no). Endocrine therapy (ET) is permitted for pts with HR+ disease. The primary endpoint is investigator-assessed PFS. Confirmed objective response rate (cORR), duration of response (DOR), and safety were evaluated in stratified subgroups. Results: Among pts assigned to TUC + HP (n = 326) or PBO + HP (n = 328), ∼69% had de novo MBC, ∼53% had HR+ status with ∼45% having received concurrent ET, and ∼12% had baseline BM. At data cutoff (Sep 5, 2025), median PFS was longer with TUC than PBO + HP in all stratified subgroups; TUC + HP consistently improved cORR vs PBO + HP (Table). Safety outcomes in subgroups aligned with the overall population. Conclusions: TUC + HP demonstrated clinically meaningful efficacy vs PBO + HP in pts with de novo or recurrent disease, HR+ or HR− disease, and baseline BM or not, with no new safety signals identified. Results were consistent with the overall population and support TUC + HP as a potential new maintenance therapy across pts with HER2+ MBC. Clinical trial information: NCT05132582 . Efficacy outcomes. Overall De novo Recurrent HR+ (± ET) † HR− BM (yes) BM (no) TUC+HP(n=326) PBO+HP(n=328) TUC+HP(n=227) PBO+HP(n=226) TUC+HP(n=99) PBO+HP(n=102) TUC+HP(n=168) PBO+HP(n=176) TUC+HP(n=158) PBO+HP(n=152) TUC+HP(n=41) PBO+HP(n=40) TUC+HP(n=285) PBO+HP(n=288) Median PFS, mos (95% CI) 24.9(21.3−NE) 16.3(12.6−18.7) 28.9(22.7−NE) 16.8(12.9−19.2) 21.3(15.6−27.2) 12.7(8.3−18.1) 25.0(16.5−NE) 18.1(13.0−20.8) 24.9(19.4−NE) 12.6(9.4−16.8) 8.5(4.2−16.5) 4.2(2.2−8.1) 27.2(24.3−NE) 18.1(14.8−20.7) cORR*, % (95% CI) 22.6(18.0−27.8) 15.2(11.3−19.7) 26.1(20.2−32.7) 18.5(13.5−24.4) 15.1(8.5−24.0) 7.0(2.6−14.6) 20.1(14.0−27.5) 12.9(8.2−19.0) 25.2(18.4−33.0) 17.9(11.8−25.5) 15.0(5.7−29.8) 8.3(1.8−22.5) 23.8(18.7−29.5) 16.1(11.9−12.1) Median DOR*, mos (95% CI) 20.9(16.4−NE) 16.9(12.3−NE) NR(16.4−NE) 16.3(10.4−NE) 17.9(8.3−NE) NR(7.2−NE) 20.9(12.6−NE) 18.7(7.8−NE) NR(8.6−NE) 14.5(10.4−NE) 12.6(8.1−NE) 16.3(12.5−NE) 20.9(16.4−NE) 18.7(10.4−NE) *ORR and DOR were assessed in patients with target or non-target lesions at baseline. † Data on HR+ w/ ET will be presented.

Real-world outcomes and safety of FGFR inhibitors in intrahepatic cholangiocarcinoma: A TriNetX analysis.

e16186 Background: Intrahepatic cholangiocarcinoma (iCCA) is a rare and aggressive malignancy associated with poor prognosis and limited systemic treatment options. FGFR inhibitors are approved for previously treated iCCA harboring FGFR2 fusions or rearrangements; however, real-world effectiveness and early toxicity outside of clinical trials remain incompletely characterized. We evaluated real-world outcomes and safety of FGFR inhibitor therapy in routine clinical practice. Methods: Using TriNetX, a federated network of de-identified electronic health records from participating healthcare organizations, we identified adults (≥18 years) with iCCA (ICD-10 C22.1) who initiated pemigatinib or futibatinib on or after 04/01/2020 and had evidence of prior systemic anticancer therapy. Overall survival (OS) and time to next treatment (TTNT) were assessed using Kaplan–Meier methods, with censoring at the last recorded clinical encounter. Treatment-related safety outcomes including hyperphosphatemia, ocular toxicity, and gastrointestinal/mucositis toxicity were assessed from 0–90 days after the first FGFR inhibitor exposure; patients with the outcome prior to treatment were excluded. Exploratory subgroup analyses were performed by age ( < 65 vs ≥65 years) and sex. Results: The cohort included 237 patients (mean age 60.3±12.9 years; 57% female) with a median follow-up of 293 days (9.6 months). Common comorbidities included hypertension (43%), diabetes (25%), and chronic kidney disease (6%). There were 132 deaths, with a median OS of 364 days (12.0 months). Overall, 83 patients initiated subsequent systemic therapy, with a median TTNT of 521 days (17.1 months). Hyperphosphatemia was the most frequent early toxicity, with serum phosphate ≥4.5 mg/dL observed in 61.0% and ≥7 mg/dL in 14.4% of patients. Ocular toxicity and gastrointestinal/mucositis toxicity were identified in 9.4% and 11.8% of patients, respectively. OS and TTNT did not significantly differ by age group or sex in exploratory analyses. Conclusions: In this real-world cohort of patients with previously treated iCCA receiving FGFR inhibitors, median OS was 12 months and median TTNT was 17 months, with early toxicity predominantly characterized by hyperphosphatemia. These findings provide clinically relevant real-world context to pivotal FGFR inhibitor trials and may inform expectations regarding outcomes and toxicity monitoring in routine practice.

Efficacy and safety of HLX43 (an anti–PD-L1 ADC) in previously treated recurrent/metastatic nasopharyngeal carcinoma: A multicenter, randomized phase 2 study.

6060 Background: Treatment options are limited and clinical outcomes remain unsatisfactory for patients with recurrent/metastatic nasopharyngeal carcinoma (r/m NPC) in the later-line setting. HLX43 is a novel anti-programmed cell death-ligand 1 (PD-L1) antibody-drug conjugate with promising antitumor activity in advanced tumors. Here we present results from a phase 2 study evaluating HLX43 in previously treated r/m NPC. Methods: This randomized, multicenter trial enrolled patients with histologically or cytologically confirmed r/m NPC who had received at least second-line chemotherapy (including one prior line of platinum-based chemotherapy) and progressed on or were intolerant to programmed death (ligand) 1 (PD-[L]1) inhibitor. Patients were randomized 1:1:1 to receive 2 mg/kg, 2.5 mg/kg, or 3 mg/kg of intravenous HLX43 every 3 weeks. The primary endpoints were objective response rate (ORR) and progression-free survival (PFS) per investigator's assessments. Results: As of September 18, 2025, 30 patients were randomized to the 2, 2.5, or 3 mg/kg group ( n = 10 for each group). The median follow-up duration was 2.8 months (range 2.1–5.6). Twenty-six patients (86.7%) had performance status 1; 27 (90.0%) had prior radiotherapy. The median line of prior systemic therapy was 3 (range 2–8). ORR was 36.7%, with partial responses (PRs) in 11 patients. ORR in the three dose groups was 20.0%, 20.0% and 70.0% (all confirmed by December 2025), respectively; disease control rate (DCR) was 50.0%, 50.0% and 80.0%. PFS data were immature. Overall, treatment-emergent adverse events (TEAEs) occurred in 29 patients (96.7%; grade ≥3, 50.0%). TEAE incidence was 90.0%, 100% and 100% in the three dose groups, respectively. TEAE leading to dose reduction was reported in 3 patients (30.0%) in the 3 mg/kg group only. TEAE leading to treatment discontinuation occurred in 1 (10.0%) each in the 2.5 mg/kg and 3 mg/kg groups. There was no death due to TEAE. The efficacy and safety findings are detailed in Table 1. Conclusions: HLX43 showed promising efficacy with a manageable safety profile in r/m NPC patients who had progressed after second-line or later chemotherapy and PD-(L)1 inhibitors. Further investigation is warranted. Clinical trial information: NCT06839066 . Efficacy and safety. 2.0 mg/kgN=10 2.5 mg/kgN=10 3.0 mg/kgN=10 TotalN=30 PR 2 (20.0) 2 (20.0) 7 (70.0) 11 (36.7) SD 3 (30.0) 3 (30.0) 1 (10.0) 7 (23.3) PD/NE 5 (50.0) 5 (50.0) 2 (20.0) 12 (40.0) ORR, 95% CI (%) 20.0(2.5, 55.6) 20.0(2.5, 55.6) 70.0(34.8, 93.3) 36.7(19.9, 56.1) DCR, 95% CI (%) 50.0(18.7, 81.3) 50.0(18.7, 81.3) 80.0(44.4, 97.5) 60.0(40.6, 77.3) TEAEs 9 (90.0) 10 (100) 10 (100) 29 (96.7) Grade ≥3 TEAEs 2 (20.0) 7 (70.0) 6 (60.0) 15 (50.0) TEAE leading to dose reduction 0 0 3 (30.0) 3 (10.0) TEAE leading to treatment discontinuation 0 1 (10.0) 1 (10.0) 2 (6.7) NE, not evaluable. PD, progressive disease. SD, stable disease.

A retrospective analysis of neoadjuvant chemotherapy (NAC) versus upfront surgery (US) in resectable pancreatic adenocarcinoma at a large tertiary care center.

e16448 Background: Resectable pancreatic adenocarcinoma (rPAC) has a notoriously high mortality worldwide, even in cases of complete resection. In previous decades, rPAC was treated with upfront surgical resection (US), however, neoadjuvant chemotherapy (NAC) is now recommended, especially for so-called high-risk cases, which are somewhat poorly characterized in both literature and guidelines. Many studies confirm that, for cases of borderline rPAC, NAC can reduce recurrence rates (RR), increase complete resection rates (R0), and increase overall survival (OS); however, the data remains conflicting for rPAC. Methods: This study aims to compare outcomes in rPAC with US versus NAC, comparing three primary endpoints: RR, R0, and OS. Initial analysis of all patients who underwent pancreatoduodenectomy between Jan 2020 - Dec 2024 was performed. Inclusion criteria included patients with pathology and imaging-proven rPAC. Exclusion criteria included patients with non-pancreatic adenocarcinoma or inconclusive biopsies, and all patients with borderline resectable tumors. A total of 27 patients were excluded, and a total of 56 patients were included. Key variables analyzed included patient demographics, tumor characteristics, R0, RR, and OS. Results: The US cohort (n=25) included 10 female and 15 male patients, with mean age at diagnosis 69.64 (SD 9.63) and mean tumor size 28.20mm (SD 10.38). The NAC cohort (n=31) included 16 female and 15 male patients, mean age at diagnosis was 72.23 (SD 9.51) and mean tumor size was 33.48mm (SD 13.46). There was no statistically significant difference in demographics or tumor size between cohorts. OS in the US cohort was 721.36 days; OS in the NAC cohort was 735.38 days. There was no statistically significant difference in overall survival between cohorts. In the US cohort, 23/25 patients achieved R0. In the NAC cohort, 23/31 patients achieved R0. Again, there was no statistically significant difference in R0 between cohorts. RR excluded patients with residual tumor after surgery, and this study found no statistically significant difference in RR between cohorts. Conclusions: This study found no statistically significant difference in outcomes between US and NAC for rPAC. Further randomized controlled trials (RCTs) are needed to fully evaluate the efficacy of NAC in rPAC, particularly high-risk rPAC. RCTs that examine the need for NAC, particularly in patients with high-risk features such as elevated Carbohydrate Antigen (CA) 19-9 levels and larger tumor size, would assist with the creation of less ambiguous evidence-based treatment guidelines. In the meantime, a multidisciplinary approach to treatment, as well as institutional guidelines for risk stratification, are critical.

Association between circulating tumor DNA and local tumor regrowth and distant metastasis during nonoperative management in stage I–III rectal cancer.

3615 Background: During nonoperative management (NOM) for rectal cancer after a clinical complete response (cCR) or near-CR (nCR), 25–30% develop local regrowth and 5–10% develop distant metastasis, highlighting the need for improved risk stratification and surveillance. Circulating tumor DNA (ctDNA) has emerged as a prognostic biomarker, but its utility in NOM decision making remains undefined. Methods: We retrospectively studied 110 patients with stages I-III, microsatellite stable rectal adenocarcinoma achieving cCR/nCR after neoadjuvant therapy (2020-2024) managed with NOM and tumor-informed ctDNA testing in the INTERCEPT program (Signatera Exome). We assessed longitudinal ctDNA status during NOM and the first post-treatment ctDNA in relation to local regrowth and/or distant metastasis (Kaplan–Meier/log-rank; Fisher’s exact). We also evaluated per-sample accuracy for events occurring within ±90 days of each blood draw. Results: Over a median follow-up of 25 months, 23 (20.9%) patients developed local regrowth and 12 (10.9%) developed distant metastases (Table 1). Patients with ever positive longitudinal ctDNA had an associated worse 2-year regrowth-free survival (41.7% vs 83.9%, P=0.0002) and metastasis-free survival (41.7% vs 94.9%, P<0.0001) than those with persistently negative ctDNA. Among patients with an evaluable first post-treatment ctDNA result (within 180 days post treatment; n=72), those with a positive result had an associated lower regrowth-free survival (P = 0.0006) and metastasis-free survival (P < 0.0001). In per-sample analysis (n=669), ctDNA showed low sensitivity and high specificity for local regrowth (41.4% and 94.3%) and higher sensitivity and specificity for distant metastasis (73.8% and 97.4%). Twenty-two of 23 patients with local regrowth underwent salvage surgery; ctDNA positivity at local regrowth was associated with more advanced pathological T stage (66.7% of ypT3–4 vs 15.4% of ypT0–2, P=0.01). Conclusions: During NOM for rectal cancer, ctDNA may be used to identify a small subgroup at high risk of local regrowth and/or distant metastasis. However, many local regrowth occurs despite persistently negative ctDNA, consistent with limited sensitivity. Negative ctDNA results should therefore not prompt de-escalation of endoscopic and radiologic surveillance when a NOM strategy is used. Overall rates of local regrowth and distant metastasis. Local regrowth (n=23) a P Distant metastasis (n=12) P Longitudinal ctDNA <.0001 <.0001  Persistently negative (n=95) 14/95 (14.7%) 3/95 (3.2%)  Ever positive (n=15) 9/15 (60.0%) 9/15 (60.0%) First post-treatment ctDNA b 0.005 <.0001  Negative (n=67) 15/67 (22.4%) 5/67 (7.5%)  Positive (n=5) 4/5 (80.0%) 4/5 (80.0%) a Two had synchronous and 5 had metachronous distant metastasis. b Within 6 months post treatment, n = 72.

Association of neutrophil-to-lymphocyte ratio and thrombotic events in US veterans with polycythemia vera.

6578 Background: Neutrophil-to-lymphocyte ratio (NLR) is a novel predictor of thrombosis in patients with Polycythemia Vera (PV), an uncommon myeloproliferative neoplasm distinguished by excessive red blood cell production within the bone marrow. However, there is no guideline-endorsed NLR cut-off that mandates cytoreduction. This study aims to assess the association of NLR and risk of thrombotic events, and evaluate the impact of different therapies based on electronic health records from the United States (US) Veterans Affairs Healthcare System (VAHS). Methods: Veterans with PV were identified based on either 2 outpatient codes separated by 30 or more days or 1 inpatient code in the VAHS databases (2017–2023). The first PV diagnosis was considered as the index date. Patients with myelofibrosis or leukemia diagnosis before the index date were excluded from the analysis. Veterans with at least one NLR value were examined for the occurrence of thrombotic events. Baseline characteristics were defined over the two-year period preceding the first PV diagnosis code. Treatments were defined within two years of the index date and categorized as: cytoreductive therapy (including hydroxyurea, interferons, or ruxolitinib), phlebotomy interventions, or neither. Cox proportional hazards regression was used to evaluate the associations between therapies and the risks of thrombotic events, controlled by the pre-index use of individual therapy. Results: A total of 11,809 Veterans with PV were identified from the VAHS, with a mean (SD) age of 67.4 (11.1) years, 96.7% male, 9.0% Black, 81.1% White, and 5.1% Hispanic. The rate of thrombotic events (per 1000 person-year) was 45 for patients treated with cytoreductive therapy, 32 for phlebotomy-treated patients, and 51 for those who received no treatment. Patients were delineated into five groups based on NLR: <1, 1-2.9, 3-4.9, 5-19.9, and above 19.9. The rate of thrombotic events was closely at 39% amongst each group with NLR below 5. For those with NLR at 5-19.9 and >19.9, thrombotic events were reported in 48% and 61% of veterans, respectively. Cytoreductive therapy and therapeutic phlebotomy were each associated with significantly lower risks of thrombotic events compared to none of these two treatments among PV patients. Adjusted risk of thrombotic events was 45% (HR: 0.55, 95%CI: 0.48-0.62, P < 0.01) and 34% (HR: 0.66, 95%CI: 0.57-0.78, P: < 0.01) lower for patients with cytoreductive and phlebotomy therapy compared to no treatment. Conclusions: The real-world evidence from VAHS yields a cut-off value of NLR at 5 to predict risks of thrombotic events among Veterans with PV. Patients receiving cytoreductive therapy or therapeutic phlebotomy had reduced risk of thrombotic events.

Utilization patterns and disparities in supportive oncology services for patients with stage IV non-small cell lung cancer.

e20649 Background: Supportive oncology (SO) services, including palliative care, social work, and dietitian support, are essential components of comprehensive cancer care. Among patients with stage IV non-small cell lung cancer (NSCLC), early supportive oncology services involvement has been associated with improved quality of life, reduced aggressive end-of-life care, and improved survival. However, Canadian data characterizing SO service utilization is limited. The primary objective of this study was to evaluate the uptake of SO services among patients with stage IV NSCLC at a regional cancer centre. Secondary objectives included assessing disparities in SO utilization based on geographic location and access to a primary care provider (PCP). Methods: We conducted a retrospective cohort study of all patients diagnosed with stage IV NSCLC and seen at the Cancer Centre of Southeastern Ontario between January 2021 and April 2024. Demographic and disease characteristics and utilization of palliative care, social work, and dietitian services were collected. Modified Poisson regression with robust error variance was used to evaluate associations between SO uptake and rural versus urban residence, as well as the presence versus absence of a PCP. Results: A total of 647 patients were included (median age 70; 54.7% male). Adenocarcinoma was the most common histology (49.8%), followed by squamous carcinoma (19.9%). Sixty-four percent resided in rural areas, and 85.5% had a PCP. Uptake of palliative care, social work, and dietitian services was 56.7%, 29.5%, and 21.3%, respectively. Urban residence was associated with higher palliative care utilization (adjusted RR 1.27, p<0.001), with nonsignificant trends toward greater social work (RR 1.24, p=0.0821) and dietitian involvement (RR 1.33, p=0.069). Patients with a PCP were less likely to receive social work services (adjusted RR 0.69, p=0.014), with no significant differences in palliative care or dietitian use. Conclusions: SO service uptake among patients with stage IV NSCLC remains suboptimal, with notable geographic disparities disadvantaging rural populations. These findings highlight opportunities to expand equitable access to SO services across our cancer centre and nationwide.

The efficacy and safety of 177Lu-PSMA-617 in metastatic castration resistant prostate cancer (mCRPC): Single-institution, real-world data.

e17040 Background: Lutetium Lu 177 vipivotide tetraxetan is a radiopharmaceutical that had received FDA approval in March 2022 for men with prostate-specific membrane antigen (PSMA) positive mCRPC who received taxane-based chemotherapy and an androgen receptor pathway inhibitor (ARPI). In the past year, the FDA expanded its indication to mCRPC patients who had received ARPI and were considered appropriate candidates for delaying taxane-chemotherapy. We present real-world data from a single institution using 177-Lu PSMA-617. Methods: After IRB approval, the electronic medical record (EMR) was retrospectively reviewed for patients who had received 177-Lu PSMA-617 from 2022-2025. We collected data on age, prior and subsequent lines of treatment (LOT), efficacy, progression-free survival (PFS), overall survival (OS), and toxicity profile. Results: A total of 81 patients received a median of 4 cycles of 177-Lu PSMA-617 at our institution. The median age was 75 years. The most common prior LOTs received were androgen deprivation therapy (84%), chemotherapy (82%), ARPI (72%), and radium-223 (19%). 16 (20%) patients were not exposed to any previous chemotherapy. PSA50 was achieved in 18 (23%) patients, and PSA90 in 15 (19%) patients. On further stratification, PSA50 was achieved in 4 (25%) chemo-naïve (CN) patients, and 14 (22%) chemotherapy-exposed (CE) patients. PSA90 was achieved in 7 (44%) CN patients, and 8(13%) CE patients. 22 (31%) patients had stable disease based on serum PSA, and 59 (73%) had progression of disease (POD) based on serum PSA and PSMA scan combined. The median PFS was 8 months (95% CI 6-10) in the entire population, with 9 months (95% CI 6-not reached) in CN patients, comparable to 9.3 months as per the PSMAfore trial, and 8 months (95% CI 5-13) in CE patients, comparable to the PFS of 8.7 months as per the VISION trial. The overall survival in either group was not reached (NR) (95% CI 24.1-NR). The toxicity profile was as follows: fatigue (53%), dry mouth (30%), anemia (14%), nausea/vomiting (12%). We had to interrupt treatment in 50 (62%) patients, mostly because of POD (37%), cytopenia (12%), patient preference (5%), skin infection/inflammation (2%), renal failure (2%), hepatotoxicity (1%), and muscle pain (1%). Among the most common subsequent LOT received are cabazitaxel (12%), DB-1311 (9%), immunotherapy (7%), chemotherapy (5%). 3 (3.7%) patients required hospitalization because of cytopenias requiring transfusion support. 25 (31%) patients expired as a result of POD. Conclusions: We reviewed the real-world efficacy and safety of177-Lu PSMA-617 in mCRPC at our institution. We found that chemotherapy naïve patients had a longer PFS, but the OS was not reached in either subgroup.

Expression analysis of molecules targeting regulatory T-cells in patients with oral squamous cell carcinoma.

e14508 Background: Immune checkpoint blockade is an important cancer treatment, but its therapeutic efficacy varies among patients. In the tumor microenvironment, PD-1 blockade reactivates PD-1+CD8+ T cells while simultaneously enhancing immunosuppression by PD-1+ regulatory T cells (Tregs); therefore, the balance between these populations has been proposed as a useful response biomarker. Because Tregs are also key therapeutic targets, multiple clinical trials using Treg depletion therapy have been conducted worldwide, but therapeutic efficacy has yet to be confirmed. In this context, we profiled the selectivity and expression intensity of representative Treg-depleting target candidates [CD25, T-lymphocyte antigen-4 (CTLA-4), C-C chemokine receptor 4 (CCR4), and CCR8] on effector Treg (eTreg), and investigated which molecules and combinations are more effective as therapeutic targets. Methods: A retrospective study was conducted on 24 patients with oral squamous cell carcinoma who underwent surgery. Peripheral blood lymphocytes (PBLs) were isolated from 24 patients and tumor infiltrated lymphocytes (TILs) from 24 patients respectively. eTreg fraction (CD4+CD45RA-FOXP3hi) was determined by flow cytometric analysis. eTreg frequency in each site and expression of CCR4, CCR8, CD25, CTLA-4 and PD-1 on the eTregs were analyzed. And PD-1 expression on CD8+ T cells was also assessed. The distribution of Tregs within the tissues was also analyzed using multi-fluorescence immunohistochemistry. Results: PD-1 expression on CD8+ T cells (mean [SD], %) was 7.9 [3.4] in PBL and 26.1 [9.2] in TIL (p < 0.001). PD-1 expression on eTregs was 1.7 [0.8] in PBL and 19.8 [9.1] in TIL (p < 0.001). The PD-1+CD8+ T cell/PD-1+eTreg ratio was 8.4 [14.6] in PBL and 1.8 [1.3] in TIL (p = 0.038), and this ratio varied across patients. CCR4 expression on eTregs was higher in PBL than in TIL (93.6 [6.6] vs 61.2 [14.0], p < 0.001), whereas CCR8 expression was higher in TIL than in PBL (61.3 [23.0] vs 23.6 [13.8], p < 0.001); accordingly, the CCR4/CCR8 balance on TIL eTregs was heterogeneous among patients. CD25 was highly expressed in both sites with slightly higher expression in TIL (PBL vs TIL: 80.5 [6.6] vs 85.8 [6.6], p = 0.008). CTLA-4 expression on eTregs was higher in TIL than in PBL (26.1 [9.5] vs 6.4 [3.2], p < 0.001). In the 5 cases of immunostaining, the PD-1+CD8+ T cell/PD-1+ Treg ratio was 11.7 [14.7] in Tumor area and 7.0 [8.9] in Stroma area (p = 0.52). Conclusions: These results suggest that for optimal Treg targeting strategies in oral cancer, it may be desirable to select different target molecules in the tumor and peripheral blood. Furthermore, because the expression of each molecule varies between patients, the optimal target molecule may differ for each patient.

Safety and efficacy of QLC5508 (MHB088C) in heavily-treated patients with metastatic castration-resistant prostate cancer: Updated data from a phase 1/2 trial.

5046 Background: QLC5508 (MHB088C), a novel B7-H3-targeted antibody-drug conjugate with high cell-binding activity and internalization rate, contains SuperTopoi payload which is 5 to 10 times more potent than Dxd. The preliminary data of a phase 1 study indicated the promising anti-tumor activity and tolerability of QLC5508 in patients (pts) with solid tumors, including metastatic castration-resistant prostate cancer (mCRPC). Here we report the updated results of efficacy and safety in pts with mCRPC. Methods: This multi-center phase 1/2 trial consisted of dose-escalation stage and dose-expansion stage. In dose-escalation stage, QLC5508 was administered via intravenous infusion at dosage ranging from 0.8 mg/kg to 4.0 mg/kg every two (Q2W) or three weeks (Q3W) in pts with various advanced solid tumors. Then, pts with mCRPC were recruited if they failed or intolerable to standard treatment, including second-generation androgen receptor pathway inhibitors (ARPIs) and/or taxane-based chemotherapy. Dose levels of 1.6 mg/kg Q2W, 2.0 mg/kg Q2W, and 2.4 mg/kg Q3W were selected. The primary endpoints were safety and tolerability. The secondary endpoints were objective response rate (ORR), disease control rate (DCR), and radiological progression-free survival (rPFS) per RECIST v1.1 and PCWG3, and prostate-specific antigen (PSA) response rate. Results: As of Nov 30, 2025, 59 pts were enrolled (≥3 lines of prior treatment: 74.6%; ≥3 lines of prior second-generation ARPIs: 28.8%; prior taxane: 84.7%; ≥2 lines of prior taxane: 16.9%). Grade ≥3 treatment-emergent adverse events (TEAEs) with incidence of > 20% were neutrophil count decreased (25.4%), anemia (23.7%), and white blood cell decreased (20.3%). Grade ≥3 gastrointestinal TEAEs occurred in two (3.4%) pts, both unrelated to the treatment. Intestinal lung disease occurred in one (1.7%) patient from 1.6 mg/kg Q2W dose level. TEAEs leading to treatment discontinuation and dose reduction occurred in one (1.7%) and six (10.2%) pts, respectively. The median rPFS was not reached (95% confidence interval [CI], 13.11-not evaluable [NE]), and the 12-month rPFS rate was 71.7% (95% CI, 52.55%-84.26%). In 38 pts at 2.0 mg/kg Q2W dose level, the median rPFS was not reached (95% CI, 13.11-NE), and 12-month rPFS rate was 78.6% (95% CI, 50.67%-91.80%). In 31 pts at 2.0 mg/kg Q2W dose level who had received prior second-generation ARPIs and taxane, the median rPFS was 13.11 months (95% CI, NE-NE). In 31 pts with target lesion at baseline, confirmed ORR and DCR was 22.6% (95% CI, 9.6%-41.1%) and 96.8% (95% CI, 83.3%-99.9%), respectively. Thirteen pts (22.8%) achieved PSA 50 response. Conclusions: QLC5508 showed prolonged rPFS as well as manageable safety profile in heavily treated pts with mCRPC. A phase 3 study is currently being planned. Clinical trial information: NCT07102004 .

PSMA PET/CT–guided intensification of salvage radiotherapy versus conventional planning for biochemical recurrence after radical prostatectomy: A GRADE-assessed systematic review and meta-analysis.

e17145 Background: Salvage radiotherapy (SRT) is the standard treatment for biochemical recurrence (BCR) after radical prostatectomy, yet outcomes remain variable. Prostate-specific membrane antigen PET/CT (PSMA-PET/CT) improves detection of recurrent disease and may allow more precise radiotherapy targeting. We conducted a systematic review and meta-analysis to compare oncologic outcomes and toxicity between PSMA-PET/CT–guided and conventionally planned SRT. Methods: PubMed, Embase, and Scopus were searched for randomized trials and comparative cohort studies published through July 2025. Eligible studies included men with BCR after radical prostatectomy treated with PSMA-PET/CT–guided or conventional SRT. The primary endpoint was failure-free survival (FFS). Secondary outcomes included biochemical progression-free survival (bPFS), treatment modification rates, and grade ≥2 gastrointestinal (GI) and genitourinary (GU) toxicities. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were estimated using random-effects models. Risk of bias was assessed using RoB-2 and the Newcastle-Ottawa Scale. Results: Six studies published between 2021 and 2025 comprising 912 patients were included. PSMA-PET/CT–guided SRT was associated with significantly improved FFS compared with conventional SRT (RR 0.56, 95% CI 0.36–0.86; p = 0.008; I² = 0%), corresponding to an absolute reduction of 178 events per 1,000 treated patients. Treatment modification rates were substantially higher with PSMA-PET/CT guidance (RR 32.03), though heterogeneity was high (I² = 95%); sensitivity analysis eliminated heterogeneity, suggesting interstudy variability as the primary driver. Rates of grade ≥2 acute and late GI and GU toxicities were similar between groups. Grade 3 toxicity was more frequent with PSMA-PET/CT–guided SRT (RR 2.34, 95% CI 1.14–4.78), although absolute event rates were low. Conclusions: PSMA-PET/CT–guided salvage radiotherapy is associated with improved failure-free and biochemical progression-free survival compared with conventional planning, without an increase in grade 2 GI or GU toxicity. While grade 3 adverse events were modestly higher, overall rates remained low. These findings support PSMA-PET/CT–guided SRT as an effective strategy for men with biochemical recurrence after prostatectomy, pending confirmation in prospective randomized studies.

T-cell prolymphocytic leukemia: A review of induction therapies.

e18617 Background: T cell prolymphocytic leukemia (T-PLL) is an aggressive neoplasm composed of mature T cells, with a median survival of under 1 year. Hematopoietic cell transplantation (HCT) is curative, but requires pre-transplant remission. While intravenous (IV) alemtuzumab has emerged as the primary induction therapy, combination therapies including pentostatin, fludarabine, cyclophosphamide, and mitoxantrone (FMC), and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) remain under-evaluated. This study aims to analyze overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and major adverse effects (AEs) across these regimens. Methods: A systematic search of PubMed and Web of Science using the terms: "Leukemia, Prolymphocytic, T-Cell" OR "T-cell prolymphocytic leukemia" AND "Alemtuzumab" OR "Campath." No date restrictions were applied. The search identified 253 documents. Titles and abstracts were screened for relevance. English language studies on chemotherapeutic interventions in T-cell prolymphocytic leukemia were included. Articles focusing on stem cell transplantation, opinion pieces, or consensus statements without transparent methodology were excluded. Eight articles were selected for qualitative analysis. Results: Alemtuzumab-based therapy significantly improved survival over historical regimens. IV administration was superior to subcutaneous (SubQ) for OS and PFS. Sequential FMC followed by alemtuzumab (FMC-A) produced similar survival outcomes but was associated with a high incidence of infectious complications. The addition of pentostatin to alemtuzumab achieved ORRs of 70–80%, although it increased cumulative myelosuppression. Historical regimens like CHOP were associated with lower ORR, OS, PFS, and rapid relapse. Conclusions: IV alemtuzumab monotherapy is a superior induction agent compared to SubQ administration and prior cytotoxic regimens. Although FMC-A achieves high response rates, it is associated with an increased risk of grade 3–4 AEs, particularly cytomegalovirus morbidity and neutropenia. As long-term survival depends on successful HCT, rapid remission is preferred to facilitate transplant bridging. Further efforts to improve outcomes in T-PLL should incorporate data on complete remission rates and efficacy of novel agents like JAK/STAT or BCL-2 inhibitors. Efficacy and safety summary of targeted vs. cytotoxic induction in T-PLL. Regimen (Key Refs) Est. N ORR (%) Median OS (mo) Median PFS (mo) Adverse Effects Alemtuzumab IV (1, 2) 210 76–92 15.0–21.6 10.0–11.2 CMV reactivation, minor infusion reactions Alemtuzumab SubQ (1, 3) 16 33 9.6 4.7 Primary refractory disease Sequential FMC-A (4, 5) 41 92 17.1 11.9 91% CMV reactivation, neutropenia Alemtuzumab+ Pentostatin (6) 50 70–80 10.0–13.0 7.0 Cumulative myelosuppression CHOP / Purine Analogs (7, 8) 150 20–40 7.0–13.0 < 6.0 Hematologic toxicity, rapid relapse

Ultra-sensitive whole-genome sequencing–based molecular residual disease detection in resectable sarcoma in MONSTAR-SCREEN-3.

11544 Background: Circulating tumor DNA (ctDNA)–based molecular residual disease (MRD) detection has shown strong prognostic value in multiple epithelial cancers, but its utility in sarcoma remains poorly defined. Sarcomas are highly heterogeneous and often represent low-shedding tumors, limiting the sensitivity of conventional assays. The MONSTAR-SCREEN-3 evaluates the clinical performance of a whole-genome sequencing (WGS)–based MRD assay in a pan-cancer cohort, including patients with sarcoma. Methods: Personalized ctDNA panels were generated using a WGS-based tumor-informed platform (Myriad Genetics), incorporating up to 1,000 tumor-specific variants identified through WGS of matched tumor tissue. Serial plasma samples were collected at baseline, 1 month post-surgery, quarterly during the first year, and biannually thereafter for up to two years. Results: As of November 2025, 35 patients with resectable soft tissue sarcoma (n=33) and osteosarcoma (n=2) were enrolled; MRD results were available for 72 samples from 24 patients. Of whom, histology was myxofibrosarcoma (n=7), undifferentiated pleomorphic sarcoma (n=7), myxoid liposarcoma (n=5), dedifferentiated liposarcoma (n=3), epithelioid sarcoma (n=3) and others (n=10). Clinical staging distribution included Stage I/II/III/IV: 15%/19%/50%/15%. Most of patients underwent upfront radical surgery (2 cases received neoadjuvant chemotherapy). Personalized panel creation succeeded in 100% of patients (24/24), identifying a median of 3,510 highly confident tumor-specific alterations per patient (range: 730-7,931) and yielding bespoke panels containing 386-1,000 alterations. Customized panels were created with 96.4% SNVs and 3.6% indels. The assay demonstrated 87.5% baseline ctDNA detection (21/24), with 16.7% detected at ultra-sensitive levels (tumor fraction <100 parts per million [ppm]). In the ctDNA-negative cases, ctDNA tumor fractions were 0.0, 0.8 and 6.2 ppm, classified as ctDNA-negative based on a statistical threshold set at 99.615% specificity. Post-surgical MRD positivity rates were 20.0% (4/20) at 1 month, 7.1% (1/14) at 3 months, and 28.6% (2/7) at 6 months. Among these patients, four patients developed radiographic recurrence, with MRD detection preceding imaging by median 1.1 months (0.1-3.0). Extended follow-up and comprehensive longitudinal ctDNA dynamics will be presented. Conclusions: The WGS-based ctDNA assay demonstrated high technical feasibility in sarcoma, enabling detection of patient-specific tumor variants across a highly heterogeneous and low-shedding tumor population. In our cohort, MRD positivity was observed exclusively in patients who subsequently developed recurrence, highlighting the potential utility of WGS-based tumor-informed MRD analysis for surveillance and risk stratification in sarcoma. Clinical trial information: UMIN000053975.

Automated eligibility screening for adjuvant CDK4/6 inhibitors in high-risk HR+/HER2− early breast cancer using natural language processing.

e23303 Background: While CDK4/6 inhibitors (CDK4/6i) have transformed the treatment landscape for high-risk, HR+/HER2- early breast cancer (EBC), identifying eligible patients in real-world settings remains labor-intensive. Manual review of unstructured clinical notes to match patients with evolving FDA criteria (e.g., abemaciclib, March 2023; ribociclib, September 2024) has led to an eligibility screening gap. We evaluated an automated pipeline to extract clinical eligibility criteria and facilitate rapid patient-treatment matching. Methods: We developed a hybrid Python-based information extraction pipeline that integrates spaCy-based named entity recognition (NER) with customized rule- and regex-based algorithms to parse both structured electronic health record (EHR) fields and unstructured clinical narratives, including pathology reports, from Yale Cancer Center. The system extracted 11 clinically relevant variables (e.g., ER/PR/HER2 status, tumor stage, Ki-67 index, nodal involvement). Eligibility for adjuvant CDK4/6 inhibitor therapy was determined using rule-based logic aligned with U.S. FDA-approved indications for abemaciclib and ribociclib. A gold-standard manual chart review was conducted by a trained clinical data coordinator on 100 randomly selected early breast cancer (EBC) patients. Extraction accuracy, eligibility classification performance (eligible vs. ineligible), and processing time were evaluated by comparing automated outputs against the manual reference standard. Results: The pipeline achieved ≥ 90% accuracy across all 11 individual data points. For the final eligibility classification, the tool demonstrated 99% accuracy, with only one false negative (classified as ineligible by NLP but eligible by manual review). Efficiency gains were significant: manual chart review required a median of 3 minutes per patient (range: 1–12), whereas the automated pipeline processed 100 patients in ~1 minute, representing a > 99% reduction in screening time. Conclusions: Automated NLP extraction is an accurate and scalable solution for identifying patients eligible for adjuvant CDK4/6i. By substantially reducing the time required for chart review, this tool can minimize treatment delays and ensure real-world adherence to changing FDA guidelines. Future work will compare this rules-based approach with ML and LLM-based extractors to improve semantic context handling and scalability across health systems. Eligibility classification performance of regex-based pipeline compared to manual chart review. Metric NLP/Regex-based pipeline performance Accuracy 99.0% Sensitivity (Recall) 100.0% Specificity 98.9% Precision 91.7% F1 Score 95.7%