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Corrigendum to “WO₃ nanoparticles: Synthesis and recent advances in their applications for radiotherapy and radioprotection” [Next Nanotechnol. 8 (2025) 100262]

Light‐Induced Entropy for Secure Vision (Adv. Mater. 33/2026)

Synchronizing the Osteochondral Regeneration Process through Spatial Patterning of Stable and Hypertrophic Cartilage Organoids

ABSTRACT Repairing deep osteochondral defects remains clinically challenging due to the intrinsic inability of articular cartilage to self‐repair and the need for integrated yet distinct regeneration of articular cartilage and subchondral bone. Here, we present a scaffold‐free, modular strategy that spatially bioassembles induced pluripotent stem cell (iPSC)‐derived chondrocytes (iChon) organoids with human periosteum‐derived cell (hPDC) organoids to engineer zonated osteochondral assembloids. The resulting iChon+hPDC assembloids exhibit intrinsic spatial organization, forming chondral‐ and osteo‐like zones with an intermediate interface without exogenous scaffolds. In vitro characterization confirmed layered glycosaminoglycan‐rich cartilage and collagen I‐rich osteo‐associated domains, with interface continuity emerging through self‐directed matrix organization. Upon implantation into full‐thickness osteochondral defects, iChon+hPDC assembloids promoted robust hyaline‐like cartilage repair, supported subchondral bone formation with ongoing repair/remodeling, and partially reestablished collagen fiber anisotropy. Protein‐level mapping further supported a surface‐associated cartilage phenotype and remodeling‐associated signatures in the deep compartment. Transcriptomic profiling revealed complementary biological programs, with iChon showing features suggestive of stable cartilage regulation and extracellular‐matrix remodeling competence, and hPDC showing a transient hypertrophic program associated with endochondral ossification. This work provides a scaffold‐free design framework for engineering zonated osteochondral implants through spatial assembly of lineage‐specific organoid modules, with translational potential for future osteochondral repair strategies.

Resting-state neural oscillations of the motor system influence the resting motor threshold

A photoactivatable Cre-loxP system for spatiotemporal genetic manipulation in mouse taste buds

Evaluation of clinical success and adverse events with endoscopic ultrasound-guided biliary drainage (EUS-BD) compared to percutaneous transhepatic biliary drainage (PTBD) after failed ERCP in malignant biliary obstruction: A systematic review and meta-analysis.

4186 Background: ERCP fails to achieve biliary decompression in ~3–10% of malignant biliary obstruction cases. Rescue drainage is typically performed using percutaneous transhepatic biliary drainage (PTBD) or endoscopic ultrasound–guided biliary drainage (EUS-BD). Although PTBD is widely available, it carries substantial morbidity, requires external catheters, and is associated with recurrent infections and reduced quality of life. EUS-BD offers internal drainage with favorable outcomes across established techniques, but comparative evidence versus PTBD remains limited. We performed a systematic review and meta-analysis comparing EUS-BD and PTBD after failed ERCP in malignant biliary obstruction. Methods: This review followed PRISMA guidelines. PubMed, Google Scholar, and ScienceDirect were searched using a comprehensive strategy. Comparative studies evaluating EUS-BD versus PTBD and reporting technical success (TS: bile duct puncture with stent/catheter placed in the intended position), clinical success (CS: > 50% bilirubin reduction at 2 weeks), adverse events (AD: graded as per the ASGE endoscopic AE severity lexicon), and reintervention (RN) were included. The data was analysed using the Meta, Metadata and the Metafor packages of R Studio. The Mantel-Haenszel method and the Inverse variance method were utilized to analyse the odds ratio for TS, CS, AD, and RN. The I 2 test was used to assess the heterogeneity of the studies. Results: Twenty-six studies were included. EUS-BD was associated with higher clinical success (OR 2.46, 95% CI 1.47–4.11) and lower odds of adverse events (OR 0.38, 95% CI 0.26–0.57) and reintervention (OR 0.19, 95% CI 0.09–0.42). Technical success did not differ significantly between groups (OR 0.49, 95% CI 0.21–1.13). Conclusions: Compared with PTBD, EUS-BD is associated with improved clinical success and fewer adverse events and reinterventions after failed ERCP in malignant biliary obstruction. Where expertise is available, EUS-BD may be favored over PTBD. Prospective randomized trials are needed to confirm these findings and support broader adoption. Pooled outcomes for EUS-BD vs PTBD. Outcome/Metric Comparison Effect measure Estimate (OR) 95% CI (lower) 95% CI (upper) p-value Direction/Interpretation Clinical success EUS-BD vs PTBD OR 2.46 1.47 4.11 0.1328 Favors EUS-BD (higher odds of success) Adverse events EUS-BD vs PTBD OR 0.38 0.26 0.57 0.1923 Favors EUS-BD (lower odds of adverse events) Reintervention EUS-BD vs PTBD OR 0.19 0.09 0.42 0.0003 Favors EUS-BD (lower odds of reintervention) Technical success EUS-BD vs PTBD OR 0.49 0.21 1.13 0.3321 Not statistically significant

Clinical characteristics, treatment patterns, and outcomes for patients with germ-cell tumor and brain metastases at diagnosis vs. relapse.

e17014 Background: Brain metastases (BM) occur in 2-3% of all patients (pts) with GCT. Data is limited for clinical characteristics, treatment patterns, and outcomes of pts with BM at diagnosis vs. at relapse. Methods: We identified pts with GCT and BM at initial diagnosis vs. relapse from the prospectively maintained Indiana University testicular cancer database. Pts were stratified by timing of BM (diagnosis vs relapse). Treatment patterns were grouped into chemotherapy (chemo) only vs. chemo plus local therapy (radiation or surgery). Start dates for progression free survival (PFS) and overall survival (OS) were date of BM diagnosis. PFS and OS were estimated using the Kaplan–Meier method and compared using the log-rank test. Results: 205 pts were included. Median age was 29.0 (16-51.5). Primary site was testis in 183 (89.3%), mediastinal in 15 (7.3%), and retroperitoneum in 7 (3.4%). 191 pts (93.2%) had nonseminomatous disease. Predominant histology was choriocarcinoma (38%), embryonal (22%), mixed (16.6%), yolk sac tumor (8.3%), teratoma (7.3%), seminoma (6.3%). IGCCCG risk at diagnosis was poor in 85.9%, intermediate in 5.4%, and good in 7.8%. 127 pts (62%) had BM at initial diagnosis; 78 pts (38%) at relapse. For those with BM at relapse, 52 (66.7%) were at 1 st relapse; 26 (33.3%) at ≥2 nd relapse. In pts with BM at relapse, 67.9% were originally IGCCCG poor risk, with 19.2% originally good risk (p < 0.001). Choriocarcinoma was the predominant histology for 45.7% of pts with BM at diagnosis vs. 25.6% of pts with BM at relapse. In pts with BM at diagnosis, median AFP was 6.9 (1-27,000) vs. 73 (1-52,207) in pts with BM at relapse (p = 0.02). Median hCG for pts with BM at diagnosis was 140,000 (1-2,000,000) vs. 36,200 (0.5-2,576,520) for pts with BM at relapse (p = 0.0018). In those with BM at diagnosis, 66 pts (52%) received chemo plus local therapy and 61 pts (48%) received chemo alone. In those with BM at 1 st relapse, 100% received chemo with local therapy. In those with BM at ≥2 relapse, 76.9% received chemo with local therapy. Median follow-up was 4.7 yrs (0.07, 30.2). Overall, 2yr PFS was 27.5%% (21.1-34.1). 2yr OS was 62.4% (54.6-69.3). For those with BM at diagnosis, 2yr PFS was 23% (15.8-31) vs. 35.7% (24.2-47.2) for those at relapse (p = 0.046). 2yr OS was 62.7% (52.8-71.1) for those with BM at diagnosis vs. 63% (49.6-73.7) for those with BM at relapse (p = 0.72). Conclusions: Pts with BM at diagnosis were more likely to have choriocarcinoma predominant histology and high levels of hCG as opposed to pts with BM at relapse. Here, there was no OS difference from time of BM diagnosis for pts with BM at diagnosis vs. relapse.

Retrospective review of the first three years of a pilot colorectal cancer screening program in the Dominican Republic.

e13630 Background: There are no national colorectal cancer (CRC) screening guidelines in the Dominican Republic (DR) and CRC screening is not routinely performed. In 2021, a primary care clinic in Santo Domingo, DR initiated a pilot CRC screening program using fecal immunochemical tests (FIT). This is a retrospective review of the first three years. Methods: We performed a retrospective cohort study of adults > 40 years old undergoing FIT testing (N = 3,696), categorized as asymptomatic (N = 2,886) or symptomatic (N = 810). Patients with positive FIT were referred for colonoscopy. We assessed FIT positivity, colonoscopy completion, adenoma detection, and FIT performance for high-risk lesions (invasive CRC or high-risk adenoma) among colonoscopy completers. Multivariable logistic regression evaluated predictors of colonoscopy completion among asymptomatic patients and predictors of adenoma detection among colonoscopy completers adjusted for symptoms. Results: Overall, 234/3,696 (6.3%) FIT tests were positive (asymptomatic: 4.4%, symptomatic 13.1%) and 10.4% of patients underwent a colonoscopy (asymptomatic 6.9%, symptomatic 23.1%). Among FIT-positive patients, 27.8% completed colonoscopy (asymptomatic 23%, symptomatic 37.7%). Among asymptomatic colonoscopy completers (n = 198), adenoma detection was higher in FIT-positive versus FIT-negative patients (31.0% versus 15.4%, p = 0.041). FIT performance for high-risk lesions showed high negative predictive value (NPV) in both cohorts (asymptomatic NPV 99.4%, symptomatic NPV 94.6%) with low positive predictive value (PPV) (asymptomatic PPV 10.3%, symptomatic PPV 17.5%) [Table 1]. Among asymptomatic patients, FIT positivity was independently associated with colonoscopy completion after adjustment for age and sex (aOR 4.27, 95% CI 2.73-6.67, p < 0.001). Among colonoscopy completers (N = 385, 70 events), FIT positivity was not independently associated with adenoma detection after adjusting for symptoms (aOR 1.46, 95% CI 0.77-2.75, p = 0.244). Among FIT-positive patients (N = 234), colonoscopy completion was associated with any alarm symptom (aOR 3.08, 95% CI 1.67-5.67; p = 0.0003) and alcohol use (aOR 2.74, 95% CI 1.34-5.60; p = 0.0056). Conclusions: Colonoscopy completion after FIT positivity was low, particularly among asymptomatic patients. FIT positivity was associated with adenoma detection in asymptomatic patients and FIT demonstrated high NPV for high-risk lesions. Improving linkage to colonoscopy after positive FIT may increase CRC prevention and early detection in this low-resource setting. FIT performance for high-risk lesions among patients completing colonoscopy. Cohort True Positive (TP) False positive (FP) False negative (FN) True negative (TN) Sensitivity (%) Specificity (%) PPV (%) NPV (%) Asymptomatic (n=198) 3 26 1 168 75.0 86.6 10.3 99.4 Symptomatic (n=187) 7 33 8 139 46.7 80.8 17.5 94.6

The lineage-defining transcription factors FOXA1 and POU2F3 as markers of poor prognosis across two large cohorts of thymic malignancies.

e20172 Background: Thymic epithelial tumors (TETs) are rare neoplasms arising in the anterior mediastinum. TETs are stratified using the WHO classification system, which remains fundamental to prognostication and clinical decision-making. However, metastasis and aggressive tendencies are observed in all WHO subtypes, warranting further understanding of the pathobiology of TETs. Although the expression of some lineage-defining transcription factors (LTFs) in TETs has been reported previously, their clinical significance remains largely unexplored. We, herein, evaluate expression of 14 LTFs and the corresponding impact on patient outcomes across two large clinicogenomic cohorts. Methods: Expression of LTFs previously identified in thymic tissues ( AIRE , FOXA1 , FOXA2 , FOXA3 , FOXJ1 , GRHL1 , GRHL2 , GRHL3 , HNF4A , HNF4G , MYOG , POU2F3 , SOX8 and SPIB ) was evaluated in two cohorts (Caris and TCGA). The Caris cohort consisted of whole-transcriptome data from FFPE-preserved TETs using the Caris Life Sciences platform, which was also supplemented with clinicopathological data curated from the Caris data repository as well as insurance claims data. Blinded histology review with WHO subtype classification was performed by a pathologist with expertise in thymic tumors (S.S.B.). TCGA data was obtained from publicly available resources. Statistical methods employed included quantitative Cox regression and Log-Rank methods for analyses with overall survival (OS) as well as the Mann-Whitney U test for single gene expression comparisons. Results: After filtering out LTFs with low expression (median TPM<1) from the Caris dataset (n=107, 71% WHO type B3/C), seven LTFs were retained for further analysis including FOXA1 , GRHL1 , GRHL2 , GRHL3 , HNF4G , POU2F3 , and SPIB . Univariate survival analyses revealed positive associations with FOXA1 , HNF4G , and POU2F3 , while only FOXA1 and POU2F3 remained independent biomarkers in a multivariate model ( FOXA1 : HR = 1.02; p = 0.05; POU2F3 : HR = 1.01; p = 0.03). Multivariate analysis from the less aggressive TCGA cohort (n=117; 18% WHO type B3/C) also validated FOXA1 and POU2F3 associations with poor outcomes ( FOXA1 : HR = 1.14, p = 0.008; POU2F3 : HR = 1.04, p = 0.05). Tumors highly expressing both LTFs were associated with exceptionally poor outcomes as compared to tumors with low expression of both (median OS: 8 mos. vs 58 mos.; p<0.0001). Thymic carcinomas were associated with higher expression of both LTFs when compared to thymomas. Robust correlation between FOXA1 and POU2F3 was observed as well as with markers of tuft cell differentiation, KIT and GFI1B . Conclusions: FOXA1 and POU2F3 expression are markers of poor outcomes and likely related to tuft cell differentiation in thymic epithelial tumors. Testing these biomarkers prospectively may improve diagnostic resolution for previously established classification systems.

Prognostic factors and impact of concomitant medication in extensive-stage small cell lung cancer (ES-SCLC) treated with first-line chemotherapy plus anti-PD-L1: A Spanish multicenter real-world study.

8107 Background: Platinum - etoposide with PD-L1 inhibitors is the standard first-line treatment for ES-SCLC. However, real-world outcome data remain limited, particularly regarding the prognostic impact of frequently used concomitant medications. Methods: Retrospective multicenter cohort (9 Spanish centers; Oct 2019 - Apr 2025) of ES-SCLC treated with first-line platinum - etoposide plus anti-PD-L1. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan - Meier. Proton pump inhibitor (PPI), corticosteroid*, and antibiotic use within 30 days before treatment initiation were recorded. Multivariable Cox models were adjusted for Eastern Cooperative Oncology Group performance status (ECOG PS), liver/bone/central nervous system (CNS) metastases (mets), and medications. The immune-related adverse event (irAE) - OS association was explored using time-fixed and 12-week landmark analyses. Results: A total of 442 patients were included (median age 66, 67% male, 90% ECOG PS 0–1); PD-L1 inhibitor: atezolizumab 97%, durvalumab 3%, pembrolizumab <1%. Liver, bone, and CNS mets were present in 40%, 34%, and 27%. PPIs, corticosteroids, and antibiotics were used in 51%, 33%, and 26%. Most (77%) completed induction (4 cycles); 79% initiated maintenance (6% after <4 cycles). ORR was 80% and DCR 90% (n=404 evaluable; routine assessment). With median follow-up of 27.2 months (reverse Kaplan - Meier), median PFS was 5.6 months (95% CI 5.3 - 6.1) and median OS 10.2 months (95% CI 8.4 - 11.3); 12-month OS 43%. On multivariable analysis (complete-case n=415; Table), ECOG PS ≥2 and liver/bone/CNS mets were associated with worse OS, while PPIs, corticosteroids, and antibiotics were not. irAEs occurred in 24%; time-fixed analysis suggested improved OS (adjusted HR 0.61; 95% CI 0.45 - 0.81; p<0.001), but this was not confirmed in 12-week landmark analysis (HR 0.84; 95% CI 0.55 - 1.29; p=0.43). Conclusions: In this large real-world ES-SCLC cohort treated with first-line chemoimmunotherapy, ECOG PS and metastatic burden remained key prognostic factors. Concomitant PPIs, corticosteroids, and antibiotics were not independently associated with OS, although residual confounding by indication cannot be excluded. The irAE - OS association was not confirmed by landmark analysis, highlighting the importance of time-dependent methods. Multivariable Cox regression for OS (n=415). Variable HR (95% CI) p-value ECOG PS ≥2 vs 0-1 1.47 (1.02–2.12) 0.039 Liver mets 1.53 (1.22–1.94) <0.001 Bone mets 1.52 (1.19–1.93) <0.001 CNS mets 1.41 (1.10–1.81) 0.006 PPI (≤30d) 1.13 (0.89–1.44) 0.311 Corticosteroids (≤30d)* 1.03 (0.79–1.33) 0.842 Antibiotics (≤30d) 1.18 (0.89–1.55) 0.245 *Non-prophylactic systemic corticosteroids (≥10 mg/day prednisone-equivalent).

Temporal trends in breast cancer case volume, subtypes, and age at diagnosis in Vietnam: An eight-year analysis of 15,227 patients.

e23375 Background: Breast cancer subtype distribution and age at diagnosis may differ between Asian and Western populations. We aimed to characterize temporal changes in age at diagnosis and breast cancer subtypes defined by hormone receptor (HR) and HER2 status in a large Vietnamese cohort. Methods: We conducted a retrospective analysis of a breast cancer pathology registry including patients diagnosed between 2015 and 2022 at Vietnam National Cancer Hospital. Collected variables included age at diagnosis, estrogen receptor (ER), progesterone receptor (PR), HER2 status assessed by immunohistochemistry (IHC), and year of diagnosis. HER2 positivity was defined as IHC 3+. Tumors with HER2 IHC 2+ were categorized as HER2-equivocal, as confirmatory in situ hybridization was not routinely available or affordable. Breast cancer subtypes were classified as HR+/HER2–, HER2-positive (IHC 3+), HER2-equivocal (IHC 2+), and triple-negative breast cancer (TNBC). Patients with missing data were excluded. Results: A total of 15,227 breast cancer patients were included. The annual number of diagnosed cases increased from 850 in 2015 to 3,260 in 2022, with a temporary decline in 2021 (1,715 cases), likely related to the COVID-19 pandemic (Table 1). The overall mean age at diagnosis was 57.3 ± 11.8 years and decreased over time, from 62.2 years in 2015 to 53.3 years in 2022. Regarding subtype distribution, 45.8% of tumors were HR+/HER2–, 28.2% were HER2-positive, 13.0% were HER2-equivocal, and 13.0% were TNBC. Overall, 67.9% of tumors were HR-positive. The distribution of HR status and HER2 IHC expression did not differ significantly between patients aged ≤40 years and > 40 years (HR-positive: 70.5% vs 67.7%; HER2 IHC 3+: 28.3% vs 28.2%, respectively; p-values > 0.05). Detailed temporal trends are shown in Table 1. Conclusions: In this large real-world cohort from Vietnam, the number of patients diagnosed with breast cancer increased substantially during the period. Patients were diagnosed at younger ages over time, with a consistently high proportion of HER2-positive disease across age groups. These findings might help to develop context-specific research and health system planning to optimize diagnostic capacity and treatment strategies. Distribution of breast cancer case volume, subtypes, and age at diagnosis over time. Year Total (N) Age, mean ± SD (years) HR+/HER2– (%) HER2-positive (%) HER2-equivocal (%) TNBC (%) 2015 850 62.2 ± 10.7 38.1 25.5 23.4 12.9 2016 1,410 61.1 ± 11.3 42.7 27.6 14.8 15.0 2017 1,640 60.2 ± 11.1 45.1 28.0 13.0 13.9 2018 1,779 59.8 ± 11.0 46.9 28.3 12.9 11.9 2019 2,197 58.3 ± 11.4 49.3 26.9 10.7 13.1 2020 2,376 54.6 ± 11.5 44.1 28.5 14.1 13.3 2021 1,715 56.2 ± 11.5 45.2 29.3 11.4 14.2 2022 3,260 53.3 ± 11.7 48.3 29.1 11.2 11.4 Overall 15,227 57.3 ± 11.8 45.8 28.2 13.0 13.0

Sex-based differences in metastasis among patients with early-onset pancreatic ductal adenocarcinoma.

e16423 Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by early systemic dissemination and a strong predilection for liver metastasis. The incidence of early-onset PDAC is rising, yet sex-specific patterns of metastasis remain poorly characterized. Preclinical evidence demonstrates that sex hormones, immune composition, and stromal signaling shape PDAC tumor biology and the hepatic metastatic niche, resulting in sex-dependent metastatic differences in experimental models. Methods: We retrospectively identified patients with early-onset metastatic PDAC between January 2015 and December 2025 using ICD-10 codes and pathologically confirmed PDAC. Clinical, demographic, molecular, and treatment data were abstracted from the EHR. The primary endpoint was presence of liver metastasis at diagnosis. Secondary endpoints included metastatic distribution and overall survival. Results: Of the 95 patients in this cohort, at diagnosis, liver metastases were present in 54.4% of males and 44.7% of females, corresponding to an absolute risk difference of 9.7% with higher prevalence among men. The unadjusted odds of liver metastasis were higher in men compared with women (OR 1.47, 95% CI 0.60–3.62). Bone metastases were about three-fold more frequent in women than in men (10.5% vs 3.5%). Among patients who developed recurrent disease following surgical resection, women had a lower proportion of liver-first recurrence compared with men (45% vs 67%), with an odds ratio of 0.42. This difference was not statistically significant (Fisher’s exact p = 0.41) and should be considered hypothesis-generating. Reproductive and hormonal factors appeared to modulate outcomes. Recent pregnancy was associated with improved overall survival (HR 1.76, 95% CI 0.60–5.17), whereas peri- or post-menopausal status was associated with worse survival compared with pre-menopausal status (HR 0.30, 95% CI 0.07–1.29). Conclusions: Sex was associated with differences in metastatic organ distribution rather than overall metastatic incidence. Men demonstrated higher prevalence of hepatic involvement at diagnosis and a greater proportion of liver-first recurrence following resection, whereas women exhibited greater extra-hepatic dissemination, including increased bone involvement. These patterns suggest sex-conditioned differences in hepatic metastatic niche permissiveness. Reproductive and hormonal state may further influence metastatic progression and survival. Although underpowered and hypothesis-generating, these trends are biologically plausible and concordant with preclinical models, warranting validation in larger, multi-institutional cohorts. Metastatic distribution at diagnosis for early-onset PDAC. Female Male Liver 44.74% 54.39% Lung 7.89% 7.02% Peritoneum/omentum 13.16% 14.04% Distant lymph node 15.79% 10.53% Bone 10.53% 3.51% Brain 0.00% 1.75% Other 10.53% 1.75%

A phase 2 study of neoadjuvant nivolumab (nivo) + relatlimab (rela) in high-risk stage II cutaneous melanoma (NeoReNi).

9502 Background: Patients (pts) with stage II melanoma account for ~50% of those who develop metastatic disease. Checkpoint inhibitor neoadjuvant therapy (NAT) is standard for resectable stage III melanoma (NADINA & SWOG 1801) and pathological response correlates with recurrence. Other NAT benefits include personalised prognosis, tailored subsequent management, and collection of translational specimens to explore response and resistance mechanisms. The NeoReNi II trial aimed to determine feasibility, response and safety of NAT nivo+rela in resectable stage II melanoma. Methods: Eligible pts had biopsy (partial) confirmed AJCC (v8) clinical stage IIA (T2b, T3a), IIB (T3b, T4a), or IIC (T4b) cutaneous melanoma with residual macroscopic primary disease at enrolment. IIA pts had ≥20% 5 yr recurrence risk according to Melanoma Institute Australia stage II risk calculator (melanomarisk.org.au). All pts underwent sentinel lymph node (SLN) mapping at baseline and peri-operatively, and resection (wide excision + SLN biopsy [RES]) at wk 6 following 2 doses of nivo (480 mg, IV) + rela (160 mg, IV). Pts without major pathological response (MPR) had 11 cycles (Q4W) of adjuvant nivo/rela. FDG PET/CT was performed at baseline; CT prior RES; dermoscopy and reflectance confocal microscopy (RCM) baseline, wk 3 and prior to RES. The primary endpoint was the path complete response (pCR) rate. Secondary endpoints included feasibility of NAT in stage II, RECIST response, RFS, OS, safety/tolerability, surgical outcomes, QOL. Exploratory; biomarker, dermoscopy and RCM analyses. Results: From 6 Oct 2023 to 21 Oct 2025, 20 pts were recruited and received NAT, demonstrating partial biopsy leaving residual macroscopic stage IIA-C primary melanoma was feasible. Median age 67 yrs (46-81yrs), 9 females, 8 IIA, 8 IIB and 4 IIC. 18 (90%) pts received both NAT doses. 12 (60%) pts had pCR in the primary melanoma, 1 near-pCR (MPR 65%), 1 pPR and 6 (30%) pNR. Drug treatment related adverse events (TRAE) gd ≤ 2 occurred in all 20 pts (100%); 11 (55%) with fatigue, 8 rash (40%) and 5 arthralgia (25%). 3 (15%) pts had gd 3 (secondary adrenal insufficiency, nephritis, pneumonitis). There were no gd 4 or 5 TRAEs. 1 (5%) pt had a gd 3 AE related to surgery (cellulitis). 19 (95%) pts had no change in SLN mapping from pre to RES. 2 pts with pNR in primary melanoma had postitive SLN and 1 pt with pCR had focal fibrosis within a negative SLN, suggestive of possible treatment effect. Dermoscopy showed regression in all 12 MPR (100%) pts; 11 also showed changes in RCM (collagen reorganization and imflammatory infiltrates) concordant with pathology. At datacut off (11 Dec 25) 2 pts recurred, 5 and 11 mo respectively (both pNR);1 died due to melanoma (15 mo after 1 st recurrence; 20 mo after enrolement. Positive SLNBx at pNR). Conclusions: NAT with nivo + rela in resectable stage II melanoma was feasible and induced a high rate of pCR and MPR in the primary melanoma. Clinical trial information: NCT05418972 .

Efficacy, safety, and quality of life outcomes of 177Lu-PSMA-617 in metastatic castration-resistant prostate cancer: A GRADE-assessed systematic review, meta-analysis, and trial sequential analysis of randomized controlled trials.

5062 Background: 177Lu-PSMA-617 radioligand therapy (RLT) offers a targeted approach for metastatic castration-resistant prostate cancer (mCRPC). However, its consolidated impact on survival, patient-reported outcomes, and safety requires rigorous validation. We conducted a systematic review, meta-analysis, and trial sequential analysis (TSA) to evaluate the robustness of evidence regarding efficacy, toxicity, and quality of life (QoL). Methods: We systematically searched PubMed, Cochrane, and Embase for prospective randomized controlled trials (RCTs) comparing 177Lu-PSMA-617 versus standard-of-care (SOC) in mCRPC. Primary outcomes included overall survival (OS), radiographic progression-free survival (rPFS), and PSA response. Secondary outcomes included QoL (FACT-P scores, pain intensity) and adverse events (AEs). TSA was performed to assess the conclusiveness of the cumulative evidence. Data were pooled using a random-effects model. Results: Six prospective RCTs comprising 2,113 patients (1,263 Lu-PSMA; 850 SOC) were included. Lu-PSMA significantly improved overall survival (HR 0.76; P = 0.02) and radiographic progression-free survival (HR 0.55; P < 0.00001) compared to SOC. QoL metrics significantly favored Lu-PSMA, including mean difference in QoL scores (MD 2.93; P < 0.00001), time to deterioration of FACT-P (RR 0.58; P < 0.00001), and worsening of pain intensity (OR 0.61; P = 0.002). TSA demonstrated conclusive evidence for PSA response (RR 2.33; P = 0.001), as the Z-curve crossed the monitoring boundary. However, TSA for ORR and PFS remained inconclusive despite favorable point estimates. Regarding safety, Lu-PSMA was associated with higher risks of Grade 1-2 dry mouth (RR 9.75), Grade ≥3 thrombocytopenia (RR 6.20), and Grade 1-2 dry eyes (RR 6.66). Conclusions: 177Lu-PSMA-617 demonstrates a significant survival benefit and conclusively improves PSA response rates in mCRPC. Crucially, it preserves quality of life by delaying the deterioration of physical function and pain. While effective, the therapy carries specific toxicity risks, notably xerostomia and high-grade thrombocytopenia, necessitating careful patient monitoring. Outcome Effect Estimate (95% CI) P-Value I² TSA Status Overall Survival HR 0.76 (0.59–0.96) 0.02 68% - Radiographic PFS HR 0.55 (0.43–0.71) <0.00001 67% Inconclusive PSA Response Rate RR 2.33 (1.38–3.93) 0.001 93% Conclusive Objective Response Rate RR 2.94 (1.55–5.55) 0.0009 72% Inconclusive Quality of Life (MD) MD 2.93 (1.80–4.07) <0.00001 20% - Time to Det. FACT-P RR 0.58 (0.51–0.66) <0.00001 0% - Worsening Pain Score OR 0.61 (0.44–0.84) 0.002 81% - Dry Mouth (Grade 1-2) RR 9.75 (6.85–13.88) <0.00001 91% - Thrombocytopenia (G≥3) RR 6.20 (2.18–17.65) 0.0006 0% - Dry Eyes (Grade 1-2) RR 6.66 (2.79–15.91) <0.0001 0% -

STK11 and/or KEAP1 alterations in KRAS-mutant NSCLC treated with immune checkpoint inhibitors or chemotherapy: An episode-based Project GENIE analysis.

8544 Background: STK11 and KEAP1 alterations are linked to aggressive biology in KRAS-mutant NSCLC and have been proposed to confer immune resistance and inferior outcomes with immune checkpoint inhibitor (ICI) though data remains inconsistent. We evaluated whether STK11 and/or KEAP1 alterations are associated with inferior overall survival (OS) and whether outcomes differ by treatment class (ICI vs chemotherapy) in a real-world clinic-genomic cohort. Methods: Using GENIE BPC NSCLC v2.0-public data, we created an episode-based cohort of KRAS-mutant NSCLC treatment regimens categorized as ICI or chemotherapy. STK11 and/or KEAP1 alteration status (single or dual) was the primary exposure. OS was measured from regimen start and analyzed with multivariable Cox models using patient-level clustering, adjusting for available covariates (age, sex, histology, tumor mutational burden [TMB], and KRAS G12C). We tested effect modification with an interaction term (STK11/KEAP1 × ICI). Sensitivity analyses included 3-, 6-, and 12-months landmark models and inverse probability of treatment weighting (IPTW). PD-L1, ECOG PS and line of therapy were not available. Results: We identified 542 treatment episodes from 293 patients (ICI = 149; chemo = 393) including 181 episodes that were STK11/KEAP1-altered. In the main cluster-robust model, STK11/KEAP1 alterations were associated with worse OS (aHR 1.68, 95% CI 1.27 - 2.24; p < 0.001). ICI (vs chemo) was associated with higher hazard ratio (aHR 1.76, 95% CI 1.42 - 2.18; p < 0.001) likely reflecting later-line use of ICI. The STK11/KEAP1 × ICI interaction was not significant as aHR 1.13, 95% CI 0.76 - 1.67; p = 0.559). In the 3-month landmark analysis STK11/KEAP1 remained adverse (aHR 1.61, 95% CI 1.19 - 2.18; p = 0.002), and the interaction estimate shifted below 1.0 (aHR 0.86, 95% CI 0.55 - 1.35; p = 0.519) suggesting a possible trend toward relatively greater ICI benefit among altered patients who survive beyond early attrition. Results were directionally consistent across 6- and 12-month landmark and IPTW analyses. Conclusions: In this real-world KRAS-mutant NSCLC cohort, STK11 and/or KEAP1 alterations were consistently associated with worse OS across treatment classes, supporting a primarily prognostic role. We did not find evidence of ICI-specific resistance by STK11/KEAP1 status, although modest interaction effects may be underpowered. Unmeasured confounding (ECOG PS, PD-L1 and line of therapy) remains a key limitation highlighting the need for larger, highly annotated datasets. Model STK11/KEAP1 aHR (95% CI); p ICI vs Chemo aHR (95% CI); p Interaction aHR (95% CI); p Main 1.68 (1.27–2.24); <0.001 1.76 (1.42–2.18); <0.001 1.13 (0.76–1.67); 0.559 3-mo Landmark 1.61 (1.19–2.18); 0.002 1.76 (1.39–2.23); <0.001 0.86 (0.55–1.35); 0.519 IPTW 1.68 (1.27–2.24); <0.001 1.76 (1.42–2.19); <0.001 1.13 (0.75–1.70); 0.546

Opportunities for lung cancer screening: A prospective cross-sectional study of patients with lung cancer treated at an academic cancer center.

e22528 Background: In 2021, the U.S. Preventive Services Task Force (USPSTF) expanded criteria for lung cancer screening (LCS) with annual low-dose CT (LDCT) for adults aged 50-80 years with ≥20 pack-years (PY) who currently smoke or quit within 15 years. We examined implementation of LCS among patients with lung cancer treated at our center prior to their cancer diagnosis. Methods: Cross-sectional questionnaire survey of patients with lung cancer and ever-smoking history, treated at our institution was conducted between June 2022 and June 2024. Demographics, cancer stage, smoking history, cessation timing, primary care physician (PCP) engagement, LCS with modality were captured. Eligibility for USPSTF 2021 LCS specifically a year preceding cancer diagnosis was assessed for each patient. Responses that allowed direct verification or reasonable inference for eligibility were analyzed. Results: Cross-sectional questionnaire survey of patients with lung cancer and ever-smoking history, treated at our institution was conducted between June 2022 and June 2024. Demographics, cancer stage, smoking history, cessation timing, primary care physician (PCP) engagement, LCS with modality were captured. Eligibility for USPSTF 2021 LCS specifically a year preceding cancer diagnosis was assessed for each patient. Responses that allowed direct verification or reasonable inference for eligibility were analyzed. Conclusions: Our study supports published data on under-utilization of LDCT and provides a peek into the real-world implications of this gap by demonstrating that > 60% of patients in this cohort were diagnosed at an advanced stage, which could perhaps have been prevented if LCS was performed years prior. This data highlights the magnitude of missed opportunities for early lung cancer detection. The percentage of patients lacking a PCP could also have been a barrier for optimal LCS. Our findings highlight the urgent need to enhance patient and clinician awareness of guidelines and improve referral pathways. Summary of patients included in the analysis. Metric Value Total respondents 244 Respondents with analyzable eligibility/number eligible 131/110 Age (years) Mean 69.8; Median 72 Gender (%) Male: 56; Female: 44 Age at first tobacco use (years) Median 16 (IQR 15.0-18.5) Stage III-IV at diagnosis 79 (60.3%) Tobacco use at time of survey 35 (26.7%) Median cessation period for those who quit (years) 2 (IQR 1-6) PY Mean 53.5; Median 47.0

Polypharmacy discussions in older adults with newly diagnosed acute myeloid leukemia (AML).

e13760 Background: Polypharmacy, the use of ≥5 medications, is common in older adults and associated with worse outcomes in AML. A greater understanding of polypharmacy concerns during upfront AML treatment decisions could facilitate medication optimization. We explored how polypharmacy concerns were discussed and addressed by the oncologist during initial treatment visits with older adults newly diagnosed with AML in a pilot randomized controlled trial of a geriatric assessment and value-based decisional intervention (UR-GOAL). Methods: Patients ≥60 years with AML were randomized to UR-GOAL or usual care. In UR-GOAL, oncologists received a geriatric assessment summary report including polypharmacy findings. Initial treatment decision-making encounters were audio-recorded and transcribed. Polypharmacy concerns were coded independently by three coders, and oncologist responses were categorized as addressed, acknowledged, or dismissed. Results: We included 53 patients (27 UR-GOAL, 26 usual care). Median age was 74 (IQR 68-79), 30% females, and 91% White. Baseline polypharmacy was less common in UR-GOAL vs. usual care (33 vs. 54%). The average number of polypharmacy concerns per patient was 0.85 for usual care and 0.63 for UR-GOAL. Concerns involved drug-related side effects (33%), drug-drug interactions (26%), high-risk medications per Beer’s criteria (13%), medication count (10%), supportive medications (8%), and unspecified issues (10%) (See Table 1 for details). Most were raised by oncologists (54%), followed by caregivers (26%), and patients (21%). Common interventions were patient information and counseling (38%), non-cancer treatment modification (34%), and interprofessional communication (13%). Concerns were more often addressed in UR-GOAL than usual care (88% vs. 77%), particularly side-effects (80% vs. 50%). Conclusions: In this secondary analysis of older adults with newly diagnosed AML, common polypharmacy concerns during treatment decision-making included drug-related side effects, drug–drug interactions, and high-risk medications per Beer’s criteria. Future interventions could be designed to better address these common concerns. Specific polypharmacy concerns by common themes. Specific concerns # of concerns Who initiated the concern (# of concerns) Interaction of vitamins, herbs, cannabis, and probiotics with chemotherapy 8 Caregiver (4), Patient (2), Oncologist (2) Side effects of home medications 7 Oncologist (5), Caregiver (1), Patient (1) Bleeding risk from antiplatelet or anticoagulation while on chemotherapy 6 Oncologist (3), Patient (2), Caregiver (1) Side effects of antimicrobials 5 Patient (3), Oncologist (2) Adjustment of home medications 4 Oncologist (3), Caregiver (1) Ability to manage multiple home medications 4 Oncologist (3), Caregiver (1) Interaction of anti-fungal and antibiotics with chemotherapy 3 Caregiver (2), Oncologist (1)

Phase 3 trial ResQ201A of nogapendekin alfa inbakicept (NAI) plus tislelizumab and docetaxel vs. docetaxel monotherapy for advanced or metastatic NSCLC resistant to ICI therapy.

TPS8671 Background: Immune checkpoint inhibitors (ICIs) are approved as monotherapy and in combination with chemotherapy in advanced NSCLC. Most patients experience progression with limited treatment options other than chemotherapy. NAI is a first-in-class IL-15 receptor agonist that induces proliferation and activation of natural killer cells, CD8+ T cells and memory T cells without activating regulatory T cells, enhancing both the innate and adaptive immune system to maximize immunogenic cell death. Phase 2 data demonstrated evidence of NAI prolonging OS when used in combination with an ICI. The rationale for ResQ201A (NCT06745908) is based on the prior QUILT-3.055 study, wherein median OS was prolonged at 14.3 months overall and 21.1 months when ALC≥1.2x10^3 was maintained with NAI as a lymphocyte stimulating agent. Randomized clinical trials have demonstrated that the standard of care docetaxel in the 2L+ NSCLC setting results in a mOS of approximately 9 months. Methods: ResQ201A is a randomized, open-label phase 3 global, registrational intent trial where 462 adult participants will be enrolled 2:1 in the experimental arm, consisting of two 3-week induction cycles of NAI [SC 1.2 mg], tislelizumab [IV 200 mg] and docetaxel [IV 75 mg/m 2 ] followed by maintenance NAI and tislelizumab, or a docetaxel monotherapy control arm [IV 75 mg/m 2 ] until disease progression or unacceptable toxicity. Participants are stratified based on histology, presence of actionable genomic alterations (AGA), and geographical region. Key inclusion criteria are pathologically confirmed stage IV NSCLC with acquired resistance to an ICI (PD after an initial response OR stable disease ≥ 6 mo. duration) to a single line of ICI with or without chemotherapy, ECOG 0 to 2, and measurable tumor lesions per RECIST v1.1. Key exclusion criteria are systemic autoimmune disease, history of organ transplant, and AGA of ALK. The primary endpoint is OS by KM with treatment arm comparison based on the stratified log-rank test and OS hazard ratio summarized based on the stratified Cox proportional hazard model, both stratified by the randomization strata. Secondary efficacy endpoints include iDCR per iRECIST; PFS, ORR and duration of response. Safety is graded using the NCI CTCAE v5.0. Exploratory analyses will be performed to meet objectives. This trial has enrolled and treated participants. Clinical trial information: NCT06745908 .

Serum miR-181-5p, miR-214-3p, and miR-223-3p expression in epithelial ovarian cancer.

e17539 Background: Detection of epithelial ovarian cancer (EOC) remains challenging because of nonspecific symptoms and the limited performance of current serum biomarkers. Circulating microRNAs (miRNAs) are stable in blood and represent promising minimally invasive biomarker candidates. This study evaluated the diagnostic and prognostic relevance of serum miR-181-5p, miR-214-3p, and miR-223-3p in patients with EOC compared with healthy controls. Methods: In this single-center case–control study, pretreatment serum samples were obtained from 77 patients with histologically confirmed EOC and 74 healthy female controls. Serum miRNA expression was quantified by quantitative real-time PCR and normalized to U6 RNA. Differences between groups were analyzed using nonparametric tests and analysis of covariance adjusting for age and body mass index. Diagnostic performance was assessed by receiver operating characteristic (ROC) analysis. Associations with clinicopathologic features, platinum sensitivity, progression-free survival, and overall survival were evaluated using logistic regression and Cox proportional hazards models. Results: Serum miR-181-5p and miR-223-3p levels were significantly reduced in EOC compared with controls (both p<0.001), whereas miR-214-3p showed no significant difference (p=0.505). After adjustment for age and BMI, reductions remained significant for miR-181-5p (p<0.001) and miR-223-3p (p=0.004); miR-214-3p remained nonsignificant (p=0.052). ROC analysis showed moderate diagnostic accuracy for miR-181-5p (AUC 0.704; 95% CI 0.614–0.794) and miR-223-3p (AUC 0.732; 95% CI 0.644–0.820); miR-214-3p had limited utility (AUC 0.573; p=0.233). A combined model modestly improved discrimination (AUC 0.764; 95% CI 0.68–0.84). No significant associations were observed between any miRNA and FIGO stage, grade, histology, platinum resistance, PFS, or OS (all p > 0.05). Conclusions: Serum miR-181-5p and miR-223-3p are downregulated in epithelial ovarian cancer and demonstrate moderate diagnostic performance but lack prognostic or predictive value at diagnosis. These findings support their potential contribution to future multimodal biomarker strategies rather than their use as standalone markers. Diagnostic performance of circulating miRNAs for discriminating epithelial ovarian cancer from healthy controls. miRNA AUC (95% CI) p-value miR-181-5p 0.704 (0.614–0.794) <0.001 miR-223-3p 0.732 (0.644–0.820) <0.001 miR-214-3p 0.573 (0.453–0.693) 0.233 Combined model (miR-181-5p + miR-223-3p) 0.764 (0.68–0.84) 0.001 AUC, area under the curve; CI, confidence interval.

Venous sinus involvement in meningiomas and its association with intracranial hypertension features.

e14109 Background: Meningiomas involving dural venous sinuses may cause symptoms mimicking idiopathic intracranial hypertension (IIH) through direct mass effect or raised intracranial pressure from impaired venous outflow. Optimal management must address both the tumor and potential venous obstruction. We sought to characterize this subset and identify factors guiding treatment selection. Methods: We retrospectively reviewed 63 meningioma patients at our institution. Cases were classified by venous sinus involvement based on invasion via imaging, compression, or occlusion of the superior sagittal sinus (SSS) or transverse-sigmoid sinus (TSS). We evaluated demographics, tumor size, WHO grade, symptoms, IIH features, treatment modality, and clinical outcomes. Results: Eleven patients (17.5%) had venous sinus involvement. Patients were predominantly female (81.8%) with mean age 51.9 ± 14.8 years. SSS involvement was most common (81.8%), followed by TSS (36.4%), with 27.3% affecting both systems. Venous sinus meningiomas were nearly twice as large as non-venous cases (2.87 vs 1.49 cm, p=0.08). Among graded tumors, 40% were WHO Grade 2-3, including one WHO Grade 3 malignant meningioma. Sinus invasion was present in 36.4%, compression in 18.2%, and occlusion in 36.4%. Importantly, 45.5% demonstrated IIH features. Four patients presented with papilledema, which was exclusive to venous-involved cases. Two patients had elevated venous pressures with SSS measurements of 27-39 mmHg and trans-stenotic gradients of 13-18 mmHg. Visual symptoms were the most common presentation (36.4%), followed by headaches (18.2%) and focal neurological deficits (18.2%). Treatment included surgical resection (36.4%), radiosurgery (9.1%), conservative monitoring (18.2%), IIH-directed therapy (18.2%), and venous stenting (9.1%). Headache resolution occurred in 60% of surgical patients. One patient treated with venous stenting achieved sustained migraine control. Two conservatively managed patients remained stable at 7-year follow-up, and no mortality was observed. Conclusions: Venous sinus meningiomas are a distinct clinical entity with larger tumor size, higher-grade histology, and IIH features in 45.5% of patients. This data supports the extrinsic venous compression hypothesis for IIH, and that venous stenting may provide symptom relief in select patients with predominant IIH features and preserved sinus patency. For clinical practice, we recommend: (1) fundoscopic examination in all meningioma patients with sinus-adjacent tumors to evaluate for papilledema; (2) diagnostic cerebral venography with pressure measurements when trans-stenotic gradients may influence treatment; (3) shorter surveillance intervals (6 months vs. 12) for conservatively managed patients given the 40% high-grade rate; and (4) evaluation incorporating both tumor resection and venous recanalization options.