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Biosynthesis of nickel oxide nanoparticles using ethnomedicinal plant Crotalaria pallida leaves extract: Evaluation of antibacterial, antioxidant, antiangiogenic, cytotoxicity and ROS expression against HCT-116 and PANC-1 cells

Unravelling the Secret of Sulfur Confinement and High Sulfur Utilization in Hybrid Sulfur‐Carbons (Adv. Mater. 34/2026)

Homocoupling‐Defect‐Free Alternating Conjugated Polymers With Enhanced Photosensitization for Phototherapy

ABSTRACT Defects are inevitably introduced to the materials during the synthesis or preparation process, and sometimes bring out huge effects on the performance. Conjugated polymers, especially the donor‐acceptor alternating ones, have been termed as good candidates in phototherapy, since their strong light‐harvesting ability and increased intersystem crossing channels from singlet to triplet states could improve the reactive oxygen species (ROS) generation efficiency. Such alternating conjugated polymers are usually prepared though Stille or Suzuki cross‐coupling polymerization between two types monomers of donor and acceptor, which in fact usually results in homocoupling defect of donor–donor or acceptor–acceptor structures in obtained polymers. In this contribution, we prepared a series of donor‐acceptor‐type alternating conjugated polymers photosensitizers through different polymerization processes, and found that all the polymers prepared by direct arylation coupling polymerization (DArP) showed much better ROS generation efficiencies and fluorescence intensities than their similar analogues prepared by Suzuki polymerization. Detailed mechanism studies confirmed that the donor‐donor or acceptor‐acceptor defects could decrease the exciton lifetimes of the donor‐acceptor alternating polymers upon laser irradiation through obstructing exciton diffusion, and the homocoupling‐defect‐free polymers prepared by DArP therefore demonstrated better performance. In addition, PTD‐DArP , constructed by triphenylamine donor and diketopyrrolopyrrole acceptor, demonstrated much better biodegradation capacity than PTD‐Suzuki , and it could also match the 660 nm clinical laser, making it good candidate in phototherapy, which has been further confirmed by both in vitro and in vivo results via two models of tumor and diabetes infection. At last, by using two previously reported high performance conjugated polymer photosensitizers as the models, the universality of our strategy was further verified.

A multi-scale feature fusion gaze estimation model based on convolutional neural network and vision transformer

A thiadiazolylidene-morpholine compound inhibits Pseudomonas aeruginosa by destabilizing the thiamine monophosphate kinase thiL

A phase II trial of fruquintinib combined with cadonilimab in refractory MSS/pMMR colorectal cancer with pulmonary metastases.

3552 Background: Immunotherapy for metastatic colorectal cancer (mCRC) with microsatellite stable/proficient mismatch repair (MSS/pMMR) remains limited. Emerging evidence suggests that the combination of antiangiogenic agents and immune checkpoint inhibitors (ICIs) exhibits synergistic antitumor effects in refractory MSS/pMMR mCRC, particularly among patients (pts) with isolated lung metastases. This open-label, single-arm, phase II trial aims to evaluate the efficacy and safety of fruquintinib plus cadonilimab in pts with MSS/pMMR mCRC who progressed after at least two prior lines of therapy. Methods: Patients aged≥18 years, with pathologically confirmed MSS/pMMR mCRC presenting pulmonary metastases and no liver metastases, and who had experienced failure of at least second-line therapy were enrolled. Eligible patients received oral fruquintinib (3 mg once daily) plus intravenous cadonilimab (6 mg/kg every two weeks) until disease progression, unacceptable toxicity, or withdrawal of consent. Tumor assessments were performed every 8 weeks. The primary endpoint was objective response rate (ORR), and secondary endpoints included overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and safety. Results: From February 2024 to June 2025, 37 pts were enrolled [median age 61 years, 68% male, 89% ECOG 0-1, 62% RAS mutant, 30% 3L+, 73% prior bevacizumab, 3 pts prior immunotherapy]. The ORR was 31.4%, and the DCR was 71.4%. Median PFS was 6.1 months (95%CI: 4.8-7.5), while OS data remain immature. Moreover, the patients with a history of liver metastases showed a trend toward shorter PFS compared to those without (4.0 vs. 6.9 months; P = 0.194). The most common treatment-related adverse events (AEs) were hypothyroidism (43%), elevated ALT/AST (27%), hypertension (24%), diarrhea (24%), thrombocytopenia (19%), hand-foot syndrome (16%), and rash (16%). Grade ≥3 treatment-related AEs occurred in 10 (27%) pts. Serious adverse events (SAEs) were reported in 5 pts, with no grade 4 or 5 SAEs observed. Conclusions: The combination of fruquintinib and cadonilimab demonstrated promising clinical activity and a manageable safety profile in patients with refractory MSS/pMMR mCRC. Clinical trial information: ChiCTR2400079429.

Multicenter open-label randomized trial of the utility of electronic patient-reported outcome monitoring system in patients with advanced solid tumors (PRO-MOTE).

11004 Background: Randomized trials have suggested that electronic patient-reported outcome (ePRO) monitoring during systemic therapy may improve health-related quality of life (HR-QOL) and overall survival (OS) in patients with advanced cancer. However, evidence remains limited outside Western healthcare settings. Here, we evaluated the utility of ePRO monitoring for OS and HR-QOL in Japanese patients with advanced solid tumors receiving systemic therapy. Methods: This multicenter, open-label, randomized trial enrolled patients aged ≥18 years with advanced solid tumors, ECOG performance status (PS) 0–2, and receiving systemic therapy. Patients were randomized 1:1 to ePRO monitoring plus usual care or usual care alone. In the ePRO monitoring group, patients completed weekly symptom monitoring using PRO-CTCAE. Predefined severity thresholds were applied, and symptom reports exceeding thresholds automatically generated e-mail alerts to the study physicians. Primary endpoints were OS and global health status (GHS) assessed by EORTC QLQ-C30. Superiority for GHS was tested at a two-sided α of 4%, and for OS at α=5% if GHS was significant or α=1% otherwise. Based on a linear mixed-effects model, 400 patients provided 91% power to detect a 5-point between-group difference in GHS. Target sample size was set at 500, allowing for 20% attrition. Results: Between June 2021 and February 2024, 501 patients were enrolled (control n=250; ePRO n=251), with a median age of 63 years (21–82) and ECOG PS 0/1/2 of 362/127/12. Major cancer types included colorectal (27%), lung (22%), breast (19%), and gastric cancer (17%). QOL analysis was conducted in 485 patients due to missing baseline data in 16. Questionnaire completion rates were high (QLQ-C30: baseline 97%, week 24: 92%). In the ePRO group, weekly PRO-CTCAE completion rates were 86% at baseline and 85% at week 24, generating 13,500 symptom reports and 1,918 alerts (14%), with a median of 4 alerts per patient. At the planned interim analysis, between-group difference in change in GHS over 24 weeks was −0.61 (95% CI −3.03 to 1.82; p=0.625), showing no superiority of ePRO monitoring. OS did not differ between groups (HR 0.91; 95% CI 0.70–1.19; p=0.240). Bayesian predictive power of eventual OS benefit was 0.3%, below the futility threshold of 10%, and the trial was terminated early. Conclusions: In contrast to previous reports from Western countries, PRO-MOTE failed to demonstrate the superiority of ePRO monitoring for GHS or OS in patients with advanced solid tumors receiving systemic therapy in Japan. Despite high feasibility, the clinical benefit of ePRO monitoring might depend on cancer type, treatment context, or healthcare system. Further subgroup and exploratory analyses are ongoing. Clinical trial information: NCT05931445 .

Neoadjuvant serplulimab combined with cisplatin plus 5-fluorouracil in locally advanced head and neck squamous cell carcinoma: A phase II single-arm trial.

e18063 Background: Head and neck squamous cell carcinoma (HNSCC) remains a formidable clinical challenge, characterized by aggressive behavior and dismal outcomes. While immunotherapy has reshaped the treatment landscape in recurrent or metastatic HNSCC, its role in the neoadjuvant setting for locally advanced disease remains to be defined. This study aimed to evaluate the efficacy and safety of serplulimab, a PD-1 inhibitor, in combination with the PF regimen (cisplatin + 5-fluorouracil) as neoadjuvant therapy for locally advanced HNSCC (LA-HNSCC). Here, we report a preliminary analysis of patients enrolled at the data cutoff in this ongoing study. Methods: This single-arm phase II trial enrolled patients with pathologically confirmed treatment-naïve LA-HNSCC. Participants received three cycles of neoadjuvant therapy comprising intravenous serplulimab (300 mg, q3w), cisplatin (25 mg/m²), and continuous intravenous infusion of 5-fluorouracil (1200 mg/m² over 96 hours). Subsequent definitive radiotherapy or surgical resection was selected based on post-treatment imaging assessment. The primary endpoint was objective response rate (ORR), and secondary endpoints include quality of life (QoL), survival, and safety. Results: As of the data cutoff, 17 patients had been enrolled, of whom 64.7% were male, and 47.05% had stage IV disease. Sixteen patients completed neoadjuvant therapy and were evaluable for response, among whom 7 achieved complete response, and 5 achieved partial response, yielding an ORR of 75.0% and a disease control rate (DCR) of 93.8%. QoL data were available for 16 patients who completed baseline and at least one follow-up assessment using the QLQ-C30 and QLQ-H&N35. Statistically significant improvements were observed in global health status, emotional functioning, and pain (QLQ-C30), as well as swallowing, speech, senses, and social eating (QLQ-H&N35) following neoadjuvant therapy; financial difficulties was the only domain that worsened. Treatment-related adverse events (TRAEs) were generally mild and manageable with appropriate interventions. At data cutoff, median follow-up was 19.0 months (range, 3.1-25.8). There were 5 overall survival (OS) events and 6 invasive disease-free survival (iDFS) events among the 17 patients, corresponding to 6-month OS and iDFS rates 100% and 94.1%, respectively. Longer-term survival outcomes are being assessed with ongoing follow-up. Conclusions: Neoadjuvant serplulimab combined with the PF chemotherapy demonstrated encouraging antitumor activity and a favorable safety profile in LA-HNSCC. The regimen was also associated with significant improvements across multiple patient-reported QoL domains. These findings support further investigation of this strategy as a potential neoadjuvant approach for LA-HNSCC. Clinical trial information: ChiCTR2500099204.

Multi-cohort validation of a multi-analyte liquid biopsy test for early-stage pancreatic cancer detection.

4139 Background: Pancreatic ductal adenocarcinoma (PDAC) has a 5-year survival rate below 12%, largely due to diagnosis at advanced, noncurative stages. Earlier detection could significantly improve survival outcomes; however, current approaches, including imaging and blood based assays lack sufficient sensitivity and specificity. Liquid biopsy methods that combine genomic, epigenomic, and glycan-based biomarkers may improve the detection accuracy by integrating a multi-analyte approach. We developed an improved prediction model for the Avantect Pancreatic Cancer Test (Avantect) using 5-hydroxymethylcytosine (5hmC) profiling, whole-genome based fragmentomics, together with genotyping and haplotype data, and CA19-9 biomarker levels. Methods: We employed a training cohort consisting of 162 PDAC cases and 983 noncancer controls. Cell-free DNA was analyzed using 5hmC profiling, low-pass whole-genome sequencing (WGS), and genotyping, alongside matched plasma CA19-9 measurements. A logistic regression model integrating 5hmC features, fragment size metrics, haplotype information, and CA19-9 levels was constructed and locked at a specificity of 97.75%. Performance was evaluated in two independent validation cohorts consisting of 1,445 individuals (259 PDAC; 1,186 noncancer participants) and 173 individuals (67 PDAC and 106 non-cancers). Sensitivity, specificity, and 95% confidence intervals (CIs) were computed. Results: In an independent validation cohort of 1,445 individuals with various high-risk features including type 2 diabetes, family history, and genetic predisposition, Avantect achieved an overall sensitivity of 82.6% (95% CI: 77.45%-87.04%) and an early stage (stage I-II) sensitivity of 76.8% (n=138; 95% CI: 68.87%-83.57%). A second validation cohort of 173 individuals, enriched for new onset type 2 diabetes, was evaluated and showed a sensitivity of 74.6% (95% CI: 62.51%-84.47%). Specificity in both cohorts remained high at 97.5% (95% CI: 96.41%-98.29%) and 98.1% (95% CI: 93.33%-99.77%) respectively, consistent with the pre-specified rate of 97.75%. Test specificity was further evaluated in a cohort comprising other cancer types, including breast, colorectal, lung, liver, prostate, ovarian, bladder, and kidney cancers, revealing a consistent high specificity of 97.70 (0.05% reduction). Conclusions: The multi-analyte model shows strong and robust performance across multiple independent cohorts detecting PDAC at high specificity. By integrating orthogonal biological signals, through the incorporation of epigenomic, genomic, and glycan biomarkers, the Avantect Pancreatic Cancer Test showed an improved PDAC detection to provide a tool that could significantly improve survival for patients with pancreatic cancer.

Phase II study of nab-paclitaxel and S-1 combined with tislelizumab as first-line treatment for advanced gallbladder cancer: Preliminary results.

e14575 Background: Chemotherapy combined with immunotherapy has become the standard treatment for advanced biliary tract adenocarcinoma; however, the objective response rate (ORR) remains below 30%, and the median overall survival (OS) is approximately one year. Gallbladder cancer (GBC) has a poorer prognosis than cholangiocarcinoma. Therefore, further exploration of optimal treatment strategies is warranted. Based on the results of our previous studies, we conducted this study to evaluate the efficacy and safety of adding tislelizumab to nab-paclitaxel and S-1 as first-line treatment in patients with advanced gallbladder cancer. Methods: This was a prospective, single-arm, phase II trial enrolling patients with unresectable or metastatic gallbladder cancer. Patients received nab-paclitaxel, S-1, and tislelizumab (nab-paclitaxel 125 mg/m², intravenous infusion on days 1 and 8; S-1 80-120 mg/day, oral administration twice daily on days 1-14; tislelizumab 200 mg, intravenous administration on day 1; every 3 weeks). The primary endpoint was ORR. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), OS, and safety. Results: Between August 9, 2023 and November 14, 2025, 38 patients were screened, and 32 patients were ultimately enrolled. The median age was 55 years (range, 39-78), with a higher proportion of female patients (65.6%). Disease stage distribution was as follows: stage IIIb in 6 patients, stage IVa in 1 patient, and stage IVb in 25 patients. The liver was the most common metastatic site, observed in 62.5% (20/32) of patients. All 32 patients were evaluated for efficacy. The ORR was 53.1%, and the DCR was 87.5%. Among the six patients with stage IIIb disease, three underwent radical resection of the primary tumor after chemotherapy. As of December 31, 2025, the median follow-up duration was 22.4 months. The estimated median progression-free survival (PFS) was 7.3 months (95% CI, 5.6-9.1). Overall survival (OS) was not reached at the time of analysis, and the 1-year OS rate was 85.2%. The most common grade 3/4 treatment-related adverse events were neutropenia (31.2%), elevated transaminases (15.6%), and diarrhea (12.5%). Grade 3/4 immune-related adverse events occurred in 18.8% of patients, including elevated transaminases (n = 2), rash (n = 2), increased bilirubin (n = 1), and pneumonitis (n = 1). Conclusions: Preliminary results of this prospective phase II study indicate that nab-paclitaxel and S-1 combined with tislelizumab as first-line treatment demonstrates promising efficacy and manageable safety in patients with advanced gallbladder cancer, which warrants further investigation. Clinical trial information: NCT02830606 .

SOCCER: A randomized phase II trial comparing complete clinical response after short course radiation or chemoradiation and consolidation chemotherapy in rectal cancer.

3618 Background: The preferred total neoadjuvant treatment (TNT) regimen for an intentional watch-and-wait (W&W) approach in patients with rectal cancer is long course chemoradiation (LCRT) and consolidation chemotherapy (CNCT). The role of short course radiation (SCRT) and CNCT in this context is not well defined. The shorter treatment time of SCRT has advantages, especially in resource-constrained settings. This study aimed to select the more promising of the two TNT strategies for a W&W approach in patients with rectal cancer for further phase III evaluation. Methods: This dual-center, randomized phase II trial was conducted in Chennai and Vellore, India. Patients with rectal adenocarcinoma within 8cm of the anal verge, T3N0 or T1-3N+ on magnetic resonance imaging (MRI) who required neoadjuvant radiation and surgery, were randomized to one of two arms: Arm A - LCRT (54Gy with capecitabine) + 6 cycles of CAPOX (capecitabine + oxaliplatin), Arm B - SCRT (25Gy) + 6 cycles of CAPOX. Tumor response was assessed at 24 weeks from completion of radiation by digital rectal examination, sigmoidoscopy and MRI and categorized by a pre-defined criterion. Primary end-point was cCR or near cCR. Patients with a cCR at first assessment or at a second assessment 12 weeks after a near cCR were offered W&W. Based on Simon’s randomized phase II pick-the-winner design, 40 patients were required to achieve a 90% probability of correct selection, assuming a 50% cCR and a 20% absolute difference, without formal superiority testing. Secondary endpoints included adverse events, treatment compliance, post-operative complications, 2-year organ preservation, local regrowth, disease-free survival, diagnostic performance of response assessment criteria, and quality of life. Results: Among 46 patients randomized between 2022 and 2025, primary endpoint was assessed in 43 (modified intention-to-treat population). Median age (range), proportion of T3, node positive tumors and mesorectal fascia involvement were 54 years (27-69), 86.3%, 54.5%, 63.6% and 49 years (31-68), 86.9%, 56.5%, 60.8% in Arm A and B, respectively. For primary and short-term secondary endpoints, see Table. Conclusions: SCRT + CNCT was superior to LCRT + CNCT in inducing cCR/near cCR in patients with rectal cancer and emerged as the preferred regimen for further evaluation of an intentional W&W approach in a phase III study. Clinical trial information: CTRI: 2021/01/030370. End-point Arm A Arm B No. of complete + near complete clinical response 8/20 (40%) 17/23 (73.9%) Adverse events ≥Grade 3 During Radiation During CNCT 2 (in 20 patients)43 in 108 cycles 1 (in 23 patients)26 in 138 cycles No. of pts with Relative dose intensity of CNCT <85% 6 (33.3%) 11 (47.8%) No. of pts with CNCT delayed ≥3 days in ≥2 cycles 5 (27.7%) 2 (8.6%) Median no. of CNCT cycles 6 6 Post-operative complicationsClavien-Dindo ≥3 2 in 11 patients 0 in 6 patients Treatment related death 1 0

Homologous recombination repair (HRR) genes and overall survival prognosis within the STRATOS-P classification in metastatic hormone-sensitive prostate cancer (mHSPC).

5108 Background: DNA repair genomic alterations are associated with worse overall survival (OS) in patients with metastatic hormone sensitive prostate cancer (mHSPC). It is less clear whether other genomic alterations may affect prognosis of actionable homologous recombination repair (HRR) and mismatch repair (MMR) genes in mHSPC. Methods: Retrospective cross-sectional study of veterans diagnosed with mHSPC (n=4401). Tumors with no alterations in HRR/MMR genes (DDRneg) were classified by the Somatic Tumor Risk Assessment for Overall Survival-Prostate (STRATOS-P) genomic system which stratifies patients into favorable, intermediate and unfavorable survival groups based on oncogenic alterations: Favorable, SPOP or no alterations; Intermediate, alterations in AR, BRCA2, CCND1, CDK12, FGF19, FGF3, FGF4, LYN, MYC, PTEN, RAD21, or TP53 ; Unfavorable, alterations in FGFR1, PRCK1, RB1 ,or both TP53 and PTEN . OS from metastatic diagnosis was determined using a multivariate Cox model controlling for age, Charleston comorbidity index (CCI) and PSA at diagnosis. Results: Among 4401 mHSPC patients, 1027 (23%) patient tumors had at least one oncogenic alteration in an HRR or MMR gene. Of 3374 DDR-Neg tumors, 1593 were classified as STRATOS-P-Favorable, 1357 as STRATOS-P-Intermediate, and 424 as STRATOS-P-Unfavorable. Comparing patients with tumors with oncogenic alterations in an HRR or MMR gene to patients with DDR-neg tumors showed that prognosis was worse in patients with tumor alterations in ATM, BRCA2, CHEK2, CDK12, ATR, PALB2, NBN and MMR genes compared to patients with STRATOS-P-Favorable tumors (Table). Prognosis was better in patients with tumor alterations in ATM, BRCA2, CHEK2, CDK12, BRCA1, FANCA and Lynch genes compared to STRATOS-P-Unfavorable tumors (Table). Conclusions: In patients with mHSPC, patients with HRR and MMR altered tumors have a worse prognosis compared to patients with STRATOS-P favorable tumors and better prognosis compared to patients with STRATOS-P unfavorable tumors. Overall, HRR and MRR gene alterations impact prognosis of mHSPC patients within the STRATOS-P classification and should be classified as intermediate risk. STRATOS-P-Favorable, DDRneg, n=1593 STRATOS-P-Unfavorable, DDRneg,n=424 Gene 1 n HR (95% CI) HR (95% CI) BRCA2 243 2.00 (1.62, 2.47) 0.69 (0.55, 0.87) CDK12 116 2.07 (1.66, 2.57) 0.74 (0.58, 0.94) ATM 259 1.55 (1.24, 1.96) 0.51 (0.39, 0.66) CHEK2 212 1.75 (1.21, 2.52) 0.50 (0.33, 0.76) ATR 38 2.05 (1.27, 3.31) 0.71 (0.43, 1.17) BRCA1 37 1.41 (0.81, 2.46) 0.48 (0.27, 0.84) FANCA 32 1.53 (0.82, 2.87) 0.51 (0.27, 0.97) NBN 23 2.59 (1.43, 4.68) 0.93 (0.51, 1.69) PALB2 21 2.31 (1.23, 4.37) 0.79 (0.40, 1.56) Lynch 128 1.72 (1.28, 2.33) 0.64 (0.47, 0.88) 1 All tumors with alterations in indicated gene regardless of STRATOS-P subgroup were compared to the indicated DDRneg STRATOS-P subgroup.

Type 2 cytokines in breast epithelial homeostasis.

e12588 Background: The widespread use of type 2 cytokine blockades (e.g., Dupilumab) has transformed treatment of inflammatory disorders, yet their impact on non-immune tissues, specifically the breast microenvironment, is unknown. This gap is notable as our prior work identified a novel, protective role of T helper 2 (Th2) immunity when induced in early breast cancer, challenging the traditional paradigm that Th2 cells are pro-tumorigenic. Interleukin-4 (IL-4) and IL-13 signal through common (IL-4Rα/IL-13Rα1) and unique receptors differentially expressed on lymphocytes and epithelial cells, and their therapeutic blockade may inadvertently affect antitumor responses. As breast cancer is the most common malignancy in women and is tightly regulated by CD4+ T cell-derived cytokines, characterizing the relative contributions of IL-4/13 to breast epithelial integrity is critical in ensuring the safety of Th2-targeted therapies. Methods: Immunofluorescence (IF) staining for IL-4Rα, CD117, and EpCAM was performed on normal female human breast glands and adjacent-to-tumor tissue across three age cohorts: ( < 30, 31-50, > 50 years). Human mammary organoids were treated with IL-4/13 to assess effects on epithelial differentiation using HALO image analysis. In vivo, IL-4Rα or IL-13 was removed from MMTV-PyMT spontaneous mammary tumor mice (Luminal B) and monitored for tumor kinetics, histopathology, and metastatic burden. Results: Quantitative IF analysis revealed an age-dependent decline in IL-4Rα expression, which was highest in young breast tissue. This loss was most prominent in the EpCAM+ luminal lineage, with significant decreases observed in both total luminal and CD117+ progenitor cells (p < 0.0001). Expression levels in both populations showed strong negative correlations with age (Total: r = -0.7085; Progenitor: r = -0.6612). Furthermore, IL-4/13 treatment at Day 7 decreased relative organoid count versus controls (p < 0.05). In murine models, global loss of either IL-4Rα receptor or IL-13 cytokine significantly accelerated breast tumor onset, increased tumor counts, reduced survival, and increased lung metastatic foci. Conclusions: Our findings establish IL-4/13 signaling axis as a critical regulator of mammary epithelial homeostasis that is diminished during aging and oncogenesis. Systemic IL-4Rα inhibition may impair antitumor responses, supporting the need for long-term clinical monitoring of breast tissue homeostasis in patients receiving Th2-targeted therapies.

Association of STK11 alterations with overall survival after immune checkpoint inhibitor therapy in TMB-low tumors: MSK-IMPACT cohort analysis.

e14551 Background: Tumor mutational burden (TMB) is associated with immune checkpoint inhibitor (ICI) outcomes, yet benefit among TMB-low tumors is heterogeneous. STK11 alterations have been linked to reduced benefit from ICI in non–small cell lung cancer (NSCLC), but their association with survival after ICI across cancer types, particularly within prespecified TMB-low tumors, remains uncertain. We evaluated the association between STK11 alterations and overall survival (OS) after ICI in a pan-cancer cohort and whether TMB modifies this association. Methods: We performed a retrospective analysis of the MSK-IMPACT ICI-treated cohort (N = 1661). TMB (nonsynonymous mutations/Mb) and tumor type (OncoTree code) were obtained from clinical annotations. STK11-altered status was defined as ≥1 nonsynonymous STK11 SNV/indel; structural variants were assessed in sensitivity analyses. OS (months) was defined from first ICI treatment to death; patients alive were censored at last follow-up. Cox proportional hazards models were stratified by tumor type (OncoTree code) and adjusted for log(1+TMB) and ICI drug type (PD-1/PDL-1, CTLA4, Combo). TMB-low was prespecified as TMB < 10. A prespecified NSCLC-only sensitivity analysis was performed within the TMB-low subgroup. Effect modification by TMB was assessed using an interaction term (STK11×log(1+TMB)). Results: STK11 alterations were present in 99/1661 (6.0%). Median OS was 7.0 months for STK11-altered versus 19.0 months for STK11–wild-type tumors. In the tumor-type–stratified multivariable Cox model adjusted for TMB and ICI drug type, STK11 alteration was associated with shorter OS (HR 1.48, 95% CI 1.10–1.99; p = 0.0099). Among TMB-low tumors (1201/1661, 72.3%), 60/1201 (5.0%) had STK11 alterations; median OS was 7.0 versus 15.0 months (STK11-altered vs wild-type). Within TMB-low, the adjusted association was attenuated and not statistically significant (HR 1.14, 95% CI 0.79–1.66; p = 0.48). STK11-altered TMB-low cases were most frequent in NSCLC (45/60, 76%). In the prespecified NSCLC-only sensitivity analysis within TMB-low (n = 238; STK11-altered = 45), STK11 alteration was not associated with OS after adjustment (HR 1.04, 95% CI 0.69–1.59; p = 0.84). There was no evidence that TMB modified the association between STK11 and OS (interaction p = 0.61). Conclusions: In this pan-cancer ICI-treated MSK-IMPACT cohort, STK11 alterations were independently associated with shorter OS after accounting for tumor type, TMB, and ICI drug type. In the prespecified TMB-low subgroup, including an NSCLC-focused sensitivity analysis, STK11 alterations were not independently associated with OS, and interaction testing did not support differential effects by TMB. These findings highlight tumor-type confounding in subgroup analyses and support tumor-specific validation of STK11 as an ICI prognostic biomarker.

The ASPIRES study: Promoting colorectal cancer surveillance in childhood cancer survivors—A randomized intervention trial from the Childhood Cancer Survivor study (CCSS).

10004 Background: Survivors of childhood cancer exposed to abdominal, pelvic, spinal, or total-body radiotherapy (RT) are at elevated risk for subsequent treatment-related colorectal cancer (CRC). However, adherence to recommended CRC surveillance screening is only ~37%, leaving survivors vulnerable to potentially preventable cancer. Innovative interventions are needed to improve screening uptake. Methods: We conducted a three-arm randomized controlled trial comparing mHealth-based patient activation (PA) and patient plus primary care provider activation (PA+PCP) with a control arm that received a survivorship care plan with screening recommendations. Nested within the CCSS, eligible participants were 5-year survivors diagnosed before age 21 who had received abdominal, pelvic, spinal, or total-body radiotherapy and were not up to date with surveillance. Participants (n = 300) were randomized in a 1:1:1 ratio, stratified by age at enrollment (30–44 vs ≥45 years). The primary outcome was the proportion of participants who completed CRC surveillance within 12 months. Each intervention arm was compared with the control in an intent-to-treat analysis using the Cochran-Mantel-Haenszel test ( ꭤ = 0.025/comparison). In secondary analyses, logistic regression, adjusted for age at enrollment, was used to estimate odds ratios (ORs) to identify moderators of the relationship between the intervention (grouping PA with PA+PCP) and the outcome. Results: Participants were 45% male and 8% non-white, with a median age of 41 years (range: 30 – 67 years). At 12 months, survivors in the PA group were significantly more likely than controls to have completed surveillance screening: 32/99 (32%) vs 14/102 (14%) [p = 0.003]. Surveillance screening completion was also higher in the PA+PCP group than in controls, but this difference did not meet the prespecified α (0.025): 26/99 (26%) vs 14/102 (14%) [p = 0.041]. Secondary analyses suggested the intervention was more effective among survivors without a chronic health condition (without: OR = 3.6; 95%CI 1.5, 10.1 vs. with: OR=1.9; 95%CI 0.8, 4.8) and with ≤ high school education (≤ high school OR=4.4; 95%CI 1.3, 20.2 vs. > high school OR=2.2; 95%CI 1.1, 4.7). Conclusions: An mHealth-based patient activation intervention more than doubled adherence to CRC surveillance compared with a survivorship care plan with surveillance recommendations alone. While patient plus PCP activation showed improvement, adding PCP activation did not confer a significant benefit compared with the control. Intervention effectiveness varied across subgroups, underscoring the importance of tailored approaches. As digital technologies continue to advance, mHealth strategies offer a promising and scalable pathway to improving surveillance screening among high-risk survivors of childhood cancer. Clinical trial information: NCT05084833 .

Molecularly defined subgroups within RAS-WT mCRC: Treatment selection and overall survival in Project GENIE BPC CRC Database.

e15626 Background: RAS wild-type (WT) metastatic colorectal cancer (mCRC) remains clinically heterogeneous despite shared eligibility for anti-EGFR–based therapy. We evaluated whether clinically actionable molecular subsets within RAS-WT mCRC (BRAF V600E, MSI-H, and ERBB2 amplification) are associated with real-world treatment selection and overall survival (OS). Methods: Using the Project GENIE Biopharma Collaborative (BPC) CRC v2.0-public database cohort, we assembled a real-world RAS-WT mCRC population with regimen level survival fields, MSI testing, somatic mutations, and copy-number data. Molecular subsets were analyzed as mutually exclusive groups (BRAF-only, MSI-only, ERBB2-amplified–only), with overlaps described when present. ERBB2 amplification was derived from copy-number segment (.seg) data using the segment mean overlapping the ERBB2 locus (high-level amplification prespecified as log2 ≥0.9). Treatment class was categorized as anti-EGFR based (cetuximab/ panitumumab) or bevacizumab-based regimens. OS from regimen start was analyzed with penalized Cox models using robust variance clustered by patient, adjusting for age at sequencing, mutation count, and fraction genome altered. Because explicit primary tumor sidedness was unavailable, an OncoTree-based anatomic proxy (COAD vs READ vs other) was used in sensitivity analyses. Due to very small molecular subgroup counts within the anti-EGFR arm, interaction testing was underpowered and not interpretable. Results: We identified 471 RAS-WT episodes and 283 deaths. Groups: triple-neg 412; BRAF-only 49; MSI-only 4; ERBB2 amp-only 5 and overlap 1. BRAF-only episodes more often received bevacizumab than anti-EGFR (42 vs 8). Adjusted OS vs triple-neg: BRAF-only HR 1.61 (95%CI 1.05-2.46), p = 0.029; MSI-only HR 5.12 (3.02-8.66), p = 1.2×10⁻9 (likely reflecting poor outcomes on chemotherapy prior to immunotherapy access); ERBB2amp-only HR 1.21 (0.79-1.87), p = 0.38. MSI-only/ERBB2amp-only estimates are exploratory given very small N and incomplete capture of modern ICI/HER2-targeted sequencing. Treatment×molecular interaction was underpowered and not interpretable. Conclusions: In real-world RAS-WT mCRC, BRAF V600E identifies a clinically meaningful high-risk molecular subgroup associated with worse OS and preferential use of bevacizumab over anti-EGFR therapy. MSI-H and ERBB2-amplified subsets were rare in this cohort; larger line-of-therapy annotated datasets are needed to contextualize outcomes in the contemporary ICI/HER2-targeted era. Group Episodes Deaths Anti-EGFR Bev Adj. HR vs TN (95% CI); p Triple-neg 412 240 155 257 Ref BRAF-only 49 34 8 41 1.61 (1.05-2.46); 0.029 MSI-only† 4 4 0 4 5.12 (3.02-8.66); 1.2e-9 ERBB2amp-only† 5 4 2 3 1.21 (0.79-1.87); 0.38 †Estimates for MSI-only and ERBB2amp-only are exploratory due to limited sample size.

Association between chemotherapy-induced neuropathy and gabapentin exposure among adults receiving chemotherapy: A National Inpatient Sample study (2017-2021).

e24085 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of neurotoxic chemotherapy agents like taxanes and vincristine. Gabapentin is frequently prescribed in clinical practice for symptomatic management of CIPN, despite limited evidence supporting its role in CIPN prevention or severity reduction. Evaluating the association between gabapentin use and CIPN ,along with CIPN risk stratification may help inform clinical decision-making and guide appropriate use. Methods: A retrospective cross-sectional study using the International Classification of Diseases, 10th Revision (ICD-10) diagnosis codes from the National Inpatient Sample Database (2017-2021) was performed using Stata/BE. Multivariate logistic regression was used to estimate adjusted odds ratios (aOR) for categorical variables. Results were adjusted for other causes of neuropathy like alcohol use, obesity, diabetes, hypothyroidism, heart failure, end-stage renal disease, vitamin B12 deficiency, bone marrow transplantation, and immunotherapy exposure. Statistical significance was defined as a 95% confidence interval (95% CI) excluding the null value. Results: A total of 594,148 patients (mean age of 59 ± 20 years; 52.5% females) were included. Multivariate analysis showed a positive correlation between gabapentin exposure and CIPN (aOR 1.37; 95% CI 1.24–1.50), likely reflecting its use for neuropathic symptom management. Female sex (aOR 1.14; 95% CI 1.10–1.19) was positively associated and Hispanic race (aOR 0.83; 95% CI 0.75-0.91) was negatively associated with CIPN. Asian and Black races had a positive correlation while White race had a negative correlation with CIPN, but these findings were not significant. Vitamin B12 deficiency (aOR 2.17; 95% CI 1.44–3.30), bone marrow transplantation (aOR 1.34; 95% CI 1.21–1.50), and immunotherapy exposure (aOR 1.21; 95% CI 1.01–1.46) were significantly associated with CIPN. Diabetes and alcohol use did not show a positive correlation with CIPN possibly because these patients might already have been receiving gabapentin before chemotherapy initiation or because of alternative diagnostic coding. Conclusions: Gabapentin use at the time of chemotherapy initiation might have a protective or modifying effect in patients at a high risk of developing CIPN. However, further studies are needed to assess the temporal association between gabapentin use and specific chemotherapy agents, as well as to evaluate CIPN severity.

Real-world evidence of response to ¹⁷⁷ Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) based on primary and metastatic sites in patients (pts) with neuroendocrine tumor (NET).

e16317 Background: NETs are rare tumors commonly originate from the gastrointestinal (GI) tract, pancreas, lung, and other sites. 177 Lu-PRRT was approved in 2018 for treatment of pts with GI or pancreatic NETs. Here we report our institutional experience in advanced NETs pts treated with PRRT and explore whether NETs of different primary sites and certain metastatic sites (liver, peritoneum, bone) respond to PRRT differently. Methods: This was a retrospective observational study evaluating the response of different primary and metastatic sites to 177 Lu–PRRT in 209 adult pts with NETs treated between Jan 1, 2015 and Mar 31, 2025. Data were collected from the electronic health record. Eligible pts were ≥18 years old, histologically confirmed metastatic NET, received at least one cycle of 177 Lu-PRRT, and had baseline and post-treatment imaging available for response assessment. Primary endpoint was overall response rate (ORR) following completion of PRRT. Secondary endpoints included overall survival (OS), progress-free survival (PFS), disease control rate (DCR), and site-specific response. Response was evaluated on imaging obtained after the final administered dose. Descriptive statistics summarized patient and disease characteristics, and multivariable regression models were used to account for potential confounding, including age, tumor grade, primary tumor site, metastatic burden, and prior systemic therapies. Results: Median age was 66 (57-72). Over half (53%) were male. The majority (71%) were Caucasian, 26% were Black. Half of the pts (49.3%) had grade (gr) 2 disease, 24.4% had gr 1, 12.2% of pts had gr 3. For the entire cohort, the median OS was 56.0 months (mo, range 50.0-64.0), median PFS was 10.0 mo (9.0-13.0). Complete response (CR) was seen in 1.5% of pts, 34.9% of pts had partial response (PR), 52.0% of pts had stable disease (SD), with progressive disease (PD) in 11.6% of pts. The overall DCR was 88.4%. The ORR according to primary site was 24.7% in GI (n = 97), 52.5% in pancreas (n = 40), 23.1% in lung (n = 13), 0% in other (n = 2), and 52% in unknown primary (n = 25). DCR according to primary site was 85.6% in GI, 85.0% in pancreas, 92.3% in lung, 100.0% in other, and 92.0% in unknown primary. The best response of liver, peritoneal, and bone metastases (mets) are summarized in Table 1. Conclusions: In this single-institution study, pts with pancreatic and unknown primary had a higher ORR to 177 Lu-PRRT compared to pts with other primaries. Response to PRRT is commonly seen in liver mets. Peritoneal and bone mets have a lower response rate but stable disease is achieved in the majority of pts. Best response of liver, peritoneal, and bone mets. Metastatic Site N CR (%) PR (%) SD (%) PD (%) Liver 187 2 (1.1) 58 (32.8) 94 (53.1) 23 (13.0) Peritoneum 78 0 (0) 19 (25.3) 49 (65.3) 7 (9.3) Bone 117 1 (0.9) 16 (15.0) 79 (73.9) 11 (10.3)

Four-year landmark survival analysis of low-dose nivolumab added to metronomic chemotherapy in advanced head and neck squamous cell carcinoma: A phase III randomized trial.

6054 Background: In advanced head and neck squamous cell carcinoma (HNSCC), the addition of low-dose nivolumab to triple metronomic chemotherapy (TMC-I) previously demonstrated an overall survival (OS) benefit versus triple metronomic chemotherapy (TMC) alone. We report extended follow-up with a 4-year landmark survival analysis to assess the durability of benefit. Methods: This was an open-label, randomised, phase III superiority trial enrolling 151 adult patients (≥18 years) with relapsed–recurrent or newly diagnosed advanced HNSCC with ECOG performance status 0–1, and adequate organ function. Patients were randomized 1:1 to receive oral TMC comprising of Methotrexate 9 mg/m² weekly, Celecoxib 200 mg twice daily and Erlotinib 150 mg daily, with (TMC-I) or without (TMC) nivolumab 20 mg intravenously every 3 weeks. Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint was OS. Survival outcomes were analyzed using Kaplan–Meier methods, log-rank tests, and Cox proportional hazards models. A 4-year landmark analysis was performed. Results: At a median follow-up of 55.6 months (95% CI, 45.0–66.2), the median OS was 6.60 months (95% CI, 5.74–7.47) in the TMC arm and 9.33 months (95% CI, 8.00–10.66) in the TMC-I arm (p = 0.045). Treatment with TMC-I was associated with a 29% reduction in the risk of death [hazard ratio (HR), 0.709; 95% CI, 0.506–0.994; p = 0.046]. At 3 years, OS was 5.1% (95% CI, 1.7–12.3) with TMC versus 13.6% (95% CI, 9.7–26.3) with TMC-I [HR 0.686; 95% CI, 0.485–0.971; p = 0.033]. On 4-year landmark analysis, overall survival curve separation was maintained, with OS remaining superior in the TMC-I arm. The median PFS was 4.50 months (95% CI, 3.89–5.12) with TMC and 6.47 months (95% CI, 4.02–8.93) with TMC-I (p = 0.007). The OS benefit with TMC-I was consistent across pre-specified subgroups including age, gender, ECOG performance status, disease site, prior platinum exposure, and tumour programmed death ligand (PD-L1) expression. Conclusions: With extended follow-up exceeding 4.5 years, the addition of low dose nivolumab to triple metronomic chemotherapy demonstrates a clinically meaningful, durable and statistically significant survival advantage at a 4-year landmark in a predominantly relapsed/refractory advanced HNSCC population compared with TMC alone, confirming the long-term clinical benefit of this strategy in the palliative setting. Clinical trial information: CTRI/2020/11/028953.

Efficacy and safety of perioperative anlotinib combined with cisplatin and doxorubicin in treatment-naive stage IIB classic osteosarcoma of the extremity: Updated results from the ALTER-S002 trial.

11526 Background: Clinical studies show overexpression of multiple tyrosine kinase receptors in osteosarcoma, supporting targeted therapy as a promising direction. Anlotinib, a multi-targeted tyrosine kinase inhibitor, exerts anti-tumor angiogenesis effects. Combining anti-angiogenic agents with chemotherapy may yield synergistic tumor control, particularly as perioperative therapy. We present updated long-term efficacy and safety data, including key secondary endpoints, to validate this regimen’s clinical value. Methods: This was an open-label, single-arm, multicenter phase II trial. Eligible patients (12-40 years) had histologically confirmed primary localized stage IIB classic extremity osteosarcoma and were operable. Patients received anlotinib (10mg, po, d1-14, q3w), doxorubicin (A, 20-25 mg/m², iv, d1-3, q3w) and cisplatin (P, 70-90 mg/m², iv, d1, q3w) for 9 weeks. Radical surgery was performed at week 10 (no contraindications). Postoperatively, A+P was given at weeks 12-14, followed by anlotinib+A+P (same doses) at weeks 15-20. From week 21, anlotinib monotherapy (12mg, po, d1-14, q3w) continued until week 104 or an event-free survival (EFS) event. Primary endpoint: 24-month EFS rate. Secondary endpoints: 36-month EFS rate, local recurrence rate, lung metastasis rate, 3-year overall survival (OS) rate, and safety. Results: From May 2020 to April 2022, 52 patients were enrolled, treated, and included in full analysis set (FAS) and safety set (SS). Of these, 84.6% (44/52) were Han and 55.8% (29/52) male. Median follow-up was 42.7 months (IQR 30.4-52.7). The 24-month and 36-month EFS rates were 73.7% (95% CI 59.0-83.9) and 46.6% (95% CI 27.4-63.7), respectively. Median OS was not reached; 36-month and post-hoc 60-month OS rates were 74.6% (95% CI 59.6-84.7) and 71.4% (95% CI 55.5-82.4). Twenty-five percent (13/52) of patients died, mostly due to lung metastasis (13%). Among 51 surgical patients, local recurrence, lung metastasis, and other-site metastasis occurred in 23.5%, 17.6%, and 9.8%, respectively. Median recurrence-free survival (RFS) was 32.4 months (95% CI 25.7-not estimable). Grade 3-4 treatment-related adverse events (TRAEs) occurred in 84.6% (44/52) of patients, with neutropenia most common (28/52 [53.8%]). No grade 5 TRAEs were observed. Serious TRAEs occurred in 40.4% (21/52), mainly myelosuppression (14/52 [26.9%]). None of the 13 on-study deaths were TRAE-related. Conclusions: Perioperative anlotinib plus cisplatin and doxorubicin shows promising efficacy in treatment-naïve stage IIB classic extremity osteosarcoma, with manageable safety. It achieves favorable long-term OS, and clinically acceptable local recurrence and lung metastasis rates, serving as a potential new perioperative option for this population. Clinical trial information: ChiCTR 2000033298.