Browse Articles

Comparing outcomes for early and late drainage of malignant ascites.

842 Background: Malignant ascites (MA) is a common sequela of peritoneal carcinomatosis resulting in significant morbidity and poses substantial management challenges for clinicians. Large volume paracentesis remains the gold standard treatment. The impact of time to drainage of MA is poorly studied. The purpose of this study was to compare clinical outcomes of hospitalized patients with MA that had drainage performed within 48 hours of admission and after 48 hours of admission. Methods: The NIS was queried between the years 2016 and 2020 to identify all adult patients hospitalized with malignant ascites (ICD-10 code R18.0) and had a drainage procedure performed (ICD-10 Procedure code 0W9Gx). These patients were then stratified into an early cohort (<48 hours after admission) and late cohort (>48 hours after admission). Baseline characteristics and clinical outcomes were collected and analyzed using chi squared tests, independent sample t-tests, and binary logistic regression (adjusted for age, gender, and Charlson comorbidity index or CCI). Adjusted Odds ratios (aOR) are presented with 95% Confidence intervals (CI). Results: A total of 129,040 patients were analyzed, with 89,905 (69.7%) hospitalizations in the early cohort and 39,135 (30.3%) in the late cohort. Baseline characteristics were similar between the groups, with no significant differences in age (63.8 vs 63.6, p = .06) or gender distribution (63.6% vs 63.1%, p = .09). However, patients in the early paracentesis group exhibited a lower CCI (9.8 vs 10.2, p<.001). Notably, early paracentesis was associated with significantly improved outcomes, including lower mortality (aOR 0.67, 95% CI 0.64–0.69), reduced incidence of sepsis (aOR 0.67, 95% CI 0.65–0.69), decreased need for transfusions (aOR 0.69, 95% CI 0.66–0.71), lower rates of mechanical ventilation (aOR 0.44, 95% CI 0.42–0.47) and vasopressor use (aOR 0.79, 95% CI 0.73–0.87). Conclusions: Early paracentesis in patients with malignant ascites was found to be associated with significantly improved clinical outcomes, independent of comorbidity burden. These findings underscore the importance of timely intervention to mitigate complications and enhance quality of life. Late ParacentesisN=39,135 EarlyN=89,905 p-value Age (years) 63.6 ± 13.1 63.8 ± 13.0 .06 Gender (% female) 24665 (63.1%) 57120 (63.6%) .09 CCI 10.2 ± 3.1 9.8 ± 3.2 <.001 Mortality 5720 (14.6%) 9030 (10.0%)aOR .67 (.64 - .69) <.001 Sepsis 7675 (19.6%) 12525 (13.9%)aOR .67 (.65 - .69) <.001 Transfusion 5275 (13.5%) 8605 (9.6%)aOR .69 (.66 - .71) <.001 Ventilation 2130 (5.4%) 2190 (2.4%)aOR .44 (.42 - .47) <.001 Vasopressor 770 (2.0%) 1385 (1.5%)aOR .79 (.73 - .87) <.001

Mechanical‐Stimuli‐Driven Pseudo‐Conductive Channels Along Dielectric Heterojunction Interfaces for Mechanoelectric Energy Conversion and Transmission (Adv. Mater. 8/2025)

Pseudotunnel Magnetoresistance in Twisted van der Waals Fe₃GeTe₂ Homojunctions

AbstractTwistronics, a novel engineering approach involving the alignment of van der Waals (vdW) integrated two‐dimensional materials at specific angles, has recently attracted significant attention. Novel nontrivial phenomena have been demonstrated in twisted vdW junctions (the so‐called magic angle), such as unconventional superconductivity, topological phases, and magnetism. However, there have been only few reports on integrated vdW layers with large twist angles θt, such as twisted interfacial Josephson junctions using high‐temperature superconductors. Herein, vdW homojunctions of the thin‐magnetic flakes, Fe3GeTe2 (FGT), with large θt ranging from 0° to 90°, without inserting any tunnel barriers are assembled. Nevertheless, these vdW homojunctions exhibit tunnel‐magnetoresistance (TMR) like behavior (pseudo‐TMR (PTMR) effect) with the ratios highly sensitive to the θt values, revealing that the vdW gap at the junction interface between the twisted FGT layers behaves like a tunnel barrier and the θt serves a control parameter for PTMR by drastically varying magnitudes of the lattice‐mismatch and the subsequent appearance of antiferromagnetic (AFM) spin alignment. First‐principles calculations considering vacuum gaps indicate strong dependence of TMR on the θt driven by the sixfold screw rotational symmetry of bulk FGT. The present homojunctions hold promise as a platform for novel AFM spin‐dependent phenomena and spintronic applications.

Pattern and predictors of D3 lymph node station positivity in patients undergoing curative surgery for adenocarcinoma of colon.

137 Background: The prognosis and surgical management of colon cancer is intricately related to its lymphatic drainage. The oncological outcome of apical node positivity has been evaluated in different studies with varying results. There is no published regional data on the rate of apical node positivity in colon cancer. An insight into the probability of apical node metastases and the risk factors for the same may help us in prognosticating colon cancer patients better. Methods: This was a prospective observational study conducted at the Regional Cancer Centre Thiruvananthapuram from September 2022 to June 2024. Our primary objective was to determine the prevalence of apical lymph node positivity in patients undergoing surgery for colon cancer with D3 lymphadenectomy. The secondary objectives were to find out the factors associated with the risk of apical node metastasis, the incidence of skip metastases to apical nodes, the adequacy of lymph node harvest and the postoperative complications. Patients undergoing primary surgery for adenocarcinoma of the colon were included. Patients with metastatic disease, synchronous colon or rectal cancers, past history of colonic surgery were excluded. All patients underwent D3 lymphadenectomy along with colectomy depending upon the tumour location. Lymphatic tissue corresponding to the D3 station was retrieved and sent separately after grossing the fresh specimen on the side table in the operating room. Results: A total of 139 patients were included in the study. Fifty two (37.4%) patients had stage III disease, 38.9% had stage II disease and the rest had stage I colon cancer. The mean nodal harvest was 17.86 and mean apical node harvest was 2.04. Node harvest was adequate in 89.21% patients. The apical node positivity rate was 7.19% (10 patients). Skip metastasis to the apical nodes was found in 2 patients. Lymphovascular invasion, number of positive lymph nodes and young age (≤45 years) had a significant correlation with apical node positivity on multivariate analysis. Clavien Dindo grade 3 and above complications were seen in 5.03%. Conclusions: Our study showed an apical node positivity rate of 7.19%, with a skip metastasis rate of 1.4%. This is the first Indian data on apical node positivity rate in colon cancer and its predictors. The prognostic value of apical nodes and the occurrence of skip metastasis to the apical nodes are compelling reasons to advocate D3 dissection, even with relatively low prevalence of apical node positivity.

An exploratory phase II trial of low-dose decitabine and sintilimab combined with chemotherapy in HER2-negative gastric or gastroesophageal junction adenocarcinoma.

390 Background: Combining epigenetic modulator with PD-1 inhibitor may enhance treatment outcomes in cancer patients. This study aimed to evaluate the efficacy and safety of epigenetic drug decitabine, sintilimab (a PD-1 inhibitor), and chemotherapy in gastric cancer. Methods: In this single-arm, exploratory phase II trial, patients with HER2-negative, locally advanced or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma were enrolled between August 12, 2021, and October 22, 2022. Treatment included low-dose decitabine (10 mg/m² for 5 days), sintilimab (a PD1 inhibitor, 200 mg every 21 days), and XELOX. The primary endpoint was objective response rate (ORR) and second endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. The protocol was approved by the ethics committee of the Changzhi Medical College Affiliated Changzhi People's Hospital (No. 2021K002). All patients provided written informed consent form before study participation. The trial is registered with Chinese Clinical Trial, number ChiCTR2100043312. Results: Sixteen patients were initially enrolled, with a median follow-up of 14.8 months. Eleven patients exhibited a PD-L1 combined positive score (CPS) < 5. In the per-protocol sets, 11 patients remained eligible for efficacy analysis. In the intention-to-treat analysis of all 16 patients, 9 achieved partial response and 2 had stable disease, resulting in an ORR of 69% and a DCR of 56%. As of the data cutoff on November 4, 2023, the median PFS was 11.1 months (95% CI, 5.1-not reached) and the median OS was 13.2 months (95% CI, 5.1-not reached). Treatment-related adverse events were generally well-tolerated, with most being grade 1-2. Three patients experienced severe AEs, including one fatal case of grade 4 immune-related pneumonia. Conclusions: The combination of low-dose decitabine, sintilimab, and chemotherapy appears promising strategy for locally advanced or metastatic G/GEJ adenocarcinoma, especially in patients with negative HER2 and low PD-L1 expression. These preliminary findings support further investigations to confirm the benefits and explore the underlying mechanisms. Clinical trial information: ChiCTR2100043312. Objective response and disease response. Full analysis set (n=16) Efficacy analysis set (n=11) Complete response 0 0 Partial response 9 9 Stable disease 2 2 Progressive disease 0 0 Non-evaluable* 5 NA Objective response 9 (56%) 9 (81.8%) Disease control 11 (69%) 11 (100%) NA=not applicable. *Included patients without any post-baseline response assessment.

Phase I/II trial of encorafenib, cetuximab, and nivolumab in microsatellite stable <i>BRAF</i> ^V600E metastatic colorectal cancer following progression on prior BRAF+EGFR targeted therapies.

182 Background: A BRAF V600E mutation, present in approximately 8-10% of all colorectal cancers (CRC), is a poor prognostic biomarker for patients with metastatic CRC. The BRAF V600E inhibitor encorafenib (E) and the anti-EGFR antibody cetuximab (C) are approved for refractory, BRAF V600E mCRC based upon on overall response rate (ORR) of 20% and median progression-free survival (PFS) of 4.2 months . A single-arm trial adding the anti-PD1 antibody nivolumab (N) to E+C in the same (BRAF-inhibitor naïve) population showed promising efficacy, with an ORR of 50% and median PFS of 7.4 months. We evaluated the efficacy of E+C+N in patients with microsatellite stable (MSS), BRAF V600E mCRC who had progressed on prior E+C. Methods: Patients with MSS, BRAF V600E mCRC with documented prior progression on E+C were eligible for treatment with E (300 mg PO daily), C (500 mg/m 2 q14 days), and N (480 mg IV q28days) were included in the study. Primary endpoint was best overall response by RECIST 1.1. Secondary endpoints were PFS, overall survival (OS), and toxicity (by CTCAE v5). Circulating tumor DNA assessment of molecular alterations in the MAPK pathway in association with response were performed by NGS. Descriptive statistics were used to summarize outcomes. Results: Among the 12 participants, none achieved a radiographic response, and 5 experienced stable disease. Disease control rate was 41.7% (95% CI, 13.8-69.6). Median PFS was 3.7 months (95% CI, 1.7-5.7), and median OS was 8.3 months (NE-NE). Four patients (16.7%) had concomitant MAPK-activating alterations at baseline, and APC , TP53 , and PIK3CA mutations were present in 25.0%, 66.7%, and 33.3% of patients, respectively. The presence of MAPK-activating mutation was not associated with disease progression (odds ratio 1.3; 95% CI 0.11-16; p=0.82). The most common grade 1-2 treatment-related adverse events (AEs) were anemia (N=5), arthralgia (N=5), rash (N=4), headache (N=4), and fatigue (N=3); 1 of the 12 patients experienced a grade 3 small bowel obstruction. Conclusions: In this pilot study, addition of N to E+C did not appear to overcome resistance to prior BRAF + EGFR targeted therapies in patients with MSS, BRAF V600E mCRC. While the addition of immunotherapy has demonstrated promising signal in early-phase clinical trials for this population, the benefit appears unlikely when offered sequentially after progression on BRAF combination therapies. Clinical trial information: NCT04017650 .

Photon‐Induced Ultrafast Multitemporal Programming of Terahertz Metadevices (Adv. Mater. 7/2025)

Water Spillover to Expedite Two‐Electron Oxygen Reduction

AbstractLimited by the activity‐selectivity trade‐off relationship, the electrochemical activation of small molecules (like O2, N2, and CO2) rapidly diminishes Faradaic efficiencies with elevated current densities (particularly at ampere levels). Nevertheless, some catalysts can circumvent this restriction in a two‐electron oxygen reduction reaction (2e− ORR), a sustainable pathway for activating O2 to hydrogen peroxide (H2O2). Here we report 2e− ORR expedited in a fluorine‐bridged copper metal–organic framework catalyst, arising from the water spillover effect. Through operando spectroscopies, kinetic and theoretical characterizations, it demonstrates that under neutral conditions, water spillover plays a dual role in accelerating water dissociation and stabilizing the key *OOH intermediate. Benefiting from water spillover, the catalyst can expedite 2e− ORR in the current density range of 0.1–2.0 A cm−2 with both high Faradaic efficiencies (99–84.9%) and H2O2 yield rates (63.17–1082.26 mg h−1 cm−2). Further, the feasibility of the present system has been demonstrated by scaling up to a unit module cell of 25 cm2, in combination with techno‐economics simulations showing H2O2 production cost strongly dependent on current densities, giving the lowest H2O2 price of $0.50 kg−1 at 2.0 A cm−2. This work is expected to provide an additional dimension to leverage systems independent oftraditional rules.

Safety and efficacy of anti-HER2 agents in the treatment of biliary tract cancers: A systematic review.

639 Background: Limited treatment options exist for patients with locally advanced or metastatic biliary tract cancers (BTCs). Recently, several clinical trials provided preliminary evidence for human epidermal growth factor receptor-2 (HER2) as a new target for patients with HER2 expressing BTC. We conducted a systematic review and pooled analysis of the safety and efficacy of anti-HER2 agents in patients with advanced BTC. Methods: A comprehensive search of PubMed/MEDLINE and EMBASE was performed to identify phase 1, 2, or 3 clinical trials published between January 2019 and March 2024 that evaluated anti-HER2 therapy in locally advanced or metastatic BTC. Primary endpoints included objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). Secondary endpoints included the incidence of treatment-related adverse events (TRAEs), rate of treatment discontinuation, and death. Forest plots were generated to summarize the results and demonstrate the effect size estimates for each study, along with their confidence intervals and the pooled estimate from the random-effects model. The random-effects models were configured to use the Restricted Maximum Likelihood method for estimating between-study variance for all analyses. Results: After excluding duplicate and irrelevant articles, data extraction and analysis were performed on eight selected clinical trials. The analysis included 368 patients with a median age of 64 (range 49-68), with 55% being female. Patients were treated with several anti-HER2 agents, including zanidatamab, pertuzumab plus trastuzumab, tucatinib plus trastuzumab, trastuzumab deruxtecan, trastuzumab plus chemotherapy, trastuzumab-pkrb plus chemotherapy and neratinib. The pooled ORR and DCR were 34% (95% CI 24-44) and 64% (95% CI 51-77) respectively. The pooled weighted PFS and median OS survival were 4.8 and 9.4 months, respectively. The pooled duration of response was 5.0 months. In our subset analysis, which included only patients who had received ≥1 prior therapy, the pooled ORR was 30% (95% CI 22-39), the pooled DCR was 62% (95% CI 48-75), and the pooled median PFS was 4.4 months. In the study cohort, 82.6% of patients experienced any adverse event, and 32.1% experienced a grade 3-4 adverse event. Only 5.7% of the patients discontinued treatment secondary to TRAEs. Conclusions: In patients with HER2 expressing BTCs, anti-HER2 therapies demonstrated preliminary signals of efficacy with manageable toxicities, particularly in the second-line setting.

Association of malnutrition at diagnosis with survival among older adults with pancreatic cancer.

680 Background: Malnutrition is common among older adults newly diagnosed with pancreatic cancer. However, the implications of malnutrition among this vulnerable population are poorly understood. We sought to understand the association between malnourishment at diagnosis and overall survival (OS) among older adults with pancreatic cancer. Methods: We included adults aged ≥ 60 years with newly diagnosed pancreatic cancer, who were enrolled in the University of Alabama at Birmingham (UAB) Cancer and Aging Resilience Evaluation (CARE) registry between October 2017 and April 2024. To assess nutritional status, we administered an abridged version of the Patient-Generated Subjective Global Assessment (abPG-SGA) to patients at baseline prior to receiving chemotherapy. Using abPGSGA scores, we categorized patients as either normal (score ≤ 5) or malnourished (score ≥ 6). All participants were followed until death or until the cutoff date of July 10, 2024. We employed Kaplan-Meier survival analysis to estimate overall survival (OS) for both malnourished and non-malnourished groups and compared them using log-rank test. Additionally, we built multivariable Cox proportional hazards models to test the association between malnutrition and OS, while controlling for age at diagnosis, sex, race/ethnicity, and cancer stage. Results: A total of 274 patients were included; the median age at diagnosis was 70 (interquartile range, IQR: 65-75) years with 52% males, 75% non-Hispanic White and 52% with Stage IV disease at diagnosis. At baseline, 59% of patients were malnourished, and the median abPGSGA score was 8 (IQR 4-14). Patients who were malnourished had a similar demographic and clinical characteristics as compared to those without malnutrition. Over a median follow up of 36 months, a total of 202 patients (74 %) died. The median overall survival (OS) was significantly lower for malnourished patients at 13 months compared to 21 months for non-malnourished patients (log-rank test, p &lt; .001). After adjusting for potential age, sex, race/ethnicity and cancer stage, malnutrition at diagnosis remained independently associated with worse survival outcomes (adjusted HR: 1.762; 95% CI: 1.316–2.358; p &lt; .001). Conclusions: Our study reports that malnutrition at baseline is significantly associated with worse overall survival in older adults with pancreatic cancer. These findings underscore the importance of early nutritional assessment and intervention to enhance outcomes in this population.

Prediction of immunotherapy response in deficient mismatch repair colorectal cancers using an immune-enhanced exome and transcriptome platform.

270 Background: While immune checkpoint blockade (ICB) is used to treat metastatic deficient mismatch repair (dMMR) colorectal cancers (CRCs), such tumors are heterogeneous and resistance to ICB is frequent. To date, biomarkers that can consistently predict patient response to ICB are lacking. We determined whether biomarkers that integrate tumor and immune-related molecular mechanisms could predict ICB response. Methods: Consecutive patients with metastatic dMMR CRCs (N=32) who had been treated with anti-PD-1 therapy were profiled using a validated immune-enhanced exome and transcriptome platform (ImmunoID NeXT, Personalis) using tumor and paired normal tissue. This platform provides antigen-specificity of T or B cells, indicated by the TCR or BCR respectively, neoantigen prediction, tumor mutation burden (TMB), immune profile, HLA allele-specific loss of heterogeneity (LOH) and a Neoantigen Presentation Score (NEOPS) that combines a neoantigen prediction tool with mechanisms of immune evasion. Tumor variables were analyzed in relationship to objective tumor response, and a Cox proportional hazards model was fit to predict progression-free survival (PFS) or overall survival (OS). Results: In CRCs, TCR and BCR repertoire diversity were each significantly increased in tumors from responders versus those with stable or progressive disease after anti-PD-1 treatment (p=0.015 and p=0.048, respectively). Neoantigen burden score, TMB, and HLA allele-specific LOH (reflects loss of antigen presentation machinery) were each unable to distinguish responders from nonresponders. An immune checkpoint gene expression signature was increased in nonresponders relative to responders (P= 0.005). Neoantigen presentation score (NEOPS) was prognostic when adjusted for tumor grade only for OS (p=0.048). Conclusions: The T-cell and B-cell receptor (TCR/BCR) repertoire, as well as NEOPS, were each significantly predictive of favorable response to anti-PD-1 therapy in dMMR tumors. In addition, an immune checkpoint gene expression signature was predictive of resistance to ICB.

Enlarging moment and regulating orientation of buried interfacial dipole for efficient inverted perovskite solar cells

Rational Design of NIR‐II Fluorescence/Photoacoustic Nanosensor Tailored for Mechanisms of Diabetes‐Related Breast Cancer

Abstract Breast cancer (BC) is the second most common cause of cancer induced death worldwide. Current statistics has disclosed that the diabetic BC patients have significantly worse survival rate compared with nondiabetic BC patients. However, the specific mechanism is still being explored. Herein, a novel NIR‐II nanosensor DNPS for nitric oxide (NO) with fluorescence/photoacoustic (FL/PA) imaging capability is developed to explore the mechanism by which diabetes promoting breast cancer progression. In diabetic BC model, DNPS exhibits great advantages of low intrinsic background, high sensitivity, and deep tissue penetration and successfully confirmed the expression level of NO is higher than BC model, indicating that diabetes causes elevated nitric oxide levels in the tumor microenvironment. RNA‐seq analysis results show that hyperglycemia caused by diabetes leads to weakened immune response and initiates the transcription and translation of the inducible nitric oxide synthase (iNOS) gene to produce NO. Besides, the increased expression of carcinogens related to Nitric oxide synthase 2 (Nos2), such as Spp1, Mmp11, and Kitl, causes breast cancer to develop more rapidly. Here, NIR‐II imaging probe is applied first to study diabetes‐related breast cancer and certain reference value is provided for subsequent research on the mechanism of diabetes promoting the progression of breast cancer.

Outcomes of durvalumab (D) with or without tremelimumab (T) in routine clinical practice according to HIMALAYA trial eligibility: Preliminary results of the international DT-real study.

552 Background: HIMALAYA showed that D+T and D are effective options for unresectable hepatocellular carcinoma (uHCC). However, data on outcomes according to the adherence to HIMALAYA inclusion criteria in routine clinical practice are lacking. Methods: In the context of a prospectively maintained database including 1293 patients (pts) with uHCC treated with immunotherapy, we analysed pts treated with D+T or D across 8 centres in USA, Asia and Europe. Pts who met &gt;1 key exclusion criterion of HIMALAYA (prior systemic therapy, Child-Pugh class B-C, Vp4 thrombosis) were defined HIMALAYA-OUT and compared with HIMALAYA-IN pts for overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) by RECIST 1.1 and treatment-related adverse events (TRAEs) per CTCAE v.5.0. Results: Up to February 2024, 108 pts (mean age 66 years, male sex 81%) started D+T (n=69, 64%) or D (n=39, 36%). 62 pts (57%) were treated in 1° line and 46 (43%) in &gt;2° line. Child-Pugh class was A in 67 pts (62%). Vp4 was present in 17 pts (16%). 31 pts (29%) were HIMALAYA-IN and 19/31 (61%) received D+T. After a median follow-up of 4.3 months (m, 95%CI 3.3-4.9), median OS (mOS) was 11.5 m and 12-m OS rate was 42%. mOS was not reached in HIMALAYA-IN pts (12-m OS rate 62%) and 8.9 m (95%CI 6.0-12.1) in HIMALAYA-OUT pts. Survival hazard ratio (HR) for HIMALAYA IN vs OUT was 0.28 (95%CI 0.09-0.93, p=0.037). Median PFS was 2.6 m (95% CI 2.2-5.2) overall, 4.6 m (95%CI 2.1-8.5) in HIMALAYA-IN and 2.6 m (95%CI 1.9-5.2) in HIMALAYA-OUT pts (HR 0.70, 95%CI 0.38-1.30, p=0.266). ORR and DCR (evaluable in 53 pts, 49%) were 15.1% (95%CI 6.5-29.7%) and 43.4% (95%CI 27.5-65.1) (Table). Any grade TRAEs occurred in 31.5% (95% 21.8-44.0%), grade 3-4 TRAEs in 8.3% (95%CI 3.8-15.8%), TRAEs requiring systemic corticosteroids in 8.3% (95%CI 3.8-15.8%) and discontinuation due to toxicity in 3.7% (95%CI 1.0-9.5%). Conclusions: Preliminary observational data from DT-Real study suggest a reproducible efficacy and safety of D+T and D in pts with uHCC fitting the inclusion criteria of HIMALAYA in routine clinical practice. HIMALAYA IN (n=31) HIMALAYA IN HIMALAYA OUT (n=77) HIMALAYA OUT D+T (n=19) D (n=12) D+T (n=50) D (n=27) mOS (m, 95%CI) NR NR NR 8.9 (6.0-12.2) 11.2 (6.6-13.2) 4.9 (2.6-12.2) 12-m OS (%) 61.8 63 88.9 37.2 37.4 44.4 mPFS (m, 95%CI) 4.6 (2.1-8.4) 8.5 (2.1-8.5) 2.4 (1.6-2.5) 2.6 (1.9-5.2) 2.4 (1.8-6.7) 2.6 (1.8-5.2) ORR (%,95%CI) (N=53) 23.1 (4.8-67.4) 25.0 (5.1-73.1) 0 12.5 (4.1-29.2) 13.8 (3.8-35.3) 9.1 (0.2-50.6) DCR (%, 95%CI) 46.2 (16.9-100) 50.0 (18.3-100) 0 42.5 (24.8-68.1) 41.4 (21.4-72.2) 45.4 (14.8-100) Any grade TRAEs (%,95%CI) 32.3 (15.5-59.3) 31.6 (11.6-68.7) 33.3 (9.1-85.4) 31.2 (20.0-46.4) 28.0 (15.3-47.0) 37.1 (17.8-68.1) Grade 3-4 TRAEs (%, 95%CI) 9.7 (2.0-28.3) 15.8 (3.3-46.1) 0 7.8 (2.9-17.0) 4.0 (0.5-14.4) 14.8 (4.0-38.0)

A 20-year population-wide cohort study on association of aspirin and risk of gastrointestinal and non-gastrointestinal cancer.

830 Background: Aspirin has been shown to reduce the risk of various gastrointestinal (GI) and non-GI cancers 1,2 . However, little was known about at what age aspirin should be started for maximal chemoprotective better on GI cancer. Furthermore, the randomised controlled trial on aspirin for primary prevention use in healthy elderly (ASPREE) showed no association between aspirin and cancer incidence despite the limitation of short follow-up duration 3 . The current study aims to investigate the 20-year risk of cancer using aspirin in a territory-wide Hong Kong population cohort. Methods: The study included all aspirin users from 2000 to 2019, and non-aspirin users matched by age and sex at a ratio of 1:2. Enrolled subjects with a history of cancer at enrolment, cancer incidence or death within 6 months were excluded. The incidence of individual GI and non-GI cancer was presented as the primary outcome. Baseline characteristics between aspirin and non-aspirin users were adjusted in the survival analysis by inverse probability of treatment weighting (IPTW). The fine-grey model has been used to address bias from competing risk of death. The sub-distribution hazard ratio was presented for the association of aspirin use and risk of GI and non-GI cancers. Results: The current study included 538,147 aspirin users and 968,378 non-users with a mean age of 64.8 years. A total number of 36,683 cases of GI cancer (2.4%) and 47,196 cases of non-GI cancers (3.1%) were observed. Aspirin was associated with a lower risk of several common individual GI cancers, including colorectal cancer (SHR 0.78, 95% CI 0.76-0.81), liver cancer (SHR 0.67, 95% CI 0.64-0.70), stomach cancer (SHR 0.79, 95% CI 0.75-0.84) and pancreatic cancer (SHR 0.85, 95% CI 0.79-0.91), but not oesophageal cancer. On the other hand, aspirin was associated with a lower risk of prostate cancer (SHR 0.95, 95% CI 0.91-1.00) and breast cancer (SHR 0.76, 95% CI 0.73-0.79), but not lung cancer and kidney cancer. In overall, aspirin was associated with a 24% lower risk of GI cancers (SHR 0.76, 95% CI 0.74-0.78) and a 3% lower risk of non-GI cancers (SHR 0.97, 95% CI 0.95-0.99). Conclusions: Aspirin was associated with a lower risk of most GI cancers, including colorectal cancer, liver cancer, stomach cancer and pancreatic cancer, but not most non-GI cancers. In general, results on the effect of aspirin on GI cancer prevention were consistent with the previously presented 10-year cohort. 1. Bosetti C, Santucci C, Gallus S, Martinetti M, La Vecchia C. Aspirin and the Risk of Colorectal and Other Digestive Tract Cancers: An Updated Meta-analysis through 2019. Ann Oncol. 2020;31(5):558-568. 2. Santucci C, Gallus S, Martinetti M, La Vecchia C, Bosetti C. Aspirin and the risk of nondigestive tract cancers: An updated meta-analysis to 2019. Int J Cancer. 2021;148(6):1372-1382. 3. McNeil JJ, Gibbs P, Orchard SG, et al. Effect of Aspirin on Cancer Incidence and Mortality in Older Adults. J Natl Cancer Inst. 2021;113(3):258-265.

Clinical characteristics and treatment outcomes for metastatic early-onset small bowel adenocarcinoma treated with first-line chemotherapy.

796 Background: Small bowel adenocarcinoma (SBA) is an aggressive rare cancer with its incidence on the rise. Although early-onset SBA (EO-SBA: diagnosed at &lt; 50 years old) accounts for approximately 10% of all SBA, characteristics and survival outcomes of advanced EO-SBA remains under-evaluated. This study aims to evaluate clinical features and treatment outcomes of patients with advanced EO-SBA receiving first-line chemotherapy. Methods: We retrospectively analyzed the clinical data of patients who received fluoropyrimidine plus oxaliplatin as first-line treatment for recurrent or metastatic SBA at our hospital between January 2012 and July 2024 Patients were divided into two groups: those who were diagnosed at age of &lt; 50 years old (EO-SBA) and those who were diagnosed at age of ≥50 years old (late-onset SBA, LO-SBA). Clinicopathological characteristics and treatment outcomes (objective response rate [ORR], progression-free survival [PFS], overall survival [OS], and adverse events [AEs]) were compared between two groups. Survival outcomes were estimated using the Kaplan–Meier method and compared by the log-rank test. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) were calculated by univariable and multivariable Cox regression analyses. Results: A total of 69 patients (EO-SBA 18, LO-SBA 51) were included in this study. Compared to the LO-SBA group, the EO-SBA group were more likely to have non-duodenum tumor (89% vs. 49%, p = 0.002), lesser number of metastatic sites (≤2, 100% vs.78%, p = 0.007), and prior resection of primary tumor (83% vs 49%, p = 0.008). The EO-SBA group had longer PFS compared to the LO-SBA group (median PFS: HR = 0.32 [95% CI 0.12 - 0.85] p = 0.022). The EO-SBA group had a trend of longer OS compared to the LO-SBA group (median OS: HR = 0.39 [95%CI 0.15 - 1.01] p = 0.053). Age group was not identified as an independent prognostic factor for OS (HR = 0.63 [95% CI: 0.21 - 1.85], p = 0.40) and PFS (HR = 0.47 [95% CI: 0.16 - 1.37], p = 0.17) by multivariable analyses adjusted for previously reported prognostic factors (performance status, liver metastasis, primary site, histological classification, prior resection of primary tumor, and carcinoembryonic antigen [CEA] elevation). Among patients with measurable lesions (EO-SBA 9, LO-SBA 41), the EO-SBA group showed a numerically higher ORR compared with the LO-SBA group (63% vs 29%, p = 0.07). There were no significant differences of AE frequencies between two groups except for anemia (grade 3/4. EO-SBA 0% vs LO-SBA 22%, p &lt; 0.001). Conclusions: Our study indicates the difference of clinical characteristics between two age groups in patients with advanced SBA. EO-SBA was not identified as independent prognostic factor for OS and PFS in patients treated with first-line chemotherapy.

Predicting climate-change impacts on the global glacier-fed stream microbiome

Phase Ib/II study of fruquintinib plus 5-fluorouracil/leucovorin after progression on fruquintinib monotherapy in metastatic colorectal cancer.

128 Background: Fruquintinib is a standard third-line treatment in metastatic colorectal cancer (mCRC). However, no standard therapeutic regimen is available for mCRC patients who progressed on third-line therapy. Preclinical experiments supported a rationale for combining antiangiogenic therapy and 5-fluorouracil (5FU) in refractory mCRC with evidence for synergy. This open-label phase Ib/II study was designed to determine the safety and efficacy of fruquintinib plus 5-fluorouracil/leucovorin for mCRC patients who progressed on fruquintinib monotherapy. Methods: The enrolled patients would receive fruquintinib at a fixed dose of 4mg once daily (three weeks on, one week off) and 5FU at two dose levels (1800mg/m 2 and 2400mg/m 2 ) CIV 46 hours on day one and day 15, with leucovorin 400mg/m 2 iv 2 hours before 5FU. Treatments were repeated every 28 days. The primary endpoint was determining the recommended phase II dose (R2PD) of 5FU in phase Ib and the six-month OS rate in phase II. Secondary endpoints for phase II included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and safety. Planned enrollment was 39 patients. Results: No dose-limiting toxicities occurred in the phase Ib dose-escalation study, and the R2PD of 5FU was 2400mg/m 2 . Between April 2020 and June 2024, 24 patients were enrolled in the phase II stage. The median age was 57.5 years old (from 35 to 68), and 58.33% were female. Left-sided colorectal cancer patients accounted for 75%. Sixteen (66.7%) patients harbored KRAS mutation, and one (4%) had BRAF V600E mutation. Regarding the number of lines of systemic therapy, 83.3% received this study regimen as fourth-line therapy and 16.7% as fifth-line or later therapy. As of June 30, 2024, efficacy was assessed in all 24 patients with a DCR of 62.5% (15 stable disease, nine progression disease). The median follow-up time was 16.5 months (95% CI:12.553-20.447). The primary endpoint six-month OS rate was 91.3%, the median PFS was 4.4 months (95% CI: 1.243-7.557), and the median OS was 17.3 months (95% CI: 12.892-21.708). The most common TRAEs were nausea (25%), hand-foot syndrome (16.7%), abnormal liver function (8.3%), and proteinuria (8.3%). One patient experienced grade 3 mucositis. No treatment-related death occurred. Conclusions: Fruquintinib plus 5-fluorouracil/leucovorin regimen preliminarily demonstrated promising efficacy with a tolerable safety profile for mCRC patients despite progression on prior fruquintinib monotherapy. Further investigation into this possible later-line regimen in mCRC is warranted. Clinical trial information: ChiCTR2000032640 .

Optimal preoperative treatment strategy for conversion surgery in unresectable locally advanced pancreatic cancer: A project study by the Japanese Society of Hepato-Biliary-Pancreatic Surgery.

718 Background: Conversion surgery (CS) for unresectable locally advanced pancreatic cancer (UR-LAPC) has been widely accepted when feasible. However, optimal preoperative treatment strategies remain unclear. To determine the most effective preoperative approach for UR-LAPC in the current treatment landscape, we conducted a project study in the Japanese Society of Hepato-Biliary-Pancreatic Surgery. Methods: We analyzed 465 UR-LAPC patients who underwent CS following chemotherapy with FOLFIRINOX (FFX), gemcitabine plus nab-paclitaxel (GnP), or modified regimens between 2015 and 2020 across 84 Japanese board-certified training institutions. Overall survival (OS) was the primary endpoint. We used the Kaplan-Meier method for estimating survival analyses, the Cox proportional hazards model for multivariate analyses, and Maximally Selected Rank Statistics to determine the optimal preoperative treatment duration. Results: Median OS was 43.8 months, with a 5-year survival rate of 37.2%. The optimal preoperative treatment duration was 6.1 months. Patients receiving &gt;6 months of preoperative treatment (n=350) showed significantly better median OS and recurrence-free survival (RFS) compared to ≤6 months (n=115) (50.4 vs 29.7 months and 15.6 vs 9.1 months, respectively; both P&lt;0.001 ). FFX-based regimens (n=116) showed better OS and RFS than GnP-based regimens (n=349) (65.0 vs 36.5 months and 19.3 vs 12.4 months, respectively; both P&lt;0.01 ). Multivariate analysis identified preoperative treatment &gt;6 months (HR 0.53, 95% CI 0.407-0.697, P&lt;0.001 ) and initial FFX-based regimens (HR 0.63, 95% CI 0.464-0.843, P=0.002 ) as independent prognostic factors. Additional favorable factors included normal CA19-9 and CEA levels, PNI&gt;45 before CS, adjuvant chemotherapy, R0 resection, and Evans grade III/IV. Conclusions: This large-scale retrospective study has demonstrated that preoperative treatment duration &gt;6 months and the use of FFX-based regimens as initial treatment were associated with improved survival outcomes in UR-LAPC patients undergoing CS. These findings provide critical information for considering CS in UR-LAPC patients, especially in current clinical practice.

Genomic alterations as predictive biomarkers for cancer-associated thrombosis (CAT) in biliary tract cancer (BTC).

634 Background: CAT is the second leading cause of cancer-related death, yet the genetic underpinnings of VTE risk in BTC remain underexplored. The evaluation of CAT risk is based on Khorana score (KS), which is limited to clinical parameters. Incorporation of a genomic signature in CAT risk assessment may allow for individualized risk assessment. Methods: We collected data from consecutive patients (pts) with BTC treated at Mayo Clinic Hospitals (Phoenix, Rochester, Jacksonville) between 1998-2024. Genomic profiling was conducted on FFPEs and blood samples through next-generation sequencing (NGS) (NextSeq, Tempus xT CDx, FoundationOne CDx). Association between CAT and clinic-pathologic features (age, gender, race, ethnicity, BMI, tumor site (TS), surgery, stage, radiotherapy, systemic therapy, history of thromboembolism (hVTE)) were assessed with multivariate Cox regression (p&lt;0.05). A separate Cox regression adjusting for age, hVTE, radiotherapy, systemic therapy, metastatic disease stratified for TS was used for gene associations. Benjamini–Hochberg method was applied (q&lt;0.1) based on previous publications. Median overall survival (mOS) was calculated from the date of diagnosis to the date of death or last follow-up. Results: 740 adult pts were included, median age 62 years (IQR: 56-71), male/female (51%/49%), median BMI 26.6 (IQR: 22.8-31.1) with intrahepatic (496, 67%) and extrahepatic BTC (173, 23%), gallbladder cancer (71, 10%). 244 (33%) had metastatic disease. 216 (29%) experienced CAT. For those with CAT, 31 (14%) scored 1, 9 (4%) scored 2 and 1 (&lt;1%) scored 3 on KS. mOS was 33 months (mos) (95% CI 28.9-38.4) vs. 55 mos (95% CI 25.1-39.1) (p=0.2) for pts with and without CAT, respectively. hVTE was associated with CAT (HR 3.14, 95% CI 1.98-4.98, p&lt;0.001) along with systemic therapy (HR 1.19, 95% CI 1.11-2.89, p&lt;0.01) and metastatic disease (HR 1.65, 95% CI 1.11-2.44, p&lt;0.01). 305 pts (41%) underwent NGS. The most common altered genes were TP53 (126, 41%), KRAS (64, 21%), CDKN2A (63, 21%). The most common altered currently targetable genes were FGFR2 (43, 14%), IDH1 (30, 10%) and HER2/ERBB2 (16, 5%). MYC (4, 1%) (HR 11.60, 95% CI 3.04-44.25, p&lt;0.001, q=0.058) and HER2/ERBB2 (HR 2.45, 95% CI 1.26-4.77, p=0.008, q=0.087) alterations were significantly associated with an increased risk of CAT. MYC alterations were all copy number gains (100%). The most frequent HER2/ERBB2 alterations were copy number gains (10, 62%). FGFR2 fusions (31, 10%) were linked to a lower CAT risk (HR 0.46, 95%CI 0.22-0.93, p=0.032, q=0.075) with FGFR2-BICC1 being the most frequent (5,16%). Conclusions: MYC and HER2/ERBB2 alterations are novel predictive biomarkers for an increased risk of CAT in BTC, while FGFR2 fusions confer lower risk. The knowledge of mutational status lends insight into guidance for anticoagulant prophylaxis management for this subgroup and integration with KS.