Browse Articles

Artificial intelligence–guided microsatellite instability classification in colorectal cancer (CRC): EfficientNet-based histopathology analysis for precision treatment planning.

e15621 Background: Microsatellite instability (MSI) represents a biomarker in CRC, affecting 15–20% of cases and guiding treatment/prognosis. MSI-high (MSI-H) tumors exhibit defective mismatch repair showing hypermutation, immunogenicity, and strong responses to ICIs (pembrolizumab, nivolumab) but poor traditional chemotherapy outcomes. Conversely, microsatellite stable (MSS) tumors respond better to fluorouracil-based regimens. Current MSI testing via immunohistochemistry or PCR is labor-intensive, time-consuming and variable. Automated deep learning systems capable of predicting MSI status directly from routine histopathology slides could accelerate diagnostics, optimize therapy, and reduce treatment delays.OBJECTIVES:To develop and validate a deep learning framework for predicting MSI status from CRC histopathology; to evaluate lightweight model performance via knowledge distillation from a higher-capacity teacher; and to assess global feasibility using expert-reviewed, multi-institutional data. Methods: We assembled 10,000 anonymized hematoxylin-eosin stained histopathological images of colorectal tissue from multi-institutional sources. MSI status was confirmed by gold-standard PCR or immunohistochemistry; pathologist confirmed ground truth. After preprocessing and stain augmentation, images were stratified into training (60%), validation (20%), and testing (20%) cohorts. EfficientNetB4 (17.4M parameters, 380×380 resolution), selected for compound resolution scaling, was trained as reference. EfficientNetB1 (7.8M parameters, 240×240 resolution, 55% parameter reduction) underwent structured knowledge distillation using soft targets from EfficientNetB4. Model performance was evaluated on accuracy, sensitivity, specificity, F1-score, and AUROC for MSI classification. The optimized EfficientNetB1 was deployed in a digital pathology platform and independently assessed by 47 pathologists across 6 continents. Results: EfficientNetB4 achieved high diagnostic accuracy for MSI status prediction. Distilled EfficientNetB1 demonstrated comparable performance, with accuracy exceeding 93% on test data, AUROC > 0.91, balanced sensitivity (94.2% MSI-H, 92.1% MSS), and specificity > 93%. Performance remained stable across geographically distinct datasets with staining protocol variation. Pathologist evaluators reported the system as valuable for MSI triage and treatment planning support. Conclusions: EfficientNet enables accurate MSI prediction from histopathology. Knowledge distillation from EfficientNetB4 to EfficientNetB1 preserved diagnostic accuracy while cutting parameters 55%, supporting rapid stratification for immunotherapy. Prospective evaluation in workflows is warranted to accelerate CRC precision oncology.

Fruquintinib in combination with tislelizumab vs trifluridine/tipiracil and bevacizumab in MSS mCRC without active liver metastases: The IKF-080/QUINTIS trial.

TPS3684 Background: Patients with metastatic colorectal cancer (mCRC) who progress after treatment with fluoropyrimidines, oxaliplatin, irinotecan, anti-angiogenic agents, and anti-EGFR therapies have limited therapeutic options and a poor prognosis. Median overall survival (mOS) is approximately 6 months with single-agent regorafenib or trifluridine/tipiracil. The addition of bevacizumab to trifluridine/tipiracil has improved mOS to 10.8 months, while fruquintinib, a selective VEGFR-1–3 inhibitor, demonstrated a mOS of 7.4 months compared with 4.8 months for placebo in refractory mCRC. However, combinations of tyrosine kinase inhibitors and immune checkpoint inhibitors have shown clinical benefit, primarily in patients with microsatellite-stable mCRC without liver metastases, likely due to liver-associated immunosuppression. The QUINTIS trial evaluates whether fruquintinib plus the PD-1 antibody tislelizumab can improve outcomes in this clinically defined subgroup compared with the current standard of care of trifluridine/tipiracil plus bevacizumab. Methods: QUINTIS is a prospective, randomized, open-label, multicenter phase II trial enrolling 140 patients with metastatic colorectal adenocarcinoma without active liver metastases who have previously received fluoropyrimidines, oxaliplatin, irinotecan, bevacizumab, and, when indicated, an EGFR inhibitor. Participants are randomized 1:1 to Arm A (experimental): fruquintinib 5 mg orally once daily (days 1–21 of a 28-day cycle) plus tislelizumab 400 mg intravenously on day 1 every 6 weeks; or Arm B (control): trifluridine/tipiracil 35 mg/m² orally twice daily (days 1–5 and 8–12 of a 28-day cycle) plus bevacizumab 5 mg/kg intravenously every 2 weeks. No prior treatment with the study drugs is permitted. Randomization is stratified by time since prior anti-angiogenic therapy ( < 12 vs. ≥12 months), BRAF/RAS mutation status, and history of liver metastases (never vs. treated). The primary endpoint is progression-free survival; secondary endpoints include overall response, overall survival, and quality of life. Translational research includes tumor, blood, and stool sampling to explore biomarkers of response and resistance, including systemic inflammation and the diet–microbiota–immune axis. Patient enrolment started in October 2025, and enrolment will take place at 30 sites. Clinical trial information: EU CTIS No. 2024-519111-34-00.

Outcomes with androgen-deprivation therapy (ADT) plus androgen receptor pathway inhibitors (ARPIs) in veterans with de novo metastatic castration-sensitive prostate cancer (mCSPC) who were elderly, frail, or had high comorbidity: A subgroup analysis of enzalutamide and high-volume disease.

5094 Background: Clinical trials show significant overall survival (OS) benefits of combining ADT with ARPIs (abiraterone, apalutamide, darolutamide, or enzalutamide [ENZA]) vs ADT in mCSPC. The effects of ADT + ARPI in patients (pts) who are elderly, frail, or have high comorbidity burden remain unclear due to underrepresentation in clinical trials. This observational cohort study examined OS in two subgroups of this population: pts who received ENZA and those with high-volume disease (HVD). Methods: Veterans Health Administration records were used to assess OS in pts with de novo mCSPC treated with ADT + ARPI ± nonsteroidal antiandrogen (NSAA; ADT + ARPI group) or ADT ± NSAA (ADT group). Pts were aged ≥75 years (y) or had Veterans Affairs Frailty Index (VA-FI) > 0.2 or Charlson Comorbidity Index (CCI) ≥3. Subgroups comprised pts who: 1) initiated ADT + ENZA (HVD or low-volume disease); or 2) had HVD with any ARPI. Pts were indexed on first ADT date (Jun 1, 2017–Dec 31, 2022) and followed until censoring (Jun 1, 2025) or death. Mortality risk was estimated using a multivariable, time-varying Cox model to account for time between ADT + ARPI initiation adjusted for volume of disease, age, body mass index, CCI, and prostate-specific antigen level. Results: Of 1,629 pts, 272 (16.7%) received ADT + ENZA and 1,357 (83.3%) received ADT; median follow-up was 34.1 and 23.4 months (mo), respectively. Compared with ADT, the ADT + ENZA subgroup was younger (median age 77.5 vs 81.2 y, standardized mean difference [SMD]: −0.34) with similar frailty (VA-FI > 0.2: 67.3% vs 71.5%, SMD: 0.09) and more HVD (71.7% vs 61.5%, SMD: 0.22). ADT + ENZA was associated with significantly lower risk of death vs ADT (adjusted hazard ratio [aHR] 0.70; 95% CI: 0.60–0.83; P < 0.001; Table). Among 1,541 pts with HVD, 706 (45.8%) received ADT + ARPI and 835 (54.2%) received ADT; median follow-up was 29.1 and 18.8 mo, respectively. Pts who received ADT + ARPI were younger (median age 77.1 vs 81.9 y, SMD: −0.44) and had less frailty (VA-FI > 0.2: 66.2% vs 72.9%, SMD: 0.15). ADT + ARPI was associated with significantly lower risk of death vs ADT (aHR: 0.73; 95% CI: 0.65–0.83; P < 0.001). Conclusions: In this real-world cohort analysis of pts with de novo mCSPC who were elderly, frail, or had high comorbidity, ADT + ENZA was associated with prolonged survival compared with ADT. In pts with HVD, ADT + ARPI was associated with longer survival vs ADT. Subgroup ADTMedian survival,mo (95% CI), n ADT + ARPI a Median survival,mo (95% CI), n aHR (95% CI) b ; P value ENZA 23.4 (21.9–25.2), n = 1,357 36.1 (32.9–40.1), n = 272 0.70 (0.60–0.83); P <0.001 HVD 18.8 (17.5–20.5), n = 835 29.1 (26.0–32.3), n = 706 0.73 (0.65–0.83); P <0.001 a ENZA subgroup treatment arm: ADT + ENZA. b ADT = reference.

Biological subtype discordance after neoadjuvant therapy in early breast cancer: Findings from a 1,500-patient cohort with residual disease.

604 Background: Although biomarker reassessment is standard in recurrent breast cancer, its role in early breast cancer with residual disease (RD) after neoadjuvant therapy (NAT) remains not well established, despite potential implications for adjuvant treatment decisions in the post-NAT setting. Methods: We retrospectively analyzed patients with early breast cancer who underwent surgery after NAT and had RD between January 2019 and May 2025. Only patients with estrogen receptor (ER), progesterone receptor (PR), and HER2 status assessed on both pretreatment biopsy and matched surgical specimens were included. Biological subtype discordance was analyzed across luminal, HER2-positive, and triple-negative breast cancer (TNBC). Multivariable logistic regression was used to identify clinicopathological factors associated with subtype change. Results: Among 1,504 eligible patients with residual disease, biomarker discordance involving ER, PR, and/or HER2 was observed in 502 cases (33.4%). A change in biological subtype occurred in 221 patients (14.7%). Subtype discordance was most frequent in tumors initially classified as HER2-positive (39.3%), compared with TNBC (10.6%) and luminal disease (6.2%) (p<0.001). Accordingly, patients with HER2-positive breast cancer at diagnosis were significantly more likely to experience subtype discordance after NAT compared with luminal tumors (absolute difference 33.1%, p<0.001) and TNBC (absolute difference 28.7%, p<0.001), with a smaller but statistically significant difference also observed between TNBC and luminal disease (absolute difference 4.4%, p=0.023). HER2-positive and TNBC tumors predominantly shifted toward a luminal phenotype, whereas luminal tumors more commonly converted to HER2-positive or TNBC subtypes, indicating substantial post-treatment biological heterogeneity. On multivariable analysis, baseline biological subtype remained the strongest independent predictor of subtype change, with higher odds for HER2-positive (OR = 9.14, p<0.001) and TNBC tumors (OR = 1.71, p=0.029) compared with luminal disease. Lobular histology was associated with a significantly lower likelihood of subtype discordance (OR = 0.50, p=0.040), whereas type of NAT, tumor grade, and Ki-67 were not associated with subtype change. Conclusions: In this large cohort of patients with residual disease after NAT, approximately one in seven experienced a change in biological subtype, with the highest discordance observed in initially HER2-positive tumors. These findings support routine biomarker reassessment in early breast cancer with residual disease to better inform adjuvant treatment decisions and to account for post-treatment biological heterogeneity.

Phase II trial of pembrolizumab in combination with odetiglucan for patients with metastatic colorectal adenocarcinoma with liver-predominant disease.

TPS3673 Background: Liver metastases are associated with resistance to immune checkpoint inhibitors in patients with mismatch repair proficient (MMRp) metastatic colorectal cancer (mCRC). (Beiter JCO 2025) Odetiglucan is a pathogen associated molecular pattern (PAMP) that modulates the tumor microenvironment and may enhance the activity of immune checkpoint inhibition. In syngeneic colon cancer mouse models, the combination of odetiglucan and PD-1/PD-L1 inhibition was associated with a larger proportion of tumor-free mice than either treatment alone. (Jonas Cancer Res. 2017; Fraser Cancer Res. 2016; Chan Frontiers Oncol. 2020) In a mouse model of pancreatic cancer liver metastases, odetiglucan reprogrammed liver-resident macrophages to stimulate tumor-specific T-cell responses, which was associated with reduced cancer cell proliferation and increased sensitivity to anti-PD-1 therapy. (Thomas Nat Commun. 2023) In a clinical trial of anti-PD-1 therapy plus odetiglucan in patients with triple negative breast cancer, tumor regression was observed in 56% of liver lesions classified as target lesions, with one patient experiencing complete regression of both target liver lesions, which remained undetectable after more than 70 weeks of treatment. (Stopeck J Immun. 2025). Methods: We are performing a single-center, investigator-initiated, single-arm phase II clinical trial with a Simon two-stage mini-max design of the combination of pembrolizumab with odetiglucan in patients with liver-predominant, MMRp mCRC who have experienced disease progression on standard therapies (3L+ setting). Treatment consists of intravenous infusion of odetiglucan (4mg/kg) and pembrolizumab on day 1 of a 21-day cycle. Patients with prior exposure to immunotherapy or odetiglucan, peritoneal metastases, symptomatic lung or bony metastases, autoimmune conditions requiring systemic immunosuppression, or a history of pneumonitis are excluded. The primary endpoint of the study is objective response by RECIST 1.1. The null hypothesis that the true response rate is 6% will be tested against a one-sided alternative. In the first stage of the study, 13 patients will be accrued and if there are no partial or complete responses, then the study will be stopped for futility. Otherwise, 14 additional patients will be accrued to a total of 27 patients. If four or more responses are observed in 27 patients, then the null hypothesis will be rejected. As of 1/2026, four patients have been enrolled and started study treatment. The study includes pre-treatment and on-treatment research biopsies and longitudinal research blood collection for immune pharmacodynamic profiling to investigate mechanisms of treatment response and resistance. Clinical trial information: NCT07082439 .

A phase II trial of lenvatinib plus pembrolizumab in patients (pts) with endometrial or ovarian carcinosarcoma.

5615 Background: Carcinosarcoma is a rare and aggressive histology of gynecologic carcinomas that has limited treatment options and is often excluded from larger therapeutic clinical trials. In KN775, treatment with multikinase inhibitor lenvatinib plus PD-1 inhibitor pembrolizumab led to significantly longer progression-free survival (PFS) and overall survival (OS) than chemotherapy among patients with previously treated advanced non-carcinosarcoma endometrial carcinomas. We report results from a phase 2 trial of lenvatinib + pembrolizumab in pts with endometrial or ovarian carcinosarcoma. Methods: In this open label, single institution, investigator initiated, phase 2 study, pts had confirmed recurrent/persistent endometrial or ovarian carcinosarcoma with progression after at least 1 prior platinum chemotherapy but no more than 3 prior lines, measurable disease, and ECOG performance status ≤1. Pts received oral lenvatinib 20 mg/day plus pembrolizumab 200 mg intravenously every 3 weeks. The primary endpoints were objective response rate (ORR) per RECIST v1.1 and PFS rate at 27 weeks (PFR27). Secondary endpoints included median duration of response (mDOR), clinical-benefit rate (CBR: complete response (CR) + partial response (PR) + stable disease (SD) at 27 weeks), median overall survival (mOS), and safety. Next generation sequencing, MSK-IMPACT, was performed on tumors from all 27 patients for exploratory analysis. Results: As of data cutoff on 12/15/2025, 27 pts enrolled; median age was 63 years (range: 51−79); and at least 26.4% pts were non-white. Primary tumor site was 63% (17/27) endometrial and 37% (10/27) ovarian; tumors were 19% (5/27) dMMR and 81% (22/27) pMMR. Confirmed ORR was 18.5% (5/27; 0 CRs, 3 PRs in endometrial, 2 PRs in ovarian), meeting the interim analysis primary endpoint. Of the 5 confirmed responses, 4 occurred in pts with pMMR tumors, and 1 in a pt with dMMR tumor. There are 2 additional unconfirmed PRs. Responses in pts with ovarian tumors included 1 platinum-sensitive and 1 platinum-resistant. PFR27 was 35.7% (90% CI: 24 - 100), mDOR was 26.5 months (80% CI: 3.8 - NE), CBR was 37% (80% CI: 24.4 - 51.2), and mOS was 15.3 months (95% CI: 7.1 – 24.4). Two pts remain on treatment and were censored for time to event analyses. All pts had at least one treatment-emergent adverse event (TEAE). The most common TEAEs were fatigue (74%), hypertension (56%), diarrhea (52%), anorexia (48%), and weight loss (48%). Grade 3 and 4 TEAEs occurred in 44% and 7.4% patients, respectively. There were no grade 5 TEAEs. 5 Pts (19%) discontinued study treatment due to TEAEs. Further genomic analyses are underway. Conclusions: Encouraging efficacy and durable responses were observed in endometrial and ovarian carcinosarcoma pts treated with lenvatinib + pembrolizumab, regardless of MMR status or primary site. The study met its predefined interim analysis endpoint. No new safety signals were identified. Clinical trial information: NCT02501096 .

Moving the surgical prostate cancer treatment to value: Early results in patient-reported outcomes from a Brazilian cohort.

e13601 Background: Prostate cancer (PCa) is the most frequently diagnosed malignancy among men in Brazil. While therapeutic advances have reduced mortality in high and intermediate-risk disease, functional sequelae such as urinary incontinence and erectile dysfunction remain highly prevalent in several patients. Value-based healthcare (VBHC) programs, centered on patient-reported outcomes (PROMs) and integrated care pathways, have emerged as a strategy to optimize care delivery and align clinical results with outcomes that matter to patients, but evidence of their structure and implementation in Brazil is scarce. This study reports early results from a value-based program for the surgical treatment of PCa in Brazil. Methods: Since 2022, a strategic value-based healthcare program has supported each cancer center with accurate real-world data and used it to deliver effective patient-centered care. PROMs have been collected using the ICHOM-recommended EPIC-CP instrument at baseline, 90 days, and 365 days. Outcomes included urinary continence, sexual function, and adherence to rehabilitation strategies. Clinical and demographic data were integrated with PROMs to assess functional recovery trajectories. In this early results report, the analyses are descriptively presented and compared over the period through the Cochran test for each outcome. Results: From August 2022 to April 2025, 535 patients were enrolled in the institutional value program, of whom 346 underwent radical prostatectomy. A subset of 118 patients completed all timepoints and composed the sample for this early results cohort. The mean age was 63.6 (SD = 8.1) years, with 79% undergoing robotic-assisted prostatectomy. At one year, 76% of patients maintained pre-treatment urinary function, with 78% of non-elderly and 74% of elderly patients reporting no pad use. Table 1 contains the results. Sexual function recovery was heterogeneous: among previously potent patients, 34% (≤65 years) and 21% (≥66 years) reported erections firm enough for intercourse at one year. Sexual rehabilitation interventions (PDE5 inhibitors, intracavernosal therapy, vacuum devices) were associated with significant improvements compared to no therapy (p = 0.033), and contributed to more than 90% of patients keeping or improving their sexual function in one year. Program adherence was high, with response rates of 84.5% at 90 days and 83% at 365 days. Conclusions: The PCa Value Program demonstrates that structured PROM collection and integrated care and rehabilitation strategies can achieve functional outcomes comparable to international benchmarks, despite resource constraints in Brazil. By embedding VBHC principles into oncology, the program highlights the feasibility of patient-centered, outcome-driven cancer care in Latin America.

Molecular and clinical characteristics of patients with non-small cell lung cancer (NSCLC) harboring the rare <i>KRAS</i> codon 12 mutations G12A, G12S, G12R, and G12F.

e20647 Background: KRAS mutations occur in approximately 30% of non-small cell lung cancers (NSCLC) and frequently involve the hotspot codon G12. While common variants such as G12C, G12V and G12D have been extensively studied, data on rare G12A, G12S, G12R and G12F substitutions remain limited. This real-world analysis characterizes the molecular and clinical features of a large cohort of NSCLC patients harboring rare KRAS codon 12 mutations. Methods: We looked for stage IV NSCLC at initial diagnosis harboring rare KRAS codon 12 mutations (G12A, G12S, G12R and G12F) from the national Network Genomic Medicine (nNGM) database diagnosed between 2018 and 2024. Clinical, pathological and molecular characteristics were analyzed, including co-mutations, smoking-history, PD-L1 expression, treatment patterns and outcomes. Results: A total of 527 individuals were included. KRAS G12A mutations were identified by next-generation sequencing (NGS) in 316 cases (60%), followed by G12S (15%), G12R (13%) and G12F (12%). The median age of the cohort was 66 years (range: 38–89), with no major differences in sex distribution (47% female, 53% male). Most patients were former or current smokers (overall: 477 (91%), G12A/S/R/F: 91/94/82/93%) and adenocarcinoma was the predominant histology (overall: 480 (91%), G12A/S/R/F: 90/89/93/99%). Median PD-L1 tumor proportion score (TPS) in the overall cohort was 5% (range: 0–100), with differences between subtypes (G12A/S/R/F: 5/30/1/10%). The most frequent co-mutations in the overall cohort were TP53 , STK11 , KEAP1 and SMARCA4 , showing subtype-specific patterns ( TP53 : 43/43/36/43%, STK11 : 21/23/36/29%, KEAP1 : 21/16/26/18%, SMARCA4 : 9/29/0/14% for G12 A/S/R/F respectively). At initial diagnosis the most common metastatic sites were bone (38%) and lung (38%) metastasis, with notable differences between subtypes (bone: 44/36/11/40%, lung: 40/36/45/21% for G12 A/S/R/F). Treatment data were available for 285 patients, of whom 36 (13%) received chemotherapy, 199 (70%) chemo-immunotherapy, and 50 (18%) immune checkpoint inhibitor monotherapy. Median overall survival (mOS) did not significantly differ between subtypes, however a trend toward shorter survival was observed in G12R-mutated tumors (mOS: 6.7 months (95% CI, 4.1–15.9)), whereas longer survival was seen in G12A-mutated tumors (mOS: 11.7 (95% CI, 9.2–16.6). Conclusions: NSCLC harboring rare KRAS codon 12 mutations (G12A, G12S, G12R and G12F) are characterized by a high prevalence of tobacco exposure, frequent co-mutations in clinically relevant genes, and a heterogeneous molecular landscape across the four analyzed subtypes. Despite comparable median overall survival, the observed subtype-specific patterns underscore the biological diversity of rare KRAS codon 12 mutations and suggest that these subgroups be considered in future clinical trials.

Plasma levels of mitochondrial gene copy number and microRNA transcripts as effective minimally invasive biomarkers for endometrial adenocarcinoma.

e17629 Background: The development of endometrial adenocarcinoma (EA) is linked to aberrations in the mitochondrial genome. Screening for molecular markers of mitochondrial metabolism—specifically, gene copy number and microRNA transcript levels in plasma—could be valuable for developing effective minimally invasive diagnostic methods for EA. The aim of this study was to identify molecular minimally invasive differential biomarkers for EA and uterine fibroids (UF). Methods: The study included 16 patients with EA (grades G2, G3) at stage IA or IB, and 4 patients with UF. The mean age was 59.7 years. No neoadjuvant therapy was administered prior to sample collection. Ten milliliters of venous blood were collected from each patient before treatment, and plasma was isolated. The relative copy number of target genes was assessed using quantitative real-time polymerase chain reaction (RT-qPCR). Synthetic oligonucleotide primers were designed using Primer-BLAST and the GenBank database (NCBI). GAPDH and B2M were used as reference genes for normalization. Amplification was performed using a CFX96 thermal cycler (Bio-Rad, USA). MicroRNA was extracted from plasma samples using the miRNeasy Serum/Plasma Kit (Qiagen, Germany) on a Qiacube Connect automated station (Qiagen, Germany). Changes in the relative expression of microRNAs were evaluated by RT-qPCR. Statistical analysis was performed using dedicated medical research software packages. Results: Statistically significant differences were found in plasma levels of the gene copy numbers for HV2 and MT-ND1, as well as in the levels of microRNA transcripts hsa-miR-122-5p and hsa-miR-7106-5p, between patients with EA and UF. All studied parameters were lower in EA compared to UF. Specifically, plasma copy numbers of HV2 and MT-ND1 genes were 1.5-fold (p&lt;0.005) and 1.4-fold (p&lt;0.05) lower, respectively, in EA than in UF. Plasma levels of hsa-miR-122-5p (p&lt;0.005) and hsa-miR-7106-5p (p&lt;0.005) transcripts were 8.9-fold and 3.9-fold lower, respectively, in EA than in UF. Conclusions: These results elucidate certain mechanisms of mitochondrial dysfunction in EA and hold potential significance for improving the minimally invasive diagnosis of this disease.

Camrelizumab combined with liposomal doxorubicin and dacarbazine as first-line therapy for advanced, recurrent, and metastatic undifferentiated pleomorphic sarcoma: A phase II study.

11513 Background: This phase II study aims to evaluate the efficacy and safety of camrelizumab combined with liposomal doxorubicin and dacarbazine in patients with advanced, recurrent and metastatic undifferentiated pleomorphic sarcoma (UPS). Methods: Patients with histologically confirmed advanced, recurrent and metastatic UPS, treatment-naïve for advanced disease, and at least one measurable lesion per RECIST v1.1 were eligible. Camrelizumab was administered in combination with liposomal doxorubicin and dacarbazine for up to six cycles, followed by camrelizumab maintenance therapy. The primary endpoint was investigator-assessed objective response rate (ORR) per RECIST v1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), duration of response (DoR), and safety. Results: Between October 2022 and August 2025, 28 pts were enrolled and received study treatment, of whom 24 were evaluable for efficacy analyses. Partial response occurred in 7 patients, with no complete responses observed, resulting an ORR of 29.2% (7/24). Stable disease was achieved in 14 patients, yielding a disease control rate of 87.5% (21/24). Two patients had progressive disease and four patients were not evaluable due to the absence of post-baseline tumor assessments. With a median follow-up of 11.9 months (data cutoff: December 29, 2025), 16 PFS events and 7 death events had occurred. The median PFS was 8.4 months (95% CI, 6.2-NA), while median OS had not been reached. Responses appeared durable, with a median DoR of 4.5 months among responders (n=7), though early progression was observed in some patients. An exploratory analysis revealed PD-L1-positive patients (CPS ≥1) showed a trend toward a higher ORR than PD-L1-negative patients (42.9% [3/7] vs 21.4% [3/14]). The most common treatment-related adverse events of any grade were neutropenia (35.7%), leukopenia (28.6%), rash (28.6%), and ALT elevation (25.0%). Grade ≥3 adverse events were infrequent, mainly ALT and AST elevations (both 7.1%). Immune-related adverse events included rash (28.6%), pneumonitis (7.1%), and hepatitis (7.1%), leading to treatment discontinuation in two patients. Conclusions: Camrelizumab combined with liposomal doxorubicin and dacarbazine demonstrated promising antitumor activity with durable responses and manageable safety as first-line therapy for advanced, recurrent and metastatic UPS. Exploratory analyses suggested that patients with higher PD-L1 expression may derive greater benefit from this regimen, warranting further investigation in larger, controlled studies. Clinical trial information: ChiCTR2100049974.

A phase II, multi-cohort study with pemetrexed plus cisplatin combination in patients with relapsed or refractory advanced soft tissue sarcoma: Leiomyosarcoma cohort (ALBATROSS-SARC-LMS01).

11559 Background: Given the promising results in previous single arm trial (NCT03809637), this histology-specific, multi-cohort, phase II trial was conducted to evaluate the efficacy and safety of pemetrexed plus cisplatin in patients with advanced and refractory soft tissue sarcoma (STS). Methods: In this trial (NCT04605770), we enrolled patients with metastatic and/or recurrent STS who had failed 1-2 prior cytotoxic regimens and maintained adequate performance status and organ function. The treatment regimen consisted of pemetrexed 500 mg/m² and cisplatin 75 mg/m² on day 1 of each 3-week cycle up to 6 cycles, followed by pemetrexed monotherapy. A total of 164 patients were planned for assignment into 4 histology- based cohorts (n=41 each) to account for a 10% drop-out rate: Cohort 1 (leiomyosarcoma, [LMS)), Cohort 2 (liposarcoma), Cohort 3 (vascular sarcoma), and Cohort 4 (other sarcomas). The primary endpoint was progression-free rate at 12 weeks (PFR12 weeks) utilizing a Simon’s two-stage design (P1=40%, P0=20%, α=β=0.1). In the first stage, 17 patients were accrued; if at least 4 successes were observed, the cohort was to be expanded to 37 evaluable patients. To account for a 10% drop-out rate, the final enrollment target was set at 41 patients per cohort. Results: As of October 2025, 74 (45.1%) patients were enrolled. Among those, cohort 1 (LMS) reached full enrolment with 40 patients (median age; 53 years, female; 87.5%, 75% had received 2 prior lines of chemotherapy). Among Of 39 evaluable patients, 7 (17.9%) achieved a confirmed partial response, and 22 (53.8%) had stable disease, resulting in a disease control rate (DCR) of 74.3%. The median progression free survival was 6.3 months (95% CI, 4.9-7.6) with 74.0% of PFR12 weeks. Notably, the observed DCR and PFR12 weeks compare favorably with historical data for other second/third-line regimens in LMS, such as gemcitabine plus docetaxel (typical DCR 50–60%; PFR12 weeks 40–50%). The median OS was 20.5 months (95% CI 14.3-26.7), with a median of 7 treatment cycles administered (range 1-31). Although treatment-related adverse events (TRAEs) occurred in the majority of patients, grade ≥3 TRAEs were observed in only 10 (25%) patients, mainly anemia (n=10, 25%), neutropenia (n=7, 17.5%), and nausea (n=3, 7.5%). One TREA (drug hypersensitivity) led to treatment discontinuation due to drug hypersensitivity. Conclusions: The combination of pemetrexed and cisplatin was well tolerated and demonstrated promising activity in patients with relapsed, advanced STS, particularly in LMS cohort. The efficacy observed exceeded historical outcomes for standard-of-care second-line therapies, warranting further investigation in future histology-specific studies. Clinical trial information: NCT03809637 .

Role of methanolic extract of Trigonella foenum-graecum seeds as a stabilizer in enhancement of metal and polymeric nanoparticles synthesis

Lightweight, Strong, and Resilient 3D Graphene Metamaterial via a Multi‐flow Assembly

ABSTRACT Materials aim to integrate excellent properties, including high strength, stiffness, significant elastic deformation, specifically at low density. However, synthetic materials usually involve trade‐offs among these characteristics, resulting in distinct categories, such as hard and soft carbon materials, despite sharing identical elemental composition. Here, we demonstrate a lightweight graphene metamaterial fabricated via multi‐flow assembly that integrates the mechanical robustness of low‐density hard carbons with the elastic deformability of soft carbons. The representative graphene metamaterial features a cuttlebone‐inspired lamella‐wall architecture. This architecture reasonably strengthens and stiffens the graphene metamaterial, akin to the house‐of‐cards carbon layer arrangement in hard carbons. The intrinsic superelasticity under huge deformation (90%) is also retained in these graphene metamaterials. Our multi‐flow assembly method is facile to prepare varied metamaterials by directly manipulating the arranged texture of individual graphene sheets, paving the way for exploring the unique properties of metamaterials in the macroscopic world and their applications.

Clinical and economic outcomes associated with inpatient palliative care in hospitalized patients with cancer: A systematic review and meta-analysis.

e24072 Background: Inpatient palliative care (IPC) is increasingly utilized for hospitalized patients with cancer to improve symptom management and support goal-concordant care. While much of the evidence supporting palliative care has focused on the outpatient setting, the clinical and economic outcomes of IPC remain less well defined. Existing studies suggest that IPC may influence outcomes beyond symptom control, including inpatient mortality (IM), hospital length of stay (LOS) and costs of care. We conducted a systematic review and meta-analysis to evaluate the association between IPC and clinical and economic outcomes among hospitalized patients with cancer. Methods: We performed a systematic search of PubMed in November 2025 to identify administrative database studies evaluating IPC among hospitalized patients with cancer. Two reviewers screened articles and discrepancies were resolved by consensus. Data analysis was conducted using a random-effects model. Pooled estimates with 95% confidence intervals (CI) were calculated, and heterogeneity was assessed using the I² statistic. Results: From 984 studies initially identified, 18 studies met our inclusion criteria, encompassing a total of 1,731,596 hospitalized cancer patients. Overall, IPC was associated with higher odds of IM compared with no IPC (OR 6.45, 95% CI 4.87–8.55; P &lt; 0.00001; I² = 100%), with no significant difference between high and low IPC utilization subgroups (P = 0.16). For LOS, no significant difference was observed between the IPC and no IPC groups (MD −0.02 days, 95% CI −0.78 to 0.73; P = 0.95; I² = 100%), with no evidence of subgroup differences between high and low IPC utilization subgroups (P = 0.92). Analysis of hospital costs demonstrated no significant difference between the IPC and no IPC groups (SMD 0.03, 95% CI −0.15 to 0.20, P = 0.78, I² = 95%). In contrast, IPC was associated with lower hospital charges compared with no IPC (MD −4,976 USD, 95% CI −7,129 to −2,823; I² = 86%). Conclusions: IPC was associated with significantly higher IM compared with no IPC. This finding is best explained by confounding by indication, as IPC is more frequently delivered to patients with a higher baseline mortality risk. Despite higher mortality in the IPC group, IPC involvement was not associated with a significant difference in LOS, suggesting that IPC does not meaningfully prolong or shorten inpatient admissions at the population level. Economic outcomes differed by metric; while no significant differences in hospital costs were observed, IPC was associated with lower hospital charges, likely reflecting variability in billing and reimbursement practices. Reduced charges associated with IPC may reflect lower utilization of high-intensity interventions. These findings highlight the potential clinical and economic implications of broader IPC involvement for hospitalized cancer patients.

Perioperative SHR-A2102, a novel nectin-4–targeted antibody-drug conjugate, in combination with adebrelimab for patients (pts) with muscle-invasive bladder cancer: Results from a phase 2/3 study.

4506 Background: Muscle-invasive bladder cancer (MIBC) is an aggressive disease, with substantial recurrence risk after radical cystectomy and pelvic lymph node dissection (RC + PLND) alone. SHR-A2102 is a nectin-4-targeted antibody-drug conjugate carrying topoisomerase I inhibitor payload. This phase 2/3 study (NCT06879145) evaluates the efficacy and safety of SHR-A2102 in combination with adebrelimab (an anti-PD-L1 antibody) as perioperative treatment for MIBC. Here, we report the preliminary results from the phase 2 study. Methods: In the multicenter phase 2 part, pts aged ≥18 years, ECOG PS 0-1, with pathologically and radiographically confirmed T2-4aN0M0 or T1-4aN1M0 MIBC, and scheduled for RC + PLND were enrolled. Pts received neoadjuvant treatment with 4 cycles of intravenous SHR-A2102 (8 mg/kg, day 1 Q3W) and adebrelimab (1200 mg, day 1 Q3W), followed by surgical resection and 5 additional cycles of adjuvant SHR-A2102 (8 mg/kg, day 1 Q3W) plus 13 additional cycles of adjuvant adebrelimab (1200 mg, day 1 Q3W). The primary endpoints are the recommended phase 3 dose (RP3D) and investigator-assessed pathological complete response (pCR, defined as pT0N0). Results: As of Nov 24, 2025, 37 pts were enrolled; 91.9% were male and the median age was 66 years (IQR 59-74). The ECOG PS was 0 in 24.3% of pts and 1 in 75.7%. Regarding disease stage, 29.7% were classified as T2N0, 51.4% as T3-4aN0, and 18.9% as T1-4aN1. Among 7 pts with target lesions, the neoadjuvant regimen achieved an objective response rate of 71.4% (5/7; 95% CI 29.0–96.3) and a disease control rate of 100.0% (95% CI 59.0–100.0). A total of 27 pts underwent RC + PLND, 13 (48.1%, 95% CI 28.7-68.1) achieved pCR and 16 (59.3%, 95% CI 38.8-77.6) attained pathological downstaging ( &lt; pT2N0). Consistent pCR benefits were observed across all predefined subgroups, with creatinine clearance ＜60 mL/min showing no discernible effect on pCR rates. Of the 10 pts who refused or were ineligible for radical surgery after neoadjuvant therapy, 5 received transurethral resection of bladder tumor and 3 of whom achieved a complete clinical response (cCR, defined as T0N0M0). With the median follow-up of 4.7 months (IQR 2.1-6.6), 3 event-free survival events were reported. Grade 3 or higher adverse events occurred in 40.5% (15/37) of the pts, primarily decreased neutrophil count (16.2%) and decreased lymphocyte count (10.8%). No patient was ineligible for surgery due to adverse events. Conclusions: Perioperative treatment with SHR-A2102 plus adebrelimab showed promising efficacy and was well tolerated in pts with MIBC. This combination holds potential benefit even for pts with renal impairment, suggesting its clinical applicability may extend beyond cisplatin-eligible populations. These results support further investigation for SHR-A2102 plus adebrelimab in this population. Clinical trial information: NCT06879145 .

Rare histologic subtypes of triple-negative breast cancer: The impact of immunotherapy on outcomes for metastatic disease.

1120 Background: The addition of immunotherapy (IO) to chemotherapy (chemo) has significantly improved survival for patients with PD-L1-positive, metastatic triple-negative breast cancer (mTNBC), establishing chemo+IO as the standard first-line treatment in this population. However, the impact of IO on real-world outcomes of rare histologic subtypes of TNBC, such as metaplastic and lobular, as well as inflammatory presentation, are unknown. Methods: We conducted a retrospective study analyzing data from the US National Cancer Database (NCDB). Patients diagnosed with de novo stage IV TNBC who received chemo alone or chemo+IO between 2019 and 2022 (after FDA approval of IO for mTNBC) were included. mTNBC was classified as ductal, lobular, inflammatory, metaplastic, or other by the NCDB. Overall survival (OS) was assessed using the Kaplan-Meier method and multivariable Cox regression models controlled for sociodemographic and clinicopathologic factors. Results: A total of 6,711 patients with de novo mTNBC were identified (mean age 59.2 years), with a median follow-up of 19.8 months. Ductal histology was the most common (74.2%), followed by inflammatory (8.7%), metaplastic (4.5%), and lobular (3.6%) cases. Overall, 40.0% of the patients received chemo+IO. Immunotherapy use was the highest in mTNBC with inflammatory presentation (46.8%), followed by ductal (40.0%), lobular (37.5%), and metaplastic (37.2%) subtypes ( P = 0.002). Among patients who received chemo+IO, the median OS time was the longest in ductal mTNBC (30.3 months) compared to the lobular (23.5 months) and metaplastic (22.9 months) subtypes and inflammatory presentation (16.5 months) (log-rank test P &lt; 0.001). In the adjusted models, inflammatory mTNBC had a significantly higher risk of mortality than ductal cases treated with chemo+IO (adjusted hazard ratio [aHR], 1.96; 95% CI, 1.31–2.92); lobular (aHR, 1.59; 95% CI, 0.84–3.00) and metaplastic (aHR, 1.10; 95% CI, 0.44–2.71) subtypes also had a higher mortality risk, though the differences were not statistically significant due to small group sample sizes. Among patients who received chemo alone, inflammatory presentation (aHR, 2.10; 95% CI, 1.58–2.80) and lobular subtype (aHR, 1.67; 95% CI, 1.03–2.70) also had a higher risk of mortality than the ductal subtype. Conclusions: In this real-world analysis, patients with inflammatory, lobular, and metaplastic de novo mTNBC continued to experience inferior survival outcomes despite the use of chemo+IO. Our findings highlight persistent disparities in mortality outcomes and support the need for biomarker-driven strategies and dedicated clinical trials for these rare subtypes and inflammatory mTNBC.

Health-related quality of life (HRQOL) with pembrolizumab or observation for high-risk muscle-invasive urothelial carcinoma after surgery: Results from the AMBASSADOR randomized trial (Alliance A031501).

4513 Background: The AMBASSADOR trial (NCT03244381) showed that in patients with high-risk muscle-invasive urothelial carcinoma after radical surgery, adjuvant pembrolizumab for one year improved disease-free survival from 14.2 to 29.6 months (Apolo et al, NEJM 2024). Here we report the HRQOL results. Methods: HRQOL was completed by 560 randomized patients and included the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 plus the bladder cancer supplement BLM30, and the EQ-5D-5L, which assesses overall quality of life or health state. Published minimally important difference thresholds for EQ-5D-5L is 0.06, and for EORTC instruments is 5-10 points. For all reported HRQOL data, higher score is better except BLM30 urinary symptoms, where higher score indicates more symptoms. Results: Mean changes from baseline to 12 months (corresponding to end of treatment) for each HRQOL measure are summarized in the Table. No statistically significant difference was seen between the observation vs. pembrolizumab arms. Further, numerical differences between arms for these HRQOL measures do not meet (are lower than) the published minimally clinically important difference thresholds. Conclusions: Adjuvant pembrolizumab after radical surgery for patients with high-risk muscle-invasive urothelial carcinoma improved disease-free survival without negatively affecting HRQOL. These HRQOL results add further support to adjuvant immune checkpoint blockade therapy in these patients. Support: U10CA180821, U10CA180882, UG1CA189823 (https://acknowledgments.alliancefound.org). Clinical trial information: NCT03244381 . HRQOL mean change from baseline to 12 months and between-arm comparisons. A) Observation B) Pembrolizumab Difference A vs B P-value EQ-5D-5L Index Value -.029 -.012 -.02 .45 QLQ-C30 Global Health 0.07 1.45 -1.38 .55 QLQ-C30 Physical Functioning -.089 -.069 -0.02 .99 QLQ-C30 Role Functioning 3.22 -1.23 4.45 .15 BLM30 Urinary Symptoms -3.44 -3.02 -.42 .87 BLM30 Sexual Functioning -.53 4.15 -4.68 .07

A phase 1 first-in-human study of BGM-2121 in patients with advanced solid tumors.

TPS3172 Background: Parathyroid hormone-related protein (PTHrP) is a hormone frequently overexpressed in tumors such as pancreatic ductal adenocarcinoma (PDAC), lung, and head and neck cancers. In some cases, this overexpression can lead to hypercalcemia in patients with malignancies. PTHrP is a ligand of G-protein–coupled receptor (GPCR) known as parathyroid hormone type 1 receptor (PTH1R), thereby activating multiple downstream signaling pathways. Despite the significant role of GPCRs in cancer biology, therapeutic options targeting these receptors in oncology remain limited. BGM-2121 is a potent, first-in-class, humanized IgG1 monoclonal antibody targeting the N-terminal region of PTHrP, aiming to inhibit the PTHrP/PTH1R pathway. Preclinical studies exhibit high affinity and specificity for PTHrP, demonstrating robust antitumor activity in pancreatic cancer xenograft models, and significantly prolonging survival. In lung squamous cell carcinoma models, BGM-2121 was found to prevent and reverse hypercalcemia and cancer-associated weight loss, which are the key features of humoral hypercalcemia of malignancy and cachexia. Methods: BGM-2121-001 (NCT07346846) is a first-in-human, open-label, phase 1 trial designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor, anti-cachexia, and anti-hypercalcemia activity in adults with advanced solid tumors. Eligible participants are adults with histologically or radiographically confirmed advanced solid tumors who are refractory to, intolerant of, or without available standard therapies. Tumor types of primary interest include pancreatic, esophageal, head and neck, and non–small cell lung cancers, particularly sub-type of squamous cell carcinoma. Participants must have ECOG performance status ≤2 and adequate organ function. Key exclusions include active central nervous system metastases, significant cardiovascular disease, uncontrolled infections, recent anticancer therapy, prior allogeneic transplantation, active viral hepatitis or HIV infection. BGM-2121 is administered intravenously every 2 weeks in sequential dose-escalation cohorts (160, 320, 480, 800, and 1200 mg) using a standard 3+3 design. Dose-limiting toxicities are assessed during the first 28 days, and the maximum tolerated dose is defined as the highest dose at which ≤1 of 6 patients experiences a dose-limiting toxicity. Dose modifications are determined by the Safety Review Committee. Treatment continues until disease progression, unacceptable toxicity, or loss of clinical benefit. Clinical trial information: NCT07346846 .

Trends in disability-adjusted life years (DALY) from colorectal cancer in Germany: A lesson to be learned?

e22543 Background: The incidence and prevalence of colorectal cancer (CRC) is on the rise globally and consequently Disability Adjusted Life Years (DALYs) from CRC are increasing as well. This trend is particularly seen in industrialized and "first world" nations, and it is primarily linked to obesity, processed food, physical inactivity, smoking, and alcohol. We report a rather peculiar decreasing trend in DALY attributable to CRC in Germany. Methods: The data from Global Burden of Disease (GBD) study 2021 was utilized. Trends in DALYs from colorectal cancer were analyzed across various regions and countries, with particular attention to Germany. Results: Linear regression analysis and non-parametric Kendall’s tau test were carried out on the data extracted from GBD study. Linear regression showed an average annual decline of approximately 5,400 DALYs per 100,000 population (p &lt; 0.001). Non-parametric Kendall’s tau test also showed a strong negative monotonic trend (τ = −0.79, p &lt; 0.001). Overall, these findings indicate a substantial and long-term reduction in disease burden from colorectal cancer in German population over the course of study population. Conclusions: Colorectal cancer is the third leading cause of mortality worldwide. Despite the advances in screening, diagnostic and therapeutic techniques, colorectal cancer is on the rise globally. Infact, globally new CRC cases are predicted to reach 3.2 million in 2040. It is attributable to obesity, long-term smoking, and high intake of red or processed meat. This trend is expected to translate into increased mortality and consequently increased DALY. However, our study shows a decreasing trend in DALYs from CRC in Germany, which is in most part attributable to aggressive screening strategies. Screening colonoscopy was introduced into German national statutory cancer screening program in 2002. And studies have shown that the incidence of CRC decreased by 17-26 % within 10 years of introduction of screening colonoscopy. This has in turn lead to decreased mortality and decreased DALY from colorectal cancer in Germany. DALY/100000 from colorectal cancer in Germany. Year DALY/100000 1990 711506.65 1993 729678.42 1996 741107.2 1999 677952.59 2002 674754.23 2005 646214.79 2011 603322.41 2014 584135.79 2017 595793.47 2021 586274.79

Lung-MAP S1800E: A randomized phase II/III study of docetaxel and ramucirumab with or without cemiplimab for patients previously treated with platinum-based chemotherapy and immunotherapy for stage IV or recurrent non-small cell lung cancer (NSCLC).

TPS8669 Background: Integration of immunotherapy into first line systemic therapy for patients with metastatic NSCLC has led to improvement in survival, but most patients experience disease progression. Blockade of PD-1 and VEGFR2 synergistically inhibits tumor growth by reducing tumor neovascularization and leads to upregulation of proinflammatory cytokines. We hypothesize that continuing second line anti-PD-1 therapy using cemiplimab in combination with docetaxel and ramucirumab may reverse immunotherapy resistance, and lead to improved overall survival (OS) compared to docetaxel and ramucirumab. Methods: Lung-MAP is a master protocol for patients with previously treated advanced NSCLC. S1800E is a phase II/III non-match Lung-MAP substudy, in which patients are randomized 1:1 to receive either standard of care treatment with intravenous docetaxel and ramucirumab (arm A) or investigational treatment with intravenous docetaxel and ramucirumab in combination with cemiplimab (arm B). The primary objective is to compare OS between patients assigned to arm A and arm B who have acquired resistance to platinum-based chemotherapy and immunotherapy for Stage IV or recurrent NSCLC. The total enrollment goal is 378 patients based on a design with 90% power to rule out an HR = 1 at the 1-sided 2.5% level, if the true HR = 0.66. The design includes 3 interim analyses, with a safety run-in for the first 10 patients on arm B. The main inclusion criteria are patients who experienced disease progression 84 days or more following initiation of anti-PD-(L)1 immunotherapy, with complete response, partial response or stable disease as their best response, in addition to progression on or following platinum-based chemotherapy. If a known sensitizing molecular alteration for which an FDA-approved targeted therapy for NSCLC exists (e.g., EGFR, ALK, ROS1, BRAF, RET, NTRK, KRAS, HER2 , and MET sensitizing mutations), patients must have previously received at least one line of targeted therapy. Prior docetaxel is not permitted, and there is a washout of 14 days from palliative radiation (shortened to 7 days for bone radiation) and 28 days from major surgery, with no plans for concurrent systemic therapy while on the clinical trial. Patients must have adequate organ and marrow function and ECOG performance status of 0-1. S1800E was activated on 4/28/2025, with first patient registered on 5/22/2025. As of 1/6/2026, 49 of the planned 378 patients have been enrolled. Clinical trial information: NCT06616584 .