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Efficacy and safety of hetrombopag for secondary prevention of chemotherapy-induced thrombocytopenia in patients with gynecologic malignancies: A single-arm phase 2 trial.
e24185 Background: Chemotherapy-induced thrombocytopenia (CIT) is common in patients (pts) with gynecologic malignancies and may cause chemotherapy dose reductions, delays, bleeding, and compromised antitumor efficacy. Pts with prior CIT have a high recurrence risk. However, evidence on secondary prevention of CIT remains limited, especially in gynecologic oncology. This study evaluated the efficacy and safety of hetrombopag, an oral thrombopoietin receptor agonist, for preventing recurrent CIT in pts with gynecologic malignancies. Methods: This single-arm study (NCT06099925) enrolled pts with histologically or cytologically confirmed gynecologic malignancies who had ≥ grade 2 thrombocytopenia in the previous cycle and whose platelet counts (PLT) recovered to ≥ 100 × 10⁹/L through routine interventions before scheduled platinum and/or taxane-based chemotherapy. Based on an 85% historical CIT recurrence rate without prophylaxis, hetrombopag was expected to reduce recurrence to 70%; 43 pts were required (one-sided α = 0.05, 80% power), and 48 were planned allowing for a 10% dropout rate. Pts received oral hetrombopag 5 mg once daily for 10 days, starting within 24 h post-chemotherapy, with dose adjustments based on PLT. The primary endpoint was the proportion of pts with PLT < 75 × 10⁹/L during the chemotherapy cycle in which hetrombopag was administered for prophylaxis. Results: Between October 2023 and June 2025, 43 pts were enrolled. Mean baseline PLT was 209.5 × 10⁹/L (SD 99.6). During the chemotherapy cycle in which hetrombopag was administered for prophylaxis, 37.2% (95% CI, 27.9–61.9) experienced PLT < 75 × 10⁹/L, and the median duration of PLT ≥75 × 10⁹/L was 15.0 days (range 0.0, 22.0). On day 21 after chemotherapy, 74.4% had PLT ≥ 75 × 10⁹/L (95% CI, 73.9–96.9), and 55.8% ≥ 100 × 10⁹/L (95% CI, 49.0–81.4). No platelet transfusions were required, and 14.0% experienced chemotherapy delays. From the initiation of hetrombopag administration to the end of the chemotherapy cycle, mean PLT declined from day 3, nadired on day 15 (124.9 × 10⁹/L, SD 71.4), and partially recovered by day 21 (130.3 × 10⁹/L, SD 76.4). Mean nadir and maximum PLT during this period were 96.3 × 10⁹/L (SD 44.4) and 215.9 × 10⁹/L (SD 89.0), respectively. Compared with the previous chemotherapy cycle, the proportions of pts in each category of nadir PLT were lower during the current cycle (PLT < 25 × 10⁹/L: 0 vs 16.3%; 25–50 × 10⁹/L: 16.3% vs 39.5%; 50–75 × 10⁹/L: 20.9% vs 44.2%). Mean PLT before initiation of the subsequent cycle of antitumor therapy was 123.7 × 10⁹/L (SD 70.9). Hetrombopag was well tolerated, with no treatment-related adverse events. Conclusions: Hetrombopag is safe and may reduce CIT recurrence and severity, decrease platelet transfusion requirements, facilitating timely chemotherapy, representing a convenient option for secondary CIT prevention. Clinical trial information: NCT06099925 .
Prognostic value of circulating tumor DNA (ctDNA) for recurrence detection across solid tumors: A real-world meta-analysis.
11177 Background: Early detection of recurrence after curative-intent treatment is a critical priority, traditional imaging often detects relapse when disease burden is high, potentially limiting treatment efficacy. ctDNA has emerged as an established prognostic biomarker for molecular residual disease (MRD) detection and early relapse. We performed a real-world meta-analysis on published datasets that utilized personalized, tumor-informed ctDNA testing to assess its performance across tumor types and clinical management approaches. Methods: Real-world studies published from December 2022 to December 2025 using the personalized, tumor-informed Signatera ctDNA assay (Natera, Inc.) were included. Eligibility required ctDNA assessment in the MRD (2–16 weeks post-surgery (histology dependent)/pre adjuvant therapy (ACT)) and/or surveillance (post-ACT/end of the MRD window if no ACT was given) settings, with outcomes stratified by ctDNA status and hazard ratios (HR) reported from univariable or time-dependent Cox regression analysis. Exclusions included: clinical trials, biobanks, metastatic disease treated with palliative intent, case reports, reviews, editorials, or commentaries. Clinical outcomes were harmonized into a composite event-free survival (EFS) endpoint (time to recurrence, progression, or death). Pooled HRs and 95% CIs were estimated using random and fixed effects models and heterogeneity between studies was assessed using the I 2 and Cochran’s Q test. Median lead time from ctDNA-positivity to radiographic or clinical recurrence was summarized when available. Results: We identified 18 eligible publications comprising 3,004 unique patients across 15 solid tumor types. During the MRD window, ctDNA positivity was associated with a significantly increased risk of an EFS event compared with ctDNA negativity (pooled HR: 8.15; 95% CI: 6.12–10.85, I 2 = 0.00%, P = 0.844, n = 13). During the surveillance window, inclusive of post-definitive treatment, ctDNA positivity conferred an even greater EFS risk (pooled HR: 18.30; 95% CI: 14.17–23.65, I 2 = 0%, P = 0.911 for heterogeneity, n = 16). Across studies, ctDNA detection during surveillance preceded radiographic or clinical recurrence by a median of 3.20 months (95% CI: 2.50-4.10, P < 0.0001, n = 10), although this varied substantially by study/tumor type (I 2 = 80.9%). Conclusions: In this pan-cancer real-world meta-analysis, ctDNA positivity assessed using a tumor-informed assay was highly prognostic following curative-intent therapy at all timepoints evaluated with low heterogeneity between studies. These findings support the broad clinical utility of tumor-informed ctDNA testing for post-treatment risk stratification and longitudinal disease monitoring across solid tumors.
Clinician-facilitated cascade genetic testing among first-, second-, and third-degree relatives.
e13584 Background: Cascade genetic testing enables identification of individuals at increased hereditary cancer risk, yet most efforts largely focus on first-degree relatives, leaving many pathogenic variant carriers unidentified. We examined uptake of clinician-facilitated cascade testing when extended to second- and third-degree relatives. Methods: In a prospective IRB-approved clinical trial at a single academic gynecologic oncology clinic, probands with BRCA1/2 pathogenic variants were offered clinician-facilitated cascade testing. Probands provided contact information for relatives, who were then contacted by the study team via telephone. Interested relatives completed genetic counseling and were mailed no-cost saliva-based multigene panel genetic testing kits. The primary outcome was genetic testing uptake at 6 months among first-degree versus extended (second- and third-degree) relatives. Results: Between 9/2022–9/2024, 37 probands enrolled and identified 61 at-risk relatives. Fifty-one (83.6%) relatives were successfully contacted. Among relatives successfully reached, 39 (76.5%) were interested in clinician-facilitated cascade testing. Extended relatives were significantly more likely to be interested in clinician-facilitated cascade testing compared to first-degree relatives (95.0% [19/20] vs. 64.5% [20/31]; p = .02). Reasons for declining clinician-facilitated testing included prior testing (n = 2) and lack of interest (n = 9) among first-degree relatives, and lack of interest among one extended relative. At 6-month follow-up, 27/39 (69.2%) relatives completed testing, with similar completion rates across groups (first-degree: 70.0% [14/20]; extended: 57.9% [11/19]; p = 0.51). Pathogenic variants were detected in 10/27 (37.0%) relatives, including 6/14 (42.9%) first-degree and 4/11 (36.4%) extended relatives ( p = 1.00). For interested relatives, the median age was 51 (IQR 32-65), and 38.5% were female. Conclusions: Extended relatives showed high receptivity to clinician-facilitated cascade genetic testing, with comparable testing completion and pathogenic variant detection to first-degree relatives. Expanding cascade testing beyond immediate family members may represent an underutilized strategy to improve identification of individuals at hereditary cancer risk. Clinical trial information: NCT04613440 . Outcomes of clinician-facilitated cascade genetic testing for first-degree relatives and extended (second- and third-degree) relatives. Step First-degree relatives Extended Relatives Total p-value Relatives successfully contacted 31 20 51 - Interested in clinician-facilitated cascade testing 20 (64.5%) 19 (95.0%) 39 (76.5%) 0.02 Completed cascade genetic testing 14 (70.0%) 11 (57.9%) 27 (69.2%) 0.51 Pathogenic variants detected 6 (42.9%) 4 (36.4%) 10 (37.0%) 1.00 Percentages are calculated relative to the number in the row above. p-values from Fisher’s exact test.
Survivorship-focused content at the American Society of Clinical Oncology (ASCO) 2022-2024 annual meetings.
1671 Background: Survivorship is a core component of comprehensive cancer care yet its representation in major oncology scientific meetings remains unclear. This study systematically evaluated survivorship-focused content presented over three years at the ASCO Annual Meetings for prevalence, characteristics, and thematic patterns. Methods: All abstracts presented at the ASCO Annual Meeting from 2022-2024 were obtained (N=8,928). Abstracts containing the root word “survivor” (e.g., survivor, survivors, survivorship) in the title, text, or submission category “Symptoms and Survivorship” were identified using an automated data-extraction tool. Each extracted abstract underwent structured review to determine relevance to survivorship and then mapped to domains of the Quality of Cancer Survivorship Framework. Two independent reviewers evaluated each abstract, with discrepancies resolved by consensus. Descriptive statistics were used to summarize abstract content. Results: A total of 568 abstracts from 2022-2024 contained the root word “survivor” in the title, text or the submission category, representing 6.4% of all presented abstracts. Prevalence of survivorship-focused abstracts increased modestly from 2.2% in 2022 to 4.1% in 2024. Reviewers identified 63.8% of the extracted abstracts as relevant to the survivorship care framework and abstracts most frequently addressed the survivorship domains of physical effects (28.3%) and contextual factors (14.6%). Additional analyses examined cancer type and stage studied (36.6% mixed, 19.5% breast; 55.2% cancer stage not specified), survivorship stage (45% not specified, 19.3% in curative treatment), study design (65.9% observational), and healthcare setting (58.2%). Conclusions: Despite a rapidly growing population of cancer survivors, survivorship-focused content at the ASCO Annual Meeting remained largely static between 2022 and 2024, highlighting a gap between emerging survivorship needs and representation within oncology research programming. Further, abstracts frequently failed to specify the study population or context, or reference specific implications to survivorship domains. This study establishes a reproducible benchmark for monitoring survivorship content and provides a scalable methodology for ongoing surveillance of future meeting abstracts. The abstraction method may have excluded relevant survivorship-focused content. These findings could guide ASCO educational planning committees as they refine strategies to strengthen and advance survivorship-focused content in future meetings, ensuring alignment with the evolving needs of the survivor community.
Impact of medically tailored meals plus nutrition counseling on treatment adherence in vulnerable lung cancer patients: Results from NutriCare randomized controlled trial.
1672 Background: This study aims to evaluate the impact of a Food is Medicine intervention on reducing treatment interruptions among vulnerable patients with lung cancer in a multi-site randomized controlled trial (RCT). Methods: Newly diagnosed stage I-IV lung cancer patients (n=249) enrolled from four cancer centers (MD Anderson Cancer Center, The Ohio State University Comprehensive Cancer Center, Fox Chase Cancer Center, and Tufts Medical Center) were randomized to the NutriCare (intervention; n=134) or NutriTool (control; n=115) arm in a 1:1 ratio. Patients on NutriTool received a nutrition toolkit for cancer survivors and monthly nutrition information and recipes. Patients on NutriCare additionally received 6-8 months (mo) of tapered home-delivered medically tailored meals (initially 21 meals/week) plus remote nutrition counseling provided by registered dietitians. Treatment interruptions, including overall interruptions and those due to treatment toxicities, were assessed using the relative dose intensity (RDI) and number of treatment cycles with dose delay or reduction among patients receiving curative or first-line palliative treatment. The primary analysis was intention-to-treat, comparing treatment interruptions between arms using Poisson regression models. Results: The mean (SD) of RDI was 0.84 (0.26) and 0.81 (0.26) for patients on NutriCare and NutriTool, respectively (p=0.24), with approximately 31% of the NutriCare patients having RDI reduction of 15% or more compared to 38% of the NutriTool patients (p=0.36). After restricting the analyses to treatment interruptions due to toxicities, 14.4% of NutriCare versus 25.4% of NutriTool patients experienced RDI reduction of 15% or more (p=0.08). After multivariable adjustments, NutriCare patients had 16% lower risk of having RDI reduction of 15% or more (relative risk [RR]=0.84, 95% confidence interval [CI]: 0.47-1.47) and 41% lower risk of having toxicity-related RDI reduction of 15% or more (RR=0.59, 95% CI: 0.28-1.24) than NutriTool patients. For dose delays, NutriCare patients had 35% lower risk of having any dose delay (RR = 0.65, 95% CI: 0.28-1.49) and 44% lower risk of having toxicity-related dose delay (RR=0.56, 95% CI: 0.16-1.97) compared to NutriTool patients. For dose reduction, NutriCare patients had 19% lower risk of having any dose reduction (RR=0.81, 95% CI: 0.49-1.34) and 35% lower risk of having toxicity-related dose reduction (RR=0.65, 95% CI: 0.35-1.22) compared to NutriTool patients. None of the differences reached statistical significance. Conclusions: Findings suggest that a Food is Medicine intervention comprising medically tailored meals and nutrition counseling may reduce treatment interruptions among vulnerable patients with lung cancer undergoing treatment. Clinical trial information: NCT04986670 .
Mortality trends of brain tumors complicated by respiratory failure: National patterns and forecasted burden through 2035.
e14050 Background: Acute respiratory failure (ARF) represents the leading indication for intensive care unit (ICU) admission among patients with malignancy and is associated with disproportionately high mortality. Patients with primary brain tumors are uniquely vulnerable due to direct brainstem involvement, elevated intracranial pressure, and impaired ventilatory drive. However, population-level mortality trends evaluating the combined burden of brain tumors and ARF remain poorly characterized. We sought to quantify national mortality patterns and project future disease burden using contemporary U.S. surveillance data. Methods: We analyzed death certificate data from the CDC Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database from 1999–2023. Adults aged ≥45 years with brain tumors (ICD-10 C71) and respiratory failure (ICD-10 J96) listed as contributing causes of death were included. Age-adjusted mortality rates (AAMRs) per 1,000,000 population were calculated and stratified by sex, race/ethnicity, U.S. census region, state, and urban–rural classification. Temporal trends were evaluated using Joinpoint regression to estimate annual percent change (APC) and average annual percent change (AAPC). Autoregressive integrated moving average (ARIMA) models were used to forecast mortality through 2035 with diagnostic validation. Results: From 1999 to 2023, 15,035 deaths were attributed to the combined burden of brain tumors and respiratory failure. Overall AAMR increased significantly to 4.7, with an AAPC of 1.4% (95% CI: −0.0006 to 2.8; p=0.05). Forecast modeling using ARIMA (0,2,1) projected a doubling of mortality burden, with AAMR reaching 9.75 (95% CI: 3.8–15.6) by 2035 (Ljung–Box p=0.50). Men demonstrated higher mortality than women (AAMR: 5.9 vs 3.7), with rising trends observed in both sexes. Among racial groups, non-Hispanic Whites exhibited the highest burden (AAMR: 5.07). Regionally, the West demonstrated the steepest increase (AAMR: 6.6), followed by the Northeast (5.1). Large central metropolitan counties experienced the highest urban burden (AAMR: 5.04). Mississippi showed the greatest state-level mortality (AAMR: 17.1), highlighting marked geographic disparities. Conclusions: Mortality from brain tumors complicated by respiratory failure is rising nationwide and is projected to nearly double by 2035. Substantial demographic and geographic disparities persist, underscoring critical gaps in early neurologic deterioration recognition, respiratory monitoring, and ICU triage strategies. These findings emphasize the urgent need for targeted preventive interventions, optimized neurocritical care pathways, and health-system preparedness to address this rapidly expanding high-risk population.
Surufatinib combined with toripalimab for the treatment of recurrent ovarian clear cell carcinoma: Update of a prospective single center, single-arm phase II clinical trial.
5586 Background: Ovarian clear cell carcinoma (OCCC) is a histologically aggressive subtype of epithelial ovarian cancer with limited effective treatment options, particularly for recurrent disease. This study aims to evaluate the efficacy and safety of surufatinib (a kinase inhibitor targeting VEGFR 1, 2, 3, FGFR 1, and CSF-1R) in combination with toripalimab (an anti PD-1 antibody) for recurrent OCCC. Here, we present the latest efficacy and safety data. Methods: 23 patients aged 18-75 with histologically confirmed recurrent OCCC, ECOG performance status of 0-2, and failed first or subsequent-line therapy was enrolled (If the patient only had first line chemotherapy, platinum-free interval should be less than 12 months or disease progression occurred during chemotherapy). Patients received orally surufatinib 250 mg once daily in combination with toripalimab 240 mg on day 1 every 3 weeks until disease progression or unacceptable toxicity. Primary endpoint is progression-free survival (PFS), and secondary endpoints include objective response rate (ORR), overall survival (OS), and safety. Results: From Jul. 2023 to Dec. 2025, 19 patients (median age 51) were enrolled, with 52.6% (10/19) had an ECOG PS of 0, 73.7% (14/19) were classified as clinical stage of I-II. 57.9% (11/19) had received prior first-line treatment, while the remaining 8 patients had received twice or more. Eight patients had previously received bevacizumab. Among the 19 patients, 10 were platinum-resistant while 9 were platinum-sensitive. The primary metastatic sites were lymph nodes (8/19, 42.1%), lungs (6/19, 31.6%), pelvic cavity (6/19, 31.6%) and peritoneum (5/19, 26.3%). With a median follow-up of 7.1 months, the median PFS was 4.4 months (95% CI: 2.6-8.8). Tumor response was evaluable in 19 patients, with 1 complete response, 4 partial response and 11 had stable disease, resulting in an ORR of 26.3% (95% CI: 9.2-51.2%), and a disease control rate of 84.2% (95% CI: 60.4-96.6%). The most common (≥20%) treatment related adverse events (TRAEs) were hyperthyroidism (42.1%), proteinuria (36.8%), hypertension (36.8%), diarrhea (36.8%), anaemia (31.6%), rash (31.6%), increased TSH (26.3%), hypoalbuminaemia (21.1%), increased AST (21.1%) and increased ALT (21.1%). Grade 3 TRAEs (≥10%) were mainly hypertension (15.8%), increased AST (15.8%), increased ALT (10.5%). All of AEs were effectively controlled after temporarily discontinuing surufatinib or toripalimab, or reducing the dose of surufatinib, or receiving symptomatic treatment. There were no cases with fatal outcome. Conclusions: The combination of surufatinib and toripalimab exhibited potential clinical activity and tolerable toxicity in patients with recurrent OCCC. Clinical trial information: ChiCTR2400083672.
Concordance of tissue and plasma NGS in early-stage non–small cell lung cancer.
11071 Background: Comprehensive molecular profiling is standard of care for patients with advanced non-small cell lung cancer (NSCLC), and plasma-based next generation sequencing (NGS) demonstrates high concordance with tissue testing in metastatic disease. However, the performance of liquid biopsy in early-stage NSCLC remains poorly defined. In early stage, tissue-based NGS may be limited by inadequate sample quantity, low tumor cellularity, or DNA degradation. We evaluated the concordance of tissue and plasma NGS in patients with stage I to III NSCLC to determine whether liquid biopsy can reliably complement tissue-testing in this setting. Methods: We conducted a retrospective analysis of patients diagnosed with stage I to III NSCLC from 2021 to 2025 at the University of Illinois Cancer Center. Clinical and demographic data were abstracted through chart review. Paired NGS results were obtained from the Tempus Hub, including tissue-based sequencing (Tempus xT) and plasma-based sequencing (Tempus xF+). Actionable genomic alterations were assessed for concordance using 2x2 contingency tables, with calculation of overall concordance and positive percentage agreement (PPA). Results: A total of 71 patients with early-stage NSCLC were identified. The cohort was 52% male and 48% female; 61% Black, 23% White, 14% Asian and 3% other; 9% Hispanic and 88% non-Hispanic. 52% were 65 years or older at diagnosis. Disease stage included stage I (20%), stage II (10.6%), stage III (41%), with stage unknown 29%. No NTRK2/3, ROS1, RET, and MET alterations were detected on liquid or tissue. PPA for actionable mutations was low overall: BRAF V600E 66.7%, KRAS G12C 40%, EGFR 16.7%, HER2 0%, and EML4-ALK 0%. Despite low PPA, overall concordance exceeded 80% for all genes, driven by high negative percent agreement. Conclusions: In early-stage NSCLC, plasma-based NGS demonstrates limited sensitivity for detecting actionable driver alterations, despite high overall concordance driven by negative agreement. Reliance on liquid biopsy alone may miss clinically meaningful oncogenic drivers, even in potentially curable disease. While plasma NGS may be useful as a complementary or rule-out tool when tissue is inadequate, tissue-based molecular profiling remains essential for accurate genomic characterization in early-stage NSCLC. Concordance and PPA analysis. Concordance PPA BRAF V600E 91.2% 66.7% EGFR 86.0% 16.7% HER2 98.6% 0% KRAS G12C 84.5% 40% EML4-ALK 98.6% 0%
National characteristics of Kaposi sarcoma–related hospitalizations and in-hospital outcomes in the United States, 2018–2022.
e23529 Background: Kaposi sarcoma (KS) is a rare malignancy predominantly affecting immunocompromised populations and may be associated with high-acuity inpatient care. Contemporary national benchmarks describing KS-related hospitalizations and outcomes are limited. Methods: A serial cross-sectional analysis of the 2018–2022 Healthcare Cost and Utilization Project National Inpatient Sample was performed. Adult (≥18 years) hospitalizations with a principal diagnosis of Kaposi sarcoma (ICD-10-CM C46) were included; all analyses were conducted at the hospitalization level. National estimates incorporated discharge-level survey weights (DISCWT) with stratification by hospital stratum (NIS_STRATUM) and clustering by hospital (HOSP_NIS). Outcomes included annual hospitalization volume, admission type (elective vs non-elective), in-hospital mortality, length of stay (LOS), and inflation-unadjusted hospitalization cost estimated using HCUP cost-to-charge ratios. Survey-weighted analyses accounted for the complex sampling design. Results: From 2018–2022, Kaposi sarcoma accounted for an estimated 315 weighted hospitalizations nationally (unweighted n=63). Annual weighted hospitalization counts were low throughout the study period, ranging from 10 to 110 admissions per year. Most KS hospitalizations were non-elective (90.5%), indicating predominantly acute or emergent presentations. Overall in-hospital mortality was approximately 16%, with similar mortality observed among elective and non-elective admissions. Mean LOS was prolonged, ranging from 9.1 to 22.1 days across study years. Hospitalization costs were substantial, exceeding $50,000 per admission on average, with year-to-year variability and wide confidence intervals reflecting small sample size. Conclusions: Kaposi sarcoma–related hospitalizations were uncommon nationally but characterized by predominantly non-elective admissions, high in-hospital mortality, prolonged LOS, and substantial inpatient costs. Despite low absolute volumes, KS represents a high-acuity and resource-intensive inpatient condition. These findings provide national benchmarks for KS-related inpatient care and support further evaluation of care delivery strategies for this rare malignancy.
Role of circRNA in modulating tumor microenvironment: From mycobacterial infection to lung cancer.
e20025 Background: Tuberculosis (TB) is significantly associated with an increased risk of lung cancer, yet the underlying immune mechanisms remain incompletely defined. TB infection alters the lung microenvironment and profoundly affects macrophages, which are key regulators of the tumor microenvironment. PD-L1 expression is upregulated in TB and can influence macrophage polarization. Circular RNAs (circRNAs) are emerging as important regulators of immune checkpoints such as PD-L1. This study investigates whether TB-induced circRNAs regulate PD-L1 expression and macrophage polarization, particularly under cancer-cell-associated conditions that enhance the formation of a tumor-permissive microenvironment. Methods: Patients with newly diagnosed lung cancer or active TB were prospectively enrolled at Taipei Veterans General Hospital. Peripheral blood mononuclear cells (PBMCs) were collected to analyze circRNA and PD-L1 expression by RT-qPCR. In vitro, THP-1 monocytes were differentiated into M0, M1, and M2 macrophages. Macrophages were stimulated with TB lysate or ESAT-6 to model TB-induced changes. A549 lung cancer cells were co-cultured with macrophages in a transwell system to assess tumor–macrophage crosstalk. siRNA knockdown was used to evaluate the effect of specific circRNAs on PD-L1 expression. Macrophage polarization and cytokine profiles were analyzed by RT-qPCR. Results: TB stimulation increased PD-L1 expression and favored an M2-skewed macrophage phenotype. In co-culture, M2 macrophages promoted A549 cell survival and further upregulated PD-L1, whereas M1 macrophages did not. A specific circRNA (hsa_circ_0000190) was differentially expressed in TB and lung cancer patients and showed dynamic, polarization-dependent changes. ESAT-6 stimulated macrophages co-cultured with A549 cells exhibited enhanced M2 polarization and elevated circRNA expression. Knockdown of this circRNA significantly reduced PD-L1 expression, confirming its regulatory role. Conclusions: These findings support a model in which TB infection remodels the lung microenvironment via circRNA-dependent PD-L1 upregulation and macrophage reprogramming toward an M2 phenotype. The identified circRNA–PD-L1–macrophage polarization axis provides a plausible mechanistic link between TB and increased lung cancer risk and suggests a potential target for early intervention and risk stratification in TB-affected populations.
Expanded germline genetic testing of patients with hematologic malignancies to identify high proportion with hereditary cancer predisposition.
10612 Background: Identifying hereditary cancer predisposition in patients with hematologic malignancies is critical for their clinical management, surveillance, donor selection, family, and reproductive counseling. However, genetic testing for patients with hematologic malignancies has been limited, largely due to the difficulty of obtaining suitable DNA samples for germline analysis. Heme Germline-MSK-IMPACT is a clinically validated assay for germline testing using nail or saliva DNA, depending on the patient’s cancer type, in a non-invasive, rapid, and high-throughput manner, with the matched tumor analysis supporting results interpretation. Methods: Genetic testing was performed on 1300 consecutive patients with a clinical diagnosis or suspicion of a hematologic malignancy on Heme Germline-MSK-IMPACT, targeting 82 hereditary cancer predisposition genes. All individuals receiving somatic testing via paired tumor-normal sequencing on MSK-IMPACT-Heme as part of their clinical care were eligible to consent for germline analysis. Results: Germline pathogenic or likely pathogenic variants (gPVs) in hereditary cancer predisposition genes were identified in 16.7% (217/1300) of patients, with 5.8% (76/1300) having high penetrance autosomal dominant gene variants. gPVs known to be associated with hematologic malignancies were detected in DDX41 (n = 14), POT1 (n = 3), RUNX1 (n = 2), ETV6 (n = 1), TP53 (n = 1). Additionally, four patients had biallelic variants in genes causing autosomal recessive disorders that confer increased risk for hematologic malignancies ( FANCA (n = 2), ATM , MSH6 ). Other high-risk cancer predisposition genes with gPVs identified in multiple patients were BRCA2 (n = 16), BRCA1 (n = 15), MSH6 (n = 4), RTEL1 (n = 4), CDKN2A (n = 3), and PALB2 (n = 3). Moderate penetrance gPVs were detected in 6.2% (81/1300) of patients in genes such as CHEK2 (n = 36), ATM (n = 24), and LZTR1 (n = 8). Twenty-four (1.8%) patients had two or more gPVs identified. Conclusions: Germline testing in a broad cohort of individuals with hematologic malignancies detected hereditary cancer predisposition in a substantial proportion of the patients. This ratio is comparable to the rate of cancer predisposition variants identified in patients with solid tumors in recent studies. Matched tumor data analysis is ongoing to uncover second hits and correlations for improving our understanding of the hereditary contribution to hematologic malignancies.
Conditional cancer-specific survival analysis by HPV status in oropharyngeal squamous cell carcinoma.
e18128 Background: HPV-positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) is known to be associated with increased survival compared to HPV-negative (HPV-) OPSCC. However, conditional survival trends between these two subtypes have not been evaluated to date. Conditional survival provides useful prognostic information for patients who have survived following initial treatment, and may inform differential surveillance guidelines for HPV+ and HPV- OPSCC. We investigated and compared conditional survival of HPV+ OPSCC with HPV- OPSCC and relevant risk factors using a large national cancer database. Methods: We identified patients diagnosed with a single primary HPV+ and HPV- OPSCC confirmed by p16 immunotesting from 2018 to 2022 using the Surveillance, Epidemiology, and End Results (SEER) database. Demographic characteristics (race, sex, age, marital status, urbanicity), treatment modality (radiation, chemotherapy, surgery), and disease staging were collected. 4-year conditional cancer-specific survival (CSS) was calculated using competing risks analyses stratified by HPV status and disease staging. CSS hazard ratios (HR) were estimated. Results: Of 14,614 patients, 11,852 had HPV+ OPSCC and 2,762 had HPV- OPSCC. Compared to HPV- OPSCC patients, HPV+ OPSCC patients were slightly younger (mean age 61.8 vs. 62.6 years), more commonly male (87.6% vs. 77.1%), white (91.0% vs. 82.3%), married (63.3% vs. 51.3%), and more likely to present with regional disease (83.7% vs. 70.2%) rather than localized or distant disease. HPV-negative status was associated with significantly worse CSS (HR = 3.28, 95% CI = (2.99, 3.61), p<0.001) for OPSCC. Despite lower baseline survival, patients with HPV- disease and those with distant disease demonstrated larger gains in conditional CSS. Conditional CSS for localized HPV+ disease remained consistently high from 0 to 3 years post-diagnosis (96.4% to 99.7%) while localized HPV- disease demonstrated marked improvement over the same period (81.9% to 98.6%). HPV- OPSCC with distant disease at diagnosis showed the largest gain in 4-year CSS from 37.5% at diagnosis to 93.5% at 3 years after diagnosis. By 3 years post-diagnosis, conditional CSS converges across HPV status and disease stage. Conclusions: Conditional survival analysis shows that while HPV+ OPSCC has better baseline prognosis, cancer-specific survival of HPV- OPSCC patients who survive the first 3 years after diagnosis improves significantly and approaches that of HPV+ disease. However, in the initial period post-diagnosis, patients with HPV- OPSCC including those with localized disease exhibit significantly lower cancer-specific survival, suggesting that more intensive early surveillance strategies may be considered for this population. Further work is required to evaluate longer-term conditional survival patterns and additional risk factors for mortality in both HPV+ and HPV- OPSCC.
Efficacy and safety of maintenance therapy in unresectable locally advanced esophageal squamous cell carcinoma.
e16123 Background: Esophageal cancer is an aggressive malignancy and the seventh leading cause of cancer-related mortality worldwide. The majority of patients are diagnosed at an advanced stage and are thus ineligible for surgical intervention. For patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC), there is no consensus on the clinical efficacy and safety of maintenance therapy following first-line treatment. Methods: This retrospective study analyzed 204 patients with ESCC, of whom 68 received maintenance therapy and 136 were under observation. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and an exploratory analysis was performed to assess the impact of maintenance therapy duration and type on survival outcomes. Results: Multivariable Cox regression analysis demonstrated a significant improvement in overall survival (OS) with maintenance therapy (hazard ratio [HR], 0.455; 95% CI, 0.259-0.799; P = 0.006) and a trend toward improved progression-free survival (PFS; HR, 0.658; 95% CI, 0.425-1.020; P = 0.062). These findings were corroborated by a propensity score-matched sensitivity analysis. Subgroup analyses indicated OS benefits across multiple patient subsets. The most common adverse event during maintenance therapy was hypothyroidism (16.2%), which was predominantly grade 1-2. Conclusions: In patients with unresectable locally advanced ESCC, maintenance therapy is associated with a significant overall survival benefit and an acceptable safety profile.
National implementation of electronic patient-reported outcomes (ePROs) for remote symptom monitoring in oncology: The OncoPRO initiative.
1571 Background: Remote symptom monitoring with electronic patient-reported outcomes (PROs) during cancer care improves quality of life, reduces acute care events, lengthens time on treatment, and can improve survival. US oncology practices are increasingly implementing PROs, but barriers to implementation remain. To facilitate uptake of PROs, the OncoPRO Initiative was established as a national PRO learning collaborative with funding from PCORI, in partnership with ASCO, the American Cancer Society, the PROTEUS Consortium, federal agencies, practice networks, and the major EHR and PRO software vendors. Oncology practices/health systems may join OncoPRO at no cost if they are committed to implementing PROs and can submit implementation metrics for monitoring progress. Practices are sorted into “affinity groups” by EHR and PRO software systems. Affinity groups meet monthly, led by coaches from the ASCO, PRO experts, and representatives of respective technology companies. Affinity groups follow a curriculum of key topics in PRO implementation, exchange training materials and information about facilitators and experiences, and provide feedback to software vendors. Little is known on how such learning collaboratives can support PRO growth. Methods: Implementation measures and characteristics were identified to quantify progress including the total number of practices joining, the phase of these practices (early implementation, scale-up, maintenance), topic areas for support requested by practices, number of personnel trained for PRO at practices, number of patients enrolled in PRO at practices, and proportion of enrolled patients completing PRO surveys. Data were collected via direct EHR data transfers and surveys. Results: Since 3/1/2024, 23 community and academic oncology practices/health systems have joined OncoPRO, across 23 different states, among which 13 practices were in early implementation, 7 in scale-up, and 5 in maintenance. These practices were sorted into four monthly affinity groups, in which the most commonly requested topics were: personnel roles/responsibilities; workflow; patient/clinician engagement; key performance metrics; technology customization; integration with quality programs; symptom management pathways; and billing/coding. Practice participation in monthly meetings has been 100%. Data are available from 12 initial practices, which collectively enrolled 47,052 patients over their initial 15 months of the program, with 24,566 patients (52%) completing at least one PRO survey. Conclusions: The OncoPRO learning collaborative is successfully supporting practices across the US to implement PROs, with strong practice engagement and high patient participation.
Organ- and histology-specific molecular and immune landscape of metastatic breast cancer.
1024 Background: Invasive lobular carcinoma (ILC) is a distinct breast cancer (BC) subtype with dissemination patterns differing from invasive breast carcinoma of no special type (IBC-NST). While genomic differences between ILC and IBC-NST have been described, the extent to which molecular and immune profiles vary by metastatic organ and histology is poorly characterized. Methods: We conducted a retrospective analysis to evaluate organ- and histology-specific molecular features of metastatic BC (mBC). Patients with metastatic IBC-NST or pure ILC underwent NGS (592, NextSeq; WES/WTS, NovaSeq; Caris Life Sciences). Tumor mutational burden (high ≥10 mut/Mb), PD-L1 expression (22C3), and immune cell fractions (RNAseq deconvolution, quanTIseq) were assessed. Analyses were restricted to sites with ≥10 biopsies per histology. Comparisons used chi-square or Mann–Whitney U tests with multiple testing correction (q < 0.05). Results: A total of 2645 mBC biopsies (605 ILC; 2040 IBC-NST) were analyzed (Table). In ILC, ERBB2 mut frequency differed by metastatic site (q<0.01), with higher prevalence in liver (32.7%) and lower in gastrointestinal (GI) lesions (3.7%). In IBC-NST, ESR1 and GATA3 mut and FGFR1 amplification were enriched in liver metastases, whereas PD-L1 expression was highest in skin (20.7%) and lowest in liver (5.0%). No organ-specific differences were observed for PIK3CA, AKT, PTEN, BRCA1/2 or RB1 . Across metastatic sites, both ILC and IBC-NST showed differences in B cells, macrophages (M1/M2), neutrophils, NK cells, dendritic cells, CD8+ T cells, and Tregs (all q < 0.05); CD4+ T-cell differences were observed only in IBC-NST (q = 0.002). In organ-specific ILC vs IBC-NST comparisons, CDH1 mut were more frequent in ILC across sites, along with higher PIK3CA mut in skin (ILC 51.3% vs IBC-NST 34.4%) and higher ERBB2 mut in liver (32.7% vs 3.3%), whereas a higher TP53 mut frequency was observed in IBC-NST in skin (28.5% vs 52.3%) and lymph nodes (LND) (23.5% vs 55.5%) (all q < 0.01). Conclusions: mBC exhibits marked organ-specific molecular and immune heterogeneity that differs by histology. These findings support histology- and site-aware interpretation of metastatic biopsies and may inform biomarker assessment and treatment decisions in advanced disease. BC-NST ILC Skin LND Bone Breast Liver Perit. CNS q-value Skin LND Bone Breast GI Liver GYN Perit. CNS q-value N (specimens) 785 401 109 361 220 15 44 - 172 84 62 56 56 54 43 37 11 - ERBB2 mut (%) 3.2 3.1 3.2 2.3 3.3 7.1 2.5 1.0 7.1 7.4 16.4 15.4 3.7 32.7 2.4 5.7 11.1 <0.01 ESR1 mut (%) 9.4 5.2 8.3 16.0 28.2 7.1 2.4 0.0 7.8 7.2 8.9 9.8 16.7 26.0 4.9 20.0 0.0 0.9 FGFR1 amp (%) 10.1 6.6 5.6 12.8 16.5 0.0 9.7 0.02 4.4 3.4 6.7 6.1 2.4 5.6 7.7 18.5 0.0 1.0 IHC-PD-L1 (%) 20.7 - 5.3 16.0 5.0 11.1 10.3 0.02 8.9 - 5.0 5.7 6.1 0.0 0.0 0.0 14.3 1.0 TMB-High (%) 10.7 10.1 8.8 8.8 8.5 14.3 21.4 0.8 27.6 11.0 19.6 28.0 11.3 19.6 9.8 32.4 22.2 0.8 Perit: peritoneum; CNS: central nervous system; GYN: genital tract.
Neoadjuvant chemotherapy followed by transanal endoscopic surgery (TES) and selective chemoradiation or total mesorectal excision (TME) for early-stage rectal cancer: The Ottawa Hospital experience.
3627 Background: Organ-sparing therapy for early-stage rectal cancer may avoid permanent ostomy or functional disturbances commonly known as low anterior resection syndrome (LARS). TES is increasingly used for treatment of selected T1N0 or T2N0 rectal cancer. The CCTG CO.28 (NEO) phase II trial evaluated neoadjuvant chemotherapy then TES surgery for early-stage rectal cancer (Kennecke et al, JCO 2023). On the CO.28 trial, patients (pts) with post-chemotherapy ypT3N0 tumours were to have neoadjuvant chemoradiation (CRT) then TME. Pts with ypT2 or poor risk ypT1 tumours were to have TME. However, several pts insisted on organ sparing alternatives such as adjuvant CRT or active surveillance. Our approach evolved from CO.28 by incorporating more selective adjuvant CRT instead of routinely resorting to TME. Methods: This retrospective study conducted at the Ottawa Hospital evaluated the outcomes of pts with early rectal cancer treated with the NEO approach and selective adjuvant CRT. The primary outcome was 3-yr TME free survival. Secondary outcomes included safety, 3-yr disease-free survival (DFS), 3-yr permanent colostomy free survival, 5-yr overall survival (OS), pathological complete response rate (pCR), proportion of pts requiring CRT and proportion of pts with LARS at 2 yrs. Results: N = 50 pts received a NEO approach and selective adjuvant chemoradiation. N = 19 were part of the previously reported CO.28 trial and N = 31 were a consecutive cohort treated off protocol. Median age was 63 (42-83) yrs, 58% were male. Rectal location was low/mid/upper in 34%/56%/10%. Baseline T stage was T2 (76%) and T3 (10%). Neoadjuvant CAPOX (64%) or FOLFOX (36%) was completed by 88% of pts and Gr 3 AEs occurred in 31%. At TES, pCR was achieved in 32% of pts. CRT was received by 33% of pts. Median follow-up was 30.2 (2.6-86.4) months. LARS was present at 2 yr in 15%. 3-yr TME-free survival was 82% (95% C.I. 69 to 94%). 3-yr permanent colostomy-free survival was 88% (95% C.I. 78 to 99%). 3-yr DFS after all local therapy was 98% (95% C.I. 93 to 99%). One pt developed both local plus distant recurrence. 5-yr OS was 95% (95% C.I. 85 to 99%). One pt who was disease free on surveillance died of an unrelated COPD exacerbation. Conclusions: The NEO approach of neoadjuvant chemotherapy then TES combined with selective adjuvant CRT demonstrated promising organ-preservation outcomes in early-stage rectal cancer, achieving high TME-free survival. This strategy offers a meaningful alternative to routine TME, potentially reducing the risk of permanent ostomy and LARS.
Taxane-based chemotherapy with or without platinum agents in metastatic castration-resistant prostate cancer: A systematic review and meta-analysis.
e17079 Background: Metastatic castration-resistant prostate cancer (mCRPC) remains a therapeutic challenge in later-line settings following progression on standard taxane-based chemotherapy. The addition of platinum agents, particularly carboplatin, to taxane therapy may enhance treatment efficacy, though optimal combination strategies remain under investigation. Methods: We systematically searched major databases for studies comparing taxane chemotherapy with or without carboplatin in mCRPC. One phase I–II randomized trial, one retrospective cohort, and one prospective biomarker study from the United States (2019–2021) were included. Primary outcomes were overall survival and PSA response (≥50% decline). Random-effects models were used to pool odds ratios and hazard ratios with 95% confidence intervals, with heterogeneity assessed using I². Results: Three studies comprising 310 mCRPC patients (median age 68 years; male population) evaluated taxane therapy (25 mg/m² IV every 21 days for up to 10 cycles) with or without carboplatin, administered alongside mandatory prednisone. Treatment was primarily delivered in post-docetaxel or later-line settings, although chemotherapy-naive patients were permitted in the randomized trial. All patients had received prior androgen-deprivation therapy, with substantial exposure to next-generation hormonal agents. Performance status was not uniformly reported; however, patients generally had good baseline functional status (ECOG 0–1). Combination taxane-carboplatin therapy significantly improved PSA response rates ≥50% compared with taxane monotherapy (OR 2.45; 95% CI, 1.44–4.16; p = 0.0009; I² = 0%). No statistically significant difference in overall survival was observed between treatment groups (HR 0.58; 95% CI, 0.21–1.55; p = 0.28), with substantial heterogeneity across studies (I² = 79%). Hematologic toxicities were more frequent with combination therapy, including higher rates of grade ≥3 thrombocytopenia and neutropenia, while treatment discontinuation rates were inconsistently reported. Conclusions: In later-line mCRPC, adding carboplatin to taxane chemotherapy improves PSA response rates, indicating enhanced antitumor activity, but does not confer a significant overall survival benefit and increases hematologic toxicity. These findings support selective use in carefully chosen patients and underscore the need for larger randomized trials to define clinical benefit, optimal dosing, and predictive biomarkers.
A phase II study of pemetrexed and pembrolizumab in patients (pts) with recurrent and/or metastatic (R/M) salivary gland cancer (SGC): Results from the adenoid cystic cohort.
6123 Background: Pemetrexed (PTX) is safe and tolerable with responses reported in pts with R/M SGC. Given enhanced responses with PTX and pembrolizumab (PMB) for lung cancer, we hypothesized that PTX and PMB will have activity for SGC. Herein we present the efficacy results in pts with adenoid cystic carcinoma (ACC). Methods: MC200708 is a single arm phase II study of PTX and PMB in pts with R/M SGC (NCT04895735) with 2 cohorts: ACC (cohort A) and non-ACC (cohort B). Key eligibility criteria: ≥18 years, ECOG 0-1, measurable disease. Prior ICI and/or PTX was allowed. Key exclusion criteria: serious comorbidities, autoimmune disease and brain metastases. Simon’s 2-stage design was used for each cohort. Primary endpoint was overall response rate (ORR) for Cohort A but was amended to clinical benefit rate (CBR=SD+PR+CR) due to prolonged SD in several pts. Secondary endpoints: progression free survival (PFS), overall survival (OS), and toxicity. Exploratory analyses in Cohort A1 (post-amendment pts) included PSMA PET imaging and circulating PSMA extravesicles (EVs) as a biomarker. All pts received PTX 500 mg/m2 IV + PMB 200 mg IV q3 weeks until progression or treatment intolerance. Imaging was q3 cycles. Results: 20 pts (11 Cohort A + 9 Cohort A1) were enrolled from August 2021-Feb 2025. All 20 patients were eligible and received ≥ 1 cycle of treatment. Median age was 60.5 yrs, 50% male, performance status 0 (80%) or 1 (20%). 11 pts had no prior therapies (55.0%). The remaining pts had 1 (35%) or 2 (10%) prior lines of therapy. 75% of pts had no prior ICI. In Cohort A, the ORR was 0% (0 of 11). Cohort A1 met criteria for success based on CBR with 1 PR (12.5%) and 5 SD (62.5%) in the first 8 pts. For the whole cohort of 20 patients, the ORR was 5% (95% CI: 0.1-24.9) and the CBR rate was 75% (95% CI: 51-91) with 1 PR and 14 pts with SD. The duration of response for the 1 PR patient was 12.4 months. The median duration of response for the 15 pts with SD was 7.5 (2.0-29.7) months. 3 pts (15%) had PD and 2 pts (10%) went off prior to response assessment. Median cycles of treatment was 4 (2-30). In the 17 pts who discontinued, treatment was stopped in 9 (53%) for PD, 4 (23.5%) due to adverse events (AE), and 4 (23.5%) due to physician/patient preference. With a median follow-up of 14.5 months (1.5-39.2), the 1-year PFS rate is 52.1% (32.6 – 83.2%) and the OS rate is 82.1% (95% CI: 65.6 – 100%). The overall grade 3+ AE rate regardless of attribution was 80% (16/20). The most common grade 3 AEs were lymphocyte count decrease (40%), hypertension (20%), fatigue (10%), and pneumonitis (10%). 2 pts had a grade 4 AE (lymphocyte count decrease and thrombotic thrombocytopenic purpura). There were no treatment-related deaths. Analysis of correlative studies for Cohort A1 with PSMA imaging and EV biomarker ongoing. Conclusions: PTX and PMB has modest activity in pts with R/M ACC with CBR of 75% and prolonged benefit for some patients. Clinical trial information: NCT04895735 .
Personality-driven roles of large language models for axillary surgery recommendation.
e13703 Background: Large language models (LLMs) are increasingly evaluated for clinical decision support. Inclinical practice, surgical oncologists vary in decision style, tolerance of uncertainty, and willingness tocommit with incomplete information. We hypothesized that LLMs may exhibit analogous“personality” profiles with different strengths and weaknesses. Methods: Oncologic history narratives from 100 breast cancer cases with adjudicated axillary surgeries (sentinellymph node biopsy [SLNB], axillary lymph node dissection [ALND], or no axillary surgery [NONE]) wereprovided verbatim to four LLMs (Gemini-3, GPT-5.2, Claude-4.5, Grok-4). Axillary surgery details wereremoved from the input. Models were prompted to recommend upcoming SLNB, ALND, or NONE, withabstention permitted. Two epistemic regimes were tested: assumption-permissive (Arm A; inference ofunspecified negatives), and assumption-conservative (Arm B, prohibiting assumptions beyond text).Coverage cases with definitive recommendation, conditional concordance the agreement with observedsurgery among non-abstaining cases. Multi-model ensembles (3-of-4, 4-of-4) were evaluated. All datawere de-identified and analyzed under IRB. Results: LLMs demonstrated clinically distinct decision-support profiles. Gemini exhibited a “permissive generalist”profile, maintaining high coverage across regimes from Arm A to Arm B (0.96→0.92) with stableconcordance (0.62→0.64), consistent with high-throughput triage behavior. Grok demonstrated a“cautious specialist” profile, with reduced coverage (0.70→0.44) but highest concordance whencommitting (0.71→0.79), consistent with selective validation. Claude showed an “over-cautious” profile,reducing coverage (0.89→0.59) without improvement in concordance (0.40→0.39), while GPT-5.2behaved as a “defensive clinician,” with the largest coverage decline (0.82→0.23) and only modestconcordance gains (0.27→0.43). Most common miss was recommendation of NONE (34%) or ABSTAIN(31%) when SLNB was performed.Ensemble strategies did not improve performance. Both 3-of-4 and 4-of-4 agreement substantiallyreduced coverage (≤0.55 in Arm A; ≤0.21 in Arm B) without exceeding the concordance of the bestindividual models. Conclusions: LLMs exhibit clinician-like personality profiles that support role-based deployment rather thaninterchangeable use. Permissive models may be suited for high-throughput triage (pre-clinic review),cautious models for high-confidence validation (decision second check), and abstention-prone models fordocumentation gaps (escalation for human review). Although observed concordance is insufficient forautonomous clinical decision-making, these patterns provide guidance for early-stage delegation ofsubtasks, in which LLMs function as complementary teammates to surgical oncologists across themanagement spectrum.
Interim analysis of efficacy and safety of adjuvant donafenib plus transarterial chemoembolization in patients with hepatocellular carcinoma and high-risk features after curative resection.
e16251 Background: Postoperative recurrence remains a major challenge in hepatocellular carcinoma (HCC), particularly among patients with high-risk pathological features. Currently, no globally accepted standard adjuvant therapy exists after curative resection. This study reports an interim analysis evaluating the efficacy and safety of adjuvant donafenib combined with transarterial chemoembolization (TACE) in patients with high-risk HCC following surgery. Methods: This prospective, single-arm, single-center study enrolled patients with hepatocellular carcinoma who underwent curative resection and had predefined high-risk recurrence features, including tumor size > 5 cm, microvascular invasion, satellite lesions, or portal vein tumor thrombus. Patients received donafenib (200 mg BID) combined with a fixed single session of postoperative transarterial chemoembolization for a planned duration of 6 months. The primary endpoint was 12-month recurrence-free survival rate, with secondary endpoints including recurrence-free survival, overall survival, time to recurrence, and safety. This study was registered at ClinicalTrials.gov (NCT05161143). Results: As of December 10, 2025, 25 patients were enrolled, with a median follow-up of 9.7 months. High-risk features included tumor size ≥5 cm (56.0%), MVI (56.0%), satellite lesions (20.0%), and multiple concurrent high-risk factors (36.0%), and notably, the inclusion of patients with concomitant PVTT (n = 2). At data cut-off, 4 patients experienced recurrence, including one death. The 6-month RFS rate was 95.2% (95% CI, 86.6-100), and the estimated 12-month RFS rate was 74.9% (95% CI, 56.0-100); median RFS was not reached. In subgroup analyses, 12-month RFS rates were 81.5% and 66.7% in patients with tumor size ≥5 cm and < 5 cm, respectively. Patients without MVI showed a numerically higher 12-month rate than those with MVI (80.8% vs 66.7%). No stable subgroup-specific differences were observed according to satellite lesions or PVTT. Overall survival data remain immature. Treatment-emergent adverse events (TEAEs) occurred in 84.0% of patients, with grade ≥3 TEAEs reported in 36.0%. No grade 4 or 5 treatment-related adverse events were observed. ALBI scores remained stable during treatment, with no significant difference between baseline and end of treatment (median −3.12 vs −3.14, p = 0.68), indicating preserved liver function. Conclusions: This interim analysis suggests that adjuvant donafenib combined with a single session of postoperative TACE demonstrates encouraging antitumor activity and a manageable safety profile in patients with high-risk HCC after curative resection. Longer follow-up and larger studies are warranted to confirm the durability of benefit. Clinical trial information: NCT05161143 .