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Operationalizing bispecific antibody therapy in community oncology: Capturing insights on clinician preparedness for using off-the-shelf immunotherapy in lymphoma and multiple myeloma.
e23221 Background: The emergence of bispecific antibodies as off-the-shelf immunotherapy for diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and multiple myeloma (MM) has important implications for community oncologists. Guidance on implementation remains incomplete despite efforts to outline integration strategies (Crombie J et al. Blood. 2024;143:1565-157; Garfall A et al. Front Oncol. 2025;15:1630146). Assessing clinician preparedness to use bispecific antibodies can inform interventions supporting safe adoption of T-cell–engaging (TCE) immunotherapy amid evolving guidelines and regulatory approvals. To assess preparedness among community clinicians, educational programs were delivered between May 2024 and January 2026 focused on bispecific antibodies in DLBCL, FL, and MM. Methods: Interventions included 10 Project ECHO sessions, 15 meetings within US Oncology Network practices, and 3 live programs at medical congresses, with associated enduring activities. Data were analyzed through qualitative evaluation of expert-facilitated peer-to-peer dialogues to identify adoption behaviors, operational strategies, and implementation barriers. Quantitative learner assessments contextualized qualitative findings. In total, 3,059 learners participated, including hematologist-oncologists, nurse practitioners, physician associates, and oncology nurses. Results: Before intervention, most clinicians reported no or limited experience with bispecific antibodies. Proficiency in integrating bispecifics was low at baseline (37% of respondents; N = 1,524), particularly for decision-making during step-up dosing, but increased to 71% post-intervention (N = 1,215; p < 0.05). Qualitative analyses (N = 396) showed growing interest in outpatient delivery, dosing de-escalation to mitigate toxicity, and greater involvement of interprofessional team members. Clinicians also reported willingness to adopt co-management models with academic colleagues. Key challenges included complex step-up dosing logistics, limited outpatient monitoring readiness, and constrained access to supportive care resources. Conclusions: Community oncology clinicians are increasingly incorporating bispecific antibodies into routine care for patients with DLBCL, FL, and MM but continue to face logistical and skill-based implementation barriers. Community-based interventions can identify challenges limiting real-world adoption and improve clinician preparedness through interprofessional education. These findings highlight the need for education addressing operational workflows, team-based care, and real-world clinical decision-making to support broader implementation of bispecific therapies in community settings.
Indirect treatment comparison of cabozantinib vs sunitinib in the treatment of pancreatic neuroendocrine tumors.
e16327 Background: Pancreatic neuroendocrine tumors vary widely in grade, functionality, growth rate and aggressiveness. Patients are often diagnosed at a locally advanced or metastatic stage. Treatment options include surgery, somatostatin analogs, targeted therapies, radionuclide therapy, and chemotherapy. Though there is no universally accepted optimal therapy sequence, tyrosine kinase inhibitors are increasingly used for disease stabilization. Sunitinib has been shown to improve progression free survival, overall survival and objective response rate in a placebo-controlled trial and more recently cabozantinib has also been shown to improve progression free survival. No direct head-to-head comparison between these two agents has been performed in a trial setting. Methods: Data pertaining to the CABINET (cabozantinib vs. placebo) and NCT00428597/SUN1111 (sunitinib vs. placebo) clinical trials was analyzed; Hazard ratios for progression free survival for these trials were extracted along with 95% confidence intervals. CABINET was a phase 3 randomized double-blind placebo controlled clinical trial with 2:1 randomization with 2 cohorts - extrapancreatic neuroendocrine tumors and pancreatic neuroendocrine tumors. NCT00428597 was a phase 3 randomized double-blind placebo controlled clinical trial with 1:1 randomization. For the CABINET trial, only data pertaining to the pancreatic neuroendocrine tumor cohort was included. The placebo arm was used as the common comparator. Baseline patient population characteristics were compared along with treatment emergent adverse events. Hazard ratios for progression free survival were compared using the Bucher method for indirect comparison. Upper and lower limits of the 95% confidence intervals were also calculated. Results: Indirect treatment comparison of the progression free survival between cabozantinib and sunitinib yields a HR of 0.55 indicating superior efficacy of cabozantinib. However, this result is not statistically significant (95% CI 0.25 to 1.25). Both medications have significant toxicities; although cabozantinib has been noted to have more frequent grade 3+ toxicities, common dose reductions, and discontinuation, it appears to have better efficacy. This result is pertinent as cabozantinib appears to be active in patients who are previously treated with sunitinib. Adjustment for baseline characteristics of the state populations did not significantly alter the results. Conclusions: Indirect treatment comparison of cabozantinib and sunitinib in the treatment of pancreatic neuroendocrine tumors appears to show superior efficacy of cabozantinib. Given the significant side effect profile of cabozantinib, it may be worthwhile to consider a head-to-head study between sunitinib and a lower dose of cabozantinib to establish the efficacy of cabozantinib with the possibility of a lower side effect profile.
First-in-human study of DM005, an anti-EGFR/c-MET bispecific antibody-drug conjugate, in patients with advanced solid tumors.
8530 Background: DM005 is a bispecific ADC (BsADC) conjugated to BLD1102, a linker/payload system composed of a linker and a DNA topoisomerase I inhibitor (BCPT02), targeting EGFR and c-MET with an average DAR value of 4. EGFR and c-MET are highly co-expressed in NSCLC, SCLC, HNSCC, breast cancer, gastric cancer, colorectal cancer, and some other solid tumors, for which DM005 has demonstrated robust anti-tumor activity in PDX/CDX models. Methods: This is a First-in-human dose-escalation study (NCT 06515990). Patients (pts) with advanced solid tumors received DM005 by IV administration from 0.5 to 6.5 mg/kg Q3W. The classical “3+3” design was utilized to evaluate safety, tolerability and preliminary efficacy. Tumor response was evaluated by the Investigators based on RECIST v1.1. A Safety Monitoring Committee (SMC) was established to determine the dose levels, dose regimen, and the maximum tolerated dose (MTD)/ recommended dose for expansion (RDE). Results: As of 2 Jan 2026, a total of 45 pts from China, United states of America and Australia were enrolled and received ≥1 dose of DM005 across 8 dose cohorts. Median age was 59 years (range 40-76). Baseline ECOG scores were 0 (n = 7), 1 (n = 38) with all pts progressed after an average of 3 (range 1-7) prior lines of available standard therapy. There were no dose limiting toxicities (DLT) observed up to 6.5 mg/kg. The MTD was not reached. Thirty-six pts (80%) experienced treatment-related adverse events (TRAEs), the most common TRAEs (≥10%) including: nausea (28.9%), anemia (28.9%), fatigue (26.7%), decreased appetite (26.7%), leukopenia (20%), aspartate aminotransferase increased (15.6%), lymphopenia (13.3%), constipation (11.1%). Most TRAEs were Grade 1-2 and Grade ≥3 TRAEs reported in 10 pts (2 lymphopenia, 1 neutropenia, anemia, leukopenia, nausea, stomatitis, vomiting, fatigue, pain, urinary tract infection, hypoxia, hypotension). No ILD or Infusion reaction were observed. Among 32 patients evaluable, there were 8 PRs, including 1pt with NSCLC EGFR-mutant (NSCLCm) at 3.3 mg/kg, 4 pts with NSCLCm and 1pt with SCLC at 4.2 mg/kg, and 1pt with NSCLCm and 1pt with NSCLC EGFR wildtype (NSCLCw) at 5.2mg/kg, and 14 pts with stable disease (SD). In the 3.3/4.2/5.2 mg/kg dose groups, a total of 13 NSCLCm pts underwent imaging tumor assessment, with 6 subjects achieving PR, and 5 subjects achieving SD. The unconfirmed objective response rate (ORR) is 46.2%, and the disease control rate (DCR) is 84.6%. Conclusions: DM005 is safe and tolerable up to 6.5 mg/kg dose level. In both NSCLCm and NSCLCw pts, and SCLC pts, DM005 has demonstrated an encouraging efficacy with a manageable safety profile. The putative RDE ranges from 4.2 to 6.5 mg/kg which will be further evaluated in phase II trials. Clinical trial information: NCT06515990 .
Characterization of genomic alterations between local breast cancers and cutaneous metastases.
1038 Background: Cutaneous metastases (CM) are a distinct manifestation of advanced breast cancer (BC), yet their genomic alterations (GA) relative to primary tumors are incompletely defined. In this study, we aimed to identify similarities and differences between GA in local BC and CM. Methods: Local BC and CM were profiled by comprehensive next-generation sequencing (FoundationOne CDx). Genomic biomarkers included tumor mutational burden (TMB), microsatellite instability (MSI), homologous recombination deficiency signature (HRDsig), reported as a laboratory professional service, and GA prevalence. Odds ratios (ORs) for enrichment in local BC versus CM were calculated using Fisher’s Exact Test with false discovery rate (FDR) correction. Results: Across 14,769 BC and 1,731 CM cases, most had TMB-low (<10 mutations/Megabase; 94% vs 90%), were not MSI-high (99%), and were HRDsig-negative (83% vs 87%), respectively. Among BC cases, the most prevalent GA included TP53 (54.1%), PIK3CA (34.5%), MYC (20.9%), RAD21 (19.0%), CCND1 (16.7%), and recurrent 11q13/8p12 amplicon–associated genes ( FGF19 , FGF3 , FGF4 , NSD3 , ZNF703 , and FGFR1 ; each 13–15%). Among CM cases, the most prevalent GA included TP53 (48.4%), PIK3CA (37.6%), MYC (22.7%), and RAD21 (20.0%), and also CDH1 (18.8%) and ESR1 (12.5%). Multiple genes differed significantly in prevalence between BC and CM, including enrichment of ESR1 , CDH1 , NOTCH1 , MAP3K1 , CTNNA1 , CBFB , NFE2L2 , AKT1 , BRAF , and GATA4 in CM, and higher frequencies of TP53 , MCL1 and KDM5A in BC biopsies (Table 1). In addition, several therapeutically relevant GA were observed at lower but clinically meaningful frequencies between BC and CM, such as alterations in the PI3K/AKT pathway beyond PIK3CA , including AKT2 (1.8% vs 2.4%), AKT3 (3.2% vs 3.6%), and PTEN (13.1% vs 13.0%); DNA damage repair genes, including BRCA1 (3.9% vs 2.7%), BRCA2 (4.1% vs 3.9%), PALB2 (1.1% vs 0.8%), RAD51 ( RAD51B/C/D combined 1.3% vs 1.1%), ATM (2.6% vs 1.9%), ATR (0.9% vs 0.7%), CHEK1 (0.1% vs 0%), and CHEK2 (1.5% vs 2.2%); and additional potentially actionable GA, such as the MTAP (4.0% vs 3.8%), SMARCA4 (1.0% vs 0.8%), CCNE1 (4.2% vs 5.3%), and ERBB2 (11.1% vs 11.3%) genes in local BC and CM biopsies, respectively. Conclusions: CM largely retain the GA profile of local BC, but may exhibit distinct enrichment of alterations in estrogen signaling, likely from selective pressure, cell adhesion, possibly due to more frequent lobular CDH1 -mutated BC involving skin, and oncogenic pathways. A substantial proportion of both BC and CM samples harbor targetable GA, underscoring opportunities for precision therapy not only in advanced disease, but also in early stages. Clinically significant genes with significant differences between local BC and CM. Gene BC (%) CM (%) Odds Ratio (CM vs BC) p-value (FDR adjusted) TP53 54.1 48.4 0.79 <0.001 CDH1 11.4 18.8 1.80 <0.001 ESR1 4.7 12.5 2.89 <0.001 AKT1 4.7 6.3 1.38 0.046
Scrambler therapy for painful chemotherapy-induced peripheral neuropathy: Extending the evidence base.
e24147 Background: Chemotherapy-induced peripheral neuropathy (CIPN) burdens patients. Six months after treatment, the incidence of CIPN ranges from 30-40%. Immunotherapies are less likely to cause peripheral neuropathies. The emergence of CIPN during treatment may require chemotherapy dose decrements, premature discontinuation of therapies, deconditioning, increased fall risk and other problems associated with increased morbidity and mortality. Medications for CIPN have limited efficacy. Methods: Scrambler Therapy was provided to 52 patients for CIPN-associated pain. Electrode pairs were placed along the sensory dermatome pathways linked to the areas of painful symptoms. Scrambler sessions lasted 35 minutes. Patients rated their pain before and after each Scrambler session on a 0-10 Visual-Analog Scale (VAS). Results: 1) 64% of patients were responders, defined as 30% or greater improvement in their pain scores. 52% of patients had 50% or more pain relief. 37% of patients were nonresponders, defined as 0-30% relief. 2) On average it took 4 sessions to achieve 30% improvement in pain. 3) Some statistically significant differences in analgesic response to Scrambler existed among groups based on what chemotherapy agent(s) they had received. Platinum-only patients demonstrated the least response, whereas patients who had received vinca alkaloids, only taxanes, and proteasome inhibitors showed the greatest magnitude relief. Conclusions: Our findings confirm and extend previous studies suggesting that Scrambler Therapy can be an efficacious treatment approach for painful symptoms of CIPN. Demographic and treatment characteristics of patients undergoing Scrambler Therapy for CIPN. Non-responders Partial Responders Full Responders Total Age 65 and over 11 (39.3%) 3 (10.7%) 14 (50%) 28 Under 65 8 (33.3%) 3 (12.5%) 13 (54.2%) 24 All ages 19 (36.5%) 6 (11.5%) 27 (52%) 52 Sex Male 11 (39.3%) 3 (10.7%) 14 (50%) 28 Female 8 (33.3%) 3 (12.5%) 13 (54.2%) 24 Baseline pain rating 4.8 ± 1.6 5.7 ± 1.2 5.6 ± 2.0 F = 1.0,P = 0.38 ST sessions completed 7.2 ± 2.7 7.2 ± 2.7 8.4 ± 2.1 F = 1.1,P = 0.34 Chemotherapy agent Platinum only 7 (58.3%) 2 (16.7%) 3 (25%) 12 Folate antimetabolites/vinca alkaloids/alkylating agents & stem cell 1 (9.1%) 2 (18.2%) 8 (72.7%) 11 Platinum and taxane 4 (40%) 0 6 (60%) 10 Proteasome inhibitors 2 (22.2%) 1 (11.1%) 6 (66.7%) 9 Immunotherapies 3 (50%) 1 (16.7%) 2 (33.3%) 6 Taxane only 1 (33.3%) 0 2 (66.7%) 3 Other 1 (100%) 0 0 1 Cancer diagnosis Blood/Myeloma 4 (25%) 2 (12.5%) 10 (62.5%) 16 Breast/Male breast 3 (30%) 1 (10%) 6 (60%) 10 Alimentary tract 3 (33.3%) 2 (22.2%) 4 (44.5%) 9 Genital/Urinary 2 (40%) 0 3 (60%) 5 Lung 3 (75%) 1 (25%) 0 4 Lymph/Thymus 1 (25%) 0 3 (75%) 4 Head & Neck 2 (100%) 0 0 2 Muscle 0 0 1 (100%) 1 Skin/Melanoma 1 (100%) 0 0 1 For the variable “baseline pain rating” and “ST sessions completed”, last column includes the ANOVA test statistic and p-value for the group comparison.
Development and multicenter validation of a machine learning framework for predicting severe myelosuppression in nasopharyngeal carcinoma: Evidence from large-scale real-world data and prospective clinical trials.
6023 Background: Severe treatment-related myelosuppression (Tr-MS) in nasopharyngeal carcinoma (NPC) necessitates dose reductions, compromising survival. Current static models rely on baseline "snapshots," failing to capture dynamic bone marrow fluctuations. We developed a dynamic deep learning system using longitudinal real-world data to predict cycle-specific Tr-MS risk. Methods: We analyzed 103,919 longitudinal records from 12,065 NPC patients (Nanfang/SYSUCC). A rolling-window strategy incorporated dynamic pre-dose labs, prior-cycle nadirs, and cumulative exposure to predict Grade ≥3 Tr-MS (CTCAE v6.0). Models (Logistic/XGBoost/LightGBM/TabPFN) were trained (6:3:1 split) and validated in two independent external cohorts (n=197) and three prospective trials (NCT03919552, NCT06767488, NCT06017895; n=173). The model was deployed as an EHR-integrated tool for automated real-time risk stratification. Results: Dynamic models demonstrated robust discrimination across all validation hierarchies (Table). In internal validation, AUCs ranged from 0.84 to 0.96. Performance remained stable in external cohorts (AUC 0.75-0.87) and prospective trials (AUC 0.79-0.86). SHAP analysis identified cumulative chemotherapy dosage and prior-cycle nadirs as dominant risk factors. Notably, the HIS-integrated tool successfully automated data retrieval, eliminating manual entry burden. Conclusions: This first EHR-integrated, cycle-specific dynamic system for Tr-MS in NPC captures longitudinal marrow exhaustion, enabling a shift from reactive rescue to precise, proactive prevention. Performance of dynamic prediction models across validation cohorts. Endpoint Cohort AUC (95% CI) Sens Spec Anemia Internal (n=1,231) 0.96 (0.96-0.98) 0.91 0.91 Anemia External (n=197) 0.87 (0.85-0.89) 0.89 0.86 Anemia Prospective (n=173) 0.86 (0.82-0.89) 0.88 0.86 PLT Internal (n=1,231) 0.90 (0.87-0.92) 0.79 0.84 PLT External (n=197) 0.80 (0.77-0.81) 0.81 0.82 PLT Prospective (n=173) 0.81 (0.80-0.83) 0.80 0.83 WBC/Neut Internal (n=1,231) 0.84 (0.82-0.85) 0.71 0.79 WBC/Neut External (n=197) 0.75 (0.73-0.77) 0.69 0.77 WBC/Neut Prospective (n=173) 0.79 (0.77-0.81) 0.69 0.78 Abbreviations: AUC, area under the ROC curve; PLT, thrombocytopenia; WBC/Neut, leukopenia/neutropenia; Sens, sensitivity; Spec, specificity.
Urinary creatine riboside for risk stratification of clinically significant prostate cancer.
e17149 Background: Distinguishing clinically significant prostate cancer from indolent disease remains a major challenge in prostate cancer diagnosis and contributes to unnecessary biopsy and overtreatment. Prostate-specific antigen (PSA) testing, while widely used, has limited specificity for clinically significant disease and provides limited information for individualized risk assessment. Creatine riboside is a tumor-associated urinary metabolite previously linked to aggressive prostate cancer biology. We evaluated whether urinary creatine riboside could provide clinically interpretable risk stratification for clinically significant prostate cancer using a likelihood-ratio–based framework designed to complement existing diagnostic approaches and inform decision-making beyond PSA alone. Methods: Urinary creatine riboside concentrations were quantified using targeted liquid chromatography–mass spectrometry in men undergoing evaluation for prostate cancer. Clinically significant prostate cancer was defined according to standard pathological criteria. Risk strata were prespecified using percentile thresholds derived from the empirical distribution of urinary creatine riboside concentrations. Diagnostic performance across strata was evaluated using sensitivity, specificity, and positive likelihood ratios (LR+), interpreted according to established clinical benchmarks to define low-risk, intermediate-risk, and high-risk categories. Results: Urinary creatine riboside concentrations were higher among men with clinically significant prostate cancer than among those without. Diagnostic discrimination increased progressively across ascending percentile thresholds. Lower-risk strata were associated with minimal changes in post-test probability (LR+ approximately 1–2), consistent with low-risk classification. Intermediate-risk strata demonstrated moderate enrichment of risk (LR+ approximately 2–5). At higher percentile thresholds, urinary creatine riboside demonstrated strong rule-in performance, with LR+ values exceeding 10 and reaching greater than 30 at the highest thresholds. This likelihood-ratio–based framework enabled clear separation of patients into clinically actionable low-risk, intermediate-risk, and high-risk categories using a single noninvasive biomarker. Conclusions: Urinary creatine riboside enables robust, likelihood-ratio–based risk stratification for clinically significant prostate cancer, providing clinically interpretable decision support beyond PSA. This approach has the potential to reduce unnecessary biopsies while improving identification of aggressive disease and advancing precision prostate cancer diagnostics.
National analysis of cancer care for refugees in Moldova during the war in Ukraine (2022–2025).
1602 Background: Following Russia's invasion of Ukraine in February 2022, Moldova, a non-EU country of 2.3 million, had one of Europe's highest refugee-to-population ratios (6.4%). To meet refugee cancer care needs, the Institute of Oncology and Moldova's Ministry of Health (MOH) established a multi-sectoral financing model with the International Organization for Migration (IOM) and the Blue Heron Foundation (BHF), an American NGO. Refugee patients received a free MOH-funded consultation and access to screening and early detection. Diagnostic tests were then funded by IOM and treatment costs covered by BHF for the initial 15 months of the war, after which all services were reimbursed by IOM-led projects. Methods: We conducted a retrospective review of Ukrainian refugee cancer patients at Moldova's main oncology centers from May 1 2022 to July 30, 2025, with near complete national data. We analyzed demographics, diagnoses, diagnostic tests and treatments, and per-patient costs adjusted for PPP. Results: Of 1,398 Ukrainian refugees evaluated with suspicion of cancer, 681 (48.7%) were diagnosed with malignancy. 412 unique patients (60.5%) remained to receive medical services in Moldova. Among these, 391 were seen at the Institute of Oncology, 25 at Medpark International Hospital (including 7 seen at both institutions), and 3 at Republican Clinical Hospital. The cohort included 221 women (53.6%) and 191 men (46.4%) with an average age at presentation of 58.8 (range 5 – 88 years-old). The most common malignancies were breast (n=71, 17.2%), urological (n=62, 15%), colorectal (n=51, 12.4%), head and neck (n=40, 9.7%), and gynecological cancers (n=38, 9.2%). 292 patients (70.9%) had locoregional disease, 82 (19.9%) were metastatic, and 38 (9.2%) were unstaged. Diagnostic tests over 39 months included 400 CT scans, 70 bone scans, 69 MRIs, 5 PET-CTs, 83 mammograms, 129 endoscopies, and 20,265 lab tests. 326 (79.1%) received treatment, including 203 surgeries, 695 chemotherapy administrations, and 46 radiotherapy courses. Total costs for diagnostics and treatments covered by IOM and BHF at the Institute of Oncology were available for 305 patients, amounting to 9,943,111 MDL, equivalent to $552,782 USD at an average exchange rate of 18.02 MDL/USD. This corresponds to a mean cost of $1,812 per patient, or $4,502 per patient in purchasing-power-adjusted (PPP) international dollars, using a Moldova PPP conversion factor of 7.24. Conclusions: This analysis shows that comprehensive cancer care for refugees in resource-limited settings is possible via rapid partnerships among different sectors. Moldova’s model offers replicable lessons for other nations facing similar humanitarian challenges. However, to this day, refugees continue to depend on humanitarian donors such as IOM for cancer services, highlighting the need to develop sustainable financing mechanisms that move beyond emergency response.
Prognostic stratification of early-stage NSCLC patients using preoperative circulating tumor DNA (ctDNA).
8031 Background: Curative-intent surgery for early-stage non-small-cell lung cancer (NSCLC) is followed by relapse in approximately 20–30% of patients. We previously reported interim results of the prospective MUSETALK-Lung01 study (multiomics sequencing technique application kick-start), showing that pre-operative, ctDNA positivity predicted increased relapse risk. Here we present the final analysis of the full cohort and incorporate pathological risk factors to conduct a more comprehensive prognostic evaluation for early-stage NSCLC. Methods: The MUSETALK-Lung01 study is a prospective, longitudinal, observational study designed to evaluate the clinical utility of a tumor-naïve ctDNA assay in patients with early-stage NSCLC. Cell-free DNA (cfDNA) was extracted, and subjected to CanCatch Surf test as described previously. The assay algorithm reports both the ctDNA detection status (positive/negative) and the estimated ctDNA levels. Longitudinal data, including vital status, treatment, relapse, and survival status, were collected over 5 years. The study was approved by the institutional review board or ethics committee at each site, with all participants providing written informed consent. Results: The complete cohort of MUSETALK-Lung01 consisted of 455 early-stage NSCLC patients, among whom the median follow-up time was 63 months, with a 2-year recurrence rate of 7.0% and a presurgical ctDNA positivity rate of 6.4%. To identify clinical and biological factors associated with survival, both univariate and multivariate analyses were performed. Presurgical ctDNA positivity was strongly associated with inferior recurrence outcomes (χ 2 p < 1 x 10 -9 ), indicating that tumor burden can be prognostic beyond clinical stage and pathological conditions. Specifically, among clinical stage I lung adenocarcinoma (LUAD) patients, ctDNA detection demonstrated robust prognostic stratification for recurrence risk (2-year RFS: 60% [95% CI: 40%–91%] vs. 96% [95% CI: 94%–98%]; log-rank p < 1 x 10 -7 ). Similar prognostic value of ctDNA was observed in stage II-IIIA LUAD patients, albeit with reduced discriminative power (log-rank p < 0.01). After incorporating pathological information, the performance of prognostic stratification was further improved. Conclusions: By evaluating ctDNA abundance, we provide highly sensitive and specific prognostic assessments and risk stratification for early-stage NSCLC patients. The non-invasive, nature of this test enables precision peri-operative management and selection of patients who may benefit from innovative treatments, with the potential to improve survival.
Dual-microbial signature as a predictor of postoperative colorectal cancer recurrence.
3611 Background: Current surveillance strategies for postoperative recurrence in colorectal cancer predominantly depend on tumor markers, imaging modalities, and endoscopic procedures; however, these approaches are challenged by suboptimal diagnostic accuracy. Consequently, the identification and validation of novel biomarkers represent an urgent clinical necessity. Sensitive microbiome-based approaches for postoperative risk stratification, surveillance optimization, and early recurrence detection may substantially influence clinical decision-making and resource allocation for colorectal cancer patients. Methods: This cohort study included CRC fecal and tumor samples from four independent cohorts (n = 615) in the Fudan University Shanghai Cancer Centre (Shanghai, China) between January 2017 and December 2020, with follow-up through December 2024. Fecal samples from the discovery (n = 250), training-validation cohorts (n = 153), as well as tumors with paired adjacent normal tissues from the investigation cohort (n = 244), were subjected to multi-omics analyses. We developed prediction models of disease-free survival by additionally incorporating dual-microbial signature including the abundance of Roseburia and Bifidobacterium. Both models were evaluated by internal validation cohort, and visual nomograms of prediction models were constructed accordingly. Results: We found that the combined high abundance of Roseburia and Bifidobacterium was associated with favorable outcomes (P = 0.039), especially in male (P = 0.018) and early-onset colorectal cancer (P = 0.047). Integration of clinical variables with a dual-microbial signature achieved a mean AUC > 0.8 for recurrence prediction. A high combined abundance of Roseburia and Bifidobacterium was linked to reduced enrichment of primary bile acid biosynthesis pathways and increased enrichment of propanoate metabolism pathways. Conclusions: This study proposes a novel strategy for CRC recurrence risk assessment and highlights the potential of gut microbiota as a tertiary preventive approach in CRC management. However, the proposed model has not yet been implemented in clinical practice and requires validation in large, multicenter prospective cohorts before clinical translation.
Impact of pathologic necrosis on clinical outcomes following neoadjuvant radiation for soft tissue sarcoma.
e23565 Background: Tumor necrosis is a common pathologic finding in soft tissue sarcomas (STS) following neoadjuvant therapy, yet its prognostic significance and associated factors remain incompletely understood within orthopedic oncology. This study examined the relationship between the extent of tumor necrosis and clinical outcomes and identified factors associated with necrosis percentage in patients with STS. Methods: We retrospectively analyzed 64 patients with STS who underwent surgical resection following neoadjuvant therapy (2020-2023). Patients were stratified into two groups based on pathologic tumor necrosis: high necrosis (≥75%, n = 32, mean 93.6%) vs minimal necrosis ( < 75%, n = 32, mean 26.8%). Demographics, tumor characteristics, radiation parameters, and surgical outcomes were compared between groups. Primary outcomes included local recurrence, distant metastasis, and mortality. Results: The two groups were similar in demographics, tumor characteristics, radiation therapy parameters, and surgical outcomes. Patients with high necrosis had statistically significantly higher rates of current/former smoking (46.9% vs 21.9%; p = 0.041). No significant correlations were found between necrosis percentage and age (p = 0.742), BMI (p = 0.241), comorbidity index (p = 0.757), tumor size (p = 0.295), or any radiation parameters (dose p = 0.911, fractions p = 0.625, timing between last radiation dose and surgery p = 0.960). A paradoxical pattern emerged in clinical outcomes: high necrosis was associated with lower local recurrence (12.5% vs 25.0%, p = 0.337) but higher distant metastasis (46.9% vs 25.0%, OR = 2.647, p = 0.117) and mortality (25.0% vs 12.5%, OR = 2.333, p = 0.337). While these outcome differences did not reach statistical significance, they represent clinically meaningful trends suggesting nearly 2-fold increased risk of systemic disease progression in high necrosis tumors. Conclusions: In this cohort of STS patients treated with neoadjuvant therapy, smoking history was significantly associated with tumor necrosis extent. Extensive necrosis demonstrated a paradoxical relationship with outcomes, associated with better local control but worse systemic disease progression. This suggests that while high necrosis may reflect effective local treatment response, it may also indicate more aggressive underlying tumor biology with a propensity for distant metastasis. These findings highlight that extensive necrosis should not provide false reassurance, and patients with high necrosis may benefit from continued surveillance for metastatic disease.
Anti–PD-1 immunotherapy with chemotherapy for poorly chemo-responsive thyroid and salivary gland tumors: The iPRIME study.
6124 Background: Clinical trial data guiding treatment of unresectable or metastatic salivary and thyroid gland cancers are limited. While targeted therapies have advanced management for selected patients, chemotherapy remains a treatment strategy for those with aggressive disease biology. Anti-PD1 therapy has shown antitumor activity in advanced, PD-L1 positive salivary and thyroid gland cancers, underscoring the need to evaluate the synergistic activity of PD-1 blockade with cytotoxic chemotherapies in these neoplasms. Methods: The iPRIME (NCT03360890) is a single center, parallel two cohort trial evaluating pembrolizumab with cytotoxic chemotherapy in patients with advanced salivary gland and thyroid cancers. Eligible patients had histologically confirmed disease that was unresectable and not amenable to curative intent therapy. Patients received pembrolizumab 200 mg IV with docetaxel or doxorubicin 75 mg/m2 for 2-6 cycles, followed by pembrolizumab monotherapy for up to 2 years. Docetaxel or doxorubicin could be reintroduced upon disease progression while on pembrolizumab or after the 2-year treatment period. The primary endpoint was response rate. Secondary endpoints included progression free survival (PFS), overall survival (OS), disease control rate, and adverse events. Results: A total of 39 patients (27 salivary and 12 thyroid cancer) were enrolled between 2018-2022. Mean age was 61 in salivary and 71 in the thyroid cancer, with 48% and 58% female patients, respectively. Salivary gland cancer histologies included adenoid cystic 15/27 (56%), ex-pleomorphic 18%, mucoepidermoid 7.4%, acinic cell 7.4%, salivary duct 7.4%, basaloid adenocarcinoma 3.7%. In the salivary gland group, the overall response rate was 25.6% (7/27; 90% CI 12.9%-43.2%), and the disease control rate was 89% (24/27; 90% CI 73.7%-96.9%). The overall response rate in the adenoid cystic patients was 27% (4/15). Median PFS was 8.6 months (90% CI: 6.0 to 12.4), including 8 months in adenoid cystic patients (90% CI: 6.0-16.7%) and 7.8 months in the non-adenoid cystic cases (90% CI: 3.8-14.6), with one and two-year PFS rates of 37% and 8.2%, respectively. Median OS was 25.5 months in the adenoid group (90% CI:8.5-32) and 22.9 months in the non-adenoid group (90% CI: 7.8-78) (p=0.26). One, two, and five-year OS rates in the salivary cohort were 66%, 50%, and 23%, respectively. In the thyroid cohort, the response rate was 16.7% (2/12), with both PR. Grade 4 events occurred in nine patients salivary patients and one grade 5 event was observed. Conclusions: The combination of pembrolizumab and cytotoxic chemotherapy did not substantially change antitumor control activity relative to historical controls in patients with advanced salivary or thyroid cancers. There were no statistically significant differences in PFS and OS between adenoid cystic and non-adenoid cystic subtypes. Clinical trial information: NCT03360890 .
Does neoadjuvant chemotherapy reduce axillary lymph node dissection in postmenopausal ER+/HER2 <i>−</i> breast cancer?
e12634 Background: The role of neoadjuvant chemotherapy (NAC) in postmenopausal estrogen receptor–positive/human epidermal growth factor receptor 2–negative (ER+/HER2−) breast cancer is debated. These tumors are typically less chemo-sensitive, with low rates of nodal pathologic complete response. Despite this, abnormal imaging findings may prompt escalation to NAC in patients with limited nodal disease. We evaluated whether NAC in this population meaningfully reduces the need for axillary lymph node dissection (ALND). Methods: We performed a retrospective analysis of postmenopausal ER+/HER2− breast cancer patients treated at a single institution between 2023 and 2025. Inclusion criteria included baseline cN1 disease defined by axillary ultrasound. The primary endpoint was the rate of ALND avoidance, defined as successful downstaging to SLNB alone, compared between patients treated with NAC versus upfront surgery. Statistical comparisons were performed using Fisher’s exact tests. All analyses were conducted using R version 4.5.3 (RStudio). Results: Of 292 eligible patients, 55 (19%) presented with ultrasound-defined cN1 disease. Among this cN1 cohort, 36 (65%) proceeded to upfront surgery without receiving NAC while 19 (35%) received NAC. Among patients who did not receive NAC, 25 (69%) underwent SLNB alone while 11 (31%) required ALND. Paradoxically, the NAC cohort had a higher rate of requiring ALND compared to the upfront surgery group (58% [11/19] vs. 31% [11/36]; p=0.08; Table 1). Successful surgical de-escalation (SLNB alone) was achieved in only 42% of the NAC group compared to 69% of the non-NAC group. Conclusions: In postmenopausal ER+/HER2− breast cancer with limited nodal disease, the use of NAC does not reliably translate into avoidance of ALND. These findings raise concern for imaging-driven escalation of neoadjuvant therapy without consistent surgical de-escalation and highlight the need for more selective use of NAC in this population. Surgical management of cN1 disease by NAC exposure. Cohort n SLNB Alone Required ALND P-value No NAC 36 25 (69%) 11 (31%) NAC 19 8 (42%) 11 (58%) 0.08
Low-dose tamoxifen for pre-cancer and early disease: A pooled analysis by menopausal status.
10515 Background: Adjuvant endocrine prevention reduces the risk of subsequent breast cancer events after ductal carcinoma in situ (DCIS) and precursor lesions, but the toxicity of standard-dose tamoxifen or aromatase inhibitors limits its use. Low-dose tamoxifen (Babytam) has demonstrated a favorable balance of efficacy and tolerability. Whether the magnitude and pattern of benefit vary by menopausal status remains undefined. We performed a pooled analysis of three studies to evaluate Babytam according to menopausal status and type of breast cancer event. Methods: Individual patient data from two randomized trials (Trial 007, JCO 2009; 27:3749; Trial Tam-01, JCO 2023; 41:3116) and one observational study (Int J Cancer 2016; 139:2127) were pooled. Babytam was administered at 5 mg/day (RCTs) or 10 mg every other day (observational). The primary endpoint was recurrence of any breast cancer event, defined as ipsilateral recurrence or new ipsilateral breast cancer, contralateral breast cancer (CBC), distant metastases, or death. Competing risk models were applied for CBC. Multivariable Cox proportional hazards models with study-level random effects were used. Analyses were stratified by menopausal status. Results: A total of 1,772 women were included, 1,568 with DCIS, 101 with ADH, 81 with LCIS, and 21 with pT1a. Babytam significantly reduced overall breast cancer events, with differential effects by menopausal status and event type (table). Reduction in any breast cancer event was driven by a marked decrease in ipsilateral events among postmenopausal women, whereas the preventive effect on CBC was confined to premenopausal women. Few distant metastases or deaths occurred. Conclusions: In this pooled analysis, Babytam significantly reduced breast cancer events following in situ and microinvasive disease, confirming and extending the preventive efficacy observed in TAM-01. Menopausal status was a key modifier of benefit, with ipsilateral risk reduction predominating in postmenopausal women and CBC prevention in premenopausal women. These findings underscore the biological heterogeneity of early breast neoplasia and support Babytam as a risk-adapted, de-escalated endocrine prevention strategy that enables individualized decision-making balancing efficacy, toxicity, and patient characteristics. Clinical trial information: NCT06982313 . Effect of low-dose tamoxifen (babytam) on overall recurrence and contralateral breast cancer by menopausal status. Population Menopausal status Babytam events/N Control events/N HR (95% CI) p-value ER+ Overall 152/678 192/629 0.68 (0.55-0.84) <0.001 Pre 109/366 98/269 0.83 (0.63-1.09) 0.17 Post 40/292 91/354 0.52 (0.36-0.76) <0.001 ER- Overall 7/19 57/225 1.20 (0.54-2.65) 0.65 Considering CBC only All patients Overall 39/812 68/960 0.66 (0.44–1.00) 0.05 Pre 22/457 40/387 0.46 (0.27–0.77) 0.003 Post 16/335 27/560 1.04 (0.55–1.96) 0.89 ER+ Overall 35/678 51/629 0.65 (0.42-0.99) 0.046
TACE-HAIC combined with low-dose donafenib for unresectable hepatocellular carcinoma: A real-world study.
e16182 Background: The treatment of unresectable hepatocellular carcinoma (uHCC) remains challenging. Although the combination of multiple effective therapeutic modalities, including transarterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC), and donafenib-based targeted therapy, has been shown to enhance tumor control, careful balancing of efficacy and safety is essential when integrating these approaches. This real-world study evaluated the efficacy and safety of TACE combined with HAIC and low-dose donafenib in patients with uHCC. Methods: This ongoing real-world study enrolled patients diagnosed with uHCC who received first-line therapy consisting of TACE-HAIC plus donafenib (100 mg twice daily) at Henan Cancer Hospital.The primary endpoint was ORR assessed according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Secondary endpoints included overall survival (OS), PFS, disease control rate (DCR), time to untreatable (unTACEable) progression (TTUP), and treatment-related adverse events (TRAEs). Results: Between Sep 4,2024 to Oct 30, 2025, 32 patients were enrolled and treated. Among all patients, median age was 61 years, 26 (81.2%) had HBV, 17 (53.1) had multiple tumors, 18 (56.3%) were at BCLC stage C. The median number of TACE sessions per patient was 2 (range: 1–6). Notably, 31 patients (96.9%) also received concomitant immunotherapy (ant–PD-1 antibodies). As of data cutoff (Dec 30, 2025), the median follow-up was 9.3 months. Median PFS and Median OS were not reached.The estimated 12-month PFS rate was 87.5% and Estimated 12-month OS rate was 91.7%. Based on the mRECIST criteria, the best ORR and DCR were 81.2% and 100% (11 of complete response [CR], 15 of partial response [PR], and 6 of stable disease[SD]) . The CR rate was 34.4%. Notably, the median time to response of 1.57 months indicated rapid therapeutic onset. Among the 32 evaluable patients, 26 patients (81.3%) maintained or improved ALBI grading at the end of treatment. The change of ALBI score from baseline to the end of treatment were -2.28 to -2.18 (p = 0.25). Grade 3 or 4 TRAEs were observed in 17 (53.1%) patients, and no treatment-related deaths occurred. The most common AEs were thrombocytopenia (75.0%), anemia (68.7%), elevated ALT (62.5%). Conclusions: TACE combined with HAIC and low-dose donafenib showed encouraging antitumor activity with a manageable safety profile in uHCC patients. This regimen may be a feasible first-line treatment option and warrants further evaluation in prospective studies. Clinical trial information: ChiCTR2400089110.
Evaluating quality of life outcomes in metastatic breast cancer: Effects of palliative home visits in northern Malaysia.
e13090 Background: Metastatic breast cancer (MBC) causes significant symptom burden and psychological distress especially in Northern Malaysia where access to palliative care is limited. With 16,430 new cases (2017–2021) and 22.2% presenting at stage IV, effective supportive interventions are needed. Universiti Sains Malaysia Medical Center Bertam pioneered volunteer-integrated palliative home visits, yet their impact on patients’ quality of life (QoL) remains unevaluated. Methods: This prospective study enrolled 81 adults with MBC in Northern Malaysia to complete a 12-week volunteer-integrated palliative home visit program (Oct 2024 to Jan 2026). Serial visits by healthcare professionals and trained volunteers provided symptom management, psychosocial support and practical assistance. QoL was assessed at baseline and 12 weeks using EORTC QLQ-C15-PAL, with item-specific changes analysed using descriptive statistics, paired t -tests and Cohen’s d . Results: Participants were predominantly middle-aged women (34% aged 40–49 years; 64% B40 income group). Of 94 recruited, 81 completed (13 excluded for mortality or progression). At baseline, none were in ECOG 4, but 38% progressed to ECOG 4 at 3 months. QoL outcomes showed improvements across all symptoms and functioning domains. Statistically significant improvements observed in physical functioning, appetite loss, and fatigue (Δ +7.47, p < 0.001; Δ −9.00, p < 0.001; Δ−10.67, p = 0.01), although the corresponding effect sizes were small to moderate. Constipation and dyspnea also showed statistically significant but small improvements (Δ -4.67; Δ -2.01; both p < 0.001). Insomnia, pain and emotional functioning showed moderate effect size improvements; however, not reach statistical significance (Table 1). Conclusions: This study showed that palliative home visits improved overall QoL and symptom control among patients with MBC in Northern Malaysia, supporting its efficacy in community-based palliative care models Pre- and post-intervention quality of life outcomes (EORTC QLQ-C15-PAL). EORTC QLQ-C15-PAL items Pre-intervention Mean (SD) Post intervention Mean (SD) p-value a Effect size (d) b Insomnia 34.35 (30.74) 16.01 (17.81) 0.48 -0.70 Pain 52.00 (28.8) 38.65 (28.86) 0.09 -0.46 Physical Functioning 50.66 (31.46) 58.13 (26.51) 0.00 0.25 Appetite Loss 32.35 (32.36) 23.35 (29.92) 0.00 -0.29 Fatigue 50.88 (24.31) 40.21 (24.39) 0.01 -0.44 Constipation 21.68 (28.42) 17.01 (23.93) 0.00 -0.18 Emotional Functioning 63.18 (29.06) 76.84 (27.26) 0.19 0.49 Nausea/Vomiting 20.01 (26.08) 13.68 (17.72) 0.62 -0.29 Dyspnea 18.02 (22.8) 16.01 (17.81) 0.00 -0.10 Global QoL 61.35 (26.85) 68.34 (21.36) 0.12 0.28 a Paired t -test b Cohen’s d was interpreted as small (0.20–0.49), moderate (0.50–0.79) and large (≥0.80); positive values indicate improvement in functioning/QoL and negative values indicate symptom improvement.
A propensity score-matched analysis comparing first-line regional, systemic, and intralesional treatments for melanoma in-transit metastases in a contemporary patient population.
9524 Background: Unresectable melanoma in-transit metastases (ITM) can pose a significant clinical challenge. Our recently published data comparing first-line treatments for ITM, isolated limb infusion or perfusion (ILI/ILP), immune checkpoint inhibitors (ICI) and intralesional talimogene laherparepvec (TVEC), found superior outcomes with TVEC. However, TVEC was used more often in patients with lower disease burden and earlier stage (IIIB vs. IIIC/D). Therefore, we sought to better investigate these differences with a propensity score-matched (PSM) analysis. Methods: A multi-institutional, international IRB- approved retrospective analysis was conducted for unresectable melanoma ITM from 2016-2022. PSM analysis comparing first-line ILI/ILP, ICI, and TVEC for was performed. Patients were matched for stage, number of ITM, anatomical site, CLND status, gender and age. Kaplan-Meier curves (OS, PFS, DMFS) and Cumulative incidence function (MSS) were used to visualize time-to-event outcomes in the PSM cohort, though both methods do not account for the matched structure. Results: 274 patients were identified, 120 female/154 male; 96 treated with ILI/ILP, 111 with ICI, and 67 with TVEC. Median follow-up was 40 months (range, 1-80). PSM was performed and identified 36 TVEC–ICI pairs and 27 TVEC–ILI pairs. These were combined resulting in a final cohort of 108 observations (45 TVEC, 36 ICI and 27 ILI). The groups were well balanced. No statistical difference was found for metastasis-free survival (DMFS), progression-free survival (PFS), melanoma-specific survival (MSS), and overall survival (OS) between treatment modalities. TVEC was associated with significant improvement in local PFS (median was 2.2 years (y) for ILI/ILP, 1.5y for ICI and not reached for TVEC, p=0.048). While not statistically significant, a clinical benefit was seen in PFS being longer for TVEC (2.1y for TVEC vs. 1.2y for ILI/ILP and 1.1y for ICI; p=0.2) and OS (not reached vs 2.9y for ILI/ILP and 5.2y for ICI; p=0.2). On mixed effect Cox regression proportional hazard model using the matched data set, there were no significant differences in any of the survival and recurrence outcomes. Conclusions: When patients are propensity-matched, there were no significant differences in first-line treatment modalities for unresectable melanoma ITM. Treatment with TVEC did result in clinically meaningful improved overall and local PFS and OS. This supports that selection of ITM therapy should incorporate an individualized approach, incorporating disease distribution, stage, burden, treatment side effects and patient priorities.
The role of combined T cell and NK cell activity in immune checkpoint inhibitor (ICI) therapy in endometrial cancer (EC).
5609 Background: The efficacy of ICI in EC has largely been attributed to high microsatellite instability (MSI-H) causing increased tumor mutational burden (TMB) and T-cell mediated immunity. However, a subset of patients with microsatellite-stable (MSS) tumors also derive clinical benefit, indicating that MSI status alone is insufficient for patient selection and contributing to the 2024 Food and Drug Administration approval of chemotherapy plus ICI for all patients with EC. We evaluated established biomarkers of a T-cell–inflamed tumor microenvironment alongside alternative immune pathways, notably natural killer (NK) cell activity, to define determinants of overall survival (OS) benefit in EC patients treated with ICI. Methods: Patients with EC treated with pembrolizumab or dostarlimab were identified from the Caris Life Sciences database with paired whole exome and transcriptome sequencing (WES/WTS). OS was defined from ICI initiation to death or last contact via insurance claims. Patients were grouped as long vs short survivors (LS/SS) by median post-ICI OS (mOS). Associations between OS and expression of pre-annotated T- and NK-cell-related genes were analyzed with Kaplan–Meier and multivariable Cox models adjusting for clinicopathologic factors. Results: Of 6,354 patients, 25% were MSI-H and 71% MSS. Immune deconvolution of WTS showed higher levels of CD8⁺ T cells (p=0.034) and regulatory T cells (p=0.026) in LS vs SS. In multivariable analyses of the MSS subset, 63 T- and NK-cell–related genes were associated with improved OS, including FASLG (mOS 19.7 months vs 14.7 months in LS vs SS, HR=0.77, CI 0.70–0.85), IFNG (mOS 18.9 months vs 15.5 months in LS vs SS, HR=0.78, CI 0.71-0.86) and SIRPG (mOS 18.8 months vs 15.6 in LS vs SS, HR=0.79, CI 0.71-0.87) (all p<0.0001). The IFN Tumor Inflammation Signature (TIS) was not associated with OS in MSS EC, whereas T-cell, NK-cell, and combined T/NK gene signatures were (Table 1). Conclusions: Improved OS after ICI in MSS EC is associated with both T-cell and NK-cell activity. NK-cell–related and combined T/NK signatures were associated with improved survival, suggesting NK-cell activation contributes to ICI efficacy. These findings warrant validation in independent cohorts prior to use as a potential biomarker for ICI use in MSS EC. T/NK signature scores are associated with improved OS in MSS EC. Label HR (95% CI) P value Gene set NK (high vs low) 0.82 (0.74–0.90) <0.001 T + NK (high vs low) 0.84 (0.77–0.93) 0.001 T (high vs low) 0.84 (0.77–0.93) 0.001 Covariate p53: mutant vs wildtype 1.54 (1.38–1.73) <0.001 TMB: high vs low 0.66 (0.49–0.90) 0.008 Chemotherapy: yes vs no 1.13 (0.98–1.31) 0.101 Biopsy site: metastasis vs primary 0.92 (0.83–1.02) 0.124 Lenvatinib: yes vs no 0.95 (0.86–1.05) 0.293 Multivariable Cox models adjusted for p53 status, TMB, site, chemotherapy and lenvatinib use.
Baseline financial and credit status of participants enrolled in SWOG S1912CD.
11049 Background: Financial hardship is associated with adverse outcomes in cancer patients. While there is a critical need for interventions to prevent financial hardship, their scale and impact depend on the baseline financial status of patients. CREDIT (SWOG S1912CD) is a national prospective, randomized pragmatic trial evaluating the impact of a financial navigation intervention versus usual care on financial, clinical, and psychosocial outcomes. We report baseline demographic and financial characteristics of trial enrollees, using a combination of self-reported and credit data. Methods: Enrollees were within 6 months of diagnosis of a metastatic/stage IV solid tumor or hematologic malignancy. A total of 329 patients were randomized between July 2021 and December 2024 (165 control, 164 intervention). We assessed baseline income, employment, debt, homeowner status, financial fragility (ability to come up with $2,000 in 30 days), mean Comprehensive Score for Financial Toxicity (COST), and financial coping strategies (e.g. loans, cost-related nonadherence). We also examined the proportion of patients with adverse credit indicators (bankruptcies, third-party collections, repossessions, tax liens, delinquent mortgage payments) in their baseline credit reports. We compared mean COST score for patients with versus without adverse credit indicators. Results: Most patients (median age 61.5) were White (78%), 51% had commercial insurance while 33% had Medicare. The most common cancer types were gastrointestinal (23%), lung (12%), and breast (11%). Median household income was $50,001-$75,000, 70% were homeowners, and 32% reported a change in employment following cancer diagnosis and prior to enrollment. 39% reported financial fragility, 71% reported debt (32% with debt greater than $25K), and 20% reported taking loans from friends or family in the prior 3 months. Mean COST score was 19.6, with 45% of patients reporting scores ≤ 17.5, consistent with significant financial toxicity. 18.5% of patients had utilized ≥ 75% of credit limit on credit cards. The proportion of patients with prior bankruptcy, third-party collection, repossession, or delinquent mortgage payment were 3.3%, 16%, 2.7%, and 2.5% respectively. Mean COST score was significantly lower in patients with an adverse credit indicator compared to those without (21.4 vs. 13.0, p<0.0001) suggesting good correlation between credit data and patient-reported outcome measure. Conclusions: A significant proportion of patients newly diagnosed with cancer reported debt, financial fragility, and significant financial toxicity. A smaller proportion had more severe financial challenges identifiable in their baseline credit reports. There is clearly a need for interventions to address and mitigate financial hardship in this population. Final primary analysis of the impact of CREDIT in this financially challenged population is forthcoming. Clinical trial information: NCT04960787 .
Donafenib plus sintilimab combined with TACE or HAIC for unresectable hepatocellular carcinoma: A prospective single-arm phase II study.
e16179 Background: The combination of targeted therapy and immunotherapy has shown promising efficacy in patients (pts) with unresectable hepatocellular carcinoma (uHCC). Interventional therapy is an effective locoregional treatment for uHCC. The purpose of this study is to evaluate the efficacy and safety of donafenib combined with sintilimab in conjunction with TACE, HAIC, or a combination of TACE and HAIC in pts with uHCC. Methods: This is a prospective, single-arm phase II study (ChiCTR2300076993). Pts with uHCC who had not received any previous systemic treatment were included, provided they had an ECOG PS of 0-1 and Child-Pugh class A or B. Enrolled pts received donafenib (200 mg, bid), sintilimab (200 mg, q3w) along with TACE (administered as needed, conventional TACE or drug-eluting bead TACE) or HAIC (administered as needed, oxaliplatin 85 mg/m² over 2h, leucovorin 400 mg/m² over 2h, fluorouracil bolus 400 mg/m² in the first 10 minutes, and fluorouracil infusion 1200 mg/m² for 23 hours, q3w), or a combination of TACE and HAIC, until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR). Results: From Dec 2023 to Aug 2025, 27 pts were enrolled: BCLC stage A/B/C: 1/5/21; Child-Pugh class A/B: 25/2; ECOG PS 0/1: 15/12. The median tumor size was 7.9 cm. Macro vascular invasion was present in 77.8% of pts, and 74.1% had Vp3/Vp4 portal vein tumor thrombus. As of Jan 2026, the median follow-up time was 11.4 months. The ORR was 59.3% (4 complete responses [CRs], 12 partial responses [PRs]) per mRECIST and 40.7% (1 CR, 10 PRs) per RECIST 1.1. The disease control rate was 96.3% for both criteria. The median progression-free survival was 10.5 months (95% CI, 10.5-NA). The 1-year overall survival rate was 96.0% (95% CI, 88.6%-100.0%). Of the 7 pts (25.9%) who achieved successful conversion therapy, 6 underwent radical surgery (all achieving R0 resection, with 5 exhibiting a major pathological response and 1 achieving a pathological complete response), and 1 received radical ablation. Currently, 3 pts have experienced recurrence. Following combination therapy, both AFP and PIVKA-II levels declined significantly. The quality of life (QoL) scores showed a slight decrease from baseline post-treatment, but this change did not meet the threshold for a minimal clinically important difference (defined as a ≥10-point decrease). Throughout treatment, the score remained stable ( P > 0.05). The incidence of any treatment-emergent adverse event (TEAE) was 100%. The most common TEAEs were thrombocytopenia, anemia, and elevated bilirubin, grade 3-4 TEAEs occurred in 18.5% of pts. No grade 5 adverse events were reported. Conclusions: This study preliminarily indicates that the combination of donafenib, sintilimab, with TACE, HAIC, or TACE-HAIC shows encouraging efficacy and acceptable toxicity in uHCC. Enrollment and follow-up are continuing. Clinical trial information: ChiCTR2300076993.