Abstract Background/Significance: Effective early-stage biomarkers are needed for improving outcomes in gynecologic cancers. Micro RNAs (miRNAs) are small non-coding RNAs that function in post-transcriptional gene regulation and their dysfunction can play key role in cancer development and progression. Recently, the role of miRNAs is gaining attention as circulating biomarkers for various malignancies. However, there is a gap in studies involving gynecologic cancers with high-mortality rates such as ovarian serous cystadenocarcinoma (OV), uterine corpus endometrial carcinoma (UCEC), and uterine carcinosarcoma (UCS). The objectives of this study are to analyze the expression profiles of selected miRNA-coding genes such as hsa-mir-6511b-1, hsa-mir-6820, and hsa-mir-3198-2 in tumor specimens from patients with OV, UCEC, and UCS cancers using The Cancer Genome Atlas (TCGA) datasets. Additionally, we evaluated the prognostic significance of these miRNAs by correlating their expression levels with overall survival and clinical outcomes. Methods: Data were obtained from TCGA, an online portal for analyzing tumor genes and survival curves. A comparison was made between the common miRNA-coding genes in OV vs UCS, OV vs UCEC, and UCS vs UCEC. Survival curves were obtained for OV (n=474) vs UCS (n=56). Clinical trials information was accessed through clinicaltrials.gov. Data was analyzed and the statistical significance was assessed by Student’s t-test (comparisons between two-groups), or one-way ANOVA (for multiple-groups), and survival curves were analyzed using Kaplan-Meier method with log-rank test. A p-value of 0.05 or less was considered significant. Results: Analyses revealed differences in patient survival based on the expression of the miRNA-coding genes of interest, hsa-mir-6511b-1, hsa-mir-6820, and hsa-mir-3198-2, in OV and UCS. High expression of hsa-mir-6511b-1 was associated with a shorter survival period in both OV (p=0.021) and UCS (p=0.035) patients. In contrast, high expression of hsa-mir-6820 showed opposite effects: it was linked to shorter survival in OV patients (p=0.024) but longer survival in UCS patients (p=0.028). High expression of hsa-mir-3198-2 was associated with longer survival in both OV (p=0.027) and UCS (p=0.046) patients. Data suggest that the role of miRNAs in these gynecologic cancers appears to be complex, showing both oncogenic and protective effects. Conclusions: These preliminary findings emphasize that miRNAs behave in a context-dependent manner in gynecologic cancers. Importance of miRNAs should be further studied to validate their potential as biomarkers for early detection, prognosis, and treatment strategies. Our laboratory is conducting translational studies to precisely understand the role of miRNA-coding genes on drug resistance to address platinum-resistance in gynecologic cancer models. Citation Format: Elizabeth Miller, Amber Hoskins, Natalie Gierat, Aneth Ochoa Negrete, Riyaz Basha. Prognostic potential of microRNA-encoding gene signatures in gynecologic cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2065.

Abstract Ovarian cancer is projected to claim approximately 13,000 lives in the United States in 2025. Current treatment options remain limited and often insufficiently effective, underscoring the need for alternative therapeutics that may improve survival outcomes. To explore such possibilities, we screened two anti-parasitic drugs: ivermectin (IV) and fenbendazole (FZ). These drugs have been reported to exhibit anti-cancer properties. Both drugs were tested on the ovarian cancer cell lines SKOV3 and ES-2 using a luminescence-based CellTiter-Glo cell viability assay kit (Promega). Previous studies indicate that these compounds can inhibit proliferation and promote apoptosis in some cancer cell lines and mouse xenograft models. FZ in particular has been reported to alter the expression of MYC, a gene involved in cancer cell growth, proliferation, and survival. Using the open-access cancer database, we retrieved data from The Cancer Genomic Atlas and found that high MYC expression in ovarian cancer patients significantly correlates with decreased survival (p = 0.044). Our cell viability assays revealed cell line-dependent anti-proliferative responses. ES-2 cells displayed a clear dose-dependent decrease in viability following IV or FZ treatment, whereas SKOV3 cells were comparatively less sensitive. For ES-2, IV at 8, 4, 2, and 1 μM doses at 48-hour post-treatment, yielded viabilities of 0.88%, 4.91%, 18.82%, and 78.97%, respectively; for SKOV3, the corresponding viabilities were 8.92%, 56.62%, 76.61%, and 100.0%. FZ produced a similar trend: ES-2 viabilities at 5, 2.5, 1.25, and 0.625 μM were 6.97%, 27.02%, 50.52%, and 69.46%, while SKOV3 viabilities were 17.32%, 19.46%, 20.49%, and 50.54%, respectively. IC50 calculations further highlighted these differences. In SKOV3, the IC50 for FZ (1.02 μM) was lower than that for IV (3.678 μM). In ES-2, both drugs produced similar IC50 values (IV: 2.5345 μM; FZ: 2.3285 μM). These findings suggest the potential anti-cancer activity of these anti-parasitic agents and further testing their efficacy as therapeutic candidates for ovarian cancer. Our laboratory is currently investigating the combination therapies involving these drugs with standard chemotherapeutics and other agents shown to modulate MYC and other emerging anti-cancer compounds to improve treatment efficacy for ovarian cancer patients. Citation Format: Aneth Ochoa Negrete, Tiffany Duque, Adithi Kankanala, Gisel Gutierrez, Riyaz Basha. Evaluation of anti-parasitic agents as potential therapeutics in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7103.

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide. Effective CRC screening in the United States has reduced incidence of CRC in populations over 50 years of age. Early-onset CRC is emerging as a significant issue. There is need for better understanding of CRC biology to develop screening techniques, diagnostic markers and novel therapies to improve outcomes. MicroRNAs (miRNAs) are involved in several cellular processes and function as tumor suppressors and oncogenes. The miRNA/cytokine networks play a critical role in CRC pathogenesis by contributing to an extended period of inflammation which promotes tumorigenesis, tumor progression, and immune evasion. Certain miRNAs such as miR-21 and miR-155 are pro-inflammatory while others like miR-34, miR-143, miR-145 and mi146a are protective against cancer. When using miRNAs as therapeutics in CRC, the therapies rely on miRNA inhibitors to either suppress the miRNAs that have a role in activating oncogenic pathways or replacing miRNAs with mimics that can upregulate tumor suppressors which have been dysregulated due to cancerous mutations. Key immune checkpoint pathways such as PD-1/PD-L1, NF-κB, MAPK, PI3/AKT, and Wnt/β-catenin signaling cascades are regulated by miRNAs. A number of miRNAs are also tested as therapeutic co-targets for boosting immunotherapy effectiveness. Several clinical trials are underway to incorporate miRNAs into CRC screening or detecting early recurrence. Since the administration of targeted treatments can result in an immune-related adverse effect, growing interest has focused on exosomes as alternative carriers for miRNA-based therapeutics. Overall, applications of miRNAs have the potential to improve CRC outcomes.

Tolfenamic acid (TA), a non-steroidal anti-inflammatory drug, has demonstrated anti-cancer properties across multiple cancer models including prostate, pancreatic, ovarian, colon, leukemia, lung, and medulloblastoma. Studies have identified potential targets of TA including transcription factors Sp1, Sp3 and Sp4, anti-apoptotic proteins survivin and Bcl2, anti-angiogenic protein VEGF, and NFkB gene products. These interactions result in inhibition of cell proliferation, induction of apoptosis, and suppression of tumor growth in mouse models. To enhance the efficacy of TA, a novel copper (II) complex of TA ([Cu(TA)2(bpy)], bpy = 2,2’-bipyridine, Cu(II)-TA) was synthesized. Cell viability assays revealed that Cu(II)-TA exhibited greater anti-proliferative activity than TA, as indicated by lower IC50 values. However, the mechanism underlying this increased activity remains unclear. In this study, we compared the mechanism of action of TA and Cu(II)-TA in medulloblastoma cells. The anti-proliferative activity of the two compounds was assessed using a cell viability assay and the apoptotic activity was evaluated by caspase 3/7 activity assay. Cell cycle effects were analyzed by flow cytometry and DNA damage was assessed by measuring levels of phospho-H2AX using western blot and immunofluorescence microscopy. Consistent with previous findings, we observed increased anti-proliferative effects with Cu(II)-TA compared to TA in medulloblastoma cells. This enhanced activity was accompanied by increased apoptosis as indicated by higher caspase 3/7 activity. Cell cycle analysis by flow cytometry revealed distinct profiles for the inhibitors. TA treatment resulted in increased G2/M population, while Cu(II)-TA did not show a prominent or dose-dependent increase with treatment. Interestingly, TA induced greater DNA damage than Cu(II)-TA as indicated by increased phospho-H2AX levels detected by western blotting and immunofluorescence staining. These findings suggest that while Cu(II) enhances the anti-proliferative activity of TA, the underlying mechanisms differ, likely involving distinct proteins and pathways. Hayden Flume, Riva Sarkar, Tanaya Washington, Ethan Schroeder, Sakariyau A. Waheed, Kaylin L. Thomas, Stephen Beebe, Riyaz Basha, Alvin Holder, Umesh T. Sankpal. Comparison of the anti-cancer mechanism of tolfenamic acid and its copper (II) complex [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 373.

Ewing Sarcoma (ES) is a rare, malignant bone neoplasm that is primarily diagnosed in childhood and adolescence. The aggressive nature of this neoplasm requires the use of surgery, radiation and a rigorous chemotherapy regimen. Metastatic ES carries a poor prognosis, which necessitates the development of new therapeutic agents. Mithramycin was tested in targeted therapy due to its specific inhibitory effects on the EWS-FLI1 fusion protein which is present in >85% of ES tumors. We tested the combination of Mithramycin with chemotherapeutic agents vincristine (VCR) and Etoposide (Eto) for inducing higher cytotoxicity against ES cells, CHLA10 and TC205. Cardiomyocyte cell line, H9C2 was used to test the effect on non-malignant cells. Cell viability was measured using the CellTiter-Glo kit, and the combination index was evaluated to determine the type of combination response (antagonistic, additive, or synergistic). Apoptotic cells were measured post-treatment with vehicle (DMSO, control), monotherapy (mithramycin or etoposide), or combination therapy (mithramycin + etoposide) using BD LSRII flow cytometer and analyzed utilizing FlowJo software V8.0. The apoptotic protein marker c-PARP in both treatment and control groups was analyzed using Western blot analysis. The results showed higher cytotoxicity for combination treatment when compared to individual agents, and the combination index confirmed the response as synergistic. H9C2 cells did not demonstrate significant decreases in cell viability when treated with combination therapy, highlighting the specificity of the treatment toward its target tissue. Flow cytometry confirmed the underlying mechanism as upregulation of apoptosis which is further supported by an increase in effector caspases 3/7 and elevated expression of c-PARP. These in vitro assays using ES cells provide preliminary evidence for the benefit of chemotherapy and mithramycin combination.

Ewing’s Sarcoma (ES) is a rare and aggressive bone cancer that primarily affects children and adolescents. The disease is characterized by the presence of the EWS-FLI1 fusion protein, a transcription factor found in 85% of ES tumors that drives oncogenesis and tumor progression. Advanced ES has a grim prognosis with survival rates below 30%. Standard chemotherapy often results in significant long-term morbidities due to side-effects. Mithramycin has shown promise in inhibiting EWS-FLI1, however, its clinical application has not been established due to dose-dependent toxicities. We hypothesize that combining mithramycin with chemotherapy could offer a potential strategy to achieve synergistic effects, enabling lower dosages of both drugs to enhance efficacy while minimizing toxicity. We tested the combination effect of Mithramycin and Etoposide using ES cell lines and determined the response on inducing higher apoptosis through altering reactive oxygen species (ROS). Cardiomyocytes were used to test systemic toxicity against non-cancerous cells. Ewing Sarcoma cells (CHLA 10 and TC205) and cardiomyocytes (H9C2) were cultured and treated with Mithramycin, Etoposide, and their combination using optimized concentrations determined for each drug. Cell viability, Caspase 3/7 activity and ROS production were measured using respective luminescence-based assays. Flow cytometry with Annexin V/7AAD staining evaluated apoptosis levels, and protein expression of apoptosis-related markers, such as c-PARP, was analyzed using a capillary-based Simple Western system. Statistical analyses were performed using GraphPad Prism to evaluate significance. The combination of Mithramycin and Etoposide significantly inhibited ES cell viability compared to either agent alone. Apoptotic markers were markedly elevated in the combination-treated cells and associated with an upregulation of Caspase 3/7 activity and ROS production. Flow cytometry analysis confirmed an elevated apoptotic response, with a higher percentage of Annexin V-positive cells in the combination group. Additionally, Western blot analysis revealed increased c-PARP expression, consistent with enhanced apoptosis. In H9C2 cardiomyocytes, no treatment exhibited significant toxicity at equivalent concentrations, indicating the potential for no cardiac side effects. These results demonstrate the synergistic effects of Mithramycin and Etoposide in targeting cancer cells while sparing healthy tissue. Protein samples were subjected to proteomics and Integrative Pathway Analyses are currently being conducted to precisely elucidate the involvement of ROS-associated markers in understanding the mechanism of action and in vivo efficacy of this combination. Investigating additional biomarkers of response and resistance may provide further insights for personalized therapy. Christoffer B. Lambring. Mithramycin and chemotherapy combination induces apoptosis in Ewing sarcoma cells by upregulating reactive oxygen species and associated pathways [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7054.

Ewing’s sarcoma (ES) is a highly aggressive cancer that primarily originates in the bones or soft tissues and is predominantly diagnosed in adolescents and young adults. The EWS-FLI1 fusion protein is considered a hallmark of ES, being expressed in approximately 85% of cases. Prognosis for advanced ES remains poor, with survival rates around 30%, and current chemotherapy regimens are associated with severe long-term side effects. Mithramycin has emerged as a promising inhibitor of EWS-FLI1; however, its clinical application is limited by dose-dependent toxicities. We hypothesize that combining mithramycin with standard chemotherapy could enhance therapeutic outcomes through synergistic effects, potentially allowing for reduced doses of both agents to maximize efficacy while minimizing toxicity. To investigate this, we evaluated the combined impact of mithramycin and etoposide on ES cell lines. Using TC205 cells, we further explored the underlying mechanisms through proteomics and integrative pathway analysis (IPA). In this study, we assessed the dose- and time-dependent effects of mithramycin and etoposide in ES cell lines (CHLA10 and TC205) and non-cancerous cardiomyocytes (H9C2) to optimize treatment conditions. In vivo assays demonstrated a significant reduction in tumor growth with combination therapy compared to single-agent treatment. Using TC205 cells, we assessed the impact of mithramycin and etoposide both as monotherapies and in combination. Cells were plated in triplicate for each group (control, mithramycin, etoposide, and mithramycin + etoposide) and treated with optimized doses. After 48 hours, cells were harvested, and protein samples were subjected to proteomics and IPA to elucidate the mechanisms of action of both mono- and combination therapies. The combination of mithramycin and etoposide significantly inhibited cell viability compared to individual treatments. Proteomics analysis identified 517 altered proteins (t-test with BH correction), with 142 upregulated and 375 downregulated. IPA revealed significant changes in markers associated with disease and physiological function networks, including homologous recombination, cytostasis of sarcoma cell lines, cell movement of sarcoma cell lines, and osteoclastogenesis of limb bones. More than 70 disease and function networks and over 200 canonical pathways were significantly affected. Key pathways included eukaryotic translation initiation, cell cycle checkpoints, neutrophil degranulation, and cell cycle control of chromosomal replication. Overall, these findings reveal that the combination of mithramycin and etoposide alters critical networks and pathways, enhancing therapeutic efficacy in ES cell lines. Christoffer B. Lambring, Khadiza Zaman, Elin Stone, Natalie Gierat, Ameya Bhargava, Laszlo Prokai, Riyaz Basha. Proteomics and integrative pathway analysis to understand the mechanism of action of mithramycin and etoposide combination induced cell death in Ewing sarcoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7053.

Abstract Purpose: Therapeutic targeting of transcription factors, Specificity protein (Sp)1 and Sp3 and their downstream effectors, such as survivin, are studied in various cancers. Due to role in in poorer cancer prognoses in several cancers their downregulation has been investigated as an effective treatment approach. Mithramycin (Mit) showed innate anti-cancer properties by targeting Sp proteins through GC/GT DNA binding interference. Recent studies have given new insights into further mechanisms of action of Mit, however in-depth binding and mechanistic studies are lacking. Our objective is to investigate Mit’s specific binding interactions with Sp1, Sp3, and survivin. Methods: Protein structures and sequences for Sp1, Sp3, and survivin (ID: P08047, Q02447, and O153392, respectively) were retrieved from UniProtKB database. Experimental predicted structures for Sp1 and Sp3 were obtained from AlphaFold. Sequence lengths of Sp1 and Sp3 were 785 and 781 amino acids (aa), domain regions of Sp1 (619-785) and Sp3 (461-781) were note. Survivin structure was obtained from PDB and was comprised of 142 aa. Co-crystallized compounds were removed during analyses using BIOVIA Discovery Studio 4.5 Visualizer. Prediction of binding sites and docking were performed using CASTp, GHECOM, DEPTH tools, glide, and AutoDock 4.2 software. Energy minimization and Molecular dynamics simulations were performed in the Schrödinger suite. Results: Binding sites were identified for Sp1, Sp3, and survivin. Simulated docking demonstrated multiple binding complexes and varying binding energies. The most efficient binding was seen with Sp1 and Sp3. RMSF and RMSD simulations revealed stabilization of Sp1-, Sp3-, and survivin-Mit complexes. This shows Mithramycin can potentially inhibit all three proteins, with slightly more stability with Sp1 and Sp3. Radius of gyration (rGyr), H-bond analysis, and solvent accessible surface area (SASA) support docking findings with Mit-protein complexes remaining stable in the binding pocket, forming new H-bonds, and altering hydrophilic and hydrophobic interaction areas. Conclusion: Our findings warrant further in vitro testing of the ability of Mit to interact with a wider range of oncogenic targets. While we only tested the ability of Mit to interact with Sp1, Sp3 and survivin, similar model can be used to evaluate the interaction with other critical proteins associated with cancer and to further elucidate mechanisms of action. These finding are crucial to understanding base mechanistic abilities and can be useful to test additional agents for their ability to interact with Sp1 or survivin. Citation Format: Christoffer Briggs Lambring, Santosh K. Behera, Riyaz Basha. Docking and molecular dynamic simulations of mithramycin against Sp1, Sp3, and survivin [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2345.

A hallmark of effective cancer treatment is the prevention of tumor reoccurrence and metastasis to distal organs, which are responsible for most cancer deaths. However, primary tumor resection is expected to be curative as most solid tumors have been shown both experimentally and clinically to accelerate metastasis to distal organs including the lungs. In this study, we evaluated the efficacy of our engineered nasal nano-vaccine (CpG-NP-Tag) in reducing accelerated lung metastasis resulting from primary tumor resection. Cytosine–phosphate–guanine oligonucleotide [CpG ODN]-conjugated nanoparticle [NP] encapsulating tumor antigen [Tag] (CpG-NP-Tag) was manufactured and tested in vivo using a syngeneic mouse mammary tumor model following intranasal delivery. We found that our nasal nano-vaccine (CpG-NP-Tag), compared to control NPs administered after primary mammary tumor resection, significantly reduced lung metastasis in female BALB/c mice subjected to surgery (surgery mice). An evaluation of vaccine efficacy in both surgery and non-surgery mice revealed that primary tumor resection reduces CD11b+ monocyte-derived suppressor-like cell accumulation in the lungs, allowing increased infiltration of vaccine-elicited T cells (IFN-γ CD8+ T cells) in the lungs of surgery mice compared to non-surgery mice. These findings suggest that the combination of the target delivery of a nasal vaccine in conjunction with the standard surgery of primary tumors is a plausible adjunctive treatment against the establishment of lung metastasis.

Therapeutic targeting of Sp1 transcription factor and survivin, are studied in various cancers due to their consistent overexpression. These markers result in poorer cancer prognoses and their downregulation has been investigated as an effective treatment approach. Mithramycin-A and Tolfenamic acid are two drugs with innate anti-cancer properties and are suggested to be able to target Sp1 through GC/GT DNA binding interference, however in-depth binding and mechanistic studies are lacking. Through docking analysis, we investigated Mithramycin-A and Tolfenamic acid in terms of their specific binding interactions with Sp1 and survivin. Through further molecular dynamics simulations including Root Mean Square (RMS) Fluctuation and RMS Deviation, rGYr, and H-bond analysis, we identified critical residues involved in drug interactions with each protein in question. We show Mithramycin-A as the superior binding candidate to each protein and found that it exhibited stronger binding with Sp1, and then survivin. Subsequent molecular dynamics simulations followed the same trend as initial binding energy calculations and showed crucial amino acids involved in each Mithramycin-A-protein complex. Our findings warrant further investigation into Mithramycin-A and its specific interaction with Sp1 and their downstream targets giving a better understanding of Mithramycin-A and its potential as an effective cancer treatment.

Colorectal cancer (CRC) is the third most commonly detected cancer with a serious global health issue. The rates for incidence and mortality for CRC are alarming, especially since the prognosis is abysmal when the CRC is diagnosed at an advanced or metastatic stage. Both type of (modifiable/ non-modifiable) types of risk factors are established for CRC. Despite the advances in recent technology and sophisticated research, the survival rate is still meager due to delays in diagnosis. Therefore, there is urgently required to identify critical biomarkers aiming at early diagnosis and improving effective therapeutic strategies. Additionally, a complete understanding of the dysregulated pathways like PI3K/Akt, Notch, and Wnt associated with CRC progression and metastasis is very beneficial in designing a therapeutic regimen. This review article focused on the dysregulated signaling pathways, genetics and epigenetics alterations, and crucial biomarkers of CRC. This review also provided the list of clinical trials targeting signaling cascades and therapies involving small molecules. This review discusses upto-date information on novel diagnostic and therapeutic strategies alongside specific clinical trials.

140 Background: Hepatocellular carcinoma (HCC) is a common and deadly cancer with a rising incidence in the US. HCC almost always develops on a background of chronic liver disease, which disproportionately affects individuals of lower socioeconomic status (SES), perpetuating existing disparities. Compounding these disparities, individuals of lower SES are less likely to participate in recommended cancer screening exams. Here, we describe the outcomes of patients diagnosed with HCC at a large urban safety-net hospital primarily serving the underserved. Methods: We identified patients diagnosed with HCC at John Peter Smith Hospital in Fort Worth, Texas from January 1, 2018, to March 31, 2021 to determine the impact of screening on survival. Patients were allocated to the screened cohort if they had undergone liver imaging within one year prior to HCC diagnosis. Kaplan-Meier methods and log-rank test were used to illustrate and compare 3-year survival curves from an index date of diagnosis until death. Cox proportional hazards model were used to calculate unadjusted and adjusted hazards ratios (HR) and 95% confidence intervals (CI). Lead time bias was adjusted in a sensitivity analysis using the Duffy adjustment and a sojourn time of 70 days and 140 days. Results: A total of 158 patients were included (n=53 screened, n=105 unscreened). The mean age was 62 years; 144 (91%) had cirrhosis, 78% were male, 34% were non-Hispanic white, and 8.2% had private insurance. Those in the unscreened cohort had more severe liver dysfunction (as measured by the ALBI grade) and produced higher levels of AFP, but were less likely to have cirrhosis than the screened cohort. The median overall survival (OS) for the screened cohort was 19.0 months (95% CI: 9.9-NA) and 5.4 months (95% CI: 3.7-8.5) in the unscreened cohort (HR death (unscreened v screened) = 2.4, 95% CI: 1.6-3.6; log rank P <0.0001). After adjusting for ALBI grade, AFP, hepatitis C, insurance status and initial treatment, there was a statistical difference in hazard of death in the three years (HR: 2.3; 95% CI: 1.5-3.6), favoring the screened cohort. The benefit for screening remained after adjusting for lead-time bias. With a mean sojourn time of 70 days, the HR death was 2.19 (95% CI 1.4-3.3, P =0.0002) and was 2.09 (1.4-3.2, P =0.0005) with a 140-day sojourn time. Conclusions: In an urban safety-net population, screening for HCC was associated with improved outcomes compared to patients with incidentally-diagnosed HCC. Altogether, this implies that earlier diagnosis and institution of treatment can positively improve survival for patients with newly diagnosed HCC in a population of patients evaluated at a safety-net hospital. Development of screening programs in accordance with accepted guidelines with outreach to high-risk individuals represents an area of high value care for safety-net hospitals.

Purpose: We describe the impact of screening on outcomes of patients diagnosed with hepatocellular carcinoma (HCC) in an urban safety-net healthcare system compared to a non-screened cohort diagnosed with HCC. Methods: Patients diagnosed with HCC at John Peter Smith Health Network were identified by querying the hospital tumor registry and allocated to the screened cohort if they had undergone any liver imaging within one year prior to HCC diagnosis, while the remainder were allocated to the non-screened cohort. Kaplan-Meier methods and log-rank tests were used to compare 3-year survival curves from an index date of HCC diagnosis. Cox proportional hazard models were used to calculate unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). The Duffy adjustment was used to address lead-time bias. Results: A total of 158 patients were included (n = 53 screened, n = 105 non-screened). The median overall survival (OS) for the screened cohort was 19.0 months (95% CI: 9.9-NA) and that for the non-screened cohort was 5.4 months (95% CI: 3.7-8.5) [HR death (non-screened vs. screened) = 2.4, 95% CI: 1.6-3.6; log rank p < 0.0001]. The benefit of screening remained after adjusting for lead-time bias (HR 2.19, 95% CI 1.4-3.3, p = 0.0002). Conclusions: In an urban safety-net population, screening for HCC was associated with improved outcomes compared to patients diagnosed with HCC outside of a screening protocol.