Yang, Ju Dong

Abstract Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. In sub-Saharan Africa, HCC is the second most common cancer in men and the sixth in women. African patients present with HCC at a young age and at advanced stage of disease. Improved surveillance can increase early HCC detection. The GALAD score has good sensitivity in the diagnosis of HCC in Asia, Europe and North America, however, it has not been validated in an African cohort. The aim of this study was to assess the performance of the GALAD score in the diagnosis of HCC in Ghanaian patients. Methods: Clinical data from patients with cirrhosis (n=93) or HCC (n=78) from out-patient hepatology clinics at 3 teaching hospitals in Ghana were abstracted, and serum samples analyzed. A logistic regression model predicting HCC status based on GALAD score was constructed to obtain the Receiver Operating Characteristics (ROC) curve for GALAD. The area under the curve (AUC) with 95% confidence interval was calculated and used to assess the performance of the GALAD score in surveillance for HCC. Results: The median AFP (5010.2 vs. 3.4), L3% (28.3 vs. 0.3) and DCP (507.6 vs. 0.2) levels were all significantly higher among HCC cases than the controls (p<0.0001). The median GALAD score was also higher among HCC patients (8.0 vs. -4.1, p<0.0001). The AUC of the GALAD score in the diagnosis of HCC was 0.86 (95% CI 0.79 - 0.92). At a cut-off value of -0.37, the GALAD score had a sensitivity of 0.81 and a specificity of 0.86. In a re-fit of the logistic regression model, the most significant factors in the GALAD model in our cohort were AFP-L3% and log(DCP). The AUC of the new GALAD model after model selection was 0.89. Conclusion: The GALAD score can be used to detect HCC in Ghana and has the potential to improve HCC surveillance in low-resource settings in sub-Saharan Africa. Citation Format: Yvonne Ayerki Nartey, Ju Dong Yang, Tyler Zemla, Joshua Ayawin, Shadrack Osei Asibey, Mohamed El-Kassas, Sally Afua Bampoh, Amoako Duah, Adwoa Agyei-Nkansah, Yaw Asante Awuku, Mary Yeboah Afihene, Hiroyuki Yamada, Jun Yin, Amelie Plymoth, Lewis Rowland Roberts. Accuracy of the GALAD serologic model in the diagnosis of hepatocellular carcinoma in Ghanaian patients [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 4802.

PURPOSE Hepatocellular carcinoma (HCC), the fourth most common cancer in Africa, has a dismal overall survival of only 3 months like in sub-Saharan Africa. This is affected by the low gross domestic product and human development index, absence of coherent guidelines, and other factors. METHODS An open forum for HCC-experienced health care workers from Africa and the rest of the world was held in October 2021. Participants completed a survey to help assess the real-life access to screening, diagnoses, and treatment in the North and Southern Africa (NS), East and West Africa (EW), Central Africa (C), and the rest of the world. RESULTS Of 461 participants from all relevant subspecialties, 372 were from Africa. Most African participants provided hepatitis B vaccination and treatment for hepatitis B and C. More than half of the participants use serum alpha-fetoprotein and ultrasound for surveillance. Only 20% reported using image-guided diagnostic liver biopsy. The Barcelona Clinic Liver Cancer is the most used staging system (52%). Liver transplant is available for only 28% of NS and 3% EW. C reported a significantly lower availability of resection. Availability of local therapy ranged from 94% in NS to 62% in C. Sorafenib is the most commonly used systemic therapy (66%). Only 12.9% reported access to other medications including immune checkpoint inhibitors. Besides 42% access to regorafenib in NS, second-line treatments were not provided. CONCLUSION Similarities and differences in the care for patients with HCC in Africa are reported. This reconfirms the major gaps in access and availability especially in C and marginally less so in EW. This is a call for concerted multidisciplinary efforts to achieve and sustain a reduction in incidence and mortality from HCC in Africa.

Background: The effectiveness of ultrasound-based surveillance for HCC in patients with cirrhosis is limited by suboptimal sensitivity for early tumor detection and poor adherence. Emerging blood-based biomarkers have been proposed as an alternative surveillance strategy. We aimed to evaluate the comparative effectiveness of a multitarget HCC blood test (mt-HBT)—with and without improved adherence—against ultrasound-based HCC surveillance. Methods: We developed a Markov-based mathematical model that simulated a virtual trial in patients with compensated cirrhosis comparing potential surveillance strategies: biannual surveillance using ultrasound, ultrasound plus AFP, and mt-HBT with or without improved adherence (+10% increase). We used published data to inform underlying liver disease progression rates, HCC tumor growth patterns, performance characteristics of surveillance modalities, and efficacy of treatments. Primary outcomes of interest were the number of early-stage HCCs detected and life years gained. Results: Per 100,000 patients with cirrhosis, mt-HBT detected 1680 more early-stage HCCs than ultrasound alone and 350 more early-stage HCCs than ultrasound + AFP, yielding an additional 5720 and 1000 life years, respectively. mt-HBT with improved adherence detected 2200 more early-stage HCCs than ultrasound and 880 more early-stage HCCs than ultrasound + AFP, yielding an additional 8140 and 3420 life years, respectively. The number of screening tests needed to detect one HCC case was 139 with ultrasound, 122 with ultrasound + AFP, 119 with mt-HBT, and 124 with mt-HBT with improved adherence. Conclusions: mt-HBT is a promising alternative to ultrasound-based HCC surveillance, particularly given anticipated improved adherence with blood-based biomarkers could increase HCC surveillance effectiveness.

Background and Aims: Magnetic resonance elastography (MRE) is an accurate, continuous biomarker of liver fibrosis; however, the optimal combination with clinical factors to predict the risk of incident hepatic decompensation is unknown. Therefore, we aimed to develop and validate an MRE-based prediction model for hepatic decompensation for patients with NAFLD. Approach and Results: This international multicenter cohort study included participants with NAFLD undergoing MRE from 6 hospitals. A total of 1254 participants were randomly assigned as training (n = 627) and validation (n = 627) cohorts. The primary end point was hepatic decompensation, defined as the first occurrence of variceal hemorrhage, ascites, or HE. Covariates associated with hepatic decompensation on Cox-regression were combined with MRE to construct a risk prediction model in the training cohort and then tested in the validation cohort. The median (IQR) age and MRE values were 61 (18) years and 3.5 (2.5) kPa in the training cohort and 60 (20) years and 3.4 (2.5) kPa in the validation cohort, respectively. The MRE-based multivariable model that included age, MRE, albumin, aspartate aminotransferase, and platelets had excellent discrimination for the 3- and 5-year risk of hepatic decompensation (c-statistic 0.912 and 0.891, respectively) in the training cohort. The diagnostic accuracy remained consistent in the validation cohort with a c-statistic of 0.871 and 0.876 for hepatic decompensation at 3 and 5 years, respectively, and was superior to Fibrosis-4 in both cohorts (p < 0.05). Conclusions: An MRE-based prediction model allows for accurate prediction of hepatic decompensation and assists in the risk stratification of patients with NAFLD.

INTRODUCTION: Intrahepatic cholangiocarcinoma (iCCA) is a primary liver malignancy with poor prognosis. Current prognostic methods are most accurate for patients with surgically resectable disease. However, a significant proportion of patients with iCCA are not surgical candidates. We aimed to develop a generalizable staging system based on clinical variables to determine prognosis of all patients with iCCA. METHODS: The derivation cohort included 436 patients with iCCA seen between 2000 and 2011. For external validation, 249 patients with iCCA seen from 2000 to 2014 were enrolled. Survival analysis was performed to identify prognostic predictors. All-cause mortality was the primary end point. RESULTS: Eastern Cooperative Oncology Group status, tumor number, tumor size, metastasis, albumin, and carbohydrate antigen 19-9 were incorporated into a 4-stage algorithm. Kaplan-Meier estimates for 1-year survival were 87.1% (95% confidence interval [CI] 76.1–99.7), 72.7% (95% CI 63.4–83.4), 48.0% (95% CI 41.2–56.0), and 16% (95% CI 11–23.5), respectively, for stages I, II, III, and IV. Univariate analysis yielded significant differences in risk of death for stages II (hazard ratio [HR] 1.71; 95% CI 1.0–2.8), III (HR 3.32; 95% CI 2.07–5.31), and IV (HR 7.44; 95% CI 4.61–12.01) compared with stage I (reference). Concordance indices showed the new staging system was superior to the TNM staging for predicting mortality in the derivation cohort, P < 0.0001. In the validation cohort, however, the difference between the 2 staging systems was not significant. DISCUSSION: The proposed independently validated staging system uses nonhistopathologic data to successfully stratify patients into 4 stages. This staging system has better prognostic accuracy compared with the TNM staging and can assist physicians and patients in treatment of iCCA.

BackgroundCurative surgical treatments afford the best prognosis for patients with intrahepatic cholangiocarcinoma (iCCA); however, the comparative effectiveness of treatment options and factors associated with curative treatment receipt for early stage iCCA remain unknown.MethodsThe authors identified patients who were diagnosed with early stage iCCA, defined as a unifocal tumor <3 cm, during 2004–2018 from the National Cancer Database. Multivariable logistic and Cox regression analyses were used to identify the factors associated with curative treatment and overall survival (OS), respectively.ResultsThe proportion of patients with early stage iCCA increased from 4.5% in 2004 to 7.3% in 2018, with the odds of early stage detection increasing by 3.1% per year (odds ratio [OR], 1.031; 95% CI, 1.015–1.049). Of 1093 patients who had early stage iCCA, 464 (42.5%) underwent resection, 113 (10.3%) underwent ablation, 62 (5.7%) underwent liver transplantation, and 454 (41.5%) received noncurative treatments. Hispanic patients (adjusted OR [aOR], 0.57; 95% CI, 0.33–0.97) and Black patients (aOR, 0.47; 95% CI, 0.28–0.77) were less likely to receive curative treatments than White patients. Compared with patients who underwent surgical resection, those who underwent liver transplantation had a trend toward improved OS (adjusted hazard ratio [aHR], 0.63; 95% CI, 0.37–1.08), whereas those who underwent local ablation (aHR, 1.39; 95% CI, 1.01–1.92) and noncurative treatments (aHR, 3.97; 95% CI, 3.24–4.88) experienced worse OS.ConclusionsMore than one third of patients with early stage iCCA did not receive curative treatment, with Hispanic and Black patients being less likely to receive curative treatments than White patients. Surgical resection and liver transplantation were associated with improved survival compared with local ablation. Future studies should investigate disparities in curative treatment receipt and outcomes for early stage iCCA.

Abstract Background and Aims Immunotherapy has emerged as an effective treatment for patients with advanced‐stage HCC. We aimed to investigate the efficacy of immunotherapy for advanced HCC in a nationwide cohort and racial and ethnic disparities in access to immunotherapy. Approach and Results We used the US National Cancer Database to identify patients with tumor‐node‐metastasis stage 3 or 4 HCC between 2017 and 2018. We performed multivariable Cox regression to identify factors associated with overall survival (OS) and logistic regression to identify factors associated with receipt of immunotherapy. Of the 3,990 patients treated for advanced HCC, 3,248 (81.4%) patients received chemotherapy and 742 (18.6%) patients received immunotherapy as a first‐line treatment. Immunotherapy was associated with improved OS compared with chemotherapy (adjusted HR: 0.76, 95% CI: 0.65–0.88) after adjusting for covariates. There were racial and ethnic disparities in access to immunotherapy, with Hispanic (adjusted OR [aOR]: 0.63, 95% CI: 0.46–0.83) and Black patients (aOR: 0.71, 95% CI: 0.54–0.89) less likely to receive immunotherapy compared with White patients. There was a significant interaction between race‐ethnicity and facility type, with higher disparity observed in nonacademic centers (interaction p = 0.004). Conclusions Immunotherapy was associated with improved OS compared with chemotherapy in advanced HCC. There are significant disparities in early access to immunotherapy, likely due to differential access to clinical trials and experimental therapies. A comprehensive approach to monitoring and eliminating racial‐ethnic disparities in the management of advanced HCC is urgently needed.

TPS486 Background: Hepatocellular carcinoma (HCC) is a major cause of cancer-related death in the U.S. HCC surveillance is associated with improved early detection and receipt of curative treatment. However, current surveillance strategies suffer from low adherence and suboptimal sensitivity. The multi-target HCC blood test (mt-HBT) is a novel early detection assay that provides a qualitative result based on a multiparametric algorithm that incorporates information from methylation markers ( HOXA1, TSPYL5, and B3GALT6), AFP, and patient sex. Here, we describe the protocol for a prospective, multicenter clinical trial designed to investigate the performance of the mt-HBT in patients at risk for HCC. Methods: ALTernative to U/S (ALTUS) is a longitudinal, multicenter, prospective study with a targeted enrollment of 3,000 participants. The main inclusion and exclusion criteria are described in the table. Participants will receive HCC surveillance imaging (either U/S or CT/MRI) and blood collection for the mt-HBT. Those with positive U/S are anticipated to receive standard-of-care imaging follow-up with a multiphase CT or MRI, and those with a negative U/S will receive a study CT/MRI within 30 days of blood collection. Imaging interpretation is based on the CT/MRI LI-RADS (LR) v2018 categories. The primary endpoints are the overall sensitivity and specificity of the mt-HBT to detect HCC, defined as pathology-confirmed HCC or hepatocellular cholangiocarcinoma (cHCC-CCA), LR-4/5, or LR-TIV/M plus definite/probable HCC or cHCC-CCA. The secondary endpoints are mt-HBT early-stage sensitivity, and performance in a) participants with LR-5 or biopsy-confirmed HCC and b) participants confirmed non-HCC. Participants not diagnosed with a liver malignancy at visit one will continue to receive HCC surveillance, returning for a second visit ̃6 months from first blood collection. Blood will be collected after the second visit for the mt-HBT. Data on treatment will be collected for those diagnosed with HCC. Study participants and providers will be blinded to the mt-HBT results. Participants are currently enrolling across the U.S., with 60 targeted sites and an anticipated 12-month enrollment window. Clinical trial information: NCT05064553. [Table: see text]

405 Background: Hepatocellular carcinoma (HCC) is the fastest rising cause of cancer mortality in the United States. Although clinical guidelines recommend ultrasound (U/S), with or without the serum biomarker alpha fetoprotein (AFP) for HCC surveillance in at-risk patients, only 24% of patients adhere to surveillance and only one-third of HCCs are detected before developing symptoms. A multi-target HCC blood-based test (mt-HBT) was recently shown to have promising sensitivity for early HCC detection and may help improve surveillance adherence given its blood-based nature. Our objective was to evaluate the comparative clinical effectiveness of mt-HBT with the current standard-of-care surveillance strategy in patients with cirrhosis. Methods: We simulated a virtual trial by developing a microsimulation model of the natural history of HCC in patients with compensated (Child Pugh A) cirrhosis over a 30-year horizon. To inform model parameters, we used published data on tumor progression, competing risks of mortality, and real-world HCC surveillance adherence. Test performance characteristics were informed by a network meta-analysis. We simulated the life course of 51-year-old patients with cirrhosis and compared no surveillance with biannual surveillance using (1) AFP only, (2) U/S only, (3) U/S+AFP, (4) mt-HBT, and (5) mt-HBT with improved adherence. We assumed a blood-based test—without U/S—would improve surveillance adherence by 10% compared with current adherence (̃4% absolute improvement). Results: Per 100,000 cirrhosis patients, mt-HBT detected 6,220 more early-stage HCC than no surveillance, 2,250 (+57%) more than AFP, 1080 (+21%) more than U/S, and 200 (-3%) less than U/S+AFP. mt-HBT with improved adherence detected 210 (+3%) more early-stage HCC than U/S+AFP (Table). The remaining HCC cases were either symptomatic or the patients died per other competing causes prior to detection. The number of screening tests needed to detect one HCC were 296 for AFP, 287 for U/S, 253 for U/S+AFP, 254 for mt-HBT and 262 for mt-HBT with improved adherence. The number of diagnostic MRI/CT needed to detect one HCC were 40 for AFP, 38 for U/S, 45 for U/S+AFP, 37 for mt-HBT, and 38 for mt-HBT with improved adherence. Conclusions: mt-HBT detects more early-HCC cases than U/S and similar number of early-HCC cases with U/S+AFP. By decreasing surveillance barriers and increasing adherence, mt-HBT could improve early HCC detection and could be promising option for HCC surveillance in patients with cirrhosis. [Table: see text]