Carcinoma Surveillance Research Articles

FRI-297 - Abbreviated magnetic resonance imaging for secondary surveillance of recurrent hepatocellular carcinoma after curative treatment

FRI-297 - Abbreviated magnetic resonance imaging for secondary surveillance of recurrent hepatocellular carcinoma after curative treatment

CME: Outpatient Management of Patients with Liver Cirrhosis

CME: Outpatient Management of Patients with Liver Cirrhosis Abstract: Many causes of cirrhosis are modifiable. Therefore, etiologic clarification is mandatory. After diagnosis, the underlying disease must be treated and patients advised as to alcohol abstinence, smoking cessation, healthy diet, vaccinations and physical exercise. Gastroscopic screening for oesophageal varices is recommended. Patients with cirrhosis should undergo surveillance for hepatocellular carcinoma (biannual sonography and alpha-fetoprotein assessment). Following a first complication (e.g., variceal haemorrhage, ascites, encephalopathy) or deterioration of liver function, listing for liver transplantation should be evaluated. Control intervals should be individualized according to disease severity and previous decompensations. Many complications (e.g., bleeding, spontaneous bacterial peritonitis, acute renal failure due to NSAIDs or diuretics) have insidious onsets but may rapidly lead to multiple organ failure. Rapid diagnostics are recommended if patients show clinical, mental or lab deterioration.

FRI-292 - Add-on benefits of AFP-L3, PIVKA-II and GALAD score to ultrasound plus AFP for surveillance of hepatocellular carcinoma

FRI-292 - Add-on benefits of AFP-L3, PIVKA-II and GALAD score to ultrasound plus AFP for surveillance of hepatocellular carcinoma

Prognostic Model for Clear-cell Renal Cell Carcinoma Based on Natural Killer Cell-related Genes.

Natural killer (NK) cells are a key factor affecting progression and immune surveillance of clear-cell renal cell carcinoma (ccRCC). This study sought to construct a natural killer cell-related prognostic signature (NKRPS) to predict the outcome of ccRCC patients and to furnish guidance for finding appropriate treatment strategies. From the TCGA and ArrayExpress databases, transcriptomic profiles and relevant clinical information of ccRCC patients were downloaded for the TCGA cohort (n=515) and the E-MTAB-1980 cohort (n=101). With the univariate Cox analysis and LASSO-Cox regression algorithm, a NKRPS was built to evaluate patients' prognosis. Receiver operating characteristic (ROC) curves and calibration curves were drawn to estimate the predictive power of the prognostic model. Then, tumor microenvironment (TME), tumor mutational burden (TMB), sensitization to immune checkpoint inhibitors (ICIs) therapy and targeted drug treatment were analyzed in ccRCC patients. Nine genes (BID, CCL7, CSF2, IL23A, KNSTRN, RHBDD3, PIK3R3, RNF19B and VAV3) were identified to construct a NKRPS. High-risk group displayed undesirable survival compared to low-risk group (P < .05). Moreover, the area under the curve (AUC) of ROC at 1-, 3- and 5-year were 0.766, 0.755, and 0.757, respectively. High-risk group was characterized by superior immune infiltration, higher TMB, and higher expression of 5 ICI-related genes. Additionally, this model enabled to predict the sensitivity of patients to chemotherapy drugs. NKRPS had a strong predictive power on prognosis of ccRCC patients, which may facilitate individualized treatment and medical decision making.

FRI-329 - Targeted surveillance for hepatocellular carcinoma is cost effective in Australia: evidence from a microsimulation study

FRI-329 - Targeted surveillance for hepatocellular carcinoma is cost effective in Australia: evidence from a microsimulation study

LBP-16 - Hepatocellular carcinoma surveillance improves early detection and curative treatment in chronic hepatitis C patients treated with direct acting antivirals

LBP-16 - Hepatocellular carcinoma surveillance improves early detection and curative treatment in chronic hepatitis C patients treated with direct acting antivirals

OS-080-YI - Platelet, elastography, age, sex and etiology for hepatocellular carcinoma surveillance in patients with advanced chronic liver disease: Please algorithm

OS-080-YI - Platelet, elastography, age, sex and etiology for hepatocellular carcinoma surveillance in patients with advanced chronic liver disease: Please algorithm

SAT-127 - A pilot study to improve the uptake of hepatocellular carcinoma surveillance

SAT-127 - A pilot study to improve the uptake of hepatocellular carcinoma surveillance

Necessity for surveillance for hepatocellualr carcinoma in older patients with chronic hepatitis C who achieved sustained virological response.

Hepatocellular carcinoma (HCC) surveillance in low-risk patients (annual incidence <1.5%) is not recommended per the American Association for the Study of Liver Diseases guidelines. Because patients with chronic hepatitis C with non-advanced fibrosis who have achieved sustained virological response (SVR) have a low risk of HCC, HCC surveillance is not recommended for them. However, aging is a risk factor for HCC; threfore, the necessity for HCC surveillance in older patients with non-advanced fibrosis needs to be verified. This multicenter, prospective study enrolled 4993 patients with SVR (1998 patients with advanced fibrosis and 2995 patients with non-advanced fibrosis). The HCC incidence was examined with particular attention to age. The 3-year incidence of HCC in patients with advanced and non-advanced fibrosis was 9.2% (95% CI: 7.8-10.9) and 2.9% (95% CI: 2.1-3.7), respectively. HCC incidence was significantly higher in patients with advanced fibrosis (P < 0.001). HCC incidence stratified by age and sex was investigated in patients with non-advanced fibrosis. The HCC incidence in the 18-49, 50s, 60s, 70s, and ≥80 age groups were 0.26, 1.3, 1.8, 1.7, and 2.9 per 100 person-years in men, and 0.00, 0.32, 0.58, 0.49, and 0.57 per 100 person-years in women, respectively. Male patients with non-advanced fibrosis aged ≥60 years have a higher risk of developing HCC and, thus, require HCC surveillance.

Hepatocellular Carcinoma Surveillance among Individuals with Cirrhosis: Trends by Payer, Etiology, and Calendar Year, from a Statewide, Multi-Payer Dataset, 2010-2018.

Hepatocellular carcinoma (HCC) surveillance is underutilized, with <25% of individuals with cirrhosis receiving surveillance exams as recommended. The epidemiology of cirrhosis and HCC in the United States has also shifted in recent years, but little is known about recent trends in surveillance utilization. We characterized patterns of HCC surveillance by payer, cirrhosis etiology, and calendar year in insured individuals with cirrhosis. We conducted a retrospective cohort study of individuals with cirrhosis using claims data from Medicare, Medicaid, and private insurance plans in North Carolina. We included individuals ≥ 18 years with a first occurrence of an ICD-9/10 code for cirrhosis between January 1, 2010, and June 30, 2018. The outcome was HCC surveillance by abdominal ultrasound, CT, or MRI. We estimated 1- and 2-year cumulative incidences for HCC surveillance and assessed longitudinal adherence to surveillance by computing the proportion of time covered (PTC). Among 46,052 individuals, 71% were enrolled through Medicare, 15% through Medicaid, and 14% through private insurance. The overall 1-year cumulative incidence of HCC surveillance was 49% and the 2-year cumulative incidence was 55%. For those with an initial screen in the first 6 months of their cirrhosis diagnosis, the median 2-year PTC was 67% (Q1, 38%; Q3, 100%). HCC surveillance initiation after cirrhosis diagnosis remains low, though it has improved slightly over time, particularly among individuals with Medicaid. This study provides insight into recent trends in HCC surveillance and highlights areas to target for future interventions, particularly among patients with nonviral etiologies.

Prediction of Hepatocellular Carcinoma Development in Korean Patients after Hepatitis C Cure with Direct-Acting Antivirals.

With the wide application of direct-acting antivirals (DAAs) for hepatitis C virus infection, the number of patients achieving a sustained virologic response (SVR) will continue to increase. However, no consensus has been achieved on exempting SVR-achieving patients from hepatocellular carcinoma (HCC) surveillance. Between 2013 and 2021, 873 Korean patients who achieved SVR following DAA treatment were analyzed. We evaluated the predictive performance of seven noninvasive scores (PAGE-B, modified PAGE-B, Toronto HCC risk index, fibrosis-4, aspartate aminotransferase-to-platelet ratio index, albumin-bilirubin, and age male albumin-bilirubin platelet [aMAP]) at baseline and after SVR. The mean age of the 873 patients (39.3% males) was 59.1 years, and 224 patients (25.7%) had cirrhosis. During 3,542 person-years of follow-up, 44 patients developed HCC, with an annual incidence of 1.24/100 person-years. Male sex (adjusted hazard ratio [AHR], 2.21), cirrhosis (AHR, 7.93), and older age (AHR, 1.05) were associated with a significantly higher HCC risk in multivariate analysis. The performance of all scores at the time of SVR were numerically better than those at baseline as determined by the integrated area under the curve. Time-dependent area under the curves for predicting the 3-, 5-, and 7-year risk of HCC after SVR were higher in mPAGE-B (0.778, 0.746, and 0.812, respectively) and aMAP (0.776, 0.747, and 0.790, respectively) systems than others. No patients predicted as low-risk by the aMAP or mPAGE-B systems developed HCC. aMAP and mPAGE-B scores demonstrated the highest predictive performance for de novo HCC in DAA-treated, SVR-achieving patients. Hence, these two systems may be used to identify low-risk patients that can be exempted from HCC surveillance.

Hepatocellular carcinoma surveillance based on the Australian Consensus Guidelines: a health economic modelling study

BackgroundHepatocellular carcinoma (HCC) is the fastest increasing cause of cancer death in Australia. A recent Australian consensus guidelines recommended HCC surveillance for cirrhotic patients and non-cirrhotic chronic hepatitis B (CHB) patients at gender and age specific cut-offs. A cost-effectiveness model was then developed to assess surveillance strategies in Australia.MethodsA microsimulation model was used to evaluate three strategies: biannual ultrasound, biannual ultrasound with alpha-fetoprotein (AFP) and no formal surveillance for patients having one of the conditions: non-cirrhotic CHB, compensated cirrhosis or decompensated cirrhosis. One-way and probabilistic sensitivity analyses as well as scenario and threshold analyses were conducted to account for uncertainties: including exclusive surveillance of CHB, compensated cirrhosis or decompensated cirrhosis populations; impact of obesity on ultrasound sensitivity; real-world adherence rate; and different cohort’s ranges of ages.ResultsSixty HCC surveillance scenarios were considered for the baseline population. The ultrasound + AFP strategy was the most cost-effective with incremental cost-effectiveness ratios (ICER) compared to no surveillance falling below the willingness-to-pay threshold of A$50,000 per quality-adjusted life year (QALY) at all age ranges. Ultrasound alone was also cost-effective, but the strategy was dominated by ultrasound + AFP. Surveillance was cost-effective in the compensated and decompensated cirrhosis populations alone (ICERs < $30,000), but not cost-effective in the CHB population (ICERs > $100,000). Obesity could decrease the diagnostic performance of ultrasound, which in turn, reduce the cost-effectiveness of ultrasound ± AFP, but the strategies remained cost-effective.ConclusionsHCC surveillance based on Australian recommendations using biannual ultrasound ± AFP was cost-effective.

Hepatocellular carcinoma surveillance in the telehealth era: A single-centre review.

Real-world hepatocellular carcinoma (HCC) surveillance uptake remains suboptimal, despite evidence that surveillance is associated with lower cancer-related mortality in patients with cirrhosis and chronic hepatitis B. We aimed to examine the impact of telehealth consultations on HCC surveillance rates within a specialist liver clinic. We conducted a retrospective observational study within an Australian outreach liver clinic within a culturally diverse community, comparing standard consultations before the COVID-19 pandemic to telehealth consultations during the pandemic. The primary outcome was surveillance uptake defined as the percentage of time up-to-date with surveillance (PTUDS) with the 6-month interval following each scan considered up-to-date. Over 18 months of follow-up for each cohort, the median PTUDS was 86.5% in the standard consultation cohort and 85.5% in the telehealth consultation cohort (p = 0.12). HCC diagnoses did not differ between groups and hospitalisation and mortality rates were low. Using multivariate regression, increasing age, the need for an interpreter and being born in South-East Asia independently predicted PTUDS in the standard consultation cohort, whereas being born in Australia or New Zealand was predictive of a lower PTUDS. Current alcohol use and distance from the clinic predicted a lower PTUDS in the telehealth consultation cohort. In both groups, missed clinic attendances were strongly predictive of a lower PTUDS. Telehealth hepatology consultations effectively coordinate HCC surveillance and are associated with similar outcomes to standard consultations. Its implementation should be widely considered given its advantages with regards to accessibility for patients.

Outcomes of National Survey of the Practice of Hepatocellular Carcinoma Surveillance.

HCC has significantly improved outcomes when detected early. Guidelines recommend biannual surveillance with ultrasound (US) and/or AFP in at-risk individuals. This survey aimed to describe HCC surveillance adherence/practices amongst the NHS hospitals in the UK. An electronic survey was sent to 79 NHS hospitals via the British Association for the Study of the Liver distribution list. The responses were captured from July 2021 to January 2022. Centres were divided into hepato-pancreato-biliary (HPB) and non-HPB centres, depending on whether the hospital undertakes major liver surgeries. A total of 39 (49.3%) centres responded: 15 HPB and 24 non-HPB centres from across the UK. HCC surveillance eligibility criteria were universally applied, but heterogeneous approaches occur outside these criteria. Eighty per cent of patients undergoing surveillance were estimated to have cirrhosis. Eighty-five per cent of centres do 6-monthly US and AFP requested by clinicians and liver clinical nurse specialists. Compliance was estimated at 80% but not routinely audited. In most centres, general sonographers and/or radiologists perform surveillance US scans without a standard reporting template, although structured reporting was viewed as desirable by the majority. Poor views on US are approached heterogeneously, with patients variably offered ongoing US, CT, or MRI with different protocols. Most responding NHS hospitals follow 6-monthly HCC surveillance guidance. Data recording is variable, with limited routine data collection regarding compliance, yield, and quality. Surveillance US is mostly performed by non-HPB specialists without standardised reporting. There is an inconsistent approach to poor views with US surveillance. Even in a universal healthcare system such as NHS, which is free at the point of care, delivery of HCC surveillance has not improved over the last decade and remains variable.

Clinical application of the anti-human telomerase reverse transcriptase (hTERT) antibody (SCD-A7) immunocytochemistry in liquid-based urine cytology: Aprospective, single institute study.

Urine cytology is the most widely used noninvasive screening tool for urothelial carcinoma diagnosis and surveillance. Although highly specific, urine cytology exhibits suboptimal sensitivity. This study aimed to determine whether hTERT immunocytochemistry (ICC) could be applicable as an ancillary test in routine cytology practice. A total of 561 urinary tract samples were initially screened in this study. All of them were prepared using SurePath liquid-based cytology (LBC), while additional LBC slides were made and subsequently used for hTERT (SCD-A7) ICC. From the 561 samples screened, 337 were finally analyzed, all having an adequate cellularity and available follow-up histology. The hTERT ICC-positive rate was 95.9% (n=208/217), 96% (n=24/25), and 100% (n=4/4) in cytology samples with high-grade urothelial carcinoma, carcinoma in situ, and low-grade urothelial carcinoma subsequent histology. Among the 64 atypical cytology cases histologically confirmed as urothelial carcinomas, 92.2% (n=59/64) were immunoreactive to hTERT, whereas the two histologically benign cases were ICC-negative. 87/90 (96.7%) of the cytology cases confirmed to be benign in follow-up were hTERT-negative. The overall sensitivity and specificity of hTERT ICC were 96.3% and 98.8%, respectively (AUROC=0.963; 95% CI=0.960-0.967). The hTERT ICC test exhibited consistent and intense staining in malignant urothelial cells, suggesting its value as an ancillary test in liquid-based urine cytology.

Abbreviated MRI for Secondary Surveillance of Recurrent Hepatocellular Carcinoma After Presumed Curative Treatment.

Little is known about the performance of abbreviated MRI (AMRI) for secondary surveillance of recurrent hepatocellular carcinoma (HCC) after curative treatment. To evaluate the detection performance of AMRI for secondary surveillance of HCC after curative treatment. Retrospective. A total of 243 patients (183 men and 60 women; median age, 65 years) who underwent secondary surveillance for HCC using gadoxetic acid-enhanced MRI after more than 2 year of disease-free period following curative treatment, including surgical resection or radiofrequencyablation(RFA). A 3.0 T/noncontrast AMRI (NC-AMRI) (T2-weighted fast spin-echo, T1-weighted gradient echo, and diffusion-weighted images), hepatobiliary phase AMRI (HBP-AMRI) (T2-weighted fast spin-echo, diffusion-weighted, and HBP images), and full-sequence MRI ASSESSMENT: Four board-certified radiologists independently reviewed NC-AMRI, HBP-AMRI, and full-sequence MRI sets of each patient for detecting recurrent HCC. Per-lesion sensitivity, per-patient sensitivity and specificity for HCC detection at each set were compared using generalized estimating equation. A total of 42 recurred HCCs were confirmed in the 39 patients. The per-lesion and per-patient sensitivities did not show significant differences among the three image sets for either reviewer (P ≥ 0.358): per-lesion sensitivity: 59.5%-83.3%, 59.5%-85.7%, and 59.5%-83.3%, and per-patient sensitivity: 53.9%-83.3%, 56.4%-85.7%, and 53.9%-83.3% for NC-AMRI, HBP-AMRI, and full-sequence MRI, respectively. Per-lesion pooled sensitivities of NC-AMRI, HBP-AMRI, and full-sequence MRI were 72.6%, 73.2%, and 73.2%, with difference of -0.6% (95% confidence interval: -6.7, 5.5) between NC-AMRI and full-sequence MRI and 0.0% (-6.1, 6.1) between HBP-AMRI and full-sequence MRI. Per-patient specificity was not significantly different among the three image sets for both reviewers (95.6%-97.1%, 95.6%-97.1%, and 97.6%-98.5% for NC-AMRI and HBP-AMRI, respectively; P ≥ 0.117). NC-AMRI and HBP-AMRI showednosignificantdifferenceindetection performance to that of full-sequence gadoxetic acid-enhanced MRI during secondary surveillance for HCC after more than 2-year disease free interval following curative treatment. Based on its good detection performance, short scan time, and lack of contrast agent-associated risks, NC-AMRI is a promising option for the secondary surveillance of HCC. 3. Stage 2.

The role of PIVKA-II in hepatocellular carcinoma surveillance in an Asian population

Dear Editor, Alpha-fetoprotein (AFP) is the most established biomarker for surveillance of hepatocellular carcinoma (HCC) in at-risk individuals. However, its sensitivity and specificity are not very satisfactory.1 Protein induced by vitamin K absence or antagonist-II (PIVKA-II) is a newer biomarker for HCC but without a widely established cut-off.2,3 Recent data suggested that the cut-off may

Updating the Clinical Application of Blood Biomarkers and Their Algorithms in the Diagnosis and Surveillance of Hepatocellular Carcinoma: A Critical Review

The most common primary liver cancer is hepatocellular carcinoma (HCC), and its mortality rate is increasing globally. The overall 5-year survival of patients with liver cancer is currently 10-20%. Moreover, because early diagnosis can significantly improve prognosis, which is highly correlated with tumor stage, early detection of HCC is critical. International guidelines advise using α-FP biomarker with/without ultrasonography for HCC surveillance in patients with advanced liver disease. However, traditional biomarkers are sub-optimal for risk stratification of HCC development in high-risk populations, early diagnosis, prognostication, and treatment response prediction. Since about 20% of HCCs do not produce α-FP due to its biological diversity, combining α-FP with novel biomarkers can enhance HCC detection sensitivity. There is a chance to offer promising cancer management methods in high-risk populations by utilizing HCC screening strategies derived from new tumor biomarkers and prognostic scores created by combining biomarkers with distinct clinical parameters. Despite numerous efforts to identify molecules as potential biomarkers, there is no single ideal marker in HCC. When combined with other clinical parameters, the detection of some biomarkers has higher sensitivity and specificity in comparison with a single biomarker. Therefore, newer biomarkers and models, such as the Lens culinaris agglutinin-reactive fraction of Alpha-fetoprotein (α-FP), α-FP-L3, Des-γ-carboxy-prothrombin (DCP or PIVKA-II), and the GALAD score, are being used more frequently in the diagnosis and prognosis of HCC. Notably, the GALAD algorithm was effective in HCC prevention, particularly for cirrhotic patients, regardless of the cause of their liver disease. Although the role of these biomarkers in surveillance is still being researched, they may provide a more practical alternative to traditional imaging-based surveillance. Finally, looking for new diagnostic/surveillance tools may help improve patients' survival. This review discusses the current roles of the most used biomarkers and prognostic scores that may aid in the clinical management of HCC patients.

An Overview of Hepatocellular Carcinoma Surveillance Focusing on Non-Cirrhotic NAFLD Patients: A Challenge for Physicians

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide and it ranges from simple steatosis to hepatocellular carcinoma (HCC). HCC represents the first liver tumor and the third source of cancer death. In the next few years, the prevalence of NAFLD and consequently of HCC is estimated to increase, becoming a major public health problem. The NAFLD-HCC shows several differences compared to other causes of chronic liver disease (CLD), including the higher percentage of patients that develop HCC in the absence of liver cirrhosis. In HCC surveillance, the international guidelines suggest a six months abdominal ultrasound (US), with or without alpha-fetoprotein (AFP) evaluation, in patients with cirrhosis and in a subgroup of patients with chronic hepatitis B infection. However, this screening program reveals several limitations, especially in NAFLD patients. Thus, new biomarkers and scores have been proposed to overcome the limits of HCC surveillance. In this narrative review we aimed to explore the differences in the HCC features between NAFLD and non-NAFLD patients, and those between NAFLD-HCC developed in the cirrhotic and non-cirrhotic liver. Finally, we focused on the limits of tumor surveillance in NAFLD patients, and we explored the new biomarkers for the early diagnosis of HCC.

Diagnostic accuracy of ultrasound and alpha-fetoprotein measurement for hepatocellular carcinoma surveillance: a retrospective comparative study

BackgroundLiver cirrhosis and chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) are major risk factors for hepatocellular carcinoma (HCC). International societies guidelines recommend HCC surveillance in patients with cirrhosis and chronic hepatitis. However, the ideal surveillance strategy is still controversial. The aim of this study is to assess and compare the diagnostic accuracy of ultrasound (US) AND alpha-fetoprotein (AFP) measurement in HCC surveillance.ResultsAll patients with cirrhosis and/or infection with HBV and HVC, who received HCC surveillance through US and AFP measurement between January 2013 and January 2016, were retrospectively evaluated. The performance of surveillance using AFP, US, and both in HCC detection was compared. After exclusion, a final cohort of 335 patients were included. Thirty-five patients (10.3%) developed HCCs. US showed no focal lesions in 259 patients, 9 benign lesions (3 cysts, 5 hemangiomas, and 1 focal fat), 16 HCCs and 51 indeterminate findings. All indeterminate findings were worked up by CT and/or MRI. For HCC detection, the area under the receiver operator characteristic (ROC) curve for US surveillance was 0.924 (95% confidence interval: 0.866–0.983, P < 0.001). For surveillance, AFP was 0.829 (95% confidence interval: 0.756– 0.902, P < 0.001) and for combined US and AFP was 0.897 (95% confidence interval: 0.854– 0.941, P < 0.001). When the traditional cutoff value of 20 ng/ml was used, the sensitivity and specificity of AFP were 63% and 88.7%, respectively. ROC curve results for AFP levels demonstrated that using 5.6 ng/ml as a cutoff, AFP will have a 77% sensitivity and 78% specificity for HCC detection. US exhibited a sensitivity and specificity of 45.7% and 100%, respectively. When indeterminate findings were considered as positive surveillance test, US exhibited a sensitivity and specificity of 91.4% and 88.3%, respectively. A combination of US and AFP exhibited a sensitivity and specificity of 97% and 87.3%, respectively.ConclusionsUS has better accuracy compared to AFP in HCC surveillance. Combined use of US and AFP improves the sensitivity for HCC detection.