Comparison of ultraSound, Abbreviated MRI witH and Without HBP aS mOdalities for HCC suRveillance in patienTs With High Risk

Официальное название

Comparison of ultraSound, Abbreviated MRI witH and Without HBP aS mOdalities for HCC suRveillance in patienTs With High Risk: a Multi-centers, Randomized Controlled Open-label Trial

Обзор

Active surveillance in high-risk hepatocellular carcinoma (HCC) populations enables early detection of tumors. The currently recommended monitoring protocol involves biannual serum alpha-fetoprotein (AFP) testing combined with liver ultrasound (US) examinations. However, conventional US demonstrates limited sensitivity in detecting early-stage HCC lesions. MRI demonstrates high sensitivity in monitoring cirrhotic patients, but prolonged scanning time limits its routine clinical application. Several abbreviated MRI protocols have been developed for HCC detection, aiming to reduce acquisition time while improving early-stage HCC diagnostic accuracy. The main question this clinical trial aims to answer is: Can non-contrast abbreviated MRI (NC-AMRI) and enhanced abbreviated MRI (E-AMRI) detect more early-stage HCC lesions compared to US-based screening? Researchers will randomly divide the participants into three groups in a 1:1:1 ratio, with different surveillance strategies, focused on early HCC detection rates.

Подробное описание

Active surveillance in high-risk hepatocellular carcinoma (HCC) populations enables early detection of tumors. Current guidelines recommend biannual AFP testing with liver ultrasound (US), but US has suboptimal sensitivity for early HCC detection.

MRI, while highly sensitive for monitoring cirrhotic patients, is limited in routine use due to long scan times.. Several abbreviated MRI protocols have been developed for HCC detection, aiming to reduce acquisition time while improving early-stage HCC diagnostic accuracy.

This is a multicenter, randomized controlled, open-label clinical trial targeting individuals at high risk for HCC, with a planned enrollment of 1,389 participants.

This trial aims to evaluate the effectiveness of three surveillance strategies-US, non-contrast abbreviated MRI (NC-AMRI; T2WI/DW sequences ) and enhanced abbreviated MRI (E-AMRI; using gadoxetic acid disodium with T2WI/DWI/HBP sequences)-in the active monitoring of HCC in high-risk populations.

Researchers will randomly assign participants (1:1:1) to three surveillance arms, followed by a 24-month long-term follow-up after the initial 18-month monitoring. The study includes 18 months of active surveillance and 24 months of extended follow-up.

The surveillance protocols of three groups:

1. Control: Biannual US + AFP; 2. NC-AMRI: Alternating NC-AMRI (T2WI/DWI) and US at 6/18 months; 3. E-AMRI: Alternating E-AMRI (T2WI/DWI/HBP with gadoxetic acid) and US at 6/18 months.

All the participants will be followed up every 6 months according to the above-mentioned grouping and follow-up contents. For those participants who are suspected HCC, an enhanced abdominal CT or enhanced MRI will be performed for confirmation. If the imaging suggests HCC, the research subject will be removed from the group and enter the clinical routine diagnosis and treatment process. If there is no evidence of HCC, the subject will continue to be followed up as planned. Finally, at the end of the 18-month follow-up period, a routine enhanced abdominal CT/MRI will be carried out to confirm the presence of HCC.

The primary focus of the clinic trial is the the early-stage (BCLC 0+A stage) HCC detection rate at 18th month post-enrollment, with pairwise comparisons among the three strategies.

χ² tests will compare detection rates, sensitivity, and specificity; Kaplan-Meier analysis with log-rank tests will evaluate survival. Survival analysis will include all HCC cases diagnosed in the study.

Вмешательства

• Устройство non-contrast abbreviated MRI (NC-AMRI)
  Non-contrast abbreviated MRI (NC-AMRI) examination include T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI), which takes 10 minutes approximately.
• Устройство enhanced abbreviated MRI (E-AMRI)
  E-AMRI examination (using gadoxetic acid disodium) including T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI)and hepatobiliary phase (HBP) images, which takes 15 minutes approximately.

Первичные конечные точки

• the early-stage and very early-stage HCC detection rate [Срок оценки: at 18th month]

Вторичные конечные точки (8)

• 18th month mortality rate in HCC patients [Срок оценки: at 18th month]
• 18th month survival rate in HCC patients [Срок оценки: at 18th month]
• 18th median survival time in HCC patients [Срок оценки: at 18th month]
• Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). [Срок оценки: at 18th month]
• the incremental cost-effectiveness ratio (ICER) [Срок оценки: at 18th month]
• Patient compliance to the study protocol [Срок оценки: at 18th month]
• Patient acceptability to the study protocol [Срок оценки: at 18th month]
• early and very early-stage HCC detection at 42th month [Срок оценки: at 42th month]

Критерии участия

Критерии включения

• According to the Guidelines for the Diagnosis and Treatment of Primary Liver Cancer (2024 Edition) from department of medical administration, nation health commission of the People's Republic of China, with any one of the following high-risk factors for liver cancer: hepatitis B and/or C virus infection, excessive alcohol consumption, hepatic steatosis or metabolic dysfunction-associated liver disease, dietary exposure to aflatoxin B1, liver cirrhosis from other causes, or a family history of liver cancer, and an aMAP score (age⁃male⁃albi⁃platelets score) of 60-100 points.
• Liver disease patients with no evidence of suspected liver cancer in any imaging examination (liver US, contrast-enhanced CT, or contrast-enhanced MRI) within the past six months.
• Signed informed consent form.

Критерии исключения

• History of previous liver cancer diagnosis.
• Baseline screening at enrollment diagnosed with liver cancer.
• Child-Pugh score ≥ 10 (class C).
• History of other malignant tumors.
• Pregnant or lactating women.
• Clinically diagnosed severe heart/lung disease or uncontrolled comorbidities, with investigator-judged life expectancy < 2 years.
• Glomerular filtration rate < 50 mL/min.
• Inability to undergo (enhanced) MRI due to contraindications or relative contraindications.
• Poor compliance or unsuitability for the clinical trial as judged by the investigator.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Скрининг

Центры проведения

Китай · 12 центров

• Peking University People's Hospital — Пекин
• The First Affiliated Hospital of Army Medical University — Чунцин
• Handan Central Hospital — Handan
• Harbin Medical University Cancer Hospital — Харбин
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Ухань
• China-Japan Union Hospital, Jilin University — Changchun
• The Second Hospital of Jilin University — Changchun
• Qilu Hospital of Shandong University — Цзинань
• … и ещё 4 центра

Публикации

• Kim SY, An J, Lim YS, Han S, Lee JY, Byun JH, Won HJ, Lee SJ, Lee HC, Lee YS. MRI With Liver-Specific Contrast for Surveillance of Patients With Cirrhosis at High Risk of Hepatocellular Carcinoma. JAMA Oncol. 2017 Apr 1;3(4):456-463. doi: 10.1001/jamaoncol.2016.3147. PMID 27657493
• Yu NC, Chaudhari V, Raman SS, Lassman C, Tong MJ, Busuttil RW, Lu DS. CT and MRI improve detection of hepatocellular carcinoma, compared with ultrasound alone, in patients with cirrhosis. Clin Gastroenterol Hepatol. 2011 Feb;9(2):161-7. doi: 10.1016/j.cgh.2010.09.017. Epub 2010 Oct 1. PMID 20920597
• Tzartzeva K, Obi J, Rich NE, Parikh ND, Marrero JA, Yopp A, Waljee AK, Singal AG. Surveillance Imaging and Alpha Fetoprotein for Early Detection of Hepatocellular Carcinoma in Patients With Cirrhosis: A Meta-analysis. Gastroenterology. 2018 May;154(6):1706-1718.e1. doi: 10.1053/j.gastro.2018.01.064. Epub 2018 Feb 6. PMID 29425931
• Colli A, Fraquelli M, Casazza G, Massironi S, Colucci A, Conte D, Duca P. Accuracy of ultrasonography, spiral CT, magnetic resonance, and alpha-fetoprotein in diagnosing hepatocellular carcinoma: a systematic review. Am J Gastroenterol. 2006 Mar;101(3):513-23. doi: 10.1111/j.1572-0241.2006.00467.x. PMID 16542288
• Simmons O, Fetzer DT, Yokoo T, Marrero JA, Yopp A, Kono Y, Parikh ND, Browning T, Singal AG. Predictors of adequate ultrasound quality for hepatocellular carcinoma surveillance in patients with cirrhosis. Aliment Pharmacol Ther. 2017 Jan;45(1):169-177. doi: 10.1111/apt.13841. Epub 2016 Nov 8. PMID 27862091
• Wong LL, Reyes RJ, Kwee SA, Hernandez BY, Kalathil SC, Tsai NC. Pitfalls in surveillance for hepatocellular carcinoma: How successful is it in the real world? Clin Mol Hepatol. 2017 Sep;23(3):239-248. doi: 10.3350/cmh.2017.0008. Epub 2017 Jul 14. PMID 28706177

Идентификаторы

NCT: NCT07010588 · 2025-Z-43

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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