A Pragmatic, Multicenter, Open-Label, Blinded-Outcome, Parallel-Group Randomized Controlled Trial of AI-Guided Risk-Adaptive Surveillance for Early Detection and Curative-Intent Salvage of Hepatocellular Carcinoma Recurrence After Resection or Thermal Ablation
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 2,000
- 试验地点
- 1
- 主要终点
- Curative-Strategy Failure-Free Survival at 24 Months
研究概览
简要总结
Hepatocellular carcinoma, the most common type of primary liver cancer, can recur after liver resection or thermal ablation performed with curative intent. Follow-up imaging is commonly scheduled at fixed intervals, although the risk of recurrence differs among patients and may change over time. This study will test whether a locked artificial intelligence system can use routinely collected clinical, laboratory, and imaging information to recommend when the next surveillance scan should occur.
Adults with no radiological evidence of viable hepatocellular carcinoma after microscopically margin-negative liver resection or complete radiofrequency or microwave ablation will be randomly assigned in a 1:1 ratio to artificial intelligence-guided risk-adapted surveillance or fixed-interval surveillance. In the artificial intelligence-guided group, participants classified as having high, intermediate, or low current recurrence risk will generally undergo the next protocol-scheduled contrast-enhanced imaging examination after 3, 4, or 6 months, respectively. Participants in the control group will undergo protocol-scheduled imaging every 4 months. The risk thresholds are designed so that the expected total number of protocol-scheduled imaging examinations is approximately comparable between the two groups over 24 months.
The artificial intelligence system provides surveillance recommendations only. It does not diagnose recurrence, determine eligibility for liver transplantation, or select anticancer treatment. Clinically indicated examinations may be performed at any time in either group. When recurrence is confirmed, participants in both groups will undergo the same protocol-defined multidisciplinary evaluation, and potentially curative-intent treatment may be considered when clinically appropriate.
The primary purpose is to determine whether artificial intelligence-guided surveillance increases the probability of being alive at 24 months without having a recurrence that is no longer amenable to protocol-defined curative-intent treatment. The study evaluates the timing and allocation of surveillance rather than an adjuvant anticancer treatment and is not intended to prevent the biological occurrence of recurrence.
详细描述
Recurrence is common after curative-intent treatment of hepatocellular carcinoma. Surveillance after liver resection or thermal ablation is therefore an essential component of long-term care. However, conventional surveillance commonly applies similar imaging intervals to patients whose recurrence risks differ substantially and may change over time. A risk-adapted strategy could allocate surveillance examinations to periods when timely detection is most likely to preserve an opportunity for curative-intent management, while avoiding unnecessary examinations during lower-risk periods.
This is a pragmatic, multicenter, open-label, parallel-group, patient-level randomized superiority trial with blinded central outcome assessment. Eligible participants will have undergone curative-intent microscopically margin-negative (R0) liver resection or complete radiofrequency or microwave ablation for hepatocellular carcinoma. Before randomization, protocol-specified contrast-enhanced computed tomography or magnetic resonance imaging must demonstrate no viable residual tumor. Complete response after thermal ablation will be established radiologically; absence of viable enhancement is not considered evidence that microscopic disease is absent.
Participants will be randomly assigned in a 1:1 ratio to an artificial intelligence-guided risk-adapted surveillance strategy or a fixed-interval surveillance strategy. Randomization will be implemented centrally and stratified by study center and initial curative-intent treatment modality. Participants and treating clinicians cannot be masked to surveillance timing. Independent central reviewers and the committee adjudicating the primary outcome will remain unaware of randomized assignment.
In the artificial intelligence-guided group, a locked artificial intelligence system will use protocol-defined baseline and longitudinal clinical, laboratory, and imaging information to estimate the participant's current risk of recurrence. Separate modality-specific components will be used for participants treated by resection and those treated by thermal ablation. Resection-specific pathological information will not be assumed to be available for participants treated by ablation.
At each protocol-defined reassessment, participants classified as having high, intermediate, or low current risk will generally have their next protocol-scheduled contrast-enhanced imaging examination arranged after 3, 4, or 6 months, respectively. Prespecified changes in clinical status, tumor-marker trajectories, or other protocol-defined findings may trigger expedited diagnostic evaluation. Symptoms or clinically concerning findings must be evaluated irrespective of the artificial intelligence score or scheduled interval. Artificial intelligence outputs are advisory and may be overridden by the treating clinician for documented clinical reasons.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Health Services Research
- 盲法
- Single (Outcomes Assessor)
盲法说明
Participants and treating clinicians cannot be masked because the surveillance intervals differ between groups. Radiologists performing independent central imaging review and members of the central multidisciplinary committee adjudicating recurrence and eligibility for protocol-defined curative-intent treatment will remain unaware of randomized assignment. Group identifiers will be concealed in materials provided for central outcome adjudication.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 years or older at the time of informed consent.
- •First diagnosis of hepatocellular carcinoma, confirmed by histopathology for participants undergoing liver resection, or by histopathology or accepted guideline-concordant imaging criteria for participants undergoing thermal ablation.
- •Completion of first curative-intent treatment consisting of either R0 liver resection with microscopically tumor-negative margins or complete radiofrequency or microwave ablation of all known hepatocellular carcinoma.
- •Qualifying multiphasic contrast-enhanced CT or MRI obtained 28 to 56 days after completion of the final curative-intent procedure.
- •Qualifying imaging confirming no viable tumor at the resection bed or ablation site, no new intrahepatic hepatocellular carcinoma, and no macrovascular invasion, regional nodal disease, or extrahepatic metastasis.
- •No unresolved lesion requiring immediate diagnostic evaluation or treatment at the time of randomization.
- •Randomization within 14 days after the qualifying post-treatment imaging assessment and before the first protocol-scheduled surveillance examination.
- •Eastern Cooperative Oncology Group performance status of 0 or
- •Child-Pugh class A liver function.
- •Medically fit for at least one protocol-defined curative-intent salvage treatment should an anatomically amenable recurrence be detected.
- •Able to undergo repeated protocol-required multiphasic contrast-enhanced CT or MRI examinations.
- •Availability of the minimum mandatory baseline data elements required to generate an output from the locked artificial intelligence system.
- •Able and willing to comply with trial procedures and provide written informed consent.
排除标准
- •Any previous episode of hepatocellular carcinoma or previous hepatocellular carcinoma-directed treatment before the current index diagnosis.
- •Microscopically or macroscopically positive surgical margins (R1 or R2 resection).
- •Residual viable tumor after thermal ablation.
- •Any radiological evidence of residual, recurrent, nodal, or metastatic hepatocellular carcinoma at screening.
- •Macrovascular invasion, regional lymph-node metastasis, or extrahepatic metastasis associated with the index hepatocellular carcinoma.
- •Index treatment involving liver transplantation, combined resection and ablation, transarterial therapy, radiotherapy, systemic anticancer therapy, or another hepatocellular carcinoma-directed treatment other than the qualifying R0 resection or complete radiofrequency or microwave ablation.
- •Previous liver transplantation, active placement on a liver-transplant waiting list, or planned liver transplantation in the absence of documented recurrent hepatocellular carcinoma.
- •Planned or ongoing adjuvant antineoplastic treatment intended to reduce hepatocellular carcinoma recurrence after the qualifying procedure. Guideline-concordant antiviral treatment and management of the underlying liver disease are permitted.
- •Concurrent participation in another interventional study expected to affect hepatocellular carcinoma recurrence, survival, surveillance intensity, or eligibility for curative-intent salvage treatment.
- •Combined hepatocellular-cholangiocarcinoma or another non-hepatocellular primary hepatic malignancy.
- •A permanent medical contraindication that would preclude all protocol-defined curative-intent salvage treatment options.
- •Inability to undergo any protocol-permitted contrast-enhanced CT or MRI modality because of contraindication to all available imaging and contrast options.
- •Active malignancy other than hepatocellular carcinoma that requires anticancer treatment or is expected to materially interfere with survival, surveillance adherence, or outcome assessment during the primary 24-month follow-up period.
- •Uncontrolled hepatic decompensation, including refractory ascites or clinically significant hepatic encephalopathy.
- •Pregnancy at the time of randomization.
- •Inability or unwillingness to provide informed consent or comply with protocol-specified follow-up.
结局指标
主要结局
Curative-Strategy Failure-Free Survival at 24 Months
时间窗: From randomization through Month 24
Time from randomization to the first occurrence of recurrent hepatocellular carcinoma that a blinded independent central multidisciplinary adjudication committee determines is not amenable to protocol-defined curative-intent liver resection, thermal ablation, or liver transplantation, or death from any cause, whichever occurs first. A recurrence adjudicated as amenable to a protocol-defined curative-intent strategy is not considered an event at that time, and the participant remains under follow-up. The reported metric will be the estimated probability of remaining event-free at Month 24.
次要结局
- Overall Survival(From randomization through Month 36)
- Conventional Recurrence-Free Survival(From randomization through Month 36)
- Curative-Intent Treatment Eligibility at First Recurrence(At the first confirmed recurrence occurring from randomization through Month 24)
- Receipt of Curative-Intent Salvage Treatment(From confirmation of first recurrence through 12 months after recurrence, for recurrences occurring through Month 24)
- Complete Response After Curative-Intent Salvage(Within 12 weeks after completion of the first curative-intent salvage treatment)
- Early-Stage Disease at First Recurrence(At the first confirmed recurrence occurring from randomization through Month 24)
- Number of Protocol-Scheduled Cross-Sectional Imaging Examinations(From randomization through Month 24)
- Total Number of Cross-Sectional Imaging Examinations(From randomization through Month 24)
- False-Positive Surveillance Evaluations(From randomization through Month 24, including a 90-day confirmation window)
- Change in EORTC QLQ-C30 Global Health Status and Quality of Life Score(At baseline and Months 6, 12, 18, and 24)
- Surveillance-Related Serious Adverse Events(From randomization through Month 24)