Heterogeneity of Treatment Effects of Adding Locoregional Therapies to Atezolizumab Plus Bevacizumab in Patients With Unresectable Hepatocellular Carcinoma Based on Clinical and Multiregional, Multiphase Contrast-Enhanced CT/MRI Features (ISMIO-026)
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 2,658
- 试验地点
- 1
- 主要终点
- Overall survival
研究概览
简要总结
uHCC imposes a substantial disease burden in China and the Asia-Pacific region. Atezo+Bev is an important first-line regimen for patients who have not received prior systemic therapy; however, not all patients achieve adequate and durable tumor control. In clinical practice, ablation, radiotherapy, or transarterial therapy is often added to Atezo+Bev to intensify intrahepatic disease control. The indications, timing, efficacy, and risk of liver-function impairment vary across LRTs. Most existing studies report average treatment effects and often use TACE as a fixed backbone, and therefore do not directly identify which patients receiving Atezo+Bev should receive early LRTs.
Using target trial emulation and HTE analysis, this study will integrate baseline clinical variables with pretreatment contrast-enhanced CT/MRI features to estimate the CATE of early LRT initiation and identify patients likely to achieve greater survival benefit.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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 on the index date.
- •Receipt of at least one dose each of atezolizumab and bevacizumab as part of the same first-line combination regimen, with an interval of ≤28 days between the first administrations of the two drugs.
- •At least one intrahepatic lesion amenable to a protocol-specified LRT on the index date, with no absolute contraindication to Atezo+Bev or to all feasible LRTs.
- •A clinical, radiologic, or pathologic diagnosis of uHCC on or before the index date; baseline EHS is permitted.
- •Survival status or the date last known alive after the index date can be ascertained.
- •No systemic therapy for HCC before the regimen initiation date.
- •No LRT within 60 days before the index date or between baseline imaging and the index date; earlier prior LRTs are permitted provided that an untreated, measurable intrahepatic lesion remains.
- •A technically adequate baseline contrast-enhanced CT/MRI examination and at least one untreated intrahepatic lesion that can be delineated and evaluated.
- •Baseline ECOG performance status of 0-2.
排除标准
- •Another primary malignancy requiring active systemic treatment on the index date, except for a malignancy that has been cured and has a low risk of recurrence.
- •Participation on the index date in an interventional study that could affect treatment allocation or outcome assessment.
- •Suitability for immediate curative resection or liver transplantation following multidisciplinary assessment.
- •An absolute contraindication to Atezo+Bev or to all feasible LRTs.
- •Active autoimmune disease or immunodeficiency requiring systemic immunosuppression or constituting a contraindication to atezolizumab.
- •Inadequately controlled high-risk esophageal/gastric varices, recent variceal bleeding, an uncorrected bleeding tendency, or clinically significant coagulopathy.
- •Inability to determine the index date, primary treatment strategy, OS outcome/censoring date, or absence of a technically adequate baseline contrast-enhanced CT/MRI examination.
研究组 & 干预措施
Training Cohort
Retrospective validation cohort
Prospective validation cohort
Biological validation cohort
结局指标
主要结局
Overall survival
时间窗: through study completion, an average of 1 year
With OS as the primary outcome, to estimate the overall treatment effect and CATE of initiating LRTs within 60 days after Atezo+Bev initiation versus not initiating LRTs within 60 days; and to integrate baseline clinical variables with multiregional radiomic, dynamic/habitat, and deep representation features from pretreatment contrast-enhanced CT/MRI to develop and validate an HTE decision model.
次要结局
- Model calibration(through study completion, an average of 1 year)
- Benefit ranking(through study completion, an average of 1 year)
- PFS/mPFS(through study completion, an average of 1 year)
研究者
Jian Lu
Prof.
Zhongda Hospital