Supplementary Material for: Assessment of Macrovascular Invasion in Advanced Hepatocellular Carcinoma: Clinical Implications and Treatment Outcomes with Systemic Therapy

Introduction: Macrovascular invasion (MVI) is a strong prognostic factor for advanced hepatocellular carcinoma (HCC). The current criteria for radiological assessment are unclear in evaluating the impact of MVI on systemic therapy. In this study, we standardized the assessment of MVI and validated its clinical relevance. Methods: Clinical data were collected from patients with advanced HCC and MVI who received first-line systemic therapy at four medical centers in Japan. First, we used macrovascular invasion progression disease (MVI-PD) to track MVI progression, and Response Evaluation Criteria in Solid Tumours version 1.1 progression disease (RECIST v1.1-PD) to evaluate tumor enlargement other than MVI and the appearance of new lesions. Next, we assessed the prognostic value of MVI-PD and RECIST v1.1-PD. Results: Of the 207 advanced HCC patients with MVI, 189 received appropriate imaging evaluation. 40 (21.2%) patients had MVI-PD and RECIST v1.1-PD, 51 (27.0%) had prior MVI-PD, and 61 (32.3%) had prior RECIST v1.1-PD. In a landmark analysis, the prognosis of 163 patients who survived more than three months was analyzed based on the assessment of imaging response during the first three months. The median overall survival (OS) was 5.4 months in those who had MVI-PD and RECIST v1.1-PD, 7.4 months in those who had RECIST v1.1-PD only, 7.2 months in those who had MVI-PD only, and 19.7 months in patients who had neither (p<0.001). The correlation coefficients between progression-free survival and OS in patients with appropriate imaging assessments were similar for MVI-PD (0.515) and RECIST v1.1-PD (0.498). Conclusion: Our findings demonstrate the link between MVI progression and poor OS in systemic therapy for advanced HCC, emphasizing the importance of an accurate method for assessing MVI progression.

引言：大血管侵犯（Macrovascular invasion, MVI）是晚期肝细胞癌（hepatocellular carcinoma, HCC）的重要预后因素。当前的影像学评估标准在评估MVI对全身治疗的影响方面仍缺乏明确规范。本研究标准化了MVI的评估流程，并验证了其临床相关性。
方法：本研究收集了日本四家医疗中心内接受一线全身治疗的晚期肝细胞癌合并MVI患者的临床资料。首先，本研究采用大血管侵犯进展性疾病（Macrovascular invasion progression disease, MVI-PD）来追踪MVI的进展情况，并采用实体瘤疗效评价标准1.1版进展性疾病（Response Evaluation Criteria in Solid Tumours version 1.1-PD, RECIST v1.1-PD）来评估除MVI之外的肿瘤增大以及新发病灶的出现。随后，本研究评估了MVI-PD与RECIST v1.1-PD的预后价值。
结果：本研究共纳入207例合并MVI的晚期肝细胞癌患者，其中189例完成了合格的影像学评估。在这189例患者中，40例（21.2%）同时存在MVI-PD与RECIST v1.1-PD，51例（27.0%）仅既往出现MVI-PD，61例（32.3%）仅既往出现RECIST v1.1-PD。本研究针对存活时长超过3个月的163例患者开展了里程碑分析（landmark analysis），基于患者前3个月的影像学应答评估结果分析其预后情况。结果显示，同时存在MVI-PD与RECIST v1.1-PD患者的中位总生存期（overall survival, OS）为5.4个月，仅存在RECIST v1.1-PD患者为7.4个月，仅存在MVI-PD患者为7.2个月，无上述两类进展的患者为19.7个月（p<0.001）。在完成合格影像学评估的患者中，无进展生存期（progression-free survival, PFS）与总生存期的相关系数在MVI-PD组为0.515，在RECIST v1.1-PD组为0.498，二者数值相近。
结论：本研究结果证实，在晚期肝细胞癌的全身治疗中，MVI进展与不良总生存期存在显著关联，强调了精准评估MVI进展方法的重要临床价值。