Park Sunmin, Rim Chai Hong, Jung Young Kul, Yim Hyung Joon, Chung Hwan Hoon, Yoon Won Sup
Department of Radiation Oncology, Ansan Hospital, College of Medicine, Korea University, Ansan, Gyeong-gi, Republic of Korea.
Department of Internal Medicine, Ansan Hospital, College of Medicine, Korea University, Ansan, Gyeong-gi, Republic of Korea.
PLoS One. 2025 May 20;20(5):e0323450. doi: 10.1371/journal.pone.0323450. eCollection 2025.
Signal changes after high dose irradiation on MRI make it difficult to assess the therapeutic response of hepatocellular carcinoma (HCC). To overcome the limitation of imaging work-up, our study predicted clinical outcomes through tumor marker dynamics in HCC after external beam radiotherapy (EBRT). As a single-center retrospective study, those who underwent conventional fractionated EBRT for viable HCC from 2010 to 2021 were analyzed. Patients with elevated tumor markers of AFP ≥ 10 ng/ml or PIVKA-II ≥ 30 mAU/ml before EBRT were enrolled. Remission of AFP, PIVKA-II, and MoRAL score (=11*√PIVKA-II + 2*√AFP) from pre-EBRT to post-EBRT at 1 month and 3 months was examined. For 1-year and 2-years OS, variables of tumor markers were examined using the receiver operation characteristics (ROC). Multivariate analyses of Cox-regression for OS were conducted. Among 111 patients, 34 patients were estimated to survive more than 2-years. In multivariate analyses for OS, tumor number (P = 0.004), portal vein tumor thrombus (P = 0.004), and Barcelona liver cancer staging (P < 0.001) were found to be significant. For 2-years OS, the degree of AFP remission at 3 months (rAFP_3M) had an AUC of 0.852 (95% CI: 0.758-0.946, P < 0.001), a sensitivity of 85.5%, and a specificity of 82.6% with a cut-off value of 3.7%. MoRAL score at 3 months (MoRAL_3M) had an AUC of 0.814 (95% CI: 0.728-0.900, P = 0.000), a sensitivity of 76.5%, and a specificity of 77.8% with a cut-off value of 111.64. In new multivariate analyses including the above significant factors plus either rAFP_3M or MoRAL_3M, rAFP_3M (P < 0.001) and MoRAL_3M (P < 0.001) were found to be independent prognostic factors in each model. This study confirmed the importance of the changed tumor marker after EBRT rather than the baseline value. Dynamic change of AFP and MoRAL score at post-EBRT 3 months could be recommended as potential indicators for clinical outcomes.
MRI上高剂量放疗后的信号变化使得评估肝细胞癌（HCC）的治疗反应变得困难。为克服影像学检查的局限性，我们的研究通过外照射放疗（EBRT）后HCC的肿瘤标志物动态变化预测临床结局。作为一项单中心回顾性研究，分析了2010年至2021年期间因存活的HCC接受常规分割EBRT的患者。纳入EBRT前甲胎蛋白（AFP）≥10 ng/ml或异常凝血酶原（PIVKA-II）≥30 mAU/ml的肿瘤标志物升高的患者。检查了从EBRT前到EBRT后1个月和3个月时AFP、PIVKA-II和MoRAL评分（=11×√PIVKA-II + 2×√AFP）的缓解情况。对于1年和2年总生存期（OS），使用受试者工作特征（ROC）曲线检查肿瘤标志物变量。进行了OS的Cox回归多因素分析。111例患者中，估计34例患者存活超过2年。在OS的多因素分析中，发现肿瘤数量（P = 0.004）、门静脉癌栓（P = 0.004）和巴塞罗那肝癌分期（P < 0.001）具有显著性。对于2年OS，3个月时AFP缓解程度（rAFP_3M）的曲线下面积（AUC）为0.852（95%可信区间：0.758 - 0.946，P < 0.001），敏感度为85.5%，特异度为82.6%，临界值为3.7%。3个月时MoRAL评分（MoRAL_3M）的AUC为0.814（95%可信区间：0.728 - 0.900，P = 0.000），敏感度为76.5%，特异度为77.8%，临界值为111.64。在包括上述显著因素加上rAFP_3M或MoRAL_3M之一的新多因素分析中，发现rAFP_3M（P < 0.001）和MoRAL_3M（P < 0.001）在每个模型中均为独立预后因素。本研究证实了EBRT后肿瘤标志物变化而非基线值的重要性。EBRT后3个月时AFP和MoRAL评分的动态变化可推荐作为临床结局的潜在指标。
