Department of Oncology-Hematology, Humanitas Cancer Center, IRCCS, Rozzano, Italy.
J Hepatol. 2012 Jul;57(1):101-7. doi: 10.1016/j.jhep.2012.02.016. Epub 2012 Mar 10.
BACKGROUND & AIMS: Tumor shrinkage has been considered a fundamental surrogate efficacy measure for new cancer treatments. However, in patients treated with sorafenib for advanced hepatocellular carcinoma (HCC), tumor shrinkage rarely accompanies increased survival, thereby questioning the prognostic value of imaging-based Response Evaluation Criteria in Solid Tumors (RECIST). We investigated the prognostic usefulness of a decrease in serum alpha-fetoprotein (AFP) and compared it to RECIST.
In HCC patients treated with sorafenib with baseline AFP >20 ng/ml, AFP response was defined as a >20% decrease in AFP during 8weeks of treatment. Patients were also assessed by RECIST and were categorized as having radiologically proven progressive disease or disease control (consisting of complete or partial responses and stable disease). Comparisons of survival by RECIST and AFP response were corrected for guarantee-time bias by the landmark method.
We evaluated 85 patients for AFP response, among them, 82 were also evaluated by RECIST. In the analysis of AFP response, 32 out of 85 patients (37.6%) were responders, whereas 58 out of 82 patients (70.7%) achieved disease control. In landmark analysis, the hazard ratios (HR) for survival according to AFP response and disease control were 0.59 (p=0.040) and 1.03 (p=0.913), respectively. In multivariate analysis, only AFP response (HR=0.52; p=0.009) and Cancer of the Liver Italian Program dichotomized stage (HR=0.42; p=0.002) were prognostic factors of survival.
Assessment of AFP response may be considered as an alternative to RECIST to capture sorafenib activity in HCC.
肿瘤缩小已被认为是新癌症治疗的基本替代疗效指标。然而，在接受索拉非尼治疗的晚期肝细胞癌（HCC）患者中，肿瘤缩小很少伴随生存时间的延长，从而对基于影像学的实体瘤反应评价标准（RECIST）的预后价值提出质疑。我们研究了血清甲胎蛋白（AFP）下降的预后意义，并将其与 RECIST 进行了比较。
在基线 AFP >20ng/ml 的接受索拉非尼治疗的 HCC 患者中，AFP 反应定义为治疗 8 周时 AFP 下降>20%。还通过 RECIST 对患者进行评估，并将其分为有影像学证实的进展性疾病或疾病控制（包括完全或部分缓解和稳定疾病）。通过 landmark 法校正保证时间偏倚，比较 RECIST 和 AFP 反应的生存情况。
我们评估了 85 例 AFP 反应患者，其中 82 例也通过 RECIST 进行了评估。在 AFP 反应分析中，85 例患者中有 32 例（37.6%）为应答者，而 82 例患者中有 58 例（70.7%）达到疾病控制。在 landmark 分析中，根据 AFP 反应和疾病控制的生存危险比（HR）分别为 0.59（p=0.040）和 1.03（p=0.913）。在多变量分析中，只有 AFP 反应（HR=0.52；p=0.009）和意大利肝癌计划（CLIP）分期（HR=0.42；p=0.002）是生存的预后因素。
评估 AFP 反应可能被认为是替代 RECIST 的方法，以捕捉索拉非尼在 HCC 中的活性。
