Department of Abdominal Imaging, UT MD Anderson Cancer Center, 1400 Pressler Street, Houston, Texas, USA.
Department of Imaging Physics, UT MD Anderson Cancer Center, Houston, Texas, USA.
J Immunother Cancer. 2019 Nov 28;7(1):329. doi: 10.1186/s40425-019-0766-y.
Currently, there are no imaging predictors of immunotherapy outcome in hepatocellular carcinoma (HCC). The study aim was to determine if stiffness changes measured by magnetic resonance elastography (MRE) can be a predictor of immunotherapy response in patients with advanced HCC.
This was a prospective study of 15 patients with biopsy proven-advanced HCC treated with Pembrolizumab. All patients had liver MRE and liver biopsy at baseline and at 6 weeks of therapy. Change in HCC stiffness on MRE was compared with overall survival (OS), time to disease progression (TTP), and number of intratumoral CD3+ T lymphocytes. Analysis was performed using descriptive statistics and Spearman correlation (R); p-value < 0.05 was considered statistically significant.
Nine patients were evaluable. Median age was 71 years (range, 54-78). Etiology of liver disease was HCV (n = 4), HBV (n = 1) and NASH (n = 4). Median OS and TTP were 44 weeks and 13 weeks, respectively. Average baseline HCC stiffness and change in HCC stiffness were 5.0 kPa and 0.12 kPa, respectively. In contrast, average non-tumor liver stiffness was 3.2 kPa, and did not significantly change at 6 weeks (p = 0.42). Average size of measured tumor and change in size were 4 cm and - 0.32 cm, respectively. Change in HCC stiffness at 6 weeks correlated significantly with OS (R = 0.81), and TTP (R = 0.88,p < 0.01). Abundance of intratumoral T lymphocytes on tumor biopsy correlated significantly with HCC stiffness (R = 0.79,p = 0.007).
Our pilot MRE data suggests early change in tumor stiffness may be an indicator of immunotherapy response in patients with advanced HCC.
目前，尚无影像学预测肝细胞癌（HCC）免疫治疗疗效的指标。本研究旨在确定磁共振弹性成像（MRE）测量的硬度变化是否可以预测晚期 HCC 患者的免疫治疗反应。
这是一项前瞻性研究，共纳入 15 例经活检证实的晚期 HCC 患者，接受 Pembrolizumab 治疗。所有患者在基线和治疗 6 周时均进行肝脏 MRE 和肝脏活检。MRE 上 HCC 硬度的变化与总生存期（OS）、疾病进展时间（TTP）和肿瘤内 CD3+T 淋巴细胞数量进行比较。采用描述性统计和 Spearman 相关分析（R）进行分析；p 值<0.05 为统计学显著。
9 例患者可评估。中位年龄为 71 岁（范围，54-78 岁）。肝脏疾病的病因是 HCV（n=4）、HBV（n=1）和 NASH（n=4）。中位 OS 和 TTP 分别为 44 周和 13 周。平均基线 HCC 硬度和 HCC 硬度变化分别为 5.0kPa 和 0.12kPa。相反，平均非肿瘤性肝脏硬度在 6 周时无显著变化（p=0.42）。平均肿瘤大小和大小变化分别为 4cm 和-0.32cm。6 周时 HCC 硬度的变化与 OS（R=0.81）和 TTP（R=0.88，p<0.01）显著相关。肿瘤活检中肿瘤内 T 淋巴细胞的丰度与 HCC 硬度显著相关（R=0.79，p=0.007）。
我们的初步 MRE 数据表明，肿瘤硬度的早期变化可能是晚期 HCC 患者免疫治疗反应的指标。
