INTRODUCTION: Immune checkpoint inhibitors (ICIs) are promising agents for the treatment of hepatocellular carcinoma (HCC). However, the establishment of noninvasive measure that could predict the response to ICIs is challenging. This study aimed to evaluate tumor responses to ICIs using the hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI), which was shown to reflect Wnt/β-catenin activating mutation. METHODS: A total of 68 intrahepatic HCC nodules from 18 patients with unresectable HCC and Child-Pugh class A liver function who received anti-programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1) monotherapy were enrolled in this study. All patients had viable intrahepatic lesions evaluable using the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI within the 6 months prior to the treatment. The relative enhancement ratio was calculated, and the time to nodular progression (TTnP) defined as 20% or more increase in each nodule was compared between higher or hypo-enhancement HCC nodules. Then, the progression-free survival (PFS) and objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) were compared between patients with and without HCC nodules with higher enhancement on hepatobiliary phase images. RESULTS: The median PFS was 2.7 (95% confidence interval [CI]: 1.4-4.0) months in patients with HCC nodules with higher enhancement (n = 8) and 5.8 (95% CI: 0.0-18.9) months in patients with hypointense HCC nodules (n = 10) (p = 0.007). The median TTnP of HCC nodules with higher enhancement (n = 23) was 1.97 (95% CI: 1.86-2.07) months and that of hypointense HCC nodules (n = 45) was not reached (p = 0.003). The ORR was 12.5% (1/8) versus 30.0% (3/10); the disease control rate was 37.5% (3/8) versus 70.0% (7/10), respectively, in patients with or without higher enhancement intrahepatic HCC nodules. CONCLUSION: The TTnP on HCC nodules with higher enhancement and the median PFS in patients who carried higher enhancement intrahepatic HCC nodules were significantly shorter than those in hypointense HCC nodules with anti-PD-1/PD-L1 monotherapy. The intensity of the nodule on the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI is a promising imaging biomarker for predicting unfavorable response with anti-PD-1/PD-L1 monotherapy in patients with HCC.
INTRODUCTION: Immune checkpoint inhibitors (ICIs) are promising agents for the treatment of hepatocellular carcinoma (HCC). However, the establishment of noninvasive measure that could predict the response to ICIs is challenging. This study aimed to evaluate tumor responses to ICIs using the hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI), which was shown to reflect Wnt/β-catenin activating mutation. METHODS: A total of 68 intrahepatic HCC nodules from 18 patients with unresectable HCC and Child-Pugh class A liver function who received anti-programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1) monotherapy were enrolled in this study. All patients had viable intrahepatic lesions evaluable using the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI within the 6 months prior to the treatment. The relative enhancement ratio was calculated, and the time to nodular progression (TTnP) defined as 20% or more increase in each nodule was compared between higher or hypo-enhancement HCC nodules. Then, the progression-free survival (PFS) and objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) were compared between patients with and without HCC nodules with higher enhancement on hepatobiliary phase images. RESULTS: The median PFS was 2.7 (95% confidence interval [CI]: 1.4-4.0) months in patients with HCC nodules with higher enhancement (n = 8) and 5.8 (95% CI: 0.0-18.9) months in patients with hypointense HCC nodules (n = 10) (p = 0.007). The median TTnP of HCC nodules with higher enhancement (n = 23) was 1.97 (95% CI: 1.86-2.07) months and that of hypointense HCC nodules (n = 45) was not reached (p = 0.003). The ORR was 12.5% (1/8) versus 30.0% (3/10); the disease control rate was 37.5% (3/8) versus 70.0% (7/10), respectively, in patients with or without higher enhancement intrahepatic HCC nodules. CONCLUSION: The TTnP on HCC nodules with higher enhancement and the median PFS in patients who carried higher enhancement intrahepatic HCC nodules were significantly shorter than those in hypointense HCC nodules with anti-PD-1/PD-L1 monotherapy. The intensity of the nodule on the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI is a promising imaging biomarker for predicting unfavorable response with anti-PD-1/PD-L1 monotherapy in patients with HCC.
Authors: P Therasse; S G Arbuck; E A Eisenhauer; J Wanders; R S Kaplan; L Rubinstein; J Verweij; M Van Glabbeke; A T van Oosterom; M C Christian; S G Gwyther Journal: J Natl Cancer Inst Date: 2000-02-02 Impact factor: 13.506
Authors: A Trotti; R Byhardt; J Stetz; C Gwede; B Corn; K Fu; L Gunderson; B McCormick; M Morrisintegral; T Rich; W Shipley; W Curran Journal: Int J Radiat Oncol Biol Phys Date: 2000-04-01 Impact factor: 7.038
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Authors: Andrew X Zhu; Yoon-Koo Kang; Chia-Jui Yen; Richard S Finn; Peter R Galle; Josep M Llovet; Eric Assenat; Giovanni Brandi; Marc Pracht; Ho Yeong Lim; Kun-Ming Rau; Kenta Motomura; Izumi Ohno; Philippe Merle; Bruno Daniele; Dong Bok Shin; Guido Gerken; Christophe Borg; Jean-Baptiste Hiriart; Takuji Okusaka; Manabu Morimoto; Yanzhi Hsu; Paolo B Abada; Masatoshi Kudo Journal: Lancet Oncol Date: 2019-01-18 Impact factor: 41.316
Authors: Angel Garcia-Diaz; Daniel Sanghoon Shin; Blanca Homet Moreno; Justin Saco; Helena Escuin-Ordinas; Gabriel Abril Rodriguez; Jesse M Zaretsky; Lu Sun; Willy Hugo; Xiaoyan Wang; Giulia Parisi; Cristina Puig Saus; Davis Y Torrejon; Thomas G Graeber; Begonya Comin-Anduix; Siwen Hu-Lieskovan; Robert Damoiseaux; Roger S Lo; Antoni Ribas Journal: Cell Rep Date: 2017-05-09 Impact factor: 9.423