Seung Yeun Chung1,2, Kyoung-Jin Kim1, Jinsil Seong1. 1. Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. 2. Department of Radiation Oncology, Ajou University School of Medicine, Suwon-si, Republic of Korea.
Abstract
Introduction: In the era of biomarker-driven cancer therapy, robust biomarkers for hepatocellular carcinoma (HCC) have not been well-defined. In this hypothesis-generating study, we investigated biomarkers that can be incorporated to predict treatment outcomes in patients with locally advanced HCC who are administered liver-directed combined radiotherapy (LDCRT). Methods: Ninety-nine patients with HCC who were treated with conventional fractionation LDCRT between July 2016 and October 2018 were enrolled in this prospective single-arm study. Clinical outcomes and possible serum biomarkers, including soluble programmed cell death ligand-1 (sPD-L1), interleukin (IL)-10, IL-6, cell-free DNA (cfDNA), inter-alpha inhibitor H4, and interferon-gamma, were analyzed. The primary endpoint was disease progression, and additional endpoints were local failure-free rate, intrahepatic failure-free rate, and lung metastasis-free rate. Results: The median follow-up period was 18.7 months. The 1-year progression-free rate was 38.2%. Increasing baseline sPD-L1 per pg/mL, previous treatment history, protein induced by vitamin K absence-II >1,629 mAU/mL, and multiple tumors were the adverse factors for progression based on multivariate analysis. Survival tree analysis revealed three prognostic groups for progression, in which patients with multiple lesions and baseline sPD-L1 ≥41.07 pg/mL showed the worst outcomes. For dynamic changes in biomarker levels, sPD-L1 fold change and cfDNA fold-change values were unfavorable factors for progression. Conclusion: Baseline sPD-L1, sPD-L1 fold change, and cfDNA fold-change values showed the highest potential as biomarkers for predicting post-treatment progression after LDCRT in HCC patients. By incorporating clinical factors, these biomarkers may be useful for devising a biomarker-driven treatment paradigm in locally advanced HCC.
Introduction: In the era of biomarker-driven cancer therapy, robust biomarkers for hepatocellular carcinoma (HCC) have not been well-defined. In this hypothesis-generating study, we investigated biomarkers that can be incorporated to predict treatment outcomes in patients with locally advanced HCC who are administered liver-directed combined radiotherapy (LDCRT). Methods: Ninety-nine patients with HCC who were treated with conventional fractionation LDCRT between July 2016 and October 2018 were enrolled in this prospective single-arm study. Clinical outcomes and possible serum biomarkers, including soluble programmed cell death ligand-1 (sPD-L1), interleukin (IL)-10, IL-6, cell-free DNA (cfDNA), inter-alpha inhibitor H4, and interferon-gamma, were analyzed. The primary endpoint was disease progression, and additional endpoints were local failure-free rate, intrahepatic failure-free rate, and lung metastasis-free rate. Results: The median follow-up period was 18.7 months. The 1-year progression-free rate was 38.2%. Increasing baseline sPD-L1 per pg/mL, previous treatment history, protein induced by vitamin K absence-II >1,629 mAU/mL, and multiple tumors were the adverse factors for progression based on multivariate analysis. Survival tree analysis revealed three prognostic groups for progression, in which patients with multiple lesions and baseline sPD-L1 ≥41.07 pg/mL showed the worst outcomes. For dynamic changes in biomarker levels, sPD-L1 fold change and cfDNA fold-change values were unfavorable factors for progression. Conclusion: Baseline sPD-L1, sPD-L1 fold change, and cfDNA fold-change values showed the highest potential as biomarkers for predicting post-treatment progression after LDCRT in HCC patients. By incorporating clinical factors, these biomarkers may be useful for devising a biomarker-driven treatment paradigm in locally advanced HCC.
Authors: J Tie; I Kinde; Y Wang; H L Wong; J Roebert; M Christie; M Tacey; R Wong; M Singh; C S Karapetis; J Desai; B Tran; R L Strausberg; L A Diaz; N Papadopoulos; K W Kinzler; B Vogelstein; P Gibbs Journal: Ann Oncol Date: 2015-04-07 Impact factor: 32.976
Authors: Won Hee Lee; Hwa Kyung Byun; Jin Sub Choi; Gi Hong Choi; Dai Hoon Han; Dong Jin Joo; Do Young Kim; Kwang-Hyub Han; Jinsil Seong Journal: Radiother Oncol Date: 2020-07-31 Impact factor: 6.280
Authors: Beom Kyung Kim; Do Young Kim; Hwa Kyung Byun; Hye Jin Choi; Seung-Hoon Beom; Hye Won Lee; Seung Up Kim; Jun Yong Park; Sang Hoon Ahn; Jinsil Seong; Kwang-Hyub Han Journal: Int J Radiat Oncol Biol Phys Date: 2020-02-19 Impact factor: 7.038