Current Landscape and Future Directions of Biomarkers for Immunotherapy in Hepatocellular Carcinoma

Yavuz, Betül Gök; Hasanov, Elshad; Lee, Sunyoung S.; Mohamed, Yehia I.; Koay, Eugene J.; Cristini, Vittorio; Kaseb, Ahmed O.

doi:10.2147/jhc.s322289

Cited by 26 publications

(21 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the CheckMate 040 trial, tumor responses were also independent of PDL1 status [ 93 ]. Other cellular factors and immune signatures that could serve as biomarkers to predict ICI immunotherapy outcomes were summarized previously [ 94 ].…”

Section: Challenges and Opportunities In Ici Therapy For Hccmentioning

confidence: 99%

Cure the Incurable? Recent Breakthroughs in Immune Checkpoint Blockade for Hepatocellular Carcinoma

Chu

Chan

2021

Cancers

View full text Add to dashboard Cite

HCC usually arises from a chronic inflammation background, driven by several factors including fatty liver, HBV/HCV viral infection and metabolic syndrome. Systemic treatment for advanced HCC remains disappointing due to its strong resistance to chemotherapy and even to tyrosine kinase inhibitors (TKIs). Recently, the use of ICI therapy has revolutionized the systemic treatment of advanced HCC. For the first time, clinical trials testing ICIs, anti-CTLA-4 and anti-PD1/PDL1 reported a survival benefit in patients with sorafenib resistance. However, it took four more years to find the right combination regimen to use ICI in combination with the anti-angiogenic agent bevacizumab to substantially prolong overall survival (OS) of patients with advanced HCC after sorafenib. This review provides a comprehensive history of ICI therapy in HCC, up-to-date information on the latest ICI clinical trials, and discusses the recent development of novel ICIs that would potentially lead to a new checkpoint blockade therapy for advanced HCC.

show abstract

Section: Challenges and Opportunities In Ici Therapy For Hccmentioning

confidence: 99%

Cure the Incurable? Recent Breakthroughs in Immune Checkpoint Blockade for Hepatocellular Carcinoma

Chu

Chan

2021

Cancers

View full text Add to dashboard Cite

show abstract

“…These questions are of particular importance for several reasons. First, immunotherapy is a developing HCC treatment 15 and the ability to combine locoregional therapies and immunotherapy is of great interest with early studies demonstrating reason to be hopeful. 16 , 17 TARE is of particular interest as preclinical studies of external beam radiation have suggested that higher doses of radiation to the tumor increase the likelihood of inducing a positive immune response.…”

Section: Introductionmentioning

confidence: 99%

Dynamic Lymphocyte Changes Following Transarterial Radioembolization: Association with Normal Liver Dose and Effect on Overall Survival

Young¹,

Ragulojan²,

Chen³

et al. 2022

JHC

View full text Add to dashboard Cite

Objective To evaluate the dynamic changes of lymphocytes following transarterial radioembolization (TARE) for hepatocellular carcinoma (HCC) and their relationship to normal liver dose (NLD). Materials and Methods A total of 93 patients who underwent 102 treatments were retrospectively reviewed. Absolute lymphocyte counts pretreatment and at 1, 3, 6, and 12 months were evaluated. Kaplan–Meier, Spearman correlation, receiver operating characteristic (ROC) curve, and area under the curve (AUC) analyses were performed. Results The mean absolute lymphocyte count at baseline was 1.25 ± 0.79 10 3 /µL which was significantly greater than 1 (0.71 ± 0.47 10 3 /µL, p <0.0001), 3 (0.79 ± 0.77 10 3 /µL, p =0.0003), and 6 (0.81 ± 0.44 10 3 /µL, p =0.0001) months, but not significantly different than 12 (0.92 ± 0.8 10 3 /µL, p =0.12) months post treatment. There was a modest negative correlation between NLD and lymphocyte count at 1 month (rho= −0.216, p =0.03), which strengthened at 3 months post treatment (rho= −0.342, p =0.008). AUC of ROC analysis between absolute lymphocyte count ≤1 10 3 /µL or >1 10 3 /µL at 1, 3, 6, and 12 months post treatment was 0.625, 0.676, 0.560, and 0.794, respectively. Univariate analysis of overall survival when separating patients by a lymphocyte count of ≤1 10 3 /µL and >1 10 3 /µL demonstrated a significant difference at 1 (HR: 0.56, 95% CI: 0.33–0.95, p =0.03), 3 (HR: 0.41, 95% CI: 0.18–0.94, p =0.035) and 6 (HR: 0.36, 95% CI: 0.17–0.77, p =0.008) months post treatment, but not pretreatment or at 12 months. Conclusion NLD may correlate with lymphocyte depression at 1 and 3 months and lymphopenia may portend a worse overall survival in the post treatment setting.

show abstract

“…Despite the promising prognostic results of immunotherapy for most patients with advanced HCC, one third of patients with advanced HCC did not benefit from immunotherapy, and up to one fourth developed high-grade immune-related adverse events [ 10 ]. Thus, not all patients benefit equally.…”

Section: Introductionmentioning

confidence: 99%

“…To date, we lack biomarkers that can predict the response to immunotherapy, and thus, provide guidance in clinical decisionmaking. To facilitate decision-making, novel biomarkers are needed, particularly as the treatment with those new agents distinctly differs from the treatment with tyrosine kinase inhibitors [9,10]. Apart from tumor cell-derived and tumor microenvironment-derived biomarkers, in advanced HCC stages, specific laboratory parameters, like alpha-fetoprotein (AFP), and its changes during treatment, and inflammatory parameters, like C-reactive protein, have shown strong correlations with patient prognosis [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

“…To facilitate decision-making, novel biomarkers are needed, particularly as the treatment with those new agents distinctly differs from the treatment with tyrosine kinase inhibitors [9,10]. Apart from tumor cell-derived and tumor microenvironment-derived biomarkers, in advanced HCC stages, specific laboratory parameters, like alpha-fetoprotein (AFP), and its changes during treatment, and inflammatory parameters, like C-reactive protein, have shown strong correlations with patient prognosis [10][11][12]. However, little is known about the potential of imaging biomarkers for predicting long-term outcomes and for identifying patients that might benefit from immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The prognostic role of early tumor shrinkage in patients with hepatocellular carcinoma undergoing immunotherapy

et al. 2022

View full text Add to dashboard Cite

Background Early tumor shrinkage (ETS) has been identified as a promising imaging biomarker for patients undergoing immunotherapy for several cancer entities. This study aimed to validate the potential of ETS as an imaging biomarker for patients undergoing immunotherapy for hepatocellular carcinoma (HCC). Methods We screened all patients with HCC that received immunotherapy as the first or subsequent line of treatment at our tertiary care center between 2016 and 2021. ETS was defined as the reduction in the sum of the sizes of target lesions, between the initial imaging and the first follow-up. The ETS was compared to the radiologic response, according to the modified response evaluation criteria in solid tumors (mRECIST). Furthermore, we evaluated the influence of ETS on overall survival (OS), progression-free survival (PFS), and the alpha-fetoprotein (AFP) response. Results The final analysis included 39 patients with available cross-sectional imaging acquired at the initiation of immunotherapy (baseline) and after 8–14 weeks. The median ETS was 5.4%. ETS was significantly correlated with the response according to mRECIST and with the AFP response. Patients with an ETS ≥10% had significantly longer survival times after the first follow-up, compared to patients with < 10% ETS (15.1 months vs. 4.0 months, p = 0.008). Additionally, patients with both an ETS ≥10% and disease control, according to mRECIST, also had significantly prolonged PFS times after the initial follow-up (23.6 months vs. 2.4 months, p < 0.001). Conclusion ETS was strongly associated with survival outcomes in patients with HCC undergoing immunotherapy. Thus, ETS is a readily assessable imaging biomarker that showed potential for facilitating a timely identification of patients with HCC that might benefit from immunotherapy.

show abstract

Current Landscape and Future Directions of Biomarkers for Immunotherapy in Hepatocellular Carcinoma

Cited by 26 publications

References 61 publications

Cure the Incurable? Recent Breakthroughs in Immune Checkpoint Blockade for Hepatocellular Carcinoma

Cure the Incurable? Recent Breakthroughs in Immune Checkpoint Blockade for Hepatocellular Carcinoma

Dynamic Lymphocyte Changes Following Transarterial Radioembolization: Association with Normal Liver Dose and Effect on Overall Survival

The prognostic role of early tumor shrinkage in patients with hepatocellular carcinoma undergoing immunotherapy

Contact Info

Product

Resources

About