TY - JOUR
T1 - Modeling the Synergistic Impact of Yttrium 90 Radioembolization and Immune Checkpoint Inhibitors on Hepatocellular Carcinoma
AU - Kang, Minah
AU - Shin, Yerim
AU - Kim, Yeseul
AU - Ha, Sangseok
AU - Sung, Wonmo
N1 - Publisher Copyright:
© 2024 by the authors.
PY - 2024/2
Y1 - 2024/2
N2 - The impact of yttrium 90 radioembolization (Y90-RE) in combination with immune checkpoint inhibitors (ICIs) has recently gained attention. However, it is unclear how sequencing and dosage affect therapeutic efficacy. The purpose of this study was to develop a mathematical model to simulate the synergistic effects of Y90-RE and ICI combination therapy and find the optimal treatment sequences and dosages. We generated a hypothetical patient cohort and conducted simulations to apply different treatments to the same patient. The compartment of models is described with ordinary differential equations (ODEs), which represent targeted tumors, non-targeted tumors, and lymphocytes. We considered Y90-RE as a local treatment and ICIs as a systemic treatment. The model simulations show that Y90-RE and ICIs administered simultaneously yield greater benefits than subsequent sequential therapy. In addition, applying Y90-RE before ICIs has more benefits than applying ICIs before Y90-RE. Moreover, we also observed that the median PFS increased up to 31~36 months, and the DM rates at 3 years decreased up to 36~48% as the dosage of the two drugs increased (p < 0.05). The proposed model predicts a significant benefit of Y90-RE with ICIs from the results of the reduced irradiated tumor burden and the associated immune activation and suppression. Our model is expected to help optimize complex strategies and predict the efficacy of clinical trials for HCC patients.
AB - The impact of yttrium 90 radioembolization (Y90-RE) in combination with immune checkpoint inhibitors (ICIs) has recently gained attention. However, it is unclear how sequencing and dosage affect therapeutic efficacy. The purpose of this study was to develop a mathematical model to simulate the synergistic effects of Y90-RE and ICI combination therapy and find the optimal treatment sequences and dosages. We generated a hypothetical patient cohort and conducted simulations to apply different treatments to the same patient. The compartment of models is described with ordinary differential equations (ODEs), which represent targeted tumors, non-targeted tumors, and lymphocytes. We considered Y90-RE as a local treatment and ICIs as a systemic treatment. The model simulations show that Y90-RE and ICIs administered simultaneously yield greater benefits than subsequent sequential therapy. In addition, applying Y90-RE before ICIs has more benefits than applying ICIs before Y90-RE. Moreover, we also observed that the median PFS increased up to 31~36 months, and the DM rates at 3 years decreased up to 36~48% as the dosage of the two drugs increased (p < 0.05). The proposed model predicts a significant benefit of Y90-RE with ICIs from the results of the reduced irradiated tumor burden and the associated immune activation and suppression. Our model is expected to help optimize complex strategies and predict the efficacy of clinical trials for HCC patients.
KW - immune checkpoint inhibitor
KW - mathematical modeling
KW - radioembolization
UR - http://www.scopus.com/inward/record.url?scp=85187260813&partnerID=8YFLogxK
U2 - 10.3390/bioengineering11020106
DO - 10.3390/bioengineering11020106
M3 - Article
AN - SCOPUS:85187260813
SN - 2306-5354
VL - 11
JO - Bioengineering
JF - Bioengineering
IS - 2
M1 - 106
ER -