Evolving development of multi-parametric normal tissue complication probability model for liver radiotherapy

The dosimetry model of normal tissue complication probability (NTCP) has been investigated for decades. Incorporation of imaging parameters and biomarkers into NTCP is a must in this modern era. El Naqa and colleagues developed a novel NTCP model with the incorporation of imaging and cytokine biomarkers for patients with hepatocellular carcinoma (HCC) undergoing radiotherapy (RT) (1). They defined the changes in albumin-bilirubin (ALBI) and Child-Pugh (C-P) score, and higher than grade 3 liver enzyme changes as clinical endpoints for radiation-induced liver disease (RILD). The changes in local dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) portal venous perfusion before, during, and one month after RT were used as imaging biomarkers. Four inflammatory cytokines including transforming growth factor beta (TGF-β1), eotaxin (CCL11), hepatic growth factor (HGF), and CD40 ligand were investigated as cytokine biomarkers, but only TGF-β1 and eotaxin showed the impact on the defined endpoints. Of note, their patients included 76% of them treated with stereotactic body RT (SBRT) and 24% treated with conventional RT. The timing of developing RILD after RT may differ between SBRT and conventional RT (2). Besides, some commonly reported cytokines after liver RT, including tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and many others were not analyzed in the study. The investigation on the specific cytokines related to radiation injury is also a potential issue