Leveraging Blood-Based Diagnostics to Predict Tumor Biology and Extend the Application and Personalization of Radiotherapy in Liver Cancers

Abstract

While the incidence of primary liver cancers has been increasing worldwide over the last few decades, the mortality has remained consistently high. Most patients present with underlying liver disease and have limited treatment options. In recent years, radiotherapy has emerged as a promising approach for some patients; however, the risk of radiation induced liver disease (RILD) remains a limiting factor for some patients. Thus, the discovery and validation of biomarkers to measure treatment response and toxicity is critical to make progress in personalizing radiotherapy for liver cancers. While tissue biomarkers are optimal, hepatocellular carcinoma (HCC) is typically diagnosed radiographically, making tumor tissue not readily available. Alternatively, blood-based diagnostics may be a more practical option as blood draws are minimally invasive, widely availability and may be performed serially during treatment. Possible blood-based diagnostics include indocyanine green test, plasma or serum levels of HGF or cytokines, circulating blood cells and genomic biomarkers. The albumin-bilirubin (ALBI) score incorporates albumin and bilirubin to subdivide patients with well-compensated underlying liver dysfunction (Child-Pugh score A) into two distinct groups. This review provides an overview of the current knowledge on circulating biomarkers and blood-based scores in patients with malignant liver disease undergoing radiotherapy and outlines potential future directions.

Keywords: circulating biomarkers; liver cancer; radiotherapy; toxicity; treatment personalization.

Figure 1

Potential candidates for prognostic and predictive biomarkers in patients with liver malignancies undergoing radiotherapy. HGF, hepatocyte growth factor; RAS, rat sarcoma; Rac1, Ras-related C3 botulinum toxin substrate 1; Cdc42, cell division cycle 42; RAF, rat fibrosarcoma; ERK, extracellular-signal regulated kinase; MAPK, mitogen-activated protein kinase; PI3K, phosphoinositide-3 kinase; AKT, protein kinase B; SAPK/JNK, stress-activated protein kinase/c-Jun NH(2)-terminal kinase; PKR, protein kinase R; NF-kB, nuclear factor kappa-light-chain-enhancer of activated B cells. This figure was created with BioRender.com.