Towards Personalized Radiation Therapy of Liver Metastasis: Importance of Serial Blood Biomarkers

PURPOSE: To assess the added value of serial blood biomarkers in liver metastasis stereotactic body radiotherapy (SBRT).
MATERIALS AND METHODS: Eighty-nine patients were retrospectively included. Preand mid-treatment blood samples were analyzed for potential biomarkers of the treatment response. Three biomarker classes were studied: gene mutation status; complete blood count (CBC); and inflammatory plasma cytokine (IPC). One-year local failure (LF) and two-year overall survival (OS) were chosen as study endpoints.
Multivariate logistic regression was used for response prediction. Added predictive benefit was assessed by quantifying the difference between the predictive performance of a baseline model (clinicopathological and dosimetric predictors) and the biomarkerenhanced model, using three metrics: (i) likelihood ratio (LR), predictive variance (PV) , and (iii) area under the receiver-operating characteristic curve (AUC).
RESULTS: The most important predictors of LF were mutation in KRAS gene (HR=2.92, 95% CI=[1.17-7.28], p=0.02), and baseline and mid-treatment concentration of plasma interleukin (IL)-6 (HR=1.15 [1.04-1.26], and 1.06 [1.01-1.13], p 0.01).
Absolute lymphocyte count (ALC) and Platelets-to-lymphocyte ratio (PLR) at baseline, as well as neutrophil-to-lymphocyte ratio at baseline and before fraction 3 (HR=1.33 [1.16-1.51] and 1.19 [1.09-1.30]) had the most significant association with OS (p 0.0003). Addition of baseline GEN and IPC biomarkers in predicting LF respectively increased AUC by 0.06 (from 0.73 to 0.79) and 0.07 (from 0.77 to 0.84). In predicting OS, inclusion of mid-treatment CBC biomarkers increased AUC from 0.72 to 0.80, along with significant boosts in LR and PV.