There is an unmet need to develop non-invasive biomarkers to stratify patients in drug-radiotherapy trials. This pilot study investigated lung cancer radiotherapy response and toxicity blood biomarkers and correlated findings with tumor volume and proliferation imaging.Patients and methodsBlood samples were collected prior and during (day-21) radiotherapy. Twenty-six cell-death, hypoxia, angiogenesis, inflammation, proliferation, invasion and tumor-burden biomarkers were evaluated. Clinical and laboratory data were collected. Univariate analysis was performed on small-cell and non-small cell lung cancer (NSCLC) while multivariate analysis focused on NSCLC.ResultsBlood samples from 78 patients were analyzed. Sixty-one (78.2%) harbored NSCLC, 48 (61.5%) received sequential chemo-radiotherapy. Of tested baseline biomarkers, undetectable IL-1b (hazard ratio (HR) 4.02, 95% confidence interval (CI) 2.04-7.93, p<0.001) was the only significant survival covariate. Of routinely-collected laboratory tests, high baseline neutrophil count was a significant survival covariate (HR 1.07, 95% CI 1.02-1.11, p=0.017). Baseline IL-1b and neutrophil count were prognostic for survival in a multivariate model. The addition of day-21 CYFRA 21-1 modestly improved this model’s survival prediction (concordance probability 0.75 to 0.78). Chemotherapy (p<0.001) and baseline KGF (p=0.019) predicted acute esophagitis, but only chemotherapy remained significant after Bonferroni correction. Baseline Ang-1 and HGF displayed a direct correlation with tumor volume while changes in VCAM-1 demonstrated significant correlations with 18F-fluorothymidine (FLT) positron emission tomography (PET).ConclusionSelect biomarkers are prognostic following radiotherapy in this lung cancer series. The correlation between circulating biomarkers and 18F-FLT PET is demonstrated for the first time, highlighting their potential role as imaging surrogates.