Pre-treatment 18F-RGD Uptake may Predict Adverse Events during Apatinib Antiangiogenic Therapy

The adverse events during antiangiogenic therapy inevitably influence a patient's quality of life. Therefore, biomarkers to identify patients who will experience adverse events would be very valuable in treatment planning. Between September 2016 and December 2019, patients scheduled for single-agent apatinib were prospectively enrolled and underwent 18F-RGD positron emission tomography/computed tomography (PET/CT) pre-treatment. Maximum and mean standard uptake values (SUVmax and SUVmean) were obtained from thyroid, liver, gastric cardia, gastric body, gastric pylorus and spleen. Statistical methods included the independent sample t-test, Mann-Whitney U-test, receiver operating characteristic curve analysis and chi-squared test. In total, 60 patients were initially screened and consented for 18F-RGD PET/CT scans. The three most frequent adverse events were fatigue (50%), hypertension (36%) and nausea (36%), accounting for 72% in the 50 patients included in the analysis. SUVmax and SUVmean of thyroid and liver were significantly associated with fatigue, whereas SUVmax and SUVmean of thyroid and spleen were significantly associated with hypertension and SUVmax and SUVmean of thyroid and gastric cardia were significantly associated with nausea (all P < 0.05). The most significant predictors of adverse events were 18F-RGD SUVmax-liver for fatigue (area under the curve [AUC] = 0.682), SUVmax-spleen for hypertension (AUC = 0.688) and SUVmax-gastric cardia for nausea (AUC = 0.698). Classified by the cut-off values for SUVmax-liver (4.57), SUVmax-spleen (6.77) and SUVmax-gastric cardia (2.10), patients with low RGD SUVmax in liver, spleen and gastric cardia had statistically higher incidence of fatigue (67.9% versus 27.3%, P = 0.002), hypertension (55.6% versus 13.0%, P = 0.004) and nausea (61.1% versus 21.9%, P = 0.006). Low pre-treatment 18F-RGD uptake in the liver, spleen and gastric cardia were predictive of the adverse events fatigue, hypertension and nausea during apatinib treatment, respectively. •The adverse events during antiangiogenic therapy inevitably influence the quality of life, and no biomarkers were available to identify those high-risk patients.•Compared with the patients with high SUVmax, those patients with low RGD in liver, spleen and gastric cardia had statistically higher incidence of fatigue, hypertension and nausea during antiangiogenic therapy.•Those biomarkers to identify patients who will experience adverse events would be useful for hi