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 (SUV_max and SUV_mean) 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. SUV_max and SUV_mean of thyroid and liver were significantly associated with fatigue, whereas SUV_max and SUV_mean of thyroid and spleen were significantly associated with hypertension and SUV_max and SUV_mean of thyroid and gastric cardia were significantly associated with nausea (all P < 0.05). The most significant predictors of adverse events were ¹⁸F-RGD SUV_max-liver for fatigue (area under the curve [AUC] = 0.682), SUV_max-spleen for hypertension (AUC = 0.688) and SUV_{max-gastric cardia} for nausea (AUC = 0.698). Classified by the cut-off values for SUV_max-liver (4.57), SUV_max-spleen (6.77) and SUV_{max-gastric cardia} (2.10), patients with low RGD SUV_max 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.