Clinical value of biochemical markers and <sup>68</sup>Ga-DOTATATE PET/CT in the follow-up of patients with pancreatic neuroendocrine tumors: a retrospective study

Abstract

INTRODUCTION: Follow-up of patients with pancreatic neuroendocrine tumors (p-NETs) remains little studied and relevant. The role of tumor markers as indicators of recurrence, as well as the relationship between the prevalence of the disease in 68Ga-DOTATATE PET/CT and levels of tumor markers, has been studied in a few publications.OBJECTIVE: To determine the significance of markers and visualization methods in the follow-up of patients with p-NETs.MATERIALS AND METHODS: 68Ga-DOTATATE PET/CT was performed in 73 patients diagnosed with pancreatic NET: 57 patients (78%) were previously treated, 16 patients (22%) underwent primary staging. The levels of serotonin and chromogranin-A (CgA) were studied at the time of PET/CT and at the onset of the disease. CT and MRI were performed within 2 months before PET/CT. Statistics: Spearman’s coefficient was used for correlations. To determine the levels of markers at which it is recommended to enroll 68Ga-DOTATATE PET/CT, a ROC-analysis was performed. The result of the ROC-analysis is presented with a 95% confidence interval.RESULTS: CT and MRI revealed metastases in 45 patients (61.6%), PET/CT revealed foci in 56 patients (76.7%), of which 13 patients had metastases of other anatomical locations, which were not previously detected. Sensitivity of 68Ga-DOTATATE PET/CT to pancreatic NET is 94.8%, specificity is 93.3%. In ROC-analysis, the area under the curve was 0.8 for serotonin (CI95% 0.676–0.924), for CgA 0.81 (CI95% 0.695–0.925). A weak relationship was revealed between the degree of oncomarkers increase and the number of foci: for serotonin r=0.32 (p<0.05), for CgA r=0.298 (p<0.05). No correlation was found between the number of foci and the tumor proliferative activity index (Ki67). Also, for all foci localizations, there was no dependence of SUV max on the levels of markers and Ki67.DISCUSSION: In our study, 68Ga-DOTATATE PET/CT revealed more metastases than routine methods, due to this, the treatment plan and the volume of surgical interventions were adjusted. An increase in the levels of tumor markers highly likely indicates a relapse of the disease. However, the low Spearman correlation coefficient between the number of foci and the levels of serotonin and CgA does not allow us to assume the prevalence of the tumor process by the degree of this rise. In addition, no significant relationship was found between the prevalence of the tumor and the levels of the studied tumor markers.CONCLUSION: 68Ga-DOTATATE PET/CT has higher accuracy in the diagnosis of p-NETs than routine imaging methods. In combination with the determination of the tumor markers levels, the probability of detecting tumor foci increases.