Prognostic value of a three-scale grading system based on combining molecular imaging with 68Ga-DOTATATE and 18F-FDG PET/CT in patients with metastatic gastroenteropancreatic neuroendocrine neoplasias

Abstract

We investigated on the added prognostic value of a three-scale combined molecular imaging with ⁶⁸Ga-DOTATATE and ¹⁸F-FDG PET/CT, (compared to Ki-67 based histological grading), in gastroenteropancreatic neuroendocrine neoplasia patients. 85 patients with histologically proven metastatic gastroenteropancreatic neuroendocrine neoplasias, who underwent combined PET/CT imaging were retrospectively evaluated. Highest Ki-67 value available at time of ¹⁸F-FDG PET/CT was recorded. Patients were classified according to World Health Organization/European Neuroendocrine Tumor Society histological grades (G1, G2, G3) and into three distinct imaging categories (C1: all lesions are ¹⁸F-FDG negative/⁶⁸Ga-DOTATATE positive, C2: patients with one or more ¹⁸F-FDG positive lesions, all of them ⁶⁸Ga-DOTATATE positive, C3: patients with one or more ¹⁸F-FDG positive lesions, at least one of them ⁶⁸Ga-DOTATATE negative). The primary endpoint of the study was Progression-Free Survival, assessed from the date of ¹⁸F-FDG PET/CT to the date of radiological progression according to Response Evaluation Criteria In Solid Tumors version 1.1. Classification according to histological grade did not show significant statistical difference in median Progression-Free Survival between G1 and G2 but was significant between G2 and G3 patients. In contrast, median Progression-Free Survival was significantly higher in C1 compared to C2 and in C2 compared to C3 patients, revealing three distinctive imaging categories, each with highly distinctive prognosis. Our three-scale combined ⁶⁸Ga-DOTATATE/¹⁸F-FDG PET imaging classification holds high prognostic value in patients with metastatic gastroenteropancreatic neuroendocrine neoplasias.

Keywords: 18F-FDG PET/CT; 68Ga-DOTATATE PET/CT; gastroenteropancreatic neuroendocrine neoplasias; molecular imaging; prognostic biomarkers.

Figure 1

124 GEP NENs patients who underwent combined ⁶⁸Ga-DOTATATE and ¹⁸F-FDG PET/CT imaging in our Institute (within a maximum time window of three months between them), were screened prior to inclusion. 85 patients were finally included and evaluated on the study.

Figure 2

The median Progression-Free Survival (mPFS) and the median Overall Survival (mOS) of the entire cohort was 12.9 months and 40.1 months respectively.

Figure 3

(A) The mPFS values of G1, G2 and G3 patients were 21.2 months, 17.9 months and 5.9 months respectively. We did not observe any statistical difference between G1 and G2 patients, while G2 patients had a statistically significant longer PFS compared to G3. Accordingly, the mOS values of G1, G2 and G3 patients were 40.1 months, 44.2 months and 25.1 months respectively and no statistical difference between any of the three categories was observed. (B) The three survival curves were completely separated with statistically different mPFS values of 40.1 months (C1 patients), 11.9 months (C2 patients) and 7.0 months (C3 patients) respectively. Similarly, C1 patients had a mOS of 103.2 months, while C2 and C3 patients demonstrated a mOS of 35.3 months and 14.0 months respectively. There was a trend toward significance between C1 and C2 patients and C3 patients had a significantly lower mOS compared to C2.

Figure 4

C1 category: all lesions are ¹⁸F-FDG negative and ⁶⁸Ga-DOTATATE positive.

Figure 5

Two cases of patients from C2 category (two pairs of PETs): patients with one or more ¹⁸F-FDG positive lesions, all of them ⁶⁸Ga-DOTATATE positive. There is no mismatch in favor of ¹⁸F-FDG.

Figure 6

Two cases of patients from C3 category (two pairs of PETs): patients with one or more ¹⁸F-FDG positive lesions, all of them ⁶⁸Ga-DOTATATE negative. A mismatch in favor of ¹⁸F-FDG is observable.