Pre-therapy extrahepatic 68Ga-DOTATATE avid tumor burden is associated with shortterm clinical outcomes of 177Lu-DOTATATE in advanced metastatic gastroenteropancreatic neuroendocrine tumors

Abstract

\n Lutetium-177 ( 177 Lu)-DOTATATE is an effective systemic therapy for metastatic somatostatin receptor positive neuroendocrine tumors (NETs). Here we report our experience with the use of pre-therapy 68 Ga-DOTATATE PET as prognostic marker for short-term clinical outcomes of 177 Lu-DOTATATE therapy in patients with advanced NETs. Materials and methods: We retrospectively reviewed patients who received at least one dose of 177 Lu-DOTATATE between Dec. 2016 and July 2019 at our institution. 50 patients (63.6 ± 10.0 years) with advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs) who had pre-therapy 68 Ga-DOTATATE PET were included in the analysis. 68 Ga-DOTATATE avid tumor volumes were determined automatically using an SUV thresholding approach. Total and extrahepatic 68 Ga-DOTATATE avid tumor volumes were measured and dichotomized into large and small tumor volume groups. Association with progression free survival (PFS) and overall survival (OS) were determined at median follow up of 32 months by Kaplan-Meier survival analysis with Log-Rank test. Results: During follow up, 38 patients (76%) had disease progression and 15 patients (30%) died. Kaplan-Meier analysis of PFS in GEP-NETs patients showed that smaller extrahepatic 68 Ga-DOTATATE avid tumor volume (<140 mL) is associated with significantly longer PFS (Median PFS 29.0 ± 6.7 months vs 9.0 ± 1.7 months, P = 0.0001). This trend in PFS is less prominent when total 68 Ga-DOTATATE avid tumor volume is analyzed. Similarly, Kaplan-Meier analysis of OS found that GEP-NETs patients with smaller extrahepatic 68 Ga-DOTATATE avid tumor volume (<150 mL) is associated with significantly longer OS (Median OS not reached vs 44.0 ± 12.3 months, P = 0.002). This association with OS is not statistically significant when total 68 Ga-DOTATATE avid tumor volume is analyzed. When 68 Ga-DOTATATE avid hepatic tumor volume is grouped into low (<500 mL), medium (500-1000mL) and large (> 1000 mL) tumor volumes, no statistically significant difference in PFS is observed, P = 0.19. The accuracy of extrahepatic 68 Ga-DOTATATE avid tumor volume as prognostic marker for PFS and OS at 32 months are moderate at 58% and 72%. Conclusions: Smaller extrahepatic 68 Ga-DOTATATE avid tumor volumes are associated with longer PFS and OS following 177 Lu-DOTATATE treatment in patients with advanced GEP-NETs. The accuracy of extrahepatic 68 Ga-DOTATATE avid tumor volume as prognostic marker for PFS and OS at 32 months are moderate, which may limit its clinical application.