Princess Alexandra Hospital & University of Queensland, Brisbane, Australia
Rahul Ladwa , David A. Pattison , Jye Smith , Steven Goodman , Matthew E. Burge , Stephen Rose , Nicholas Dowson , David Wyld
Background: Peptide receptor radionuclide therapy (PRRT) is an effective treatment option in patients with advanced neuroendocrine tumours (NETs). Patients are pre-selected based on 68Gallium-DOTA-(0-Tyr3)-octreotate Positron Emission Tomography (68Ga-DOTATATE PET) uptake. The level of uptake in tumour on the baseline 68Ga-DOTATATE PET scan has been explored as a predictor of response in NETs with inconclusive evidence. The aim of this study is to determine the correlation between 68Ga-DOTATATE PET SUV parameters to survival outcomes. Methods: We retrospectively analysed 142 lesions (up to five lesions per patient) in 73 patients with NET undergoing PRRT with 177Lutetium octreotate (8.0-8.3GBq) and pretherapeutic 68Ga-DOTATATE PET/CT in a single institution. Standardised uptake values (SUVs) max and mean were correlated with progression-free survival (PFS) and overall survival (OS). Results: A total of 73 patients were included in the analysis. The median age was 63 (28-89) years. NET origin was gastroenteric (49%), pancreatic [pNET] (38%), bronchial (10%) and other (3%). Ki-67 proliferation index ( < 3%: 36%, 3-20%: 36%, > 20%- < 50%: 8%, unknown: 21%) was seen. Pretherapeutic SUV max but not SUV mean was higher in pNETs (P = 0.04). No difference was seen with Ki-67 index. The median PFS was 32 (95%CI: 26-38) months. Median PFS was reduced with increasing ECOG performance status [PS] (P= 0.029), increasing tumour grade (P = 0.003), increasing Ki-67 proliferation index (P = 0.013), reduced SUV max (P= 0.003), reduced SUV mean (P= 0.001). Multivariate analysis confirmed SUV mean (HR =-1.71 [95%CI: -2.66- -0.80]; P<0.01) and Ki-67 index (HR = 1.11 [1.06-1.17]; P < 0.01) as maintaining significance when incorporating ECOG PS (HR = 1.96 [0.68-5.47]; P = 0.22). The mean OS was 40 [37-44] months. A higher SUV max (SUV max < 30: 34 [30-40] months vs SUV max > 30: 48 [44-51]; P<0.01) and higher SUV mean (SUV mean < 20: 33 [28-39] months vs SUV mean > 20: 47 [43-51]; P<0.01) were associated with improved mean OS. Mean OS was not affected by ECOG performance status (P = 0.896), primary site of origin (P = 0.567) and Ki-67 index (P = 0.110). Conclusions:68Ga-DOTATATE PET SUV measures correlated with an improved PFS on multivariate analysis as well as improved OS in this select group of patients suitable for PRRT. Those patients with lower SUV mean may benefit from escalation of therapy such as increasing administered therapeutic activity.
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