Are outcomes of patients with advanced well-differentiated GEP-NETs on somatostatin analogues similar, irrespective of tracer uptake on 68gallium DOTA SSTR peptide PET CT scans?

Background: Neuroendocrine tumours (NETs) are a rare and heterogeneous group of neoplasms that mainly originate from the gastroenteropancreatic tract (GEP-NETs). The vast majority of NETs tend to overexpress somatostatin receptors (SSTRs), which can be targeted by somatostatin analogues (SSAs). 68Gallium DOTA SSTR peptide positron emission tracer computed tomography (68Ga PET-CT) has emerged as superior to other imaging modalities in identifying SSTRs. This study aimed to assess whether patients with GEP- NETs treated with SSAs have similar outcomes irrespective of tracer uptake intensity on 68Ga PET-CT.Methods: Patient cases undergoing 68Ga PET-CT imaging between November 2015 and September 2020 at The Christie NHS Foundation Trust, with diagnosis of histologically-confirmed advanced GEP-NETs receiving SSAs, were reviewed retrospectively. Kaplan-Meier and Cox regression were utilised to analyse progression free (PFS) and overall survival (OS).Results: Of 644 patients imaged with 68Ga PET-CT, 132 met inclusion criteria. The median age of patients was 62 years; ECOG performance status 0: 62 (47%), 1: 56 (42%), 2: 13 (10%); primary sites: ileum: 54 (41%), pancreas: 26 (20%), cancer of unknown primary: 20 (15%), Grade (G)1: 63 (47%), G2: 56 (42%), G3: 3 (2%), unknown: 11 (8%); 68Ga PET-CT tracer uptake increased: 124 (94%), no increased tracer uptake: 8 (6%). 66 patients (50%) progressed, and 99 (74%) were alive at analysis. Median PFS on SSAs was 20.82 months (95% confidence interval (CI) 12.2–30.03) for patients with increased tracer uptake (n=63) and 8.26 months (95% CI 4.55-not available (NA)) for patients with no increased tracer uptake (n=3) (Hazard Ratio (HR): 4.19 (95% CI 1.238–14.28), P=0.022). Median OS from commencement of SSA was: 99.51 months (95% CI 95.96 – NA) for patients with increased tracer uptake and 47.67 months for patients with no increased tracer uptake (95% CI 13.41 – NA) (HR 2.93 (95% CI 1.011–8.49), P=0.048).Conclusions: 68Ga PET-CT scans are an accurate tool for diagnosis and localisation of NETs. Median PFS and OS appears to be greater in patients receiving SSAs with increased uptake on the 68Ga PET-CT. However, further evaluation in larger cohorts is needed to definitively assess clinical benefit of SSAs in the 68Ga PET-CT negative cohort.