Prognostic Utility of Total 68Ga-DOTATATE-Avid Tumor Volume in Patients With Neuroendocrine Tumors

Abstract

Background & aims: Survival times vary among patients with neuroendocrine tumors (NETs) - even among those with the same site, stage, and grade of primary tumor. This makes it difficult to select treatment for patients with unresectable NETs because some patients can survive decades without treatment. ⁶⁸Gallium-DOTATATE positron emission tomography with computed tomography (⁶⁸Ga-DOTATATE PET/CT) is a sensitive imaging technique for detection of NETs. We investigated the prognostic accuracy of ⁶⁸Ga-DOTATATE PET/CT-based analysis of tumor volume in patients with NETs.

Methods: We performed a prospective study of 184 patients with NETs (128 [69.6%] with metastases and 11 patients [6.0%] with locally advanced disease) at the National Institutes of Health Clinical Center (Bethesda, MD) from 2013 through 2017. All patients underwent ⁶⁸Ga-DOTATATE PET/CT image analysis and total ⁶⁸Ga-DOTATATE-Avid tumor volume (⁶⁸Ga-DOTATATE TV) was determined. We also measured fasting serum chromogranin A, neuron-specific enolase, gastrin, glucagon, vasoactive intestinal peptide, pancreatic polypeptide, and 24-hour urinary 5-hydroxyindoleacetic acid levels in all patients. Disease progression was defined as a new lesion or a growth of a known lesion during the interval between baseline ⁶⁸Ga-DOTATATE PET/CT scan and follow-up imaging (14.0 ± 6.1 months; range, 1-35 months). The primary outcomes were progression-free survival (PFS) and disease-specific mortality during a median follow-up time of 18 months (range, 4-35 months).

Results: We found an inverse correlation between quartiles of ⁶⁸Ga-DOTATATE TV and PFS (P = .001) and disease-specific survival (P = .002). A ⁶⁸Ga-DOTATATE TV of 7.0 mL or more was associated with higher odds of disease progression (hazard ratio, 3.0; P = .04). A ⁶⁸Ga-DOTATATE TV of 35.8 mL or more was associated with increased risk of disease-specific death (hazard ratio, 10.6) in multivariable analysis (P = .01), as well as in subgroup analysis of patients with pancreatic NETs.

Conclusions: In a prospective study, we demonstrated the prognostic utility of ⁶⁸Ga-DOTATATE TV in a large cohort of patients with NETs, in terms of PFS and disease-specific mortality.

Keywords: Pancreas; Radiology; Survival; Tumor Size.