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.

Figure 1

⁶⁸Ga-DOTATATE positron-emission tomography (PET)/computerized tomography (CT) of patients with metastatic neuroendocrine tumors (NETs) from each total ⁶⁸Ga-DOTATATE-avid volume (⁶⁸Ga-DOTATATE TV) quartile: (A) small-intestine NET (SINET) with metastases to the spine, mesenteric lymph-node and sacrum (red, green and yellow arrows, respectively) and ⁶⁸Ga-DOTATATE TV of 2·2 mL (first quartile range); (B) pancreatic NET (PNET, blue arrow) with metastases to the left 4^th rib (red arrow), liver (green arrows), retroperitoneal and mesenteric lymph nodes (⁶⁸Ga-DOTATATE TV 6·2 mL, second quartile range); (C) PNET metastases to the liver, mediastinum, spine (green, red and yellow arrows respectively) and pleura (⁶⁸Ga-DOTATATE TV of 10·8 mL, third quartile range); and (D) PNET with metastases to the spine (green arrows), left scapula (yellow arrow), mediastinum (red arrow) and liver (white arrows) with a ⁶⁸Ga-DOTATATE TV of 127·8 mL (forth quartile).

Figure 2

Comparison of metastatic disease rates according to total ⁶⁸Ga-DOTATATE-avid tumor volume quartiles (n=46 in each quartile)

Figure 3

Survival analysis in patients with neuroendocrine tumors. Progression-free survival by ⁶⁸Ga-DOTATATE-avid tumor volume (n=139, A). Kaplan-Meier survival analysis by ⁶⁸Ga-DOTATATE-avid tumor volume in the entire cohort (n=184, B), and among patients with pancreatic (n=99, C) and small-intestine neuroendocrine tumors (n=57, D). HR, hazard ratio; CI, confidence interval