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. 2023 Dec 31;16(1):200.
doi: 10.3390/cancers16010200.

Prediction of 177Lu-DOTATATE Therapy Outcomes in Neuroendocrine Tumor Patients Using Semi-Automatic Tumor Delineation on 68Ga-DOTATATE PET/CT

Hwan Lee  1 , Sarit T Kipnis  2   3 , Remy Niman  4 , Sophia R O'Brien  1 , Jennifer R Eads  2 , Bryson W Katona  2 , Daniel A Pryma  1   5
Affiliations

Prediction of 177Lu-DOTATATE Therapy Outcomes in Neuroendocrine Tumor Patients Using Semi-Automatic Tumor Delineation on 68Ga-DOTATATE PET/CT

Hwan Lee et al. Cancers (Basel). .

Abstract

Background: Treatment of metastatic neuroendocrine tumors (NET) with 177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) results in favorable response only in a subset of patients. We investigated the prognostic value of quantitative pre-treatment semi-automatic 68Ga-DOTATATE PET/CT analysis in NET patients treated with PRRT.

Methods: The medical records of 94 NET patients who received at least one cycle of PRRT at a single institution were retrospectively reviewed. On each pre-treatment 68Ga-DOTATATE PET/CT, the total tumor volume (TTV), maximum tumor standardized uptake value for the patient (SUVmax), and average uptake in the lesion with the lowest radiotracer uptake (SUVmin) were determined with a semi-automatic tumor delineation method. Progression-free survival (PFS) and overall survival (OS) among the patients were compared based on optimal cutoff values for the imaging parameters.

Results: On Kaplan-Meier analysis and univariate Cox regression, significantly shorter PFS was observed in patients with lower SUVmax, lower SUVmin, and higher TTV. On multivariate Cox regression, lower SUVmin and higher TTV remained predictive of shorter PFS. Only higher TTV was found to be predictive of shorter OS on Kaplan-Meier and Cox regression analyses. In a post hoc Kaplan-Meier analysis, patients with at least one high-risk feature (low SUVmin or high TTV) showed shorter PFS and OS, which may be the most convenient parameter to measure in clinical practice.

Conclusions: The tumor volume and lowest lesion uptake on 68Ga-DOTATATE PET/CT can predict disease progression following PRRT in NET patients, with the former also predictive of overall survival. NET patients at risk for poor outcomes following PRRT can be identified with semi-automated quantitative analysis of 68Ga-DOTATATE PET/CT.

Keywords: 177Lu-DOTATATE; 68Ga-DOTATATE; neuroendocrine tumor; positron emission tomography computed tomography; prognostic factor.

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Conflict of interest statement

R.N. is an employee of MIM Software Inc. J.R.E. discloses employment-spouse at Janssen, advisory board/consultant at Merck, and institutional research support from Seagen, Merck, Gilead, Oncolys, Hutchmed, Arcus, Amgen, and Replimune. D.A.P. discloses research funding from Lantheus, Point Biopharma, and Fusion Pharmaceuticals; honoraria from Molecular Targeting Technologies Inc.; and stock options from Molecular Targeting Technologies Inc. and Trevarx. The other authors declare no conflict of interest relevant to the study.

Figures

Figure 1
Figure 1
A coronal maximum intensity projection image of 68Ga-DOTATATE PET showing an example of the semi-automatic tumor delineation in red.
Figure 2
Figure 2
Kaplan–Meier plot of progression-free survival and overall survival in 94 NET patients who received PRRT. Median progression-free survival was 21.0 months and median overall survival was not reached.
Figure 3
Figure 3
Kaplan–Meier plots of post-PRRT progression-free survival based on pre-treatment 68Ga-DOTATATE PET/CT parameters. Progression-free survival was significantly shorter in the (A) low SUVmax (p = 0.032), (B) low SUVmin (p = 0.006), and (C) high TTV (p = 0.034) groups. * p < 0.05, ** p < 0.01.
Figure 4
Figure 4
Kaplan–Meier plots of post-PRRT overall survival based on pre-treatment 68Ga-DOTATATE PET/CT parameters. (A) Low SUVmax (p = 0.40) and (B) low SUVmin (p = 0.22) were not predictive of mortality risk, but patients with (C) higher TTV showed significantly shorter overall survival (p < 0.001). *** p < 0.001.
Figure 5
Figure 5
Kaplan–Meier plots of post-PRRT survival based on high vs. low-risk stratification using pre-treatment 68Ga-DOTATATE PET/CT. High-risk patients showed significantly shorter (A) progression-free survival (p = 0.001) and (B) overall survival (p = 0.006). ** p < 0.01.
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