Semiautomatic Tumor Delineation for Evaluation of 64Cu-DOTATATE PET/CT in Patients with Neuroendocrine Neoplasms: Prognostication Based on Lowest Lesion Uptake and Total Tumor Volume

Abstract

Patients with neuroendocrine neoplasms (NENs) have heterogeneous somatostatin receptor expression, with highly differentiated lesions having higher expression. Receptor expression of the total tumor burden may be visualized by somatostatin receptor imaging, such as with ⁶⁴Cu-DOTATATE PET/CT. Assessment of maximal lesion uptake is associated with progression-free survival (PFS) but not overall survival (OS). We hypothesized that the lesion with the lowest, rather than the highest, ⁶⁴Cu-DOTATATE uptake would be more prognostic, and we developed a semiautomatic method for evaluating this hypothesis. Methods: Patients with NENs underwent ⁶⁴Cu-DOTATATE PET/CT. A standardized semiautomatic tumor delineation method was developed and used to identify the lesion with the lowest uptake, that is, with the lowest SUV_mean Additionally, we assessed total tumor volume derived from the semiautomatic tumor delineation. Kaplan-Meier and Cox regression analyses were used to determine whether there was any association with OS and PFS. Results: In 116 patients with NENs, median PFS (95% CI) was 23 mo (range, 20-31 mo) and median OS was 85 mo (range, 68-113 mo). Minimum SUV_mean and total tumor volume were significantly associated with PFS and OS in univariate Cox regression analyses, whereas SUV_max was significant only for PFS. In multivariate Cox analyses, both minimum SUV_mean and total tumor volume remained statistically significant. Minimum SUV_mean and total tumor volume were then dichotomized by their median, and patients were categorized into 4 groups: high or low total tumor volume and high or low minimum SUV_mean Patients with a low total tumor volume and high minimum SUV_mean had a hazard ratio of 0.32 (95% CI, 0.20-0.51) for PFS and 0.24 (95% CI, 0.13-0.43) for OS, both with P values of less than 0.001 (reference: high total tumor volume and low minimum SUV_mean). Conclusion: We propose a standardized semiautomatic tumor delineation method to identify the lesion with the lowest ⁶⁴Cu-DOTATATE uptake and total tumor volume. Assessment of the lowest, rather than the highest, lesion uptake greatly increases prognostication by ⁶⁴Cu-DOTATATE PET/CT. Combining lesion uptake and total tumor volume, we derived a novel prognostic classification system for patients with NENs.

Keywords: 64Cu-DOTATATE PET; minimum SUVmean; neuroendocrine neoplasms; semiautomatic tumor delineation; total tumor volume.

Graphical abstract

FIGURE 1.

Patient examples of classification based on lowest lesion uptake combined with total tumor volume. Maximum-intensity projections are shown without and with delineated tumor volume. Window setting for all images was 0–30. All separate lesions were analyzed individually to obtain minimum SUV_mean. (A) Patient in group with high total tumor volume (1.041 cm³) + low minimum SUV_mean (9.6); OS, 17 mo; PFS, 11 mo. (B) Patient in group with low total tumor volume (54 cm³) + low minimum SUV_mean (13.1); OS, 51 mo; PFS, 42 mo. (C) Patient in group with high total tumor volume (415 cm³) + high minimum SUV_mean (25.3); OS, 68 mo; PFS, 34 mo. (D) Patient in group with low total tumor volume (45 cm³) + high minimum SUV_mean (15); OS, 118 mo; PFS, 80 mo.

FIGURE 2.

Kaplan–Meier plots of PFS and OS for patients grouped by total tumor volume and minimum SUV_mean. VhSh = high total tumor volume + high minimum SUV_mean; VhSl = high total tumor volume + low minimum SUV_mean; VlSh = low total tumor volume + high minimum SUV_mean; VlSl = low total tumor volume + low minimum SUV_mean.