TY - JOUR

T1 - Semi-automatic tumor delineation for evaluation of 64Cu-DOTATATE PET/CT in patients with neuroendocrine neoplasms

T2 - prognostication based on lowest lesion uptake and total tumor volume

AU - Carlsen, Esben Andreas

AU - Johnbeck, Camilla Bardram

AU - Loft, Mathias

AU - Pfeifer, Andreas

AU - Oturai, Peter

AU - Langer, Seppo Wang

AU - Knigge, Ulrich

AU - Ladefoged, Claes Nøhr

AU - Kjaer, Andreas

N1 - Copyright © 2021 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

PY - 2021

Y1 - 2021

N2 - Patients with neuroendocrine neoplasms (NEN) 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, e.g. 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 lowest, rather than highest, 64Cu-DOTATATE uptake would be more prognostic and developed a semi-automatic method for evaluating this. Methods: Patients with NEN underwent 64Cu-DOTATATE PET/CT. A standardized semi-automatic tumor delineation method was developed and used to identify the lesion with the lowest uptake, i.e. lowest of lesion mean standardized uptake values (SUV)mean. Additionally, we assessed total tumor volume derived from the semi-automatic tumor delineation. Kaplan-Meier and Cox regression analyses were used to determine association with OS and PFS. Results: In 116 patients with NEN, median PFS (95% confidence interval) was 23 (20-31) months and median OS was 85 (68-113) months. Minimum SUVmean and total tumor volume were significantly associated with PFS and OS in univariate Cox regression analyses, while SUVmax was only significant for PFS. In multivariate Cox analyses, both minimum SUVmean and total tumor volume remained statistically significant. Minimum SUVmean and total tumor volume were then dichotomized by their median, and patients were categorized into 4 groups: High/low total tumor volume and high/low minimum SUVmean. Patients with low total tumor volume and high minimum SUVmean had a hazard ratio (95% confidence interval) of 0.32 (0.20-0.51) for PFS and 0.24 (0.13-0.43) for OS, both P<0.001 (reference: high total tumor volume and low minimum SUVmean). Conclusion: We propose a standardized semi-automatic tumor delineation method to identify the lesion with lowest 64Cu-DOTATATE uptake and total tumor volume. Assessment of lowest, rather than highest lesion uptake greatly increases prognostication by 64Cu-DOTATATE PET/CT. Combing lesion uptake and total tumor volume, we derived a novel prognostic classification of patients with NEN.

AB - Patients with neuroendocrine neoplasms (NEN) 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, e.g. 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 lowest, rather than highest, 64Cu-DOTATATE uptake would be more prognostic and developed a semi-automatic method for evaluating this. Methods: Patients with NEN underwent 64Cu-DOTATATE PET/CT. A standardized semi-automatic tumor delineation method was developed and used to identify the lesion with the lowest uptake, i.e. lowest of lesion mean standardized uptake values (SUV)mean. Additionally, we assessed total tumor volume derived from the semi-automatic tumor delineation. Kaplan-Meier and Cox regression analyses were used to determine association with OS and PFS. Results: In 116 patients with NEN, median PFS (95% confidence interval) was 23 (20-31) months and median OS was 85 (68-113) months. Minimum SUVmean and total tumor volume were significantly associated with PFS and OS in univariate Cox regression analyses, while SUVmax was only significant for PFS. In multivariate Cox analyses, both minimum SUVmean and total tumor volume remained statistically significant. Minimum SUVmean and total tumor volume were then dichotomized by their median, and patients were categorized into 4 groups: High/low total tumor volume and high/low minimum SUVmean. Patients with low total tumor volume and high minimum SUVmean had a hazard ratio (95% confidence interval) of 0.32 (0.20-0.51) for PFS and 0.24 (0.13-0.43) for OS, both P<0.001 (reference: high total tumor volume and low minimum SUVmean). Conclusion: We propose a standardized semi-automatic tumor delineation method to identify the lesion with lowest 64Cu-DOTATATE uptake and total tumor volume. Assessment of lowest, rather than highest lesion uptake greatly increases prognostication by 64Cu-DOTATATE PET/CT. Combing lesion uptake and total tumor volume, we derived a novel prognostic classification of patients with NEN.

U2 - 10.2967/jnumed.120.258392

DO - 10.2967/jnumed.120.258392

M3 - Journal article

C2 - 33637589

VL - 62

SP - 1564

EP - 1570

JO - The Journal of Nuclear Medicine

JF - The Journal of Nuclear Medicine

SN - 0161-5505

IS - 11

ER -