TY - JOUR
T1 - Pre-therapy Somatostatin Receptor-Based Heterogeneity Predicts Overall Survival in Pancreatic Neuroendocrine Tumor Patients Undergoing Peptide Receptor Radionuclide Therapy
AU - Werner, Rudolf A.
AU - Ilhan, Harun
AU - Lehner, Sebastian
AU - Papp, László
AU - Zsótér, Norbert
AU - Schatka, Imke
AU - Muegge, Dirk O.
AU - Javadi, Mehrbod S.
AU - Higuchi, Takahiro
AU - Buck, Andreas K.
AU - Bartenstein, Peter
AU - Bengel, Frank
AU - Essler, Markus
AU - Lapa, Constantin
AU - Bundschuh, Ralph A.
N1 - Funding Information:
We express our gratitude to Michaela Mooz (Department of Nuclear Medicine, University Hospital W?rzburg) for her assistance in data collection. This project has received funding from the European Union?s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 701983.
Funding Information:
Acknowledgments. We express our gratitude to Michaela Mooz (Department of Nuclear Medicine, University Hospital Würzburg) for her assistance in data collection. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 701983.
Publisher Copyright:
© 2018, The Author(s).
PY - 2019/6/17
Y1 - 2019/6/17
N2 - Purpose: Early identification of aggressive disease could improve decision support in pancreatic neuroendocrine tumor (pNET) patients prior to peptide receptor radionuclide therapy (PRRT). The prognostic value of intratumoral textural features (TF) determined by baseline somatostatin receptor (SSTR)-positron emission tomography (PET) before PRRT was analyzed. Procedures: Thirty-one patients with G1/G2 pNET were enrolled (G2, n = 23/31). Prior to PRRT with [177Lu]DOTATATE (mean, 3.6 cycles), baseline SSTR-PET computed tomography was performed. By segmentation of 162 (median per patient, 5) metastases, intratumoral TF were computed. The impact of conventional PET parameters (SUVmean/max), imaging-based TF, and clinical parameters (Ki67, CgA) for prediction of both progression-free survival (PFS) and overall survival (OS) after PRRT were evaluated. Results: Within a median follow-up of 3.7 years, tumor progression was detected in 21 patients (median, 1.5 years) and 13/31 deceased (median, 1.9 years). In ROC analysis, the TF entropy, reflecting derangement on a voxel-by-voxel level, demonstrated predictive capability for OS (cutoff = 6.7, AUC = 0.71, p = 0.02). Of note, increasing entropy could predict a longer survival (> 6.7, OS = 2.5 years, 17/31), whereas less voxel-based derangement portended inferior outcome (< 6.7, OS = 1.9 years, 14/31). These findings were supported in a G2 subanalysis (> 6.9, OS = 2.8 years, 9/23 vs. < 6.9, OS = 1.9 years, 14/23). Kaplan–Meier analysis revealed a significant distinction between high- and low-risk groups using entropy (n = 31, p < 0.05). For those patients below the ROC-derived threshold, the relative risk of death after PRRT was 2.73 (n = 31, p = 0.04). Ki67 was negatively associated with PFS (p = 0.002); however, SUVmean/max failed in prognostication (n.s.). Conclusions: In contrast to conventional PET parameters, assessment of intratumoral heterogeneity demonstrated superior prognostic performance in pNET patients undergoing PRRT. This novel PET-based strategy of outcome prediction prior to PRRT might be useful for patient risk stratification.
AB - Purpose: Early identification of aggressive disease could improve decision support in pancreatic neuroendocrine tumor (pNET) patients prior to peptide receptor radionuclide therapy (PRRT). The prognostic value of intratumoral textural features (TF) determined by baseline somatostatin receptor (SSTR)-positron emission tomography (PET) before PRRT was analyzed. Procedures: Thirty-one patients with G1/G2 pNET were enrolled (G2, n = 23/31). Prior to PRRT with [177Lu]DOTATATE (mean, 3.6 cycles), baseline SSTR-PET computed tomography was performed. By segmentation of 162 (median per patient, 5) metastases, intratumoral TF were computed. The impact of conventional PET parameters (SUVmean/max), imaging-based TF, and clinical parameters (Ki67, CgA) for prediction of both progression-free survival (PFS) and overall survival (OS) after PRRT were evaluated. Results: Within a median follow-up of 3.7 years, tumor progression was detected in 21 patients (median, 1.5 years) and 13/31 deceased (median, 1.9 years). In ROC analysis, the TF entropy, reflecting derangement on a voxel-by-voxel level, demonstrated predictive capability for OS (cutoff = 6.7, AUC = 0.71, p = 0.02). Of note, increasing entropy could predict a longer survival (> 6.7, OS = 2.5 years, 17/31), whereas less voxel-based derangement portended inferior outcome (< 6.7, OS = 1.9 years, 14/31). These findings were supported in a G2 subanalysis (> 6.9, OS = 2.8 years, 9/23 vs. < 6.9, OS = 1.9 years, 14/23). Kaplan–Meier analysis revealed a significant distinction between high- and low-risk groups using entropy (n = 31, p < 0.05). For those patients below the ROC-derived threshold, the relative risk of death after PRRT was 2.73 (n = 31, p = 0.04). Ki67 was negatively associated with PFS (p = 0.002); however, SUVmean/max failed in prognostication (n.s.). Conclusions: In contrast to conventional PET parameters, assessment of intratumoral heterogeneity demonstrated superior prognostic performance in pNET patients undergoing PRRT. This novel PET-based strategy of outcome prediction prior to PRRT might be useful for patient risk stratification.
KW - PET/CT
KW - Pancreatic neuroendocrine tumor
KW - SSTR
KW - Tumor heterogeneity
KW - [Ga]
KW - [Lu]-DOTATATE/-DOTATOC
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U2 - 10.1007/s11307-018-1252-5
DO - 10.1007/s11307-018-1252-5
M3 - Article
C2 - 30014345
AN - SCOPUS:85049974480
SN - 1536-1632
VL - 21
SP - 582
EP - 590
JO - Molecular Imaging and Biology
JF - Molecular Imaging and Biology
IS - 3
ER -
