Objective To identify the impact of segmentation methods and intensity discretization on radiomic features (RFs) extraction from 68Ga-DOTA-TOC PET images in patients with neuroendocrine tumors. Methods Forty-nine patients were retrospectively analyzed. Tumor contouring was performed manually by four different operators and with a semi-automatic edge-based segmentation (SAEB) algorithm. Three SUVmax fixed thresholds (20, 30, 40%) were applied. Fifty-one RFs were extracted applying two different intensity rescale factors for gray-level discretization: one absolute (AR60 = SUV from 0 to 60) and one relative (RR = min-max of the VOI SUV). Dice similarity coefficient (DSC) was calculated to quantify segmentation agreement between different segmentation methods. The impact of segmentation and discretization on RFs was assessed by intra-class correlation coefficients (ICC) and the coefficient of variance (COVL). The RFs’ correlation with volume and SUVmax was analyzed by calculating Pearson’s correlation coefficients. Results DSC mean value was 0.75 ± 0.11 (0.45–0.92) between SAEB and operators and 0.78 ± 0.09 (0.36–0.97), among the four manual segmentations. The study showed high robustness (ICC > 0.9): (a) in 64.7% of RFs for segmentation methods using AR60, improved by applying SUVmax threshold of 40% (86.5%); (b) in 50.9% of RFs for different SUVmax thresholds using AR60; and (c) in 37% of RFs for discretization settings using different segmentation methods. Several RFs were not correlated with volume and SUVmax. Conclusions RFs robustness to manual segmentation resulted higher in NET 68Ga-DOTA-TOC images compared to 18F-FDG PET/CT images. Forty percent SUVmax thresholds yield superior RFs stability among operators, however leading to a possible loss of biological information. SAEB segmentation appears to be an optimal alternative to manual segmentation, but further validations are needed. Finally, discretization settings highly impacted on RFs robustness and should always be stated.

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Aim: This work aims to evaluate whether the radiomic features extracted by 68Ga-DOTATOC-PET/CT of two patients are associated with the response to peptide receptor radionuclide therapy (PRRT) in patients affected by neuroendocrine tumor (NET).Methods: This is a pilot report in two NET patients who experienced a discordant response to PRRT (responder vs. non-responder) according to RECIST1.1. The patients presented with liver metastasis from the rectum and pancreas G3-NET, respectively. Whole-body total-lesion somatostatin receptor-expression (TLSREwb-50) and somatostatin receptor-expressing tumor volume (SRETV wb-50) were obtained in pre- and post-PRRT PET/CT. Radiomic analysis was performed, extracting 38 radiomic features (RFs) from the patients' lesions. The Mann–Whitney test was used to compare RFs in the responder patient vs. the non-responder patient. Pearson correlation and principal component analysis (PCA) were used to evaluate the correlation and independence of the different RFs.Results: TLSREwb-50 and SRETVwb-50 modifications correlate with RECIST1.1 response. A total of 28 RFs extracted on pre-therapy PET/CT showed significant differences between the two patients in the Mann–Whitney test (p < 0.05). A total of seven second-order features, with poor correlation with SUVmax and PET volume, were identified by the Pearson correlation matrix. Finally, the first two PCA principal components explain 83.8% of total variance.Conclusion: TLSREwb-50 and SRETVwb-50 are parameters that might be used to predict and to assess the PET response to PRRT. RFs might have a role in defining inter-patient heterogeneity and in the prediction of therapy response. It is important to implement future studies with larger and more homogeneous patient populations to confirm the efficacy of these biomarkers.

To evaluate the prognostic value of somatostatin receptor tumor burden (SRTB) at 68 Ga-DOTATOC positron emission tomography/computed tomography (PET/CT) in patients with welldifferentiated neuroendocrine tumors (WD-NETs). Methods:We retrospectively analyzed 68 Ga-DOTATOC-PET/CT of 84 patients with histologically confirmed WD-NETs (51 G1, 30 G2 and 3 G3). For each PET/CT, all DOTATOC-avid lesions were independently segmented by 2 operators using a customized threshold based on the healthy liver maximum standardized uptake value (SUVmax) using LIFEx 5.1. Somatostatin receptor expressing tumor volume (SRETV) and total lesion somatostatin receptor expression (TLSRE=SRETV*SUVmean) were extracted for each lesion and then whole-body SRETV and TLSRE (SRETVwb and TLSREwb) were defined as the sum of SRETV and TLSRE of all segmented lesions in each patient, respectively. Time to progression (TTP) was defined as the combination of disease-freesurvival in patients undergoing curative surgery (n=10) and progression-free survival for patients with unresectable/metastatic disease (n=74). TTP and overall survival (OS) were calculated by Kaplan-Meier analysis, log-rank test, and Cox's proportional hazard model. Results:After a median follow-up period of 15.5 months disease progression was confirmed in 35 patients (41.7%) and 14 patients died. Higher SRETVwb (>39.1ml) and TLSREwb (>306.8g) were significantly correlated with shorter median TTP (TTP=12months vs not reached; p<0.001). In multivariate analysis, SRETVwb (p=0.005) was the only independent predictor of TTP regardless of histopathologic grade and TNM staging. Conclusion:According to our results, SRETVwb and TLSREwb extracted from 68 Ga-DOTATOC-PET/CT could predict TTP/OS and might have an important clinical utility in the management of in patients with WD-NETs.