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A [68Ga]Ga-DOTANOC PET/CT Radiomic Model for Non-Invasive Prediction of Tumour Grade in Pancreatic Neuroendocrine Tumours.

ABSTRACT: Predicting grade 1 (G1) and 2 (G2) primary pancreatic neuroendocrine tumour (panNET) is crucial to foresee panNET clinical behaviour. Fifty-one patients with G1-G2 primary panNET demonstrated by pre-surgical [68Ga]Ga-DOTANOC PET/CT and diagnostic conventional imaging were grouped according to the tumour grade assessment method: histology on the whole excised primary lesion (HS) or biopsy (BS). First-order and second-order radiomic features (RFs) were computed from SUV maps for the whole tumour volume on HS. The RFs showing the lowest p-values and the highest area under the curve (AUC) were selected. Three radiomic models were assessed: A (trained on HS, validated on BS), B (trained on BS, validated on HS), and C (using the cross-validation on the whole dataset). The second-order normalized homogeneity and entropy was the most effective RFs couple predicting G2 and G1. The best performance was achieved by model A (test AUC = 0.90, sensitivity = 0.88, specificity = 0.89), followed by model C (median test AUC = 0.87, sensitivity = 0.83, specificity = 0.82). Model B performed worse. Using HS to train a radiomic model leads to the best prediction, although a "hybrid" (HS+BS) population performs better than biopsy-only. The non-invasive prediction of panNET grading may be especially useful in lesions not amenable to biopsy while [68Ga]Ga-DOTANOC heterogeneity might recommend FDG PET/CT.

SUBMITTER: Bevilacqua A

PROVIDER: S-EPMC8150289 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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A [68Ga]Ga-DOTANOC PET/CT Radiomic Model for Non-Invasive Prediction of Tumour Grade in Pancreatic Neuroendocrine Tumours.

Bevilacqua Alessandro A Calabrò Diletta D Malavasi Silvia S Ricci Claudio C Casadei Riccardo R Campana Davide D Baiocco Serena S Fanti Stefano S Ambrosini Valentina V

Diagnostics (Basel, Switzerland) 20210512 5

Predicting grade 1 (G1) and 2 (G2) primary pancreatic neuroendocrine tumour (panNET) is crucial to foresee panNET clinical behaviour. Fifty-one patients with G1-G2 primary panNET demonstrated by pre-surgical [68Ga]Ga-DOTANOC PET/CT and diagnostic conventional imaging were grouped according to the tumour grade assessment method: histology on the whole excised primary lesion (HS) or biopsy (BS). First-order and second-order radiomic features (RFs) were computed from SUV maps for the whole tumour v ...[more]

PMID: 34065981

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Project description:BACKGROUND:Lanreotide is a long-acting somatostatin analogue with proven antitumour effects against well-differentiated (WD) gastroenteropancreatic-neuroendocrine tumours (GEP-NETs). However, there are no globally established prognostic factors associated with the efficacy of lanreotide as a treatment for GEP-NETs. We investigated the prognostic value of [68Ga]Ga-DOTA-TOC positron emission tomography (PET)/computed tomography (CT) somatostatin receptor imaging for patients with WD GEP-NETs treated with lanreotide. METHODS:In this retrospective study, we included 31 patients with unresectable or metastatic WD GEP-NETs who received lanreotide and underwent [68Ga]Ga-DOTA-TOC PET/CT before receiving lanreotide. We captured the following clinicopathological variables: Eastern Cooperative Oncology Group (ECOG) performance status, primary tumour site, NET World Health Organization grade, existence of carcinoid symptoms, previous surgery, previous chemotherapy, and hepatic tumour volume assessed by CT or magnetic resonance imaging (MRI). We also assessed the following [68Ga]Ga-DOTA-TOC PET/CT variables: Krenning score, tumour-to-liver ratio (TLR), maximum standardized uptake value (SUVmax), whole tumour volume (WTV), and total receptor expression (TRE, WTV multiplied by SUVmean). The associations between these markers and progression-free survival (PFS) with lanreotide were analysed. RESULTS:The mean age was 55.1 ± 15.5?years (range 16.0-81.0). The most common primary tumour site was the pancreas, followed by the stomach, and rectum. The median PFS interval with lanreotide was 14.4?months (range 1.3-34.9), with identified disease progression in 20 patients (64.5%). Among the [68Ga]Ga-DOTA-TOC PET/CT variables, TLR (< 8.1 vs. ? 8.1; p = 0.013), SUVmax (< 42.9 vs. ? 42.9; p = 0.037), and WTV (? 58.9?cm3 vs. < 58.9?cm3; p = 0.030) were significantly associated with PFS in the univariate analyses, but only TLR (hazard ratio 3.182 [95% CI 1.189-8.514], p = 0.021) remained an independent factor for PFS in the multivariate analysis. CONCLUSIONS:Low TLR, determined via [68Ga]Ga-DOTA-TOC PET/CT, can be a factor of worse prognosis in patients with advanced WD GEP-NETs treated with lanreotide.

Project description:Purpose Fluorine-18 (18F)-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and gallium-68 (68Ga)-somatostatin analog (SSA) PET/CT imaging have been increasingly used in ectopic adrenocorticotropic hormone syndrome (EAS); however, the diagnostic efficacies of these two methods in patients with EAS remain unclear. Our study aimed to compare the diagnostic efficacies of 18F-FDG PET/CT and 68Ga-DOTANOC PET/CT in EAS. Methods The clinical and imaging data of 68 patients with EAS who underwent 18F-FDG PET/CT and 68Ga-DOTANOC PET/CT examinations from December 2016 to April 2021 were analyzed retrospectively, and the diagnostic efficacies of these methods were compared. Results In 37 cases, imaging was performed to locate the primary tumor lesion (localization group), and in 31 to evaluate tumor load or metastasis (staging group). Primary tumors were detected in 48.65% (18/37) of the localization group patients. According to scan-based analysis, the tumor lesion detection rates and false positive rates of 18F-FDG PET/CT imaging and 68Ga-DOTANOC PET/CT imaging were 18.92% vs. 45.95% (p < 0.05) and 21.62% vs. 2.70% (p < 0.05) respectively. For lesion-based analysis, the tumor lesion detection rates and false positive rates were 24.13% vs. 58.62% (p >0.05) and 31.04% vs. 3.45% (p < 0.05). In 90.32% (28/31) of the staging group patients, 286 of 292 lesions were confirmed as tumor lesions. Based on scan analysis, the detection rates and false positive rates of 18F-FDG PET/CT imaging and 68Ga-DOTANOC PET/CT imaging were 83.87% vs. 67.74% (p > 0.05) and 12.90% vs. 9.68% (p > 0.05) respectively. Based on lesion analysis, the detection rate and false positive rates were 93.84% vs. 54.80% (p < 0.05) and 1.37% vs. 1.03%(p > 0.05). Conclusion 68Ga-DOTANOC PET/CT imaging may be more suitable than 18F-FDG PET/CT for identifying the primary tumor in patients with EAS, while 18F-FDG PET/CT may be more advantageous than 68Ga-DOTANOC PET/CT for patients with suspected metastasis.

Project description:ObjectivesTo assess how patients' dependent parameters may affect [68Ga]Ga-DOTANOC image quality and to propose a theoretical body mass index (BMI)-adjusted injected activity (IA) scheme, to improve imaging of high weight patients.MethodsAmong patients prospectively enrolled (June-2019 and May-2020) in an Institutional Ethical Committee-approved electronic archive, we included those affected by primary gastro-entero-pancreatic (GEP) or lung neuroendocrine tumour and referred by our Institutional clinicians (excluding even minimal radiopharmaceutical extravasation, movement artefacts, renal insufficiency). All PET/CT images were acquired following EANM guidelines and rated for visual quality (1 = non-diagnostic, 2 = poor, 3 = moderate, 4 = good). Collected data included patient's body mass, height, BMI, age, IA (injected activity), IA/Kg (IAkg), IA/BMI (IABMI), liver SUVmean, liver SUVmax standard deviation, liver-signal-to-noise (LSNR), normalised_LSNR (LSNR_norm) and contrast-to-noise ratio (CNR) for positive scans and were compared to image rating (poor vs moderate/good).ResultsOverall, 77 patients were included. Rating concordance was high (agreement = 81.8%, Fleiss k score = 0.806). All patients' dependent parameters resulted significantly different between poor-rated and moderate/good-rated scans (IA: p = 0.006, IAkg: p =< 0.001, body weight: p =< 0.001, BMI: p =< 0.001, IABMI: p =< 0.001). Factors significantly associated with moderate/good rating were BMI (p =< 0.001), body weight (p =< 0.001), IABMI (p =< 0.001), IAkg (p = 0.001), IA (p = 0.003), LSNR_norm (p = 0.01). The BMI-based model presented the best predictive efficiency (81.82%). IABMI performance to differentiate moderate/good from poor rating resulted statistically significant (IA-AUC = 0.78; 95% CI: 0.68-0.89; cut-off value of 4.17 MBq*m2/kg, sensitivity = 81.1%, specificity = 66.7%). If BMI-adjusted IA (=4.17*BMI) would have been applied in this population, the median IA would have slightly inferior (-4.8%), despite a different IA in each patient.Advances in knowledgeBMI resulted the best predictor of image quality. The proposed theoretical BMI-adjusted IA scheme (4.17*BMI) should yield images of better quality (especially in high-BMI patients) maintaining practical scanning times (3 min/bed).

Project description:ContextThe 68 Ga-labelled somatostatin analogues (68 Ga-DOTA-SSAs) is becoming popular as an important diagnostic tool in neuroendocrine tumours as evidenced by a growing number of reports detailing institutional experience with various DOTA peptides. However, only few prospective studies have compared 68 Ga-DOTA-SSAs and somatostatin receptor scintigraphy (SRS) in gastroenteropancreatic neuroendocrine tumours (GEP-NETs) and pulmonary neuroendocrine tumours.ObjectiveThe aim of our prospective study was to perform head-to-head comparison between 68 Ga-DOTATATE PET/CT and standard imaging work-up (SI) that included multiphasic CT, liver MRI and SRS using single photon emission computed tomography.DesignIn this prospective study, the patients were enrolled only if they met any of the following inclusion criteria: (i) initial staging of a NETs without distant metastases on SI or neuroendocrine tumour with unknown primary on SI; (ii) restaging of NETs that could be treated by focused therapeutic interventions; (iii) elevated serum neuroendocrine hormones or peptides. The exclusion criteria was grade 3 GEP-NETs.ResultsThirty-two patients were enrolled in the study. Eleven patients (6 pancreas, 4 ileum, 1 duodenal) were included for initial evaluation and staging of NETs, 8 patients (5 pancreas, 1 ileal, 1 lung, 1 duodenal gastrinoma) for restaging, and 13 patients for elevated serum neuroendocrine biomarkers (5 ectopic Cushing's syndrome, 5 organic hypoglycaemia, 1 patient each with elevated vasoactive inhibitory peptide, chromogranin A and neuron-specific enolase). 68 Ga-DOTATATE PET/CT detected more primary tumours than SRS (15/18 vs 10/18: P = .074). The missed tumours on 68 Ga-DOTATATE PET/CT were located in the lung in two cases and duodenum in one case. For other anatomical regions (nodal and distant metastasis), no statistical difference was observed between imaging modalities using 68 Ga-DOTATATE PET/CT and SRS. Overall, 68 Ga-DOTATATE PET/CT+CT+MRI detected 31/33 of the involved regions (including primaries) (29 and 22 for 68 Ga-DOTATATE and SRS, respectively).ConclusionOur study shows that 68 Ga-DOTATATE PET/CT detected similar number of sites than combination of SRS, liver MRI and thoraco-abdominopelvic CT on region-based analysis. 68 Ga-DOTATATE PET/CT missed half of primary lung carcinoids with ectopic Cushing's syndrome.

Project description:Somatostatin receptors are overexpressed in GEP-NETs and can be visualized in vivo by radiolabeled somatostatin-analogs. During the last decades, conventional scintigraphy using 111In-DTPA-Octreotide (often named somatostatin receptor scintigraphy or SRS) was considered as the gold standard nuclear imaging technique in the evaluation of GEP-NETs. However, SRS may be suboptimal in this clinical setting because of the low intrinsic resolution of the technique and its selectivity for SST2 only. Its overall sensitivity is estimated to 60-70% (per lesion analysis), even when using the most recent SPECT-CT cameras. MRI have also a higher sensitivity than CT and SRS for the detection of liver metastases from GEP-NETs. In recent years, positron emission tomography (PET) imaging, a high resolution and sensitive technology, has gained an increasing role in oncology. It has also been evaluated in GEP-NETs with somatostatin agonists (SSTa) radiolabelled with Gallium-68 [68Ga], a positron emitter with very promising results. Its diagnostic sensitivity is clearly superior to SRS and many European centers have already replaced SRS by [68Ga]-PET-SSTa. Currently, three different [68Ga]-coupled peptides can be used in trials: DOTA-TOC, DOTA-TATE and DOTA-NOC with excellent affinities for SST2 (IC50: 2.5; 0.2 and 1.9 nM, respectively). Sensitivities of DOTA-TOC and DOTA-TATE PET/CT are quite similar. [68Ga]-DOTANOC which also binds to SST5 was recently found to detect significantly more lesions than the SST2-specific radiotracer [68Ga]-DOTATATE in patients with GEP-NETs but this requires further evaluation. It is therefore important to determine the interest of [68Ga]-DOTANOC combined with the standard diagnosis strategy in GEP-NETs and evaluate medicoeconomic impact of adding [68Ga]-DOTANOC in the work-up of patients. The investigators hypothesis is that [68Ga]-DOTANOC will modify the management in at least 20% of patients in a more adapted way according to the 2012 ENETS guidelines in comparison to the decision based on the standard imaging work up (multiphasic WB CT, liver MRI and SRS). 110 patients will be included prospectively in 5 different French experienced centers (Marseille, Bordeaux, Toulouse, Paris, Clermond-Ferrand).

Dataset Information

A [68Ga]Ga-DOTANOC PET/CT Radiomic Model for Non-Invasive Prediction of Tumour Grade in Pancreatic Neuroendocrine Tumours.

Publications

A [68Ga]Ga-DOTANOC PET/CT Radiomic Model for Non-Invasive Prediction of Tumour Grade in Pancreatic Neuroendocrine Tumours.

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