A [68Ga]Ga-DOTANOC PET/CT Radiomic Model for Non-Invasive Prediction of Tumour Grade in Pancreatic Neuroendocrine Tumours.
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ABSTRACT:
SUBMITTER: Bevilacqua A
PROVIDER: S-EPMC8150289 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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.
| S-EPMC7295884 | biostudies-literature
Project description:The aim of this study was to correlate immunohistochemical (IHC) tissue levels of SSTR1-5 with the receptor density generated from [68Ga]Ga-DOTANOC uptake in a prospective series of NF-PNENs. Twenty-one patients with a total of thirty-five NF-PNEN-lesions and twenty-one histologically confirmed lymph node metastases (LN+) were included in this prospective study. Twenty patients were operated on, and one underwent endoscopic ultrasonography and core-needle biopsy. PET/CT with both [68Ga]Ga-DOTANOC and [18F]F-FDG was performed on all patients. All histological samples were re-classified and IHC-stained with monoclonal SSTR1-5 antibodies and Ki-67 and correlated with [68Ga]Ga-DOTANOC and [18F]F-FDG PET/CT. Expression of SSTR1-5 was detected in 74%, 91%, 80%, 14%, and 77% of NF-PNENs. There was a concordance of SSTR2 IHC with positive/negative [68Ga]Ga-DOTANOC finding (Spearman's rho 0.382, p = 0.043). All [68Ga]Ga-DOTANOC-avid tumors expressed SSTR2 or SSTR3 or SSTR5. Expression of SSTR5 was higher in tumors with a low Ki-67 proliferation index (PI) (-0.353, 95% CI -0.654-0.039, p = 0.038). The mean Ki-67 PI for SSTR5 positive tumors was 2.44 (SD 2.56, CI 1.0-3.0) and 6.38 (SD 7.25, CI 2.25-8.75) for negative tumors. SSTR2 was the only SSTR subtype to correlate with [68Ga]Ga-DOTANOC PET/CT. Our prospective study confirms SSTR2 to be of the highest impact for SST PET/CT signal.
| S-EPMC8750461 | biostudies-literature
Project description:The aim of this multicentric study was to prospectively compare 68Ga-DOTANOC PET/CT versus somatostatin receptor scintigraphy (SRS) with SPECT/CT, combined with multiphasic CT scan and MRI in patients with grade 1 or 2 gastroenteropancreatic neuroendocrine tumors (GEP-NET). Patients with histologically proven grade 1 or 2 GEP-NET with suspicion of recurrence or progression, or with typical aspects of GEP-NET on morphological imaging, were explored with conventional imaging (CI): SRS with SPECT/CT, multiphasic CT scan and/or liver MRI followed by 68Ga-DOTANOC PET/CT. The gold standard was based on histology and imaging follow-up. The data of 105 patients (45 woman and 60 men; median age) were analyzed. 68Ga-DOTANOC PET/CT sensitivity was significantly higher than CI sensitivity in per-patient (98.9% vs. 88.6%, p = 0.016) and per-region (97.6% vs. 75.6%, p < 0.001) analyses, in the detection of the primary (97.9% vs. 78.7%; p = 0.016), peritoneal carcinomatosis (95% vs. 30%, p < 0.001), and bone metastases (100% vs. 33.3%, p = 0.041). 68Ga-DOTANOC PET/CT had an impact on the therapeutic management of 41.9% (44/105) patients compared to decisions based on CI explorations. Our data confirm the superiority of 68Ga-DOTANOC PET/CT over CI in the detection of peritoneal carcinomatosis and bone metastasis, as well as its strong therapeutic impact on the management of patients with grade 1-2 GEP-NETs.
| S-EPMC9856693 | biostudies-literature
Project description:Prostate cancer is the second most commonly diagnosed neoplasm in men. This neoplasm has usually excellent prognosis, mostly consequent to the early diagnosis and the effective hormonal therapy. However, significant percentages of patients treated with total androgen blockade therapy, escape to treatment and evolve toward a more aggressive type of cancer. This clinical entity, named castration-resistant prostate cancer, has few and less effective therapeutic opportunities. Therefore, any additional information concerning possible biological targets to therapy is welcome. Here we describe two cases in which 68Ga-DOTANOC PET/CT evidenced the somatostatin receptor overexpression by prostate metastases. The presence of these receptors may support with a more strong evidence the possibility to administer somatostatin analogs as an adjuvant therapy.
| S-EPMC5649877 | biostudies-literature
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.
| S-EPMC9538925 | biostudies-literature
Project description:PurposeFocal congenital hyperinsulinism (CHI) is curable by surgery, which is why identification of the focal lesion is crucial. We aimed to determine the use of 18F-fluoro-dihydroxyphenylalanine (18F-DOPA) PET/CT vs. 68Ga-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic-acid-1-Nal3-octreotide (68Ga-DOTANOC) PET/CT as diagnostic tools in focal CHI.MethodsPET/CT scans of children with CHI admitted to Odense University Hospital between August 2005 and June 2016 were retrospectively evaluated visually and by their maximal standardized uptake values (SUVmax) by two independent examiners, blinded for clinical, surgical and pathological data. Pancreatic histology was used as the gold standard. For patients without surgery, the genetic profile served as the gold standard.ResultsFifty-five CHI patients were examined by PET/CT (18F-DOPA n = 53, 68Ga-DOTANOC n = 18). Surgery was performed in 34 patients, no surgery in 21 patients. Fifty-one patients had a classifiable outcome, either by histology (n = 33, 22 focal lesions, 11 non-focal) or by genetics (n = 18, all non-focal). The predictive performance of 18F-DOPA PET/CT to identify focal CHI was identical by visual- and cut-off-based evaluation: sensitivity (95% CI) of 1 (0.85-1); specificity of 0.96 (0.82-0.99). The optimal 18F-DOPA PET SUVmax ratio cut-off was 1.44 and the optimal 68Ga-DOTANOC PET SUVmax cut-off was 6.77 g/ml. The area under the receiver operating curve was 0.98 (0.93-1) for 18F-DOPA PET vs. 0.71 (0.43-0.95) for 68Ga-DOTANOC PET (p < 0.03). In patients subjected to surgery, localization of the focal lesion was correct in 91%, and 100%, by 18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT, respectively.Conclusion18F-DOPA PET/CT was excellent in predicting focal CHI and superior compared to 68Ga-DOTANOC PET/CT. Further use of 68GA-DOTANOC PET/CT in predicting focal CHI is discouraged.
| S-EPMC5745571 | biostudies-literature
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).
| S-EPMC10996427 | biostudies-literature
Project description:BACKGROUND:Cardiac sarcoidosis (CS) is a potentially fatal condition lacking a single test with acceptable diagnostic accuracy. (18)F-FDG PET/CT has emerged as a promising imaging modality, but is challenged by physiological myocardial glucose uptake. An alternative tracer, (68)Ga-DOTANOC, binds to somatostatin receptors on inflammatory cells in sarcoid granulomas. We therefore aimed to conduct a proof-of-concept study using (68)Ga-DOTANOC to diagnose CS. In addition, we compared diagnostic accuracy and inter-observer variability of (68)Ga-DOTANOC vs. (18)F-FDG PET/CT. METHODS:Nineteen patients (seven female) with suspected CS were prospectively recruited and dual tracer scanned within 7 days. PET images were reviewed by four expert readers for signs of CS and compared to the reference standard (Japanese ministry of Health and Welfare CS criteria). RESULTS:CS was diagnosed in 3/19 patients. By consensus, 11/19 (18)F-FDG scans and 0/19 (68)Ga-DOTANOC scans were rated as inconclusive. The sensitivity of (18)F-FDG PET for diagnosing CS was 33 %, specificity was 88 %, PPV was 33 %, NPV was 88 %, and diagnostic accuracy was 79 %. For (68)Ga-DOTANOC, accuracy was 100 %. Inter-observer agreement was poor for (18)F-FDG PET (Fleiss' combined kappa 0.27, NS) and significantly better for (68)Ga-DOTANOC (Fleiss' combined kappa 0.46, p?=?0.001). CONCLUSIONS:Despite prolonged pre-scan fasting, a large proportion of (18)F-FDG PET/CT images were rated as inconclusive, resulting in low agreement among reviewers and correspondingly poor diagnostic accuracy. By contrast, (68)Ga-DOTANOC PET/CT had excellent diagnostic accuracy with the caveat that inter-observer variability was still significant. Nevertheless, (68)Ga-DOTANOC PET/CT looks very promising as an alternative CS PET tracer. TRIAL REGISTRATION:Current Controlled Trials NCT01729169 .
| S-EPMC4912521 | biostudies-literature
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.
| S-EPMC7450718 | biostudies-literature
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).
| 2202581 | ecrin-mdr-crc