Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate: an analysis of the NETTER-1 study

Purpose: To assess the impact of baseline liver tumour burden, alkaline phosphatase (ALP) elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate. Methods: In the phase 3 NETTER-1 trial, patients with advanced, progressive midgut neuroendocrine tumours (NET) were randomised to 177Lu-Dotatate (every 8 weeks, four cycles) plus octreotide long-acting release (LAR) or to octreotide LAR 60 mg. Primary endpoint was progression-free survival (PFS). Analyses of PFS by baseline factors, including liver tumour burden, ALP elevation, and target lesion size, were performed using Kaplan-Meier estimates; hazard ratios (HRs) with corresponding 95% CIs were estimated using Cox regression. Results: Significantly prolonged median PFS occurred with 177Lu-Dotatate versus octreotide LAR 60 mg in patients with low ( 50%) liver tumour burden (HR 0.187, 0.216, 0.145), and normal or elevated ALP (HR 0.153, 0.177), and in the presence or absence of a large target lesion (diameter > 30 mm; HR, 0.213, 0.063). Within the 177Lu-Dotatate arm, no significant difference in PFS was observed amongst patients with low/moderate/high liver tumour burden (P = 0.7225) or with normal/elevated baseline ALP (P = 0.3532), but absence of a large target lesion was associated with improved PFS (P = 0.0222). Grade 3 and 4 liver function abnormalities were rare and did not appear to be associated with high baseline liver tumour burden. Conclusions: 177Lu-Dotatate demonstrated significant prolongation in PFS versus high-dose octreotide LAR in patients with advanced, progressive midgut NET, regardless of baseline liver tumour burden, elevated ALP, or the presence of a large target lesion. Clinicaltrials.gov : NCT01578239, EudraCT: 2011-005049-11

Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate: an analysis of the NETTER-1 study

Purpose: To assess the impact of baseline liver tumour burden, alkaline phosphatase (ALP) elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate. Methods: In the phase 3 NETTER-1 trial, patients with advanced, progressive midgut neuroendocrine tumours (NET) were randomised to 177Lu-Dotatate (every 8 weeks, four cycles) plus octreotide long-acting release (LAR) or to octreotide LAR 60 mg. Primary endpoint was progression-free survival (PFS). Analyses of PFS by baseline factors, including liver tumour burden, ALP elevation, and target lesion size, were performed using Kaplan-Meier estimates; hazard ratios (HRs) with corresponding 95% CIs were estimated using Cox regression. Results: Significantly prolonged median PFS occurred with 177Lu-Dotatate versus octreotide LAR 60 mg in patients with low ( 50%) liver tumour burden (HR 0.187, 0.216, 0.145), and normal or elevated ALP (HR 0.153, 0.177), and in the presence or absence of a large target lesion (diameter > 30 mm; HR, 0.213, 0.063). Within the 177Lu-Dotatate arm, no significant difference in PFS was observed amongst patients with low/moderate/high liver tumour burden (P = 0.7225) or with normal/elevated baseline ALP (P = 0.3532), but absence of a large target lesion was associated with improved PFS (P = 0.0222). Grade 3 and 4 liver function abnormalities were rare and did not appear to be associated with high baseline liver tumour burden. Conclusions: 177Lu-Dotatate demonstrated significant prolongation in PFS versus high-dose octreotide LAR in patients with advanced, progressive midgut NET, regardless of baseline liver tumour burden, elevated ALP, or the presence of a large target lesion. Clinicaltrials.gov: NCT01578239, EudraCT: 2011-005049-11

EVALUATION PROSPECTIVE DE LA SCINTIGRAPHIE A L'123 I-META-IODO-BENZYLGUANIDINE DANS LE SYNDROME DE BRUGADA (A PROPOS DE 19 CAS)

LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

18F-FDOPA PET Compared With 123I-Metaiodobenzylguanidine Scintigraphy and 18F-FDG PET in Secreting Sporadic Pheochromocytoma

International audienceWe report the case of a 23-year-old man presenting a right hypersecreting pheochromocytoma, falsely negative on 18 F-FDG PET/CT and on 123 I-metaiodobenzylguanidine (123 I-MIBG) scintigraphy but strongly positive on 18 F-FDOPA PET/CT. Functional imaging has a key role in diagnosis and prognosis of pheochromocytomas, but choosing the most relevant modality remains difficult. Despite its high specificity, 123 I-MIBG has a limited sensitivity. 18 F-FDG can be used, but it is an unspecific tracer, and 18 F-FDG uptake in brown adipose tissue can hinder the analysis. However, 18 F-FDOPA shows very high sensitivity and specificity in pheochromocyto-mas with fewer drug interferences than 123 I-MIBG

99m Tc-MIBI pinhole SPECT in primary hyperparathyroidism: comparison with conventional SPECT, planar scintigraphy and ultrasonography

International audiencePURPOSE: A pinhole collimator is routinely used to increase the resolution of scintigraphy. This prospective study was conducted to determine the interest of (99m)Tc-MIBI pinhole single-photon emission computed tomography (SPECT) for the preoperative localisation of parathyroid lesions in primary hyperparathyroidism. METHODS: All patients underwent a neck ultrasonography (US), (99m)TcO4- and (99m)Tc-MIBI planar images and two consecutive SPECT with a parallel (C-SPECT) and a pinhole collimator (P-SPECT). P-SPECT was performed with a tilted detector equipped with a pinhole collimator and reconstructed with a dedicated OSEM algorithm. A diagnostic confidence score (CS) was assigned to each procedure considering intensity and extra-thyroidal location of suspected lesions: 0 = negative, 1 = doubtful, 2 = moderately positive, 3 = positive. The results of these preoperative localisation studies were compared with surgical, pathological and 6-month biological findings. RESULTS: Fifty-one patients cured after surgery were included. Surgery revealed 55 lesions (median weight 0.5 g, 11 in ectopy). Sensitivities of US, planar imaging, C-SPECT and P-SPECT were, respectively, 51, 76, 82 and 87%. Nine glands were only detected by tomography and five glands only by P-SPECT. 99mTc-MIBI/99mTcO4- planar scans and P-SPECT were complementary and, when combined together, showed the highest sensitivity (93%). Compared with planar imaging and C-SPECT, P-SPECT increased CS for 42 and 53% of lesions, respectively, and contributed to markedly reduce the number of uncertain results. CONCLUSIONS: A combination of planar 99mTc-MIBI/99mTcO4- scintigraphy and P-SPECT appears to be a highly accurate preoperative imaging procedure in primary hyperparathyroidism

Metastatic Solitary Fibrous Tumor With Doege-Potter Syndrome : Hypoglycemia Treated by 90 Y Radioembolization

International audienceSolitary fibrous tumor is a rare type of mesenchymal neoplasm that can be associated to a paraneoplastic severe hypoglycemia due to the overproduction of insulinlike growth factor type 2: Doege-Potter syndrome. When surgical resection is impossible or unsuccessful, alternative therapies were described with heterogeneous efficiency. We report the use of radioembolization with 90 Y-labeled glass microspheres in this application. Regarding the excellent results obtained and the potential interest of peptide receptor radionuclide therapy suggested by overexpression of somatostatin receptors in our patient, the place of targeted radionuclide therapies deserves to be explored in this group of tumors

Carcinoembryonic Antigen Increase in a Patient with Colon Cancer Who Have Achieved Complete Remission and Negative 18F-FDG PET/CT: Don’t Forget the Thyroid!

International audienceSerum carcinoembryonic antigen (CEA) is a tumor marker especially used to follow a patient with colorectal cancer. However, it is non-specific and could be increased in several cancers and some benign conditions. We report the case of a 70-year-old man followed since 2014 for a left colon adenocarcinoma with the persistence of an increased CEA. There was no evidence of recurrence, but a right lobar thyroid nodule without a significantly increased uptake was incidentally discovered on the CT scan of 18F-fluorodeoxyglucose (18F-FDG) PET/CT. We suspected a medullary thyroid carcinoma (MTC) explaining the persistent elevation of CEA. Plasma calcitonin levels were 47 ng/L (N < 10). Fine needle aspiration cytology found atypia of undetermined significance and the patient was reluctant to undergo surgery without any further exploration. We performed a 18Ffluorodihydroxyphenylalanine (18F-FDOPA) PET/CT preoperatively which revealed a punctiform focus of the right thyroid lobe corresponding to a pT1aN1aMxR0 medullary thyroid carcinoma, histopathologically confirmed. This case highlights that despite the potential usefulness of 18F-FDG PET/CT in case of an unknown source of elevated CEA this imaging may be falsely negative as in the case of MTC and should lead to further explorations

Revisiting the Robustness of PET-Based Textural Features in the Context of Multi-Centric Trials.

This study aimed to investigate the variability of textural features (TF) as a function of acquisition and reconstruction parameters within the context of multi-centric trials.The robustness of 15 selected TFs were studied as a function of the number of iterations, the post-filtering level, input data noise, the reconstruction algorithm and the matrix size. A combination of several reconstruction and acquisition settings was devised to mimic multi-centric conditions. We retrospectively studied data from 26 patients enrolled in a diagnostic study that aimed to evaluate the performance of PET/CT 68Ga-DOTANOC in gastro-entero-pancreatic neuroendocrine tumors. Forty-one tumors were extracted and served as the database. The coefficient of variation (COV) or the absolute deviation (for the noise study) was derived and compared statistically with SUVmax and SUVmean results.The majority of investigated TFs can be used in a multi-centric context when each parameter is considered individually. The impact of voxel size and noise in the input data were predominant as only 4 TFs presented a high/intermediate robustness against SUV-based metrics (Entropy, Homogeneity, RP and ZP). When combining several reconstruction settings to mimic multi-centric conditions, most of the investigated TFs were robust enough against SUVmax except Correlation, Contrast, LGRE, LGZE and LZLGE.Considering previously published results on either reproducibility or sensitivity against delineation approach and our findings, it is feasible to consider Homogeneity, Entropy, Dissimilarity, HGRE, HGZE and ZP as relevant for being used in multi-centric trials

Mild sporadic primary hyperparathyroidism: high rate of multiglandular disease is associated with lower surgical cure rate

International audienceBACKGROUND:Mild primary hyperparathyroidism (serum calcium ≤ 2.85 mmol/L) is the most representative form of pHPT nowadays. The aim of this study was to evaluate its subtypes and the multiglandular disease (MGD) rate as it may lower the sensitivity of preoperative parathyroid scintigraphy and the surgical cure rate.METHODS:We retrospectively included patients with mild pHPT who underwent parathyroid dual-tracer scintigraphy with 99mTc-MIBI SPECT/CT and surgery between January 2013 and December 2015. Cure was defined as normalization of serum calcium (or PTH in the normocalcemic form) at 6 months. MGD was defined by either two abnormal resected glands or persistent disease after resection of at least one abnormal gland.RESULTS:We included 121 patients. Median preoperative serum calcium was 2.68 mmol/L and median PTH was 83.4 pg/mL. A total of 141 glands were resected (95 adenomas, 33 hyperplasias). The subtypes were 57% classic, 32.2% normohormonal, and 10.7% normocalcemic. MGD occurred in 23.5% of patients divided as 13%, 30%, and 64% respectively (p = 0.0011). The surgical cure rate was 85.2%. The normocalcemic form had lower cure rate than the normohormonal (45% vs 84%, p = 0.018) and classic forms (45% vs 93%, p = 0.0006). MIBI scintigraphy identified at least one abnormal lesion, later confirmed by the pathologist in 90/98 patients, making the sensitivity per patient 91.8% (95% CI 84.1-96.2%).CONCLUSIONS:MGD is strongly associated with mild pHPT, especially the normocalcemic form where it accounts for 64% of cases. Bilateral neck exploration should be performed in this population to improve the cure rate, even if the scintigraphy shows a single focus

Assessment of acquisition protocols for routine imaging of Y-90 using PET/CT.

International audienceABSTRACT: BACKGROUND: Despite the early theoretical prediction of the 0+-0+ transition of 90Zr, 90Y-PET underwent only recently a growing interest for the development of imaging radioembolization of liver tumors. The aim of this work was to determine the minimum detectable activity (MDA) of 90Y by PET imaging and the impact of time-of-flight (TOF) reconstruction on detectability and quantitative accuracy according to the lesion size. METHODS: The study was conducted using a Siemens Biograph(R) mCT with a 22 cm large axial field of view. An IEC torso-shaped phantom containing five coplanar spheres was uniformly filled to achieve sphere-to-background ratios of 40:1. The phantom was imaged nine times in 14 days over 30 min. Sinograms were reconstructed with and without TOF information. A contrast-to-noise ratio (CNR) index was calculated using the Rose criterion, taking partial volume effects into account. The impact of reconstruction parameters on quantification accuracy, detectability, and spatial localization of the signal was investigated. Finally, six patients with hepatocellular carcinoma and four patients included in different 90Y-based radioimmunotherapy protocols were enrolled for the evaluation of the imaging parameters in a clinical situation. RESULTS: The highest CNR was achieved with one iteration for both TOF and non-TOF reconstructions. The MDA, however, was found to be lower with TOF than with non-TOF reconstruction. There was no gain by adding TOF information in terms of CNR for concentrations higher than 2 to 3 MBq mL-1, except for infra-centimetric lesions. Recovered activity was highly underestimated when a single iteration or non-TOF reconstruction was used (10 % to 150 % less depending on the lesion size). The MDA was estimated at 1 MBq mL-1 for a TOF reconstruction and infra-centimetric lesions. Images from patients treated with microspheres were clinically relevant, unlike those of patients who received systemic injections of 90Y. CONCLUSIONS: Only one iteration and TOF were necessary to achieve an MDA around 1 MBq mL-1 and the most accurate localization of lesions. For precise quantification, at least three iterations gave the best performance, using TOF reconstruction and keeping an MDA of roughly 1 MBq mL-1. One and three iterations were mandatory to prevent false positive results for quantitative analysis of clinical data.Trial registration: IDRCB 2011-A00043-38 P101103