Everolimus is the only approved therapy for patients with advanced neuroendocrine tumors (NET) of lung and thymus and new treatment options are urgently needed. Expression of somatostatin receptor 2 (SSTR2) is frequently seen in functional imaging in lung-NETs opening the opportunity to treat SSTR2 positive patients with radioligand therapies (RLT). Retrospective data suggest a potential meaningful benefit of RLT directed to SSTR2 in lung-NET patients. The LEVEL trial is a randomized, open-label, phase III international trial of 177Lu-edotreotide versus everolimus in patients with progressive, locally advanced or metastatic, and well/moderately differentiated NETs of lung (typical/atypical) or thymic origin. Patients could be treatment-naïve or have progressed (PD) on somatostatin analogues or ≤ 2 additional systemic treatments. Prior RLT or mTOR inhibitors are not permitted. Eligible patients are randomly assigned 3:2 to 6 cycles of 177Lu-edotreotide (total administered activity 7.5 ± 0.7 GBq / cycle) or to oral everolimus 10 mg once daily until PD or unacceptable toxicity. Only patients with positivity in somatostatin receptor imaging will be included. CT or MRI scans are performed every 12 weeks until PD. Blood samples are analyzed at baseline, at 1st tumor assessment, and at PD for pharmacodynamic endpoints. Archival tumor tissue samples will be analyzed for ancillary studies. The primary endpoint is progression-free survival (PFS) according to RECIST v1.1 based on local investigator assessment. Secondary endpoints include overall survival, overall response rate, safety, and quality of life (EORTC QLQ-C30). The expected sample size is 120 patients to demonstrate statistical significant risk reduction of 46.4 www.clinicaltrials.gov : NCT05918302 (June 23rd, 2023).

BACKGROUND:Peptide receptor radionuclide and targeted therapy are both approved treatment options for patients with metastatic gastroenteropancreatic neuroendocrine tumours (GEP NETs), but clinical evidence for preferred sequencing is scarce. The COMPETE trial evaluated the efficacy and harms of peptide receptor radionuclide therapy ([177Lu]Lu-edotreotide) versus targeted molecular therapy (everolimus) in patients with advanced, progressive, somatostatin receptor-positive GEP NETs. METHODS:This phase 3, open-label, superiority trial included patients aged 18 years or older with treatment-naive or previously treated unresectable or metastatic (or both) grade 1-2 GEP NETs. Patients were enrolled from 49 specialist neuroendocrine tumour treatment centres across 14 countries in Africa, Europe, North America, and Oceania and randomised (2:1) to intravenous [177Lu]Lu-edotreotide (7·5 ± 0·7 GBq every 3 months, maximum four cycles) or oral everolimus (10 mg/day) for up to 30 months. Random assignment was via a central, web-based randomisation system (block size of 6) and stratified by primary tumour origin and previous therapy. The primary endpoint was progression-free survival, assessed via blinded independent central review in all randomly assigned patients at 30 months. Harms were assessed in all enrolled patients who received at least one dose of a study drug. This study was registered with ClinicalTrials.gov (NCT03049189) and is no longer recruiting. FINDINGS:Between April 13, 2017, and June 20, 2022, 324 patients were enrolled and 309 patients (including 168 [54%] male patients and 141 [46%] female patients) were randomly assigned to treatment: 207 to the [177Lu]Lu-edotreotide group and 102 to the everolimus group. The median follow-up for progression-free survival was 27·5 months (IQR 19·6-30·4) for the [177Lu]Lu-edotreotide group and 21·2 months (8·9-29·4) for the everolimus group. Median progression-free survival was significantly longer with [177Lu]Lu-edotreotide versus everolimus (23·9 months [95% CI 18·7-30·0] vs 14·1 months [9·2-20·9]; stratified hazard ratio 0·67 [95% CI 0·48-0·95]; p=0·022). Treatment-related adverse events occurred in 178 (82%) of 217 patients in the [177Lu]Lu-edotreotide group and 96 (97%) of 99 patients in the everolimus group. 40 (18%) patients in the [177Lu]Lu-edotreotide group and 40 (40%) in the everolimus group had at least one treatment-related grade 3-4 adverse event. The most common treatment-related adverse events in the [177Lu]Lu-edotreotide group were diarrhoea and nausea (both 79 [36%] patients) and asthenia (66 [33%] patients), whereas those in the everolimus group were diarrhoea (45 [45%] patients), asthenia (36 [36%] patients), and anaemia (27 [27%] patients). No treatment-related deaths occurred in either study group. INTERPRETATION:[177Lu]Lu-edotreotide led to statistically significant and clinically meaningful improvements in progression-free survival. Efficacy and harms results support the use of [177Lu]Lu-edotreotide in early lines of therapy in patients with advanced, progressive GEP NETs. FUNDING:ITM Solucin.

PURPOSE:There is no consensus on functional imaging modalities for lesion assessment in medullary thyroid carcinoma. The aim of this single-center retrospective study was to analyze the performance of [18F]F-DOPA-PET/CT, [18F]F-FDG-PET/CT and morphologic imaging in a cohort of patients with medullary thyroid carcinoma and extrathyroidal lesions. METHODS:Forty-three patients (10 women and 33 men; median age, 62.8years), including 28 with RET mutation (germline: n=13, somatic: n=15), all with extrathyroidal morphological lesions, underwent conventional imaging, plus [18F]F-DOPA-PET/CT with early and late acquisitions (n=40), [18F]F-FDG-PET/CT (n=29) or both (n=26), for initial staging or follow-up. PET/CT scans were analyzed visually and semi-quantitatively (SUVmax of the hottest lesion). The gold standard was based on histology and imaging follow-up. RESULTS:According to the gold standard, a median 2 extrathyroidal regions were involved per patient. Per-patient sensitivity was 95.0% (38/40) for [18F]F-DOPA-PET/CT, 93.1% (27/29) for [18F]F-FDG-PET/CT, and 76.9% (30/39) for morphologic imaging. [18F]F-DOPA-PET/CT identified more hepatic and osteomedullary involvement than did [18F]F-FDG-PET/CT. The combination of both PET modalities detected at least 1 additional metastatic site in 10/26 patients (38.5%). [18F]F-DOPA SUVmax was significantly higher on early than late acquisitions (P=0.0001) and correlated positively with blood calcitonin (P=0.0069). [18F]F-FDG SUVmax correlated with shorter calcitonin doubling time (P=0.0203). SUVmax and RET status did not correlate. CONCLUSIONS:Our results provide insight into the complementary role of [18F]F-DOPA and [18F]F-FDG-PET/CT in a high-risk population with morphologically proven metastatic disease.

Peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTATATE is an established treatment option for progressive, gastroenteropancreatic neuroendocrine tumors (GEP-NETs). While this approach provides durable disease control in many patients, objective response rates remain modest. Targeted alpha therapy (TAT) has emerged as a potential next-generation strategy by delivering higher linear energy transfer (LET) radiation, which may enhance tumor cytotoxicity while limiting off-target damage. Preclinical studies using alpha-emitters, including 212Pb, 213Bi and 225Ac, with more limited evidence available for 211At, have suggested antitumor activity and manageable toxicity profiles. Early clinical trials and first-in-human studies report preliminary signals of activity and acceptable short-term safety profiles in selected patient populations. However, these findings remain based on small, heterogeneous cohorts with limited follow-up. Ongoing clinical trials will be essential to better define the efficacy, safety and optimal positioning of alpha therapy within current treatment algorithms. This review summarizes current clinical indications for PRRT in GEP-NETs and discusses emerging strategies to optimize its efficacy, with a particular focus on the development of alpha-based radionuclide therapies.

BACKGROUND:To our knowledge, no randomised trial with peptide receptor radionuclide therapy has been done in patients with metastatic pancreatic neuroendocrine tumours. We aimed to evaluate the antitumour activity and safety of [177Lu]Lu-dota-tate in this setting. METHODS:OCLURANDOM is a randomised, open-label, non-comparative, phase 2 trial conducted in ten academic centres in France. Patients aged 18 years and older with pretreated, progressive, somatostatin receptor-positive, metastatic pancreatic neuroendocrine tumours and an Eastern Cooperative Oncology Group performance status of 0-2 were randomly assigned (1:1) using web-based software to receive intravenous [177Lu]Lu-dota-tate (7·4 GBq every 8 weeks up to four cycles) with concomitant amino acid infusion or oral sunitinib (37·5 mg once daily). Amino acid infusion was for at least 4 h starting 30 min before [177Lu]Lu-dota-tate infusion and included 16·8 g of arginine and 22 g of lysine in 2 L until May, 2018, and, from that date, a solution of 25 g of arginine and 25 g of lysine in 2 L. Randomisation was stratified according to Ki-67, liver involvement, and previous therapies. The primary endpoint was progression-free survival at 12 months assessed by real-time central review using Response Evaluation Criteria in Solid Tumours version 1.1 in the intention-to-treat population. Cross-over was allowed. Adverse events in the as-treated population were assessed continuously during the active phase of treatment and then every 3 months. Patients and the public were not involved in the design, conduct, reporting, or dissemination plans of this research. This trial was registered with ClinicalTrials.gov, NCT02230176, and is closed to enrolment. FINDINGS:Between Feb 13, 2015, and July 16, 2020, 84 patients were enrolled and randomly assigned to the [177Lu]Lu-dota-tate group (n=41) or the sunitinib group (n=43). 44 (52%) patients were women and 40 (48%) were men. Median follow-up was 72·5 months (IQR 61·4-88·4). Progression-free survival rate at 12 months was 33 (80·5% [90% CI 67·5-89·9]) of 41 patients in the [177Lu]Lu-dota-tate group versus 18 (41·9% [29·1-55·5]) of 43 patients in the sunitinib group. Grade 3-4 adverse events occurred in 18 (44%) of 41 patients in the [177Lu]Lu-dota-tate group and 31 (72%) of 43 patients in the sunitinib group. The most common grade 3-4 adverse events for all treatment groups were neutropenia (two [5%] of 41 in the [177Lu]Lu-dota-tate group vs 13 [30%] of 43 in the sunitinib group) and hypertension (four [10%] in the [177Lu]Lu-dota-tate group vs eight [19%] in the sunitinib group). Drug-related serious adverse events occurred in six (15%) patients in the [177Lu]Lu-dota-tate group (transaminase increase, neutropenia, thrombosis, and fever) and ten (23%) in the sunitinib group (gastrointestinal, general disorders, and sepsis). There was a 10·3-point (95% CI 2·4-18·2) difference in the Global Health Status score between the two groups in favour of [177Lu]Lu-dota-tate. Late adverse events (grade 2 or worse) were reported in 24 (60%) patients in the [177Lu]Lu-dota-tate group and in three (43%) of seven patients in the sunitinib group. One treatment-related death (acute leukaemia) occurred in the [177Lu]Lu-dota-tate group. INTERPRETATION:Using sunitinib as an internal control, our results show clinically significant antitumour efficacy of [177Lu]Lu-dota-tate in pretreated, progressive, somatostatin receptor-positive, metastatic pancreatic neuroendocrine tumours, and a better quality of life during the treatment phase. Late adverse events were reported in the [177Lu]Lu-dota-tate group that might affect the tolerance of subsequent lines of treatment. FUNDING:French Ministry of Health, through the National Institute for Cancer.

4171 Background: The Phase 3 COMPETE trial demonstrated a significant treatment effect in favor of 177 Lu-edotreotide over everolimus in patients with Grade 1/2, well-differentiated, gastroenteropancreatic neuroendocrine tumors; 177 Lu-edotreotide significantly improved progression-free survival (primary endpoint) and objective response rate (secondary endpoint) compared to everolimus. Nowadays, treatment choice also considers the impact of therapy on patients’ quality of life (QoL); here, we present QoL results from the COMPETE trial. Methods: The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 and EORTC QLQ-gastrointestinal neuroendocrine tumors (GI.NET) were completed by patients at baseline, each month during the first year, and every 3 months thereafter until disease progression or end of study. Mean change from baseline, duration of maximum health-related quality of life (HRQoL) improvement (until deterioration), and time to deterioration were calculated. Between-group comparisons were conducted using repeated measure analysis with factors for treatment, randomization stratification factors, visit, baseline value, and treatment-by-visit interaction; all HRQoL analyses were prespecified and exploratory. Results: Based on repeated measure analysis, mean change from baseline was in favor of 177 Lu-edotreotide: overall mean change (95% confidence interval [CI]) in global health score was 0.9 (-2.7, 4.4) in the 177 Lu-edotreotide arm vs -9.9 (-13.9, -6.0) in the everolimus arm (nominal p<0.0001) (positive change corresponds to improvement). Time to deterioration in global health status/QoL was longer in the 177 Lu-edotreotide arm vs the everolimus arm (Table 1). Similar trends were observed in the EORTC QLQ-C30 and EORTC QLQ-GI.NET subdomains. In the 177 Lu-edotreotide arm, 90/207 (43.5%) participants had a clinically meaningful improvement (≥10 points) in global HRQoL score, vs 31/102 (30.4%) participants in the everolimus arm. Among these participants, the median duration of improvement was 22.0 (95%CI: 10.1, not evaluable [NE]) vs 10.2 (95%CI: 3.3, NE) months in the 177 Lu-edotreotide and everolimus arm, respectively. Conclusions: Consistent with the overall COMPETE outcomes, this analysis demonstrated clinically meaningful and durable HRQoL benefits for 177 Lu-edotreotide compared with everolimus. Clinical trial information: NCT03049189 . Time to deterioration in global health status/QoL (≥10 points). Parameter / Statistics 177 Lu-edotreotide(N=207) Everolimus(N=102) Patients with ≥10 points deterioration, n (%) 114 (55.1) 78 (76.5) Median, months (95% CI) a 10.251 (7.359, 15.901) 2.267 (2.004, 3.253) Nominal stratified p-value b <0.0001 Stratified hazard ratio (95% CI) 0.392 (0.292, 0.527) a Estimated via Kaplan-Meier method. b Derived from a two-sided test between the two groups.

Background: Multiglandular parathyroid disease, which is particularly frequent in patients with mild primary hyperparathyroidism, is a surgical challenge requiring bilateral cervicotomy with 4-gland exploration. Near-infrared autofluorescence of the parathyroid is increasingly used to prevent hypocalcemia after total thyroidectomy. However, its utility in decreasing operating time and aiding parathyroid identification during bilateral 4-gland exploration remains debated. Methods: In our prospective trial, we enrolled consecutive patients with sporadic mild primary hyperparathyroidism (serum calcium <2.85 mmol/L with elevated or nonadapted serum parathyroid hormone levels). With randomization, we assigned patients to classic parathyroidectomy or parathyroidectomy with near-infrared autofluorescence using the Fluobeam 800 device (near-infrared autofluorescence group). All procedures involved planned bilateral neck exploration conducted by 2 experienced surgeons. The primary outcome was mean operating time. Secondary outcomes included the number of visualized and excised glands, complication rates, and cure rates. Results: In total, 132 patients were included (66 per group). Mean age was 64.0 +/- 12.0 years, with 85.6% female. Mean preoperative serum calcium level was 2.63 +/- 0.11 mmol/L, and median serum PTH level 86.1 [65.6-109.8] pg/mL. The mean operating time did not significantly differ between the classic parathyroidectomy and near-infrared autofluorescence groups (46.9 +/- 15.3 minutes and 51.2 +/- 22.9 minutes, respectively, P 1/4 .21). The use of near-infrared autofluorescence did not significantly modify the number of identified or resected glands nor the rate of complications. Cure rates were similar between groups (92.2% and 94.8%; P 1/4 .72). Conclusion: In this study, near-infrared autofluorescence, in the hands of experienced surgeons, did not reduce operating time for parathyroidectomy during bilateral neck exploration in mild primary hyperparathyroidism. Although not increasing operating time, further evaluation is needed, particularly regarding its role in the surgeon's training. (c) 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Les cancers thyroïdiens de souche folliculaire (CT) sont rares chez les enfants et les adolescents nécessitant une prise en charge experte multidisciplinaire conformément aux recommandations ETA 2022. Cette étude rétrospective multicentrique du réseau national TUTHYREF a pour objectif de décrire le parcours de soins actuel et le devenir de ces patients. 52 patients mineurs pris en charge pour un CT entre 2010 et 2022 ont été inclus ce jour avec un âge médian de 14 ans. 63 % des patients avaient un nodule Bethesda V ou IV ; 11 % Bethesda IV et 4 % Bethesda III. La chirurgie thyroïdienne était validée en RCP dans 31 % des cas, impliquant un pédiatre dans 35 % des cas et une consultation génétique dans 26 % des cas. 16 % des patients étaient opérés par un chirurgien pédiatrique. 88 % et 12 % des cancers étaient respectivement papillaires ou folliculaires. 40 % des patients présentaient une hypoparathyroïdie transitoire et 10 % une hypoparathyroïdie définitive. Après une thyroïdectomie totale dont 77 % avec un curage ganglionnaire, un traitement par iode radioactif était proposé à 98 % des patients, dont 58 % en sevrage et 42 % sous Thyrogen®, avec une Tg médiane au moment de l’iode à 4,8ng/mL et plusieurs cures pour 38 % des patients. Des métastases ganglionnaires et à distance étaient présentes chez 50 % et 9 % enfants. Après le traitement initial, 65 % des patients étaient d’emblée en rémission, 26 % présentaient une récidive locorégionale. Après un suivi médian de 3 ans, 93 % des patients étaient en rémission et 7 % en réponse biologique incomplète sans aucun décès.

To evaluate the dosimetry and pharmacokinetics of the novel radiolabelled somatostatin receptor antagonist [177Lu]Lu-satoreotide tetraxetan in patients with advanced neuroendocrine tumours (NETs). This study was part of a phase I/II trial of [177Lu]Lu-satoreotide tetraxetan, administered at a median cumulative activity of 13.0 GBq over three planned cycles (median activity/cycle: 4.5 GBq), in 40 patients with progressive NETs. Organ absorbed doses were monitored at each cycle using patient-specific dosimetry; the cumulative absorbed-dose limits were set at 23.0 Gy for the kidneys and 1.5 Gy for bone marrow. Absorbed dose coefficients (ADCs) were calculated using both patient-specific and model-based dosimetry for some patients. In all evaluated organs, maximum [177Lu]Lu-satoreotide tetraxetan uptake was observed at the first imaging timepoint (4 h after injection), followed by an exponential decrease. Kidneys were the main route of elimination, with a cumulative excretion of 57–66

Although peptide radionuclide therapy (PRRT) using a somatostatin analog (SSA) radiolabeled with a beta- emitter: [177Lu]Lu-DOTATATE has shown a good clinical efficacy in neuroendocrine tumors (NETs), most of the patients only achieved tumoral stabilization and rare but severe long-term hematological toxicities have been reported. One of the promising options to improve PRRT is targeted alpha therapy. It is therefore essential to propose animal models that can mimic systemic spread disease, especially microscopic disease such as early stage of NET liver metastases to explore targeted alpha therapy. Herein, we report the evaluation of efficacy and toxicity of [225Ac]Ac-DOTATOC in an original preclinical murine model simulating the development of well-characterized liver metastases of pancreatic NETs with SSTR overexpression. A mouse model of liver metastases of pancreatic NETs was developed by intraportal injection of AR42J cells and explored using [68 Ga]Ga-DOTATOC and [18F]F-FDG PET/MRI. Biodistribution study and radiation dosimetry of [225Ac]Ac-DOTATOC were determined in subcutaneous tumor-bearing NMRI-nude mice. Efficacy and toxicity were determined by intravenous injection of increasing activities of [225Ac]Ac-DOTATOC 10 days after intraportal graft. Liver tumors showed a high uptake of [68 Ga]Ga-DOTATOC and no uptake of [18F]F-FDG confirming the well-differentiated phenotype. All groups treated with [225Ac]Ac-DOTATOC showed a significant increase in overall survival compared with DOTATOC-treated mice, especially those treated with the highest activities: 53 days with 240 kBq (p = 0.0001), and 58 days with 2 × 120 kBq (p < 0.0001) vs 28 days with non-radiolabeled DOTATOC. On blood tests, a transient and moderate decreased in white blood cells count after treatment and no severe hepatic or renal toxicity were observed after treatment which was consistent with pathological and radiation dosimetry findings. [225Ac]Ac-DOTATOC exhibit a favorable efficacy and toxicity profile in a mouse model of liver micrometastatic pancreatic NET.

Introduction Il n’existe pas de consensus concernant les modalités d’imagerie fonctionnelle pour le bilan lésionnel du carcinome médullaire thyroïdien (CMT), compte tenu de sa rareté et des données limitées de la littérature. Méthodologie Cette étude menée au CHU de Nantes a évalué rétrospectivement les performances des TEP-DOPA et TEP-FDG chez des patients porteurs de CMT avec atteinte morphologique extra-thyroïdienne, en comparaison à l’imagerie morphologique et à un gold-standard composite (histologie, imagerie, suivi). Résultats Les données de 43 patients ont été analysées : 10 femmes, 33 hommes, d’âge médian : 62,8ans (3–83), calcitoninémie médiane : 1014 pg/mL (21–118000), ACE médian : 40,1 ng/mL (2–8172). Au total, 28 patients étaient mutés RET (germinal : 13, somatique : 15). La sensibilité de la TEP-DOPA était de 95 % (38/40), celle de la TEP-FDG 93,1 % (27/29) en regard d’une sensibilité de l’imagerie morphologique de 76,9 % (30/39). La TEP-DOPA semblait détecter plus d’extension hépatique et ostéomédullaire que la TEP-FDG. La SUVmax de la DOPA était significativement plus élevée sur l’acquisition précoce que tardive (p=0,0001), ce paramètre était corrélé à la calcitoninémie (p=0,0069). La SUVmax du FDG était corrélée au temps de doublement (TD) de la calcitonine (p=0,0203). Il n’existait aucune corrélation des SUVmax avec le statut mutationnel. Au moins un site métastatique supplémentaire était détecté pour 10 des 26 patients (38,5 %) explorés par les 2 TEP. Conclusion Cette étude monocentrique menée sur 43 patients confirme l’intérêt de la TEP-DOPA pour le bilan lésionnel corps entier, et la complémentarité de la TEP-FDG chez certains patients, notamment avec un TD de la calcitonine rapide.

Purpose We present the results of an open-label, phase I/II study evaluating the safety and efficacy of the novel somatostatin receptor (SSTR) antagonist [ 177 Lu]Lu-satoreotide tetraxetan in 40 patients with previously treated, progressive neuroendocrine tumours (NETs), in which dosimetry was used to guide maximum administered activity. Methods This study was conducted in two parts. Part A consisted of 15 patients who completed three cycles of [ 177 Lu]Lu-satoreotide tetraxetan at a fixed administered activity and peptide amount per cycle (4.5 GBq/300 µg). Part B, which included 25 patients who received one to five cycles of [ 177 Lu]Lu-satoreotide tetraxetan, evaluated different administered activities (4.5 or 6.0 GBq/cycle) and peptide amounts (300, 700, or 1300 μg/cycle), limited to a cumulative absorbed radiation dose of 23 Gy to the kidneys and 1.5 Gy to the bone marrow. Results Median cumulative administered activity of [ 177 Lu]Lu-satoreotide tetraxetan was 13.0 GBq over three cycles (13.1 GBq in part A and 12.9 GBq in part B). Overall, 17 (42.5%) patients experienced grade ≥ 3 treatment‑related adverse events; the most common were lymphopenia, thrombocytopenia, and neutropenia. No grade 3/4 nephrotoxicity was observed. Two patients developed myeloid neoplasms considered treatment related by the investigator. Disease control rate for part A and part B was 94.7% (95% confidence interval [CI]: 82.3–99.4), and overall response rate was 21.1% (95% CI: 9.6–37.3). Conclusion [ 177 Lu]Lu-satoreotide tetraxetan, administered at a median cumulative activity of 13.0 GBq over three cycles, has an acceptable safety profile with a promising clinical response in patients with progressive, SSTR-positive NETs. A 5-year long-term follow-up study is ongoing. Trial registration ClinicalTrials.gov, NCT02592707. Registered October 30, 2015.

The aims of the study were to evaluate the performance and robustness of [18F]fluorocholine PET/CT in detecting hyperfunctioning parathyroid glands in MEN1-related primary hyperparathyroidism (pHPT) at different stages of their disease. Retrospective French multicenter study including patients with MEN1 pHPT who underwent [18F]fluorocholine PET/CT at initial diagnosis or for evaluation of persistent/recurrent disease. PET/CT were independently reviewed by two readers in a blinded manner. The assessment of PET/CT on a per-patient basis was assessed using a comprehensive set of criteria that considered pathological findings or agreement with alternative diagnostic methods in non-operated patients. The secondary objectives included the analysis of the performance of PET/CT at a per-lesion level, with reference to a pathological Gold Standard, and examining its interobserver reproducibility. A total of 71 MEN1 patients were included (73 PET/CT) in the study. At the per-patient level (entire cohort), [18F]fluorocholine PET/CT sensitivity ranged from 98.5 to 100

Although there is a close relationship between cortisol and growth hormone (GH) levels, glucose intolerance and hepatosteatosis, changes in GH and the hypothalamo-pituitary-adrenal (HPA) axis were not previously studied in prediabetes. The main purpose of the present study was to assess changes in GH and HPA axis and their relationship with hepatosteatosis in prediabetic patients.Forty prediabetic patients, with body-mass index (BMI) 25–35 kg/m2, and 23 healthy individuals, with normal glucose tolerance and similar age and BMI, were included. The 75 g oral glucose tolerance test and glucagon stimulation test (GST) were used.No significant differences were detected between prediabetic patients and healthy individuals in terms of insulin-like growth factor-1 (IGF-1), insulin-like growth factor-binding protein-3 (IGFBP-3), IGF-1/IGFBP3 ratio or adrenocorticotropic hormone (ACTH). GH responses to GST did not differ between groups. On the other hand, peak cortisol and area under the curve (AUC) (cortisol) response on GST were significantly lower in prediabetic patients. Both peak GH and AUC (GH) response on GST correlated negatively with waist circumference and body weight. The degree of hepatosteatosis correlated negatively with peak cortisol, GH, AUC (cortisol) and AUC (GH) response on GST.Cortisol response to GST is decreased in prediabetic patients, with relatively well conserved GH response. This suggests altered HPA axis responsiveness in prediabetes, as is known in diabetes. Thus, HPA axis changes in patients with diabetes probably start before the development of diabetes as such.

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.

TPS3177 Background: Everolimus is the only approved drug for the treatment of patients with neuroendocrine tumors (NETs) of lung and thymic origin, showing a median progression-free survival (PFS) of 11 months. Retrospective data for peptide receptor radionuclide therapy (PRRT) have demonstrated promising activity in somatostatin receptor (SSTR)-positive lung NETs. This study aims to compare the efficacy, safety, and patient-reported outcomes of 177Lu-edotreotide versus the standard of care everolimus in patients with advanced lung and thymic NETs. Methods: The LEVEL trial is a randomized, open-label, phase 3 international trial of 177Lu-edotreotide versus everolimus in patients with progressive, advanced, and well/moderately differentiated NETs of lung (typical/atypical) or thymic origin. Patients could be treatment naïve or have progressed (PD) on somatostatin analogues or ≤2 additional systemic treatments. Prior PRRT or mTOR inhibitors are not permitted. Eligible patients are randomly assigned 3:2 to 6 cycles of 177Lu-edotreotide (7.5±0.7 GBq / cycle) or to oral everolimus 10 mg once daily until PD or unacceptable toxicity. Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) scans are performed every 12 weeks until PD. Blood samples are analyzed at baseline, at 1st tumor assessment, and at PD for pharmacodynamic endpoints. Archival tumor tissue samples will be analyzed for ancillary studies. The primary endpoint is PFS according to RECIST v1.1. Secondary endpoints include overall response rate, duration of response, overall survival, safety, and quality of life (assessed through EORTC QLQ-C30). The expected sample size is 120 patients using a two-sided group sequential Lan-DeMets with O’Brien-Fleming-like boundaries test to demonstrate statistically significant risk reduction of 46.4% (HR= 0.536) in PFS between arms (α=0.05, β=0.2). The study has received institutional review board/ethics committee approval. Recruitment started in Oct 2023. Thirteen patients are already included. Clinical trial information: NCT05918302 .

Déterminer les performances de la TEP-DOTATOC dans le bilan lésionnel initial (détection du primitif, de l’envahissement ganglionnaire et métastatique), en préopératoire, chez des patients présentant une NNE bronchique bien différenciée, par comparaison aux performances de la TEP-FDG et de la TDM. Analyse rétrospective des TEP DOTATOC et FDG de TNE bronchiques prouvées histologiquement sur 6 ans, avant prise en charge médicale ou chirurgicale. Au total, 40 patients inclus (22 CT, 3 CA, DIPNECH, 12 tumeurs NOS) dont 11 patients métastatiques et 30 ayant bénéficié d’une TEP FDG. Sensibilité dans détection du primitif : 70,4 % (IC95 % 0,52–0,84) pour TEP DOTATOC contre 74 % (IC95 % 0,55–0,87) pour TEP FDG. Fixation plus intense en DOTATOC pour les CT ; et en FDG pour les tumeurs métastatiques. Performances dans détection de l’envahissement ganglionnaire : sensibilité plus importante en DOTATOC (57 %) qu’en TDM (14 %) et FDG (33 %). Spécificité meilleure en DOTATOC et TDM (94 %) qu’en FDG (77 %). Performances dans détection de l’envahissement métastatique : TEP DOTATOC plus sensible pour détecter lésions osseuses (Se 100 %) et cérébrales ; et plus spécifique dans pour détecter lésions surrénaliennes. Moins sensible pour la détection des métastases pulmonaires comparés au TDM. Les sensibilités pour la détection des métastases hépatiques étaient identiques entre les 3 examens et médiocres. L’association des examens augmente les performances diagnostique. La TEP DOTATOC s’impose dans le bilan lésionnel initial des NNE. La TEP DOTATOC est meilleure dans la détection des CT, dans l’évaluation de l’envahissement ganglionnaire des CT, et en cas de lésions secondaires osseuses, surrénaliennes ou cérébrales.