Efficacy of [177Lu]Lu-DOTATATE in metastatic neuroendocrine neoplasms of different locations: data from the SEPTRALU study

Neuroendocrine tumor; Radionuclide therapyTumor neuroendocrí; Teràpia amb radionúclidsTumor neuroendocrino; Terapia con radionúclidosBackground Peptide receptor radionuclide therapy (PRRT) is one of the most promising therapeutic strategies in neuroendocrine neoplasms (NENs). Nevertheless, its role in certain tumor sites remains unclear. This study sought to elucidate the efficacy and safety of [177Lu]Lu-DOTATATE in NENs with different locations and evaluate the effect of the tumor origin, bearing in mind other prognostic variables. Advanced NENs overexpressing somatostatin receptors (SSTRs) on functional imaging, of any grade or location, treated at 24 centers were enrolled. The protocol consisted of four cycles of 177Lu-DOTATATE 7.4 GBq iv every 8 weeks (NCT04949282). Results The sample comprised 522 subjects with pancreatic (35%), midgut (28%), bronchopulmonary (11%), pheochromocytoma/ paraganglioma (PPGL) (6%), other gastroenteropancreatic (GEP) (11%), and other non-gastroenteropancreatic (NGEP) (9%) NENs. The best RECIST 1.1 responses were complete response, 0.7%; partial response, 33.2%; stable disease, 52.1%; and tumor progression, 14%, with activity conditioned by the tumor subtype, but with benefit in all strata. Median progression-free survival (PFS) was 31.3 months (95% CI, 25.7–not reached [NR]) in midgut, 30.6 months (14.4-NR) in PPGL, 24.3 months (18.0-NR) in other GEP, 20.5 months (11.8-NR) in other NGEP, 19.8 months (16.8–28.1) in pancreatic, and 17.6 months (14.4–33.1) in bronchopulmonary NENs. [177Lu]Lu-DOTATATE exhibited scant severe toxicity. Conclusion This study confirms the efficacy and safety of [177Lu]Lu-DOTATATE in a wide range of SSTR-expressing NENs, regardless of location, with clinical benefit and superimposable survival outcomes between pNENs and other GEP and NGEP tumor subtypes different from midgut NENs.The SEPTRALU registry received external funding from Novartis

Autonomous cortisol secretion in patients with primary aldosteronism: prevalence and implications on cardiometabolic profile and on surgical outcomes

Purpose: The aim of this study was to evaluate the prevalence of autonomous cortisol secretion (ACS) in patients with primary aldosteronism (PA) and its implications on cardiometabolic and surgical outcomes. Methods: This is a retrospective multicenter study of PA patients who underwent 1 mg dexamethasone-suppression test (DST) during diagnostic workup in 21 Spanish tertiary hospitals. ACS was defined as a cortisol post-DST >1.8 μg/dL (confirmed ACS if >5 μg/dL and possible ACS if 1.8–5 μg/dL) in the absence of spe cific clinical features of hypercortisolism. The cardiometabolic profile was compared with a control group with ACS without PA (ACS group) matched for age and DST levels. Results: The prevalence of ACS in the global cohort of patients with PA (n = 176) was 29% (ACS–PA; n = 51). Ten patients had confirmed ACS and 41 possible ACS. The cardiometabolic profile of ACS–PA and PA-only patients was simil ar, except for older age and larger tumor size of the adrenal lesion in the ACS–PA group. When comparing the ACS–PA group (n = 51) and the ACS group (n = 78), the prevalence of hypertension (OR 7.7 (2.64–22.32)) and cardiovascular events (OR 5.0 (2.29–11.07)) was higher in ACS–PA patients than in ACS patients. The coexistence of ACS in patien ts with PA did not affect the surgical outcomes, the proportion of biochemical cure and clinical cure being similar between ACS–PA and PA-only groups. Conclusion: Co-secretion of cortisol and aldosterone affects almost one-thi rd of patients with PA. Its occurrence is more frequent in patients with larger tumors and advanced age. However, the cardiometabolic and surgical outcomes of patients with ACS–PA and PA-only are similar

Raynaud’s phenomenon caused by cabergoline during the treatment of a macroprolactinoma: a case report

Digital vasospasm is a known adverse effect of dopamine agonists such as bromocriptine; however, it has rarely been reported with cabergoline. We describe a case of Raynaud's phenomenon as a side effect of treatment with the latter in a 52-year-old woman with a macroprolactinoma, forcing discontinuation. In this context, we conducted a review of the literature, with emphasis on the possible criteria for discontinuation of treatment with dopaminergic agonists in patients with macroprolactinoma

Metanephrin-producing adrenocortical carcinoma: a case report

Adrenocortical carcinoma is a rather infrequent neoplasm that mostly occurs with an autonomous secretion of steroids or steroid precursors. Previous cases have been reported with simultaneous production of metanephrines, but they were associated with intercurrent pheochromocytoma or mixed corticomedular tumors. So far, only two cases of adrenocortical carcinoma that deliver medullar hormones had been published. We herein report a singular case of a 58-year-old man with a finding of an incidental adrenal mass that demonstrated metanephrine production in the hormonal study. Consequently, initial diagnosis of pheochromocytoma was established. Microscopic examination showed an adrenal mass with marked pleomorphism and frequent mitosis. Large areas of coagulative necrosis were interspersed within the tumour. After immunohistochemistry staining there was a high expression of Ki67 (>70%) showing highly proliferative behaviour.  Both cytokeratin AE1/AE3 and vimentin were positive, synaptophysin and chromogranin were negative. The surgical margins were free. Given these features, a diagnosis of metanephrin-producing adrenocortical carcinoma was done

Metanephrin-producing adrenocortical carcinoma: a case report

Adrenocortical carcinoma is a rather infrequent neoplasm that mostly occurs with an autonomous secretion of steroids or steroid precursors. Previous cases have been reported with simultaneous production of metanephrines, but they were associated with intercurrent pheochromocytoma or mixed corticomedular tumors. So far, only two cases of adrenocortical carcinoma that deliver medullar hormones had been published. We herein report a singular case of a 58-year-old man with a finding of an incidental adrenal mass that demonstrated metanephrine production in the hormonal study. Consequently, initial diagnosis of pheochromocytoma was established. Microscopic examination showed an adrenal mass with marked pleomorphism and frequent mitosis. Large areas of coagulative necrosis were interspersed within the tumour. After immunohistochemistry staining there was a high expression of Ki67 (>70%) showing highly proliferative behaviour.  Both cytokeratin AE1/AE3 and vimentin were positive, synaptophysin and chromogranin were negative. The surgical margins were free. Given these features, a diagnosis of metanephrin-producing adrenocortical carcinoma was done

Tumor mesenquimal variante no fosfatúrica: a propósito de un caso

Osteomalacia-inducing tumors (OIT) are usually benign, small and slow growing. OIT have an abnormal production of fibroblast growth factor 23 (FGF-23) which causes the inhibition of phosphate reabsorption in the proximal convoluted tubule and the inactivation of 1α-hydroxylase with consequent hypophosphatemia, phosphaturia and alteration of vitamin D metabolism, leading to the appearance of acquired osteomalacia. Recently a non-phosphaturic variant has been described. This clinical case presents a patient with a non-phosphaturic mesenchymal tumor, whose diagnosis was complicated by nonspecific initial symptoms. Keywords: mesenchymal tumor, phosphaturia, osteomalacia, FGF-23, diagnosisLos tumores mesenquimales inductores de osteomalacia (TIO) suelen ser benignos, pequeños, de crecimiento lento. Los TIO tienen una producción anormal del factor de crecimiento fibroblástico 23 (FGF-23) que ocasiona la inhibición de la reabsorción de fosfato en el túbulo contorneado proximal y la inactivación de la 1α-hidroxilasa con la consecuente hipofosfatemia, fosfaturia y alteración del metabolismo de la vitamina D que conlleva a la aparición de osteomalacia adquirida. Recientemente se ha descrito la variante no fosfatúrica. En este caso clínico se presenta un paciente con un tumor mesenquimal no fosfatúrico cuyo diagnóstico fue complicado debido a los síntomas iniciales inespecíficos. Palabras clave: tumor mesenquimal, fosfaturia, osteomalacia, FGF-23, diagnóstico

External Validity of Somatostatin Analogs Trials in Advanced Neuroendocrine Neoplasms: The GETNE-TRASGU Study

[Introduction] Somatostatin analogs (SSA) prolong progression-free survival (PFS) in patients with well-differentiated gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). However, the eligibility criteria in randomized clinical trials (RCTs) have been restricted, which contrasts with the vast heterogeneity found in NENs.[Methods] We identified patients with well-differentiated (Ki-67% ≤20%), metastatic GEP-NENs treated in first line with SSA monotherapy from the Spanish R-GETNE registry. The therapeutic effect was evaluated using a Bayesian Cox model. The objective was to compare survival-based outcomes from real-world clinical practice versus RCTs.[Results] The dataset contained 535 patients with a median age of 62 years (range: 26–89). The median Ki-67% was 4 (range: 0–20). The most common primary tumor sites were as follows: midgut, 46%; pancreas, 34%; unknown primary, 10%; and colorectal, 10%. Half of the patients received octreotide LAR (n = 266) and half, lanreotide autogel (n = 269). The median PFS was 28.0 months (95% CI: 22.1–32.0) for octreotide versus 30.1 months (95% CI: 23.1–38.0) for lanreotide. The overall hazard ratio for lanreotide versus octreotide was 0.90 (95% credible interval: 0.71–1.12). The probability of effect sizes >30% with lanreotide versus octreotide was 2 and 6% for midgut and foregut NENs, respectively.[Conclusion] Our study evaluated the external validity of RCTs examining SSAs in the real world, as well as the main effect-modifying factors (progression status, symptoms, tumor site, specific metastases, and analytical data). Our results indicate that both octreotide LAR and lanreotide autogel had a similar effect on PFS. Consequently, both represent valid alternatives in patients with well-differentiated, metastatic GEP-NENs.The study has been funded by a restricted grant from Novartis Farmacéutica, S.A. RGETNE and the GETNE group is partially funded by Ipsen, Novartis, Pfizer and AAA. Dr Angela Lamarca received funding from ASCO Conquer Cancer Foundation Young Investigator Award and The Christie Charity. Dr Jorge Barriuso received funding from the received funding from the ENETS Centre of Excellence Fellowship Grant Award.Peer reviewe

Prediction of Progression-Free Survival in Patients With Advanced, Well-Differentiated, Neuroendocrine Tumors Being Treated With a Somatostatin Analog: The GETNE-TRASGU Study

PURPOSE: Somatostatin analogs (SSAs) are recommended for the first-line treatment of most patients with well-differentiated, gastroenteropancreatic (GEP) neuroendocrine tumors; however, benefit from treatment is heterogeneous. The aim of the current study was to develop and validate a progression-free survival (PFS) prediction model in SSA-treated patients. PATIENTS AND METHODS: We extracted data from the Spanish Group of Neuroendocrine and Endocrine Tumors Registry (R-GETNE). Patient eligibility criteria included GEP primary, Ki-67 of 20% or less, and first-line SSA monotherapy for advanced disease. An accelerated failure time model was developed to predict PFS, which was represented as a nomogram and an online calculator. The nomogram was externally validated in an independent series of consecutive eligible patients (The Christie NHS Foundation Trust, Manchester, United Kingdom). RESULTS: We recruited 535 patients (R-GETNE, n = 438; Manchester, n = 97). Median PFS and overall survival in the derivation cohort were 28.7 (95% CI, 23.8 to 31.1) and 85.9 months (95% CI, 71.5 to 96.7 months), respectively. Nine covariates significantly associated with PFS were primary tumor location, Ki-67 percentage, neutrophil-to-lymphocyte ratio, alkaline phosphatase, extent of liver involvement, presence of bone and peritoneal metastases, documented progression status, and the presence of symptoms when initiating SSA. The GETNE-TRASGU (Treated With Analog of Somatostatin in Gastroenteropancreatic and Unknown Primary NETs) model demonstrated suitable calibration, as well as fair discrimination ability with a C-index value of 0.714 (95% CI, 0.680 to 0.747) and 0.732 (95% CI, 0.658 to 0.806) in the derivation and validation series, respectively. CONCLUSION: The GETNE-TRASGU evidence-based prognostic tool stratifies patients with GEP neuroendocrine tumors receiving SSA treatment according to their estimated PFS. This nomogram may be useful when stratifying patients with neuroendocrine tumors in future trials. Furthermore, it could be a valuable tool for making treatment decisions in daily clinical practice.The authors thank GETNE for sponsoring this study and generating thenecessary network for this collaborative work. The authors also thankPriscilla Chase Duran for editing and translating the manuscript and themFAR team for the support of the Web site registry. The authors thankAndreas Bender for help in the analysis of time-varying effects.S

Differences in the presentation and evolution of primary aldosteronism in elderly (≥65 years) and young patients (<65 years).

To compare the presentation and evolution of primary aldosteronism (PA) in the elderly (≥65 years) and young patients ( A retrospective multicenter study was performed in 20 Spanish hospitals of PA patients in follow-up between 2018 and 2021. Three hundred fifty-two patients with PA Older patients with PA have a worse cardiometabolic profile than young patients with PA that it is related to a longer duration of hypertension. However, the results of the AVS, and adrenalectomy are similar in both groups. Therefore, the management of elderly patients with PA should be based not only on age, but rather on the overall medical, physical, social, and mental characteristics of the patients