Bilateral Chylothorax Following Neck Dissection: A Systematic Review and Proposed Management Algorithm.

Aims: Bilateral chylothoraces are rare but potentially life-threatening complications of neck dissections (ND). The condition is generally treated with a combination of dietary, medical, procedural, and surgical approaches. The aim of this review is to highlight the management options currently utilized in clinical practice and propose a management algorithm for this condition. Methods: In accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines; utilizing the Pubmed, EMBASE, and Web of Science databases, a systematic review of all available literature on bilateral chylothoraces was conducted. Primary outcomes measures included clinical presentations and type of neck dissection performed with interventions employed to manage the condition. Secondary outcome measures included the time to resolution alongside patient outcomes. Results: We identified 37 patients (female n = 27, male n = 10) who presented with bilateral chylothoraces within the years 1951-2018. The mean age was 51.4 ± 16.5 years within the age ranges of 17-78 years. Most common pathologies included papillary thyroid carcinoma (n = 16), squamous cell carcinoma (SCC) of the larynx (n = 3), supraglottic SCC (n = 3). Left sided ND was done in (n = 18); bilateral ND in (n = 17); central/left ND in (n = 2). Chylothorax was treated by surgery in n = 10, n = 5 of which performed lymph node embolization; and n = 5 used lymph node ligation. Resolution was found in all cases. Discharge times ranged from 2 to 40 days. Conclusions: This systematic review highlights the different management modalities in treating bilateral chylothoraces alongside providing a decision algorithm in treating the condition by suggesting diagnostic tools and management modalities to optimize patient care.

Octreotide subcutaneous depot for acromegaly: A randomized, double-blind, placebo-controlled phase 3 trial, ACROINNOVA 1.

CONTEXT: Acromegaly, characterized by excessive growth hormone (GH) and insulin-like growth factor-1 (IGF-1), impacts quality of life (QoL) and mortality. Standard of care (SoC; octreotide long-acting repeatable or lanreotide autogel) treatment typically requires healthcare provider administration. CAM2029, a novel subcutaneous octreotide depot with increased bioavailability using FluidCrystal technology, enables self-administration and room-temperature storage. OBJECTIVE: Assess superiority of CAM2029 versus placebo for biochemical control in patients with controlled acromegaly. DESIGN: 24-week, multinational, randomized, double-blind, phase 3 trial (NCT04076462). SETTING: 45 sites; ten countries. PATIENTS: 72 patients on SoC with biochemical control at screening (IGF-1 ≤upper limit of normal [ULN]; mean GH <2.5 µg/L). INTERVENTIONS: Patients were randomized 2:1 to once-monthly CAM2029 (n=48) or placebo (n=24). MAIN OUTCOME MEASURES: Primary endpoint was proportion of patients with IGF-1 ≤ULN (Week 22/24 mean), with dose-reduced patients classified as non-responders; first key secondary endpoint was the same, including dose-reduced responders. Second key secondary endpoint was proportion of patients with IGF-1 ≤ULN (Week 22/24) and mean GH <2.5 µg/L (Week 24). RESULTS: At Week 22/24 (intention-to-treat analysis), CAM2029-treated patients demonstrated superior response rates versus placebo for IGF-1 (72.2% versus 37.5%; risk difference: 34.6, 95% confidence interval: 11.3, 57.9; p=0.0018), and combined IGF-1/GH (70.0% versus 37.5%; p=0.0035). CAM2029-treated patients had well-controlled symptoms, improved QoL and treatment satisfaction versus placebo and baseline. CAM2029 was well tolerated; safety was consistent with SoC. CONCLUSIONS: CAM2029 provides a convenient and effective treatment option for acromegaly, with superior biochemical control versus placebo. Symptom control, QoL and satisfaction were improved from baseline SoC.

The current status of somatostatin analogs in the treatment of neuroendocrine tumors and future perspectives.

INTRODUCTION: Somatostatin analogs (SSAs) were developed as antisecretory agents to palliate hormonal symptoms in patients with functioning neuroendocrine tumors (NETs). Their antiproliferative activity has been established in the phase 3 PROMID and CLARINET trials. SSAs currently represent the standard first-line therapy for the majority of well-differentiated G1/G2 gastroenteropancreatic NETs as well as for pulmonary NETs. AREAS COVERED: An update on the clinical applications of established SSAs for the treatment of NETs is provided. Perspectives on emerging nonpeptide SSAs such as paltusotine and innovative formulations of octreotide (CAM2029) are included. EXPERT OPINION: SSAs represent the cornerstone of treatment for both functioning and nonfunctioning NETs. While standard-dose SSAs have a defined place in the therapeutic algorithm of well-differentiated NETs, uncertainties remain on how to best integrate above-label doses of SSAs in the treatment sequence, particularly when tumor control is the goal. Octreotide and lanreotide appear to be clinically interchangeable, and no signs of superiority of one agent over the other has been observed so far. Whether SSAs may be exploited in the maintenance setting following more aggressive treatments, whether continuing SSAs beyond-progression after first-line therapy could be an effective treatment strategy, and whether new-generation SSAs such as pasireotide could overcome resistance to established SSAs are key areas of investigation.

Octreotide Causing Hyperkalemia: A Case Report and Review of the Literature.

Octreotide, a synthetic analog of somatostatin, is widely utilized for its inhibitory effects on various hormones, including growth hormone, insulin, and glucagon. Its applications span conditions such as acromegaly, carcinoid tumors, and gastrointestinal bleeding due to its ability to reduce portal venous pressure. Additionally, it serves a crucial role in nuclear medicine imaging and the management of hepatorenal syndrome. We report a case of a 44-year-old man with type 2 diabetes mellitus (T2DM) and stage 5 chronic kidney disease (CKD), not yet on hemodialysis, who presented with persistent severe hypoglycemia. Despite multiple oral glucose administrations, his blood glucose levels remained critically low. The patient was treated with octreotide for sulfonylurea-induced hypoglycemia. However, he developed hyperkalemia as a side effect of octreotide treatment. Traditional therapies for sulfonylurea-induced hypoglycemia often involve intravenous and oral dextrose and glucagon, which may lead to recurrent hypoglycemia due to their stimulatory effects on insulin release. Octreotide directly inhibits insulin release from the pancreas, thus preventing rebound hypoglycemia. However, its administration in patients with renal impairment poses a risk of hyperkalemia due to its suppression of insulin-mediated cellular potassium uptake, and it should be used with caution. This case highlights the potential for life-threatening hyperkalemia induced by octreotide in non-dialysis CKD patients. Physicians must be vigilant about this side effect, particularly in patients with underlying renal impairment. Close monitoring of potassium levels and appropriate management strategies are essential to ensure the safe use of octreotide. This case aims to raise awareness and contribute to a better understanding of octreotide-induced hyperkalemia in CKD patients.

Real-world effectiveness of adjuvant octreotide therapy in patients with pancreatic neuroendocrine tumors at high recurrence risk: A multicenter retrospective cohort study.

Adjuvant therapy for pancreatic neuroendocrine tumors (PanNETs) after radical resection lacks evidence-based data and remains controversial. This study aimed to validate whether long-acting octreotide is a potential candidate for adjuvant therapy in patients with G2 PanNETs at high recurrence risk by clustering real-world data. A retrospective review of patients with nonmetastatic grade 2 PanNETs who underwent radical resection at six research centers between 2008 and 2020 was conducted. Propensity score matching and inverse probability of treatment weight analysis were used to control confounding factors. Overall, 357 patients (octreotide group, n = 82; control group, n = 275) were analyzed. Kaplan-Meier survival analyses showed that the octreotide group had longer disease-free survival (DFS) compared with the control group (36 months: 93.3% vs. 79.0%, p = .0124; 60 months: 71% vs. 67.6%, p = .0596, respectively), as well as overall survival (OS) (60 months: 98% vs. 83.8%, p = .0117, respectively). Multivariate analyses indicated that octreotide long-acting repeatable (LAR) adjuvant therapy was associated with higher OS (p = .0270) at 60 months. Propensity score matching analysis showed that octreotide adjuvant therapy was associated with higher DFS (p = .0455) and OS (p = .0190) at 60 months. Similar results were obtained via inverse probability of treatment weight analysis. Subgroup analysis indicated that octreotide LAR was associated with a high DFS in patients with lymph node metastasis or Ki-67 <10% PanNETs. Adjuvant therapy with long-acting octreotide following radical resection of nonmetastatic G2 PanNETs may be associated with improved DFS and OS in a real-world setting.

Utilizing erythrosine B absorption spectrum shifts for quantitative determination of octreotide and bromocriptine in their pure forms and pharmaceutical formulations. Evaluation of the method greenness.

In the present study, two drugs for treating acromegaly are investigated which are either synthetic growth hormone inhibiting hormone (GHIH) or dopamine receptor agonist. Octreotide (OCT) and bromocriptine (BCT) were quantified with a quick, simple, and sensitive spectrophotometric approach in their authentic forms and commercial dosage forms. This approach was based upon formation of ion pair complex between erythrosine B and investigated drugs in an aqueous buffered solution. For OCT determination the higher sensitivity was obtained using ΔA at 525 nm. On the other hand, BCT was estimated using the absorbance at 556 nm. Under optimal conditions for the reaction, construction of calibration curves were performed within concentration range of 0.4-4 µg ml-1 for OCT and 1-9 µg ml-1 for BCT with with low detection limits (0.094 and 0.235 µg ml-1) and low quantitation limits (0.29 and 0.71 µg ml-1) for OCT and BCT respectively. The developed approach was assessed for linearity, accuracy, precision, limits of detection, and limits of quantitation in compliance with ICH validation recommendations. The suggested approaches demonstrated good linearity, as evidenced by determination coefficients (r2) of 0.999 with a slope 0.14 for OCT and 0.9989 with a slope 0.06 for BCT. Additionally, the environmental friendliness of the investigated method was assessed with some of the recent green analytical chemistry metrics.

Clinical Benefits of Octreotide for Managing Persistent Gastrointestinal Fluid Loss in Malignant Small Bowel Obstruction: A Case Report and Literature Review.

Malignant small bowel obstruction (mSBO) is a frequent complication in patients with gastrointestinal or gynecologic cancers. For those with inoperable cancers and persistent obstructive symptoms, symptom palliation with a percutaneous gastrostomy tube (PGT) may be required. However, excessive fluid loss from the PGT can lead to significant fluid, electrolyte, and acid-base imbalances. We present a case of a man with metastatic colonic adenocarcinoma who developed mSBO, acute kidney injury, and metabolic alkalosis, all of which were effectively managed with octreotide.

Medical treatment of acromegaly - When the tumor size matters: A narrative review.

Medical treatment of acromegaly is generally positioned as a second line of treatment after pituitary adenoma surgery. With the rising availability and variety of medications for acromegaly increases our understanding of their effectiveness and safety. Volume of the published data on the impact of medical therapy on biochemical control of acromegaly, contrasts a relative lack of publications which comprehensively address pituitary tumor alterations under different drug modalities. Assessment of changes in GH-secreting adenoma volume is often overshadowed by clinicians' focus on GH and IGF-I levels during acromegaly treatment. Close analysis of studies published in the last two decades, reveals that both an increase and decrease in somatotropinoma volume are possible during treatment with any of available drugs for acromegaly. Changes in pituitary tumor size may arise from the biological nature of adenoma itself, independently of the administered medications. Therefore, an individual approach is necessary in the treatment of patients with acromegaly, based on repeated insight to their clinical, biochemical, pathological and imaging characteristics. In this review, we summarize and comment how pituitary tumor size is affected by the treatment with all currently available drugs in acromegaly: long-acting somatostatin receptor ligands of the first generation (octreotide LAR and lanreotide autogel) and the second generation (pasireotide-LAR), as well as pegvisomant (PEG) and cabergoline (CAB).

Clinical Profile and Efficacy of Long-Acting Octreotide in Hyperinsulinemic Hypoglycaemia.

Introduction: Hyperinsulinemic hypoglycaemia (HH) is characterised by unregulated insulin secretion, leading to persistent non-ketotic hypoglycaemia with a lack of alternate fuel that induces a severe risk for brain damage and neurodevelopmental abnormalities. Octreotide, a somatostatin analogue, has been effectively administered as subcutaneous injections or depot preparations in diazoxide-unresponsive HH. Methods: Children and infants with HH receiving short-acting octreotide injections were included. Anthropometric values, hypoglycaemic episodes, HbA1C, and side effects were noted from the records and were followed up for 12 months. Informed written consent was obtained from the parents before administration of a single dose of LAR (long-acting octreotide). Based on home-based glucose monitoring (HBGM), the dosage of LAR was modified, and short-acting octreotide was eventually withdrawn. The patients shared the injection's cost for cost-effectiveness. HH affects the quality of life (QoL) if not diagnosed and controlled adequately. A QoL questionnaire was given before starting LAR and after 6 months of receiving LAR, and the changes were noted accordingly. Results: Twenty-two patients were diagnosed with HH, of which 11 infants and children were included in the study. Mutations were identified in 7 (63.63%) children. Daily octreotide could be tapered and stopped with the addition of sirolimus in one patient with an increasing dose of LAR to maintain euglycaemia. The hypoglycaemic episodes decreased with increasing dose of LAR with a decrease in the severity. Eight (72.7%) patients showed an improved lifestyle on LAR quantified through a QoL questionnaire. Conclusion: LAR was found effective in reducing hypoglycaemic episodes with no adverse effects. The patient's parent's satisfaction was higher. Given its high cost, this trial achieved cost-effectiveness by sharing a single sitting of LAR injection.

Utility of an Alpha-1 Adrenergic Agonist in the Management of Chylothorax: A Case Series and Management Algorithm.

Chylothorax is the accumulation of lymphatic fluid (chyle) within the pleural space. There are multiple causes, including traumatic and non-traumatic mechanisms. Trauma can cause disruption of the thoracic duct either by direct damage or indirect crushing or avulsion mechanisms. Non-traumatic causes include infections, inflammatory processes, malignancies, and iatrogenic injury (during surgery or central venous access). The traditional management of traumatic chylothorax has been either a conservative approach, including complete Nil Per Os (NPO), or a low-fat diet with medium-chain triglyceride supplementation with the administration of somatostatin or its analog, octreotide, versus a surgical approach consisting of thoracic duct ligation. Recently a less invasive approach via thoracic duct embolization has gained popularity. There have been a few reports of the successful use of an α 1-adrenergic agonist (midodrine) as an adjunct in the conservative approach. We describe the utility of midodrine in three cases of chylothorax and propose a management algorithm. LEARNING POINTS: The initial diagnosis of chylothorax is based on clinical suspicion and proper imaging.The clinical success of midodrine use as a first-line medical treatment for chylothorax will support the use of midodrine before considering invasive procedures.We propose a management algorithm for patients with chylothorax that will stimulate researchers to conduct prospective studies to assess its efficacy.

Sweet Saboteur: Insulinoma Presenting As Recurrent Hypoglycemic Seizures.

Insulinoma, a rare neuroendocrine tumor of the pancreas, often presents diagnostic challenges due to its diverse clinical manifestations. We present the case of a 25-year-old female with recurrent hypoglycemic seizures and neuroglycopenic symptoms, ultimately diagnosed with insulinoma. Despite an initial asymptomatic period, the patient experienced progressively worsening symptoms over three years, culminating in eight episodes of generalized tonic-clonic seizures per week. Biochemical investigations during hypoglycemic episodes revealed elevated C-peptide and insulin levels, consistent with endogenous hyperinsulinemia. Imaging studies, including contrast-enhanced computed tomography (CECT) and Ga-DOTATATE scan, confirmed a hyper-enhancing lesion in the distal body of the pancreas, indicative of insulinoma. Histopathological examination (HPE) further corroborated the diagnosis. Prompt recognition and surgical excision led to the complete resolution of symptoms and improved long-term prognosis. This case underscores the importance of considering insulinoma in young individuals presenting with recurrent hypoglycemic episodes and highlights the significance of early diagnosis and intervention in preventing morbidity and mortality associated with this condition.

Anesthetic key points in a patient with a terminal ileum neuroendocrine tumor and a rare carcinoid left heart disease presented for non-cardiac surgery: case report.

BACKGROUND: Carcinoid tumors are rare neuroendocrine malignancies presenting in an increasing number in our center. The incidence of carcinoid tumors is approximatively between 2.5 and 5 cases per 100,000 people of whom about 50% develop carcinoid syndrome. Once the carcinoid syndrome has developed, a carcinoid cardiomyopathy can occur. Carcinoid heart disease (CaHD) remains a serious and rare complication associated with a significant increase in morbidity and mortality. Although carcinoid tumors have been known and studied for several years, there are still scarce data on the anesthetic management and the peri operative period. CASE PRESENTATION: We describe a case of a Caucasian 44-year-old woman with an unusual presentation of left CaHD with an ileal neuroendocrine tumor and liver metastases. Our preoperative somatostatin administration protocol, limit the cardiac damage. The maintenance of stable hemodynamics, the use of balanced anesthetic technique, all along with a good understanding of the pathology, played a major role in the successful management of anesthesia. This case report allows us to introduce our decision algorithm for the management of this type of pathology in our tertiary hospital, Cliniques Universitaires Saint-Luc. CONCLUSION: Despite the paucity of data, anesthetic management of patients with carcinoid tumor can be safely performed with effective hemodynamic monitoring and a good understanding of the pathophysiology. Knowledge and application of a clear institutional algorithm for octreotide administration and multidisciplinary consultation at a referral center are essential for the management of these patients.

Cytotoxicity on low-grade canine meningioma with the use of somatostatin analog (octreotide): An in vitro study.

Background: Meningioma is the most common tumor of the central nervous system of dogs. For this tumor, surgery remains the treatment of choice, either alone or in combination with radiotherapy. Unfortunately, chemotherapeutic strategies are practically absent in dogs and palliative therapies are the only option to surgery. Somatostatin receptor subtype 2 (SSTR2) is expressed in canine meningioma. Since the potent cell-proliferation inhibiting effect of somatostatin (SST), the aim of this study was to investigate in vitro the effects of octreotide, as SST analog, in the viability of canine meningioma. Methods: Four surgical canine meningiomas were used in this study to establish cell cultures. Expression of SSTR2 was verified with immunolabelling in FFPE samples and cell cultures. The effects of octreotide on cell viability were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT). After 24 hours they were exposed to different concentrations of octreotide (0.1 nM, 1 nM, 10 nM, 100 nM) for 24 and 48 hours. Results: All meningiomas consisted of grade I tumors. The cultured neoplastic cells expressed SSTR2 from 80% to 100%. Octreotide significantly increased cell death after 48 hours of continuous exposure, with 10 and 100 nM octreotide doses. The percentage of cell viability was 80.92 ±â€…4.9 and 80.49 ±â€…3.61, compared to the control, respectively, consistent with decreased cell viability of about 20% for both doses. Conclusions: Octreotide reduced the alive neoplastic cultured cells of low-grade canine meningioma in a dose-dependent pattern with continuous exposition for 48 hours. These results support an alternative systemic treatment of meningioma with octreotide in the dog.

Structural insights into somatostatin receptor 5 bound with cyclic peptides.

Somatostatin receptor 5 (SSTR5) is highly expressed in ACTH-secreting pituitary adenomas and is an important drug target for the treatment of Cushing's disease. Two cyclic SST analog peptides (pasireotide and octreotide) both can activate SSTR5 and SSTR2. Pasireotide is preferential binding to SSTR5 than octreotide, while octreotide is biased to SSTR2 than SSTR5. The lack of selectivity of both pasireotide and octreotide causes side effects, such as hyperglycemia, gastrointestinal disturbance, and abnormal glucose homeostasis. However, little is known about the binding and selectivity mechanisms of pasireotide and octreotide with SSTR5, limiting the development of subtype-selective SST analog drugs specifically targeting SSTR5. Here, we report two cryo-electron microscopy (cryo-EM) structures of SSTR5-Gi complexes activated by pasireotide and octreoitde at resolutions of 3.09 Å and 3.24 Å, respectively. In combination with structural analysis and functional experiments, our results reveal the molecular mechanisms of ligand recognition and receptor activation. We also demonstrate that pasireotide preferentially binds to SSTR5 through the interactions between Tyr(Bzl)/DTrp of pasireotide and SSTR5. Moreover, we find that the Q2.63, N6.55, F7.35 and ECL2 of SSTR2 play a crucial role in octreotide biased binding of SSTR2. Our results will provide structural insights and offer new opportunities for the drug discovery of better selective pharmaceuticals targeting specific SSTR subtypes.

Pediatric Idiopathic Chylopericardium: A Case Managed with Thoracoscopic Window Pericardiotomy.

Idiopathic chylopericardium (CP) in the pediatric population is a rare entity with very few reported cases and is characterized by the accumulation of chyle in the pericardial cavity. There are no guidelines for the management of this rare entity. The present study reports a case of idiopathic CP in an infant and our experience of managing it by pericardial window creation using VATS and a multidisciplinary approach providing the optimum care for the child.

18F-AlF-NOTA-octreotide PET/CT in the localization of tumor-induced osteomalacia: case series and literature review.

Introduction: This study explores tumor-induced osteomalacia (TIO) through a case series and literature review, assessing the diagnostic potential of 18F-AlF-NOTA-octreotide (18F-OC) positron emission tomography/computed tomography (PET/CT). Methods: We analyzed TIO patients who underwent 18F-OC PET/CT. Parameters such as tumor dimension, the maximum standardized uptake value (SUVmax), the mean standardized uptake value (SUVmean) and metabolic tumor volume (MTV) were meticulously assessed. Clinical features and imaging characteristics pertinent to TIO were reviewed. Results: 6 patients with clinical suspicion of TIO exhibited hypophosphatemia (0.25 to 0.64 mmol/L), elevated alkaline phosphatase (ALP) levels (142 to 506 U/L), and increased parathyroid hormone (PTH) levels (92.9 to 281.7 pg/mL). Of these patients, two underwent FGF-23 testing, with results of 3185.00 pg/ml and 17.56 pg/ml, respectively. Conventional imaging modalities depicted widespread osteoporosis, with several cases demonstrating fractures indicative of osteomalacic and associated pathological fractures. Subsequent 18F-OC PET/CT facilitated the accurate localization of causative tumors, with histopathological examination confirming the diagnosis of phosphaturic mesenchymal tumor (PMT). The interval from initial clinical presentation to definitive TIO diagnosis spanned approximately 2.5 years (range: 1 - 4 years), with tumors varying in size (maximum diameter: 7.8 to 40.0 mm), SUVmax (5.47 to 25.69), SUVmean (3.43 to 7.26), and MTV (1.27 to 18.59 cm3). Conclusion: The implementation of whole-body 18F-OC PET/CT imaging emerges as a critical tool in the identification of occult tumors causing TIO. Future investigations incorporating a broader cohort are imperative to further delineate the diagnostic and therapeutic implications of 18F-OC PET/CT in managing TIO.

Oral octreotide capsules for acromegaly treatment: application of clinical trial insights to real-world use.

INTRODUCTION: Acromegaly is a rare endocrine disorder usually caused by a benign growth hormone‒secreting pituitary adenoma. Surgical adenoma resection is typically the first line of treatment, and medical therapy is used for patients with persistent disease following surgery, for adenoma recurrence, or for patients ineligible for, or declining, surgery. Approved somatostatin receptor ligands (SRLs) have been limited to injectable options, until recently. Oral octreotide capsules (OOC) are the first approved oral SRL for patients with acromegaly. AREAS COVERED: We review published reports and provide case study examples demonstrating practical considerations on the use of OOC. Using two hypothetical case scenarios, we discuss current treatment patterns, breakthrough symptoms and quality of life (QoL), efficacy of SRLs, OOC dose titration, evaluation of OOC treatment response, and incidence and management of adverse events. EXPERT OPINION: OOC are an option for patients with acromegaly including those who experience breakthrough symptoms, who have preference for oral therapies, or other reasons for declining injectable SRLs. OOC have been associated with improved patient-reported QoL measures compared with those reported for lanreotide and octreotide. Continued real-world experience will determine whether OOC, alone or in combination with other therapies, provides further advantages over current injectable acromegaly treatments.

Standards of care for medical management of acromegaly in pituitary tumor centers of excellence (PTCOE).

PURPOSE: A series of consensus guidelines on medical treatment of acromegaly have been produced in the last two decades. However, little information is available on their application in clinical practice. Furthermore, international standards of acromegaly care have not been published. The aim of our study was to report current standards of care for medical therapy of acromegaly, using results collected through an audit performed to validate criteria for definition of Pituitary Tumor Centers of Excellence (PTCOE). METHODS: Details of medical treatment approaches to acromegaly were voluntarily provided by nine renowned international centers that participated in this audit. For the period 2018-2020, we assessed overall number of acromegaly patients under medical treatment, distribution of patients on different treatment modalities, overall biochemical control rate with medical therapy, and specific control rates for different medical treatment options. RESULTS: Median number of total patients and median number of new patients with acromegaly managed annually in the endocrinology units of the centers were 206 and 16.3, respectively. Median percentage of acromegaly patients on medical treatment was 48.9%. Among the patients on medical treatment, first-generation somatostatin receptor ligand (SRL) monotherapy was used with a median rate of 48.7%, followed by combination therapies with a median rate of 29.3%. Cabergoline monotherapy was used in 6.9% of patients. Pegvisomant monotherapy was used in 7 centers and pasireotide monotherapy in 5 centers, with median rates of 7.9% and 6.3%, respectively. CONCLUSIONS: Current standards of care in PTCOEs include use of first-generation SRLs as the first medical option in about 50% of patients, as recommended by consensus guidelines. However, some patients are kept on this treatment despite inadequate control suggesting that cost-effectiveness, availability, patient preference, side effects, and therapeutic inertia may play a possible role also in PTCOE. Moreover, at odds with consensus guidelines, other monotherapies for acromegaly appear to have a marginal role as compared to combination therapies as extrapolated from PTCOE practice data. Presence of uncontrolled patients in each treatment category suggest that further optimization of medical therapy, as well as use of other therapeutic tools such as radiosurgery may be needed.

Clinical impact of using [18F]AlF-NOTA-octreotide PET/CT instead of [68Ga]Ga-DOTA-SSA PET/CT: Secondary endpoint analysis of a multicenter, prospective trial.

[18F]AlF-NOTA-octreotide ([18F]AlF-OC) is a promising alternative for [68Ga]Ga-DOTA-somatostatin analogs (SSAs) in positron emission tomography (PET) imaging of the somatostatin receptor (SSTR). Our aim is to assess changes in TNM staging and differences in patient management between [18F]AlF-OC PET/CT and [68Ga]Ga-DOTA-SSA PET/CT in the work-up of neuroendocrine tumor (NET) patients. Patients who underwent both [18F]AlF-OC and [68Ga]Ga-DOTA-TATE or [68Ga]Ga-DOTA-NOC PET/CT in our multicenter study (Pauwels et al., J Nucl Med.2023;63:632-638) with a NET were included for analysis. TNM staging was determined and compared for both tracers. For each patient, the blinded [68Ga]Ga-DOTA-SSA or [18F]AlF-OC PET/CT images were presented in random order at a multidisciplinary team board. The images were presented together with clinical information and compared with previous SSTR and [18F]FDG PET/CT imaging. After a consensus decision for patient management was recorded, the board was presented with the PET/CT images from the other SSTR tracer and a decision was made for the second tracer. Differences in management were classified as major if it entailed an intermodality change and minor if it led to an intramodality change. Compared with [68Ga]Ga-DOTA-SSA, the use of [18F]AlF-OC led to a change in 16/75 patients: TNM staging changes in 10/75 patients (13.3%; downstaging in 3/10, upstaging in 7/10) and differences in clinical management were seen in 10/75 patients (13.3%), leading to a major difference in 7/10 cases and a minor change in 3/10 cases. All 10 cases with a difference in patient management between both PET tracers were caused by additional lesion detection by [18F]AlF-OC. The use of [18F]AlF-OC did not impact TNM staging or clinical management in the large majority of the patients (86.7%), further validating the potential for routine clinical use of [18F]AlF-OC PET/CT as an alternative for [68Ga]Ga-DOTA-SSA PET/CT. The trial is registered under ClinicalTrials.gov identifier NCT04552847 and EudraCT 2020-000549-15.