Prevention and Management of Hormonal Crisis during Theragnosis with LU-DOTA-TATE in Neuroendocrine Tumors. A Systematic Review and Approach Proposal

Abstract

Neuroendocrine tumors (NETs) frequently overexpress somatostatin receptors (SSTR) on their cell surface. The first-line pharmacological treatment for inoperable metastatic functioning well-differentiated NETs are somatostatin analogs. On second line, Lu-DOTA-TATE (177Lu-DOTA0 Tyr 3 octreotate) has shown stabilization of the disease and an increase in progression free survival, as well as effectiveness in controlling symptoms and increasing quality of life. The management of functional NETs before and during LU-DOTA-TATE treatment is specially challenging, as several complications such as severe carcinoid and catecholamine crisis have been described. The aim of this review is to establish practical guidance for the management and prevention of the most common hormonal crises during radionuclide treatment with Lu-DOTA-TATE: carcinoid syndrome (CS) and catecholamine hypersecretion, as well as to provide a brief commentary on other infrequent metabolic complications. To establish a practical approach, a systematic review was performed. This systematic review was developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and conducted using MEDLINE (accessed from PubMed), Google Scholar and ClinicalTrials.gov. Literature searches found 449 citations, and finally nine were considered for this systematic review.

Highly Symptomatic Progressing Cardiac Paraganglioma With Intracardiac Extension Treated With 177Lu-DOTATATE: A Case Report

“…However, it is thought to increase the risk of a catecholaminergic crisis by increasing the production and release of catecholamines into the circulation, and by its synergistic pharmacodynamic effects, particularly at the level of the vascular endothelium (21). In view of the few cases of catecholaminergic crises reported following treatment of PRRT in patients who have received premedication with dexamethasone, some authors discourage its use (22). For our patient, it was judged that there were more benefits than risks to administer dexamethasone premedication given the location of the PGL and the risk of vascular compromise.…”

Treatment of Neuroendocrine Neoplasms with Radiolabeled Peptides—Where Are We Now

“…This can arise more commonly in patients with functioning tumors and with poor pharmacological symptom control but is overall considered rare with an occurrence rate of 1% in one study [100]. Sudden massive release of bioactive mediators has been implicated, which cause alterations in fluid dynamics leading to hemodynamic instability, arrhythmia, metabolic acidosis, and alteration in mental status [101,102]. Susceptible patients should be considered for overnight hospitalization and closer clinical review, especially during the first cycle to monitor for these features.…”

“…Medications blocking histamine receptors (ranitidine and chlorphenamine) have also been suggested on the assumption that radiation-induced tumor lysis can be contributory [103]. Although somatostatin analogues are generally avoided in the period before PRRT to avoid interference with the treatment, high-risk patients can be considered for pre-treatment and maintenance octreotide [102]. Other prophylactic measures depend on the nature of the functioning syndrome and include pre-hydration, proton-pump inhibitors, anti-emetics, anti-diarrheal medication, and rectification of biochemical abnormalities [104].…”

Peptide Receptor Radionuclide Therapy Targeting the Somatostatin Receptor: Basic Principles, Clinical Applications and Optimization Strategies

“…Sub-acute effects are hematotoxicity, transient fatigue, tumor pain or low-grade hair loss (secondary to irradiation), which are commonly mild and self-limiting [ 70 ]. Furthermore, the occurrence of carcinoid crisis during PRRT is very rare and usually takes places after the first administration [ 85 ]. Long-term toxicity side-effects are mainly radiation nephropathy and persistent hematological dysfunction (PHD).…”