Gastroenteropancreatic neuroendocrine tumours (GEP NET) are malignant neoplasms that impact survival. Somatostatin analogues (SSA) are used for treating hormonal symptoms caused by GEP NET and have antiproliferative effects. They are used as first-line therapy in patients with advanced GEP NET, but disease control is limited to a median progression-free survival (mPFS) of 14–32 months. Second-line treatment options include targeted therapy (everolimus or sunitinib), or peptide receptor radionuclide therapy (PRRT) with ¹⁷⁷Lu-DOTATATE. In patients suffering from a NET-related hormonal syndrome, SSA is generally continued life-long. However, there is no consensus on whether it is beneficial to continue SSA in non-functional NET upon disease progression. Due to the ongoing activity of the somatostatin receptor pathway in GEP NET progressing on first-line SSA, we hypothesise that SSA have an added efficacy in second-line therapy.

The SAUNA trial is an international, multicentre, open-label, randomised, controlled, pragmatic clinical trial. 270 patients with advanced, non-functional GEP NET and progression under first-line SSA will be included in substudy 1 (PRRT; n=142) or substudy 2 (targeted therapy (everolimus/sunitinib); n=128) per investigator’s choice of second-line therapy and will be randomised (1:1) per substudy between SSA continuation or SSA withdrawal arms. Co-primary endpoints are the difference in progression-free survival (PFS) according to the RECIST (Response Evaluation Criteria In Solid Tumours) V.1.1 criteria and difference in time to deterioration (TTD) in quality of life (QoL) per substudy after initiating second-line therapy with or without SSA. Secondary endpoints include the PFS rate at 18 months, the difference in pooled PFS and TTD combining both substudies, overall survival, response rates, QoL, costs, cost-effectiveness and toxicity. The study design was developed in cooperation with the Belgium and Dutch patient organisations.

The study has been approved on 31 May 2023 by the Ethical Committees and Regulatory Authorities of the concerned member states (EU CT number 2022-502703-30-00). Both the trial management group and the steering committee will oversee good governance of this trial. Results of the study will be published in peer-reviewed international journals and presented at international conferences.

NCT05701241.

Traditionally, surgical intervention has been the standard treatment for children with metopic synostosis, assuming that it reduces the risk of raised intracranial pressure, thereby preventing vision and cognitive impairment, and also restores the abnormal head shape. However, recent research suggests a sporadic occurrence of raised intracranial pressure in patients with metopic synostosis. In addition, following surgery, an overall tendency to have worse cognitive and behavioral outcomes and more refractive errors compared to healthy peers is observed. Research on conservative (non-surgical) treatment in metopic synostosis is limited and lacks a comparative design. The purpose of this study is to compare the (cost-)effectiveness of conservative and surgical treatment in patients with metopic synostosis.

This is the protocol for an observational cohort study with a duration of 8 years. A total of 450 patients with metopic synostosis will be included. The primary outcome is head growth as a predictor for increased intracranial pressure. Non-inferiority with regard to head growth from 0 to 8 years (yearly difference in SD) is determined using a linear mixed model adjusted for potential confounders. Secondary outcomes include papilledema, orthoptic outcomes; forehead shape; cognitive, behavioural and psychological outcomes; and societal costs. A cost-effectiveness analysis will be performed.

The study has been reviewed and approved by the Medical Research Ethics Committee of the Erasmus MC, University Medical Center Rotterdam (MEC-2022-0142). Written informed consent will be obtained from both parents of each participant. The results will be disseminated by publication in international peer-reviewed journals.

ClinicalTrials.gov NCT06069479.