••• What are Neuroendocrine Tumors (NET)?
Neuroendocrine tumors (NET) are malignant tumors that arise from neuroendocrine cells. They can occur in all organ systems of the body but are more commonly found in the stomach, intestines, or pancreas. These tumors grow slowly and often cause late-onset symptoms, leading to diagnoses typically made at an advanced stage when the disease has already metastasized. Consequently, a cure is sometimes no longer possible through surgery, for example, but therapy is initiated to slow tumor growth and manage any symptoms.
A characteristic feature of NETs is that the tumor cells often have hormone receptors on their surface, to which somatostatin can bind. Somatostatin is a hormone produced by our body that plays a role in hormone regulation (inhibiting other hormones). This function of somatostatin also forms the basis of the first-line therapy for NET with somatostatin analogs. This is a form of hormone therapy with substances that are similar to somatostatin (hence the name somatostatin analogs (SSA)) and have a similar effect on the body as somatostatin itself. The administration of SSA slows tumor growth by binding to hormone receptors and also reduces hormones produced by the tumor, alleviating symptoms. Therefore, patients with a functional (hormonally active) NET usually receive lifelong SSA to suppress symptoms.
For patients with a non-functional (hormonally inactive) NET, it is known that these tumors also have hormone receptors. They often start with hormone therapy with SSAs as the first-line therapy to slow tumor growth. When the tumor continues to grow despite SSA administration, it is unclear whether it is better to stop or continue SSAs during second-line therapy with peptide receptor radionuclide therapy (PRRT) or targeted therapy (Afinitor/everolimus or Sutent/sunitinib). This decision depends on the hospital’s practices and/or the treating physician. With the SAUNA study, researchers hope to demonstrate the best approach to control the disease.
••• Objective
The SAUNA study was initiated to answer the clinically relevant question of whether or not to continue SSA alongside second-line therapy. Through this study, researchers hope to demonstrate the best approach for advanced non-functional (hormonally inactive) NET of the stomach, intestines, or pancreas that start second-line therapy with targeted therapy or radionuclide therapy (PRRT). If the study shows benefits of SSA therapy alongside second-line therapy, this research data will be used for additional analyses. Examples include a cost-benefit analysis to see if the treatment costs are justified by the expected health gains and an analysis of the quality of life.
••• Study Design
••• Study Procedures and Progression
Step 1: Eligibility to Participate
If a patient is eligible to participate in the SAUNA study and decides to join, the information and consent form will be signed with the treating physician to agree to the study procedures at the predetermined times.
Step 2: Treatment
Participating patients will be divided into the targeted therapy group or the PRRT group, depending on the second-line therapy chosen in consultation with the treating physician. Within each group, half of the patients will continue SSA treatment, while the other half will no longer receive SSA. This will be determined by randomization to obtain an objective picture. Therefore, it is not possible to choose. If SSA treatment is continued, the dose, batch numbers, and expiration dates of the administered SSA must be recorded in a diary.
Step 3: Examinations and Measurements
From the start of second-line therapy, a study visit will take place every three months for a maximum of 18 months. During these three-monthly visits, a CT or MRI scan will be performed. All study visits will be scheduled to coincide as much as possible with a planned doctor’s visit. Additionally, during each visit, participants will be asked to complete four questionnaires on paper or via email, taking about 15 minutes in total. The final study visit will occur 18 months after starting second-line therapy or if the disease worsens. After discussing with the treating physician, SSA treatment may be continued, restarted, or stopped.
Step 4: Follow-up
After the final study visit, there will be a follow-up period of five years. During this period, annual telephone contact will be made to answer some questions about the disease’s status. Participants will also be asked to complete the questionnaires from home annually.
Optional
With specific consent, additional blood samples (30 mL per draw) will be taken for future scientific research at four time points: before starting second-line therapy, three months after starting second-line therapy, during the last study visit, and if the disease worsens. A maximum of 120 mL of blood will be drawn in total, a safe amount for adults. For comparison, a blood donation at a blood bank involves giving 500 mL per donation.
