Project title: Increasing the therapeutic window in PRRT with long-acting SSAs

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Description

Dr. de Vries-Huizing and her colleagues will perform a clinical trial to evaluate the effect of using long-acting somatostatin analogues during peptide receptor radionuclide therapy (PRRT).  Current guidelines advise temporary discontinuation of somatostatin analogues while continuous use could prevent increased functional symptoms like flushing and diarrhea.

What critical NET problem/question will researchers try to answer?

Long-acting somatostatin analogues (like lanreotide and octreotide) and PRRT all target the somatostatin receptor to treat NET tumors. Although current guidelines recommend discontinuation of somatostatin analogues prior to PRRT, recent research suggests that the uptake of PRRT may not be affected by continuous use of long-acting somatostatin analogues and both treatments could be combined safely. In a clinical prospective study, Dr. de Vries-Huizing and her co-investigator, Dr. Else Aalbersberg, will evaluate whether treatment with long-acting somatostatin analogues with PRRT does not negatively affect the PRRT radiation dose. The combination of both therapies could also lead to a reduction of the radiation dose delivered to healthy tissues. Also, continuous use of long-acting somatostatin analogues could prevent an increase in functional NET symptoms like flushing and diarrhea.

Why is this important?

Halting long-acting somatostatin analogues prior to PRRT can be challenging for patients and treatment logistics. Discontinuation could also increase functional NET symptoms like diarrhea and flushing. As an alternative, patients can switch to short-acting somatostatin analogues but these require multiple daily injections. The burden for patients would therefore be much less if long-acting somatostatin analogues could be continued during PRRT.

What will the researchers do?

The investigators will perform a clinical trial in which patients receive long-acting lanreotide, octreotide or no somatostatin analogue on set days prior to PRRT. They will compare the radiation dose delivered to tumors and healthy tissues between these groups and evaluate the quality of life in the different treatment groups.

How might this improve treatment of NETs?

Combining long-acting somatostatin analogues might improve the therapeutic window in PRRT by increasing the radiation dose to tumors and reducing the dose to healthy tissue, thereby improving treatment outcomes with less toxicity. This approach may also obliterate the need for switching between long-acting and short-acting somatostatin analogues prior to each cycle of PRRT.

What is the next step?

The next step for the investigators is to apply for ethical approval for the clinical trial and work toward including the first patient.

Outcomes:

Patients with NET undergoing peptide receptor radionuclide therapy (PRRT) are withdrawn from somatostatin analogues (SSAs) 4-6 weeks prior to PRRT. This is done to prevent receptor saturation and competition as both PRRT and SSA bind to the same receptor. Preliminary retrospective data has shown that this might be necessary. Therefore, a clinical trial was designed and is being performed to determine the effect of SSAs on the radiation dose delivered to tumors during PRRT.

In this clinical trial patients undergoing PRRT have a cycle of PRRT shortly after an SSA injection (1-8 days), and another cycle of PRRT after a waiting period of 4-6 weeks after an SSA injection. After each cycle, imaging is performed to determine the radiation dose to both tumors and healthy tissue. Currently, 21 of 34 patients have completed the trial or are actively in the trial.

Preliminary data suggests that giving PRRT shortly after an SSA injection, slightly increased the radiation dose in tumors but lowered the radiation dose to the healthy spleen. Although the final results need to be awaited, this suggests that patients no longer need to withdraw from SSAs prior to PRRT. Since withdrawing from SSAs can increase cancer-related symptoms, this would make the PRRT protocol more patient-friendly.

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