Research project

Drug profiling for Hepatic Artery Infusion (HAI) therapy for neuroendocrine tumor liver metastases using patient-derived preclinical models

Many people with neuroendocrine tumors (NETs) develop cancer spread to the liver. While treatments exist, most slow tumor growth rather than shrink tumors, and liver-directed options often provide only temporary benefit. As a result, patients with liver-dominant NETs have limited long-term treatment choices if surgery is not feasible.

This project studies a treatment called hepatic artery infusion pump (HAIP) therapy, which delivers chemotherapy directly to the liver. HAIP is effective for other cancers that spread to the liver but has not been properly studied in NETs. Using tumor samples donated by patients, we will test which drugs work best when delivered this way and whether combining them with current NET treatments improves effectiveness.

Our goal is to generate the scientific evidence needed to design future clinical trials. Ultimately, this research aims to expand treatment options and improve outcomes and quality of life for people living with NETs and liver metastases.

Research project

Clinical Validation of an SSTR2-Targeted Liquid Biopsy for Circulating Tumor Cells in Well-Differentiated Pancreatic and Ileal Neuroendocrine Tumors

Neuroendocrine tumors (NETs) are difficult to monitor because they often grow slowly, behave unpredictably, and may not cause symptoms for long periods. Doctors rely on specialized scans, such as DOTATATE PET imaging, to see where tumours are and how active they may be. While these scans are essential, they only provide information at one point in time. As a result, patients and their care teams may not know early enough whether treatment is working or if the cancer is changing.

Our team which consists of an expert in NETs and a clinical fellow who will be doing the work, aiming to develop a new blood test, called a liquid biopsy, that detects NET tumour cells circulating in the bloodstream. These circulating tumour cells (CTCs) can reveal important details about how the cancer is behaving throughout the body. Older CTC tests did not work well for NETs because they used markers that NET cells do not reliably express. To solve this, we created a NET-specific method based on SSTR2, the same receptor used for NET imaging and radioligand therapy. Using a fluorescent probe that binds to SSTR2, along with advanced tools that isolate and visualize single cells, we can detect NET CTCs with much greater accuracy.

This research aims to lead to a blood test that tracks NET progression. This test may help identify sooner whether treatment is effective, whether resistance is emerging, or whether the disease is returning, ultimately improving care and outcomes for people living with NETs.

Research project

A population-based evaluation of extra-hepatic GEP-NET metastases identified by 68Ga-DOTATATE PET/CT

Gastroenteropancreatic neuroendocrine tumours (GEP-NETS) frequently present with metastatic disease (spread beyond the primary tumour) at time of diagnosis. The most common sites of metastasis are local lymph nodes and liver, while other sites of metastasis were previously thought to be rare. However, traditional imaging has been limited by the small size of these metastases.

GEP-NETS have special receptors that bind an injectable tracer that lights up on imaging, such as the 111In-Octreotide or the 68Gallium-DOTATATE PET/CT scan (68Ga-DOTA).

The 68Ga-DOTA scan has started to replace Octreotide scans due to faster imaging times, lower costs, and better ability to detect small tumours and metastasis. However, it still remains less readily available across Canada. Recent publications have shown that 68Ga-DOTA revealed 25 to 36% of patients have metastasis outside of the regional lymph nodes and liver, which is significantly higher than previously reported. Other studies have shown that 68Ga-DOTA leads to change in management in up to 56% of patients.

Our study aims to review the rates and locations of metastatic disease in Canadian patients with GEP-NETS that have undergone 68Ga-DOTA and compare this to cross-sectional imaging to see if there is a change in staging and management based on this information.