CNETS is committed to improving the quality of life and survival for Neuroendocrine (NET) cancer patients across Canada and in support of this vision introduced a new Research Funding Framework in 2016.

NET Cancer Research Grants provide grant-in-aid for NET cancer research projects up to a maximum of $40,000 per project.

An additional NET Cancer Research Grant was made possible thanks to the tremendous fundraising efforts of Bailey and Jonathan Daniels. In their honour, this NET research grant is named: The Daniels Constellation Grant for Neuroendocrine Cancer Research.


Dr. Venkata Manem
Dr. Venkata ManemAdjunct Professor, Faculty of Pharmacy, Laval University Researcher, Quebec Heart and Lung Institute Research Center

Marching ahead: Radiomics-based biomarker to identify spatially distinct tumor immune microenvironments in neuroendocrine tumors



High-grade neuroendocrine (NET) lung tumors represent around 23% of all neuroendocrine cancers, and constitute small cell lung carcinoma and large cell neuroendocrine carcinoma. These are clinically aggressive tumors diagnosed in heavy-smoking patients, and have poor prognosis with limited treatment options. Recently, immunotherapy has emerged as a new standard of care by harnessing the body’s immune system to treat several aggressive malignancies, including lung cancer. Given the scarcity of therapeutic interventions to treat NETs, and the success of immunotherapy in treating smoking-associated cancers, certainly makes it as a viable therapeutic option. Here we aim to better understand how the tumor immune landscape will influence the response to immunotherapy in NET patients. We will leverage pathological slides to obtain PD-L1 expression, CD8 localization and radiological data to build a digital biomarker in order to identify immune microenvironments based on CD8 inflitration.


Dr. Jonathan Abele
Dr. Jonathan AbeleAssociate Professor, Department of Radiology and Diagnostic Imaging, University of Alberta

Lesion-to-lesion comparison of 68Ga-HA-DOTATATE, 18F-DOPA, and 18F-FDG activity in the evaluation of metastatic neuroendocrine tumors



18F-DOPA PET/CT, 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT are imaging techniques that can identify the location of neuroendocrine tumors (NETs) by different mechanism: 68Ga-DOTATATE binds to somatostatin receptors, 18F-DOPA relates to increased amino acid uptake in NETs, and 18F-FDG relates to increased glucose uptake in NETs.  18F-DOPA and 68Ga-DOTATATE have a reported high accuracy in identifying NETs, although there have been no reported direct comparisons of the same lesions in the same patients. The goal of our study is to evaluate patients with metastatic NETs with all three tracers to determine the prevalence of NET lesions that are 68Ga-DOTATATE avid (concordant with 177Lu-DOTATATE therapy) versus non-68Ga-DOTATATE avid (discordant with therapy).  Non-68Ga-DOTATATE avid lesions will be identified using 18F-DOPA (for well-differentiated lesions) and 18F-FDG (for poorly-differentiated lesions). It is expected that patients with discordant lesions will have poorer response to PRRT.


Dr. Ozgur Mete
Dr. Ozgur MeteAssociate Professor, Pathology Laboratory Medicine Program, UHN/ Toronto General Hospital

Appendix Neuroendocrine Tumors (NETs): Implications of cell typing


Neuroendocrine tumors (NETs) of the pituitary, stomach, duodenum, pancreas and rectum have been recognized to be composed of different cell types that have distinct growth patterns, different invasiveness and variable responses to therapies. This study will examine the cell types that comprise neuroendocrine tumors of the appendix to determine if there are multiple different tumor types that make different hormones and have different clinical and biologic features. The information obtained from this study will allow re-classification of appendiceal NETs into categories that may have different requirements for aggressive surgery and post-surgical treatments and will provide unique circulating biomarkers to monitor patients for recurrent disease.


Dr. Girish Shah
Dr. Girish ShahFull Professor, Université Laval / Laval University CHU de Québec Université Laval Research Centre (CHUL Hospital)

Chemotherapy followed by PRRT can deliver one-two punch to NET   


The incidence of neuroendocrine tumors (NET) is increasing and due to delayed diagnosis, patients have few conventional therapeutic options. Peptide receptor radionuclide therapy (PRRT) is a targeted therapy that directly delivers radioactive drug to the docking sites or somatostatin-receptors on the NET cells. PRRT is recommended for many types of NET but there is a need to improve its therapeutic efficacy. Based on our recent in vitro data with NET cells growing in culture medium, we will examine in animal model of NET whether pre-treatment with low doses of chemo drugs can upregulate these receptors so that a subsequent PRRT treatment will deliver a one-two knockout punch to the tumors without causing adverse incidental toxicity to the animal. This approach will not only improve therapeutic efficacy of PRRT but also allow previously ineligible NET patients become eligible to receive PRRT.


Dr. Simron Singh
Dr. Simron SinghMedical Oncologist, Department of Medical Oncology Sunnybrook Odette Cancer Centre
Dr. Ur Metser
Dr. Ur MetserProfessor, Medical Imaging Department of Medical Imaging, Princess Margaret Hospital

Examining the Utility of Combined of 68Ga-DOTATATE and 18F-FDG PET/CT Imaging on Clinical Management of Patients with Well differentiated, G2-G3, Gastroenteropancreatic (GEP)-Neuroendocrine Tumors (NETs)


The variable clinical outcome of patients with G2 and G3 well differentiated GEP-NETs makes the selection of an optimal treatment strategy challenging. Therefore the prospective validation of the clinical impact of addition of 18F-FDG PET/CT imaging to 68Ga-DOTATATE imaging to planned clinical treatment of patients with G2-G3 well differentiated GEP-NETs, along with the validation of novel comprehensive imaging biomarkers is critical to develop new prognostic tools that could help individualizing patient management deciding which patients might potentially be managed and treated “less aggressively” with observation, somatostatin analogs or peptide receptor radionuclide therapy (PRRT) and which might need more “aggressive” approach systemic therapies such as chemotherapy.


Dr. Rachel Goodwin
Dr. Rachel GoodwinMedical Oncologist, Ottawa Hospital Research Institute (OHRI)

Cognitive assessment of GI NET patients with carcinoid syndrome – a pilot and feasibility study

About 40% of patients with small bowel tumors develop carcinoid syndrome (CS) but it takes multiple years before a diagnosis is made. Pasieka et al. reported significant cognitive impairment in NET patients with CS. We plan a prospective, multicentre study to test the hypothesis that somatostatin analogs therapy improves the cognitive dysfunction in these patients.

We propose a pilot feasibility study to assess the research protocol, data collection instruments, recruitment strategies, research techniques in preparation for the larger study. The pilot will enroll 10 CS patients in 4-5 tertiary Canadian cancer centres. We will test with researchers whether the protocol is workable, recruitment of subjects achievable, identify logistical problems with data collection, adequacy of cognitive assessment tools and patients’ adherence to the re-test schedule. Preliminary data collected will help researchers concentrate the protocol on a narrow spectrum of specific cognitive dysfunctions.


Dr. Neil Renwick
Dr. Neil RenwickClinician Scientist, Pathology & Molecular Medicine

Laying the groundwork for a simple microRNA-based blood test to diagnose and monitor all neuroendocrine tumors

Neuroendocrine tumors (NETs) are increasingly common cancers that are hard to diagnose and monitor. Some NET patients wait many years before getting an accurate diagnosis, giving their cancer time to spread. Even after diagnosis, patients with aggressive disease may need frequent imaging follow-up to plan their care. Earlier diagnosis and easier monitoring would allow faster access to effective treatment. microRNAs are genetic control molecules that are present in all human cells. Some microRNAs are also excellent disease markers because they are found in only one cell type.

We believe we have found a single microRNA that is only found in neuroendocrine and neuroendocrine tumor cells. In this proposal, Drs. Renwick and Singh combine their expertise in microRNA detection and NET clinical care to develop a simple blood test to diagnose and monitor all NETs. This simple test is expected to improve the lives of Canadian NET patients by enabling faster access to life-preserving treatment.


Dr. Sten Myrehaug
Dr. Sten MyrehaugPhysician, Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences

Extending immunotherapy to NET patients with radiotherapy: A correlative study



Although used in other tumor sites, immunotherapy has not shown great clinical results for patients with neuroendocrine tumors (NETs). NETs typically have a low rate of genetic mutations, making it difficult for the body to mount an effective immune response. Radiation has been shown to cause DNA breaks and will stimulate an immune response to tumors. Therefore, combining radiation and immunotherapy may produce improved results in NETs patients.

This study aims to identify how radiation may cause immune-related changes in neuroendocrine tumors, which may be harnessed to increase the effectiveness of immunotherapy agents. Patients will be selected to receive high-dose radiation to a site of cancer, which will be biopsied (sampled) afterwards to analyze what changes radiation may be effecting on the cancer cell or surrounding tissue. If radiation is proven to cause immune-related changes, it would provide evidence to combine radiation and immunotherapy in future clinical trials.


Dr. Philippe Joubert
Dr. Philippe JoubertQuebec Heart & Lung Institute (IUCPQ) – Université Laval

Comprehensive clinical and molecular characterization of diffuse idiopathic pulmonary neuroendocrine cells hyperplasia (DIPNECH)


DIPNECH is a recently described respiratory disease defined by the proliferation of several foci of neuroendocrine cells affecting both lungs, and leading to airway obstruction, development of multiple neuroendocrine tumors, and sometimes to respiratory failure. Unfortunately, the disease is poorly characterized both at clinical and molecular levels, which explains why the current clinical criteria are ill-defined and the condition under recognized and misdiagnosed. Furthermore, there is no standard treatment for the patients symptomatic of the disease or progressing towards respiratory failure. It is therefore urgent to better understand the pathophysiology and the molecular alterations underlying the development of this condition in order to develop animal and in vitro models to identify potential targets that may lead to new treatments.  The  study proposes to refine the clinical diagnostic criteria and to analyze the key-genomic events involved in the development of DIPNECH.


Dr. Simron Singh
Dr. Simron SinghMedical Oncologist, Department of Medical Oncology Sunnybrook Odette Cancer Centre

Predicting response to immunotherapy in neuroendocrine carcinoma



Neuroendocrine tumours can vary widely in behaviour, but Grade 3, poorly-differentiated neuroendocrine carcinomas (NECs) are aggressive. Patients with metastatic NECs, on average, live for less than a year. Chemotherapy is often used for Grade 3 NECs but has many side effects and generally stops working after several months. We are trialing immunotherapy (using a drug called avelumab) to see whether this drug is effective in controlling disease in patients with metastatic NEC. We plan to look at aspects of the tumour tissue (mutational load, T cell repertoire) in order to determine whether this can help predict responses to immunotherapy in Grade 3 NECs.


Dr. Jean-Mathieu Beauregard
Dr. Jean-Mathieu BeauregardUniversité Laval, Quebec City

PARP-inhibitor radiosensitization in 177Lu-octreotate PRRT of neuroendocrine tumors.  


Neuroendocrine tumours (NETs) often present at an advanced stage when cure is not possible with surgery. For patients suffering from advanced NETs, peptide receptor radionuclide therapy (PRRT) is a NET-specific treatment involving the administration of a radioactive drug that specifically recognizes these tumors and delivers a payload of radiation that can destroy them. Although PRRT is one of the most effective treatments against NETs, cure remains rare because the amount of radiation that could be delivered to the tumours is limited by the side-effects caused to healthy organs. Our team of cancer researchers, composed of a biologist and a nuclear medicine physician, will examine if a novel and promising approach of co-administering a medication (called an inhibitor of the PARP enzyme) along with PRRT can improve its efficacy without augmenting toxicity. Our research has therefore the potential to significantly improve the outcome of patients suffering from NETs.


Dr. Hagen Kennecke
Dr. Hagen KenneckeMedical Oncologist, British Columbia Cancer Agency (BCCA)

The PET NET Study: impact of 68Ga-DOTA-TOC and 18F-FDG PET/CT on multimodal management among NET patients.


Neuroendocrine tumors (NETs) are a diverse group of slow-growing tumors arising from a variety of different sites within the body, mostly from the gastro-intestinal system. These tumors present some diagnostic challenges: NETs are often diagnosed late in the disease and sometimes it is hard to determine locations where the disease has spread. There are many different types of therapies for these tumors and sequencing these therapies is a major current consideration in the clinical management of NETs. Depending on their tumor grade, NETs can progress rapidly, so it is important to accurately identify and characterize the tumors so that they can be treated most appropriately. The purpose of this study is to test a combination of two functional imaging techniques to characterize NET. This study will determine how the information gained from this imaging affects the choice of treatment therapy. It also measures how changes in the therapy as a result of the imaging impact the patient.

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