NET CANCER RESEARCH GRANT RECIPIENTS

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.

2023 DANIELS CONSTELLATION GRANT FOR NEUROENDOCRINE CANCER RESEARCH

Dr. Lina Chen
Dr. Lina ChenStaff Pathologist, Assistant Professor Sunnybrook Research Institute

Single-Cell Gene Expression and Spatial Tumour Microenvironment Profiling in Gastroenteropancreatic Neuroendocrine Neoplasms

 

 

In the digestive tract, there are certain types of cancers called gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). These cancers can affect patients differently and result in different outcomes. About half of patients discover these cancers when they’ve already spread in the body (metastasis). Unfortunately, responses to current treatments in these cases are usually limited. Scientists believe that the environment in and around GEP-NENs, called the tumor microenvironment (TME), might be one reason why treatments aren’t effective and the tumors are aggressive. Research suggests that categorizing GEP-NENs based on their genetic characteristics could help better identify patient groups and improve treatment choices. Our study will use 600 archival GEP-NENs to establish the immune landscape of their TME, with a focus on their potential impact on tumor progression, treatment response, and patient outcomes. Additionally, we will use a technique called single-cell RNA sequencing to study how genes are active in individual cells. This will help us understand the communication between different types of cells in the tumor environment. This project will identify new prognostic and predictive biomarkers that could improve management strategies for patients with GEP-NENs. Overall, the proposed study seeks to bridge the existing knowledge gap and contribute to the development of personalized and effective management of GEP-NENs.

2023 STUART BREMNER MEMORIAL GRANT FOR NEUROENDOCRINE CANCER RESEARCH

Dr. Philippe Joubert
Dr. Philippe JoubertClinician-Scientist, Institut Universitaire de Cardiologie et de Pneumologie de Québec-Université Laval

Using metabolomics to predict treatment response in advanced pulmonary neuroendocrine carcinoma

 

 

Lung cancers are the most lethal tumors in Canada. Neuroendocrine tumors (NET) represent 20% of pulmonary malignant tumors. Neuroendocrine carcinomas are very aggressive subsets of NET and usually present with extrapulmonary dissemination. Systematic treatments remain the only therapeutic options for most of these individuals and while a significant number (about 50%) will respond to standard chemo-immunotherapy, the majority will relapse. In this project, we aim to leverage the properties of the tumor cells to produce specific metabolites, to develop and validate a blood-based test to monitor treatment response, and to adapt the management of the patients more efficiently, without using limited and expensive clinical resources such as CT scans. This project will allow us to confirm the validity of metabolomics in plasma to assess tumor burden, which will allow us to apply for additional funding to increase the size of the cohort, but also to include patients at different stages of the disease and treated with different therapeutic modalities.

2023 NET RESEARCH GRANT RECIPIENT

Dr. Julie Hallet
Dr. Julie HalletMedical Oncologist, University Health Network / Princess Margaret Cancer CentreAssociate Professor of Surgery, Sunnybrook Health Sciences Centre; University of Toronto

Prospective assessment of quality of life after surgery for neuroendocrine tumors

 

 

Neuroendocrine tumors (NETs) are a type of cancer that, despite their slow progression, present a unique challenge for patients and doctors alike. Treatment often focuses on careful management rather than a complete cure, with a special emphasis on maintaining the patient’s quality of life (QOL). Recognizing that surgery is a key treatment but comes with its own risks, there’s a pressing need for more information on how patients actually feel and function after their operations. To address this, the current project led by NETs surgery centers in Toronto, Canada, and Milan, Italy, will involve multiple centers across North America and Europe. We will observe adults who undergo surgery for NETs, tracking their recovery and well-being over time using well-established QOL measures and symptom assessments. The approach is not just about numbers and data; it’s about engaging with patients throughout their journey to ensure that the care they receive is truly centered on their needs. The insights gained from this study will not only contribute to enhancing shared decision-making around surgeries for patients with NETs but also to improving the overall treatment experience for patients with NETs globally.

2023 NET RESEARCH GRANT RECIPIENT

Dr. Kirstie Lithgow
Dr. Kirstie LithgowPhysician (Endocrinologist), Tom Baker Cancer Centre, Cumming School of Medicine, University of Calgary

Impact of SSA Cross-over on Outcomes in NET (ICON)

 

 

Somatostatin analogs are the first-line treatment for patients with metastatic neuroendocrine tumours (NET). There are currently two different types of somatostatin analogs available: octreotide LAR and lanreotide. Both are given to patients as injections every four weeks. Octreotide LAR is given as a deep injection into the muscle (intramuscular or IM injection) whereas lanreotide is given under the skin (subcutaneous or SC injection). While both medications have been shown to benefit patients with metastatic NET, we don’t know if one works better than the other, as there has been no high-quality research comparing them head to head. Some smaller studies have suggested that there might be an advantage of lanreotide over octreotide LAR since giving the octreotide injection is technically more difficult and can end up in the wrong spot, resulting in the patient not getting the full benefit of the medication. Furthermore, lanreotide has improved convenience for patients. With its simpler SC administration protocol, lanreotide can be given at home by patients/caregivers, while octreotide must be given by a trained nurse. The goal of our study is to compare outcomes for patients taking lanreotide with patients taking octreotide LAR. We will look at outcomes related to their cancer ( i.e. how well their symptoms are controlled and how long it takes for their cancer to progress) as well as their quality of life and perspectives about the treatment. Our results are expected to reveal whether two different somatostatin analogues, which are used interchangeably in NET treatment, differentially impact clinical outcomes and/or patient experiences.

2023 NET RESEARCH GRANT RECIPIENT

Dr. Sten Myrehaug
Dr. Sten MyrehaugRadiation Oncologist, Odette Cancer Centre, Sunnybrook Health Sciences Centre

A Phase II Randomized Feasibility Study Comparing Standard Of Care Systemic Therapy Plus Stereotactic Ablative Body Radiotherapy To Address Tumor Heterogeneity In Neuroendocrine Neoplasms

 

 

Neuroendocrine tumour behaviour and response to treatment not only varies upon the type of tumour but also between different cell types/locations within a single patient. This is a treatment challenge and is a focus of research to combine therapies to maximize treatment response. In any given patient, there may be multiple sites of disease that may represent different degrees of aggressiveness and response to treatment. It may be these specific sites that require treatment-intensification.

One strategy to determine the variability of tumour behaviour in a patient is the use of dual PET imaging (utilizing both Ga- and FOG-PET). By using this imaging, we can identify specific sites of disease that may not respond optimally to standard systemic treatments. The proposed trial is designed to assess whether the use of dual PET imaging to focus the use of localized high-dose radiation therapy to specific sites of potentially more aggressive or less responsive disease can provide an additive benefit to systemic treatment. This is a feasibility study to gain more information needed to develop larger clinical trials evaluating this concept.

2022 DANIELS CONSTELLATION GRANT FOR NEUROENDOCRINE CANCER RESEARCH

Dr. Lucy Ma
Dr. Lucy MaMedical Oncologist, University Health Network / Princess Margaret Cancer Centre

Plasma whole genome sequencing for molecular residual disease detection in resected gastroenteropancreatic neuroendocrine tumours

 

 

Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are a group of malignant neoplasms with variable clinical behaviour, ranging from indolent to aggressive. There is a need for the development of biomarkers to identify patients at high risk of recurrence who may be more likely to derive benefit from adjuvant therapies.
In this study, we will investigate the use of plasma whole genome sequencing to detect molecular residual disease (MRD) in patients with resected GEP-NET and evaluate the underlying biologic mechanisms that lead to recurrence. Patients who are found to have MRD will be offered participation in a clinical trial of adjuvant systemic therapy. Results from this study will inform the design of a larger clinical trial of adjuvant therapy to reduce disease recurrence for patients with molecular residual disease.

2022 NET RESEARCH GRANT RECIPIENT

Dr. Sarah Mattonen
Dr. Sarah MattonenAssistant Professor, Western University / London Regional Cancer Program

Radiomics and Machine Learning for Response Prediction to Lu-DOTATATE in Patients With 68Ga-DOTATATE Somatostatin Receptor Positive Neuroendocrine Tumors

 

 

Neuroendocrine tumours form from cells that release hormones into the blood in response to a signal from the nervous system. These tumours have unique characteristics that allow for the development of radiopharmaceuticals, which are drugs that contain a radioactive substance that can be used to both diagnose cancer via imaging and treat disease. However, not all patients will benefit from treatment with radiopharmaceuticals. Therefore, we need to identify clinical and imaging-based markers that may distinguish good responders from poor responders prior to treatment, so we can identify patients that would most benefit from this therapy. As images of the tumour are taken prior to treatment, they may provide valuable insight into the underlying causes of the disease. Radiomics is the process of extracting quantitative features from medical images to predict outcomes and typically these features are not visible to a clinician’s eye. In this study, we will extract features from pre-treatment medical images and combine these with clinical indicators to predict progression-free survival (length of time that a patient lives with cancer but it does not get worse) and overall survival. This non-invasive software model will allow us to better determine the likely course of the disease and will aid clinicians in identifying patients at a lower risk of treatment failure who will most benefit from this therapy. This will allow for more personalized treatment for patients with neuroendocrine tumours.

2022 NET RESEARCH GRANT RECIPIENT

Dr. Christopher O'Callaghan
Dr. Christopher O'CallaghanSenior Investigator / Professor, Canadian Cancer Trials Group, Queen's University

STOPNET – A Randomized Study of Cessation of Somatostatin Analogues after Peptide Receptor Radionuclide Therapy in Mid-Gut Neuroendocrine Tumours

 

 

Neuroendocrine tumours (NET), are increasing in incidence around the world, including Canada. Most NETs are diagnosed as low-grade and are relatively slow-growing tumours. Nonetheless, they commonly present as advanced (metastatic) and incurable cancers which will result in death over time. Some of these NETs will also cause the overproduction and release of hormones, causing “carcinoid syndrome” which can result in severe symptoms for the patient. The main treatment for these tumours is a type of inhibitory hormone injection called somatostatin analogues (SSA). These slow tumour growth and relieve carcinoid syndrome. Unfortunately, despite SSA treatment usually working, most patients will experience tumour growth over time. Nonetheless, SSA are continued for the long term. After this tumour growth, specialised targeted radiotherapy (PRRT) is used; however, it is not known if continuing SSA after PRRT is worthwhile or not. These injections can cause side effects and are expensive for the healthcare system. Therefore, it is important to know whether their use after PRRT is helpful for the patient. In the STOPNET trial, we will stop SSA injections in some patients following PRRT and compare tumour growth, side effects and quality of life with patients in whom the SSA injections are continued.

2022 NET RESEARCH GRANT RECIPIENT

Dr. Girish Shah
Dr. Girish ShahProfessor, CHU de Quebec - University Laval Research Centre

Screening of gastroenteropancreatic neuroendocrine tumors from patients for temozolomide-induced upregulation of SSTR2: Towards improved PRRT

 

 

The somatostatin receptor subtype 2 (SSTR2) expressed by many NETs is targeted by peptide receptor radionuclide therapy (PRRT) with radiopharmaceuticals, such as 177Lu-DOTATATE (LuTate). Although LuTate-PRRT is the most successful targeted therapy for NET, it does not deliver complete remission, and many NET patients with low SSTR positivity are ineligible for PRRT. Recently, we identified that the SSTR2 expression can be upregulated in different NET cell lines for better therapeutic response to LuTate PRRT by a prior exposure to temozolomide (TMZ), an approved drug for NETs.
We further validated these results in vivo in mouse model with human NET cell-derived tumors, and noted this SSTR2 upregulation preferentially occurred in NETs and not in other healthy organs including liver. Lastly, we observed that even the tumors harvested from mice and treated outside (ex-vivo) with TMZ showed similar SSTR2 upregulation. This and other evidence from literature led us to hypothesize that the SSTR2 upregulation by a brief pre-treatment with TMZ can be a good therapeutic modality to improve PRRT of NETs.
The short-term goal of the project is to screen at least 25 different GEP-NETs from patients, for their ability to upregulate SSTR2 after ex-vivo with TMZ. The long -term goal is to provide a map of NETs that can benefit from upregulation of SSTR2, which can be verified in clinical trials.

2021 NET RESEARCH GRANT RECIPIENT

Dr. Guillaume Chaussé
Dr. Guillaume ChausséAssistant Professor, Nuclear Medicine Specialist, Research Institute – McGill University Health Center (RI-MUHC)

Pre-clinical assessment of the relevance of using kidney-sparing amino-acid infusion to prevent renal toxicity in lutetium-177 labelled Peptide Receptor Radionuclide Therapy (177Lu-PRRT)

 

 

Non-resectable metastatic patients with neuroendocrine tumors benefit from an injected radioactive treatment, 177Lu-peptide receptor radionuclide therapy (PRRT) (recently Health Canada-approved), with longer time before progression and longer survival. The protocol includes a slow infusion of amino acids (arginine/lysine) IV before, during and after treatment, a substance which presumably decreases kidney accumulation of the therapy agent. This however causes the most frequent side effects of this therapy, nausea and vomiting, and increases time spent in hospital, complexity of scheduling, and treatment costs. The reasons for the use of amino acids come from old cases of patients treated with a different version of PRRT. Validation that amino acids decrease renal accumulation was also done with another different (imaging) agent. Moreover, PSMA-radionuclide therapy (PRLT) such as 177Lu-PSMA-617 is a different therapy (for prostate cancer) with similar or higher accumulation in the kidneys, yet very little kidney toxicity. We conclude that little is known regarding the true efficacy and necessity of amino-acid infusion for 177Lu-PRRT.

2021 DANIELS CONSTELLATION GRANT FOR NEUROENDOCRINE CANCER RESEARCH

Dr. Iacovos Michael
Dr. Iacovos MichaelScientist, Sunnybrook Research Institute

Molecular classification of gastroenteropancreatic neoplasms using novel tissue biomarkers

 

 

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are highly heterogeneous diseases with a variable patient prognosis. The current grading system of GEP-NENs is primarily based on the proliferation status of the tumors. While this grading has some prognostic value, it can be subjective, and variable between different centers. Thus, there is an urgent need to identify superior methods to stratify GEP-NENs.

In this study, first, we aim to construct a comprehensive tissue microarray (TMA) from archival tissue from patients with GEP-NENs. This TMA will include 600 samples, in duplicate, from GEP-NENs from various primary sites (pancreas, stomach, small intestine, colon, and rectum), as well as patients with disease recurrence, and metastasis. We foresee that this GEP-NEN-TMA will facilitate the discovery of better prognostic markers, a better understanding of the biology of NENs, and the identification of therapeutic vulnerabilities. Herein, we propose to examine the prognostic value of two molecular subtypes, MLP and YAP-OFF, that our groups and others have shown to be involved in the progression of NENs. Notably, these molecular subtypes are currently not used in clinical practice, and this will be the first study to examine their clinical utility. Incorporating molecular subtypes in diagnosing patients with NENs can lead to better classification and prognosis, patient-specific treatment, and improve quality of life and overall survival.

2021 NET RESEARCH GRANT RECIPIENT

Dr. Girish Shah
Dr. Girish ShahProfessor, CHU de Quebec - University Laval Research Centre

Potentiation of PRRT by chemotherapy-mediated upregulation of somatostatin receptor 2 in NET cell lines-derived tumors in mice and in Lung NET patient-derived tumor explants

 

 

The somatostatin receptor subtype 2 (SSTR2) expressed by many neuroendocrine tumors (NET) is targeted by peptide receptor radionuclide therapy (PRRT) with radiopharmaceuticals, such as 177Lu-DOTATATE (LuTate). Although LuTate-PRRT is the most successful targeted therapy for NET, it does not deliver complete remission, and many NET patients with low SSTR positivity are ineligible for PRRT. Recently, we identified that two different patient -derived NET cell lines specifically upregulate SSTR2 expression for a period of 14 days after a short exposure to small doses of chemotherapeutic drugs. Moreover, this results in a greater uptake of LuTate and better therapeutic impact as compared to cells that were not exposed to chemotherapy.

The short-term goals of this project are to validate this combination approach in vivo with these NET cell lines-derived tumors in mice and in multiple Lung NET patient-derived tumor explants ex-vivo.

The long -term goal is to provide a convincing pre-clinical evidence that will permit launch of clinical trials to examine the efficacy of these combination approach in NET patients to not only improve their response to LuTate but also make more NET patients eligible for LuTate PRRT.

2021 NET RESEARCH GRANT RECIPIENT

Dr. Simron Singh
Dr. Simron SinghAssociate Professor, Sunnybrook Research Institute

Temozolomide based treatment in Well Differentiated Lung Neuroendocrine Neoplasms: A Multicenter Retrospective Review

 

 

The only approved therapy for advanced LNENs is everolimus, which is associated with low response rates and important toxicities. Temozolomide based chemotherapy has been explored in gastroenteropancreatic NETs demonstrating efficacy. However, it has not been studied as treatment option for well differentiated LNENs in prospective trials or as large real world data, given the rarity of this disease. Therefore, collaborative efforts like this project is an important opportunity to clarify a role for treatments in well differentiated LNENs, that have demonstrable activity in NENs of other sites of origin.

2020 NET RESEARCH GRANT RECIPIENT

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.

2020 DANIELS CONSTELLATION GRANT FOR NEUROENDOCRINE CANCER RESEARCH

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.

2019 NET RESEARCH GRANT RECIPIENT

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.

2019 NET RESEARCH GRANT RECIPIENT

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.

2019 DANIELS CONSTELLATION GRANT FOR NEUROENDOCRINE CANCER RESEARCH

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.

2018 NET RESEARCH GRANT RECIPIENT

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.

2018 NET RESEARCH GRANT RECIPIENT

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.

2018 DANIELS CONSTELLATION GRANT FOR NEUROENDOCRINE CANCER RESEARCH

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.

2017 NET RESEARCH GRANT RECIPIENT

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.

2017 NET RESEARCH GRANT RECIPIENT

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.

2016 NET RESEARCH GRANT RECIPIENT

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.

2016 NET RESEARCH GRANT RECIPIENT

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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