Researcher Insights
Dr. Mauro Cives: Latest Updates in Translational NET Research
Dr. Mauro Cives works as Associate Professor of Medical Oncology in the Department of Interdisciplinary Medicine of the University of Bari “Aldo Moro”, Italy.
Dr. Cives’ work focuses on the preclinical and clinical evaluation of innovative neuroendocrine tumor treatments, particularly regarding adoptive T-cell therapies.
Dr. Cives is a co-author of over 75 peer-reviewed publications. He serves as member of the ENETS Advisory Board and is co-secretary of ENETS’s Basic and Translational Group (BTRG).
In this presentation, recorded for INCA in 2024, Dr. Mauro Cives presents the latest updates in translational NET research. Dr. Cives explores the innovative research tools, innovative NEN models and innovative immunotherapy approaches.
Highlights:
- Single-cell and single-nuclei sequencing technologies will help researchers in gaining a better understanding of the biology of neuroendocrine neoplasms by knowing which cells are expressing different transcripts.
- In the future, we will be able to understand what the differences are, for example, between cells that are able to metastasize and cells that are not able to metastasize. Then we will know the mechanisms of metastasization and fight them.
- By exploring new NEN models, we will be able to test treatments in vitro before administering that specific treatment to a patient. This is how in the future we may be able to tailor treatment according to clinical knowledge.
- Antibody–drug conjugates (ADCs) are an emerging class of drugs in oncology. If you link a toxic substance to an antibody, you will be able to specifically bring this poison to the tumor cell.
- The next generation of CAR T cells are not only able to redirect the specificity of T cells against tumor cells, but also lead to the secretion of specific molecules when they encounter the protein that makes the tumor cell. The T cells are isolated from the blood of the patient, then they are engineered and fused back into the patient – to target the right tumor cells and to kill them.
- The first tumor-infiltrating lymphocyte (TIL) therapy was recently approved and heralds a new era for precision cancer immunotherapy.
- BiTEs are emerging immunotherapy products – they play the role of immune cell connector, connecting the immune cells to the tumor cells and enabling the immune cells to exercise their killing effect.
- Cancer vaccines are investigated also in the NEN field.
- Transformative translational research is needed to improve patients’ outcomes and eventually cure NENs.
- An alliance must be built between patients, patient advocates, researchers and clinicians – we do not need “science for science”, we need a truly transformative, bench-to-bedside approach in research to bring results in the next decade.
Dr. Grace Kong: Current NET Research: Nuclear Medicine Clinical Trials
Assoc. Prof. Grace Kong is a Nuclear Medicine Physician at the Peter MacCallum Cancer Centre
(PMCC) Australia, a Clinical Associate Professor at the University of Melbourne, Sir Peter MacCallum
Department of Oncology. She is the Co-Chair of the PMCC Neuroendocrine Tumour (NET) Unit, a
European Neuroendocrine Tumor Society (ENETS) Center of Excellence.
In this presentation, recorded for INCA in 2024, Dr. Grace Kong presents and explains the current
nuclear medicine clinical trials in the NEN field.
Highlights:
- It is certainly very encouraging to see that there is now increasing evidence showing that lutetium DOTA-octreotate therapy is effective. And certainly, there are more trial data coming through, also supporting that this treatment is superior to some other treatments as well.
- There are more than 35 PRRT clinical studies registered in clinicaltrials.gov that are active and recruiting.
- Currently in 2024 there are a number of combination treatment trials combining PRRT with a number of agents.
- The clinical interest at the momentis of actinium-225 and lead-212. Currently there are several prospective clinical trials using these new radionuclides.
- Albinum binding is an interesting concept, which is to alter the actual PRRT chemical structure to make it longer-lasting and potentially more effective for patients.
- 2024 and beyond is really looking very bright. There is certainly an increasing number of prospective PRRT and imaging trials.
- The future focus should be on performing more multicenter collaborative studies, particularly important for uncommon complex cancers like neuroendocrine tumors.
- Performing clinical trials is very, very important because we need to provide the evidence to enable support and reimbursements for NET imaging and treatment for patients.
Dr. Thorvardur Halfdanarson: Meaningful Involvement of Patients in NET Research
Dr. Thorvardur Halfdanarson is a Professor of Oncology at the Mayo Clinic College of Medicine and Science and a Consultant in Medical Oncology at the Mayo Clinic. He serves as NANETS President 2024.
In this presentation, recorded for INCA in 2024, Dr. Thorvardur Halfdanarson explores how patient advocates can contribute to improvements in research and offers a practical model for involving patients.
Highlights:
- Most patients with advanced NETs will run out of options, and we need to expand our treatment choices. There is need for more NET therapy trials in the future, and these trials should be patient-centered and importantly informed by input from patients and patient advocates, because at the end of the day this is all being done for the patients.
- Active, meaningful and collaborative interaction between patient advocates and researchers, across all stages of the research process is very important, because it fosters a sense of urgency and purpose.
- When we design clinical trials, we need to know what is important to patients. It really, truly improves the design of the trials.
- Patients are indeed the major stakeholders in cancer research, and you can raise awareness more than anyone else can. So, it enhances the focus and the goals of the research.
- Patients can be involved in any part of the research process, and they can provide valuable contributions in terms of feasibility, acceptability, relevance, and engagement.
- You have to have a collective mission to integrate the patient perspective with the institution’s goals and to promote research, which is patient-centered obviously, evidence-based, and accessible to as many as possible.
Prof. Pamela Kunz: Meaningful Involvement of Patients in NET Research
Dr. Pamela L. Kunz is Professor of Internal Medicine (Medical Oncology) and Director, Center for Gastrointestinal Cancers at Smilow Cancer Hospital and Yale Cancer Center.
In this presentation recorded for INCA in 2023, Dr. Kunz explored how neuroendocrine cancer patient advocates and researchers can partner in identifying unmet needs and advancing NET knowledge.
Highlights:
- It is one thing to know cancer as a physician, but it is another to experience it first-hand as a patient.
- The importance of partnering with patients as a foundation for everything: from patient care, to research and clinical trials and education.
- Formalized cancer patient advocate training programs – a critical way for patients and patient advocates to empower themselves on how to best advise on cancer research and clinical trials.
- Patient advocates belong in all of the places where decisions are being made about them.
- The medical community needs to be intentional and deliberate in ways to include and partner with patients.
Dr. Jaydira Del Rivero: Practice-Changing Trials in NETs
Dr. Jaydira Del Rivero is a Medical Oncologist and Endocrinologist at the National Cancer Institute, National Institutes of Health in the USA.
In this presentation recorded for INCA in 2023, Dr. Del Rivero gives a snapshot of NET incidence, treatment landscape and the practice-changing clinical trials to date.
Highlights:
- We still need to understand more about the benefit of different therapies on different types of neuroendocrine tumors.
- A comprehensive classification system that incorporates tumor clinical stage, genomic and epigenetic expression profiles could serve to better define the biology of NET and hopefully establish correlations with clinical outcomes and develop effective therapies.
- Developing an easily accessible national and international patient engagement network for NET research and patient care with advocacy/support groups, will address the patient needs and increase access to research for patients.
- We need to discuss with the industry how to avoid redundancy and complement what is done instead of having competition – our ethics and moral need to play here to make therapies accessible for patients.
- We need to rethink how we run clinical trials so that therapies can be used by patients sooner.
Dr. Enrique Grande: How Clinical Practice Has Been Changed by Clinical Trials in the Last 10 Years
Dr. Enrique Grande, MD, PhD, Msc, is the Director of the Medical Oncology Program
and Clinical Research lead at the MD Anderson Cancer Center Madrid.
In this presentation recorded for INCA in 2022, Dr. Grande gives a snapshot of NET research,
how neuroendocrine cancer clinical trials change clinical practice, as well as outlines
potentially practice-changing trials.
Highlights:
- “PROMID TRIAL was first with SSA’s demonstrating delayed tumor growth. Prior to this, SSA’s only given to control symptoms so it was a major breakthrough to learn that SSA’s could control tumor growth for quite some time”
- “2011 was the next big breakthrough for treatments to postpone and delay the growth of PNETS in G1 and G2 tumors”
- “Gallium PET Scans allowed us to better identify tumor cells and their activity”
- “TELESTAR trial gave us tumor growth control and quality of life improvement”
- “We need better drugs to control the symptoms and the quality of life. It is important to live longer but it is also important to live better. Sometimes researchers are forgetting about this and that is why we need the patient’s input”
Prof. Jonathan Strosberg: Practice Changing Research in NETs
Prof. Jonathan R. Strosberg is President of NANETS (2022) and a medical oncologist in the Department of Gastrointestinal Oncology, section head of the Neuroendocrine Division and chair of the Gastrointestinal Department Research Program at Moffitt Cancer Center.
In a presentation еspecially recorded for INCA in 2022, Prof. Strosberg speaks about the current practice-changing clinical trials related to neuroendocrine cancer.
Highlights:
- “Alpha emitting PRRT using heavier particles with higher energy but shorter range is hoped to lead to better outcomes and lesser toxicity with two studies in progress”
- “There are often conflicts between the benefits for a patient in a trial vs the benefit for the data collected, e.g. when design is against a placebo”
- “Trials can be very burdensome on the patient but do patients really need to always be seen in person for follow-ups … telemedicine has proven very useful to reduce the patient burden”
- “We need more trials on poorly differentiated NECs and cell therapies with the potential for long-term remission”
- “There are conflicts between the benefits for a patient enrolling in a trial vs the outcome of the study”
Prof. Michael Michael: What is the Role of Patients in Trial Design and Efficacy
Prof. Michael is a Gastrointestinal and Neuroendocrine Medical Oncologist at the Peter MacCallum Cancer Centre, Melbourne.
In this presentation recorded especially for INCA in 2022, Prof. Michael speaks about NET clinical trials that are practice-changing, and highlights the gaps in current NET research, as well as the role of patients in clinical trials design.
Highlights:
- “We need to better define the disease biology to help us to better select an individualized treatment, in other words precision medicine, in terms of what is being done with other malignancies”
- “We need better biomarkers to predict disease behavior, and these need to be built in within all prospective research”
- “We also need better studies to define the sequential therapy for all sub-classes of neuroendocrine tumors”
- “Patients need to be involved in trial design to both refine and answer the right questions, to produce good quality results, and also to ensure that trial recruitment is completed”