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Thirty years of progress tackling neuroendocrine tumours

A neuroendocrine tumour (NET) in the pancreatic islet cells, one of the rarer forms of NET.Credit: OGphoto/ Getty Images

Neuroendocrine tumours (NETs) begin in specialist cells at the intersection of the nervous and hormonal systems. As such, NETs can arise at many different locations across the body, although two-thirds occur in the intestines (known as carcinoid tumours). Despite this diversity, NETs share commonalities based on the basal cell type.

NETs are not common cancers, affecting around 7 people per 100,000 in the United States each year1. Clinical research and therapeutic innovations have improved awareness, diagnosis and treatment of NETs over the past 30 years — and particularly over the past decade. As with many rare diseases, these advances have been a community achievement, driven by healthcare professionals, patients and industry.

Here are perspectives from key members of this NET community on the progress made, and the challenges that remain, when it comes to managing this form of cancer. Contributors are:

* Dermot O’Toole, a gastroenterologist and clinician at Trinity College Dublin and St. James's and St. Vincent's University Hospitals, and past-chairperson of the European NET Society (ENETS)

* Teodora Kolarova, executive director of the International Neuroendocrine Cancer Alliance (INCA)

* Riccardo Canevari, Chief Commercial Officer for Advanced Accelerator Applications (AAA), a Novartis Company, based in Saint-Genis-Pouilly France

* Rachel Levine, Head of Communications and Patient Advocacy, also at AAA.

Dermot O’Toole, a gastroenterologist and clinician at Trinity College Dublin and St. James's and St. Vincent's University Hospitals, and past-chairperson of the European NET Society (ENETS)Credit: Dermot O’Toole

Can we still consider NETs to be a rare cancer?

Dermot O’Toole:

The epidemiology of NETs is evolving. In recent years, we have seen an increase in their incidence, mainly driven by improved diagnostic techniques resulting in more patients being diagnosed every year. In parallel, we are also witnessing a significant prolonging of survival rates, which is extremely encouraging for health-care workers in this interesting and evolving field. Data from the United States show improvements in prognosis regardless of tumour primary and stage.1 The combination of increasing incidence and prevalence of NETs mean that it soon may no longer be appropriate to view them as rare forms of cancer. Indeed, the incidence rate has increased 6.4-fold between 1973 and 2012, mostly for early stage tumours.1

Is society sufficiently educated and aware of NETs?

Dermot O’Toole:

Although prevalence of NETs is increasing, many people and doctors are still unaware of this cancer, which can delay diagnosis and treatment initiation. One survey found an average time of nearly 3.5 years from first symptoms to diagnosis for carcinoid tumours; many patients are thus diagnosed at metastatic stage and might suffer from carcinoid syndrome.2 More sensitive and precise diagnostic tools will help, but specialists and primary care services will benefit from more education. Continued engagement between researchers, patient groups and industry can contribute to raising awareness and help improve health outcomes.

What are the most recent advancements in NET research?

Dermot O’Toole:

Somatostatin receptor imaging, which uses single photon-emitting or positron-emitting radiopharmaceuticals to detect the somatostatin receptors on the surface of neuroendocrine cells, has been used for nearly 20 years for both diagnosis and staging of NETs. However, the last four years has seen the approval of newer agents with increased sensitivity,4 including 68Ga-DOTATATE. These give more accurate information and help us to plan therapies more confidently for our patients.

The past ten years have also given us more treatment options including targeted therapies, such as everolimus and sunitinib, and peptide receptor radionuclide therapy4 such as 177Lu-DOTATATE. These agents can be used in patients with metastatic gastrointestinal or lung NETs, and many have shown significant improvements in progression-free survival.5

Equally, we’ve seen treatment advances in disease management. New drugs such as telotristat can treat carcinoid syndrome, which commonly affects NET patients. And the ‘centre of excellence’ model is improving the way NETs are managed at the country level. In summary, diagnostic and therapeutic advances are increasing overall survival for the majority of NET patients.

Teodora Kolarova, executive director of the International Neuroendocrine Cancer Alliance (INCA)Credit: Teodora Kolarova

What is the power of the patient voice?

Teodora Kolarova:

Our commitment to be the global voice of NET patients has multiple aspects. As an umbrella patient organization, representing 26 countries on 6 continents, INCA’s major focus lies in creating platforms for collaboration with key stakeholders. We aim to raise awareness of NETs, improve access to optimal care and treatment for all NET patients, and involve NET patients in research. We are passionate about improving the lives of those living with NETs, and have come a long way in our efforts to address the needs of the NET patient community. For example, we set up the INCA Unmet Needs Assessment Survey, reaching out to NET patients, patient advocates and healthcare professionals in 26 countries, in collaboration with ENETS, North American Neuroendocrine Tumor Society (NANETS), Asia Pacific Neuroendocrine Tumor Society (APNETS), the Commonwealth Neuroendocrine Tumor Society (CommNETs), and Japan Neuroendocrine Tumor Society (JNETS). This survey reached important conclusions regarding patients’ information needs, access to optimal diagnostics and treatment, and involvement in research. Its results were presented at all the major oncology and NET-specialized conferences, notably winning best poster awards at ESMO Congress 2018 and ENETS Conference 2019. The results were published in an open-access manuscript3 in the International Journal of Cancer, and was one of its top downloaded papers 2018-2019.

This survey inspired another global effort: SCAN (the Survey of Challenges in Access to Diagnostics and Treatment for NET Patients). SCAN examined the reasons for the gaps in diagnosis and care for NET patients around the world, with the prospect of driving optimal care. It was completed by 2,795 NET patients and healthcare professionals from 68 countries across 6 continents. SCAN represents the largest compendium of data on management of NETs so far, and its findings have been presented at all major conferences in 2020.

How have you helped improve care and treatment of NETs?

Teodora Kolarova:

Within the European Union (EU), we are involved in a number of initiatives to help patients access the best care possible, such as EURACAN (the European Reference Network for Rare and Adult Cancers), and the European Cancer Organisation Code of Cancer Practice. We are also active in a European political initiative to contribute to debates on how health-care systems can welcome innovative cancer therapies and also engage with policy-makers and EU institutions to overcome geographical variation in access to radioligand therapies.

Furthermore, since access is ultimately a country-based issue, we are working to equip our member organizations around the world with evidence-based tools to advocate for optimal care for NET patients in their communities. Working with governments and decision-makers is really crucial if we are to bring about meaningful policy change and improve the lives of those living with NETs. For example, our UK member organization, Neuroendocrine Cancer UK, has worked closely with the National Institute for Health and Care Excellence (NICE) on its health technology appraisals, which resulted in broader coverage. INCA is also active globally, in other health technology assessment systems.

We are proud of our past successes, and are committed to continue to make a difference. We are looking to strike more effective partnerships that can ensure access to equitable care worldwide.

Riccardo Canevari, Chief Commercial Officer for Advanced Accelerator Applications (AAA), a Novartis Company, based in Saint-Genis-Pouilly FranceCredit: Advanced Accelerator Applications, a Novartis Company

How are patients and industry collaborating around NETs?

Riccardo Canevari:

It has been an absolute privilege for AAA to partner with the NET patient community. We have so many passionate people from a range of backgrounds who are driven to make the lives of cancer patients better. We are proud to continue Novartis’s legacy: they helped to form INCA and create patient awareness programmes and improve disease awareness for NETs.

Partnering with the NET patient community has been so important, and our journey together in recent years has been incredibly rewarding. We know there is more to do, like sharing best practice and pursuing more innovation in NET cancer treatment. Doing this effectively requires deeper partnerships in the future. This approach should be the norm across all cancers and beyond, not just NET.

Rachel Levine, Head of Communications and Patient Advocacy, also at AAA.Credit: Advanced Accelerator Applications, a Novartis Company

What does the future of NET cancer look like?

Rachel Levine:

The future looks more promising for those living with NETs. People are living longer than ever before, and we’re getting a better understanding of NETs through new research efforts. For instance, the ENETS Registry, which opened in 2016, is collecting information on diagnostic and therapeutic strategies and investigating the epidemiology of NET. Tools like this mean we can improve multicentre and multinational collaborations and better understand the evolving therapeutic landscape for NETs.

There are still challenges. There needs to be more shared data on sequencing of treatments, especially for new agents, and we want to see equitable access for NET patients around the world. We’re continually making new discoveries, and future innovations must be rolled out for therapeutic use.

We need to see more research into immunotherapy for NET treatment, as well as into the best combination of treatment approaches. These data could bring personalized NET treatment based upon individual patient tumour biology.

Importantly, the future has to be based on meaningful partnerships. Patient advocacy groups have to be front and centre to ensure that the lives of people with NETs will genuinely improve day-by-day. We have a new shared responsibility to make sure that all patients live better lives, wherever they are.

Job ref: AAA-NP-GL-0136-20

These are the views of the presenters, not necessarily those of Advanced Accelerator Applications, a Novartis company.

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