Selective internal radiation therapy has recently been given the green light by NICE, offering a less-invasive, non-surgical treatment option for neuroendocrine tumours (NETs) that have metastasised to the liver. Here, Drs Brian Stedman and Sachin Modi discuss the treatment landscape of NETs, the significance of this recommendation for patients in England, Wales and beyond, remaining challenges and the importance of the multidisciplinary team in the planning and delivery of this treatment.
New interventional procedures guidance from the National Institute for Health and Care Excellence (NICE) recommends the consideration and use of selective internal radiation therapy (SIRT) for neuroendocrine tumours that have metastasised to the liver.
The treatment involves injecting tiny radioactive spheres into the blood vessels that supply the liver metastases to control the growth of these tumours and reduce symptoms, all while limiting exposure to healthy surrounding tissue.
The guidance highlights that while there are well-recognised and infrequent serious complications with SIRT, this treatment may be better tolerated in some people than other available options.
As such, patient selection for SIRT should be carried out by an experienced multidisciplinary team – much like the one led by Dr Brian Stedman, consultant interventional radiologist, and Dr Sachin Modi, consultant interventional radiologist and oncologist at University Hospital of Southampton.
What are the current key challenges in neuroendocrine tumour diagnosis and management?
Dr Stedman: Neuroendocrine cancer is typically a tumour that’s diagnosed late because patients present with very vague symptoms that are often overlooked or confused with irritable bowel symptoms and dyspepsia.
A lot of patients will have spent years seeing primary care physicians with fairly nondescript symptoms and never getting an accurate diagnosis. Often, it’s when patients end up having a CT scan that the diagnosis is made because the CT appearance is pathognomonic.
The tumours can be either very indolent – that is they can stay without progressing for 10 years – or they can be aggressive, and people can die within three months of diagnosis. There’s such a broad range of biology and behaviours, it can be hard to select the right way of managing patients.
What has the treatment landscape looked like over the last decade for neuroendocrine tumours?
Dr Stedman: With disease management, there’s a shift towards more aggressively managing metastatic disease by removing primary tumours surgically, whether they are in the bowel or in the pancreas, because there’s good evidence now that patients live better and longer. Systemic chemotherapies have been shown to be effective in the most aggressive neuroendocrine tumours.
There’s also been the development of peptide receptor therapy where you use a radio isotope attached to a peptide receptor that can be useful for treating the differentiated tumours. These are the indolent tumours that are demonstrating or displaying these receptors.
Please give some detail around the patient profile who have NETs in the liver
Dr Stedman: Looking at our local practice, we get the impression that there are quite a lot of reasonably well, middle-aged people who are working, have young kids and are living fairly normal lives despite having metastatic cancer. Males and females are affected.
Like most cancers, the age demographic is more common for those in their 60s and 70s. However, we are now seeing a lot of patients in their late 20s, early 30s presenting with metastatic neuroendocrine tumours.
There is a bit of a lead time: many more people in their 20s and 30s are having CT scans and quite a lot of these tumours are detected incidentally on those scans. Now those patients would have probably presented five years later with symptoms, but we’re picking them up at a stage when sometimes the diagnosis is just made, incidentally, almost by luck, because these patients are having increased amounts of cross-sectional imaging.
What types of conditions are being scanned for when CT leads to incidental NET diagnosis?
Dr Modi: About 10-15 years ago there was a lot more reliance on clinical acumen. If a patient came in with abdominal pain, they would be seen by someone, and a diagnosis would be made although not necessarily with imaging. Now when someone comes into a A&E with abdominal pain, it’s almost certain they’re going to have some form of imaging whether that’s ultrasound or CT.
Dr Stedman: A good example would be people having trauma scans, or patients who have renal colic who think they’ve got kidney stones. Both of those are common areas where we pick up these tumours.
How has selective internal radiation therapy (SIRT) progressed in recent years and what are the main benefits for patients with liver NETs?
Dr Modi: SIRT has been around for about 10 to 12 years, but it has shown some significant advances over the last couple of years, particularly in the field of dosimetry.
This treatment essentially involves delivering radiation loaded onto glass beads into the liver arteries These beads are attracted to the liver tumours because the tumours tend to take their blood supply from the liver arteries.
The aim is to deliver millions of these beads in and around the tumour so that they have a radiation effect essentially from the inside out. They all emit a beta emission of radiation between one to two millimetres, which in theory kills the tumour from the inside out.
We’ve been delivering this therapy in Southampton for the last 10 years. We’ve significantly developed our technique in terms of the radiation dose that we can safely give to patients using software, which enables us to tailor therapy to kill a tumour and not damage the surrounding background liver. We work as part of a collaborative team with oncologists and nuclear medicine physicians to deliver this service safely for our patients.
SIRT is a significant step because it represents another option to treat these patients who have liver tumours that have spread from a primary net cancer. These patients can be quite difficult to manage. Traditional treatments, such as bland embolisation or transarterial chemoembolisation, involve multiple visits to hospital, which can have some side effects on patients in terms of their quality of life.
SIRT is a very well-tolerated, minimally invasive treatment in our experience. Clinicians have the opportunity to give patients a one-off treatment that benefits them without affecting their quality of life and, in fact, patients’ quality of life returns pretty much back to baseline very soon after SIRT.
What are some of the challenges and barriers of SIRT?
Dr Stedman: Despite NICE advocating the use of SIRT and it’s an independent panel saying this is probably the most effective treatment for this group of patients, there’s still currently no NHS funding or commissioned service in place. NHS patients cannot get access to this therapy due to a lack of funding from NHS England.
One of the challenges is that the breadth of experience and breadth of clinicians that are required to deliver this service. You need medical oncologists, radiation oncologists, medical physicists and a radiopharmacy. You need access to gamma cameras, which provide specialised nuclear medicine imaging, and you need an interventional oncology unit which is trained up and certified for the delivery of these services.
Around the country quite a lot of centres struggle to get that team up and running; you only need to lose one of those key players and the service falls down.
With this technology, it takes two to three years to get a SIRT centre commissioned and up and running. Costs run between £0.5m and £1m in terms of equipment and staff facilities. There’s a big implicit risk here if commissioning is turned off even for a short period of time – expertise gets lost.
Dr Modi: The other barrier is geographical discrepancy in England in terms of centres that can deliver SIRT. There are some areas where the services are deficient due to a lack of local expertise especially with nuclear physicists.
Where do you see SIRT’s place in therapy, and how might its NICE recommendation impact patients and the multidisciplinary team in England and Wales?
Dr Stedman: It would be nice to see the expert clinicians around the table to decide on what they think is the most appropriate therapy. At the moment the experts around the table at a multidisciplinary team (MDT) meeting are being limited in the treatment options because there isn’t a commissioned service.
It would be much better to allow expert clinicians in specialist centres the ability to decide what’s the most appropriate treatment for patients. I would like to see those decisions given over to the MDT since NICE has recommended SIRT.
Now, it may be that the NHS will put some limits and caveats on which patients they think will benefit most from it. The NICE guidance is fairly broad, but there’s a danger of commissioners bringing up arbitrary barriers.
On a personal level, I would like commissioners to trust the expertise of the MDT: they have an anxiety about the volume of patients that get treated, but that’s a discussion between the manufacturers and the acute trusts that deliver this service about volume and value. If we expanded access to this treatment by increasing the volume, we should be able to drive down the cost and make it a more streamlined and efficient service and, therefore, more patients should benefit.
How are other health systems across the UK and Europe approaching SIRT, and what can these health systems learn from the NICE recommendation?
Dr Stedman: Looking at the European model, they have an independent panel of experts in health economics and public health which has reviewed the data and advocate for SIRT treatment in this patient group. That’s quite a useful benchmark for clinicians in Europe because there’s a lot of vested interest in medicine: a lot of societies and specialist medical groups will come forward with guidelines, but they’re not truly independent.
NICE evaluations are seen as a gold standard. I think it will have an impact on European guidelines going forward as NICE has so strongly come down in favour of recommending this therapy.
Scotland and Northern Ireland have limited SIRT centres, and they also have European neuroendocrine tumour centres of excellences. They do have the expertise and I’m sure they will look at the NICE guidance.
What next steps are required for SIRT to ensure more patients benefit from this treatment?
Dr Modi: The biggest unmet need is commissioning. As previously mentioned, despite the NICE recommendation for SIRT, we still find ourselves in a position unable to offer this treatment to patients in our centre.
Dr Stedman: The NHS needs to get more robust about how they commission specialist services so that all patients with complex cancers get access to specialists. Patients with neuroendocrine tumours should be discussed at a super-regional specialist neuroendocrine cancer centre.
That doesn’t mean that all their care needs to be delivered there; I think there’s nothing wrong with cancer care, surgical oncology and medical oncology being delivered locally.
But I think patients miss out by not having their case discussed by a specialist team that has knowledge and insight into all the latest therapies such as SIRT.
I think it’s such a specialised area of medicine now that small regional hospitals managing these patients without getting a specialist review are probably prejudicing some patients’ treatment.
