Interventional radiology techniques and results for the management of neuroendocrine liver metastases

Maxime Ronot and Valérie Vilgrain

Interventional radiology techniques are widely performed and useful in liver metastases from neuroendocrine tumours, but the level of scientific proof is paradoxically low, especially when considering that these techniques are used in patients with cancer, write Maxime Ronot and Valérie Vilgrain.

A vast spectrum of interventional radiology techniques is used in the management of liver metastases from neuroendocrine tumours (NET): ablation, transarterial embolization (TAE) or chemoembolization (TACE), and more recently selective internal radiation therapy (SIRT) also called radioembolization. In order to understand the role and specificities of these techniques in patients with NET liver metastases, several clinical and pathological data have to be kept in mind. First of all, primary NET tumours are commonly associated with liver metastases (71–89 % for the jejunum/ileum tumours and 54–88 % for pancreatic NET. Second, if surgery is the standard of care and the sole curative treatment, leading to five-year survival rates of 80%, it is not suitable for all patients, especially those with diffuse liver metastases. Third, NET liver metastases differ from other liver metastases. Often several tumours are found together and they are hypervascular, which makes them amenable to endovascular techniques.

Overall, liver metastases may be defined according to three different macroscopic patterns: a simple pattern corresponding to metastases confined to one liver lobe or limited to two adjacent segments; a complex pattern assessed when the metastases primarily affects one lobe but with smaller satellites contralaterally, and; a diffuse pattern corresponding to diffuse and multifocal liver metastases.

In the single pattern, the standard of care is surgical resection, if possible, but ablation plays a significant role. Among all ablation techniques, radiofrequency has been the most widely used and studied, but recent studies using microwave ablation seem to report similar results. As in other liver metastases, ablation techniques are useful in combination with liver resection, in order to expand the number of patients amenable to complete resection. This leads to overall and disease free survival rate similar to that observed in patients treated with resection alone, but with significantly higher morbidity. Aside from that, and due to the large number of lesions, ablations are also useful in tumour debulking and in controlling functional syndromes due to specific hormones with significant or complete symptom relief in the vast majority of patients. This explains why intraoperative approach is often preferred rather than percutaneous approach.

In diffuse or complex patterns, surgery and local ablative therapies are no longer indicated. The role of transarterial treatments (transarterial embolization (TAE), transarterial chemoembolization (TACE), and SIRT is crucial. The rationale for transarterial hepatic techniques is based on the tumour hypervascularisation. Intra-arterial liver-directed therapies are generally used in NET patients with liver-dominant metastatic disease who have symptoms related to hormonal excess or tumour bulk or to those who present with rapid progression of liver disease, especially in patients with refractory, unresectable, or recurrent disease. However, as opposed to systemic therapies, and despite the large number of chemoembolization or embolization studies performed in patients with liver metastases from NET, there is a lack of consensus among interventional radiologists regarding the best chemoembolic regimen, procedure endpoints, the degree of vascular stasis to be achieved, and the ideal time interval between treatment sessions. In addition, no randomised trial has been conducted or published. Therefore, the level of scientific proof on which treatment protocols can rely is rather low. Nevertheless, few important facts, consistently reported by many studies, can be established.

First of all, transarterial treatments are particularly interesting in lesions from the jejunum/ileum because the efficacy of systemic chemotherapy has not been proved in these tumours. In liver metastases, secondary to neuroendocrine tumours of the pancreas, transarterial treatments are competing with systemic therapy including targeted therapy. Second, among all non-surgical treatments, TACE and TAE lead to the highest rate of tumoural objective response. Third, most patients experience a rapid partial or complete symptoms relief, and significant decrease in tumour markers can be observed. However, the influence on overall survival is still unclear, and remains to be proven. Drug-eluting beads, recently introduced and initially considered as promising, have not shown significant increase in overall or progression free survivals, and have been associated with significantly higher morbidity than the conventional technique, particularly with regard to biliary complications. Radiologists should be aware of the few limitations of these treatments, particularly the high risk of secondary septic complications in patients with bilioenteric anastomosis.

Recently, several studies have reported the results of SIRT in patients with NET liver metastases, and have shown high objective response (60–70%), and survival rates (median >35 months). Interestingly, the toxicity profile is significantly better than that observed with TAE or TACE. Therefore, this probably indicates that SIRT is a valid alternative therapy for patients with liver NET metastases. More studies are required to better understand the role of this technique for the management of patients.

In conclusion, as these tumours largely differ from the other liver metastases (number, imaging findings, prognosis, and treatment, etc), tumour boards dedicated to neuroendocrine tumors are advisable. Interventional radiologists should also be aware of the indications and specific contraindications of liver-directed therapies in these tumours. Indeed, interventional radiology techniques are widely performed and useful in liver metastases from neuroendocrine tumours, but the level of scientific proof is paradoxically low, especially when considering that these techniques are used in patients with cancer. In oncology, no other treatment suffers from such a low level of validation and high level of variability. We need to address these issues collectively, by adopting a true oncological perspective.

Maxime Ronot is with the Radiology department, Beaujon University Hospital, Clichy, France. Valérie Vilgrain is with the Radiology department. Beaujon University Hospital, Assistance-Publique, APHP, Clichy, France. Both Ronot and Vilgrain are affiliated to the Université Paris Diderot. Vilgrain is also affiliated to the Sorbonne Paris Cité, France, and INSERM U1149 CRB3, Paris, France. The authors have reported no disclosures pertaining to this article.