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Ronny Allan
There can be no doubt that the discovery of somatostatin receptors as a means to treat Neuroendocrine Tumours has been a huge success. Additionally, scientists looked at a theranostic angle and provided somatostatin receptor based imaging for diagnosis and surveillance purposes.
Many patients are prescribed somatostatin anlaogues shortly after diagnosis and this has led to a reduction in the morbidity that comes from active carcinoid syndrome and has reduced the incidence of carcinoid heart disease.
More recently, the introduction of somatostatin receptor based PETs, taking over from the elderly Octreotide scans, has meant speedier and higher quality identification of NETs leading to more focussed treatment. Moreover, the use of somatostatin receptor based therapy via radioligands (e.g. Ga68 PET/Cu64 PET) is nothing short of a theraputic revolution now being introduced into other cancers using targeted entry points specifric to those cancers. NETs were at the forefront of this revolution for many years. Add in the use of Alpha-emitter radioligands and the excitement levels increase, albeit this is currently an investigatory option still in clinical trials.
But one issue still remains unclear. When to deploy this therapy approach? i.e. Sequencing of treatment for somatostatin receptor positive NETs.
The view of experts
If you put lots of experts in a room, expect lots of different opinions. But what matters is they eventually come to a consensus, thus why you will see guidelines described using words such as “the consensus view” or “consensus guidelines” etc.
I came across this review paper written by some big names in the NET world in US and was published in January 2024. It is focussed on the sequencing of treatment using somatostatin based therapies, i.e. using somatostatin analogues (SSA) and Peptide Receptor Radionuclide Therapy (PRRT). It also touches on what remains a key question in management of patients with gastroenteropancreatic and lung NETs is the sequencing of 177Lu-DOTATATE in relation to other systemic treatments such as everolimus, chemotherapy and liver-directed therapies. This question is particularly complicated given the heterogeneity of NETs and the near absence of randomised trials comparing active treatment options. This state-of-the-art review examines the evidence supporting use of somatostatin-receptor–targeted treatments within the larger landscape of NET therapy and offers insights regarding optimal patient selection, assessment of benefit versus risk, and treatment sequencing.
The timing of this paper is interesting because it almost coincides with the big announcement from Novartis which suggests using PRRT as a first line treatment alongside SSA using evidence from the clinical trial NETTER-2. You would be excused for pointing out that NETTER-1 was mainly midgut grade 1 well differentiated NET patients whereas NETTER-2 was exclusivley grade 2 and 3 well differentiated NETs and included pancreatic NETs, hinting that comparing the two trials is not the best comparison. Or to quote one NET specialist online, “As many of my colleagues have observed, NETTER-1 & 2 enrolled different NET populations (former midgut only, the latter midgut & PNET; former 66% grade 1/34% grade 2; the latter all grade 2/3)”.
I leave you to read this excellent review paper (it has many mini-primers which alone are useful) and if you’re not temtped by my intro, I’ve also listed the section headlines below.
Sequencing of Somatostatin-Receptor–Based Therapies in Neuroendocrine Tumor Patients
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