Somatostatin receptor scintigraphy in patients with metastatic uveal melanoma

Abstract

As uveal melanoma originates in the neural crest, we aimed to explore whether somatostatin receptor (SSTR) expression is present and plays any role in these patients. Heavily pretreated metastatic uveal melanoma patients were tested with somatostatin receptor scintigraphy (SRS). Planar images of the whole body complemented by single-photon emission computed tomography on suspected sites were acquired between 4 and 24 h after an intravenous administration of 185-222 MBq (5-6 mCi) of indium-octeotride. SSTR expression in metastatic tissues was confirmed by immunohistochemistry. In seven patients, sandostatin LAR was used with therapeutic intention. Thirty white patients were tested. All had extensive metastatic disease and the median number of previous treatments was three. SRS was found to be positive in 14 (46%) of the patients, but was not related to sex, type of previous treatments, tumor site, or histological type. In 10 patients, sufficient tumor specimens were available to perform immunohistochemical staining for SSTR. All cases with positive SSTR-2A staining were also positive by SRS. Two of the seven patients who received sandostatin LAR died within a month after receiving the first dose, whereas another two (28.5%) had stable disease for more than 5 months. The median time to progression after starting sandostatin was 2.1 months (range: 0.2-5.5 months). Approximately 50% of the uveal melanoma patients with extensive metastatic disease were positive for SSR, which was consistent with immunohistochemical staining for SSTR-2A. Therapeutic approaches targeting SSTR might be beneficial in patients with metastatic uveal melanoma.

A phase 2 trial of everolimus and pasireotide long-acting release in patients with metastatic uveal melanoma

“…This rate is somewhat higher than the 44% rate described by Valsecchi et al despite using the same cutoff for positivity of two-fold increase above background [14]. Our study is the first, to our knowledge, to describe intrapatient heterogeneity in In 111 octreotide avidity between multiple tumors and suggests there is intrapatient heterogeneity in tumor expression of SSTR-2A.…”

“…This suggests that nuclear imaging with an octreotide analog such as Indium-111 octreotide (Octreoscan) that binds to SSTR-2A may be used to select for patients with advanced uveal melanoma that may be more likely to respond to IGF1R pathway inhibition. A recent report by Valsecchi and colleagues [14] demonstrated In 111 octreotide avidity in 14/30 patients (44%) with advanced uveal melanoma. In their cohort, 7 patients with positive In 111 octreotide scans received Sandostatin long-acting release (LAR) outside of a formal clinical trial, and two patients had clinically stable disease for over 5 months [14].…”

“…A recent report by Valsecchi and colleagues [14] demonstrated In 111 octreotide avidity in 14/30 patients (44%) with advanced uveal melanoma. In their cohort, 7 patients with positive In 111 octreotide scans received Sandostatin long-acting release (LAR) outside of a formal clinical trial, and two patients had clinically stable disease for over 5 months [14]. …”

International Union of Basic and Clinical Pharmacology. CV. Somatostatin Receptors: Structure, Function, Ligands, and New Nomenclature

“…Furthermore, a moderate to strong SST 2 expression was observed in 13% of prostate cancers in general and in 50% of prostate cancers with endocrine differentiation ( Matei et al, 2012 ; Hennigs et al, 2014 ). SST 2 was detected in 59% of Merkel cell carcinomas ( Gardair et al, 2015 ) and in melanomas ( Ardjomand et al, 2003 ; Valsecchi et al, 2013 ). Finally, SST 2 expression in normal exocrine pancreatic tissue is progressively lost during pancreatic ductal adenocarcinoma progression ( Buscail et al, 1996 ; Laklai et al, 2009 ), which participates in tumor aggression, as demonstrated in mouse models of pancreatic cancer combined with SST 2 KO mice ( Chalabi-Dchar et al, 2015 ).…”

Somatostatin Receptors 3, 4 and 5 Play Important Roles in Gallbladder Cancer

“…An amount of research has shown that SSTR expression has an intimately relationship with multiple tumor diseases including breast cancer, pulmonary neuroendocrine tumor and uveal melanoma (Seitz et al, 2013;Treglia et al, 2013;Valsecchi et al, 2013). However, how SSTR participates in gallbladder cancer focus less attention.…”