Evidence for truncated somatostatin receptor 5 modulation of therapy response to somatostatin analogues in two patients with acromegaly and severe headache

Background: We aimed to characterize γ-H2AX and 53BP1 foci formation in patients receiving somatostatin receptor-targeted radioligand therapy, and explored its role for predicting treatment-related hematotoxicity, and treatment response. Methods: A prospective analysis of double-strand break (DSB) markers was performed in 21 patients with advanced gastroenteropancreatic neuroendocrine tumors. γ-H2AX and 53BP1 foci formation were evaluated in peripheral blood lymphocytes (PBLs) at baseline, +1 h and +24 h after administration of 7.4 GBq (177Lu)Lu-DOTA-TATE. Hematotoxicity was evaluated using standard hematology. Therapy response was assessed using (68Ga)Ga-DOTA-TATE PET/CT before enrollment and after 2 cycles of PRRT according to the volumetric modification of RECIST 1.1. Results: DSB marker kinetics were heterogeneous among patients. Subclinical hematotoxicity was associated with γ-H2AX and 53BP1 foci formation (e.g., change in platelet count vs change in γ-H2AX+ cells between baseline and +1 h (r = −0.6080; p = 0.0045). Patients showing early development of new metastases had less γ-H2AX (p = 0.0125) and less 53BP1 foci per cell at +1 h (p = 0.0289), and demonstrated a distinct kinetic pattern with an absence of DSB marker decrease at +24 h (γ-H2AX: p = 0.0025; 53BP1: p = 0.0008). Conclusions: Assessment of γ-H2AX and 53BP1 foci formation in PBLs of patients receiving radioligand therapy may hold promise for predicting subclinical hematotoxicity and early treatment response.

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Somatostatin receptor subtype 2-mediated uptake of radiolabelled somatostatin analogues in the human kidney

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-007-0457-7 ◽

2007 ◽

Vol 34 (11) ◽

pp. 1854-1860 ◽

Cited By ~ 19

Author(s):

Edgar J. Rolleman ◽

Peter P. M. Kooij ◽

Wouter W. de Herder ◽

Roelf Valkema ◽

Eric P. Krenning ◽

...

Keyword(s):

Somatostatin Receptor ◽

Human Kidney ◽

Somatostatin Analogues ◽

Receptor Subtype ◽

Somatostatin Receptor Subtype 2

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Expression of Somatostatin Receptor 2 in Somatotropinoma Correlated with the Short-Term Efficacy of Somatostatin Analogues

International Journal of Endocrinology ◽

10.1155/2017/9606985 ◽

2017 ◽

Vol 2017 ◽

pp. 1-7 ◽

Cited By ~ 4

Author(s):

Wenjuan Liu ◽

Lina Xie ◽

Min He ◽

Ming Shen ◽

Jingjing Zhu ◽

...

Keyword(s):

Tumor Size ◽

Tumor Volume ◽

Somatostatin Receptor ◽

Somatostatin Analogues ◽

Receptor Subtypes ◽

Short Term ◽

Pituitary Growth Hormone ◽

Term Efficacy ◽

Somatostatin Receptor Subtypes ◽

Pretreated Group

The expression of somatostatin receptor subtypes (SSTRs) in pituitary growth hormone- (GH-) secreting adenomas may predict the response to somatostatin analogues (SSA). Our aim was to evaluate the value of the immunohistochemical (IHC) scores of 2 subtypes, SSTR2 and SSTR5, in predicting the short-term efficacy of SSA therapy in patients with active acromegaly. Ninety-three newly diagnosed acromegalic patients were included in our study. These patients were categorized into either a SSA-pretreated group (SA, n=63) or a direct-surgery group (DS, n=30), depending on whether or not presurgical SSA treatment was received. IHC analysis, using a 12-grade scoring system, with rabbit monoclonal antibodies against SSTR2 and SSTR5, was performed on all adenoma tissues. The reduction of GH, IGF-1, and tumor size after treatment with SSA for 3 months was measured. Compared with that in the DS group, SSTR2 expression was lower in the SA group. Additionally, in the SA group, SSTR2 expression was positively correlated with the reduction of IGF-1 and tumor volume. However, there was no correlation between the SSTR5 score and the efficacy of SSA. In conclusion, the protein expression of SSTR2, but not of SSTR5, is a valuable indicator in predicting biochemical and tumor size response to short-term SSA treatment in acromegalic patients.

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Treatment of Advanced Hepatocellular Carcinoma with Somatostatin Analogues: A Review of the Literature

International Journal of Molecular Sciences ◽

10.3390/ijms20194811 ◽

2019 ◽

Vol 20 (19) ◽

pp. 4811

Author(s):

Hendrik Reynaert ◽

Isabelle Colle

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cancer ◽

Current Knowledge ◽

Primary Liver Cancer ◽

Somatostatin Receptor ◽

Somatostatin Receptors ◽

Somatostatin Analogues ◽

Receptor Expression ◽

Surrounding Tissue ◽

Advanced Hepatocellular Carcinoma

Hepatocellular carcinoma, one of the most dreaded complications of cirrhosis, is a frequent cancer with high mortality. Early primary liver cancer can be treated by surgery or ablation techniques, but advanced hepatocellular carcinoma remains a challenge for clinicians. Most of these patients have underlying cirrhosis, which complicates or even precludes treatment. Therefore, efficacious treatments without major side effects are welcomed. Initial results of treatment of advanced hepatocellular carcinoma with somatostatin analogues were promising, but subsequent trials have resulted in conflicting outcomes. This might be explained by different patient populations, differences in dosage and type of treatment and differences in somatostatin receptor expression in the tumor or surrounding tissue. It has been shown that the expression of somatostatin receptors in the tumor might be of importance to select patients who could benefit from treatment with somatostatin analogues. Moreover, somatostatin receptor expression in hepatocellular carcinoma has been shown to correlate with recurrence, prognosis, and survival. In this review, we will summarize the available data on treatment of primary liver cancer with somatostatin analogues and analyze the current knowledge of somatostatin receptor expression in hepatocellular carcinoma and its possible clinical impact.

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Inter and intra-tumor somatostatin receptor 2 heterogeneity influences peptide receptor radionuclide therapy response

Theranostics ◽

10.7150/thno.51215 ◽

2021 ◽

Vol 11 (2) ◽

pp. 491-505

Author(s):

Danny Feijtel ◽

Gabriela N. Doeswijk ◽

Nicole S. Verkaik ◽

Joost C. Haeck ◽

Daniela Chicco ◽

...

Keyword(s):

Radionuclide Therapy ◽

Somatostatin Receptor ◽

Therapy Response ◽

Peptide Receptor Radionuclide Therapy ◽

Peptide Receptor

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P09.05 177Lu-DOTATATE therapy in progressive meningioma

Neuro-Oncology ◽

10.1093/neuonc/noz126.137 ◽

2019 ◽

Vol 21 (Supplement_3) ◽

pp. iii39-iii39

Author(s):

M Müther ◽

W Roll ◽

B Zinnhardt ◽

M Schäfers ◽

K Rahbar ◽

...

Keyword(s):

Stable Disease ◽

Treatment Options ◽

Somatostatin Receptor ◽

Therapy Response ◽

Response To Therapy ◽

Current Evidence ◽

Promising Alternative ◽

Multifocal Disease ◽

Post Therapy

Abstract BACKGROUND Progressive meningioma is a challenging condition with a decreasing number of treatment options over the course of disease. Neurovascular involvement and multifocal disease often complicate surgical management. In addition, repeated radiotherapy carriers a risk of side effects. In somatostatin receptor expressing meningioma, peptide receptor radiotherapy (PPRT) with 177Lu-DOTATATE poses a promising alternative. However, current evidence is scarce. Hereby we present our single center experience of (PPRT) with 177Lu-DOTATATE in progressive meningioma. METHODS Eight patients (median age: 71 years; range 56–77) with progressive meningioma underwent PRRT using 177Lu-DOTATATE were included in this retrospective analysis. Response to therapy was assessed by interim and post-therapy 68Ga-DOTATATE-PET-CT and MRI. 177Lu-DOTATATE scintigraphies 48h p.i. were evaluated according to Krenning scale. Additionally, clinical outcome and follow up imaging were analyzed for progression free interval times. RESULTS Eight patients were included: Six patients with grade II and two patients with grade I meningiomas, according to the 2016 WHO classification. Six of eight patients harbored multifocal disease. One patients suffered systemic metastatic disease. Patients received a median of three cycles (range: 1 - 5) of PRRT with 177Lu-DOTATATE (mean injected dose 7.1 GBq) between 1/2015 and 1/2019. Tumor uptake in 48h p.i. 177Lu-Scintigraphies was heterogeneous (Krenning scale; median: 3; range: 1–4). Post-therapy imaging scheduled eight weeks after completion of therapy showed progressive disease in five patients, three patients had stable disease. Median follow-up post therapy response evaluation was 24 months in patients with stable disease. Median time to progression was 10 months. CONCLUSION In this cohort of eight progressive meningioma patients 177Lu-DOTATATE therapy showed heterogeneous efficacy.

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[111In-DTPA-D-Phe1]Octreotide scintigraphy in patients with carcinoid tumours: the predictive value for somatostatin analogue treatment

Acta Endocrinologica ◽

10.1530/eje.0.1310577 ◽

1994 ◽

Vol 131 (6) ◽

pp. 577-581 ◽

Cited By ~ 73

Author(s):

Eva Tiensuu Janson ◽

Jan-Erik Westlin ◽

Barbro Eriksson ◽

Håkan Ahlström ◽

Sten Nilsson ◽

...

Keyword(s):

Predictive Value ◽

Somatostatin Receptor ◽

Somatostatin Receptors ◽

Somatostatin Analogues ◽

University Hospital ◽

Somatostatin Analogue ◽

Carcinoid Tumours ◽

Malignant Carcinoid ◽

Receptor Scintigraphy ◽

Octreotide Scintigraphy

Tiensuu Janson E, Westlin J-E, Eriksson B, Ahlström H, Nilsson S, Öberg K. [111In-DTPA-D-Phe1]Octrotide scintigraphy in patients with carcinoid tumours: the predictive value for somatostatin analogue treatment. Eur J Endocrinol 1994:131:577–81. ISSN 0804–4643 This study was performed to evaluate whether the presence or absence of somatostatin receptors in malignant carcinoid tumours detected by [111In-DTPA-D-Phe1]octreotide scintigraphy can be used to predict response to somatostatin analogue treatment. Thirty patients were investigated, 28 with midgut carcinoid tumours and two with foregut carcinoid tumours. Twenty-seven patients showed pathological uptake in tumour lesions at scintigraphy: of these, 22 responded to somatostatin analogue treatment using octreotide, somatuline or octastatin, while five patients failed to respond. None of the three patients displaying negative scintigraphic investigations responded to treatment with somatostatin analogues. These results show a good correlation between the somatostatin receptor status and the patients' ability to respond to somatostatin analogue treatment (p = 0.014). We conclude that somatostatin receptor scintigraphy using [111In-DTPA-D-Phe1]octreotide can be used to select patients with malignant carcinoid tumours suitable for somatostatin analogue treatment and exclude those that will not benefit from such medication. Eva Tiensuu Janson, Dept of Internal Medicine, University Hospital, S-751 85 Uppsala, Sweden

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