The prognostic and predictive value of sstr2-immunohistochemistry and sstr2-targeted imaging in neuroendocrine tumors

Philippe Brunner; Ann-Catherine Jörg; Katharina Glatz; Lukas Bubendorf; Piotr Radojewski; Maria Umlauft; Nicolas Marincek; Petar-Marko Spanjol; Thomas Krause; Rebecca A Dumont; Helmut R Maecke; Jan Müller-Brand; Matthias Briel; Anja Schmitt; Aurel Perren; Martin A Walter

doi:10.1007/s00259-016-3486-2

The prognostic and predictive value of sstr₂-immunohistochemistry and sstr₂-targeted imaging in neuroendocrine tumors

Eur J Nucl Med Mol Imaging. 2017 Mar;44(3):468-475. doi: 10.1007/s00259-016-3486-2. Epub 2016 Aug 18.

Authors

Philippe Brunner^{1

2}, Ann-Catherine Jörg², Katharina Glatz¹, Lukas Bubendorf¹, Piotr Radojewski³, Maria Umlauft³, Nicolas Marincek^{2

3}, Petar-Marko Spanjol³, Thomas Krause³, Rebecca A Dumont³, Helmut R Maecke⁴, Jan Müller-Brand², Matthias Briel^{5

6}, Anja Schmitt⁷, Aurel Perren⁷, Martin A Walter⁸

Affiliations

¹ Institute of Pathology, University Hospital Basel, CH, Basel, Switzerland.
² Institute of Nuclear Medicine, University Hospital Basel, CH, Basel, Switzerland.
³ Institute of Nuclear Medicine, University Hospital Bern, CH, 3010, Bern, Switzerland.
⁴ Division of Radiological Chemistry, University Hospital Basel, Basel, Switzerland.
⁵ Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, CH, Switzerland.
⁶ Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada.
⁷ Institute of Pathology, University Bern, Bern, Switzerland.
⁸ Institute of Nuclear Medicine, University Hospital Bern, CH, 3010, Bern, Switzerland. m.a.walter@gmx.net.

PMID: 27539020
DOI: 10.1007/s00259-016-3486-2

Abstract

Purpose: Our aim was to assess the prognostic and predictive value of somatostatin receptor 2 (sstr₂) in neuroendocrine tumors (NETs).

Methods: We established a tissue microarray and imaging database from NET patients that received sstr₂-targeted radiopeptide therapy with yttrium-90-DOTATOC, lutetium-177-DOTATOC or alternative treatment. We used univariate and multivariate analyses to identify prognostic and predictive markers for overall survival, including sstr₂-imaging and sstr₂-immunohistochemistry.

Results: We included a total of 279 patients. In these patients, sstr₂-immunohistochemistry was an independent prognostic marker for overall survival (HR: 0.82, 95 % CI: 0.67 - 0.99, n = 279, p = 0.037). In DOTATOC patients, sstr₂-expression on immunohistochemistry correlated with tumor uptake on sstr₂-imaging (n = 170, p < 0.001); however, sstr₂-imaging showed a higher prognostic accuracy (positive predictive value: +27 %, 95 % CI: 3 - 56 %, p = 0.025). Sstr₂-expression did not predict a benefit of DOTATOC over alternative treatment (p = 0.93).

Conclusions: Our results suggest sstr₂ as an independent prognostic marker in NETs. Sstr₂-immunohistochemistry correlates with sstr₂-imaging; however, sstr₂-imaging is more accurate for determining the individual prognosis.

Keywords: Individualized therapy; Metabolic therapy; PRRT; Tailored therapy; Targeted therapy.

Publication types

Controlled Clinical Trial

MeSH terms

Adolescent
Adult
Aged
Aged, 80 and over
Female
Humans
Male
Middle Aged
Neuroendocrine Tumors / diagnostic imaging*
Neuroendocrine Tumors / metabolism
Octreotide / adverse effects
Octreotide / analogs & derivatives*
Pancreatic Neoplasms / diagnostic imaging*
Pancreatic Neoplasms / metabolism
Predictive Value of Tests
Radiopharmaceuticals / adverse effects*
Receptors, Somatostatin / metabolism

Substances

177Lu-octreotide, DOTA(0)-Tyr(3)-
Radiopharmaceuticals
Receptors, Somatostatin
SSTR2 protein, human
90Y-octreotide, DOTA-Tyr(3)-
Octreotide