Philippe Brunner1,2, Ann-Catherine Jörg2, Katharina Glatz1, Lukas Bubendorf1, Piotr Radojewski3, Maria Umlauft3, Nicolas Marincek2,3, Petar-Marko Spanjol3, Thomas Krause3, Rebecca A Dumont3, Helmut R Maecke4, Jan Müller-Brand2, Matthias Briel5,6, Anja Schmitt7, Aurel Perren7, Martin A Walter8. 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.
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.
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 DOTATOCpatients, 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.
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