Dieter Hörsch1, Samer Ezziddin2, Alexander Haug3, Klaus Friedrich Gratz4, Simone Dunkelmann5, Matthias Miederer6, Mathias Schreckenberger6, Bernd Joachim Krause5, Frank M Bengel4, Peter Bartenstein3, Hans-Jürgen Biersack7, Gabriele Pöpperl8, R P Baum9. 1. Department of Gastroenterology/Endocrinology, Center for Neuroendocrine Tumors Bad Berka - ENETS Center of Excellence, Zentralklinik Bad Berka GmbH, Bad Berka, Germany. Electronic address: dieter.hoersch@zentralklinik.de. 2. Klinik für Nuklearmedizin, Universitätsklinikum des Saarlandes, Kirrberger Straße, Gebäude 50, D-66421 Homburg, Germany. 3. Klinik und Poliklinik für Nuklearmedizin, Ludwig Maximilian Universität München, Ziemssenstraße 1, 80336 München, Germany. 4. Klinik für Nuklearmedizin, Medizinische Hochschule Hannover, Carl-Neuberg-Straße 1, 30625 Hannover, Germany. 5. Klinik und Poliklinik für Nuklearmedizin, Universitätsklinikum Rostock, Gertrudenplatz 1, D-18057 Rostock, Germany. 6. Klinik und Poliklinik für Nuklearmedizin, Universitätsmedizin Mainz, Langenbeckstraße 1, 55131 Mainz, Germany. 7. Klinik und Poliklinik für Nuklearmedizin am Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany. 8. Klinik für Nuklearmedizin, Katharinenhospital Stuttgart, Kriegsbergstraße 60, 70174 Stuttgart, Germany. 9. Clinic of Molecular Radiotherapy, Center for Neuroendocrine Tumors Bad Berka - ENETS Center of Excellence, Zentralklinik Bad Berka GmbH, Bad Berka, Germany.
Abstract
BACKGROUND: Monocentric and retrospective studies indicate effectiveness of peptide receptor radionuclide therapy targeting somatostatin receptors of neuroendocrine neoplasms. We assessed overall and progression-free survival and adverse events of peptide receptor radionuclide therapy by a multi-institutional, board certified registry with prospective follow-up in five centres in Germany. METHODS: A total of 450 patients were included and followed for a mean of 24.4 months. Most patients had progressive low- or intermediate grade neuroendocrine neoplasms and 73% were pretreated with at least one therapy. Primary neuroendocrine neoplasms were mainly derived of pancreas (38%), small bowel (30%), unknown primary (19%) or bronchial system (4%). Patients were treated with Lutetium-177 in 54%, with Yttrium-90 in 17% and with both radionuclides in 29%. Overall and progression-free survival was determined with Kaplan-Meier curves and uni-variate log rank test Cox models. FINDINGS: Median overall survival of all patients was 59 (95% confidence interval [CI] 49-68.9) months. Overall survival was significantly inferior in the patients treated with Yttrium-90 solely (hazard ratio, 3.22; 95% CI, 1.83-5.64) compared to any peptide receptor radionuclide therapy with Lutetium-177. Grade II (hazard ratio, 2.06; 95% CI, 0.79-5.32) and grade III (hazard ratio, 4.22; 95% CI, 1.41-12.06) neuroendocrine neoplasms had significantly worse overall survival than grade I neuroendocrine neoplasms. Patients with small neuroendocrine neoplasms of small bowel had significantly increased survival (hazard ratio, 0.39; 95% CI, 0.18-0.87) compared to neuroendocrine neoplasms of other locations. Median progression-free survival was 41 (35.9-46.1) months and significantly inferior in patients treated with Yttrium solely (hazard ratio, 2.7; 95% CI, 1.71-4.55). Complete remission was observed in 5.6% of patients, 22.4% had a partial remission, 47.3% were stable and 4% were progressive as best response. Adverse events of bone marrow and kidney function higher than grade III occurred in 0.2-1.5% of patients. INTERPRETATION: These results indicate that peptide receptor radionuclide therapy is a highly effective therapy for patients with low to intermediate grade neuroendocrine neoplasms with minor adverse events.
BACKGROUND: Monocentric and retrospective studies indicate effectiveness of peptide receptor radionuclide therapy targeting somatostatin receptors of neuroendocrine neoplasms. We assessed overall and progression-free survival and adverse events of peptide receptor radionuclide therapy by a multi-institutional, board certified registry with prospective follow-up in five centres in Germany. METHODS: A total of 450 patients were included and followed for a mean of 24.4 months. Most patients had progressive low- or intermediate grade neuroendocrine neoplasms and 73% were pretreated with at least one therapy. Primary neuroendocrine neoplasms were mainly derived of pancreas (38%), small bowel (30%), unknown primary (19%) or bronchial system (4%). Patients were treated with Lutetium-177 in 54%, with Yttrium-90 in 17% and with both radionuclides in 29%. Overall and progression-free survival was determined with Kaplan-Meier curves and uni-variate log rank test Cox models. FINDINGS: Median overall survival of all patients was 59 (95% confidence interval [CI] 49-68.9) months. Overall survival was significantly inferior in the patients treated with Yttrium-90 solely (hazard ratio, 3.22; 95% CI, 1.83-5.64) compared to any peptide receptor radionuclide therapy with Lutetium-177. Grade II (hazard ratio, 2.06; 95% CI, 0.79-5.32) and grade III (hazard ratio, 4.22; 95% CI, 1.41-12.06) neuroendocrine neoplasms had significantly worse overall survival than grade I neuroendocrine neoplasms. Patients with small neuroendocrine neoplasms of small bowel had significantly increased survival (hazard ratio, 0.39; 95% CI, 0.18-0.87) compared to neuroendocrine neoplasms of other locations. Median progression-free survival was 41 (35.9-46.1) months and significantly inferior in patients treated with Yttrium solely (hazard ratio, 2.7; 95% CI, 1.71-4.55). Complete remission was observed in 5.6% of patients, 22.4% had a partial remission, 47.3% were stable and 4% were progressive as best response. Adverse events of bone marrow and kidney function higher than grade III occurred in 0.2-1.5% of patients. INTERPRETATION: These results indicate that peptide receptor radionuclide therapy is a highly effective therapy for patients with low to intermediate grade neuroendocrine neoplasms with minor adverse events.
Authors: Jonathan Strosberg; Ghassan El-Haddad; Edward Wolin; Andrew Hendifar; James Yao; Beth Chasen; Erik Mittra; Pamela L Kunz; Matthew H Kulke; Heather Jacene; David Bushnell; Thomas M O'Dorisio; Richard P Baum; Harshad R Kulkarni; Martyn Caplin; Rachida Lebtahi; Timothy Hobday; Ebrahim Delpassand; Eric Van Cutsem; Al Benson; Rajaventhan Srirajaskanthan; Marianne Pavel; Jaime Mora; Jordan Berlin; Enrique Grande; Nicholas Reed; Ettore Seregni; Kjell Öberg; Maribel Lopera Sierra; Paola Santoro; Thomas Thevenet; Jack L Erion; Philippe Ruszniewski; Dik Kwekkeboom; Eric Krenning Journal: N Engl J Med Date: 2017-01-12 Impact factor: 91.245
Authors: Giuseppe Lo Russo; Sara Pusceddu; Natalie Prinzi; Martina Imbimbo; Claudia Proto; Diego Signorelli; Milena Vitali; Monica Ganzinelli; Marco Maccauro; Roberto Buzzoni; Ettore Seregni; Filippo de Braud; Marina Chiara Garassino Journal: Tumour Biol Date: 2016-07-27
Authors: Thomas A Hope; Lisa Bodei; Jennifer A Chan; Ghassan El-Haddad; Nicholas Fidelman; Pamela L Kunz; Josh Mailman; Yusuf Menda; David C Metz; Erik S Mittra; Daniel A Pryma; Diane L Reidy-Lagunes; Simron Singh; Jonathan R Strosberg Journal: J Nucl Med Date: 2020-02 Impact factor: 11.082