Elettra Merola1,2,3, Anja Rinke4, Stefano Partelli5, Thomas M Gress4, Valentina Andreasi5, Attila Kollár6, Aurel Perren7, Emanuel Christ8, Francesco Panzuto9, Andreas Pascher10,11, Henning Jann12, Ruza Arsenic13, Birgit Cremer14, Daniel Kaemmerer15, Patrizia Kump16, Rainer W Lipp17, Abbas Agaimy18, Bertram Wiedenmann12, Massimo Falconi5, Marianne E Pavel19,12. 1. Department of Gastroenterology, Azienda Provinciale per i Servizi Sanitari (APSS), Trento, Italy. elettra.merola@gmail.com. 2. Department of Medicine 1, Division of Endocrinology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany. elettra.merola@gmail.com. 3. Digestive and Liver Diseases Unit, Sant'Andrea Hospital, Rome, Italy. elettra.merola@gmail.com. 4. Department of Gastroenterology, Endocrinology, Metabolism and Infectiology, University Hospital Marburg and Philipps University Marburg, Marburg, Germany. 5. Pancreatic Surgery Unit, Vita-Salute University, San Raffaele Hospital IRCCS, Milan, Italy. 6. Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. 7. Institute of Pathology, University of Bern, Bern, Switzerland. 8. Department of Endocrinology, Diabetology and Metabolism, Center of Endocrine and Neuroendocrine Tumors, University Hospital of Basel, Basel, Switzerland. 9. Digestive and Liver Diseases Unit, Sant'Andrea Hospital, Rome, Italy. 10. Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Münster, Münster, Germany. 11. Department of Surgery, Charité Universitätsmedizin, Berlin, Germany. 12. Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum and Campus Mitte, Charité Universitätsmedizin, Berlin, Germany. 13. Department of Pathology, Campus Mitte, Charité Universitätsmedizin, Berlin, Germany. 14. Department of Internal Medicine I, Center for Integrated Oncology Cologne/Bonn, University Hospital of Cologne, Cologne, Germany. 15. Department of General and Visceral Surgery, Zentralklinik Bad Berka, Bad Berka, Germany. 16. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University, Graz, Austria. 17. Division of Oncology, Department of Internal Medicine, Medical University, Graz, Austria. 18. Institute of Pathology, Friedrich-Alexander University Erlangen-Nuremberg, University Hospital, Erlangen, Germany. 19. Department of Medicine 1, Division of Endocrinology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
Abstract
BACKGROUND: While platinum-based chemotherapy represents the standard treatment for advanced grade 3 (G3) neuroendocrine neoplasms (NENs) according to the European Neuroendocrine Tumor Society guidelines, the role of radical-intended surgery in these patients, as well as the use of adjuvant chemotherapy, are still controversial. The aim of the present work is to describe, in a retrospective series of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) G3, the overall survival (OS) rate and risk factors for death after radical surgery. Secondary aims are the description of median recurrence-free survival (RFS) and of the role of adjuvant chemotherapy. PATIENTS AND METHODS: Multicenter analysis of a series of stage I-III GEP-NEN G3 patients receiving radical surgery (R0/R1) with/without adjuvant chemotherapy was performed. RESULTS: Sixty patients from eight neuroendocrine tumor (NET) referral centers, with median follow-up of 23 months (5-187 months) were evaluated. While 28.6% of cases had NET G3, 71.4% had neuroendocrine carcinoma G3 (NEC G3). The 2-year OS rate after radical surgery was 64.5%, with a statistically significant difference in terms of Ki67 threshold (cut-off 55%, P = 0.03) and tumor differentiation (NEC G3 vs. NET G3, P = 0.03). Median RFS after radical surgery was 14 months, and 2-year RFS rate was 44.9%. Use of adjuvant chemotherapy provided no benefit in terms of either OS or RFS in this series. CONCLUSIONS: Surgery with radical intent might represent a valid option for GEP-NEN G3 patients with locoregional disease, especially with Ki67 value ≤ 55%.
BACKGROUND: While platinum-based chemotherapy represents the standard treatment for advanced grade 3 (G3) neuroendocrine neoplasms (NENs) according to the European Neuroendocrine Tumor Society guidelines, the role of radical-intended surgery in these patients, as well as the use of adjuvant chemotherapy, are still controversial. The aim of the present work is to describe, in a retrospective series of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) G3, the overall survival (OS) rate and risk factors for death after radical surgery. Secondary aims are the description of median recurrence-free survival (RFS) and of the role of adjuvant chemotherapy. PATIENTS AND METHODS: Multicenter analysis of a series of stage I-III GEP-NEN G3 patients receiving radical surgery (R0/R1) with/without adjuvant chemotherapy was performed. RESULTS: Sixty patients from eight neuroendocrine tumor (NET) referral centers, with median follow-up of 23 months (5-187 months) were evaluated. While 28.6% of cases had NET G3, 71.4% had neuroendocrine carcinoma G3 (NEC G3). The 2-year OS rate after radical surgery was 64.5%, with a statistically significant difference in terms of Ki67 threshold (cut-off 55%, P = 0.03) and tumor differentiation (NEC G3 vs. NET G3, P = 0.03). Median RFS after radical surgery was 14 months, and 2-year RFS rate was 44.9%. Use of adjuvant chemotherapy provided no benefit in terms of either OS or RFS in this series. CONCLUSIONS: Surgery with radical intent might represent a valid option for GEP-NEN G3 patients with locoregional disease, especially with Ki67 value ≤ 55%.
Authors: Elettra Merola; Andrea Michielan; Umberto Rozzanigo; Marco Erini; Sandro Sferrazza; Stefano Marcucci; Chiara Sartori; Chiara Trentin; Giovanni de Pretis; Franca Chierichetti Journal: World J Gastrointest Surg Date: 2022-02-27