J Schumacher1, P Malfertheiner2,3, M Venerito4,5, T Stolze2, S Franke6, J Haybaeck6,7,8, M Moehler9, P P Grimminger10, H Lang10, W Roth11, I Gockel12, N Kreuser12, H Bläker13, C Wittekind13, F Lordick14, M Vieth15, L Veits15, O Waidmann16,17, P Lingohr18, U Peitz19, C Schildberg20, M Kruschewski21, N Vassos22, E Goni3, C J Bruns23, K Ridwelski24,25, S Wolff26, H Lippert25,26. 1. Human Genetics Center, Philipps University of Marburg, Marburg, Germany. 2. Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital Magdeburg, Magdeburg, Germany. 3. Department of Medicine II, University Hospital, LMU Munich, Munich, Germany. 4. Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital Magdeburg, Magdeburg, Germany. m.venerito@med.ovgu.de. 5. Department of Gastroenterology, Hepatology and Infectious Diseases, Medizinische Fakultät der Otto-Von-Guericke-Universität, Leipziger Straße 66, 39120, Magdeburg, Germany. m.venerito@med.ovgu.de. 6. Institute of Pathology, Otto-von-Guericke University Hospital Magdeburg, Magdeburg, Germany. 7. Institute of Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck, Innsbruck, Austria. 8. Diagnostic and Research Center for Molecular BioMedicine, Institute of Pathology, Medical University Graz, Graz, Austria. 9. Department of Internal Medicine I, Johannes Gutenberg-University of Mainz, Mainz, Germany. 10. Department of General, Visceral and Transplant Surgery, Johannes Gutenberg-University of Mainz, Mainz, Germany. 11. Institute of Pathology, University Hospital Mainz, Mainz, Germany. 12. Department of Medicine II and University Cancer Center Leipzig (UCCL), Leipzig University Medical Center, Leipzig, Germany. 13. Institute of Pathology, University Hospital Leipzig, Leipzig, Germany. 14. University Cancer Center Leipzig, University Hospital Leipzig, Leipzig, Germany. 15. Institute of Pathology, Friedrich-Alexander University Erlangen-Nuremberg, Klinikum Bayreuth, Bayreuth, Germany. 16. Department of Internal Medicine 1, Main Area Gastroenterology and Hepatology, University Hospital Frankfurt, Frankfurt am Main, Germany. 17. University Cancer Center, University Hospital Frankfurt, Frankfurt am Main, Germany. 18. Department of General, Visceral, Thoracic and Vascular Surgery, University Hospital Bonn, Bonn, Germany. 19. Department of Gastroenterology, Raphaelshospital, Münster, Germany. 20. Department of General and Visceral Surgery, Brandenburg, University Hospital of Visceral Surgery, Brandenburg, Germany. 21. Department of General and Visceral Surgery, Hospital Frankfurt (Oder), Frankfurt (Oder), Germany. 22. Division of Surgical Oncology and Thoracic Surgery, Department of Surgery, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany. 23. Department of General, Tumor and Transplantation Surgery, University Hospital Cologne, Köln, Germany. 24. Department of General and Visceral Surgery, Municipal Hospital, Magdeburg, Germany. 25. AN-Institute of Quality Assurance in Operative Medicine, Otto-von-Guericke University Hospital, Magdeburg, Germany. 26. Department of General, Visceral, Vascular and Transplantation Surgery, Otto-von-Guericke University Hospital, Magdeburg, Germany.
Abstract
PURPOSE: In a post hoc analysis of the MAGIC trial, patients with curatively resected gastric cancer (GC) and mismatch repair (MMR) deficiency (MMRd) had better median overall survival (OS) when treated with surgery alone but worse median OS when treated with additional chemotherapy. Further data are required to corroborate these findings. METHODS: Between April 2013 and December 2018, 458 patients with curatively resected GC, including cancers of the esophagogastric junction Siewert type II and III, were identified in the German centers of the staR consortium. Tumor sections were assessed for expression of MLH1, MSH2, MSH6 and PMS2 by immunohistochemistry. The association between MMR status and survival was assessed. Similar studies published up to January 2021 were then identified in a MEDLINE search for a meta-analysis. RESULTS: MMR-status and survival data were available for 223 patients (median age 66 years, 62.8% male), 23 patients were MMRd (10.3%). After matching for baseline clinical characteristics, median OS was not reached in any subgroup. Compared to perioperative chemotherapy, patients receiving surgery alone with MMRd and MMRp had a HR of 0.67 (95% CI 0.13-3.37, P = 0.63) and 1.44 (95% CI 0.66-3.13, P = 0.36), respectively. The meta-analysis included pooled data from 385 patients. Compared to perioperative chemotherapy, patients receiving surgery alone with MMRd had an improved OS with a HR of 0.36 (95% CI 0.14-0.91, P = 0.03), whereas those with MMRp had a HR of 1.18 (95% CI 0.89-1.58, P = 0.26). CONCLUSION: Our data support a positive prognostic effect for MMRd in GC patients treated with surgery only and a differentially negative prognostic effect in patients treated with perioperative chemotherapy. MMR status determined by preoperative biopsies may be used as a predictive biomarker to select patients for perioperative chemotherapy in curatively resectable GC.
PURPOSE: In a post hoc analysis of the MAGIC trial, patients with curatively resected gastric cancer (GC) and mismatch repair (MMR) deficiency (MMRd) had better median overall survival (OS) when treated with surgery alone but worse median OS when treated with additional chemotherapy. Further data are required to corroborate these findings. METHODS: Between April 2013 and December 2018, 458 patients with curatively resected GC, including cancers of the esophagogastric junction Siewert type II and III, were identified in the German centers of the staR consortium. Tumor sections were assessed for expression of MLH1, MSH2, MSH6 and PMS2 by immunohistochemistry. The association between MMR status and survival was assessed. Similar studies published up to January 2021 were then identified in a MEDLINE search for a meta-analysis. RESULTS: MMR-status and survival data were available for 223 patients (median age 66 years, 62.8% male), 23 patients were MMRd (10.3%). After matching for baseline clinical characteristics, median OS was not reached in any subgroup. Compared to perioperative chemotherapy, patients receiving surgery alone with MMRd and MMRp had a HR of 0.67 (95% CI 0.13-3.37, P = 0.63) and 1.44 (95% CI 0.66-3.13, P = 0.36), respectively. The meta-analysis included pooled data from 385 patients. Compared to perioperative chemotherapy, patients receiving surgery alone with MMRd had an improved OS with a HR of 0.36 (95% CI 0.14-0.91, P = 0.03), whereas those with MMRp had a HR of 1.18 (95% CI 0.89-1.58, P = 0.26). CONCLUSION: Our data support a positive prognostic effect for MMRd in GC patients treated with surgery only and a differentially negative prognostic effect in patients treated with perioperative chemotherapy. MMR status determined by preoperative biopsies may be used as a predictive biomarker to select patients for perioperative chemotherapy in curatively resectable GC.
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