Mismatch repair deficiency, chemotherapy and survival for resectable gastric cancer: an observational study from the German staR cohort and a meta-analysis

被引：9

作者：

Stolze, T. ^{[1
]}

Franke, S. ^{[2
]}

Haybaeck, J. ^{[2
,3
,4
]}

Moehler, M. ^{[5
]}

Grimminger, P. P. ^{[6
]}

Lang, H. ^{[6
]}

Roth, W. ^{[7
]}

Gockel, I ^{[8
,9
]}

Kreuser, N. ^{[8
,9
]}

Blaker, H. ^{[10
]}

Wittekind, C. ^{[10
]}

Lordick, F. ^{[11
]}

Vieth, M. ^{[12
]}

Veits, L. ^{[12
]}

Waidmann, O. ^{[13
,14
]}

Lingohr, P. ^{[15
]}

Peitz, U. ^{[16
]}

Schildberg, C. ^{[17
]}

Kruschewski, M. ^{[18
]}

Vassos, N. ^{[19
]}

Goni, E. ^{[20
]}

Bruns, C. J. ^{[21
]}

Ridwelski, K. ^{[22
,23
]}

Wolff, S. ^{[24
]}

Lippert, H. ^{[23
,24
]}

Schumacher, J. ^{[25
]}

Malfertheiner, P. ^{[1
,20
]}

Venerito, M. ^{[1
]}

机构：

[1] Otto von Guericke Univ Hosp Magdeburg, Dept Gastroenterol Hepatol & Infect Dis, Leipziger Str 66, D-39120 Magdeburg, Germany

[2] Otto von Guericke Univ Hosp Magdeburg, Inst Pathol, Magdeburg, Germany

[3] Med Univ Innsbruck, Inst Pathol Neuropathol & Mol Pathol, Innsbruck, Austria

[4] Med Univ Graz, Diagnost & Res Ctr Mol BioMed, Inst Pathol, Graz, Austria

[5] Johannes Gutenberg Univ Mainz, Dept Internal Med 1, Mainz, Germany

[6] Johannes Gutenberg Univ Mainz, Dept Gen Visceral & Transplant Surg, Mainz, Germany

[7] Univ Hosp Mainz, Inst Pathol, Mainz, Germany

[8] Leipzig Univ Med Ctr, Dept Med 2, Leipzig, Germany

[9] Leipzig Univ Med Ctr, Univ Canc Ctr Leipzig UCCL, Leipzig, Germany

[10] Univ Hosp Leipzig, Inst Pathol, Leipzig, Germany

[11] Univ Hosp Leipzig, Univ Canc Ctr Leipzig, Leipzig, Germany

[12] Friedrich Alexander Univ Erlangen Nuremberg, Inst Pathol, Klinikum Bayreuth, Bayreuth, Germany

[13] Univ Hosp Frankfurt, Dept Internal Med 1, Main Area Gastroenterol & Hepatol, Frankfurt, Germany

[14] Univ Hosp Frankfurt, Univ Canc Ctr, Frankfurt, Germany

[15] Univ Hosp Bonn, Dept Gen Visceral Thorac & Vasc Surg, Bonn, Germany

[16] Raphaelshosp, Dept Gastroenterol, Munster, Germany

[17] Brandenburg Univ Hosp Visceral Surg, Dept Gen & Visceral Surg, Brandenburg, Germany

[18] Hosp Frankfurt Oder, Dept Gen & Visceral Surg, Frankfurt, Germany

[19] Heidelberg Univ, Univ Med Ctr Mannheim, Dept Surg, Div Surg Oncol & Thorac Surg, Mannheim, Germany

[20] Ludwig Maximilians Univ Munchen, Dept Med 2, Univ Hosp, Munich, Germany

[21] Univ Hosp Cologne, Dept Gen Tumor & Transplantat Surg, Cologne, Germany

[22] Municipal Hosp, Dept Gen & Visceral Surg, Magdeburg, Germany

[23] Otto von Guericke Univ Hosp, AN Inst Qual Assurance Operat Med, Magdeburg, Germany

[24] Otto von Guericke Univ Hosp, Dept Gen Visceral Vasc & Transplantat Surg, Magdeburg, Germany

[25] Philipps Univ Marburg, Human Genet Ctr, Marburg, Germany

来源：

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY | 2023年 / 149卷 / 03期

关键词：

Gastric cancer; Mismatch repair deficiency; Chemotherapy; Survival; Meta-analysis; EPSTEIN-BARR-VIRUS; MICROSATELLITE INSTABILITY; PROGNOSTIC VALUE; CARCINOMA; ACTIVATION; DIAGNOSIS; THERAPY; RISK;

D O I：

10.1007/s00432-022-03953-y

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：1007 / 1017

页数：11

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