title: Survival benefit and additional value of preoperative chemoradiotherapy in resectable gastric and gastro-oesophageal junction cancer: a direct and adjusted indirect comparison meta-analysis.
abstract: Several phase I/II studies of chemoradiotherapy for gastric cancer have reported promising results, but the significance of preoperative radiotherapy in addition to chemotherapy has not been proven. In this study, a systematic literature search was performed to capture survival and postoperative morbidity and mortality data in randomised clinical studies comparing preoperative (chemo)radiotherapy or chemotherapy versus surgery alone, or preoperative chemoradiotherapy versus chemotherapy for gastric and/or gastro-oesophageal junction (GOJ) cancer. Hazard ratios (HRs) for overall mortality were extracted from the original studies, individual patient data provided from the principal investigators of eligible studies or the earlier published meta-analysis. The incidences of postoperative morbidities and mortalities were also analysed. In total 18 studies were eligible and data were available from 14 of these. The meta-analysis on overall survival yielded HRs of 0.75 (95% CI 0.65-0.86, P < 0.001) for preoperative (chemo)radiotherapy and 0.83 (95% CI 0.67-1.01, P = 0.065) for preoperative chemotherapy when compared to surgery alone. Direct comparison between preoperative chemoradiotherapy and chemotherapy resulted in an HR of 0.71 (95% CI 0.45-1.12, P = 0.146). Combination of direct and adjusted indirect comparisons yielded an HR of 0.86 (95% CI 0.69-1.07, P = 0.171). No statistically significant differences were seen in the risk for postoperative morbidity or mortality between preoperative treatments and surgery alone, or preoperative (chemo)radiotherapy and chemotherapy. Preoperative (chemo)radiotherapy for gastric and GOJ cancer showed significant survival benefit over surgery alone. In comparisons between preoperative chemotherapy and (chemo)radiotherapy, there is a trend towards improved survival when adding radiotherapy, without increased postoperative morbidity or mortality.
authors.affiliation: Center for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden. Electronic address: koshi.kumagai@gmail.com.
authors.forename: K
authors.initials: K
authors.lastname: Kumagai
authors.affiliation: Center for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: I
authors.initials: I
authors.lastname: Rouvelas
authors.affiliation: Center for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: J A
authors.initials: JA
authors.lastname: Tsai
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: D
authors.initials: D
authors.lastname: Mariosa
authors.affiliation: Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden; Centre for Clinical Research Sörmland, Uppsala University, Uppsala, Sweden.
authors.forename: P A
authors.initials: PA
authors.lastname: Lind
authors.affiliation: Center for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Lindblad
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: W
authors.initials: W
authors.lastname: Ye
authors.affiliation: Center for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Lundell
authors.affiliation: Department of Surgery, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Muenchen, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Schuhmacher
authors.affiliation: EORTC Headquaters, Statistic Department, Brussels, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Mauer
authors.affiliation: Division of Cancer Services, University of Queensland, Princess Alexandra Hospital, Queensland, Australia.
authors.forename: B H
authors.initials: BH
authors.lastname: Burmeister
authors.affiliation: Division of Cancer Services, University of Queensland, Princess Alexandra Hospital, Queensland, Australia.
authors.forename: J M
authors.initials: JM
authors.lastname: Thomas
authors.affiliation: Department of Medical Oncology and Hematology, Kliniken Essen-Mitte, Essen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Stahl
authors.affiliation: Center for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Nilsson
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000628:therapy*; D059186:Chemoradiotherapy, Adjuvant; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D016629:Esophagectomy; D004943:Esophagogastric Junction / Q000601:surgery*; D005743:Gastrectomy; D006801:Humans; D020360:Neoadjuvant Therapy / Q000379:methods; D018714:Radiotherapy, Adjuvant; D013274:Stomach Neoplasms / Q000401:mortality / Q000628:therapy*; D016896:Treatment Outcome
keywords: Adenocarcinoma; Gastro-oesophageal junction; Preoperative chemoradiotherapy; Preoperative chemotherapy; Stomach