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. 2024 Aug 1;7(8):e2425581.
doi: 10.1001/jamanetworkopen.2024.25581.

Preoperative Chemoradiotherapy vs Chemotherapy for Adenocarcinoma of the Esophagogastric Junction: A Network Meta-Analysis

Ulrich Ronellenfitsch  1 , Juliane Friedrichs  1 , Emilie Barbier  2 , Gary A Bass  3 , Bryan Burmeister  4 , David Cunningham  5 , Ben M Eyck  6 , Maurizio Grilli  7 , Ralf-Dieter Hofheinz  8 , Meinhard Kieser  9 , Jörg Kleeff  1 , Fredrik Klevebro  10 , Ruth Langley  11 , Florian Lordick  12 , Manfred Lutz  13 , Murielle Mauer  14 , Christoph W Michalski  15 , Patrick Michl  16 , Matthew Nankivell  11 , Magnus Nilsson  10 , Svenja Seide  9   17 , Manish A Shah  18 , Qian Shi  19 , Michael Stahl  20 , Susan Urba  21 , Jan van Lanschot  6 , Dirk Vordermark  22 , Thomas Noel Walsh  23 , Marc Ychou  24 , Tanja Proctor  9 , Johannes A Vey  9
Affiliations

Preoperative Chemoradiotherapy vs Chemotherapy for Adenocarcinoma of the Esophagogastric Junction: A Network Meta-Analysis

Ulrich Ronellenfitsch et al. JAMA Netw Open. .

Abstract

Importance: The prognosis of patients with adenocarcinoma of the esophagus and esophagogastric junction (AEG) is poor. From current evidence, it remains unclear to what extent preoperative chemoradiotherapy (CRT) or preoperative and/or perioperative chemotherapy achieve better outcomes than surgery alone.

Objective: To assess the association of preoperative CRT and preoperative and/or perioperative chemotherapy in patients with AEG with overall survival and other outcomes.

Data sources: Literature search in PubMed, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov, and International Clinical Trials Registry Platform was performed from inception to April 21, 2023.

Study selection: Two blinded reviewers screened for randomized clinical trials comparing preoperative CRT plus surgery with preoperative and/or perioperative chemotherapy plus surgery, 1 intervention with surgery alone, or all 3 treatments. Only data from participants with AEG were included from trials that encompassed mixed histology or gastric cancer. Among 2768 initially identified studies, 17 (0.6%) met the selection criteria.

Data extraction and synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed for extracting data and assessing data quality by 2 independent extractors. A bayesian network meta-analysis was conducted using the 2-stage approach.

Main outcomes and measures: Overall and disease-free survival, postoperative morbidity, and mortality.

Results: The analyses included 2549 patients (2206 [86.5%] male; mean [SD] age, 61.0 [9.4] years) from 17 trials (conducted from 1989-2016). Both preoperative CRT plus surgery (hazard ratio [HR], 0.75 [95% credible interval (CrI), 0.62-0.90]; 3-year difference, 105 deaths per 1000 patients) and preoperative and/or perioperative chemotherapy plus surgery (HR, 0.78 [95% CrI, 0.64-0.91]; 3-year difference, 90 deaths per 1000 patients) showed longer overall survival than surgery alone. Comparing the 2 modalities yielded similar overall survival (HR, 1.04 [95% CrI], 0.83-1.28]; 3-year difference, 15 deaths per 1000 patients fewer for CRT). Similarly, disease-free survival was longer for both modalities compared with surgery alone. Postoperative morbidity was more frequent after CRT plus surgery (odds ratio [OR], 2.94 [95% CrI, 1.01-8.59]) than surgery alone. Postoperative mortality was not significantly more frequent after CRT plus surgery than surgery alone (OR, 2.50 [95% CrI, 0.66-10.56]) or after chemotherapy plus surgery than CRT plus surgery (OR, 0.44 [95% CrI, 0.08-2.00]).

Conclusions and relevance: In this meta-analysis of patients with AEG, both preoperative CRT and preoperative and/or perioperative chemotherapy were associated with longer survival without relevant differences between the 2 modalities. Thus, either of the 2 treatments may be recommended to patients.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Langley reported receiving a grant from the Medical Research Council during the conduct of the study and travel funding from the International Aspirin Foundation outside the submitted work. Dr Lordick reported receiving grant funding from AstraZeneca, BMS, Daiichi Sankyo, Eli Lilly and Company, and Gilead Sciences Inc and personal fees from Amgen Inc, Astellas Pharma, AstraZeneca, BMS, Daiichi Sankyo, Incyte Corporation, MSD, Merck-Serono, F. Hoffmann–La Roche AG, Servier Laboratories, and PAGE Therapeutics outside the submitted work. Dr Shi reported serving on the data safety monitoring board for Yiviva Inc and Mirati Therapeutics Inc, consulting for Regeneron Pharmaceuticals Inc and Kronos Bio, and receiving grant funding from Regeneron Pharmaceuticals Inc, BMS, Roche/Genentech, Janssen Global Services LLC, Novartis AG, and MPAACT to institution outside the submitted work. Dr Stahl reported personal fees from Amgen Inc, BMS, Eli Lilly and Company, MSD, and Servier Laboratories outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. PRISMA Flow Diagram
CINAHL indicates Cumulative Index to Nursing and Allied Health Literature; ICTRP, International Clinical Trials Registry Platform.
Figure 2.
Figure 2.. Summary Forest Plot of Survival Outcomes
The plot displays the network estimates of the age- and sex-adjusted hazard ratios (HRs) and the 95% credible interval (CrI) for each survival outcome. The numbers of studies, patients, and events are related to the direct comparison through the HR and 95% CrI, estimated from the network using direct and indirect evidence for each outcome. CRT indicates chemoradiotherapy; CT, chemotherapy; DFS, disease-free survival; OS, overall survival; RFS, recurrence-free survival; and surg, surgery. aFavors surgery plus CRT. bFavors surgery plus CT.
Figure 3.
Figure 3.. Summary Forest Plot of Binary Outcomes
The plot displays the network estimates of the odds ratios (ORs) and the 95% credible interval (CrI) for each binary outcome. The numbers of studies, patients, and events are related to the direct comparison through the OR and 95% CrI, estimated from the network using direct and indirect evidence for each outcome. CRT indicates chemoradiotherapy; CT, chemotherapy; and surg, surgery. aFavors surgery plus CT. bFavors surgery plus CRT.
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