Individual Participant Data Network Meta-Analysis of Neoadjuvant Chemotherapy or Chemoradiotherapy in Esophageal or Gastroesophageal Junction Carcinoma

Matthieu Faron, Maurice Cheugoua-Zanetsie, Jayne Tierney, Pierre Thirion, Matthew Nankivell, Kathryn Winter, Hong Yang, Joel Shapiro, Dewi Vernerey, B. Mark Smithers, Thomas Walsh, Guillaume Piessen, Magnus Nilsson, Jurjen Boonstra, Marc Ychou, Simon Law, David Cunningham, Florent de Vathaire, Michael Stahl, Susan UrbaMichele Valmasoni, Danièle Williaume, Janine Thomas, Florian Lordick, Joel Tepper, Jack Roth, Val Gebski, Bryan Burmeister, Xavier Paoletti, Johanna van Sandick, Jianhua Fu, Jean Pierre Pignon, MANATEC-02 collaborative group, Michel Ducreux, Stefan Michiels

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The optimal neoadjuvant treatment for resectable carcinoma of the thoracic esophagus (TE) or gastroesophageal junction (GEJ) remains a matter of debate. We performed an individual participant data (IPD) network meta-analysis (NMA) of randomized controlled trials (RCTs) to study the effect of chemotherapy or chemoradiotherapy, with a focus on tumor location and histology subgroups. 


All, published or unpublished, RCTs closed to accrual before December 31, 2015 and having compared at least two of the following strategies were eligible: upfront surgery (S), chemotherapy followed by surgery (CS), and chemoradiotherapy followed by surgery (CRS). All analyses were conducted on IPD obtained from investigators. The primary end point was overall survival (OS). The IPD-NMA was analyzed by a one-step mixed-effect Cox model adjusted for age, sex, tumor location, and histology. The NMA was registered in PROSPERO (CRD42018107158). 


IPD were obtained for 26 of 35 RCTs (4,985 of 5,807 patients) corresponding to 12 comparisons for CS-S, 12 for CRS-S, and four for CRS-CS. CS and CRS led to increased OS when compared with S with hazard ratio (HR) = 0.86 (0.75 to 0.99), P = .03 and HR = 0.77 (0.68 to 0.87), P < .001 respectively. The NMA comparison of CRS versus CS for OS gave a HR of 0.90 (0.74 to 1.09), P = .27 (consistency P = .26, heterogeneity P = .0038). For CS versus S, a larger effect on OS was observed for GEJ versus TE tumors (P = .036). For the CRS versus S and CRS versus CS, a larger effect on OS was observed for women (P = .003, .012, respectively). 


Neoadjuvant chemotherapy and chemoradiotherapy were consistently better than S alone across histology, but with some variation in the magnitude of treatment effect by sex for CRS and tumor location for CS. A strong OS difference between CS and CRS was not identified.

Original languageEnglish
Pages (from-to)4535-4547
Number of pages13
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology
Issue number28
Early online date12 Jul 2023
Publication statusPublished - 1 Oct 2023

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© 2023 American Society of Clinical Oncology.


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