Individual Participant Data Network Meta-Analysis of Neoadjuvant Chemotherapy or Chemoradiotherapy in Esophageal or Gastroesophageal Junction Carcinoma
Authors: Faron Matthieu , Cheugoua-Zanetsie Maurice , Tierney Jayne , Thirion Pierre , Nankivell Matthew , Winter Kathryn , Yang Hong , Shapiro Joel , Vernerey Dewi , Smithers B. Mark , Walsh Thomas , Piessen Guillaume , Nilsson Magnus , Boonstra Jurjen , Ychou Marc , Law Simon , Cunningham David , de Vathaire Florent , Stahl Michael , Urba Susan , Valmasoni Michele , Williaume Danièle , Thomas Janine , Lordick Florian , Tepper Joel , Roth Jack , Gebski Val , Burmeister Bryan , Paoletti Xavier , van Sandick Johanna , Fu Jianhua , Pignon Jean-Pierre , Ducreux Michel , Michiels Stefan ,   on behalf of the MANATEC-02 Collaborative Group, Apinop Chanvitan , Arezina Anne , Barbier Emilie , Bass Gary , Blanchard Pierre , Boonstra Jurjen , Bosset Jean-François , Burmeister Bryan H. , Cheugoua-Zanetsie Armel Maurice , Cunningham David , Ducreux Michel , Faron Matthieu , Fu Jianhua , Gebski Val , Girling D. J. , Kelsen David , Klevebro Fredrik , Law Simon , Le Prise Elisabeth , Lordick Florian , Maipang Tanaphon , Mauer Murielle , Michiels Stefan , Moughan Jennifer , Nankivell Matthew , Nygaard Knut , Owens Patrick , Paoletti Xavier , Piessen Guillaume , Pignon Jean Pierre , Raoul Jean-Luc , Roth Jack , Ruol Alberto , Schlag Peter , Schumacher Christoph , Shapiro Joel , Smithers B. Mark , Stahl Michael , Tepper Joel , Thirion Pierre , Thomas Janine M. , Tierney Jayne , Urba Susan , Valmasoni Michele , van der Gaast Ate , van Sandick Johanna , Williaume Danièle , Winter Kathryn , Wong John , Yang Hong , Ychou Marc 
Published: July 2023

PURPOSE 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. PATIENTS AND METHODS All, published or unpublished, RCTs closed to accrual before December 31, 2015 and having compared at least two of the following strategies were eligible: upfront surgery (S), chemotherapy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). RESULTS 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). CONCLUSION 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.