Predictors of overall and recurrence-free survival after neoadjuvant chemotherapy for gastroesophageal adenocarcinoma: Pooled analysis of individual patient data (IPD) from randomized controlled trials (RCTs)

U Ronellenfitsch; M Schwarzbach; R Hofheinz; P Kienle; K Nowak; M Kieser; T E Slanger; B Burmeister; D Kelsen; D Niedzwiecki; C Schuhmacher; S Urba; C van de Velde; T N Walsh; M Ychou; K Jensen

doi:10.1016/j.ejso.2017.05.005

Predictors of overall and recurrence-free survival after neoadjuvant chemotherapy for gastroesophageal adenocarcinoma: Pooled analysis of individual patient data (IPD) from randomized controlled trials (RCTs)

Eur J Surg Oncol. 2017 Aug;43(8):1550-1558. doi: 10.1016/j.ejso.2017.05.005. Epub 2017 May 18.

Authors

U Ronellenfitsch¹, M Schwarzbach², R Hofheinz³, P Kienle⁴, K Nowak⁵, M Kieser⁶, T E Slanger⁷, B Burmeister⁸, D Kelsen⁹, D Niedzwiecki¹⁰, C Schuhmacher¹¹, S Urba¹², C van de Velde¹³, T N Walsh¹⁴, M Ychou¹⁵, K Jensen¹⁶

Affiliations

¹ Department of Surgery, University Medical Center Mannheim, Medical Faculty Mannheim of the University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany. Electronic address: [email protected].
² Department of General, Visceral, Vascular, and Thoracic Surgery, Klinikum Frankfurt Höchst, Gotenstraße 6-8, 65929 Frankfurt am Main, Germany. Electronic address: [email protected].
³ Day Treatment Center (TTZ), Interdisciplinary Tumor Center Mannheim (ITM) & 3rd Department of Medicine, University Medical Centre Mannheim, Medical Faculty Mannheim of the University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany. Electronic address: [email protected].
⁴ Department of Surgery, University Medical Center Mannheim, Medical Faculty Mannheim of the University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany. Electronic address: [email protected].
⁵ Department of Surgery, University Medical Center Mannheim, Medical Faculty Mannheim of the University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany. Electronic address: [email protected].
⁶ Institute of Medical Biometry and Informatics, University of Heidelberg, Im Neuenheimer Feld 130, 69120 Heidelberg, Germany. Electronic address: [email protected].
⁷ Department of Surgery, University Medical Center Mannheim, Medical Faculty Mannheim of the University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany. Electronic address: [email protected].
⁸ University of Queensland, Princess Alexandra Hospital, Brisbane, QLD 4102, Australia. Electronic address: [email protected].
⁹ Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, NY 10021, USA. Electronic address: [email protected].
¹⁰ The Alliance for Clinical Trials in Oncology (Alliance) Statistics and Data Center, Duke University Medical Center, Hock Plaza, 2424 Erwin Rd, Room 8040, Durham, NC 27705, USA. Electronic address: [email protected].
¹¹ Department of Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaninger Str. 22, 81675 Munich, Germany. Electronic address: [email protected].
¹² Division of Hematology/Oncology, University of Michigan Medical Center, 1500 E Medical Center Drive, C347, SPC 5848, Ann Arbor, MI 48109, USA. Electronic address: [email protected].
¹³ Department of Surgery, Leiden University Medical Center, K6-R, P.O. Box 9600, 2300 RC Leiden, The Netherlands. Electronic address: [email protected].
¹⁴ Department of Surgery, Connolly Hospital, Blanchardstown, Dublin 15, Ireland. Electronic address: [email protected].
¹⁵ Centre Régional de Lutte Contre le Cancer, Val d'Aurelle, Montpellier Cedex 05, France. Electronic address: [email protected].
¹⁶ Institute of Medical Biometry and Informatics, University of Heidelberg, Im Neuenheimer Feld 130, 69120 Heidelberg, Germany. Electronic address: [email protected].

PMID: 28551325
DOI: 10.1016/j.ejso.2017.05.005

Abstract

Background: Neoadjuvant chemotherapy improves prognosis of patients with locally advanced gastroesophageal adenocarcinoma. The aim of this study was to identify predictors for postoperative survival following neoadjuvant therapy. These could be useful in deciding about postoperative continuation of chemotherapy.

Methods: This meta-analysis used IPD from RCTs comparing neoadjuvant chemotherapy with surgery alone for gastroesophageal adenocarcinoma. Trials providing IPD on age, sex, performance status, pT/N stage, resection status, overall and recurrence-free survival were included. Survival was calculated in the entire study population and subgroups stratified by supposed predictors and compared using the log-rank test. Multivariable Cox models were used to identify independent survival predictors.

Results: Four RCTs providing IPD from 553 patients fulfilled the inclusion criteria. (y)pT and (y)pN stage and resection status strongly predicted postoperative survival both after neoadjuvant therapy and surgery alone. Patients with R1 resection after neoadjuvant therapy survived longer than those with R1 resection after surgery alone. Patients with stage pN0 after surgery alone had better prognosis than those with ypN0 after neoadjuvant therapy. Patients with stage ypT3/4 after neoadjuvant therapy survived longer than those with stage pT3/4 after surgery alone. Multivariable regression identified resection status and (y)pN stage as predictors of survival in both groups. (y)pT stage predicted survival only after surgery alone.

Conclusion: After neoadjuvant therapy for gastroesophageal adenocarcinoma, survival is determined by the same factors as after surgery alone. However, ypT stage is not an independent predictor. These results can facilitate the decision about postoperative continuation of chemotherapy in pretreated patients.

Keywords: Esophageal cancer; Individual patient data meta-analysis; Preoperative chemoradiotherapy; Preoperative chemotherapy; Stomach cancer; Survival.

Publication types

Meta-Analysis

MeSH terms

Adenocarcinoma / drug therapy*
Adenocarcinoma / surgery*
Chemotherapy, Adjuvant*
Esophageal Neoplasms / drug therapy*
Esophageal Neoplasms / surgery*
Humans
Neoadjuvant Therapy*
Prognosis
Randomized Controlled Trials as Topic
Stomach Neoplasms / drug therapy*
Stomach Neoplasms / surgery*
Survival Rate
Treatment Outcome