title: Phase II study of bevacizumab and preoperative chemoradiation for esophageal adenocarcinoma.
abstract: BACKGROUND
  A standard-of-care for locally advanced esophageal and gastroesophageal junction (GEJ) adenocarcinoma is pre-operative chemoradiation. Elevated levels of vascular endothelial growth factor (VEGF) have been associated with worse outcomes following chemoradiation and anti-VEGF therapies can potentiate radiation efficacy.
  
  
  METHODS
  In this single-arm phase II study, we added bevacizumab to induction chemotherapy and concurrent chemoradiation with cisplatin/irinotecan for locally advanced esophageal and GEJ adenocarcinomas.
  
  
  RESULTS
  Thirty-three patients were enrolled, with all evaluable. All tumors involved the GEJ and 67% were node-positive by endoscopic ultrasound (EUS) and imaging. Twenty-eight patients completed chemoradiation and 26 patients underwent surgery (25 R0 resections). Toxicities were not clearly increased. The pathologic complete response (pCR) rate was 15%. Median progression-free survival (PFS) and overall survival (OS) were 15.1 and 30.5 months respectively. Higher baseline VEGF-A levels were associated with a trend toward improved OS (not reachedvs. 21.0 months, P=0.11). Response on positron emission tomography (PET) scan after induction chemotherapy was predictive of PFS and showed trends toward improved OS and pCR rate.
  
  
  CONCLUSIONS
  The addition of bevacizumab to chemoradiation was not associated with clear worsening of toxicities but also led to no improvement in outcomes, when compared to a prior phase II study of 55 patients. Higher baseline VEGF-A levels correlated with a trend toward improved survival and might be used to stratify or select patients for future studies incorporating this or similar agents. PET scan to assess response following induction chemotherapy and change chemotherapy in non-responders during chemoradiation is the subject of a fully-accrued national trial (NCT01333033).
authors.affiliation: Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA.
authors.forename: Geoffrey Y
authors.initials: GY
authors.lastname: Ku
authors.affiliation: Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, USA.
authors.forename: Manjit S
authors.initials: MS
authors.lastname: Bains
authors.affiliation: John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, USA.
authors.forename: Do Joong
authors.initials: DJ
authors.lastname: Park
authors.affiliation: Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA.
authors.forename: Yelena Y
authors.initials: YY
authors.lastname: Janjigian
authors.affiliation: Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, USA.
authors.forename: Valerie W
authors.initials: VW
authors.lastname: Rusch
authors.affiliation: John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, USA.
authors.forename: Nabil P
authors.initials: NP
authors.lastname: Rizk
authors.affiliation: Gastric and Mixed Tumor Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, USA.
authors.forename: Sam S
authors.initials: SS
authors.lastname: Yoon
authors.affiliation: Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA.
authors.forename: Brittanie
authors.initials: B
authors.lastname: Millang
authors.affiliation: Department of Epidemiology/Biostatistics, Memorial Sloan Kettering Cancer Center, New York, USA.
authors.forename: Marinela
authors.initials: M
authors.lastname: Capanu
authors.affiliation: Department of Radiation Oncology, University of Colorado School of Medicine, Denver, USA.
authors.forename: Karyn A
authors.initials: KA
authors.lastname: Goodman
authors.affiliation: Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Ilson
keywords: Bevacizumab; adenocarcinoma; chemoradiation; chemotherapy; esophageal cancer; radiation