title: The relationship between pathologic nodal disease and residual tumor viability after induction chemotherapy in patients with locally advanced esophageal adenocarcinoma receiving a tri-modality regimen.
abstract: BACKGROUND
  A complete pathologic response to induction chemo-radiotherapy (CRT) has been identified as a favorable prognostic factor for patients with loco-regionally advanced (LRA) adenocarcinoma (ACA) of the esophagus and gastro-esophageal junction (E/GEJ). Nodal involvement at the time of surgery has been found to be prognostically unfavorable. Less is known, however, about the prognostic import of less than complete pathologic regression and its relationship to residual nodal disease after induction chemotherapy.
  
  
  METHODS
  Between February 2008 and January 2012, 60 evaluable patients with ACA of the E/GEJ enrolled in a phase II trial of induction chemotherapy, surgery, and post-operative CRT. Eligibility required a clinical stage of T3-T4 or N1 or M1a (AJCC 6(th)). Induction chemotherapy with epirubicin 50 mg/m(2) d1, oxaliplatin 130 mg/m(2) d1, and fluorouracil 200 mg/m(2)/day continuous infusion for 3 weeks, was given every 21 days for three courses and was followed by surgical resection. Adjuvant CRT consisted of 50-55 Gy at 1.8-2.0 Gy/d and two courses of cisplatin (20 mg/m(2)/d) and fluorouracil (1,000 mg/m(2)/d) over 4 days during weeks 1 and 4 of radiotherapy. Residual viability (RV) was defined as the amount of remaining tumor in relation to acellular mucin pools and scarring.
  
  
  RESULTS
  Of the 60 evaluable patients, 54 completed induction therapy and underwent curative intent surgery. The Kaplan-Meier projected 3-year overall survival (OS) for patients with pathologic N0 (n=20), N1 (n=12), N2 (n=13), and N3 (n=9) disease is 73%, 57%, 35%, and 0% respectively (P<0.001). The Kaplan-Meier projected 3-year OS of patients with low (0-25%, n=19), intermediate (26-75%, n=26), and high (>75%, n=9) residual tumor viability was 67%, 42%, and 17% respectively (P=0.004). On multivariable analysis (MVA), both the pN descriptor and RV were independently prognostic for OS. In patients with less nodal dissemination (N0/N1), RV was prognostic for OS [3-year OS 85% (0-25% viable) vs. 51% (>25% viable), P=0.028]. Outcomes were poor, however, for patients with advanced nodal disease (N2/N3) regardless of RV [3-year OS 20% (0-25% viable) vs. 21% (>25% viable), P=0.55].
  
  
  CONCLUSIONS
  RV and the pN descriptor after induction chemotherapy are independent pathologic prognostic factors for OS in patients with LRA ACA of the E/GEJ. Patients with extensive nodal disease, however, have poor outcomes irrespective of residual tumor viability.
authors.affiliation: 1 Hematology and Oncology, Taussig Cancer Institute, 2 Quantitative Health Sciences, 3 Department of Pathology, 4 Radiation Oncology, Cleveland Clinic, Cleveland, OH 44195, USA ; 5 Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA 98109, USA ; 6 Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McNamara
authors.affiliation: 1 Hematology and Oncology, Taussig Cancer Institute, 2 Quantitative Health Sciences, 3 Department of Pathology, 4 Radiation Oncology, Cleveland Clinic, Cleveland, OH 44195, USA ; 5 Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA 98109, USA ; 6 Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Rybicki
authors.affiliation: 1 Hematology and Oncology, Taussig Cancer Institute, 2 Quantitative Health Sciences, 3 Department of Pathology, 4 Radiation Oncology, Cleveland Clinic, Cleveland, OH 44195, USA ; 5 Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA 98109, USA ; 6 Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Davendra
authors.initials: D
authors.lastname: Sohal
authors.affiliation: 1 Hematology and Oncology, Taussig Cancer Institute, 2 Quantitative Health Sciences, 3 Department of Pathology, 4 Radiation Oncology, Cleveland Clinic, Cleveland, OH 44195, USA ; 5 Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA 98109, USA ; 6 Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Daniela S
authors.initials: DS
authors.lastname: Allende
authors.affiliation: 1 Hematology and Oncology, Taussig Cancer Institute, 2 Quantitative Health Sciences, 3 Department of Pathology, 4 Radiation Oncology, Cleveland Clinic, Cleveland, OH 44195, USA ; 5 Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA 98109, USA ; 6 Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Gregory M M
authors.initials: GM
authors.lastname: Videtic
authors.affiliation: 1 Hematology and Oncology, Taussig Cancer Institute, 2 Quantitative Health Sciences, 3 Department of Pathology, 4 Radiation Oncology, Cleveland Clinic, Cleveland, OH 44195, USA ; 5 Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA 98109, USA ; 6 Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Cristina P
authors.initials: CP
authors.lastname: Rodriguez
authors.affiliation: 1 Hematology and Oncology, Taussig Cancer Institute, 2 Quantitative Health Sciences, 3 Department of Pathology, 4 Radiation Oncology, Cleveland Clinic, Cleveland, OH 44195, USA ; 5 Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA 98109, USA ; 6 Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Stephans
authors.affiliation: 1 Hematology and Oncology, Taussig Cancer Institute, 2 Quantitative Health Sciences, 3 Department of Pathology, 4 Radiation Oncology, Cleveland Clinic, Cleveland, OH 44195, USA ; 5 Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA 98109, USA ; 6 Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Sudish C
authors.initials: SC
authors.lastname: Murthy
authors.affiliation: 1 Hematology and Oncology, Taussig Cancer Institute, 2 Quantitative Health Sciences, 3 Department of Pathology, 4 Radiation Oncology, Cleveland Clinic, Cleveland, OH 44195, USA ; 5 Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA 98109, USA ; 6 Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Siva
authors.initials: S
authors.lastname: Raja
authors.affiliation: 1 Hematology and Oncology, Taussig Cancer Institute, 2 Quantitative Health Sciences, 3 Department of Pathology, 4 Radiation Oncology, Cleveland Clinic, Cleveland, OH 44195, USA ; 5 Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA 98109, USA ; 6 Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Raymond
authors.affiliation: 1 Hematology and Oncology, Taussig Cancer Institute, 2 Quantitative Health Sciences, 3 Department of Pathology, 4 Radiation Oncology, Cleveland Clinic, Cleveland, OH 44195, USA ; 5 Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA 98109, USA ; 6 Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Denise I
authors.initials: DI
authors.lastname: Ives
authors.affiliation: 1 Hematology and Oncology, Taussig Cancer Institute, 2 Quantitative Health Sciences, 3 Department of Pathology, 4 Radiation Oncology, Cleveland Clinic, Cleveland, OH 44195, USA ; 5 Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA 98109, USA ; 6 Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Joanna W
authors.initials: JW
authors.lastname: Bodmann
authors.affiliation: 1 Hematology and Oncology, Taussig Cancer Institute, 2 Quantitative Health Sciences, 3 Department of Pathology, 4 Radiation Oncology, Cleveland Clinic, Cleveland, OH 44195, USA ; 5 Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA 98109, USA ; 6 Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Adelstein
keywords: Esophageal cancer; preoperative chemotherapy; prognosis; regression