title: Persistent Dysphagia After Induction Chemotherapy in Patients with Esophageal Adenocarcinoma Predicts Poor Post-Operative Outcomes.
abstract: OBJECTIVE
  Preoperative therapy is frequently employed in the management of esophageal adenocarcinoma. However, many patients are found to have advanced pathologic stage and have poor outcomes. A prognostic factor which identifies this patient population before surgery would be desirable, as alternative treatment strategies may be warranted.
  
  
  METHODS
  Between 2/08 and 1/12, 60 evaluable patients with locally advanced esophageal adenocarcinoma enrolled in single-arm phase II trial of induction chemotherapy, surgery, and post-operative adjuvant chemo-radiotherapy (CRT). A clinical stage of T3, N1, or M1a (AJCC 6th) was required for eligibility. Induction chemotherapy with epirubicin 50 mg/m2d1, oxaliplatin 130 mg/m2d1, and fluorouracil 200 mg/m2/day continuous infusion for 3 weeks, was given every 21 days for 3 cycles and was followed by surgical resection. Adjuvant CRT consisted of 50-55 Gy @ 1.8-2.0 Gy/day and 2 cycles of cisplatin (20 mg/m2/day) and fluorouracil (1000 mg/m2/day) given as 96-h infusions during weeks 1 and 4 of radiotherapy. Dysphagia was assessed at baseline and after induction chemotherapy.
  
  
  RESULTS
  Persistent dysphagia was associated with worse distant metastatic control [HR 3.48 (1.43-8.43), p = 0.006], recurrence free survival [HR 3.04 (1.34-6.92), p = 0.008], and overall survival [HR 3.31 (1.43-7.66), p = 0.005]. Persistent dysphagia was associated with more advanced pathologic T descriptor (pT) (p = 0.048) and N descriptor (pN) (p = 0.002), a greater median number of involved lymph nodes (3 v 1, p = 0.003), and greater residual tumor viability (p = 0.05). No patients with persistent dysphagia had pT0-T2 or pN0 disease.
  
  
  CONCLUSIONS
  Persistent dysphagia after induction chemotherapy is associated with more advanced pathologic stage and inferior outcomes.
authors.affiliation: Cleveland Clinic, Taussig Cancer Institute, Hematology and Oncology, 9500 Euclid Avenue, R35, Cleveland, OH, 44195, USA. mcnamam@ccf.org.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McNamara
authors.affiliation: Cleveland Clinic, Taussig Cancer Institute, Hematology and Oncology, 9500 Euclid Avenue, R35, Cleveland, OH, 44195, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Adelstein
authors.affiliation: Department of Pathology, Cleveland Clinic, 9500 Euclid Avenue, L25, Cleveland, OH, 44195, USA.
authors.forename: Daniela S
authors.initials: DS
authors.lastname: Allende
authors.affiliation: Cleveland Clinic, Taussig Cancer Institute, Hematology and Oncology, 9500 Euclid Avenue, R35, Cleveland, OH, 44195, USA.
authors.forename: Joanna W
authors.initials: JW
authors.lastname: Bodmann
authors.affiliation: Cleveland Clinic, Taussig Cancer Institute, Hematology and Oncology, 9500 Euclid Avenue, R35, Cleveland, OH, 44195, USA.
authors.forename: Denise I
authors.initials: DI
authors.lastname: Ives
authors.affiliation: Cleveland Clinic, Heart and Vascular Institute, Thoracic and Cardiovascular Surgery, 9500 Euclid Avenue, J4-1, Cleveland, OH, 44195, USA.
authors.forename: Sudish C
authors.initials: SC
authors.lastname: Murthy
authors.affiliation: Cleveland Clinic, Heart and Vascular Institute, Thoracic and Cardiovascular Surgery, 9500 Euclid Avenue, J4-1, Cleveland, OH, 44195, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Raymond
authors.affiliation: Cleveland Clinic, Heart and Vascular Institute, Thoracic and Cardiovascular Surgery, 9500 Euclid Avenue, J4-1, Cleveland, OH, 44195, USA.
authors.forename: Siva
authors.initials: S
authors.lastname: Raja
authors.affiliation: Department of Medicine, Division of Medical Oncology, University of Washington, 825 Eastlake Ave E. MS G4-940, Seattle, WA, 98109, USA.
authors.forename: Cristina P
authors.initials: CP
authors.lastname: Rodriguez
authors.affiliation: Cleveland Clinic, Taussig Cancer Institute, Hematology and Oncology, 9500 Euclid Avenue, R35, Cleveland, OH, 44195, USA.
authors.forename: Davendra
authors.initials: D
authors.lastname: Sohal
authors.affiliation: Cleveland Clinic, Taussig Cancer Institute, Radiation Oncology, 9500 Euclid Avenue, T28, Cleveland, OH, 44195, USA.
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Stephans
authors.affiliation: Cleveland Clinic, Taussig Cancer Institute, Radiation Oncology, 9500 Euclid Avenue, T28, Cleveland, OH, 44195, USA.
authors.forename: Gregory M M
authors.initials: GMM
authors.lastname: Videtic
authors.affiliation: Cleveland Clinic, Quantitative Health Sciences, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Rybicki
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D059186:Chemoradiotherapy, Adjuvant; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000627:therapeutic use; D003680:Deglutition Disorders / Q000139:chemically induced / Q000453:epidemiology*; D018572:Disease-Free Survival; D015251:Epirubicin / Q000627:therapeutic use; D004938:Esophageal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D060828:Induction Chemotherapy / Q000009:adverse effects*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology* / Q000628:therapy; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D000077150:Oxaliplatin; D011182:Postoperative Care / Q000379:methods; D011300:Preoperative Care / Q000379:methods; D057234:Preoperative Period; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D015251:Epirubicin; D002945:Cisplatin; D005472:Fluorouracil
keywords: Dysphagia; Esophageal cancer; Preoperative chemotherapy