title: A multifactorial histopathologic score for the prediction of prognosis of resected esophageal adenocarcinomas after neoadjuvant chemotherapy.
abstract: BACKGROUND
  For esophageal adenocarcinoma treated with neoadjuvant chemotherapy, postoperative staging classifications initially developed for non-pretreated tumors may not accurately predict prognosis. We tested whether a multifactorial TNM-based histopathologic prognostic score (PRSC), which additionally applies to tumor regression, may improve estimation of prognosis compared with the current Union for International Cancer Control/American Joint Committee on Cancer (UICC) staging system.
  
  
  METHODS
  We evaluated esophageal adenocarcinoma specimens following cis/oxaliplatin-based therapy from two separate centers (center 1: n = 280; and center 2: n = 80). For the PRSC, each factor was assigned a value from 1 to 2 (ypT0-2 = 1 point; ypT3-4 = 2 points; ypN0 = 1 point; ypN1-3 = 2 points; ≤ 50 % residual tumor/tumor bed = 1 point; >50 % residual tumor/tumor bed = 2 points). The three-tiered PRSC was based on the sum value of these factors (group A: 3; group B: 4-5; group C: 6) and was correlated with patients' overall survival (OS).
  
  
  RESULTS
  The PRSC groups showed significant differences with respect to OS (p < 0.0001; hazard ratio [HR] 2.2 [95 % CI 1.7-2.8]), which could also be demonstrated in both cohorts separately (center 1 p < 0.0001; HR 2.48 [95 % CI 1.8-3.3] and center 2 p = 0.015; HR 1.7 [95 % CI 1.1-2.6]). Moreover, the PRSC showed a more accurate prognostic discrimination than the current UICC staging system (p < 0.0001; HR 1.15 [95 % CI 1.1-1.2]), and assessment of two goodness-of-fit criteria (Akaike Information Criterion and Schwarz Bayesian Information Criterion) clearly supported the superiority of PRSC over the UICC staging.
  
  
  CONCLUSIONS
  The proposed PRSC clearly identifies three subgroups with different outcomes and may be more helpful for guiding further therapeutic decisions than the UICC staging system.
authors.affiliation: Institute of Pathology, University of Bern, Bern, Switzerland, rupert.langer@pathology.unibe.ch.
authors.forename: Rupert
authors.initials: R
authors.lastname: Langer
authors.forename: Karen
authors.initials: K
authors.lastname: Becker
authors.forename: Inti
authors.initials: I
authors.lastname: Zlobec
authors.forename: Ralf
authors.initials: R
authors.lastname: Gertler
authors.forename: Leila
authors.initials: L
authors.lastname: Sisic
authors.forename: Markus
authors.initials: M
authors.lastname: Büchler
authors.forename: Florian
authors.initials: F
authors.lastname: Lordick
authors.forename: Julia
authors.initials: J
authors.lastname: Slotta-Huspenina
authors.forename: Wilko
authors.initials: W
authors.lastname: Weichert
authors.forename: Heinz
authors.initials: H
authors.lastname: Höfler
authors.forename: Marcus
authors.initials: M
authors.lastname: Feith
authors.forename: Katja
authors.initials: K
authors.lastname: Ott
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000556:secondary* / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D016629:Esophagectomy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate