title: Assessment of tumor regression of esophageal adenocarcinomas after neoadjuvant chemotherapy: comparison of 2 commonly used scoring approaches.
abstract: Histopathologic determination of tumor regression provides important prognostic information for locally advanced gastroesophageal carcinomas after neoadjuvant treatment. Regression grading systems mostly refer to the amount of therapy-induced fibrosis in relation to residual tumor or the estimated percentage of residual tumor in relation to the former tumor site. Although these methods are generally accepted, currently there is no common standard for reporting tumor regression in gastroesophageal cancers. We compared the application of these 2 major principles for assessment of tumor regression: hematoxylin and eosin-stained slides from 89 resection specimens of esophageal adenocarcinomas following neoadjuvant chemotherapy were independently reviewed by 3 pathologists from different institutions. Tumor regression was determined by the 5-tiered Mandard system (fibrosis/tumor relation) and the 4-tiered Becker system (residual tumor in %). Interobserver agreement for the Becker system showed better weighted κ values compared with the Mandard system (0.78 vs. 0.62). Evaluation of the whole embedded tumor site showed improved results (Becker: 0.83; Mandard: 0.73) as compared with only 1 representative slide (Becker: 0.68; Mandard: 0.71). Modification into simplified 3-tiered systems showed comparable interobserver agreement but better prognostic stratification for both systems (log rank Becker: P=0.015; Mandard P=0.03), with independent prognostic impact for overall survival (modified Becker: P=0.011, hazard ratio=3.07; modified Mandard: P=0.023, hazard ratio=2.72). In conclusion, both systems provide substantial to excellent interobserver agreement for estimation of tumor regression after neoadjuvant chemotherapy in esophageal adenocarcinomas. A simple 3-tiered system with the estimation of residual tumor in % (complete regression/1% to 50% residual tumor/>50% residual tumor) maintains the highest reproducibility and prognostic value.
authors.affiliation: *Institute of Pathology, University of Bern, Bern, Switzerland †Department of Surgery, University of Heidelberg, Heidelberg ‡Department of Surgery, Klinikum Rechts der Isar §Institute of Pathology, Technische Universität München, Munich ∥University Cancer Center Leipzig, Leipzig, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Karamitopoulou
authors.forename: Svenja
authors.initials: S
authors.lastname: Thies
authors.forename: Inti
authors.initials: I
authors.lastname: Zlobec
authors.forename: Katja
authors.initials: K
authors.lastname: Ott
authors.forename: Marcus
authors.initials: M
authors.lastname: Feith
authors.forename: Julia
authors.initials: J
authors.lastname: Slotta-Huspenina
authors.forename: Florian
authors.initials: F
authors.lastname: Lordick
authors.forename: Karen
authors.initials: K
authors.lastname: Becker
authors.forename: Rupert
authors.initials: R
authors.lastname: Langer
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D004396:Coloring Agents; D004801:Eosine Yellowish-(YS); D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D006416:Hematoxylin; D006801:Humans; D053208:Kaplan-Meier Estimate; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D018365:Neoplasm, Residual; D015588:Observer Variation; D011237:Predictive Value of Tests; D012074:Remission Induction; D015203:Reproducibility of Results; D013194:Staining and Labeling / Q000379:methods; D016896:Treatment Outcome
chemical_list: D004396:Coloring Agents; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin