title: Effect of Extending the Original Eligibility Criteria for the CROSS Neoadjuvant Chemoradiotherapy on Toxicity and Survival in Esophageal Cancer.
abstract: BACKGROUND
  Patients with curable esophageal cancer (EC) who proceed beyond the original Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study (CROSS) eligibility criteria are also treated with neoadjuvant chemoradiotherapy (nCRT). This study assessed the effect that extending the CROSS eligibility criteria for nCRT has on treatment-related toxicity and overall survival (OS) in EC.
  
  
  METHODS
  The study enrolled 161 patients with locally advanced EC (T1N1-3/T2-4aN0-3/M0) treated with the CROSS schedule followed by esophagectomy. Group 1 consisted of 89 patients who met the CROSS criteria, and group 2 consisted of 72 patients who met the extended eligibility criteria, i.e. a tumor length greater than 8 cm (n = 24), more than 10% weight loss (n = 35), more than 2-4 cm extension in the stomach (n = 21), celiac lymph node metastasis (n = 13), and/or age over 75 years (n = 2). The study assessed the differences in nCRT-associated toxicity [National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3] and 90-day postoperative mortality. Moreover, the prognostic value for OS was assessed with multivariate Cox regression analysis.
  
  
  RESULTS
  No difference was found in nCRT-associated toxicity (P = 0.117), postoperative complications (P = 0.783), and 90-day mortality (P = 0.492). The OS differed significantly (P = 0.004), with a median of 37.3 months [95% confidence interval (CI), 10.4-64.2 months] for group 1 and 17.2 months (95% CI 13.8-20.7 months) for group 2. Pathologic N stage (P = 0.023), pathologic T stage (P = 0.043), and group 2 (P = 0.008) were independent prognostic factors for OS.
  
  
  CONCLUSIONS
  Extension of the CROSS study eligibility criteria for nCRT did not affect nCRT-associated toxicity, postoperative complications, and postoperative mortality, but was prognostic for OS.
authors.affiliation: Department of Surgical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.|Department of Medical Oncology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: E C
authors.initials: EC
authors.lastname: de Heer
authors.affiliation: Department of Surgical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: J B
authors.initials: JB
authors.lastname: Hulshoff
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: Klerk
authors.affiliation: Department of Epidemiology, University of Groningen, Groningen, The Netherlands.
authors.forename: J G M
authors.initials: JGM
authors.lastname: Burgerhof
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: D J A
authors.initials: DJA
authors.lastname: de Groot
authors.affiliation: Department of Surgical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: J Th M
authors.initials: JTM
authors.lastname: Plukker
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen, Groningen, The Netherlands. g.a.p.hospers@umcg.nl.
authors.forename: G A P
authors.initials: GAP
authors.lastname: Hospers
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality* / Q000556:secondary / Q000628:therapy; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000401:mortality* / Q000556:secondary / Q000628:therapy; D059248:Chemoradiotherapy / Q000401:mortality*; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D016629:Esophagectomy / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000401:mortality*; D009361:Neoplasm Invasiveness; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies; D015996:Survival Rate