title: Residual tumor after neoadjuvant chemoradiation outside the radiation therapy target volume: a new prognostic factor for survival in esophageal cancer.
abstract: OBJECTIVE
  The aim of this study was to analyze the accuracy of gross tumor volume (GTV) delineation and clinical target volume (CTV) margins for neoadjuvant chemoradiation therapy (neo-CRT) in esophageal carcinoma at pathologic examination and to determine the impact on survival.
  
  
  METHODS
  The study population consisted of 63 esophageal cancer patients treated with neo-CRT. GTV and CTV borders were demarcated in situ during surgery on the esophagus, using anatomical reference points to provide accurate information regarding tumor location at pathologic evaluation. To identify prognostic factors for disease-free survival (DFS) and overall survival (OS), a Cox regression analysis was performed.
  
  
  RESULTS
  After resection, macroscopic residual tumor was found outside the GTV in 7 patients (11%). Microscopic residual tumor was located outside the CTV in 9 patients (14%). The median follow-up was 15.6 months. With multivariate analysis, only microscopic tumor outside the CTV (hazard ratio [HR], 4.96; 95% confidence interval [CI], 1.03-15.36), and perineural growth (HR, 5.77; 95% CI, 1.27-26.13) were identified as independent prognostic factors for OS. The 1-year OS was 20% for patients with tumor outside the CTV and 86% for those without (P<.01). For DFS, microscopic tumor outside the CTV (HR, 5.92; 95% CI, 1.89-18.54) and ypN+ (HR, 3.36; 95% CI, 1.33-8.48) were identified as independent adverse prognostic factors. The 1-year DFS was 23% versus 77% for patients with or without tumor outside the CTV (P<.01).
  
  
  CONCLUSIONS
  Microscopic tumor outside the CTV is associated with markedly worse OS after neo-CRT. This may either stress the importance of accurate tumor delineation or reflect aggressive tumor behavior requiring new adjuvant treatment modalities.
authors.affiliation: Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. Electronic address: c.t.muijs@umcg.nl.
authors.forename: Christina
authors.initials: C
authors.lastname: Muijs
authors.affiliation: Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Justin
authors.initials: J
authors.lastname: Smit
authors.affiliation: Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Arend
authors.initials: A
authors.lastname: Karrenbeld
authors.affiliation: Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Jannet
authors.initials: J
authors.lastname: Beukema
authors.affiliation: Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Veronique
authors.initials: V
authors.lastname: Mul
authors.affiliation: Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Go
authors.initials: G
authors.lastname: van Dam
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Geke
authors.initials: G
authors.lastname: Hospers
authors.affiliation: Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Phillip
authors.initials: P
authors.lastname: Kluin
authors.affiliation: Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Johannes
authors.initials: J
authors.lastname: Langendijk
authors.affiliation: Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: John
authors.initials: J
authors.lastname: Plukker
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D059925:Anatomic Landmarks; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D017024:Chemotherapy, Adjuvant / Q000379:methods* / Q000401:mortality; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000000981:diagnostic imaging / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018365:Neoplasm, Residual; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D011446:Prospective Studies; D011859:Radiography; D011880:Radiotherapy Planning, Computer-Assisted; D012044:Regression Analysis; D047368:Tumor Burden
chemical_list: D016190:Carboplatin; D017239:Paclitaxel