title: Chromosomal copy number alterations are associated with persistent lymph node metastasis after chemoradiation in locally advanced rectal cancer.
abstract: BACKGROUND
  Lymph node metastasis is an important indicator of oncologic outcome for patients with rectal cancer. Identifying predictive biomarkers of lymph node metastasis could therefore be clinically useful.
  
  
  OBJECTIVE
  The aim of this study was to assess whether chromosomal copy number alterations can assist in predicting persistent lymph node metastasis in patients with locally advanced rectal cancer treated with preoperative chemoradiation therapy.
  
  
  METHODS
  This is a nonrandomized, prospective phase II study.
  
  
  METHODS
  This study took place in a multi-institutional setting.
  
  
  METHODS
  Ninety-five patients with stage II (cT3-4, cN0) or stage III (any cT, cN1-2) rectal cancer were included.
  
  
  METHODS
  Patients were treated with preoperative chemoradiation therapy followed by total mesorectal excision. Pretreatment biopsy tumor DNA and surgical margin control DNA were extracted and analyzed by oligonucleotide array-based comparative genomic hybridization. Chromosomal copy number alterations were correlated with persistent lymph node metastasis. Finally, a model for predicting persistent lymph node metastasis was built.
  
  
  METHODS
  The primary outcomes assessed were whether chromosomal copy number alterations are associated with persistent lymph node metastasis in patients with rectal cancer and the accuracy of oligonucleotide array-based comparative genomic hybridization for predicting lymph node metastasis.
  
  
  RESULTS
  Twenty-five of 95 (26%) patients had lymph node metastasis after chemoradiation. Losses of 28 chromosomal regions, most notably in chromosome 4, were significantly associated with lymph node metastasis. Our predictive model contained 65 probes and predicted persistent lymph node metastasis with 68% sensitivity, 93% specificity, and positive and negative predictive values of 77% and 89%. The use of this model accurately predicted lymph node status (positive or negative) after chemoradiation therapy in 82 of 95 patients (86%).
  
  
  CONCLUSIONS
  The patient cohort was not completely homogeneous, which may have influenced their clinical outcome. In addition, although we performed rigorous, statistically sound internal validation, external validation will be important to further corroborate our findings.
  
  
  CONCLUSIONS
  Copy number alterations can help identify patients with rectal cancer who are at risk of lymph node metastasis after chemoradiation.
authors.affiliation: Department of Surgery, City of Hope, Duarte, California 91010, USA.
authors.forename: Zhenbin
authors.initials: Z
authors.lastname: Chen
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Xutao
authors.initials: X
authors.lastname: Deng
authors.forename: Charles
authors.initials: C
authors.lastname: Warden
authors.forename: Wenyan
authors.initials: W
authors.lastname: Li
authors.forename: Julio
authors.initials: J
authors.lastname: Garcia-Aguilar
mesh_terms: D001706:Biopsy; D059248:Chemoradiotherapy; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D005260:Female; D052138:Genes, Neoplasm; D056726:Genetic Association Studies; D005819:Genetic Markers; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics* / Q000473:pathology*; D008297:Male; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012004:Rectal Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000628:therapy*; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D005819:Genetic Markers