title: Does histologic grade have a role in the management of head and neck cancers?
abstract: OBJECTIVE
  High histologic grade is usually associated with a greater propensity to distant metastases (DM). Its role to predict DM in head and neck cancer is not yet defined. The aim of this study is to evaluate the role of histologic grade as an independent predictor of DM and to determine a subgroup of patients who may benefit from systemic chemotherapy.
  
  
  METHODS
  This is a retrospective study of 1,266 consecutive patients treated by definitive or postoperative radiotherapy between 1989 and 1997. All patients received at least 50 Gy. All stages and subsites of head/neck were included. DM rates were evaluated by the Kaplan-Meier method with a subsequent Cox analysis.
  
  
  RESULTS
  There is a strong correlation of grade with N stage (P <.000001). The metastases-free survival (MFS) was 98%, 90%, and 72% for grades 1, 2, and 3, respectively (P <.000001). In patients with N0 stage, MFS is always greater than 90%, whatever the grade. In the 222 N1 patients, MFS was more than 90% in grade 1 and 2 but dropped to 75% for grade 3 (P =.001). In patients with N2 and N3, MFS was 91%, 79%, and 59% for grades 1, 2, and 3, respectively (P =.008). The same conclusion is applicable when only patients with neck control are analyzed. In a Cox model, grade was an independent predictor of DM (P =.000001) as well as T stage (P =.003), N stage (P =.000001), and neck failure (P =.0003). Higher grade was also an independent predictor of survival (P =.02).
  
  
  CONCLUSIONS
  Patients with histologic grade 1 and grade 2 (except N3) are at low risk of DM. Patients with grade 2 and N3 or patients with grade 3 and N1 to N3 have a higher risk of distant metastases and should be considered for systemic treatment.
authors.affiliation: Department of Radiation Oncology and Department of Pathology, L'Hôtel-Dieu de Québec, Québec, Canada. afortin@videotron.ca
authors.forename: A
authors.initials: A
authors.lastname: Fortin
authors.forename: C
authors.initials: C
authors.lastname: Couture
authors.forename: R
authors.initials: R
authors.lastname: Doucet
authors.forename: M
authors.initials: M
authors.lastname: Albert
authors.forename: J
authors.initials: J
authors.lastname: Allard
authors.forename: B
authors.initials: B
authors.lastname: Tetu
mesh_terms: D000368:Aged; D003131:Combined Modality Therapy; D005260:Female; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy / Q000601:surgery; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase