title: In vivo measurement of the potential doubling time by flowcytometry in oropharyngeal cancer treated by conventional radiotherapy.
abstract: OBJECTIVE
  Experimental and clinical studies suggest that the pre-treatment potential doubling time could be predictive of tumor control in patients treated by conventional radiotherapy and could help to identify the rapidly growing tumors for which accelerated radiotherapy is required.
  
  
  METHODS
  To test this hypothesis, we studied prospectively 48 patients with a squamous cell carcinoma of the oropharynx and treated by conventional radiotherapy (70 Gy/7 weeks). The duration of S phase, the labeling index and the potential doubling time were obtained by flowcytometry measurements of a tumor biopsy obtained after injection of 200 mg bromodeoxyuridine to the patient.
  
  
  RESULTS
  Three parameters were significantly associated with an increased risk of relapse namely the tumors size (T4; p < 0.01), the nodal status (> or = N2; p < 0.05) and the site of the primary within the oropharynx (p = 0.08). The S phase, labeling index, DNA index and potential doubling time were not significantly associated with an increased risk of relapse. However when considering only the T2 subgroup of patients, high labeling indexes and short potential doubling time were associated with an increased risk of relapse: the mean pre-treatment potential doubling time of the tumors which relapsed was 3.21 versus 5.5 days when there was no evidence of local relapse (p < 0.05). The mean labeling index for the group of tumors associated with a tumor recurrence was 11.7% compared to 7.3% when there was no evidence of relapse (p = 0.02).
  
  
  CONCLUSIONS
  Factors other than proliferation play a role in determining the outcome of oropharyngeal cancers treated by conventional radiotherapy. However there was a significant correlation between short potential doubling time, high labeling index and tumor recurrence in the T2 subgroup of patients. The finding of significance for potential doubling time and labeling index in the T2 subset of tumors may be a reflexion of the more homogeneous nature of these tumors with regard to prognostic variables.
authors.affiliation: Radiotherapy Department, Institut Gustave Roussy, Villejuif, France.
authors.forename: J
authors.initials: J
authors.lastname: Bourhis
authors.forename: G
authors.initials: G
authors.lastname: Wilson
authors.forename: P
authors.initials: P
authors.lastname: Wibault
authors.forename: J
authors.initials: J
authors.lastname: Bosq
authors.forename: N
authors.initials: N
authors.lastname: Chavaudra
authors.forename: F
authors.initials: F
authors.lastname: Janot
authors.forename: B
authors.initials: B
authors.lastname: Luboinski
authors.forename: F
authors.initials: F
authors.lastname: Eschwege
authors.forename: E P
authors.initials: EP
authors.lastname: Malaise
mesh_terms: D000368:Aged; D001973:Bromodeoxyuridine; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000453:epidemiology / Q000473:pathology / Q000532:radiotherapy*; D011446:Prospective Studies; D015996:Survival Rate
chemical_list: D001973:Bromodeoxyuridine