title: Potential doubling time in head and neck tumors treated by primary radiotherapy: preliminary evidence for a prognostic significance in local control.
abstract: OBJECTIVE
  The aim of the study was to determine preliminarily whether cell kinetic parameters evaluated using in vivo infusion of bromodeoxyuridine (BrdUrd) and flow cytometry, play a role as prognostic factors of loco-regional control in squamous cell head and neck carcinoma treated with radiotherapy.
  
  
  METHODS
  Between April 1989 and December 1991, 42 patients with unresectable Stage II-IV squamous cell carcinoma of the oral cavity, pharynx or larynx were given an infusion of BrdUrd solution prior to primary tumor biopsy sampling at 4-6 hr later. The simultaneous labeling S-phase fraction (LI) and duration (Ts) as well as the estimated potential doubling time (Tpot) were measured using flow cytometric analysis of BrdUrd and DNA content. Twenty-six patients received standard radiotherapy (70 Gy/35 fractions/7 weeks) whereas 15 patients were treated with the concomitant boost technique (75 Gy/40 fractions/6 weeks).
  
  
  RESULTS
  A complete set of flow cytometric data was available for 31 patients. The median value of LI, Ts, and Tpot were 9%, 9 hr and 5 days, respectively. Univariate analysis among the patients treated homogeneously by standard radiotherapy, indicated that local control was affected by Tpot value (p = 0.02). When the same analysis was performed for the patients treated with either standard radiotherapy or concomitant boost regimen, we found a p = 0.04. Thus, patients with a tumor Tpot value < or = 5 days had a significantly lower three-year local control than patients with Tpot > 5 days. Log-rank test univariate analysis showed, in addition, that nodal status was the strongest prognostic factor of local control (p = 0.005). Age, tumor stage, tumor site, performance status, grading, radiotherapy regimen, DNA ploidy and LI value were, instead, not significantly related to loco-regional control. Finally, when comparing the type of radiotherapy for tumors with Tpot < or = 5 days, we found a trend toward a better local control after concomitant boost regimen, with respect to standard regimen (p = 0.06).
  
  
  CONCLUSIONS
  The present preliminary results suggest that Tpot could play a role as additional prognostic factor influencing the disease outcome in head and neck carcinoma treated by radiotherapy.
authors.affiliation: Divisione di Oncologia Radioterapica, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Corvò
authors.forename: W
authors.initials: W
authors.lastname: Giaretti
authors.forename: G
authors.initials: G
authors.lastname: Sanguineti
authors.forename: E
authors.initials: E
authors.lastname: Geido
authors.forename: R
authors.initials: R
authors.lastname: Orecchia
authors.forename: S
authors.initials: S
authors.lastname: Barra
authors.forename: G
authors.initials: G
authors.lastname: Margarino
authors.forename: A
authors.initials: A
authors.lastname: Bacigalupo
authors.forename: V
authors.initials: V
authors.lastname: Vitale
mesh_terms: D000206:Actuarial Analysis; D000328:Adult; D000367:Age Factors; D000368:Aged; D001973:Bromodeoxyuridine; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D002455:Cell Division; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D007700:Kinetics; D007822:Laryngeal Neoplasms / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000473:pathology / Q000532:radiotherapy; D009303:Nasopharyngeal Neoplasms / Q000473:pathology / Q000532:radiotherapy; D009367:Neoplasm Staging; D010610:Pharyngeal Neoplasms / Q000473:pathology / Q000532:radiotherapy; D011003:Ploidies; D011379:Prognosis
chemical_list: D001973:Bromodeoxyuridine