title: Patterns and variability of tumor oxygenation in human soft tissue sarcomas, cervical carcinomas, and lymph node metastases.
abstract: OBJECTIVE
  The validity of tumor pO2 measurement as a predictive outcome assay depends upon demonstrating that intrapatient pO2 variation is less than interpatient variation. No consensus exists regarding the appropriate distance between individual measurements. This distance could affect the calculation of the hypoxic fraction (% pO2s < 5 mm Hg) and the assessment of intra/interpatient heterogeneity. This study was performed to evaluate tumor oxygenation and to assess the effects of two different measurement intervals on pO2 heterogeneity in three different sets of patients.
  
  
  METHODS
  Fifteen patients with soft tissue sarcoma, nine patients with cervical carcinoma, and eight patients with squamous carcinoma metastatic to lymph nodes underwent pretreatment polarographic pO2 measurements. Two grossly distinct sites were studied in each tumor, and 2-3 linear tracks were measured at each site. Track lengths varied from 20-36 mm. Distance between measured points was either 0.7-0.8 mm or 0.4 mm. Mean pO2, median pO2, and hypoxic fraction were calculated for each track. Data for each patient were also averaged across all tracks obtained for that patient. Track-specific data were used to evaluate intrapatient variation. The range of average values for each patient was used to assess interpatient heterogeneity. The ratio of these measures provided an assessment of within- vs. between-patient heterogeneity.
  
  
  RESULTS
  The median number of pO2 measurements/patient was 200 (range: 88-356). The average length of hypoxic regions varied from 4.5-5.6 mm. Median tumor pO2s for the cervix, lymph node, and sarcoma patients were 4.5 mm Hg, 12.6 mm Hg, and 18.0 mm Hg, respectively (p = 0.07). Median hypoxic fractions were 0.61, 0.36, and 0.31, respectively (p = 0.07). Intrapatient heterogeneity was less than interpatient heterogeneity for all parameters in all patients, except for mean pO2 for the cervix patients measured at 0.7-mm increments (1.51). Assessment of oxygenation was not affected by the distance between samples.
  
  
  CONCLUSIONS
  Heterogeneity of tumor oxygenation within tumors is less than that between tumors. Both 0.4 mm and 0.7-0.8 mm sampling increments provide similar data. Longer term follow-up of large numbers of uniformly treated patients is required to define the value of tumor oxygen measurement as a predictor of treatment outcome.
authors.affiliation: Department of Radiation Oncology, Duke University Comprehensive Cancer Center, Durham, NC 27710, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Brizel
authors.forename: G L
authors.initials: GL
authors.lastname: Rosner
authors.forename: L R
authors.initials: LR
authors.lastname: Prosnitz
authors.forename: M W
authors.initials: MW
authors.lastname: Dewhirst
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D015687:Cell Hypoxia; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D010101:Oxygen Consumption; D012509:Sarcoma / Q000378:metabolism* / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology