title: Interstitial fluid pressure predicts survival in patients with cervix cancer independent of clinical prognostic factors and tumor oxygen measurements.
abstract: The purpose of this study was to determine the independent prognostic significanceof interstitial fluid pressure (IFP) measurements in cervix cancer. A total of 102 patients with newly diagnosed cervix cancer were accrued to this prospective study. There were 31 International Federation of Gynecology and Obstetrics stage IB or IIA tumors, 40 IIB tumors, and 31 IIIB tumors. The median size was 5 cm (range, 2-10 cm). Pelvic lymphadenopathy was identified radiographically in 20 patients. IFP was measured at examination under anesthesia using a wick-in-needle technique. Multiple measurements were made in each tumor. The mean IFP in individual tumors ranged from -3 to 48 mm Hg, and the median for the entire cohort was 19 mm Hg. Treatment consisted of external beam and intracavitary radiation without chemotherapy. Median follow-up was 2.5 years. The 3-year disease-free survival of all of the patients was 53%. Disease-free survival was 34% in patients with IFP >19 mm Hg, and 68% in those with lower IFP (P = 0.002). To evaluate rigorously the independent prognostic significance of IFP measurements relative to established clinical factors, a multivariate model was first developed using stepwise selection of clinical covariates. Tumor size (P = 0.0003) and pelvic lymph node status (P = 0.0016) comprised the clinical model. IFP, when added to this model, provided additional independent prognostic information (P = 0.0013). IFP was also significant (P = 0.0027) when the clinical factors and hypoxic proportion as determined with the Eppendorf electrode were analyzed together. Patients with high IFP were more likely to recur both locally and at distant sites. This study is the first to document a strong, independent prognostic importance of pretreatment IFP measurements in cervix cancer. Patients with high IFP are significantly more likely than those with low IFP to recur after radiotherapy and die of progressive disease, independent of clinical prognostic factors and the results of tumor oxygen measurements.
authors.affiliation: Department of Radiation Oncology, Princess Margaret Hospital, Toronto, Canada M5G 2M9. mike.milosevic@rmp.uhn.on.ca
authors.forename: M
authors.initials: M
authors.lastname: Milosevic
authors.forename: A
authors.initials: A
authors.lastname: Fyles
authors.forename: D
authors.initials: D
authors.lastname: Hedley
authors.forename: M
authors.initials: M
authors.lastname: Pintilie
authors.forename: W
authors.initials: W
authors.lastname: Levin
authors.forename: L
authors.initials: L
authors.lastname: Manchul
authors.forename: R
authors.initials: R
authors.lastname: Hill
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D018572:Disease-Free Survival; D005110:Extracellular Space / Q000502:physiology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D010100:Oxygen / Q000378:metabolism*; D011446:Prospective Studies; D015996:Survival Rate; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*
chemical_list: D010100:Oxygen