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Interstitial Hypertension in Carcinoma of Uterine Cervix in Patients: Possible Correlation with Tumor Oxygenation and Radiation Response¹

Department of Radiation Oncology, University of Pittsburgh and Magee-Womens Hospital, Pittsburgh Cancer Institute, and Joint Radiation Oncology Center [H. D. R., S. K., R. B., W. D. B., R. K. J], and Department of Chemical Engineering, Carnegie Mellon University [H. D. R., Y. B., R. K. J.], Pittsburgh, Pennsylvania 15213

Elevated tumor interstitial fluid pressure (IFP) is believed to be responsible, at least in part, for the poor penetration and heterogeneous distribution of blood-borne therapeutic agents and nutrients in solid tumors. Using the wick-in-needle technique, IFP was measured in human patients with squamous cell carcinoma of the uterine cervix at the initial and final stages of fractionated external beam radiotherapy. Mean IFP values ranged from 10 to 26 mm Hg with an overall mean of 15.7 ± 5.7 (SD) mm Hg in stage IIB and IIIB tumors (n = 12) and from 0 to 3 mm Hg in normal cervix (n = 3). IFP decreased in some patients with therapy while in others it increased. The changes in IFP values agree well with the clinical response to radiotherapy (n = 7, P < 0.05). Oxygen tension, measured in selected tumors (n = 3) with polarographic oxygen micro-electrodes, inversely correlated with IFP. These results show for the first time that the IFP in human cervical carcinomas is elevated, and that it can be lowered in some tumors using fractionated radiation therapy. These findings also suggest that IFP values may provide an indication of tumor oxygenation and that IFP modifications could be prognostic indicators of radiation response.

¹ This work was supported by grants from the Claude Worthington Benedum Foundation (H. D. R. and W. D. B.) and the National Cancer Institute (R. K. J.) and by a Humboldt Senior Scientist Award (R. K. J.). This is the second paper in a series on interstitial hypertension in human tumors. Preliminary reports of this work were presented at the 16th Gray Conference, Manchester, England, September 17–21, 1990, and at the 9th International Congress of Radiation Research, Toronto, Canada, July 7–12, 1991.

² Present address: Steele Laboratory, Department of Radiation Oncology, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114.

³ To whom requests for reprints should be addressed.

Received 8/28/91. Accepted 10/21/91.

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