PROLIFERATION MEASUREMENTS WITH FLOW-CYTOMETRY T-POT IN CANCER OF THEUTERINE CERVIX - CORRELATION BETWEEN 2 LABORATORIES AND PRELIMINARY CLINICAL-RESULTS

Purpose: To assess the prognostic value of the pretreatment potential doubling time (T-pot) in carcinoma of the uterine cervix, relative to other established clinical factors. Methods and Materials: Fifty-two p atients with cervical cancer were studied prospectively from March 199 1 to October 1993. Pretreatment evaluation included examination under anesthesia and tumor biopsy 6 h following the intravenous administrati on of bromodeoxyuridine (200 mg). T-pot was determined by deriving the labeling index (LI) and S-phase synthesis time (T-s) using flow cytom etry. Six patients were not evaluable and excluded. The remaining 46 p atients (average age 55 years) were treated uniformly with radical rad iation therapy. There were 39 squamous carcinomas and 7 adenocarcinoma s. Federation Internationale de Gynecologie et d'Obstetrique (FIGO) st ages were: Ib and IIa, 12 patients; IIb, 18 patients; III and IV, 16 p atients. The median external beam dose was 50 Gy (range, 45-52.8 Gy) d elivered in 25 fractions. The median intracavitary dose was 40 Gy (ran ge. 25.5-40 Gy) delivered with a single line source to a point 2 cm la teral of the midline, with a mean dose rate of 0.71 Gy/h. The median o verall treatment time was 45 days (range, 34-73 days). As of July 31, 1994, 12 patients had died of disease, and the average followup for al ive patients was 1.4 years (range, 0.5-3.3 years). Results: There were 27 tumors with diploid deoxyribonucleic acid (DNA) content and 19 tum ors were aneuploid. The median acid mean T-pot for the 46 patients wer e 5.5 and 6.6 days, respectively [range, 2.0-25.6 days; coefficient of variation (CV), 74%]. For 25 patients where T-pot measurements were p erformed at two separate laboratories, there was a fair correlation (r = 0.74), but systematic differences were detected suggesting that the lack of agreement was not simply due to intratumoral variation. To da te, 30 patients remained disease free, while 8 patients had pelvic fai lure and 9 patients developed distant metastases as the first failure site (1 patient developed both at the same time). In univariate analys is, the only significant prognostic factor for disease-free survival w as tumor size (p = 0.004). A short T-pot (or high LI) and long overall treatment time (OTT) were weakly associated with poorer disease-free survival, although not statistically significant (1/T-pot, p = 0.14; L I, p = 0.23; OTT, p = 0.04). Age, FIGO stage, hemoglobin level, S-phas e fraction, DNA ploidy, and T-s were not associated with disease-free survival. Multiple regression analysis was not performed because of th e relatively srmall number of patients and short follow-up. Conclusion s: T-pot values determined with current techniques by different labora tories cannot be used interchangeably for the purpose of therapy decis ions. Vigorous quality assurance and standardization of the laboratory procedures and analysis methods are important to reduce interlaborato ry variation. In this uniformly treated group of patients with cancer of the uterine cervix, traditional clinical prognostic factors remain the most important. Preliminary data suggest that the flow cytometry-d etermined T-pot and labeling index predict for disease-free survival, although a larger number of patients with longer follow-up is required to assess the true prognostic significance of these assays and to det ermine if their effect is independent of other clinical factors.