Micronucleus assay in vivo provides significant prognostic information in human cervical carcinoma; the updated analysis.

PURPOSE: Reanalysis after a 5-year follow-up previously presented relationships between spontaneous and radiation-induced micronucleus frequencies in tumour cells and the clinical outcome of patients with advanced stages (II B-IV B) of cervix carcinomas treated with radiotherapy. MATERIALS AND METHODS: Spontaneous and induced in vitro and in vivo micronucleus frequencies were determined and related to clinical parameters. Data were analysed by the univariate Kaplan-Meier method and multivariate Cox proportional hazards model. RESULTS: In univariate analysis stage, spontaneous micronucleus frequency before radiotherapy (MNSP) and per cent increment of micronucleus level in vivo after 20 Gy in relation to spontaneous pretreatment level were statistically significant predictors of 5-year recurrence-free, disease-free and overall survival. Neither micronucleus frequency (MN/BNC at 2 Gy) nor proliferating fraction (%BNC at 0 Gy) estimated in vitro (in primary culture) were related to radiotherapy outcome. The age of patients was not associated with clinical results. Multivariate analysis demonstrated that the clinical stage of disease, the high frequency of spontaneous micronuclei and low-induced micronucleus frequency were independent and significantly unfavourable predictive factors for disease-free and overall survival. But for local control, only high MNSP and low-induced MN frequency were significant negative predictive variables. CONCLUSIONS: A high frequency of micronuclei before radiotherapy and a slight increase of micronucleus frequency during radiotherapy measured after 10 fractions of 2 Gy were independent on stage, statistically significant adverse predictors of clinical outcome in cervical carcinoma patients treated with radiotherapy.

The increment of micronucleus frequency in cervical carcinoma during irradiation in vivo and its prognostic value for tumour radiocurability.

A potential usefulness of micronucleus assay for prediction of tumour radiosensitivity has been tested in 64 patients with advanced stage (II B-IV B) cervical carcinoma treated by radiotherapy. The study of cellular radiosensitivity in vitro was conducted in parallel with the study of cellular damage after tumour irradiation in vivo. Radiosensitivity of in vitro cultured primary cells isolated from tumour biopsies taken before radiotherapy was evaluated using cytokinesis-block micronucleus assay. Frequency of micronuclei per binucleated cell (MN/BNC) at 2 Gy was used as a measure of radiosensitivity. Radiation sensitivity in vivo was expressed as per cent increment of micronucleus frequency in cells isolated from biopsy taken after 20 Gy (external irradiation, 10 x 2 Gy) over the pre-treatment spontaneous micronucleus level and was called MN20. Very low correlation (r = 0.324) was observed between micronucleus frequency in vitro and in vivo. Although micronucleus frequency at 2 Gy differed widely between tumours evaluated (mean MN/BNC was 0.224; range 0.08-0.416), no significant correlation was observed between this parameter and clinical outcome. The average increment of micronucleus frequency after 20 Gy amounted to 193% of spontaneous level (range 60-610%) and was independent of spontaneous micronucleation before radiotherapy. In contrast to in vitro results, these from in vivo assay seem to have a predictive value for radiotherapy of cervix cancer. The micronucleus increment in vivo that reached at least 117.5% of pretreatment value (first quartile for MN20 data set) correlated significantly with better tumour local control (P < 0.008) and overall survival (P < 0.045). Our results suggest that evaluation of increment of micronucleus frequency during radiotherapy (after fixed tested dose of 20 Gy) offers a potentially valuable approach to predicting individual radioresponsiveness and may be helpful for individualization of treatment strategy in advanced stage cervical cancer.

[Evaluation of 5-year surgical treatment outcome in patients with vulvar tumors]. / Ocena 5-letnich wyników leczenia chirurgicznego chorych na raka sromu.

A retrospective study of all patients with carcinoma of the vulva treated by surgery and/or radiation therapy, between 1980 and 1985, is reported. Sixty eight patients were analyzed for survival, recurrence patterns, complications and clinical features. The stages of disease were as follows: Stage I or II 49 pts, Stage III 13 pts and Stage IV 6 pts. The 5-year survival rate was 45.2%. Recurrences were diagnoses in 25% of the patients. With the less aggressive surgical approach used, combined with radiation therapy to eradicate subclinical disease, the morbidity rate was acceptable and the survival rate comparable to the reported after more aggressive surgery.