Prognostic significance of proliferation rate and DNA ploidy in astrocytic gliomas treated with radiotherapy

Abstract

Aim

The proliferative potential, and DNA ploidy in 50 brain tumours (15 grade I & II, and 35 grade III & IV astrocytomas) were investigated using bromodeoxyuridine (BrdUrd) incorporation and flow cytometry.

Materials/Methods

Tumour samples taken from each patient during surgery were incubated in vitro for one hour at 37°C with bromodeoxyuridine (BrdUrd), using the high pressure oxygen method. The percentage of BrdUrd-labelled cells (BrdUrd Labelling index, BrdUrd LI), and the total DNA content were evaluated. After surgery, 21 patients received conventionally fractionated radiotherapy (RT), 11 patients received accelerated RT, and 18 patients underwent hypofractionated RT.

Results

The tumours showed variability in BrdUrd LI values, which ranged from 0.3 to 15.8%. A significantly higher mean value for BrdUrd LI was shown in grades AIII & IV (3.5%), than in astrocytomas of grades AI & II (1.5%, p=0.005). A lower though not statistically significant percentage of DNA aneuploidy was observed in low-grade (40.2%) glioma than was seen in high-grade (65.7%) glioma. Univariate analysis showed that younger (≤50 years) patients (p=0.001), those with AI & II glioma (p=0.000), low tumour proliferation rate (BrdUrd LI ≤2.1%, p=0.006) and conventional or hypofractionated RT (p=0.000) had a significantly higher 5-year survival rate. Tumour ploidy had no influence on patients’ survival (p=0.261). However, a Cox multivariate analysis showed that only the patients’ age (>50 years), high grade tumours (AIII & IV) and accelerated RT were significantly unfavourable prognostic factors in terms of survival.

Conclusions

To improve RT results, younger patients (≤50 years) with fast proliferating tumours should receive more aggressive treatment.