Age and bromodeoxyuridine labelling index as prognostic factors in high-grade gliomas treated with surgery and radiotherapy.

AIMS: To determine the prognostic value of proliferative potential and DNA ploidy in 72 brain tumours (36 grade III and 36 grade IV astrocytomas) using bromodeoxyuridine (BrdUrd) incorporation and flow cytometry. MATERIAL AND METHODS: All 72 patients underwent excision, mostly incomplete of the tumour. After surgery, eight patients received conventionally fractionated radiotherapy, 11 patients received accelerated radiotherapy, and 53 patients received hypofractionated radiotherapy. Tumour samples taken during surgery from each patient were incubated in vitro for 1 h at 37 degrees C with 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: RESULTS: The tumours showed variability in the BrdUrd LI values, which ranged from 0.3 to 19.1%. No difference was observed in mean BrdUrd LI between grade III and grade IV sub-groups. A significantly higher percentage of DNA aneuploidy was observed in grade III gliomas (69.4%) than in grade IV gliomas (52.8%). Univariate analysis showed that younger patients (< or = 51 years) (P = 0.021) with grade III gliomas (P = 0.030) and low tumour proliferation rate (BrdUrd LI < or = 2.7%, P = 0.028) had significantly higher 5-year survival rates. Tumour ploidy had no influence on patients' survival (P = 0.591). However, Cox multi-variate analysis showed that only age over 51 years, and high tumour proliferation rate (BrdUrd LI > 2.7%), were significant unfavourable prognostic factors in patient survival. CONCLUSION: In this study, independent prognostic factors for patients with high-grade gliomas treated with surgery and post-operative radiotherapy are age and tumour proliferation rate assessed according to the BrdUrd LI.

Flow cytometric analysis of DNA ploidy and proliferative potential in brain tumours.

The proliferative potential and DNA ploidy in 203 brain tumours (27 astrocytomas grade I, 37 grade II, 80 grade III, and 59 grade IV) were investigated using bromodeoxyuridine (BrdUrd) incorporation and flow cytometry. One to three tumour samples from each patient were incubated in vitro for one hour at 37 degrees C with bromodeoxyuridine (BrdUrd) using the high preasure oxygen method. After incubation, fixation and staining, the cell preparations were analysed by flow cytometry. The percentage of BrdUrd-labelled cells (BrdUrd Labelling Index, BrdUrdLI), the predicted potential doubling time (predTpot) and the total DNA content were evaluated. The percentage of unlabelled S-phase cells (SPF) and proliferative index (PI, the percentage of cells in S + G2 phases) were also estimated. DNA aneuploidy was found in 61.1% of high-grade (III-IV) and 50.0% of low-grade (I-II) astrocytomas. The tumours showed variability in the BrdUrdLI values which ranged from 0.2 to 15.8%. Significantly higher mean value for BrdUrdLI was shown in grade III-IV astrocytomas (3.4%), than in grade I-II astrocytomas (1.5%), p = 0.0068. Also significantly shorter mean predTpot was shown in high grade III-IV astrocytomas (28 days) than in low grade I-II tumours (51 days), p = 0.0096. However, no relationship was shown between other cell proliferation parameters and histological grade. The mean intratumoral variability calculated on the basis of BrdUrdLI values on 2-3 samples from each tumour amounted to 31.2% +/- SD 15.9%.

Expression of oncoprotein Bcl-2 and bax protein in the infiltration zone and in the parenchyma of primary glia-derived supratentorial neoplasms.

The aim of the study was to determine the survival of cells in the infiltration zone of the glia-derived primary tumors of the central nervous system and in the core of the tumor tissue with the use of immunocytochemical methods. According to the recent studies the proper functional relation of bcl-2 and bax proteins may play a major role in one of the possible pathways leading to cell survival or to cell death. From the point of view of the biological activity of a tumour the evaluation of cell population demonstrating the ability for survival is of importance for predicting tumour recurrence. We found that in the infiltration zone neurocytes and reactive glial cells had a strong expression of bcl-2 and weak expression of bax protein. Thus, we have concluded that the use of bcl-2 and bax can be a useful tool in the evaluation of survival activity of non-neoplastic cells in the infiltration zone and of the neoplastic cells within the tumour core. The latter cell populations can be regarded as germs responsible for tumour recurrence.

Some remarks on adherence reactivity of autologous PHA--transformed lymphocytes on human glial tumor cells in vitro.

In 16 patients with primary supratentorial and in 1 with cerebellar tumor among them 5 multiforme glioblastomas, 3 malignant astrocytomas, 6 astrocytomas of other subtypes and 1 mixed glioma (oligo-astrocytoma) the peripheral blood was drawn and lymphocytes were separated from it. Out of the removed part of the tumors about 10 cultures in each case were prepared and cultivated at least 14 days. When the growth zone was well developed the cultures were used for further studies. All samples of the separated lymphocytes activated with PHA were cultivated for 72 h. So prepared lymphocytes were added to the tumor culture in vitro and observed for 24 h. After that time the not adhered lymphocytes were removed and the remaining tissue cultures with adhered lymphocytes were fixed and stained and the number of lymphocytes was counted. It was found that 1 h after the addition of lymphocytes the number of lymphocytes was very high, though a great part of them did not adhere to the tumor tissue. After 24 h the number of adhered lymphocytes was small or minute. Taking into consideration the results obtained it seems that the low efficiency of therapy of gliomas with autologous lymphocytes in vivo can result from the very weak direct contact with tumor cells. The influence of lymphocytes can be very limited so more as the tumor cells can secret biological active substances like PGE2, which counteract the cytotoxic activity of lymphocytes. For that reason the number of lymphocytes can be of significant value as counterbalance to that properties of the tumor cells. Taking into account even secretion of tumor cells of the same biological active substances such as PGE2 which counteract the cytotoxic activity of lymphocytes for the efficient activity of lymphocytes the number of them may be of significant value.

[Comparison of two methods of postoperative radiotherapy in anaplastic cerebral oligodendroglioma]. / Porównanie dwu metod pooperacyjnego napromieniania chorych na anaplastycznego skapodrzewiaka mózgu. Wstepne wyniki prospektywnego badania klinicznego.

Preliminary results of prospective clinical study--49 adult patients with histologically proven anaplastic oligodendroglioma received postoperative radiotherapy. Patients were randomized to two treatment arms: Conventionally Fractionated Radiotherapy (CFR) and Large Fractionated Radiotherapy (LFR). In CFR group the whole brain was irradiated to the total dose of 50 Gy in 25 fractions over 5 weeks, then a 10 Gy "boost" in 5 fractions was delivered to the site of primary lesion in 5 days. In LFR group there were 3 courses of irradiation separated with one month interval. In each of the two first series the patients received 20 Gy in 5 fractions in five days to the whole brain, and in the third course, 10 Gy "boost" was delivered like in CFR regimen. The tolerance to treatment was good in both groups. Actuarial survival rates 2 and 4 years were 20% and 4% respectively for CFR group, and they were 27% and 0% respectively for LFR.

[Diagnosis and treatment of recurrent brain glioma]. / Rozpoznawanie i leczenie wznowy glejopochodnych guzów mózgu.

In the period from Jan 1 1984 to Dec 31 1990 clinical and radiological evidence of brain glioma was found in 120 cases treated previously surgically. The group comprised 55 women (46%) and 65 men (54%). At the time of tumour diagnosis their age was ranged 40 to 60 years. All patients received non-radical surgical treatment, supplemented with Co60 radiation in 104 cases, in 3 cases Co60 treatment was given together with chemotherapy (CCNU) and 12 patients received no complementary treatment. Thirty four patients (28%) had reoperations, in two cases even twice. In 86 cases (72%) treatment was palliative. Three types of secondary tumour regrowth were discerned. Reoperation prolonged survival and its effectiveness was greatest in regrowth type I. The shortest survival till the appearance of regrowth signs and the shortest survival after recurrence were in type II of regrowth.

Postoperative radiotherapy and radiotherapy combined with CCNU chemotherapy for treatment of brain gliomas.

A prospective, randomized trial evaluates the effects of two postoperative treatment regimens on survival in 198 adult patients with supratentorial gliomas. All patients were irradiated with 6,000 rads after possibly radical removal of tumors. CCNU administration in the doses of 100 mg/sq m of body surface every 6-8 weeks following surgery proved to have no significant effect on the survival of patients. The median survival time in patients receiving radiation therapy alone was 61 +/- 7 weeks, while in those receiving additional chemotherapy was 56 +/- 4 weeks. Tumor histological malignancy and patients age were found to be the only important prognostic factors, irrespective of the treatment modality.

[Results of combined treatment (by surgery, ionizing radiation and the cytostatic drug CCNU) of patients with anaplastic glial neoplasms of the brain]. / Wyniki skojarzonego leczenia (operacyjnego, promieniami jonizujacymi i cytostatykiem CCNU) chorych z anaplastycznymi glejopochodnymi nowotworami mózgu.

For estimating the effectiveness of combined treatment of cases of anaplastic gliomas of the cerebral hemispheres retrospective analysis was undertaken of 83 patients treated only surgically and prospective analysis of 81 patients treated by the combined method. In the group treated only surgically 47 patients had glioblastoma multiforme, and 36 had anaplastic oligodendroglioma. The general condition and the neurological status were evaluated using the score of Karnofsky. In the group of combined treatment the patients were given telegammatherapy from Co-60 cobalt source by the method of Skolyszewski and CCNU (Belustine) every 6-8 weeks for 1 year in doses of 100 mg/m2. In about 25% of patients transient leucopenia was observed, and 20% had transient thrombocytopenia. In about 30% of cases transient increase of intracranial pressure occurred. In the compared groups it was possible to establish, using the statistical method of representation probability of Kaplan-Meier and statistical analysis of Gehan as modified by Wilcoxon, that the mean survival time in the surgically treated patients was 6.25 months, while in the patients treated by combined method it was 13.97 months.

[Results of surgical treatment of anaplastic cerebral gliomas]. / Wyniki leczenia operacyjnego chorych z anaplastycznymi glejakami mózgu.

In the years 1971 through 1977 247 patients with anaplastic cerebral gliomas were treated. Out of this material a group of 119 patients was completed who were treated only surgically and had follow-up examinations or responded to an inquiry form sent to them. In the light of this follow-up study it was established that the survival time was shortest, only up to 6 months, in the patients with preclinical symptoms lasting up to 3 months. In the remaining patients the survival time was longer, reaching over one year in 11 cases and over 2 years in 3 cases. In view of the mode of spread of recurrent neoplasm the authors differentiated exophytous expansion - with the infiltration filling the postoperative tissue defect and extending beyond its margins, infiltrative expansion - with the infiltration spreading on the walls of the postoperative tissue defect, destructive expansion - with the neoplasm infiltrating and destroying the brain tissue. Two latter modes of growth were most frequent and led to death of the patients without producing signs of intracranial hypertension.