Prognostic implications of the bromodeoxyuridine labeling index of human gliomas

This study includes 182 patients with intracranial gliomas who received bromodeoxyuridine (BUdR), 200 mg/sq m intravenously, at the time of craniotomy but before tumor biopsy. The tumor specimens were stained for BUdR using the immunoperoxidase method; the BUdR labeling index (LI), or S-phase fraction, was calculated as the percentage of BUdR-positive cells. The median BUdR LI's for 127 primary moderately anaplastic astrocytomas, highly anaplastic astrocytomas, and glioblastomas (less than 1%, 2.7%, and 7.3%, respectively; range 0% to 38.1%) were not significantly different from those of 55 similar recurrent tumors (less than 1%, 4.3%, and 7.4%, respectively; range 0% to 30.5%). The mean LI was significantly higher in tumors from patients over 50 years of age than in tumors from younger patients (p less than 0.001). The age-related difference in LI's was found in both groups of patients with astrocytomas but not in those with glioblastomas. Kaplan-Meier survival curves showed a significantly greater probability of survival among patients whose tumors had LI's of less than 1% than among those with LI's greater than 5%; survival probability of patients with tumor LI's of 1% to 5% was intermediate between the two extremes. Thus, the BUdR LI appears to reflect the proliferative potential more accurately than the histopathological diagnosis and should therefore be considered an important factor in determining the prognosis of individual patients with intracranial gliomas and in selecting their treatment.     

Meningiomas: clinical implications of a high proliferative potential determined by bromodeoxyuridine labeling.

The clinical behavior of meningiomas with a high proliferative potential was analyzed to determine if the bromodeoxyuridine (BUdR) labeling index (LI) could be used to predict recurrence and the time to reoperation. Each patient received an intraoperative infusion of BUdR to label cells in DNA synthesis; the percentage of S-phase cells, or BUdR LI, of each tumor was determined immunohistochemically. Of 178 meningiomas studied, 53 had BUdR LIs greater than or equal to 1%. Of these 53 tumors, 21 were diagnosed histopathologically as malignant meningioma. Twenty-two percent of nonmalignant tumors and 81% of malignant tumors were recurrent or recurred after the BUdR study; repeat studies were performed in four patients. The mean BUdR LI of recurrent tumors was significantly higher than that of the nonrecurrent tumors [3.9 +/- 2.6 versus 1.9 +/- 1.0% (SD), P less than 0.005]. The recurrence rate was 100% for tumors with LIs greater than or equal to 5%, 55.6% for those with LIs of 3 to 5%, and 30.6% for those with LIs of 1 to 3%; the percentages of malignant meningiomas in these groups were 88%, 78%, and 19%, respectively. Logarithmic regression analysis showed that the time to reoperation (in months) can be predicted from the BUdR LI as: 70.0 x LI (%)-1.2 (R = 0.76). This formula can be used to estimate the doubling time of individual tumors and to predict the period of greatest risk of recurrence of meningiomas with a high proliferative potential.     

Correlation of in vitro bromodeoxyuridine labeling index and DNA aneuploidy with survival or recurrence in brain-tumor patients.

There are no previous reports correlating the in vitro bromodeoxyuridine (BUdR) labeling index (LI) with the clinical outcome in patients with brain tumors. The reliability of the LI as a predictor of patient survival or recurrence was examined in this study of 66 human brain tumors (19 gliomas, 18 meningiomas, and 29 others). Anti-BUdR staining was performed on surgically extirpated tumor tissue that had been treated with BUdR as previously described. Correlation of the BUdR LI with patient survival or tumor recurrence rate was carried out by the method of Kaplan and Meier. Deoxyribonucleic acid (DNA) aneuploidy was estimated in 52 cases. The results of this study indicate that BUdR LI values correlated well with the clinical course of patients with brain tumor. In comparison with patients with higher LI's, there was both a significantly higher survival rate for tumors other than meningiomas and a higher recurrence-free rate for meningiomas in patients with LI's of less than 4% and 1%, respectively. Although there was a tendency for patients without tumor aneuploidy to show better survival data than the others, no statistical difference was observed. These results suggest that the in vitro BUdR labeling method is reliable for prediction of a patient's prognosis, whereas prognosis on the basis of DNA aneuploidy alone is uncertain.     

Prediction of tumor doubling time in recurrent meningiomas. Cell kinetics studies with bromodeoxyuridine labeling

Eight patients with recurrent meningiomas (four malignant, two hemangiopericytic, and two nonmalignant) were given intravenous bromodeoxyuridine (BUdR), 200 mg/sq m, at the time of surgery to label cells in the deoxyribonucleic acid (DNA) synthesis phase; labeled cells were detected in excised tumor specimens by immunoperoxidase staining using anti-BUdR monoclonal antibody. These tumors showed a wide range of BUdR labeling indices (LI's), calculated as the percentage of BUdR-labeled cells divided by the total number of cells scored, from 0.3% to 5.4%. The tumor doubling times (Td's), estimated from serial computerized tomography scans, ranged from 8 to 440 days and showed a close inverse correlation with the BUdR LI's. A semilogarithmic linear regression analysis of these values yielded a correlation coefficient of 0.99. Tumor doubling time (Td) can be estimated using the formula: Td = 500 X Exp (-0.73 X LI), where Exp signifies the natural log base. By predicting the growth rate of meningiomas, the BUdR LI may supplement histopathological diagnosis and improve both the determination of prognosis and the design of treatment modalities in individual patients.     

Correlation of histopathological features and proliferative potential of gliomas

One hundred fifty-two intracranial gliomas of various types were reviewed in order to correlate the histopathological features with the proliferative potential of each tumor as reflected by the bromodeoxyuridine (BUdR) labeling index (LI). Patients undergoing surgical removal of gliomas were given a 30-minute intravenous infusion of BUdR (150 to 200 mg/sq m) to label S-phase tumor cells. The tumor specimens were stained immunohistochemically for BUdR and processed for routine histopathological diagnosis. The BUdR LI was calculated as the percentage of labeled cells among cells analyzed. Twenty-seven histological features in three categories (degenerative, vascular, and cellular changes) were considered. A significantly higher BUdR LI (p less than 0.05) was found in tumors with necrosis than in those without this feature; tumors with both coagulative and liquefactive necrosis had the highest BUdR LI (p less than 0.05). Increased vascularity was also associated with a higher BUdR LI (p less than 0.05). Although tumors with abnormal mitotic figures had a significantly higher BUdR LI than those without, the number of mitoses did not correlate with a higher BUdR LI. These results suggest that the number of mitoses is not a good indicator of tumor growth rate. Necrosis and increased vascularity should be heavily weighted in predicting the proliferative potential of individual gliomas.     

Proliferative characteristics of juvenile pilocytic astrocytomas determined by bromodeoxyuridine labeling.

Bromodeoxyuridine (BUdR) labeling studies were performed to characterize the biological and clinical behavior of 50 juvenile pilocytic astrocytomas (JPAs) from 47 patients. Each patient received an i.v. infusion of BUdR before tumor resection; the excised tumor specimens were stained by the immunoperoxidase method with anti-BUdR monoclonal antibody to determine the BUdR labeling index (LI), or percentage of S-phase cells. The BUdR LI ranged from 0.22 to 4.3% (less than 1% in 34 and greater than or equal to 1% in 16; mean +/- SE, 1.05 +/- 0.13%). Tumors from younger patients often had higher LIs, but as the age of the patients increased, the frequency of tumors with LIs greater than or equal to 1% decreased. Tumors from male patients had higher LIs than those from female patients (1.36 +/- 0.20% [SE] vs. 0.75 +/- 0.13%; P less than 0.01), and tumors in the cerebellum had higher LIs than those in the hypothalamus (1.39 +/- 0.24% vs. 0.87 +/- 0.15%; P less than 0.05). The LI did not correlate with the gross appearance of the tumor (solid or cystic) or with outcome after the initial diagnosis. Overall, there was no difference in the LIs of primary and recurrent tumors. Four tumors (3 primary and 1 recurrent) that recurred after subtotal resection had a higher mean LI than 32 tumors that did not recur after subtotal resection (2.6 +/- 0.7% vs. 0.74 +/- 0.09%; P less than 0.005). None of 14 totally resected tumors (mean LI, 1.3 +/- 0.2%) has recurred.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of bromodeoxyuridine labeling indices obtained from tissue sections and flow cytometry of brain tumors

Sixteen patients with brain tumors were given a 30- to 60-minute intravenous infusion of bromodeoxyuridine (BUdR), 200 mg/sq m. Grossly viable fragments were taken from the biopsied tumor specimens and divided into two portions. One portion was dissociated into single cells, stained both with fluorescein isothiocyanate (FITC) using anti-BUdR monoclonal antibody as the first antibody and with propidium iodide (for deoxyribonucleic acid), and analyzed by flow cytometry (FCM). The labeling index (LI) was calculated as the number of FITC-labeled cells expressed as a percentage of the total number of cells analyzed. The other portion was fixed in 70% ethanol, embedded in paraffin, sectioned, and stained with immunoperoxidase using anti-BUdR monoclonal antibody as the first antibody. The LI of these tissue sections was calculated in two ways: from selected areas in which the labeled cells were evenly distributed and from the entire tissue section. The LI's obtained by FCM correlated closely with those from the entire tissue sections (r = 0.99, p less than 0.000001) and were usually lower than LI's from selected areas of tissue sections. The LI's determined by FCM also correlated well with the LI's from selected areas of tissue sections (r = 0.82, p less than 0.00012), despite the difference in values between them. Thus, the FCM-derived LI and the tissue LI can both provide useful information for predicting the biological malignancy of individual tumors and for designing treatment regimens for individual patients with brain tumors; however, different standards should be used to interpret the LI's obtained by these two methods.     

A review of cell kinetic studies on brain tumors with special reference to anti-bromodeoxyuridine monoclonal antibody method

Cell kinetic studies on various human brain tumors were reviewed. Most studies have been carried out by means of 3H-thymidine and autoradiography in the past two decades. The average labeling index (LI) obtained from a pulse of 3H-thymidine is very high in medulloblastomas and glioblastoma multiforme (5-15%), low in well-differentiated gliomas (less than 1%), and intermediate in anaplastic astrocytomas. The higher the LI, the faster the tumor grows, probably reflecting a larger growth fraction. Therefore, measurement of the LI appears to be very helpful in predicting the prognosis of the patient as well as potentially helpful in the design of chemotherapy. However, isotopic studies not only take a long time to complete, but also have severe limitations because of potential radiation hazard to patients and environmental pollution. Development of an anti-BUdR (or BrdUrd) monoclonal antibody to detect nuclei which incorporate BUdR is a breakthrough that can expand this line of research, since: 1) BUdR is non-radioactive and doses needed for this purpose are virtually non-toxic; 2) use of flow cytometric analysis of FITC conjugated anti-BUdR antibody facilitates rapid acquisition and data analysis and, 3) it will be technically easier to study the proliferative capacity of patients with brain tumors. A 30 min exposure of 9L monolayer cells to 10 X 2-10 X 2(-4) microM BUdR produced satisfactory results against a 1: 60 dilution of FITC conjugated antibody (Becton-Dickinson, Mt. View, CA). Also 9L cells which were exposed various concentrations of BUdR (10 X 2-10 X 2(-4) microM) for 30 min were harvested in single cell suspension and reacted with the antibody and analysed with flow cytometry. Fluorescent nuclei (48.6%) were similar to the fraction of cells in S phase analysed from DNA histograms as well as the LI obtained from autoradiographic study after a pulse of 3H-thymidine. After 1-40 mg/kg of BUdR were injected into the peritoneal cavity of rats with 9L brain tumors, tumors were removed 1 hr later and digested with enzyme cocktail, fixed with 70% ETOH, denatured with HCl, and stained with FITC conjugated anti-BUdR antibody. The nuclei which reacted with the antibody were discriminated well with flow system at 488 nm light through LP 515 and SP 560 filters. 10.0-15.5% of the cells were fluorescent in each group and the intensity of fluorescence was dose dependent although not strictly proportional to the amount of BUdR administered.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pediatric central nervous system tumors: a cell kinetic study with bromodeoxyuridine

Bromodeoxyuridine (BrdU), 150 to 200 mg/m2, was administered at the time of operation to 20 pediatric patients with neuroectodermal tumors to label tumor cells in the S phase. Immunocytochemical techniques were used on excised tumor specimens to detect cells containing BrdU, and the BrdU labeling index (LI) was calculated as the number of BrdU-labeled cells divided by the total number of cells counted. Four medulloblastomas, three glioblastomas multiforme, and two highly anaplastic astrocytomas had average BrdU LIs of 13.0 +/- 3.0% (SE), 12.7 +/- 4.3%, and 14.6 +/- 6.7%, respectively. Three of nine moderately anaplastic astrocytomas had BrdU LIs of greater than 1% (average, 6.5 +/- 2.4%), whereas six had LIs of less than 1%. In two juvenile pilocytic astrocytomas, which are considered slow-growing, the BrdU LIs were unexpectedly high, averaging 6.5 +/- 1.4%. Thus pediatric medulloblastomas, glioblastomas multiforme, highly anaplastic astrocytomas, and a minority of moderately anaplastic astrocytomas had high proliferative potentials, whereas most of the moderately anaplastic astrocytomas had low proliferative potentials. Although the number of cases in this study is still too small to yield statistically significant comparisons, the results indicate that some pediatric tumors have considerably higher LIs than histologically similar adult tumors studied previously.     

In situ cell kinetics studies on human neuroectodermal tumors with bromodeoxyuridine labeling

Thirty-eight patients undergoing surgical removal of neuroectodermal tumors of the central nervous system were given a 1-hour intravenous infusion of bromodeoxyuridine (BUdR), 150 to 200 mg/sq m, to label tumor cells in the deoxyribonucleic acid (DNA) synthesis phase (S-phase). The excised tumor specimens were divided into two portions: one was fixed with 70% ethanol and embedded in paraffin and the other was digested with an enzyme cocktail to make a single-cell suspension. The paraffin-embedded tissues were stained by an indirect peroxidase method using anti-BUdR monoclonal antibody (MA) as the first antibody. Single-cell suspensions were reacted with fluorescein isothiocyanate (FITC)-conjugated anti-BUdR MA's for flow cytometric analysis. S-phase cells that had incorporated BUdR into their DNA were well stained by both methods. The percentage of BUdR-labeled cells, or S-phase fraction, was calculated in tissue sections by microscopic examination and in single-cell suspensions by flow cytometric analysis. The biological malignancy of the tumors was reflected in the S-phase fractions, which were 5% to 20% for glioblastoma multiforme, medulloblastoma, and highly anaplastic astrocytoma, but less than 1% in most moderately anaplastic astrocytomas, ependymomas, and mixed gliomas. Two juvenile pilocytic astrocytomas and two low-grade astrocytomas from children had high S-phase fraction despite the fairly benign and slow-growing nature of these tumors. These results indicate that the S-phase fraction obtained immunocytochemically with anti-BUdR MA's may provide useful information in estimating the biological malignancy of human central nervous system tumors in situ.     

Histological grading and bromodeoxyuridine labeling index of astrocytomas. Comparative study in a series of 60 cases.

The histological grade and the bromodeoxyuridine (BUdR) labeling index of 60 astrocytomas of "ordinary" cell types (fibrillary, protoplasmic, gemistocytic, and anaplastic astrocytomas and glioblastomas) were compared to determine whether the grading system reflects the proliferative potential of the tumors. The tumor grade was based on the presence or absence of four criteria (nuclear abnormalities, mitosis, necrosis, and vascular endothelial proliferation): Grade 1, no criterion, Grade 2, one criterion, Grade 3, two criteria; and Grade 4, three or four criteria. The BUdR labeling index, or percentage of S-phase cells, was calculated in paraffin-embedded tumor sections after in situ labeling by intraoperative intravenous infusion of BUdR, 200 mg/sq m. Exponential regression analyses showed a positive correlation between the histological grade and labeling index (r = 0.88, p less than 0.001) that was stronger than the correlations between log labeling index and age (r = 0.55, p less than 0.001) and between grade and age (r = 0.55, p less than 0.001). These results indicate that the histological grading system reflects the proliferative potential of "ordinary" astrocytomas.     

Expression of tenascin-C in astrocytic tumors: its relevance to proliferation and angiogenesis

BACKGROUND: The expression and distribution of the extracellular matrix protein tenascin-C (TN-C) may be enhanced in human astrocytomas. The purpose of this study is to evaluate the expression of TN-C according to histological malignancy of tumor cells and its relevance to neoplastic angiogenesis in human astrocytic tumors.METHODS: Between 1994 and 1998, 52 astrocytic tumor specimens including 4 pilocytic astrocytomas, 13 astrocytomas, 3 anaplastic astrocytomas, and 32 glioblastomas were used in this study. A retrospective analysis was performed to evaluate a statistical correlation between TN-C expression and proliferative indices. We characterized the expression of TN-C in neoplastic vessels, around individual tumor cells as a tumor network, and in tumor cells by immunohistochemistry using antibodies against human TN-C. The proliferative indices were also investigated by immunostaining with the MIB-1 antibody against the Ki-67 proliferation antigen.RESULTS: TN-C immunoreactivity was found to be enhanced in tumor vessels and tumor networks of high-grade astrocytic tumors. The vascular TN-C deposition was greater in high-grade than in low-grade astrocytic tumors (p < 0.05). Its expression was the most intense in glioblastomas. Proliferation indices increased with tumor grade and MIB-1 labeling index (LI) was highest in glioblastomas. Moreover, expression of TN-C in tumor vessels was correlated with proliferative indices. CONCLUSIONS: Our data show that TN-C in human astrocytic tumors may be identified as a factor contributing to malignant progression. And also, enhanced expression of TN-C in tumor vessels having a high proliferative index indicates that TN-C could be involved in neoplastic angiogenesis.     

Flow cytometric determination of modal DNA population in relation to proliferative potential of human intracranial neoplasms

Paraffin-embedded specimens of brain tumors from 256 patients who had received an intravenous infusion of bromodeoxyuridine (BUdR) at the time of craniotomy were analyzed retrospectively by flow cytometry to determine the modal deoxyribonucleic acid (DNA) population. A single G1 peak was considered to represent a unimodal DNA population; two or more G1 peaks indicated a multimodal population. Most of the pituitary tumors and moderately anaplastic astrocytomas had unimodal DNA populations, whereas a higher percentage of other slow-growing tumors, such as meningiomas, ependymomas, and neurilemmomas, had multimodal populations (46.2%, 50.0%, and 60.0%, respectively). A relatively high percentage of the rapidly growing or highly malignant brain tumors, including highly anaplastic astrocytomas, glioblastomas multiforme, metastatic tumors, and medulloblastomas, also had multimodal populations (52.9%, 48.7%, 57.1%, and 66.7%, respectively). In most tumor groups, however, the percentage of tumors with a multimodal DNA population did not correlate with the BUdR labeling index or with the percentage of BUdR-labeled S-phase cells. Thus, modal DNA analysis by flow cytometry may provide information about the degree of heterogeneity and the biological behavior of individual brain tumors, but the results do not necessarily correlate with the rate of tumor growth or the prognosis in individual patients.     

Astroblastomas: a pathological study of 23 tumors, with a postoperative follow-up in 13 patients

Astroblastomas are rare, usually circumscribed, supratentorial tumors of young subjects and are characterized by a perivascular arrangement of the tumor cells. Their clinical behavior is unpredictable and their prognosis has been regarded as intermediate between that of astrocytomas and glioblastomas. A personal series of 23 astroblastomas was reviewed, adequate postoperative follow-up being available in 13 patients. Two distinct histological types were encountered: low-grade and high-grade. The low-grade type comprised tumors with better differentiated and more benign-appearing microscopical features. Five of the 8 patients with tumors of this type who were available for follow-up have survived from 3 to 20 years after treatment; in 1 patient the tumor converted into a fatal glioblastoma after 4 1/2 years. The high-grade type consisted of tumors with more anaplastic features. Three of the 4 patients with tumors of this type available for follow-up died after 1 1/2 to 2 1/2 years, the astroblastomas in 2 of them having converted into a glioblastoma and a gliosarcoma, respectively. One patient, however, has had an unexpected length of postoperative survival of 11 1/2 years. The best clinical results were obtained after total or subtotal resection of the tumor, followed by radiotherapy. The role of chemotherapy is still uncertain. This form of glioma illustrates the discrepancies that may sometimes be apparent between histopathological features and length of postoperative survival. The prognosis is also further complicated by the potential of the astroblastoma to convert into a more malignant type of glioma.     

A commentary on the biology and growth kinetics of low-grade and high-grade gliomas

Cell kinetics studies of patients with various gliomas published in the past decade have shown that the average labeling index (LI) obtained from a pulse of 3H-thymidine is very high in medulloblastomas (12.0% +/- 1.3%, standard error of the mean) and glioblastoma multiforme (9.3% +/- 1.0%), low in well differentiated gliomas (less than 1%), and intermediate in anaplastic astrocytomas (4.0% +/- 0.8%). The higher the LI, the faster the tumor grows, probably reflecting a larger growth fraction. In tumor tissues obtained at autopsy, two glioblastomas diluted out the labeling compound in the 2- to 4-month interval after labeling, whereas three glioblastomas and two anaplastic astrocytomas retained labeled neoplastic cells for 3 weeks to 5 months. Most patients whose tumors contained foci of labeled cells at autopsy survived longer. Well differentiated gliomas harbored labeled cells for 2 1/2 to 7 years. These findings indicate that the kinetics of proliferation in well differentiated gliomas are different from those in glioblastomas or anaplastic astrocytomas.     

Cell proliferation of human bladder tumors

The cell proliferation of bladder tumors was assessed via an immunohistochemical technique using anti-bromodeoxyuridine (BrdUrd) antibody. The incorporation of the thymidine analogue, BrdUrd, into DNA synthesis phase was performed by an in vitro labeling technique. The percentage of labeled S-phase cells was expressed as the labeling index (LI). Discrimination between BrdUrd-labeled and unlabeled cells was easy because of the absence of background staining. The average LI obtained using this method in normal, normal epithelium bearing bladder tumors and cystitis was 5.0%, 4.0% and 5.0%, respectively. On the other hand, LI in bladder tumors was 13.0%, while the difference from non-malignant bladder epithelium was significant. As in high grade tumors, the labeled cells distributed throughout both the basal and surface layers of epithelium, compared to low grade tumors and controls. However, there was some variation in the distribution pattern within the same tumor depending on the histological site. On the other hand, the higher S-phase fraction was found in high grade or invasive bladder tumors. Bladder tumors with lymph node involvement had higher LI than those without the involvement. In patients who underwent TUR, the LI was as high as 10.0% in the recurrent group compared with 7.3% in the non-recurrent group. Moreover, in the total cystourethrectomy group, higher LI's were obtained in a patient dying of cancer (20.0%) and a patient with postoperative metastasis (21.0%) than in the non-recurrent group (14.8%). The high frequency of S-phase cells within tumor tissue appears to indicate a more malignant potential and thus a poor prognosis. Although further studies are required for its full significance, the measurement of BrdUrd labeling index by in vitro labeling method promises to afford useful information regarding the biological behavior of bladder tumors.     

Evaluation of radiation therapy in pediatric brain stem glioma by computed tomography: CT findings and tumor response to radiotherapy

The effects of radiation therapy on 29 brain stem gliomas in childhood were evaluated by computed tomography (CT). The patients received radiation of 2 Gy/day as a single fraction, 5 day a week with a total dose of 40 to 60 Gy. Initial CT findings of brain stem gliomas were divided into two types: diffuse and localized. Of 29 children, 5 had localized and 24 had diffuse tumor. Histological diagnoses were available for 18 patients, 4 with localized and 14 with diffuse tumor. All of the localized tumors were astrocytomas and diffuse tumors included 13 anaplastic gliomas (glioblastomas), 3 anaplastic astrocytomas, and one astrocytoma. Complete response or partial response to radiation therapy was observed on CT in 100% (5/5) of the localized tumors and 46% (11/13) of the diffuse tumors at the first evaluation. Contrary to expectation, low-grade gliomas responded much better to radiation therapy than high-grade gliomas. The response rates were 80% (4/5) in astrocytoma, 67% (2/3) in anaplastic astrocytoma, and 38% (5/13) in anaplastic glioma. In the follow-up CT after radiation therapy, a delayed effect was observed in only one of the 24 diffuse tumors. Nine of 10 children who had a re-irradiation following the recurrence experienced very little benefit. None of the patients with localized tumors have shown evidence of tumor progression or recurrence, and the quality of their life has been excellent. On the other hand, all of the patients with diffuse tumor died within 20 months after initial treatment. The results of this study suggest that radiation therapy is beneficial for localized tumors but not for diffuse tumors, and new treatments need to be developed for diffuse tumors.     

Adult intramedullary astrocytomas of the spinal cord.

In this series, 25 adult patients with intramedullary astrocytomas were treated by radical excision alone. Six patients proved to have anaplastic astrocytoma; five of them died within approximately 2 years and the sixth has demonstrated disease progression. The other 19 patients were diagnosed as having low-grade astrocytoma (16 cases) or ganglioglioma (three cases); two of these had advanced preoperative neurological disability and died of medical complications. Fifteen of the remaining 17 patients have no clinical evidence of tumor recurrence after a mean follow-up period of 50.2 months; the other two have a small residual neoplasm that demonstrates no progression. Of these 17 patients, seven had previously received radiation therapy, but had clear evidence of tumor growth subsequently. This experience suggests that surgery is not beneficial for anaplastic spinal astrocytoma. However, in cases of low-grade tumor, radical excision is associated with minimal morbidity and an excellent long-term prognosis when carried out before significant disability occurs.     

Proliferative potential of malignant glioma cells before and after interstitial brachytherapy.

The viability of tumor cells in radionecrotic tissue after interstitial brachytherapy (BRTX) was evaluated using immunohistochemical markers of proliferative potential in primary and recurrent tumors. Tumor specimens from 30 patients with malignant gliomas (14 anaplastic astrocytomas, 16 glioblastomas) taken before and after BRTX were examined using MIB-1 monoclonal antibody. Histological examination of specimens obtained by craniotomy or stereotactic biopsy after BRTX revealed tumor recurrence in 18 patients and radionecrosis in 12 patients including two with pure radionecrosis and 10 with a mixture of both tumor and radionecrosis. The MIB-1 index of the tumors with radionecrosis was 7.6 +/- 5.5%, and that of the primary tumors was 17.0 +/- 11.2%, showing a significant difference (p < 0.05). There was no significant difference between the MIB-1 index of the primary tumors with local recurrence after BRTX and the primary tumors which underwent radionecrosis. Although morphologically viable tumor cells were found in the radionecrotic tissue, BRTX causes a reduction in the proliferative potential of these tumor cells.     

Stereotactic interstitial radiosurgery with a miniature X-ray device in the minimally invasive treatment of selected tumors in the thalamus and the basal Ganglia

The aim of this study was to evaluate the role of interstitial radiosurgery (IR) using the photon radiosurgery system (PRS) in the treatment of selected tumors within the thalamus and the basal ganglia. The PRS is a miniature X-ray generator that was developed for interstitial irradiation. This series included 14 patients (5 with glioblastomas, 4 with low-grade astrocytomas and 5 with metastases) harboring spheroidal lesions with dimensions ranging from 13 to 42 mm (mean 30 mm). After stereotactic biopsy, a radiation dose ranging from 6 to 15.4 Gy (mean 11.3 Gy) was delivered at the target volume margins. Follow-up varied from 3 to 26 months (mean 10.2 months). In the group of glioblastomas, 3 patients died (3-12 months after the procedure) because of tumor progression, while the remaining had tumor control. Two patients with metastases died from systemic disease (4-9 months after the treatment), and 3 were alive and well at the end of the study. Local control was achieved in all metastases. Patients with low-grade astrocytomas were well and imaging studies showed tumor control PRS IR is a minimally invasive procedure for the treatment of selected glial or secondary brain tumors. Compared to conventional radiosurgery (brachytherapy and external radiosurgery), PRS IR presents dose delivery characteristics useful for the treatment of tumors in the thalamus and basal ganglia, without inconveniences such as handling radioisotopes, the need of expensive facilities and radiation protection measures. Although the clinical value needs further investigations, PRS IR seems to be effective in metastases while it provides less benefit in malignant gliomas. PRS IR could have a major role in the treatment of low-grade astrocytomas.