Reoperation for recurrent glioblastoma and anaplastic astrocytoma

The advisability of a second operation for recurrent glioblastoma multiforme or anaplastic astrocytoma depends on the expected duration and quality of subsequent survival. We reviewed the results in 70 consecutive patients who underwent reoperation for supratentorial glioblastoma multiforme (n = 39) or anaplastic astrocytoma (n = 31) between 1975 and 1984. The operative morbidity rate was 5.7% (4 of 70 patients); the 6-week postoperative mortality rate was 4.3% (3 of 70 patients). The median duration of survival after reoperation was 36 weeks in patients with glioblastoma multiforme and 88 weeks in those with anaplastic astrocytoma. The median duration of high quality survival (defined as the period during which the patient had a Karnofsky performance score of at least 70) after reoperation was 10 weeks for patients with glioblastoma multiforme and 83 weeks for patients with anaplastic astrocytoma. Age and preoperative Karnofsky score in patients with glioblastoma multiforme and age in patients with anaplastic astrocytoma had statistically significant effects on the duration of high quality survival after reoperation, but not on postoperative survival independent of quality. Although age and functional status do not significantly affect the duration of survival after reoperation, they do have a significant effect on the quality of life after reoperation. Frequently, a patient can expect to spend a greater portion of his life at a higher level of function than he would have without reoperation. As adjunctive forms of therapy improve, reoperation will play an increasingly prominent role in the management of recurrent malignant astrocytic tumors.     

Clinicopathological study of diffuse type brainstem gliomas: analysis of 40 autopsy cases

Diffuse type brainstem glioma is one of the most malignant types of brain tumors and the prognosis is extremely poor. The proliferative potential of these tumors is presumed to be very high, but there is little information about the cell kinetics of brainstem glioma because surgical resection is rarely performed. The histological grade, tumor spread, growth potential, and prognosis were evaluated in 40 autopsy cases of diffuse type brainstem glioma. To quantify the growth potentials of individual tumors, the proliferating cell indices of Ki-67 (MIB-1) and proliferating cell nuclear antigen (PCNA) monoclonal antibodies were measured. Mean MIB-1 and PCNA proliferating cell indices were 20.4% (24 cases) and 37.0% (28 cases), respectively, in 34 glioblastomas. The median survival time was 40 weeks in 22 treated patients. The mean PCNA proliferating cell index was 10.8% in four of five anaplastic astrocytomas and the median survival time in four treated patients was 91 weeks. The MIB-1 and PCNA proliferating cell indices of one astrocytoma were 2.9% and 20.3%, respectively, and the survival time was 56 weeks. The overall median survival time was 32 weeks. There was a significant difference in PCNA proliferating cell indices between glioblastomas and anaplastic astrocytomas (p < 0.05) and there was a significant difference in survival time between glioblastomas (40 weeks) and anaplastic astrocytomas plus astrocytoma (74 weeks) among the treated patients (p < 0.05). Supratentorial extension was more frequent in glioblastomas than in anaplastic astrocytomas (p < 0.05). Our results suggest that the majority of diffuse type brainstem gliomas are glioblastoma and the proliferative potential is probably as high as that of adult supratentorial glioblastoma. Supratentorial extension and dissemination are relatively frequent in the advanced stage. Anaplastic astrocytoma or astrocytoma is rarer and less infiltrative and proliferative, and carries a slightly better prognosis than glioblastoma.     

Efficacy of temozolomide is correlated with 1p loss and methylation of the deoxyribonucleic acid repair gene MGMT in malignant gliomas

Promoter methylation of the deoxyribonucleic acid (DNA) repair gene, O(6)-methylguanine-DNA methyltransferase (MGMT), is associated with improved outcome of patients with glioblastoma multiforme and anaplastic astrocytoma treated with temozolomide (TMZ). Molecular genetic analysis of loss of heterozygosity (LOH) of 1p, 19q, or 10q, p53 mutation, and MGMT promoter methylation was performed in 44 assessable tumor specimens obtained from 46 patients with recurrent malignant gliomas, including 21 with glioblastoma multiforme, 17 with anaplastic astrocytoma, and eight with anaplastic oligoastrocytoma, which have heterogeneous features and variable histological diagnosis, to assess the correlation with the response to TMZ. LOHs of 1p and 19q, and MGMT promoter methylation showed positive correlations with the clinical response to TMZ therapy (p < 0.005, 0.05, and 0.05, respectively; Fisher's exact test). In addition, LOH of 1p and MGMT promoter methylation were associated with longer progression-free survival (p < 0.05 and 0.05, respectively; Cox regression analysis). LOH of 1p in the heterogeneous population of malignant gliomas may be one of the important factors besides MGMT methylation that predict better outcome in patients treated with TMZ.     

The conditional probabilities of survival in patients with anaplastic astrocytoma or glioblastoma multiforme

BACKGROUND: By the use of conditional probabilities of survival, we studied the yearly survival rates for individual tumor survivors. METHODS: Conditional survival rate was estimated in 114 consecutive patients with anaplastic astrocytoma or glioblastoma multiforme. Conditional probabilities of surviving some years given survival to a specific period of time after craniotomy and 95% confidence intervals were calculated in the individual tumor survivors. RESULTS: The estimated median survival was 30 months for 45 patients with anaplastic astrocytoma and 12 months for 69 patients with glioblastoma multiforme. The conditional probabilities of surviving next one year given survival to 1 year, 2 years, 3 years, 4 years, or 5 years after craniotomy for anaplastic astrocytoma were 86.2%, 75.0%, 85.9%, 77.8%, or 85.7%, respectively; for glioblastoma multiforme 64.8%, 58.7%, 85.7%, 80.0%, or 75.0%, respectively. The conditional probability of surviving to 5 years given survival to 2 years after craniotomy for anaplastic astrocytoma, i.e., surviving an additional 3 years, was 50.1%, which was better than observed 5-year survival rate (28.6%); for glioblastoma multiforme it was 40.2%, which also was better than observed 5-year survival rate (12.4%). CONCLUSIONS: The conditional probability of survival was a good method to clinically predict yearly survival rate for individual tumor survivors. In addition, the method can estimate the probabilities of surviving next some years given survival to a specific period of time after craniotomy. It also showed a more encouraging result than observed survival rate in patients with supratentorial malignant astrocytomas.     

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.     

Thalamic Gliomas: A clinicopathologic analysis of 20 cases with reference to patient age

Summary Twenty patients (M 11, F 9; ranging from 1–77 years old) with histologically proven glial tumours in the thalamic region, treated from 1979 until 1994 at Kyushu University Hospital were retrospectively reviewed and analysed in order to elucidate their clinical and neuropathological characteristics. The initial common clinical manifestations were those of increased intracranial pressure or motor weakness. The histological diagnosis of the tumour was pilocytic astrocytoma in 2 patients, fibrillary astrocytoma in 7, anaplastic astrocytoma in 7, and glioblastoma multiforme in 4. The initial treatment was surgery alone in 4 patients, surgery followed by radiation therapy in 5, surgery followed by radiation therapy and chemotherapy in 9, and conventional radiation therapy alone in 2 patients. The 3-year overall actuarial survival rate for all patients was 20% but was related to both the histological type and the age of the patients: As a result, the rate was 44% for patients with low-grade astrocytoma compared to 0% for those with high-grade astrocytoma. While 5 out of 11 patients under the age of 25 years at their initial presentation have survived for from 2–16 years after the diagnosis, all patients presenting after the age of 25 years died within 3 years after treatment. Thalamic glial tumours are not a homogeneous group of tumours in terms of clinical behaviour and histopathological features, and the poor overall results, especially in adult tumours, thus emphasise the need for continued research in the treatment of these tumours.     

Neoadjuvant chemotherapy in stage III breast cancer

Neoadjuvant chemotherapy in advanced breast cancer can potentially downstage disease prior to definitive surgery. In this study, a doxorubicin-based neoadjuvant regimen was administered to stage III breast cancer patients to assess 1) primary tumor response, 2) tumor involvement of resection margins, and 3) predictive value in cancer outcome. Eighty-two patients with stage IIIA and IIIB breast cancer diagnosed between 1990 and 2003 were studied. All patients received similar chemotherapy regimens, consisting of doxorubicin, cisplatin, and 5-fluorouracil, plus surgery and radiation therapy. End points measured include primary tumor response [complete response (CR) = 100%, partial response (PR) > 50%, or no response (NR) < or = 50%], resection margins for tumor, disease-free, and overall survival. Kaplan-Meier and log-rank tests were performed. Of the 82 patients studied, 34 received neoadjuvant therapy, 48 received conventional postoperative treatment. Seventy-two per cent of the stage IIIB and 22 per cent of the stage IIIA patients received neoadjuvant therapy. In the neoadjuvant group, 29 (85%) patients demonstrated tumor response, 9 (26%) of which were CR. Tumor-free resection margins were achieved in 94 per cent of the neoadjuvant group. Survival analysis demonstrated no benefit comparing neoadjuvant versus postoperative adjuvant therapy but hints at improved disease-free survival in neoadjuvant CR patients (log-rank test, P = 0.07). Eighty-five per cent of patients with stage III breast cancer treated with neoadjuvant chemotherapy experienced clinical response, with 26 per cent CR, and 97 per cent tumor-free resection margins. CR may portend a better cancer outcome.     

Reoperation in the treatment of recurrent intracranial malignant gliomas

Fifty-five consecutive patients with recurrent intracranial malignant gliomas were reoperated at Memorial Sloan-Kettering Cancer Center from 1972 to 1983. The patients were 10 to 70 years old (median, 48 years). Thirty-five patients (64%) had glioblastoma multiforme, and 20 (36%) had anaplastic astrocytoma. The median interval between the first operation and reoperation was 43 weeks. The Karnofsky rating before reoperation ranged from 40 to 90 (median, 70). Eleven patients (20%) had more than one reoperation. The mortality rate was 1.4% per procedure, and the morbidity rate was 16% per procedure. After reoperation, 41 patients (75%) had chemotherapy and/or radiation therapy. The median survival for all patients was 92 weeks. The median survival after reoperation was 36 weeks. Patients with Karnofsky ratings of greater than or equal to 70, with anaplastic astrocytomas, or in whom gross total removal of the tumor was undertaken lived longer than their respective counterparts (P less than 0.05). Prereoperation Karnofsky rating and extent of surgical resection were the most important independent factors related to survival after reoperation according to multivariate analysis (P less than 0.01 and P less than 0.05, respectively). Twenty-five patients (45%) had improved Karnofsky ratings after reoperation, and the 32 patients (58%) who were independent after reoperation were able to stay so for more than 6 months of their survival time (median value). Reoperation is feasible and can be accomplished with acceptable mortality and morbidity. When intracranial malignant gliomas recur, the combined use of reoperation and adjuvant therapy prolongs good quality life.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intra-arterial chemotherapy in combination with radiotherapy for invasive bladder cancer and prostate cancer

Forty-five patients with muscle-invasive bladder cancer treated with intra-arterial doxorubicin chemotherapy plus low-dose radiotherapy between September 1979 and March 1990 were retrospectively studied. Twenty-eight (62%) patients achieved a complete response (CR) and in all of them, a functional bladder could be preserved. The 10-year cause-specific survival rate of patients with CR was 95.5%, but that of patients not achieving a CR was 39%. These results demonstrate that in patients who achieve a CR with this treatment, we may be able to preserve a functional bladder. In a prospective study, we designed a new intra-arterial chemotherapy regimen in order to achieve a higher degree of effectiveness and to preserve a functional bladder. Twenty-three patients were treated with concurrent pirarubicin/cisplatin intra-arterial chemotherapy and radiotherapy after complete transurethral resection. Twenty-one (91%) patients achieved CR. One of these patients had relapse with lung metastases and was treated surgically. Two patients who did not achieve a CR died of cancer, and 21 patients are alive with preservation of functional bladder. For treatment of prostate cancer, we now administer only adjuvant intra-arterial chemotherapy plus irradiation for patients after radical prostatectomy.     

Brachytherapy of recurrent malignant brain tumors with removable high-activity iodine-125 sources

Thirty-seven patients harboring recurrent malignant primary or metastatic brain tumors were treated by 40 implantations of high-activity iodine-125 (125I) sources. All patients had been treated with irradiation and most had been treated with chemotherapeutic agents, primarily nitrosoureas. Implantations were performed using computerized tomography (CT)-directed stereotaxy; 125I sources were held in one or more afterloaded catheters that were removed after the desired dose (minimum tumor dose of 3000 to 12,000 rads) had been delivered. Patients were followed with sequential neurological examinations and CT scans. Results of 34 implantation procedures were evaluable: 18 produced documented tumor regression (response) for 4 to 13+ months; five, performed in deteriorating patients, resulted in disease stability for 4 to 12 months. The overall response rate was 68%. In 11 patients, implantation did not halt clinical deterioration. At exploratory craniotomy 5 to 12 months after implantation, focal radiation necrosis was documented in two patients whose tumor had responded initially and then progressed, and in three patients whose disease had progressed initially (four glioblastomas, one anaplastic astrocytoma); histologically identifiable tumor was documented in two of these patients. All improved after resection of the focal necrotic mass and are still alive 10, 15, 19, 24, and 25 months after the initial implantation procedure; only one patient has evidence of tumor regrowth. The median follow-up period after implantation for the malignant glioma (anaplastic astrocytoma and glioblastoma multiforme) group is 9 months, with 48% of patients still surviving. While direct comparison with the results of chemotherapy is difficult, results obtained in this patient group with interstitial brachytherapy are probably superior to results obtained with chemotherapy.     

Sarcoma of the breast. A study of 32 patients with reappraisal of classification and therapy.

A retrospective clinicopathologic review of 32 patients with mammary sarcoma exclusive of angiosarcoma or lymphoma was performed. For 25 patients with previously untreated lesions, the median tumor diameter was 4 cm and 14 patients had high or intermediate grade lesions. One of 22 patients treated by mastectomy and one of three patients treated by local excision died of sarcoma yielding an actuarial 5-year survival of 91%. None of the 25 patients had received adjuvant chemotherapy and only one treated by mastectomy had post-operative radiation therapy. Seven other patients were referred for treatment of recurrent mammary sarcoma. In this group, median size of the primary tumor was 6 cm and four had high or intermediate grade histology. Tumor control was achieved for only one of five patients with local recurrence and neither of the two with distant metastases. Median survival was 6 months following initiation of treatment for recurrence. Whenever possible breast sarcomas should be classified according to histologic cell type and grade. For lesions not readily classified, the terms unclassified or anaplastic sarcoma should be used. The diagnosis of stromal sarcoma is best reserved for those infrequent sarcomas that can be traced to the specialized periductal and perilobular stroma of the breast. Total mastectomy is recommended for most patients with postoperative radiation therapy indicated when the adequacy of the margin is in doubt. The role of adjuvant chemotherapy in the primary management of mammary sarcoma is yet to be determined.     

Supratentorial anaplastic gliomas in adults. The prognostic importance of extent of resection and prior low-grade glioma

A retrospective analysis is presented of factors affecting the length of survival of 285 consecutive adults with newly diagnosed biopsy-proven supratentorial anaplastic glioma (188 cases of glioblastoma multiforme, 76 of anaplastic astrocytoma, 11 of anaplastic mixed glioma, and 10 of anaplastic oligodendroglioma) treated at a regional cancer center from July, 1982, through December, 1987. The approach to initial therapy included maximum feasible resection and radiotherapy. The median survival time for all patients was 35 weeks. Multivariate analysis demonstrated that age, duration of symptoms, preirradiation performance status, tumor histology, accessibility to resection, extent of resection, radiotherapy, and prior low-grade glioma were significant independent variables influencing survival. The prognostic importance of age, duration of symptoms, performance status, and tumor histology are already recognized, but three "new" findings are reported. First, patients with anaplastic oligodendroglioma had the longest median survival time (278 weeks). Second, corrected for accessibility and all other variables, patients with gross total resection lived longer than those with partial resection, and patients with any degree of resection lived longer than those who underwent only a biopsy procedure. Third, patients with anaplastic glioma in whom there was a prior history of low-grade glioma lived significantly longer after the diagnosis of anaplastic glioma than did patients in whom the anaplastic glioma apparently arose de novo.     

Intraoperative radiation therapy for malignant glioma.

Intraoperative radiation therapy (IORT) was used as part of the initial therapy for malignant glioma in 32 of 73 patients with histologically verified anaplastic astrocytoma (grade III astrocytoma) and glioblastoma multiforme. The initial treatment for all cases was subtotal or total tumor resection combined with external irradiation and chemotherapy. IORT was performed 1 week after tumor resection, with doses of 10-50 Gy (mean 26.7 Gy) in one session. Fourteen of 32 cases had IORT two times because of tumor recurrence. The IORT patients had survival rates at 24 and 36 months after initial treatment of 57.1 and 33.5% (median survival 26.2 months). The other 41 patients had 23.6 and 13.1% survivals (median survival 20.7 months), which were significantly lower (p less than 0.01). Tumor recurrence within the original lesion site was suspected because of clinical condition, computed tomography, and magnetic resonance imaging studies in 65.6% of the IORT group (21 cases) 12 months after initial treatment. Twenty cases of death in the IORT group, including five autopsy cases, demonstrated regional tumor recurrence with a high incidence of intraventricular tumor invasion. The authors consider IORT is beneficial for selected malignant glioma patients, including tumor recurrence, because of prolonged survival.     

Gemistocytic astrocytomas: a reappraisal

Although gemistocytic astrocytomas are considered slow-growing astrocytomas, they often behave aggressively. To clarify the biological and clinical behavior of these rare tumors, the authors retrospectively identified 59 patients with gemistocytic astrocytoma whose tumors were diagnosed and treated between June, 1976, and July, 1989. Three patients who were lost to follow-up review were excluded, as were two whose original slides could not be obtained and three whose tumors were diagnosed at recurrence or at autopsy. The pathological material of the remaining 51 patients was reviewed using two sets of histological criteria. Thirteen patients (Group A) had "pure" gemistocytic astrocytoma, defined as a glial tumor with more than 60% gemistocytes/high-power field and a background of fibrillary astrocytes. Fifteen patients (Group B) had "mixed" gemistocytic astrocytoma, defined as a glial tumor with 20% to 60% gemistocytes/high-power field and a background of anaplastic astrocytes. Twenty-three tumors did not meet these criteria and were excluded from analysis. The median age of the patients was 48.5 years in Group A and 38.3 years in Group B (p less than 0.05). In both groups, the median Karnofsky Performance Scale score was greater than 90%. All patients underwent surgical procedures (four total and 19 partial resections, and five biopsies) and postoperative radiation therapy. The majority also had interstitial brachytherapy, chemotherapy, or both. Ten patients had one reoperation for tumor recurrence and one had two reoperations; other treatments for recurrence included brachytherapy, chemotherapy, and repeat irradiation. All four patients who originally underwent gross total resection are still alive; all five who had a biopsy have died. There was no significant difference in median survival times between groups: 136.5 weeks in Group A (range 10 to 310+ weeks) and 135.6 weeks in Group B (range 31 to 460+ weeks). Analysis of all 28 patients showed a better prognosis for patients less than 50 years of age (185 vs. 36 weeks survival time; p less than 0.001), patients with preoperative symptoms lasting for more than 6 months (228.1 vs. 110.2 weeks survival time; p less than 0.05), and patients with seizures as the first symptom (185.7 vs. 80 weeks survival time; p less than 0.01). Survival time did not correlate with the presence of perivascular lymphocytic infiltration. The authors conclude that the presence of at least 20% gemistocytes in a glial neoplasm is a poor prognostic sign, irrespective of the pathological background. It is proposed that gemistocytic astrocytomas be classified with anaplastic astrocytomas and treated accordingly.     

Controlled multimodality treatment of brain stem gliomas

Thirty-eight children were diagnosed as having a brain stem glioma at Nagoya University. Thirty-three patients in our previous series from 1957 to 1983, were treated traditionally with radiation and at late stage with shunting operation for hydrocephalus and/or suboccipital decompression, but not with direct operation for tumors. In general, tumors constantly grew regardless histology and their mean survival time was only 7.0 months even with transient neurological remission. On the other hand, recent five patients since 1984 were treated with prospective multimodality treatment. According to neuroradiological studies by X ray and/or NMR, CT scanning, the brain stem glioma cases were classified into subgroups of intrinsic and exophytic. Then the former were treated non-surgically with adjuvant therapy of Interferon-ACNU-Radiation (IAR) and the latter were treated surgically at first by resection of the tumor followed by adjuvant therapy of IAR or interferon-CDDP. Four out of five patients responded to adjuvant therapy (complete response = 2, partial response = 2, response rate = 80%) and they are all alive after 7-28 months follow-up period. It is concluded from our results that CT scanning can diagnose the accurate location and nature of brain stem gliomas, surgical therapy benefits at least in exophytic cases, and IAR adjuvant therapy may prolong the survival time of patients.     

Re-operations of supratentorial anaplastic astrocytomas

Summary Results of re-operations of 99 adult patients with recurrent supratentorial lobar glioblastomas (60 patients) and anaplastic astrocytomas (39 patients) have been reviewed. In all cases both surgical interventions were performed at the same institute. Age of patients with glioblastoma varied between 19 and 64 and with anaplastic astrocytoma between 21 and 68 years, with a mean value of 48 and 36 years, respectively. The median interval between the first and second operations was 47 weeks for patients with glioblastoma and 83 weeks with anaplastic astrocytoma. The mortality rate of the re-operations was 3%. Following re-operation radio-and/or chemotherapy was applied in most of the cases. Median survival time after re-operation was 18.5 weeks in patients with glioblastoma and 55 weeks with anaplastic astrocytoma. Survival curves were calculated according to Kaplan-Meier method and for statistical evaluation the generalized Wilcoxon test and multiple linear regression method were used. Histologically lower grade tumour at the first operation and longer interval between the two operations proved to influence positively and differentiation of the primary tumour negatively the survival time.     

Preoperative history and postoperative survival of supratentorial low-grade astrocytomas

The preoperative history and postoperative course of histologically verified 348 low-grade and 383 anaplastic astrocytomas have been reviewed. In 71.2 and 48.0% of patients epilepsy was the initial symptom of a suspected astrocytoma, and the history was longer than 3 years in 28.1 and 19.5% of cases, respectively. Before the advent of CT, angiography was performed because of a suspected tumour 2-9 years before surgery in 34 cases. The second angiography years later demonstrated the tumour which in 18 cases at surgery proved to be low-grade astrocytoma or anaplastic astrocytoma in 16 cases. During the last 10 years CT or MRI demonstrated a low-density lesion in 21 patients years before surgery. Operation was postponed for different reasons. Ten tumours appeared at 'delayed' surgery as low-grade, but 11 as anaplastic astrocytoma. In the same period 29 further patients were operated on after a history of seizures, longer than 3 years. Histology showed anaplastic astrocytoma in 10 cases also. Malignant transformation occurred nearly in half of the patients during the observation period. This strongly suggests that dedifferentiation is a spontaneous process, an intrinsic feature of astrocytomas and does not depend on any kind of external stimulus. Another 51 patients' surgery was performed following a shorter (1-24 months) history of epilepsy. The 5-year survival rate was 44 and 39.5% Median survival times (53.5 and 51 months) did not show a significant difference between the two groups, but the total survival, including second survivals after reoperation displayed a significant difference (57.5 vs 67.5 months) in favour of patients with a shorter history of seizures. These experiences confirm the difficulties in decision of the time of surgery. Considering the frequent malignant transformation among patients with a long history of seizures, followed by a relatively shorter survival, it may be supposed that an early radical removal in suitable cases might prevent the late dedifferentiation and recurrence.     

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.     

The treatment of oligodendrogliomas and mixed oligodendroglioma-astrocytomas with PCV chemotherapy.

Malignant oligodendrogliomas have been shown to be responsive to chemotherapy. The authors administered systemic chemotherapy to seven patients with oligodendroglioma or anaplastic oligodendroglioma, and to 14 with mixed oligodendroglioma-astrocytoma. Fourteen patients underwent chemotherapy before and seven after irradiation. The PCV (procarbazine, methyl-1-(2-chloroethyl)-1-nitrosourea (CCNU), and vincristine) chemotherapy was administered every 6 weeks (42-day cycles) for two to five cycles as follows: CCNU, 110 mg/sq m on Day 1; procarbazine, 60 mg/sq m/day on Days 8 to 21; and vincristine, 1.4 mg/sq m/day on Days 8 and 29. Complete or partial (greater than 50% reduction in tumor mass) responses at 20 to 100+ weeks after treatment were noted in 11 (79%) of the 14 patients treated before irradiation, including two with anaplastic oligodendroglioma and nine with mixed tumors. Complete responses were seen in two patients, one with anaplastic oligodendroglioma and one with a mixed tumor. Partial responses were seen in three of seven patients treated after radiotherapy. Stabilization of tumor growth followed PCV chemotherapy in four patients (two treated before and two after radiotherapy). Tumor growth progressed in two patients during therapy despite an initial response and in two patients despite therapy. The authors conclude that mixed oligodendroglial tumors as well as anaplastic oligodendrogliomas are responsive to PCV chemotherapy.