Bjarne Hager

Survival, prognostic factors, and therapeutic efficacy in low-grade glioma: a retrospective study in 379 patients.

PURPOSE We report survival, prognostic factors, and treatment efficacy in low-grade glioma. PATIENTS AND METHODS A total of 379 patients with histologic intracranial low-grade glioma received post-operative radiotherapy (n = 361) and intraarterial carmustine (BCNU) chemotherapy (n = 153). Overall survival and prognostic factors were evaluated with the SPSS statistical program (SPSS Inc, Chicago, IL). RESULTS Median survival (all patients) was 100 months (95% confidence interval [CI], B7 to 113); in age group 0 to 19 years (n = 41), 226 months; in age group 20 to 49 years (n = 263), 106 months; in age group 50 to 59 years (n = 49), 76 months; and for older patients (n = 26), 39 months. Projected survival at 10 and 15 years was 42% and 29%, respectively. Patient age, World Health Organization (WHO) performance status, tumor computed tomography (CT) contrast enhancement, mental changes, or initial corticosteroid dependency were significant independent prognostic factors (p < .05), while histologic subgroup, focal deficits, presence of seizures, prediagnostic symptom duration, tumor category, and tumor stage were not. Patients aged 20 to 49 years with no independent negative prognostic factors (n = 132) had a median survival time of 139 months versus 41 months in patients with two or more factors (n = 33). Patients who presented with symptoms of expansion (n = 97) survived longer when resected (P < .03); otherwise no survival benefit was associated with initial tumor resection compared with biopsy. Intraarterial chemotherapy and radiation doses more than 55 Gy were not associated with prolonged survival. Among 66 reoperated patients, 45% progressed to high-grade histology within 25 months. CONCLUSION Prognosis in low-grade glioma following postoperative radiotherapy seems largely determined by the inherent biology of the glioma and patient age at diagnosis.

Prognostic significance of CT contrast enhancement within histological subgroups of intracranial glioma

We report the prognostic significance of tumor CT contrast enhancement within histological subgroups in 831 consecutive adult glioma patients of high-grade (n=516) and low-grade (n=315) histology. In the present report, a negative prognostic factor is associated with shortened survival. Methods: Survival analysis including Kaplan-Meier plots, log-rank tests, Cox analysis, and Aalens linear model as implemented in SPSS and S-PLUS. Results: Sensitivity and specificity of contrast enhancement as a test for high-grade glioma was 0.87 and 0.79, respectively. Enhancement was a strong negative prognostic factor comparable to high-grade histology in the total patient population. Enhancement was also a negative prognostic factor within the subgroups adult high-grade (Grade 3–4), anaplastic (Grade 3), and low-grade (Grade 1–2) gliomas (p < 0.001). The prognostic implications of initial enhancement declined in high-grade patients surviving beyond 36 months. Tumor contrast enhancement or calcifications (in parentheses) were present in 96% (3.6%) of glioblastomas, in 87% (7.4%) of high-grade gliomas, in 56.5% of anaplastic gliomas, and in 21% (16.2%) of low-grade gliomas. Calcification was a positive prognostic factor within the high-grade group of patients (p < 0.0001). Conclusion: Enhancement was a major prognostic factor comparable to high-grade histology in this glioma patient population. Enhancement was a negative prognostic factor within each of the adult subgroups high-grade, anaplastic (grade 3), and low-grade gliomas. Enhancement was strongly associated with but not pathognomonic for high-grade histology.

Reversible oedema and necrosis after irradiation of the brain. Diagnostic procedures and clinical manifestations.

One hundred and twelve patients with primary brain tumour were followed every 3 months during and after brain irradiation and chemotherapy with brain scanning, EEG and neurological examination. Early delayed radiation reactions were seen in 6 patients. The symptoms developed 2-8 months after irradiation and lasted for 2-3 months. Two types of reactions were observed. One mild form appeared after 2-3 months and was characterized by low-attenuated expansive areas within the irradiated volume, without contrast enhancement on CT scan. Severe reactions appeared in some patients after 6 months, with exacerbation of earlier clinical signs and contrast enhancing lesions on CT. Regression of the CT finding was seen after 3 months. Recognition of this syndrome is important, as a new neurosurgical procedure might cause lasting neurological sequelae in patients who otherwise would recover without treatment.

Cerebral and cerebellar uptake of 99mTc-(d,1)-hexamethyl-propyleneamine oxime (HM-PAO) in patients with brain tumor studied by single photon emission computerized tomography

The cerebral and cerebellar distribution of 99mTc-(d,1)-hexamethylpropyleneamine oxime (HM-PAO) was investigated by means of a rotating gamma camera in 12 patients with cerebral glioma. Using the corresponding contralateral region as control, reduced uptake of HM-PAO in the tumor region was demonstrated in 10 of the 12 patients. Reduced blood flow in a brain area remote from a circumscribed lesion reflects reduced activation following the interruption of afferent nervous pathways. Reduced HM-PAO uptake indicative of such diaschisis was demonstrated in the visual cortex contralateral to homonymous hemianopia in the two patients with this deficit. In the three patients with the most marked hemiparesis, the cerebellar hemisphere contralateral to the tumor showed significantly reduced HM-PAO uptake indicative of crossed cerebellar diaschisis. SPECT using commonly available gamma cameras and 99mTc-HM-PAO seems capable of depicting reduced flow in functionally inactivated brain areas, and may be clinically interesting as an alternative to more specialized techniques for the investigation of local cerebral blood flow.

Combined Intra-arterial and Systemic Chemotherapy for Recurrent Malignant Brain Tumors

Seventy-nine patients harboring recurrent brain tumors received four cycles of infraophthalmic carotid injections of 160 mg of carmustine. Two milligrams of intravenous vincristine and 50 mg of oral procarbazine was also administered three times daily for 1 week in conjunction with each BCNU treatment. The response rate was 60% with a median survival for patients with astrocytomas, anaplastic astrocytomas, and glioblastomas of 32, 20, and 6.5 months, respectively. The median survival of the responding patients was 20 months, and the survival at 30 months was 45%. The survival in patients not responding to treatment was 5 months, reflecting the natural history of the tumor. There have been no deaths related to the treatment procedure. No incidents of severe or permanent eye complications or leukoencephalopathy were observed. Based on multivariate survival analysis, only patients with a good performance status who are not steroid dependent are candidates for this treatment.

Prognostic factors in malignant gliomas with special reference to intra-arterial chemotherapy.

Survival was analyzed in 173 patients with malignant gliomas to study the importance of possible pretreatment prognostic factors. Seventy-nine of these patients received preirradiation intra-arterial chemotherapy with BCNU combined with vincristine intravenously and procarbazine orally; the others received only postoperative whole-brain irradiation. To judge by univariate and multivariate analyses the most important pretreatment prognostic factors were histology, corticosteroid dependency, pretreatment performance status and frontal lobe location of the tumors. Patients with anaplastic astrocytoma, not corticosteroid-dependent, with pretreatment performance status of 0-2 and with a frontal lobe location of the tumor seemed to benefit most from preirradiation chemotherapy.

Primary malignant lymphoma of the brain. A report of 24 cases from the Norwegian Radium Hospital.

Between 1975 and 1987, 24 patients with primary central nervous system lymphoma were seen and treated at the Norwegian Radium Hospital. The overall median survival was 24 months. Patients with poor performance status (WHO 3-4) had a median survival of 3 months whereas patients with good performance status (WHO 0-2) had a median survival of 40 months (p < 0.0001). Patients who were not steroid-dependent after operation had a better survival than those patients who were steroid-dependent (p = 0.02). Nine patients were still living without evidence of disease at last follow-up, 18-130 months after the initial treatment.

Combined intra-arterial chemotherapy followed by radiation in astrocytomas

SummarySeventy-five patients harboring astrocytomas received 4 cycles of infra-ophtalmic carotid injections of BCNU, combined with vincristine intravenously and procarbazine orally. All of the patients thereafter, received radiation therapy. The five year survival was 73% for all patients. The age of the patients had no significant impact on survival.The treatment results were compared with the results of 57 patients with astrocytomas who were treated with surgery followed by radiation in the same period. These 57 patients had a 5 year survival of 45% with a five year survival in patients >- 40 years and patients < 40 years of 70% and 22%, respectively (p < 0.05).In multivariate survival analysis of the BCNU group and radiation group together, treatment group and corticosteroid dependency were the only prognostic factors. No leukoencephalopathy was seen during the treatment or in the follow-up of the patients.We conclude that pre-radiation infra-arterial chemotherapy can be given without significant morbidity and produces an improvement in survival in patients older than 40 years.

Treatment of recurrent esthesioneuroblastoma with combined intra-arterial chemotherapy. A case report

A 65 year old woman presented with a recurrent locally advanced esthesioneuroblastoma. She had earlier been treated with radiation followed by surgery. The recurrence was located in earlier radiated tissues with intracranial infiltration. She underwent treatment with combined intra-arterial chemotherapy (BCNU) i.a., vincristine i.v., procarbazine orally). 6 courses of chemotherapy were given with complete remission. The patient is free of disease and asymptomatic 24 months after treatment.

Combined intra-arterial chemotherapy and irradiation of malignant gliomas.

Seventy-nine patients with malignant gliomas (19 anaplastic astrocytomas and 60 glioblastoma multiforme) received 4 cycles of infra-ophthalmic carotid injection of 160 mg carmustine, 2 mg vincristine IV and procarbazine orally 50 mg 3 times daily for 1 week, followed by whole-brain irradiation, with a midpoint dose of 54 Gy/6 weeks. Response, judged by CT-scan, was seen in 31 out of 57 evaluable patients with a median survival of 30 months and 40% survival at 3 years. In all patients who responded to the treatment, a tumour regression was seen on CT-scan after chemotherapy before irradiation. In the 26 patients with progressive disease under chemotherapy, the median survival was 5 months. None of the patients who had progressive disease during chemotherapy had benefit from irradiation. The most important prognostic factors were good pretreatment performance status, glucocorticoid dependency and age. Few serious side-effects of the angiographic procedure were seen. Leukoencephalopathy was not observed in this study.