A retrospective study of the value of chemotherapy as adjuvant therapy to surgery and radiotherapy in grade 3 and 4 gliomas.

The aim of this retrospective study was to evaluate the effect of adjuvant chemotherapy among patients < 55 years of age with anaplastic gliomas (historical grade 3, n = 85) with four cycles 4 weeks apart of 160 mg carmustine (BCNU) infused into the internal carotid artery, combined with vincristine 2 mg and procarbazine 50 mg x 3 for 1 week (i.a.BCNU-PV) versus no adjuvant chemotherapy. In glioblastomas (histological grade 4, n = 257) the same chemotherapy was evaluated versus two cycles 4 weeks apart of 160 mg lomustine (CCNU) orally instead of BCNU, combined with vincristine and procarbazine (PCV) versus no chemotherapy. All patients in both groups received radiotherapy. Among glioblastoma patients < 55 years of age there was a significant (P = 0.03), but moderately increased survival in the i.a.BCNU-PV group versus the two other arms that did not differ from each other. This difference could be explained by an uneven distribution of prognostic factors, especially age group (< 50 years versus 50-54 years) in favour of the i.a.BCNU-PV group. In anaplastic gliomas, the median survival in the i.a.BCNU-PV group was 80 months versus 25 months for the no chemotherapy arm (P = 0.004). No significant differences in the distribution of prognostic factors were found between the two therapy arms. We suggest that the role of adjuvant chemotherapy in glioblastomas is unclear, while i.a.BCNU-PV as adjuvant chemotherapy among patients < 55 years of age and with anaplastic gliomas increased survival markedly.

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.

Distinguishing between life-saving and life-sustaining treatments: when the physician and spouse disagree.

There is a fine distinction between life-saving measures and life-sustaining ones. In the case presented below the husband of a wife with cancer did not understand the continuation of life-sustaining treatment after the decision to reject life-saving measures was made. This resulted in a conflict between the husband and physician that placed the nurse, as family advocate, in the middle. The case is followed by an analysis with recommendations on how to handle this type of situation.

Tumours in the pineal and supra-sellar region. A review of clinical manifestations and managements.

The records of 14 patients with a tumour in the pineal or supra-sellar region seen at The Norwegian Radium Hospital, Oslo between 1973-1980 have been studied retrospectively. The problems with a widely accepted classification are discussed, as well as the choice of treatment (surgery versus radiation) and the indications for local or total CNS radiation. All patients should start radiation treatment to a local field with a generous margin. After 20 Gy a CT scan should be performed. A marked reduction in tumour size indicate a radiosensitive tumour (germ cell tumour or pineoblastoma) and the radiation field should be extended to total CNS who receives 30 Gy. No change on CT scan after 20 Gy indicate a tumour of glial origin or pineocytoma, the radiation should then continue with a local field to 50 Gy.

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.

Intra-arterial BCNU in the treatment of recurrent medulloblastoma.

Two patients with recurrent medulloblastomas were treated with combined oral and intravenous chemotherapy followed by intra-arterial BCNU. The 7 days course of oral and intra-venous chemotherapy consisted of CCNU and Procarbazin orally and Vincristine intravenously (PCV), repeated after 6 weeks. Intra-arterial chemotherapy consisted of 4 cycles of BCNU. Both patients responded well to treatment, evaluated by CT scans. One of the patients died of a new local recurrence 6 months after initiation of chemotherapy, whereas the other patient remains well, without CT evidence of tumour 36 months after the start of the treatment. No serious adverse side-effects related to the treatment were seen.

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.

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.

Pre-radiation chemotherapy in glioma patients with poor prognostic factors.

Nineteen patients in an age group from 56-67 years (mean age 62.5 years) with histologically verified glioblastoma multiforme were treated with chemotherapy consisting of two cycles of oral CCNU, intravenous vincristine and oral procarbazine prior to radiation therapy. Ten of the patients had stable disease, monitored by CT scan and neurological examination, and received whole brain radiation. The median survival was 12 months. Nine patients who had progressive disease during chemotherapy did not receive radiation treatment and were put on palliative treatment with dexamethasone. This group had a median survival of 3 months. The median survival in all of the 19 patients who entered the study was 9 months which was comparable to the survival of 56 patients with glioblastoma multiforme who, in a retrospective study, received post-operative radiotherapy. The most important factor predicting survival was steroid-dependency after surgery.

Ocular complications after intracarotid BCNU for intracranial tumors.

112 patients with intracranial tumors treated with intracarotid BCNU to a cumulative dose of 370 mg/m2 body surface have been examined retrospectively for ocular complications. Average follow-up was 494 days (range 5 months-5 years). The rate of ocular complications was 2.7%. There was 1 case of hemorrhagic glaucoma with amaurosis and an accompanying oculomotor palsy, 1 case of retinal branch artery occlusion combined with third nerve paresis and 1 case of oculomotor palsy.

[Treatment of spinal cord compression caused by malignant disease]. / Behandling av tverrsnittslesjon forårsaket av malign sykdom.

Patients suffering from metastatic spinal cord compression can be treated with decompressive surgery and/or radiotherapy. The best treatment regimen remains to be established. In the present paper we report our experience of a therapeutic regimen with main emphasis on radiotherapy, but where selected patients were treated with laminectomy followed by radiotherapy. 67 patients were treated during a two year period, 60 with radiotherapy as the sole treatment modality. The ambulation rate after treatment was 56.7%. Degree of loss of neurological function before treatment and tumour histology were prognostic factors for a successful outcome, defined as the patient's ability to walk after treatment. We emphasize the importance of starting treatment before development of advanced neurological deficits.

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.

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 chemotherapy followed by radiation in astrocytomas.

Seventy-five patients harboring astrocytomas received 4 cycles of infra-ophthalmic 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 < or = 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 intra-arterial chemotherapy can be given without significant morbidity and produces an improvement in survival in patients older than 40 years.

High incidence of serious side effects of high-dose dexamethasone treatment in patients with epidural spinal cord compression.

Twenty-eight consecutive patients were given high-dose dexamethasone (96 mg i.v. loading dose, decreasing doses to zero in 14 days) and radiotherapy for epidural spinal cord compression due to malignant disease. There were eight events classified as side effects of the dexamethasone treatment. Four of these were considered as serious (one fatal ulcer with haemorrhage, one rectal bleeding and one gastrointestinal perforation from undetermined origins, and one perforation of the sigmoid colon) giving a total rate of serious side effects of 14.3 percent. Due to the high incidence of serious side effects of the high dexamethasone dose, the regimen was abandoned in favor of a standard dexamethasone dose of 16 mg daily reduced to zero in 14 days. There were three events classified as side effects, but none were considered as serious in 38 consecutive patients receiving this dose. The differences both in total number of side effects and number of serious side effects are statistically significant. There was no significant difference in the number of ambulant patients in the group that received the high dexamethasone dose. We conclude that the high dexamethasone dose in our experience gives an unacceptably high incidence of serious side effects and we have therefore abandoned the regimen in favour of a more standard dexamethasone dose.

[Intracranial stereotaxic external radiation using a linear accelerator]. / Intrakraniell stereotaktisk ekstern strålebehandling med lineaerakselerator.

The article describes a method making it possible to give high radiation doses to a localized volume of the brain while sparing normal surrounding brain tissue. The treatment consists of sending multiple narrow radiation beams from different directions to the volume of tissue to be treated by rotating the radiation source and the patient table in relation to each other. Mega-voltage radiation from a linear accelerator is used. A non-invasive stereotactic frame is mounted on the patient and a CT scan of the brain is performed to localize the center and extent of the tissue to be treated. The radiation treatment is then given by using the coordinates on the frame to assure that the center of rotation of the treatment table and the linear accelerator pass through the center of the volume of tissue. The method has been used to give radiation boosts after external radiation to brain tumours, and to treat patients with recurrent tumours. Small localized benign intracranial tumours and AV-malformations have also been treated.

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.

Intracavity fractionated balloon brachytherapy in glioblastoma.

In order to reduce hospitalisation time for patients receiving postoperative radiotherapy a phase I-II study of intracavity balloon brachytherapy was instituted. An indwelling balloon catheter was implanted during the closing phase of the initial operation. Starting on the second or third postoperative day the catheter was afterloaded with a high dose rate isotope via a remotely controlled afterloading system. The treatment consisted of 10-12 fractions over a period of 5-6 days, with each treatment session requiring approximately 15 minutes. No external beam radiation was given. Forty-four newly diagnosed patients were treated. A total dose of either 60 Gy (33 patients) or 72 Gy (11 patients) was given. The overall median survival was 11.7 months, (range 2.7-50.9). The treatment was well tolerated and none of the applicators were removed prematurely. The total median hospital stay for this group of patients was significantly reduced compared to more conventional protocols. This study indicates that intracavity high dose rate balloon brachytherapy can achieve survival rates equivalent to those of conventional radiotherapy and is both cost and time efficient.