Supratentorial Malignant Gliomas Research Articles

Survival and quality of life after interstitial implantation of removable high-activity iodine-125 sources for the treatment of patients with recurrent malignant gliomas

Between January 1980 and January 1988, 95 evaluable patients with recurrent, unifocal, supratentorial malignant gliomas were reirradiated with high-activity iodine-125 sources implanted directly into tumor in afterloaded, removable catheters using computerized tomography-directed stereotaxy. A tumor dose of 5270-15,000 cGy was delivered at a maximum distance of 0.5 cm from the rim of the contrast-enhancing mass seen on CT scans. The median survival for the 50 patients with anaplastic astrocytoma was 81 weeks and for 45 patients with glioblastoma multiforme it was 54 weeks. The 18- and 36-month survival rates for patients with anaplastic astrocytoma were 46% and 28%, respectively; the 18- and 36-month survival rates for patients with glioblastoma multiforme were 22% and 8%, respectively. Because of clinical deterioration, increasing steroid dependency, and increasing mass effect at the implantation site seen on CT scans, necrotic tissue was excised from 47 patients (49%) at craniotomy; in some patients, tumor was mixed with nectotic tissue. The survival of reoperated patients was significantly longer compared with patients who did not undergo this procedure. Serial determination of the Karnofsky Performance Score (KPS) showed that there was no significant deterioration for the group as a whole during the 6 months immediately after implantation. At 18 months, 33 of the patients were alive; KPS ranged between 50 to 90 (mean 79) and 67% were steroid dependent. At 36 months, 18 patients were alive; 17 patients were evaluable with KPS that ranged between 40 to 90 (mean 76) and 53% were steroid dependent. Eleven of the 17 evaluable long-term survivors had a KPS of 80 or higher with a mean of 87. Interstitial brachytherapy may provide long-term survival in selected patients with recurrent malignant gliomas who have been irradiated previously with conventional teletherapy. The quality of life in the majority of long-term survivors appears to be quite satisfactory. Further attempts to control tumor growth using this modality appear to be warranted.

Results of a randomized trial comparing BCNU plus radiotherapy, streptozotocin plus radiotherapy, BCNU plus hyperfractionated radiotherapy, and BCNU following misonidazole plus radiotherapy in the postoperative treatment of malignant glioma

In Brain Tumor Cooperative Group Study 77-02, eleven institutions randomized 603 adult patients with supratentorial malignant glioma to one of four treatment groups following surgery: conventional radiotherapy (6000 cGy in 30–35 fractions) + BCNU, conventional radiotherapy + streptozotocin, hyperfractionated (twice daily) radiotherapy (6600 cGy in 60 fractions) + BCNU, and conventional radiotherapy with misonidazole followed by BCNU. Data were analyzed for the total randomized population and for the 557 patients (86% with glioblastoma multiforme) who met protocol eligibility specifications (including confirmed histopathology on central review). Median survival was approximately 10 months following randomization. Overall there was no statistically significant difference in survival among the four groups. Among non-glioblastoma patients, the misonidazole group appeared to have poor survival. Peripheral neuropathy was a dose-limiting toxicity with misonidazole. It is concluded that neither the addition of misonidazole nor hyperfractionated radiotherapy as given in this protocol offered any advantage over conventional radiotherapy plus either BCNU or streptozotocin for treatment of malignant glioma.

Treatment of supratentorial high grade gliomas with split course high fractional dose postoperative radiotherapy

Ninety-two patients with malignant supratentorial gliomas diagnosed from 1977 to 1983 received split course external beam radiotherapy. The initial course of radiation consisted of 3000 cGy whole brain in ten fractions 5 days a week. After a 2-week rest, treatment was continued to a portal restricted to the computerized tomography scan demonstrated abnormality plus a margin for an additional 2100 cGy (total 5100 cGy/17 fx/36 days). The optic chiasm and hypothalamus were excluded from the high dose region. Following review of all pathologic specimens, three patients with grade II glioma, three lacking histologic confirmation, two unbiopsied and eleven not receiving the prescribed treatment were excluded from the survival analysis. No patients were lost to follow-up. Surviving patients were followed 85 months (median); range 68–125 months. All remaining patients were followed until death. The median actuarial survival for 73 grade III and IV patients was 12.5 months. The 5-year actuarial survival was 10%. The median survival for 54 grade IV patients was 10 months. The 5-year survival was 4%. For 19 grade III patients the median survival was 22.5 months. The 5-year survival was 26%. There was one long-term grade IV survivor (68 mos.) and four long-term grade III survivors (76, 85, 108, 125 mos). No patient developed optic nerve or chiasm injury. One patient, an 85 months survivor, had biopsy documented radionecrosis and hemiparesis. The incidence of necrosis among 62 patients alive 6 months or more (and therefore at risk of brain necrosis) is 1 62 (2%). The incidence among survivors is 1 5 . The nominal standard dose for this regimen is 1749 ret. The predictive value of the “nominal standard dose” and “equivalent dose” formulae for brain necrosis is explored. We conclude (a) that this regimen provides a survival probability equivalent to conventional treatment for grade III and IV supratentorial gliomas, (b) that neither the equivalent nor nominal standard doses predicted the incidence of brain necrosis, (c) that the time dose schedule is well tolerated and has an acceptable risk-benefit ratio, (d) that its advantage to the patient is decreased time requirement and cost.

Absence of contrast enhancement on CT brain scans of patients with supratentorial malignant gliomas.

The medical records of 229 consecutive patients with supratentorial malignant gliomas were reviewed with respect to histology, age at diagnosis, tumor location, and enhancement pattern on the CT obtained after the administration of contrast material at the time of operation. Nonenhancing tumors were identified in four (4%) of 93 patients with glioblastoma multiforme (GM), three (30%) of ten with gemistocytic astrocytoma (GA), 23 (31%) of 74 with highly anaplastic astrocytoma (HAA), and 28 (54%) of 52 with moderately anaplastic astrocytoma (MoAA). The age-related incidence of the various glioma histiotypes (both enhancing and nonenhancing) was reflected by the median age at diagnosis: 50 years in GM, 52 years in GA, 40 years in HAA, and 34 years in MoAA. The age and CT contrast enhancement pattern were similar in patients with GM, GA, and MoAA; patients with nonenhancing HAAs tended to be younger at presentation. The tumor location and the frequency of enhancing and nonenhancing lesions were similar for all groups except MoAA, in which nonenhancing tumors were most often frontotemporal and enhancing tumors were usually frontoparietal. Our results demonstrate that it is important to obtain histologic confirmation of the diagnosis in patients with supratentorial gliomas regardless of the presence or absence of contrast enhancement of the tumor on CT, because neither of these characteristics correlates with the tumor histology.

Photodynamic therapy of malignant primary brain tumours: clinical effects, post-operative ICP, and light penetration of the brain.

Abstract We are reporting our experience with intraoperative PDT in 32 patients with malignant supratentorial gliomas; in 19 cases the tumour was recurrent. There were 20 males and 12 females with an age range of 17‐73 (mean = 45) yr. The first 8 patients in this series received HpD (Photofrin I) and the next 24 received DHE (Photofrin II). A photo‐illuminating device, of the author's design, was coupled to an argon dye pump laser in order to deliver light at 630 nm to a tumour cavity created by radical tumour resection and/or tumour cyst drainage. The total light energy delivered ranged from 440 to 3888 J and the light energy density ranged from 8 to 68 J cm−2.There were two post‐operative deaths as the consequence of hematoma accumulation in an extensive tumour resection cavity. In two patients neurological function was worse post‐operatively and did not recover. Post‐operative cerebral edema was pronounced in eight cases and required emergency craniotomy in two patients (the histology from both showed hemorrhagic necrosis of residual tumour). We have fashioned continuous post‐operative ICP measurements in the last 15 patients treated with PDT and compared the values to those obtained from cases with malignant gliomas who did not have PDT; the mean ICP was significantly greater in the PDT group. Four patients developed wound infections; two of these required surgical treatment. Four patients, two of whom were hemiparetic, developed deep vein thrombosis and required anticoagulant therapy. There were no adverse systemic reactions to the administration of either photosensitizer and only 3 skin photosensitivity reactions.Follow up has ranged from 1 to 26 months at the time of writing; 38% were still alive; in the interval between PDT and death, the deaths per observation year was 1.11 for the whole group and 1.00 when the two post‐operative deaths are excluded. In the interval between first diagnosis and death the rate was 0.45 deaths per observation year. Photodynamic therapy of malignant brain tumours using surface or cavitary photo‐illumination can be carried out with acceptable risk.In eight patients we determined the penetration depth of light in brain tissue in vivo by reading the detected light flux from a fiber passed radially into the brain towards the centre of the irradiation volume. The optical fiber consisted of a single 400 μ.m, cleaved fiber fixed in a 17‐gauge biopsy needle coupled to a photometer. The light penetration depth ranged from 0.8 to 4.9. The mean PD values in the‘tumour’group and the‘brain’group was 2.9 ± 1.5 and 1.5 ± 0.43, respectively. We attribute this significant difference to the differences in the absorption and scattering properties of brain and tumour.

Supratentorial malignant gliomas in childhood: a review of fifty cases.

From 1977 to 1986, 50 children aged 15 months to 18 years were treated for supratentorial malignant gliomas at the Memorial Sloan-Kettering Cancer Center and the New York University Medical Center. Thirteen patients had glioblastoma multiforme, 29 had anaplastic astrocytomas, and 8 had malignant gliomas. In 10 patients the tumor evolved from a low-grade lesion. Seven patients, including 2 patients with neurofibromatosis, developed multiple primary malignant neoplasms. The median time to tumor progression after surgery was 31 weeks, with local recurrence representing the mode of treatment failure in nearly all patients. Notable clinical features included symptomatic leptomeningeal metastasis (13 patients) and intratumoral hemorrhage (9 patients). The estimated median survival time for all 50 patients was 98 weeks, with a 3-year survival rate of 32%. A trend toward longer survival was seen in patients 12 years of age or younger at diagnosis. There was no apparent correlation between survival and tumor histology or tumor location. Recommendations for management are presented.

Computerized tomography in the prognosis of malignant cerebral gliomas.

Ninety-seven patients with supratentorial malignant gliomas who received postoperative radiation therapy and chemotherapy at the University of California, San Francisco, from 1977 through 1984 showed improvement in their follow-up computerized tomography (CT) scans. Twenty-one of these 97 "CT responders" were designated "complete responders" because on serial CT scans they had complete disappearance of the tumor mass and contrast enhancement, which had been present postoperatively. In the remaining 76 patients, CT scans showed reduction in the size, but not disappearance, of the lesions, and these were designated "partial responders." Fifty-eight partial responders had glioblastoma multiforme (GM); their median survival time was 72 weeks. The median survival time for the 11 complete responders with GM has not yet been achieved, but survival at the 53rd percentile is 172 weeks. Among patients with highly anaplastic astrocytoma, the median survival time was 211 weeks for the 10 complete responders and 125 weeks for the 18 partial responders. Eleven of the 21 complete responders are alive at a median postoperative follow-up time of 163 weeks (range 114 to 470 weeks). Eighteen of these patients had subtotal resection of tumor; three patients had gross total tumor resections, but postoperative CT scans showed evidence of residual or possibly recurrent tumor within 1.5 to 4.5 months. Resolution of the tumor mass and contrast enhancement took 9 to 151 weeks; the time to resolution did not depend upon the configuration of the remaining tumor mass and contrast enhancement after surgery. In this study, patients with malignant gliomas whose CT scans eventually showed sustained complete disappearance of the tumor mass and contrast enhancement had a more favorable prognosis than did patients whose CT scans showed improvement, but not complete disappearance, of the tumor. These CT findings may prove useful in determining the prognosis of patients with malignant gliomas.

Leptomeningeal metastasis from supratentorial malignant gliomas.

The clinical and diagnostic findings in 13 patients with leptomeningeal metastasis from supratentorial malignant gliomas are reported. Criteria for inclusion in this study were positive myelographic examination, positive cerebrospinal fluid cytology on two or more samples, or evidence of leptomeningeal seeding at autopsy. Eight patients had premortem symptoms of leptomeningeal metastasis, with the diagnosis confirmed during life in 5 patients. Average survival after the onset of symptoms was 3 months (range, 1 to 5 months). Comparison of the autopsied group with 10 concurrent autopsied patients without leptomeningeal gliomatosis did not reveal any significant differences in age, but leptomeningeal gliomatosis was more prevalent in patients with longer postoperative survival. Leptomeningeal involvement at autopsy was more extensive in symptomatic patients. Cerebrospinal fluid examination often gave nondiagnostic or nonspecific results. Computed tomography of the brain showed evidence of ventriculomegaly, periventricular contrast enhancement, or multifocal tumor involvement in every case. Iophendylate myelography was the most reliable diagnostic tool and established the diagnosis whenever performed. The natural history and clinical significance of leptomeningeal metastasis from supratentorial malignant gliomas are discussed.

Present status and future role of surgery for malignant supratentorial gliomas.

Despite a voluminous literature it remains difficult to draw conclusions about the precise place of surgery in the management of patients with supratentorial malignant gliomas (anaplastic astrocytoma and glioblastoma multiforme). If the beneficial effects of radiotherapy are discounted, excisional surgery itself probably achieves no more than a survival of 4 to 6 months. The apparently beneficial effects of excisional surgery are related more to radiotherapy than to the surgery itself, beyond the immediate relief of raised intracranial pressure. So far in EORTC Brain Tumour Group studies there is no evidence of any significant beneficial effect from chemotherapy after excisional surgery. Whatever adjuvant methods of therapy are developed in the future, it will remain necessary to separate the effects of surgery from those of the adjuvant therapy. There will therefore be a continuing need for a basic human model whereby the effects of surgery can be clarified, and for that reason it will always be necessary to have a treatment arm without excisional surgery. A format is proposed taking into account favorable prognostic factors such as age and Karnofsky index, which should provide a basis for critical evaluation. The difficulties of adhering to the format are stressed.

Dibromodulcitol-based combined postoperative chemotherapy of malignant astrocytomas and glioblastomas.

Continuing our earlier studies with dibromodulcitol (DBD), in a series of 38 evaluable consecutive patients who were operated on for malignant supratentorial gliomas, radiotherapy with smaller daily but higher total doses of DBD has been started 3-5 weeks after surgery. This was followed alternately by a combination chemotherapy of CCNU and DBD or CCNU and Procarbazine. No severe myelotoxicity occurred. Survivals were compared with a group of patients who got irradiation alone. Statistical analysis showed a significantly better survival in the presently treated group: median survival was 55 weeks, p = 0.02. These values were very similar to those groups which were treated by intermittent DBD schedule during irradiation. This study seems to confirm our previous suggestion that the concurrent use of DBD during irradiation might be an important factor in improving survival times.

Fast neutron therapy for malignant astrocytomas. A review.

The treatment of supratentorial malignant gliomas has continued to be a major problem for neurosurgeons and oncologists. Post-operative conventional radiotherapy is known to prolong survival and to enhance the quality of life. Local persistence of tumor kills the majority of patients. Fast neutron irradiation is being utilized to treat malignant gliomas based on its reputed radiobiological advantages for treatment of large tumors and the encouraging preliminary reports showing tumor eradication in post-radiation biopsy and autopsy specimens. This paper reviews the results of fast neutron irradiation alone and in combination with photons and hypoxic cell sensitizers. Survival comparisons do not show any superiority for neutrons compared to conventional radiation. However, post-neutron radiation tissue samples have shown less aggressive and minimal residual tumor in many instances. At the same time radiation necrosis has emerged as a significant problem. In summary, even though neutron irradiation can eradicate malignant gliomas a therapeutic window has yet to be identified.

Familial intracranial gliomas

The pedigree of two interrelated families with 10 affected members suffering from malignant supratentorial gliomas is reported. In addition, three other unrelated families with two members each who were treated for different types of brain tumors are described. Genetic implications are discussed.

Supratentorial malignant gliomas of childhood. Results of treatment with radiation therapy and chemotherapy.

Twenty-seven patients aged 1 to 18 years harboring supratentorial (20 in the cerebrum and seven in the thalamus) malignant gliomas were treated between 1975 and 1982. There were four glioblastomas multiforme, 14 anaplastic astrocytomas, and nine malignant gliomas. All patients had a subtotal resection or biopsy as the initial procedure and received postoperative radiation therapy (RT). Fifteen of 27 patients were treated by RT alone; 14 had tumor progression with a median time to tumor progression (MTP) of 65 weeks. Twelve patients were treated with chemotherapy as an adjuvant to RT; only seven had tumor recurrence, with an MTP of 130 weeks. Of the 21 patients with recurrent tumors in both groups, 18 were treated with chemotherapy alone, or chemotherapy with a second surgical procedure or second course of RT. For all histological grades of tumor, the MTP for first recurrence was 75 weeks and the median survival time was 180 weeks. Age at initial diagnosis was found to be a statistically significant prognostic factor, with patients younger than 10 years of age surviving longer than patients aged over 10 years (p = 0.02).

Misonidazole in radiotherapy of supratentorial malignant brain gliomas in adult patients: a randomized double-blind study

The effect of misonidazole on the duration of the free interval (time to recurrence) and total survival of adults bearing malignant supratentorial brain gliomas was measured in a randomized double-blind study. Radiotherapy consisted of 9 × 3.5-Gy fractions given on alternate days during 3 weeks followed by 6 × 3-Gy fractions delivered in 2 weeks. Misonidazole, 1.3 g/m 2 , administrated 4 hr before the 9 first irradiations to 82 patients, had no effect on the duration of the free interval or total survival compared with 81 controls. The two groups were comparable in respect to the main prognostic factors: median age, performance status or tumour location. The overall tolerance of misonidazole was good.

Cerebral space-occupying cysts following radiation and chemotherapy of malignant gliomas

Eight cases of cerebral cyst formation among 50 patients (= 16%) with malignant supratentorial gliomas treated by surgery, megavoltage radiation, and multiple-agent chemotherapy are reported. Five of them developed signs of intracranial hypertension or progressive neurological deficit, while in three patients cerebral cysts were detected by CT without clinical deterioration. At operation or autopsy, or both, the large fluid-filled, smooth-walled cysts were lined by glio-mesenchymal scar tissue with no or little tumour recurrence in five, while three patients showed large recurrent tumour masses associated with necrosis and cyst formation. Clinical signs or CT evidence, or both, of cerebral cysts developed 4 to 12 months (average 10 months) after the first craniotomy, and 3 to 9 months after termination of radiotherapy, usually after the second to fourth course of polychemotherapy. The cystic cavities which are attributed to increased necrosis and other effects of radiation and cytostatic treatment, may mimic tumour progression or recurrence, and cerebral abscess, but are usually recognized by CT. Surgical treatment produced transient clinical improvement in 5 patients, but usually did not prevent the fatal outcome of the disease, which in these paticrosis and other effects of radiation and cytostatic treatment, may mimic tumour progression or recurrence, and cerebral abscess, but are usually recognized by CT. Surgical treatment produced transient clinical improvement in 5 patients, but usually did not prevent the fatal outcome of the disease, which in these paticrosis and other effects of radiation and cytostatic treatment, may mimic tumour progression or recurrence, and cerebral abscess, but are usually recognized by CT. Surgical treatment produced transient clinical improvement in 5 patients, but usually did not prevent the fatal outcome of the disease, which in these patients occurred 3 weeks to 6 months after surgical treatment of cyst formation, their life span ranging from 9 to 22 months. The pathogenesis and clinical problems related to cerebral cysts arising following multimodality treatment of malignant brain tumours are discussed.

Putrescine diffusion in cat brain and capillary permeability in rat brain: Relation to CSF putrescine levels in brain tumor patients

Cerebrospinal fluid (CSF) putrescine (Pu) levels are extremely useful measures of active tumor growth in patients harboring medulloblastoma but not in patients harboring most supratentorial malignant gliomas. This study was designed to determine the diffusion coefficient (D) for Pu in cat brain and the capillary permeability coefficient (Pc) in rat brain to explain the failure of supratentorial gliomas to manifest a consistent increase in CSF Pu with progressive tumor growth. The Pc for Pu was found to be greater than the Pc for urea, while the apparent brain D for Pu was lower than that for urea. This implies that Pu crosses capillaries and enters cells more rapidly than urea, which would reduce the amount of Pu that might ultimately reach the CSF by diffusion from tumor. These data explain why CSF levels of Pu are correlated best in medulloblastoms—generally located adjacent to the CSF pathways—and why levels are correlated least in malignant supratentorial gliomas—usually located within the brain hemispheres, from which diffusion to the ventricles and into the CSF would be difficult.

Vm-26 monochemotherapy trial in the treatment of recurrent supratentorial gliomas: Preliminary report

Twenty-five adults with recurrent supratentorial malignant gliomas were treated with VM-26 in a monochemotherapy schedule, the antiblastic regimen covering a period of 24 weeks. Five cases were excluded from the final evaluation, 4 because of protocol violations and I due to intolerance to the drug. In the group of 20 patients who met the criteria for evaluation, 7 (35%) showed a partial or complete response, with clinical or radiological tumor regression, and the conditions of 7 (35%) were unchanged at the end of the chemotherapy courses. The progression-free intervals turned out to be 10.4 months and 8.5 months, respectively. Six patients (30%) complained of tumor progression despite the treatment. Most of the patients are still alive, and the actuarial survival rate is encouraging. Toxicity was mainly hematologic, but usually moderate and easily reversible.

Maintenance immunochemotherapy for gliomas (author's transl)

Adjuvant immunochemotherapy and irradiation therapy were applied following surgery for gliomas from 1975 to 1978. It is the authors' principle to remove the tumor extensively. About one week after the operation, irradiation was started. Along with the irradiation, adjuvant immunochemotherapy was also started. For supratentorial gliomas, initially, adriamycin was given in three divided dosis of 0.5 mg/kg, up to 30 mg, on every other day. After a rest of 6 weeks, methyl-CCNU was given in a single dose of 3 mg/kg orally. This course of treatment was repeated after another 6 weeks. Along with the chemotherapy, OK-432 was given as an immunopotentiator. For medulloblastomas, methyl-CCNU was given at first, in a single dose of 3 mg/kg. After a rest of 6 weeks, methotrexate was given intrathecally via an Ommaya reservoir on five successive days in a single dose of 0.25 mg/kg. After another 6 weeks methyl-CCNU was repeated every 6 weeks. Methotrexate was also given during the spring, summer and winter vacations. OK-432 was also administered. This combined therapy was applied to 14 cases of supratentorial malignant gliomas, seven cases of supratentorial low grade gliomas, and 10 cases of medulloblastomas. In addition, nine low grade gliomas in the brain stem without surgery received this therapy. The survival rate ofsupratentorial malignant gliomas was 79% for one year, 50% for two years and 46% for three years. The survival rate of medulloblastomas was 80% for one year, 67% for two years, and 57% for three years. All the survivors among medulloblastoma cases could go to school or kindergarden. Toxicity was examined by white blood cell count, liver function, renal function and lymphocyte count. The difference of mean white blood cell counts between the first postoperative year and thereafter was not significant. GOT and GPT were elevated in the early postoperative period, but returned to normal values in the late postoperative period. ALP increased in the late postoperative period. Throughout the course of immunotherapy, it is necessary to measure immunoparameters. Lymphocyte count and PPD skin test were measured. Difference of lymphocyte counts between the first postoperative year and thereafter was not significant. Although the lymphocyte count was said to be depressed in glioma cases, and especially during chemotherapy, this series showed no apparent immunosuppression. Because some toxicity, such as elevating ALP, was noted, it seems better to discontinue the combined therapy at the end of the second postoperative year.

High dose radiation therapy in the treatment of malignant gliomas: Final Report

One hundred patients with supratentorial malignant gliomas were prescribed to receive postoperative whole brain irradiation with doses ≥5000 rad; 41 had astrocytoma grade III and 59 had grade IV tumors. The median survival was 91 weeks for patients with grade III tumors and only 42 weeks for those with grade IV (p < 0.01). For both grades, patients who were ≤45 years of age survived significantly better than patients who were older at diagnosis (p < 0.05). Patients with tumors at each grade were divided into three groups depending on the total dose delivered to the tumor; 5000, 6000, 7500 rad (median doses). For patients with grade IV tumors the median survival was 30, 42 and 56 weeks respectively, these differences were significant (p < 0.05) between the extremes but not between consecutive dose groups and were maintained only up to 2 years from the initiation of treatment. For patients with grade III tumors, the median survival was 43, 82 and 204 weeks respectively; these differences were significant (p < 0.05) between consecutive dose groups and between extremes and were maintained up to 4 years from the initiation of treatment. For 22 patients with grade IV who were treated with high-doses (7500 rad), the median time for recurrence was 43 weeks while for six patients with grade III tumors it was 158 weeks. The use of higher radiation doses was well tolerated; it did not compromise the quality of survival, and did not yield normal brain tissue necrosis. However, these doses did not seem to alter the total survival of patients, nor did they seem capable of sterilizing these tumors. Histopathological changes that were observed in normal brain tissue that was irradiated with 7000–8000 rad suggest that increasing total doses beyond this range might attain tumor sterilization, but could also lead to frank radiation necrosis in these patients.

Evaluation of malignant glioma patients during the postirradiation period

✓ The syndrome of increased focal or generalized central nervous system (CNS) dysfunction in the early postirradiation period in patients treated with radiation therapy (RT) for malignant gliomas has not been well documented. The authors have undertaken retrospective study of 51 patients with supratentorial malignant gliomas who survived longer than 26 weeks from the time of diagnosis. All patients received irradiation and chemotherapy and were evaluated at 8-week intervals. Each evaluation consisted of a neurological examination, computerized tomography (CT) and radionuclide scans, Karnofsky rating, and an evaluation of glucocorticoid levels needed to maintain neurological function. In all, 263 evaluable periods, consisting of 1290 individual evaluable tests (parameters), were analyzed. In the first 18 weeks after RT, 26 of the 51 patients studied (51%) showed deterioration in one or more tests; 14 of the 26 (53%) did not improve. These 14 patients had a median time to tumor progression (MTP) of 31 weeks. The remaining 12 patients in this group (47%) improved and had an MTP of 73 weeks. Of the 51 patients, 25 (49%) showed deterioration significant enough to presume tumor progression (two of the following three tests were unequivocally worse: neurological examination, CT scan, and radionuclide scan), seven improved with no change in therapy and had an MTP of 66 weeks, while the other 18 had an MTP of 32 weeks. Excluding the Karnofsky rating, any individual test that showed worsening during the first 18-week period had a 33% probability of significant improvement at a subsequent evaluation period. After 18 weeks the probability of the test improving was only 4%. The authors conclude that CNS decompensation up to 18 weeks after RT, as ascertained from clinical examination, scans, or glucocorticoid dosage, does not invariably predict tumor progression, because in 28% (7/25) of such cases there will be subsequent improvement.