Radiotherapy for high grade gliomas.

This presentation will review recent data on the treatment of high grade gliomas. It deals primarily with results of radiotherapy even though several of the clinical trials to be considered also included chemotherapy. Present emphasis will be on, but not limited to, the larger prospective randomized trials conducted by various cooperative clinical groups in the United States, the United Kingdom and on the continent.

Postoperative radiotherapy of primary spinal cord tumors.

During the 30 year period from 1957 to 1986, 42 patients with primary tumors arising from the spinal cord or cauda equina received postoperative irradiation at the University of California, San Francisco. Twenty-one patients had ependymomas: 18 were localized to one site, and 3 diffusely involved the cord. There were 12 patients with low grade astrocytomas and 3 with highly anaplastic astrocytoma or glioblastoma multiforme. All astrocytomas were localized at presentation. In 6 cases tissue was insufficient to permit a histologic diagnosis. Thirty-nine patients (93%) received total radiation doses ranging between 45.0-54.7 Gy using standard fractionation. The 10-year actuarial disease-specific survival rate for patients with localized ependymoma was 93%; 33% of these tumors recurred locally. The corresponding rate for diffuse ependymomas was 50%; the spinal disease was controlled in all 3 patients, but one developed a cerebral metastasis despite prophylactic cranial irradiation. Low-grade astrocytoma patients had a 10-year actuarial disease-specific survival rate of 91%, with 33% of these tumors recurring locally. No patient with highly anaplastic astrocytoma or glioblastoma multiforme survived longer than 8 months; all of these tumors recurred locally, and two of the three also developed diffuse craniospinal axis metastases. Local recurrence for ependymoma was delayed as long as 12 years following treatment, while all but one astrocytoma failure occurred within 3 years of treatment. No significant dose-response relationship with respect to local control was noted for either localized ependymomas or low grade astrocytomas. One patient developed radiation myelitis after receiving 50.4 Gy with standard fractionation. These results indicate that patients who undergo postoperative irradiation for low grade spinal astrocytomas and localized spinal ependymomas achieve excellent survival. However, despite treatment with total radiation doses taken to the practical limit of spinal cord tolerance, local failure remains common.

Treatment results of juvenile pilocytic astrocytoma.

Treatment results for 36 patients with juvenile pilocytic astrocytoma treated from 1942 through 1985 at the University of California, San Francisco, were reviewed. Twenty-two tumors were located in the posterior fossa, 10 were in the hypothalamic region, and four were in the cerebral hemispheres. Twenty-eight patients were less than 18 years of age. The overall survival rate was 83% and 70% at 10 and 20 years, respectively. All 12 patients who had total tumor resection remain disease-free; only two of the 12 received postoperative irradiation. The 10- and 20-year freedom-from-progression for the 19 patients who had incomplete resection and received at least 40 Gy of postoperative irradiation was 74% and 41%, respectively. All patients who failed treatment had local recurrence. One patient developed diffuse meningeal seeding, after four local recurrences in the posterior fossa over a 23-year period. Six patients failed treatment and had a repeat biopsy at the time of recurrence or at postmortem examination, and three showed histological progression of the tumor to an anaplastic astrocytoma. Based on this study and others in the literature, a protocol has been adopted whereby patients who have total tumor resection are not treated with postoperative irradiation. Patients who have incomplete tumor resection and are older than 3 years of age are currently treated with postoperative partial-brain irradiation, to a dose of 45 to 60 Gy. In general, young children with incomplete resection are followed closely with computerized tomography or magnetic resonance imaging and are treated with chemotherapy or irradiation if tumor progression is documented.

Radiotherapy of primary intracranial germinomas: the case against routine craniospinal irradiation.

A retrospective study was performed on all patients with biopsy-proven intracranial germinomas and unbiopsied suprasellar or pineal region tumors treated during the past 30 years in the Department of Radiation Oncology, University of California, San Francisco. A total of 33 patients were treated: 13 with biopsy-proven germinomas, and 20 others who were unbiopsied. All patients were treated with megavoltage equipment; total dose varied between 40-55 Gy. Only two patients were treated with prophylactic spinal irradiation. No patient received initial or adjuvant chemotherapy. Follow-up times for biopsy-proven patients ranged from 0.5 to 16.7 years with a median 5.3 years. No biopsy-proven patient had a recurrence of the tumor or died; thus, actuarial relapse-free and determinate survivals at 5 years were 100%. Although only one patient in this group received prophylactic spinal irradiation, no patient failed in the spinal axis. The 20 unbiopsied patients had follow-up times ranging from 0.1 to 27.5 years with a median of 5.5 years. Six unbiopsied patients died: two from recurrent disease at the primary site, one from distant peritoneal metastases, two from complications of treatment, and one from intercurrent disease. For this group, actuarial relapse-free survival at 5 years was 72%; the corresponding determinate survival was 73%. Nineteen unbiopsied patients were treated without craniospinal irradiation. Only one developed spinal metastases. The results from this and other series indicate that the risk of spinal metastases from intracranial germinoma is too low to warrant routine prophylactic spinal irradiation. However, patients with gross tumor spill causing contamination of the CSF, malignant CSF cytology, or documented subependymal or subarachnoid metastases presumably are at higher risk for leptomeningeal failure. Craniospinal irradiation is recommended for these patients.

Treatment of oligodendrogliomas with or without postoperative irradiation.

The authors have reviewed the treatment results in 42 patients with intracranial oligodendroglioma treated from 1940 through 1983 at the University of California, San Francisco. Two patients who died postoperatively were excluded from analysis. Eleven patients had mixed tumors, with a minor astrocytic component. The overall survival rates for the 29 patients with pure oligodendroglioma were 61% and 33% at 5 and 10 years, respectively; these rates for the 11 patients with mixed tumors were 57% and 38% at 5 and 10 years, respectively. The 10-year survival rate for 14 patients with pure oligodendroglioma who received greater than 45 Gy irradiation was 56% versus 18% for 11 patients who did not receive postoperative irradiation (p = 0.09). Nine patients with mixed tumor who received more than 45 Gy postoperatively had survival rates similar to those for the 14 patients with pure tumors irradiated with more than 45 Gy (p = 0.89). All patients who died of their tumor had evidence of intracranial recurrence. One patient, who did not receive initial postoperative irradiation, also had clinical and myelographic evidence of spinal seeding. All five patients examined postmortem had tumor recurrence at the primary site; one patient also had intraventricular seeding. Six of the 10 patients with pure oligodendroglioma who had a repeat biopsy at the time of tumor recurrence or at postmortem examination showed histological progression to an anaplastic astrocytoma or glioblastoma multiforme. Based on this study, adult patients with pure or mixed oligodendroglioma currently are treated with partial-brain irradiation to a dose of about 60 Gy. In general, children are treated with partial-brain irradiation to about 50 Gy.

Radiation therapy for the treatment of non-eight nerve intracranial neurilemmoma.

The records of 19 patients treated for intracranial neurilemmomas, other than of the eighth nerve, at the University of California, San Francisco from 1945 through 1983 were reviewed. One patient who died within 30 days following surgery was excluded from the analysis. The 5th and the 9/10/11th nerve complex were the most common sites of tumor origin. Patients were classified by the extent of surgical resection: total (90-99% resection, NTR), subtotal (less than 90% resection, STR) and biopsy. Five patients had total excision of their tumor without post-operative irradiation and none had recurred. One of the 2 patients who had STR and did not receive post-operative irradiation recurred, while 2 of the 3 patients who received post-operative irradiation following STR recurred. One of the 2 patients who had NTR and did not receive post-operative irradiation recurred, while 1 of the 3 patients who received post-operative irradiation following NTR recurred. Two patients were treated with post-operative irradiation following biopsy and one recurred. One patient was treated with planned preoperative irradiation to reduce tumor vascularity, followed by total resection. Because of the small number of patients, no firm conclusion regarding the efficacy of irradiation for non-eighth nerve intracranial neurilemmoma can be made.

Efficacy of irradiation for incompletely excised acoustic neurilemomas.

The records of 124 patients treated for acoustic neurilemoma at the University of California, San Francisco, from 1945 through 1983 were reviewed. Patients were classified by the extent of surgical resection: total, nearly total (90% to 99% resection), subtotal (less than 90% resection), or biopsy. Thirty-one patients received irradiation as part of their primary treatment. Total resection of tumor, without irradiation, was associated with a 3% chance of local recurrence. One of 15 patients who had nearly total resection of their tumor and did not receive postoperative irradiation suffered a recurrence, compared with neither of the two patients who received postoperative irradiation (greater than 45 Gy) following nearly total resection. Postoperative irradiation (greater than 45 Gy) decreased the recurrence rate after subtotal resection from 46% (six of 13 cases without irradiation) to 6% (one of 17 cases: p = 0.01). All three patients treated by biopsy alone received postoperative irradiation (greater than 45 Gy), and none had a recurrence. Six patients were treated with preoperative irradiation because of excessive tumor vascularity; four are without evidence of disease 12 to 23 years later. Only three of seven patients treated with irradiation for tumor recurrence after surgical resection survived. It is concluded that postoperative irradiation significantly decreased the chance for local tumor progression following subtotal resection of acoustic neurilemoma, and that postoperative irradiation may be effective therapy following treatment by biopsy. Patients with total or nearly total resection appeared not to benefit from postoperative irradiation.

Optic gliomas. A reanalysis of the University of California, San Francisco experience.

Thirty-eight cases of optic gliomas seen at the University of California, San Francisco, were reviewed. Two patients died in the postoperative period and were excluded from the follow-up analysis. Twenty-nine cases (76%) involved the optic chiasm, nine (24%) cases were confined to one optic nerve. Most tumors were slow growing and progressive although there were three cases of adult chiasmal gliomas which exhibited unusually aggressive behavior. The three cases are presented in detail. After a mean follow-up period of 9.4 years, the 10-year overall actuarial survival was 87%. Relapse-free survival was 55% at 10 years. Chiasmal tumors had a poorer prognosis compared to optic nerve tumors with 56% of chiasmal tumors recurring versus 22% of optic nerve tumors. Radiotherapy was beneficial in chiasmal gliomas, initially improving vision in 35% (6/17) and decreasing recurrence from 86% (6/7) without radiation therapy to 45% (9/20) with radiation therapy. Optic gliomas are not benign, self-limiting lesions, and therefore require treatment. Radiotherapy is effective in chiasmal gliomas and should be used early in the management of these tumors. No advantage to radiotherapy could be demonstrated for optic nerve gliomas, although the number of these cases analyzed was small.

Radiotherapy of pituitary tumors.

The treatment of pituitary adenomas with conventional radiotherapy is safe and effective. Radiation controls the mass effects of large tumors in 80 to 90 per cent of patients and is especially valuable in preventing recurrence after partial resection. In acromegaly, about 80 per cent of patients are controlled; with Cushing's disease, the ultimate cure rate is from 50 to 80 per cent; the control rate for prolactin-secreting adenomas is not yet established. With appropriate radiation technique, including proper dose and daily fraction size, clinically significant complications other than hypopituitarism are rare.

Radiation therapy in the treatment of partially resected meningiomas.

To address the question of whether radiation therapy is beneficial in the management of partially resected meningiomas, we reviewed the records of all patients admitted to the University of California, San Francisco, between 1968 and 1978 who had a diagnosis of intracranial meningioma. The patients were divided into three groups: 51 patients had gross total resection and did not receive radiation therapy, 30 patients had subtotal resection and no radiation therapy, and 54 patients had subtotal resection followed by radiation therapy. The subtotal resection groups were similar in average age, male:female ratio, and tumor location, which allowed a valid comparison of the effects of irradiation. The recurrence rate in the total resection group was 4% (2 of 51 patients). Among patients in the subtotal resection groups, 60% of nonirradiated patients had a recurrence, compared with only 32% of the irradiated patients. The median time to recurrence was significantly longer in the irradiated group than in the nonirradiated group (125 vs. 66 months, P less than 0.05). There was no complication related to irradiation. These results provide convincing evidence that radiation therapy is beneficial in the treatment of partially resected meningiomas.

Radiation therapy for neoplasms of the brain.

The effectiveness and complications of radiation therapy for brain neoplasms are reviewed. While the available data suggest a favorable influence and outcome, randomized studies are needed to further optimize radiation therapy techniques and to integrate new therapeutic modalities.

Intracranial ependymomas: results of treatment with partial or whole brain irradiation without spinal irradiation.

Twenty patients with intracranial ependymoma (16) or anaplastic ependymoma (4) received post-operative radiation therapy at the University of California, San Francisco from 1959 through 1981. No patient received prophylactic spinal irradiation. The actuarial survival at 5, 10, and 15 years for 15 patients with ependymoma who received greater than 45 Gy was 67, 57, and 46%, respectively. Only one patient (7%) developed clinically recognized spinal metastases; this patient was eventually shown to have tumor at the primary site, within the irradiated volume. Six of 11 patients treated with partial brain irradiation had an intracranial recurrence, versus 1 of 4 patients treated with whole brain irradiation. Three patients were autopsied after failing partial brain irradiation for an ependymoma and the site of failure was within the irradiated volume of each patient. Partial brain irradiation was used to treat 4 patients with anaplastic ependymoma. One developed a local recurrence within the irradiated volume. The other three survived longer than 10 years. At UCSF, most patients with low grade ependymomas are presently treated with partial brain irradiation, but whole brain plus spinal irradiation is used for anaplastic tumors.

Radiation oncology. Programs for the present and future.

Radiation oncology in 1984 continues to make major advances in the multidisciplinary clinical programs. This has been possible by virtue of the radiation oncologist, who is an active participant in these clinical programs. The changing role for the radiation oncologist has dictated a greater participation in the primary management of the patient's disease process and also participation in multidisciplinary research programs.