Hyperfractionated irradiation for adults with brainstem gliomas

Hyperfractionated irradiation appears to have improved survival for pediatric patients with brainstem gliomas. However, the efficacy and safety of this technique are less well established for adults with brainstem tumors. In 1984 the UCSF Department of Radiation Oncology began treating adults with brainstem gliomas using 100 cGy fractions given twice daily to total doses ranging between 6600-7800 cGy (median dose 7200 cGy). By the end of 1989, a total of 14 patients had been irradiated with follow-up times for surviving patients ranging between 4-69 months (median follow-up 33 months). Tumor histologies included five moderately anaplastic astrocytomas, one highly anaplastic astrocytoma, and eight which were unbiopsied. At the time of this analysis, six patients had failed locally, with five dying as a result of recurrent tumor. There were no deaths caused by complications or intercurrent illness. The 3-year actuarial survival rate was 59%, with a corresponding 3-year actuarial local control rate of 48%. The projected median survival was in excess of 5 years, whereas the actuarial median time to progression was 31 months (134 weeks). The treatments were well tolerated: the mean pretreatment Karnofsky Performance Status was 74% (range 60-90%); at the end of treatment the mean KPS was 78% (range 60-100%). In terms of neurologic status, six patients improved by the end of treatment, seven were stable, and one experienced only minor deterioration without change in KPS. There were no significant long-term complications (specifically, no instances of either radiation brain necrosis or myelitis). Seven patients required prolonged steroid administration after completing radiotherapy; six of these eventually recurred locally. These results appear to be substantially better than those achieved using conventional radiotherapy regimens, and suggest that this technique merits further investigation.     

Heavy charged particle therapy of bone and soft tissue sarcoma. A phase I-II trial of the University of California Lawrence Berkeley Laboratory and the Northern California Oncology Group

At the University of California Lawrence Berkeley Laboratory and the Northern California Oncology Group, a preliminary study of heavy charged particle radiotherapy in soft tissue and bone sarcoma has been carried out. Fifty-two patients with bone or soft tissue tumors were treated wholly or in part with heavy charged particles from 1978 to 1985. Eleven patients, considered inevaluable for purposes of this analysis, received less than 50 Gray-equivalents (GyE) because of the following: progressive disease (three patients); palliative treatment due to recurrent disease after previous radiation therapy (three patients); or since they were part of preliminary studies of relative biological effectiveness (RBE) (five patients). Forty-one patients received from 50 to 78.5 GyE, with a mean of 65 GyE. They had an average of 23 months follow-up, ranging from 4 to 78 months. In patients with paraspinal chondrosarcoma 9 of 11 had local control, with a mean follow-up time of 32 months. In the remaining patients with other histologies, 19 of 30 were controlled within the irradiated area, with a mean follow-up time of 20 months. Serious complications were encountered in the CNS (four patients), in the bowel (one patient), and in bone (one patient). Heavy charged particle radiotherapy appears to be of value in treating bone or soft tissue sarcoma; further trials are planned.     

Vision following helium ion radiotherapy of uveal melanoma: a Northern California Oncology Group study

One hundred eighty-six uveal melanoma patients were treated with helium ion radiotherapy at Lawrence Berkeley Laboratory and followed for at least 6 months. (Follow-up times ranged from 6 to 90 months; median 26.4 months.) At last examination, 92 of 186 patients (49%) had visual acuity of 20/200 or better in the treated eye. Univariate statistical analysis revealed that post-treatment vision correlated with tumor size, distance between tumor and optic disc, distance between tumor and fovea, pretreatment visual acuity, dose delivered to the optic disc, and dose delivered to the fovea (p less than .05). Neither the maximum tumor dose nor site of tumor origin (ciliary body vs. choroid) correlated with post-treatment vision on a univariate basis. However, multivariate statistical analysis revealed that the strongest independent risk factors influencing vision outcome (p less than .05) were tumor size, pretreatment visual acuity, tumor-fovea distance, and maximum tumor dose. Neither the fovea dose nor the dose to optic disc appeared to significantly affect vision outcome when other variables were taken into account. These results suggest that post-treatment visual acuity of 20/200 or better can be achieved in one-half of uveal melanoma patients treated using helium ion irradiation. Several independent risk factors affecting vision outcome have been identified.     

Charged particle radiotherapy for lesions encircling the brain stem or spinal cord

Since 1981, a specialized technique has been under development at the University of California Lawrence Berkeley Laboratory for charged particle irradiation of tumors partially or completely encircling the brain stem or spinal cord. By dividing the target volume into two or more portions and using a combination of beams, a reasonably homogeneous irradiation of the target volume can be obtained which protects critical CNS structures from over-irradiation. This technique requires knowledge of the physical and biological effects of charged particles, precise, reproducible patient immobilization, careful treatment planning based upon Metrizamide contrast CT and/or MRI scanning, compensation for tissue inhomogeneities, and accurate, verifiable radiation delivery. Uncertainties in the dose distribution must be taken into account when prescribing treatment. We have used this technique in 47 patients with a variety of tumors abutting the brain stem and spinal cord, including chordoma, chondrosarcoma, meningioma, osteosarcoma and metastatic tumors. The results have shown a significant local control rate (62%) and the incidence of serious complications has been acceptable (13%). The median follow-up is 20 months with a range of 6-90 months. We conclude that charged particles can be safely and effectively used to irradiate lesions encircling the brain stem or spinal cord to doses higher than can be achieved with low-LET irradiation.     

Long-term results of helium ion irradiation of uveal melanoma

Between 1978 and 1988, 307 patients with uveal melanoma were irradiated using helium ions at Lawrence Berkeley Laboratory. The length of follow-up ranged from 1-115 months (median 42 months). The 5-year actuarial treatment results were: local control rate, 96.8%, determinate survival rate, 81%, freedom from distant metastases, 76%, eye retention rate, 83%, and risk of developing neovascular glaucoma, 36%. Long-term vision outcome was analyzed in 81 patients with a minimum follow-up of 5 years. Forty-seven percent of patients retained vision of 20/200 or better. The median change in vision was a loss of four lines on the standard eye chart. Thirty-eight percent of patients had visual acuity either improve or remain within two lines of their pretreatment vision. A multivariate analysis identified tumor size as the only independently significant risk factor affecting survival, development of neovascular glaucoma, or the risk of enucleation; no risk factor correlated with local recurrence. Tumor size, tumor-fovea distance, and pretreatment visual acuity were independently significant risk factors influencing vision outcome. These results confirm that helium ion irradiation is an effective treatment for uveal melanoma which combines high rates of local control, survival, and eye retention with a substantial likelihood of long-term vision preservation.     

Uveal melanoma: development of metastases after helium ion irradiation

Forty-two (16%) of 261 patients with ocular melanoma who were treated with helium ions between January 1978 and November 1986 have developed metastatic disease. The time between start of helium ion treatment and recognition of metastatic disease ranged from 3 to 67 months (median, 27 months). The mean pretreatment tumor height in the patients with metastases was 7.7 mm. All 42 patients who developed metastatic disease have died. The median survival after diagnosis of metastatic disease was 5 months; the longest survival was 49 months. The most common site of metastasis was the liver (n = 34). Four (10%) of the 42 patients with metastases also had local recurrence of the tumor. Multivariate analysis identified three variables that predicted independently the development of metastases and lack of survival. These variables are anterior location of tumor (P = .027), tumor height greater than 5 mm (P = .02), and tumor diameter greater than 10 mm (P = .0075).     

Comparison of helium-ion radiation therapy and split-course megavoltage irradiation for unresectable adenocarcinoma of the pancreas. Final report of a Northern California Oncology Group randomized prospective clinical trial

Forty-nine patients with locally advanced carcinoma of the pancreas were treated in a randomized, prospective study comparing definitive helium ion radiation therapy with conventional split-course megavoltage photon irradiation. Patients in each treatment arm underwent exploratory staging laparotomy followed by concurrent radiation therapy and 5-fluorouracil chemotherapy. Patients treated with photons received 6,000 cGy over a period of 10 weeks; patients treated with helium irradiation received a 6,000-7,000-cGy-equivalent dose over a period of 8-9 weeks. There was no significant difference in overall survival between patients in the two treatment arms (P = .29). Patients treated with helium ions had a slightly longer median survival (7.8 months) than the photon-treated patients (6.5 months). Local control rates were slightly higher in the helium-treated patients (10% vs 5%). Complications included one chemotherapy-related death. Four of the five helium-treated patients who survived longer than 18 months died of local failure without distant metastases. These results suggest that more aggressive local therapy could result in improved survival in helium-treated patients.     

Salvage whole-abdominal irradiation following chemotherapy failure in epithelial ovarian carcinoma

During the period 1977 to 1985, 12 patients with FIGO stage II and III epithelial ovarian carcinoma failed to achieve a pathologic complete response with chemotherapy and underwent salvage whole-abdominal irradiation (WAXRT). Six of these patients had gross residual disease present at the time of irradiation, and three (50%) were unable to complete the planned radiotherapy. All eventually failed in the treatment field; their 5-year actuarial survival and local control rates were zero. The other six were irradiated without residual macroscopic disease. Five of the six (83%) were able to complete WAXRT as planned without prolonged delays. The 5-year actuarial survival and local control rates for this group were 21 and 25%, respectively. The actuarial laparotomy rate to relieve bowel obstruction following WAXRT was 40% at 2 years. The results from this and other series indicate that salvage WAXRT is not effective for patients irradiated with macroscopic tumor. However, WAXRT appears to be potentially curative for a small but significant percentage of patients irradiated without gross disease, although the risk of significant complications is high.     

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.