California Lawrence Berkeley Laboratory Research Articles

Experience in charged particle irradiation of tumors of the skull base: 1977–1992

Purpose : To review the experience at University of California Lawrence Berkeley Laboratory in using charged particles to irradiate primary neoplasms of the skull base and those extending to the skull base from the nasopharynx and paranasal sinuses. Methods and Materials : During the period from 1977 to 1992, 223 patients were irradiated with charged particles at the Lawrence Berkeley Laboratory for tumors either arising in or extending to the skull base, of whom 48 (22%) had recurrent lesions, either post previous surgery or radiotherapy. One hundred twenty-six patients had lesions arising in the cranial base, mostly chordoma (53), chondrosarcoma (27), paraclival meningioma (27) with 19 patients having other histologies such as osteosarcoma or neurofibrosarcoma. There were also 31 patients with primary or recurrent squamous carcinoma of the nasopharynx extending to the skull base, 44 patients with major or minor salivary gland tumors, mostly adenocarcinoma, and 22 patients with squamous carcinoma of the paranasal sinuses, all with cranial base extension. Results : Local control and survival appeared improved in tumors arising in the skull base, following the ability with charged particles to deliver high doses (mean of 65 Gy-equivalent) with relative sparing of the adjacent normal tissues. The Kaplan-Meier 5-year local control was 85% for meningioma, 78% for chondrosarcoma, 63% for chordoma and 58% for other sarcoma. Follow-up ranged from 4–191 months with a median of 51 months. Conclusion : Charged particle radiotherapy is highly effective in controlling cranial base lesions which have have been partially resected. Better tumor localization with CT and MRI, improved 3-D treatment planning and beam delivery techniques have continued to reduce the level of serious complications and increase local control and survival.

Helium charged particle radiotherapy for meningioma: Experience at UCLBL

Purpose : Evaluate the use of helium charged particle radiotherapy in the treatment of residual or unresectable meningioma adjacent to critical structures. Methods and Materials : Twenty-nine patients with meningioma of the skull base or spine were irradiated with helium charged particle radiotherapy at the University of California Lawrence Berkeley Laboratory (UCLBL) during the period 1981–1992. Twenty-six patients were treated for intracranial and three for spinal tumors. Total doses of 53.0–80.4 Gray equivalent (GyE) with a mean of 63 GyE were delivered using the helium ion beam. Results : Ten-year local control and survival rates calculated by the Kaplan-Meier product limit method were 84% and 80% respectively. Doses of 60.0 GyE were delivered with a low rate of complications. The only failures were in massive, recurrent tumors. Conclusion : High doses using helium charged particle radiotherapy can be safely and effectively delivered to large residual or unresectable meningioma near radiosensitive structures.

Charged particle radiotherapy of paraspinal tumors

Between 1976 and 1987, 52 patients with tumors adjacent to and/or involving the cervical, thoracic, or lumbar spinal cord were treated with charged particles at the University of California Lawrence Berkeley Laboratory. The histologies included chordoma and chondrosarcoma (24 pts), other bone and soft tissue sarcoma (14 pts), and metastatic or unusual histology tumors (14 pts). Radiation doses ranged from 29 to 80 Gray-equivalent (GyE), with a median dose of 70 GyE. Twenty-one patients received a portion of their treatment with photons. Median followup was 28 months. For 36 previously untreated patients, local control was achieved in 21 36 patients and the 3-year actuarial survival was 61%. Of 16 patients treated for recurrent disease, 7 16 were locally controlled and the 3-year actuarial survival was 51%. For patients treated for chordoma and chondrosarcoma, probability of local control was influenced by tumor volume (< 100 cc or > 150 cc) and whether disease was recurrent or previously untreated. Complications occurred in 6 52 patients, including one spinal cord injury, one cauda equina and one brachial plexus injury, and three instances of skin or subcutaneous fibrosis. Charged particle radiotherapy can safely deliver high tumor doses to paraspinal tumors with good local control.

Preliminary results in heavy charged particle irradiation of bone sarcoma

Between 1979 and 1989, 17 patients with unfavorable bone sarcoma were treated wholly or in part with heavy charged particle irradiation (helium and/or neon ions) at the University of California Lawrence Berkeley Laboratory. The majority of tumors were located near critical structures such as the spinal cord or brain. Gross tumor was present in all but two patients at the time of irradiation. Six patients were treated for recurrent disease. Histologies included osteosarcoma, Ewing's sarcoma, and recurrent osteoblastoma. Four of the osteosarcomata were believed to have been induced by previous therapeutic irradiation for various tumors. Follow-up time since initiation of radiation ranged from 7 to 118 months (median 40 months). The 5-year Kaplan-Maier local control rate was 48%; the corresponding survival rate was 41%. Over half the patients succumbed to distant metastases despite the majority of patients receiving chemotherapy. In this preliminary study, we have shown that heavy charged particle irradiation can be effectively used for control of bone sarcoma. A Phase II trial is warranted to determine optimal treatment for unresectable or gross residual disease.

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.

Charged particle irradiation of chordoma and chondrosarcoma of the base of skull and cervical spine: The lawrence berkeley laboratory experience

Forty-five consecutive patients with chordoma or chondrosarcoma at the base of skull or cervical spine were treated at the University of California Lawrence Berkeley Laboratory (UCLBL) and University of California School of Medicine, San Francisco (UCSF) between November 1977 and October 1986. All patients had undergone a subtotal surgical resection. Twenty-three patients were treated definitively with charged particles, 13 patients were treated with photons and particles, and 9 patients were treated for recurrent disease. Total doses ranged from 36 to 80 Gray equivalent (GyE). Thirty-three patients are alive with a minimum followup of 1 year. The actuarial survival and local control for all patients at 5 years is 62% and 59%, respectively. Patients treated for primary disease had a 78% actuarial local control rate at 2 years, whereas the rate for patients with recurrent disease was 33%. Patients with smaller visible tumor volumes (<20 cc) had a significantly better local control rate than patients with larger tumor volumes (80% vs 33% actuarial rate at 5 years). Patients with chondrosarcoma had the highest local control rate, as did patients treated with particles alone. Complications included 3 patients with unilateral visual loss, two patients who became blind, and 4 patients with radiation injury to the brainstem.

Energy Saving from the Adoption of More Efficient Appliances

In our October 1987 issue (pp. 85-89), we published a Comment by J. Daniel Khazzoom on a paper given by Amory Lovins at the November 1986 North American Conference of the IAEE. The subject, certain aspects of energy savings from the use of more efficient appliances, has important research and policy implications. Dr. Lovins's reply (plus a follow-up note by three staff members of the University of California's Lawrence Berkeley Laboratory) appears below. Professor Khazzoom's rejoinder will appear in a subsequent issue. I encourage additional comments and letters from our readers. Comments Energy Saving Resulting from the Adoption of More Efficient Appliances: Another View Amory B. Lovins J. Daniel Khazzoom's objection (1987) to my November 1986 IAEE presentation' is wrong in at least a dozen distinct respects. Its errors are variously noted, by, among others, Goldstein &amp; Watson (1986), the follow- up by Henly et al. (see p. 156) to this note, and (contrary to Khazzoom's claim that I ignored rebound effects) myself (e.g. 1985). Khazzoom's 1987 article simply reasserts his position without offering a convincing response.

Charged particle radiotherapy of selected tumors in the head and neck

For selected tumors in some sites in the head and neck region, charged particles such as protons or helium, carbon, neon and silicon ions provide improved dose distributions, higher tumor doses, and an increased chance of local control and prolonged survival. In tumors with “radioresistant” histologies, slow growth kinetics and/or hypoxic cells, the high-LET component of neon or silicon ions may also offer an added potential for increased effect on tumors. Sixty-seven (67) evaluable patients with tumors in the head and neck region having a histology other than squamous carcinoma received partial or full treatment with charged particles at the University of California Lawrence Berkeley Laboratory. The tumor sites included base of skull or cervical spine, salivary glands, paranasal sinuses, nasopharynx, and miscellaneous sites such as lacrimal gland, soft tissues of the neck, or thyroid. Follow-up ranges from 1–9 years with a mean of 36 months and a median survival (Kaplan-Meier technique) of 50 months. The actuarial local control rate is 60% at 24 months post-treatment. Thirty-one (31) patients with squamous carcinoma of various sites in the head and neck have also been treated using charged particle irradiation; local control was lower (11 of 31 pts) and survival shorter (mean: 9 months) in this group of patients with advanced squamous carcinoma.

Proton Radiotherapy: Some Perspectives

ABSTRACT DEVELOPMENT of stereotaxic radiosurgery is the result of contributions from physicists, radiologists, and neurosurgeons, says Jacob Fabrikant, MD, head of the Arteriovenous Malformation Program at the University of California's Lawrence Berkeley Laboratory (JAMA 1987;258:3217-3220). It also appears to have been the product of Harvard University (Boston) and University of California (Berkeley) cooperation.Robert R. Wilson, PhD, now a professor emeritus at Cornell University, Ithaca, NY, is credited with proposing the medical use of charged particles (Radiology 1946;47:487-491).Wilson, a physicist, says that the idea occurred to him while he was at Berkeley in the mid-1940s, designing the cyclotron to be built at Harvard. Although he was aware of their work, he does not remember discussing it with Robert Stone, MD, or John Lawrence, MD (brother of Ernest O. Lawrence, PhD, builder and designer of Berkeley's cyclotron), who only a few years earlier at Berkeley had begun the initial medical experiments

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.

Current Considerations in Heavy Charged-Particle Radiotherapy: A Clinical Research Trial of the University of California Lawrence Berkeley Laboratory, Northern California Oncology Group, and Radiation Therapy Oncology Group

Current Considerations in Heavy Charged-Particle Radiotherapy: A Clinical Research Trial of the University of California Lawrence Berkeley Laboratory, Northern California Oncology Group, and Radiation Therapy Oncology Group

Current Considerations in Heavy Charged-Particle Radiotherapy: A Clinical Research Trial of the University of California Lawrence Berkeley Laboratory, Northern California Oncology Group, and Radiation Therapy Oncology Group

Phase I and II radiotherapy trials with accelerated high-energy heavy charged-particle beams have been carried out at the University of California Lawrence Berkeley Laboratory in conjunction with the Northern California Oncology Group and the Radiation Therapy Oncology Group. Clinical experience with several anatomical regions and tumor types has been accumulated. Preliminary observations suggest that toxicity is acceptable with treatment techniques developed for neon ions. Further data must be accumulated for carbon or silicon ion therapy. Initial Phase III trials with neon ions should begin shortly; evaluation of optimal ions and techniques for improved dose localization is ongoing. Future directions for optimization of heavy charged-particle radiotherapy are presented.

A phase I–II trial of heavy charged particle irradiation of malignant glioma of the brain: A Northern California oncology group study

Thirty-nine patients with primary or recurrent glioma of the brain were irradiated wholely or in part with heavy charged particle beams at the University of California Lawrence Berkeley Laboratory in a Phase I–II clinical trial of the Northern California Oncology Group. During the course of this trial, treatment techniques have been developed and tumor doses have been escalated in order to obtain data on normal brain toxicity and response of malignant glioma of the brain. Toxicity has been acceptable with a low level of brain injury. Survival and tumor control has been approximately the same as historical results in glioma of the brain. Further dose escalation is planned together with possible trial of combined modality therapy.

Using Multiprocessor Systems in Scientific Applications

The MIDAS multiprocessor system is a multi-level, hierarchial structure developed at the Advanced Computer Architecture Laboratory of the University of California's Lawrence Berkeley Laboratory. A two-stage, 11-processor system has been operational for about 18 months. It has been employed to investigate techniques for decomposing a variety of problems and algorithms into a parallel processor environment. The performance results for a number of different applications will be discussed. These include scientific data analysis, Monte Carlo calculations, solutions to partial differential calculations (using finite-difference methods), and problems in accelerator design. Language extensions and programming techniques for the data-flow architecture will also be presented.

Current status of clinical particle radiotherapy at Lawrence Berkeley Laboratory.

Clinical experience with charged particle irradiation of human cancers has been underway at the University of California Lawrence Berkeley Laboratory. Over 150 patients have been irradiated with heavy charged particle beams including helium, carbon, neon, and argon ions. Pilot studies have included such tumor sites as glioma of the brain, carcinoma of the esophagus, carcinoma of the pancreas, carcinoma of the stomach, ocular melanoma, and carcinoma of the uterine cervix. Prospective studies are planned to investigate the improved dose localization potential (helium) and the enhanced biologic and physical dose potential (carbon, neon) in a controlled trial against the best available megavoltage irradiation techniques.

Volcanic energy studied at Mount Hood

Geochemical and geophysical measurements at Mount Hood are being made by a team of scientists from various institutions for the Department of Energy. Norman Goldstein of the University of California's Lawrence Berkeley Laboratory explains that locating sources and track pathways of hot water circulating within the volcano may help engineers use the geothermal potential of Mount Hood. Hot geothermal waters could help heat nearby ski lodges in the Mount Hood resort area, and if higher temperatures are available, they could operate steam‐driven turbines to generate electricity for the nearby city of Portland.