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Biomedical subjects

G T Chen

Publications and source records attributed to G T Chen.

At least 91 records · Page 5Linked to original sources

The brain: integrated three-dimensional display of MR and PET images.

Three patients with intractable epilepsy, two with brain tumors, and one with encephalitis were imaged with magnetic resonance (MR) and positron emission tomography (PET). MR data were used to construct a three-dimensional (3D) computer model of the brain surface depicting the precentral (movement), postcentral (sensation), left inferior frontal (speech), and left superior temporal (hearing) gyri. PET-derived measurements of average surface metabolism were encoded as colors and mapped onto the 3D model by means of a retrospective technique for registering the two scans. The integrated 3D model depicted the location of PET-detected metabolic abnormalities with respect to the gyral anatomy visualized with MR. In each case, the predicted relationships were confirmed intraoperatively by means of inspection of the brain and electroencephalography. Multimodality 3D displays are likely to be particularly valuable for interpreting PET studies of epileptic patients and others with normal MR anatomy.

Brain↗

Treatment planning study for carcinoma of the esophagus: helium ions versus photons.

Helium ion radiotherapy significantly reduces dose to adjoining critical structures in the treatment of carcinoma of the esophagus when the same treatment plan is compared with megavoltage photon therapy. A five-field 18 MV photon treatment plan, selected to minimize lung dose, is compared with helium ions using the same field configuration. Dose volume histograms show target coverage, as well as dose delivered to critical structures lung, heart, mediastinum, and spinal cord. Although both helium ions and photons deliver approximately the same lung dose for this treatment plan, radiation to the heart and spinal cord from this field arrangement is significantly reduced with the helium ion beam. The concentration of dose at the tumor site, while sparing surrounding normal tissue, is characteristic of charged particle therapy, particularly with light ions, which includes particles with Z from that of protons (Z = 1) through that of neon (Z = 10).

Esophageal Neoplasms↗

Retrospective geometric correlation of MR, CT, and PET images.

Magnetic resonance imaging, computed tomographic, and positron emission tomographic studies of the brain provide complementary information, and many patients undergo more than one of these studies during the course of their diagnostic workup and treatment. A new technique for quantitative geometric correlation of such studies makes it possible to create integrated multimodality images by mapping features from one image onto an image obtained with another modality. The coordinate transformation between any pair of images is found by a semiautomatic algorithm for matching models of the patient's external surface as depicted in the two data sets. The resultant hybrid images, which combine complementary features of different studies, are often more useful for diagnosis and treatment planning than are the original single-modality images. The algorithm can also be used for spatial registration of baseline studies with follow-up images created with the same modality, which allows tracking of a lesion to detect subtle interval changes in size and shape. This technique can be applied to images acquired in routine clinical practice, since it is completely retrospective and does not necessitate special positioning or landmarking of the patient.

Adolescent↗

Dose volume histogram analysis of liver radiation tolerance.

Eleven patients with carcinoma of the pancreas or biliary system received heavy charged particle radiation treatments and whole liver heavy charged particle radiation at Lawrence Berkeley Laboratory. Doses to the whole liver ranged from 10 to 24 Gray-equivalent (the biological equivalent of 10 to 24 Gray of low-LET photon radiation), whereas the dose to the primary lesion ranged from 53.5 to 70 Gray-equivalent (GyE). The fraction size was 2 to 3 GyE. The liver received partial as well as whole organ irradiation. Integral dose volume histograms for the liver were obtained in all 11 patients. An integral dose volume histogram displays on the ordinate the percentage of liver that was irradiated in excess of the dose specified on the abcissa. In this study, the clinical liver radiation tolerance of these patients is correlated with the information contained in an integral dose volume histogram. One patient developed radiation hepatitis. The integral dose volume histogram of this patient differed from the dose volume histograms of the other 10 patients. This difference was greatest in the range of doses between 30 and 40 GyE. Our results suggest that liver doses in excess of 30 to 35 GyE should be limited to 30% of the liver or less when 18 GyE of whole liver radiation is delivered at 2 GyE per fraction in addition to primary radiation of the pancreas or biliary system.

Helium↗

Neovascular glaucoma after helium ion irradiation for uveal melanoma.

Neovascular glaucoma developed in 22 of 169 uveal melanoma patients treated with helium ion irradiation. Most patients had large melanomas; no eyes containing small melanomas developed anterior segment neovascularization. The mean onset of glaucoma was 14.1 months (range, 7-31 months). The incidence of anterior segment neovascularization increased with radiation dosage; there was an approximately three-fold increase at 80 GyE versus 60 GyE of helium ion radiation (23% vs. 8.5%) (P less than 0.05). Neovascular glaucoma occurred more commonly in larger tumors; the incidence was not affected by tumor location, presence of subretinal fluid, nor rate of tumor regression. Fifty-three percent of patients had some response with intraocular pressures of 21 mmHg or less to a combination of antiglaucoma treatments.

Anterior Eye Segment↗

Degradation of the Bragg peak due to inhomogeneities.

The rapid fall-off of dose at the end of range of heavy charged particle beams has the potential in therapeutic applications of sparing critical structures just distal to the target volume. Here we explored the effects of highly inhomogeneous regions on this desirable depth-dose characteristic. The proton depth-dose distribution behind a lucite-air interface parallel to the beam was bimodal, indicating the presence of two groups of protons with different residual ranges, creating a step-like depth-dose distribution at the end of range. The residual ranges became more spread out as the interface was angled at 3 degrees, and still more at 6 degrees, to the direction of the beam. A second experiment showed little significant effect on the distal depth-dose of protons having passed through a mosaic of teflon and lucite. Anatomic studies demonstrated significant effects of complex fine inhomogeneities on the end of range characteristics. Monoenergetic protons passing through the petrous ridges and mastoid air cells in the base of skull showed a dramatic degradation of the distal Bragg peak. In beams with spread out Bragg peaks passing through regions of the base of skull, the distal fall-off from 90 to 20% dose was increased from its nominal 6 to well over 32 mm. Heavy ions showed a corresponding degradation in their ends of range. In the worst case in the base of skull region, a monoenergetic neon beam showed a broadening of the full width at half maximum of the Bragg peak to over 15 mm (compared with 4 mm in a homogeneous unit density medium). A similar effect was found with carbon ions in the abdomen, where the full width at half maximum of the Bragg peak (nominally 5.5 mm) was found to be greater than 25 mm behind gas-soft-tissue interfaces. We address the implications of these data for dose computation with heavy charged particles.

Humans↗

Early results of ion beam radiation therapy for sacral chordoma. A Northern California Oncology Group Study.

The authors report on eight patients with sacral chordoma treated with ion beam radiation therapy. Ion beams have favorable physical and biological characteristics when compared to conventional radiation therapy beams of x-rays, gamma rays, or electrons. This treatment technique has been developed to exploit those advantages. With this technique it is possible to deliver a much higher tumor dose than that usually given with conventional beams, and to date no significant normal-tissue morbidity has been noted. Seven of the eight patients currently have local control of their tumor; however, follow-up time is too short to judge the long-term local control rate of this treatment technique.

Adult↗

Correlation of visual field, treatment fields, and dose in helium ion irradiation of uveal melanoma.

We correlated predicted radiation distributions in 29 patients with uveal melanoma (treated with 5,000 to 8,000 rads of helium ion therapy) with fundus photography and visual field deficits. The tumor was entirely within the treatment region in all patients. The fraction of the predicted high-dose and low-dose regions corresponding with an absolute scotoma was fitted by a linear regression model (r2 = .721) with three independent variables: dose region, initial condition, and time since therapy. The defect in the maximum-dose region increased at an average rate of 0.270/year. This differed (P = .002) from the rate in the penumbra region: (0.104/year). The rate in the penumbra differed (P = .01) from that in the predicted low-dose region, where scotoma did not increase with time. The pattern and time course of visual field loss in the different radiation dose regions tended to support the conclusion that isodose calculations are accurate. The data were consistent with the hypothesis that visual loss secondary to irradiation results primarily from radiation vasculopathy and not from direct damage to photoreceptors or ganglion cells. Development of an absolute scotoma may require a dose in excess of 5,000 rads.

Helium↗

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.

Adult↗

Precision, high dose radiotherapy: helium ion treatment of uveal melanoma.

We report on 75 patients with uveal melanoma who were treated by placing the Bragg peak of a helium ion beam over the tumor volume. The technique localizes the high dose region very tightly around the tumor volume. This allows critical structures, such as the optic disc and the macula, to be excluded from the high dose region as long as they are 3 to 4 mm away from the edge of the tumor. Careful attention to tumor localization, treatment planning, patient immobilization and treatment verification is required. With a mean follow-up of 22 months (3 to 60 months) we have had only five patients with a local recurrence, all of whom were salvaged with another treatment. Pretreatment visual acuity has generally been preserved as long as the tumor edge is at least 4 mm away from the macula and optic disc. The only serious complication to date has been an 18% incidence of neovascular glaucoma in the patients treated at our highest dose level. Clinical results and details of the technique are presented to illustrate potential clinical precision in administering high dose radiotherapy with charged particles such as helium ions or protons.

Adult↗

Precision, high dose radiotherapy. II. Helium ion treatment of tumors adjacent to critical central nervous system structures.

In this paper we present a technique for treating relatively small, low grade tumors located very close to critical, radiation sensitive central nervous system structures such as the spinal cord and the brain stem. A beam of helium ions is used to irradiate the tumor. The nearby normal tissues are protected by exploiting the superb dose localization properties of this beam, particularly its well defined and controllable range in tissue, the increased dose deposited near the end of this range (i.e., the Bragg peak), the sharp decrease in dose beyond the Bragg peak, and the sharp penumbra of the beam. To execute this type of treatment, extreme care must be taken in localization of the tumor and normal tissues, as well as in treatment planning and dosimetry, patient immobilization, and verification of treatment delivery. To illustrate the technique, we present a group of 19 patients treated for chordomas, meningiomas and low grade chondrosarcomas in the base of the skull or spinal column. We have been able to deliver high, uniform doses to the target volumes (doses equivalent to 60 to 80 Gy of cobalt-60) while keeping the doses to the nearby critical tissues below the threshold for radiation damage. Follow-up on this group of patients is short, averaging 22 months (2 to 75 months). Currently, 15 patients have local control of their tumor. Two major complications, a spinal cord transection and optic tract damage, are discussed in detail. Our treatment policies have been modified to minimize the risk of these complications in the future, and we are continuing to use this method to treat such patients. We are enthusiastic about this technique, since we believe there is no other potentially curative treatment for these patients.

Aged↗

A comparison of water equivalent thickness measurements: CT method vs. heavy ion beam technique.

The purpose of this study was to evaluate existing X-ray CT methods for determining water-equivalent path length from body surface to a tumour site. In the method, the CT numbers are used to obtain linear attenuation coefficients which provide a measure of the electron density. These numbers are averaged over the energy spectrum of the diagnostic X-ray beam and other parameters which have a dependence on energy. From range measurements with heavy charged particles, it is also possible to obtain an independent and direct measure of electron density along the beam path. In the results reported here, the beam path electron density or water-equivalent path length was measured with charged particle beams, using radiation sensitive diodes as target markers. To minimise error which would be introduced by motion of the target volume, a frozen dog cadaver was used. Comparison was made between the water-equivalent path length measured with high energy particle beams, and the water-equivalent path length estimated from an X-ray CT image of the same target volume by the methods presently used in charged particle therapy (Chen et al. 1979). There was good agreement between the values determined directly with neon or helium ion beams, but when these values were compared with estimated path lengths derived from X-ray CT data, it was observed that the CT range could be in error by as much as 11% for adverse conditions of marked inhomogeneity and the presence of high atomic number bone. Under the best conditions of moderate inhomogeneity and absence of bone, the derived CT range values agreed reasonably well with the direct measurements.

Animals↗

Helium-ion radiation therapy at the Lawrence Berkeley Laboratory: recent results of a Northern California Oncology Group Clinical Trial.

We report on the first decade of the helium-ion radiotherapy clinical trial being carried out at the Lawrence Berkeley Laboratory. Over 500 patients have now been treated. We have had very good results to date in treating patients with small tumors critically located near a radiation-sensitive organ which would preclude delivering a curative dose with conventional radiotherapy. On the other hand, patients with larger tumors where the tumor dose cannot be increased more than 10% over conventional radiotherapy have not responded well to helium ion radiotherapy. This is illustrated by discussing selected patient groups in detail, namely those with uveal melanoma, small, low-grade tumors near the central nervous system, carcinoma of the pancreas, and carcinoma of the esophagus.

Adenocarcinoma↗

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.

Brain Neoplasms↗