Stereotactic radiosurgery for primary and metastatic brain tumors.
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Brain Neoplasms↗
Biomedical subjects
G Luxton
Publications and source records attributed to G Luxton.
Surgery with adjuvant irradiation in patients with pathologic stage C adenocarcinoma of the prostate.
BACKGROUND: In recent years, the routine use of prostate-specific antigen (PSA) to detect cancer of the prostate (CaP) early has renewed the controversy regarding radiotherapy versus radical prostatectomy as the superior definitive treatment. Radiotherapy alone has been reported to result in a high incidence of local recurrence, whereas on the other hand surgical treatment has resulted in a high incidence of microscopic residual tumor. The purpose of this study was to review our treatment results with radical prostatectomy followed by planned courses of postoperative irradiation in patients with pathologic Stage (PS) C disease. METHODS: From 1972 to 1989, 95 patients with CaP with PS C tumors were treated with radical prostatectomy and bilateral pelvic lymphadenectomy. Pathologic stage distribution was: C1 in 26 (27%), C2 in 37 (39%), and C3 in 32 (34%) patients. The median follow-up was 6 years. All 95 study patients received postoperative pelvic irradiation as the only adjuvant treatment. Radiotherapy treated volume included the prostatic fossa and its immediate vicinity. The RT dose ranged from 33 Gy to 61.8 Gy (median, 45 Gy). RESULTS: The overall 5- and 10-year actuarial survival rates were 94% and 73%, respectively, with the 5 and 10 year disease specific survival of 98% and 91%, respectively. Clinical and/or prostate specific antigen recurrence was 31% at 5 years and 44% at 10 years. Prostate specific antigen elevation without clinical evidence of recurrent disease was recorded in 26 (27%) patients. Seminal vesicle involvement (C3) and high Gleason's score (8-10) were the most important factors predicting recurrence. Of the 95 patients treated, 2 had pelvic recurrence alone and 1 had local and distant metastatic disease. Radiotherapy was well tolerated with no clinically important morbidity. CONCLUSION: Based on this experience, moderate dose adjuvant radiotherapy after radical prostatectomy in patients with PS C CaP is recommended.
Adenocarcinoma↗
Single isocenter treatment planning for homogeneous dose delivery to nonspherical targets in multiarc linear accelerator radiosurgery.
PURPOSE: Conventional radiosurgery refers to single isocenter focused beam irradiation of small intracranial targets with a single collimator. Conventional radiosurgery is characterized by spherical-shaped isodose surfaces. Nonspherical targets require a different approach to avoid exposing a large volume of nontarget brain tissue to high dose, particularly for lesions larger than 25 mm. Multiple isocenters are frequently used to treat nonspherical large targets, but multiple isocenter treatments are associated with a relative dose inhomogeneity of approximately 100% within the target volume, and may be correlated with an increased rate of complications. The feasibility of conformally treating elongated targets to an approximately homogeneous dose using a single isocenter methodology will be demonstrated. METHODS AND MATERIALS: A prolate ellipsoid of revolution, 25 mm in diameter, 35 mm in length, positioned at five representative locations in a head phantom, was used as a target model. The alignment of the target was taken to be parallel in turn to each of the three principal axes of the head model (A/P, R/L, and C/C). Dose conformation is achieved by nonuniform arc weighting, selective limitation of the extent of individual arcs, and the use of different collimator apertures for the different arcs in accordance with the aperture size required to encompass the target for that arc. Treatment plans were selected based on considerations of dose-volume histograms and conformation of the 80% dose surface with the surface of the target. The goal was that the minimum target dose would not be less than 80% of the maximum dose. RESULTS: Practical treatment plans for which the minimum target dose exceeded 80% were obtained for the three orthogonal orientations of the target for the five target locations. Plan parameters were essentially independent of the target position, dependent only on target orientation. The 80% isodose contour surface enclosed on average 2.8 cm3 larger volume (range: 2.1-3.9 cm3) than the prescribed 11.45 cm3 target. The minimum dose to the target ranged from 80.1 to 84.5%, and the average dose to the target was 94.26%. The 80-to-50% dose volume enclosed an average of 14.8 cm3 of nontarget volume (range: 12.7-15.9 cm3). Average deviation in the principal planes of the 80% isodose lines from the surface of the target volume was 0.95 mm for the 25 mm dimension (range 0.0 to +1.9 mm) and 0.86 mm (range 0.0 to + 2.4 mm) for the 35 mm dimension. CONCLUSION: Standardized single isocenter treatment plans with the isocenter at the center of the target can achieve good conformation of the dose distribution to targets elongated along any of the principal axes, and located anywhere in the brain.
Humans↗
Dosimetry of interstitial brachytherapy sources: recommendations of the AAPM Radiation Therapy Committee Task Group No. 43. American Association of Physicists in Medicine.
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Brachytherapy↗
Comparison of radiation dosimetry in water and in solid phantom materials for I-125 and Pd-103 brachytherapy sources: EGS4 Monte Carlo study [Med. Phys. 21, 631-641 (1994)].
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Biophysical Phenomena↗
Comparison of radiation dosimetry in water and in solid phantom materials for I-125 and Pd-103 brachytherapy sources: EGS4 Monte Carlo study.
A model based on the EGS4 Monte Carlo system is developed for calculating dose rate to water from an embedded low-energy brachytherapy source, given measurement data of dose rate to water within a water-substitute solid phantom for a source of given strength. The EGS4-based model is used to calculate point source dose rate distributions per unit source strength for water and for several species of solid phantoms. As a model for the dose rate distribution to an infinitesimal water inhomogeneity embedded in the solid phantom, the Monte Carlo is used to calculate dose rate to a thin spherical shell of water contained within the solid phantom at various distances centered on the source. Comparing this distribution to that calculated for a homogeneous water phantom, one can derive correction factors to determine dose rate to homogeneous water medium from measurements with water dose-calibrated detectors within the solid phantom. These factors are calculated for polymethylmethacrylate (PMMA or acrylic), solid water (WT1), and RW-1, a material optimized for low-energy dosimetry, with photon spectra from Pd-103 and from two commercial models of I-125 seed used as input. For model 6711 I-125 seeds at 1 cm in PMMA and WT1, the calculated ratios of dose rate to water to dose rate to water in the solid phantom are 0.893 and 1.038, respectively. Applying these factors to published, apparently divergent measurements of the specific dose rate constant based on measurements in PMMA and WT1 phantoms, the specific dose rate constant inferred for the model 6711 seed are found to be in excellent agreement: 0.878 cGy h-1U-1 (1.115 cGy- cm2h-1mCi-1) from the mean of the WT1 measurements and 0.879 cGy h-1U-1 from the PMMA measurements. Among the phantoms studied for Pd-103 and I-125, measurements in RW-1 would most closely approximate those for water.
Biophysical Phenomena↗
Stereotactic radiosurgery: principles and comparison of treatment methods.
Methods of stereotactic radiosurgery are reviewed and compared with respect to technical factors and published clinical results. Heavy-ion beams, the Leksell cobalt-60 gamma knife, and the conventional linear accelerator (linac) are compared with respect to dosimetry, radiobiology, treatment planning, cost, staffing requirements, and ease of use. Clinical results on the efficacy of treatment of arteriovenous malformations are tabulated, and other applications of radiosurgery are described. It is concluded that although there are dosimetric and radiobiological advantages to charged-particle beams that may ultimately prove critical in the application of radiosurgery to large (> 30 mm) lesions, these advantages have not yet demonstrated clinical effect. On the other hand, equally excellent clinical results are obtained for small lesions with photon beams--the gamma knife and the linac. There are only minor differences between gamma and x-ray beam dose distributions for small, spherical-shaped targets. Mechanical precision is superior for the gamma knife as compared with the linac. The superior mechanical precision is of limited importance for most clinical targets, because inaccuracy of cranial target localization based on radiological imaging is greater than the typical linac imprecision of +/- 1 mm. Treatment planning for the linac is not standardized, but existing systems are based on well-known algorithms. The linac allows flexible, ready access to individualized beam control, without intrinsic field size limitations. Thus, it is more readily possible to achieve homogeneous dose distributions for nonspherical targets with one or more dimensions greater than 25 mm, as compared with that achieved with the gamma unit.(ABSTRACT TRUNCATED AT 250 WORDS)
Equipment Design↗
Episcleral plaque thermoradiotherapy in patients with choroidal melanoma.
From 1988 to 1991, 21 patients with uveal melanoma were treated in a Phase I study with episcleral plaque radiotherapy (EPRT). This irradiation was combined with localized current field episcleral hyperthermia (LCFHT). Tumor stage was: T3 = 15 (71%) and T2 = 6 (29%). Follow-up ranged from 2 to 42 months (mean 9.2 months). EPRT was given using custom built I-125 gold plaques. Radiation doses to the tumor apex ranged from 13 to 123 Gy (mean dose 70.0 Gy) given at a mean dose rate of 55 cGy/hr. LCFHT was given with 500 KHz frequency for 45 min immediately before EPRT. The temperature was controlled on the scleral surface using four thermocouples. T mean ranged from 42.5 degrees C to 45 degrees C +/- 0.5 degrees C (mean 43.4 degrees C). The study patients showed rapid tumor necrosis. A 25% mean decrease of apical tumor dimension was noted, p = 0.0007. At least ambulatory vision (greater than 5/200) was maintained by 17/21 (81%) patients. Visual acuity was seen to improve greater than 6 months post-plaque therapy in 10 (48%) study patients. This was following an intermediate decrease in visual acuity. Severe complications, including large hemorrhagic retinal detachment and large vitreous hemorrhage, were seen in two (9.5%) of the early study patients. A mean scleral temperature reduction to less than or equal to 44 degrees C +/- 0.5 degrees C resulted in good treatment tolerance and a lack of serious complications in subsequently treated patients. A Phase II prospective randomized trial comparing LCFHT with 60 versus 80 Gy EPRT dose to the tumor apex is currently being activated for patients with choroidal melanoma.
Adolescent↗
Episcleral plaque radiotherapy in the treatment of uveal melanomas.
During an 8-year period, 85 patients with uveal melanomas were treated with episcleral plaque radiotherapy (EPRT). The T-stage was: T1-3 (4%), T2-29 (34%) and T3-53 (62%). The mean tumor elevation was 6.1 mm. Radiation dose was prescribed at the tumor apex and at D5mm. The mean D5mm dose was 150.1 Gy (range 70.5-430 Gy) and the mean dose at the apex was 102.6 Gy (range 29.8-200 Gy). Useful vision (greater than 5/200) was maintained in 73% of patients. The 5-year actuarial survival was 88%. Metastatic disease developed in 9 (11%) patients, 6 of whom died of their disease. Basal tumor dimensions were important factors predicting metastatic disease, p = 0.002. A decrease in tumor evaluation was seen in 82%. There was a much lower incidence of decrease in tumor radial and circumferential dimensions, 47.5 and 46%, respectively, p less than 0.001. Treatment complications were common (56%), particularly in patients with large tumors (72%), p = 0.04. The incidence of complications was higher in patients treated prior to 1988 as compared to those who were treated more recently (67 vs 35%, p = 0.010). There were 13 (15%) patients who had enucleation. This included 12 treated before 1986 and 1 patient treated subsequently (46 vs 2%, p less than 0.001). In a univariate analysis, tumor height and radiation dose at D5mm were important factors predicting enucleation, p = 0.004. In a multivariate analysis, however, the most important factor predicting enucleation was treatment administration prior to 1986, p less than 0.001). A sharp decrease in the incidence of severe complications, including enucleation, as seen after 1985, is likely due to a major effort in treatment optimization.
Adult↗
Radionecrosis secondary to interstitial brachytherapy: correlation of magnetic resonance imaging and histopathology.
Radiation-induced tissue damage in the central nervous system is a well-known complication of interstitial brachytherapy for brain tumors, yet imaging correlates have historically been based upon computed tomographic scans. We now present magnetic resonance imaging (MRI) to correlate radiation changes after interstitial brachytherapy with the histopathology. The central nervous system of a 38-year-old man with a left frontal cerebral glioma diagnosed by stereotactic biopsy was treated with interstitial brachytherapy (iridium-192, 47 Gy), followed by limited-field irradiation (45 Gy). With progressive deterioration, a second biopsy demonstrated radiation changes. Despite aggressive medical management, the patient died 9 months after completion of radiation therapy. Postmortem evaluation compared MRI scans of the intact, fixed brain with the histopathology. Axial sections (10 mm) obtained by MRI scan and autopsy brain slices were cut in the identical plane. Neuroimaging and histopathological findings of the lesion correlated within 2 to 3 mm resolution. In the peripheral white matter, MRI scan did not indicate the extent of radiation effect histologically. We suggest that MRI has limited utility in assessing the extent of impact of radiation on surrounding brain.
Adult↗
Treatment results of stereotactic interstitial brachytherapy for primary and metastatic brain tumors.
A total of 41 stereotactic interstitial brain implants in 39 patients were performed for recurrence after teletherapy (recurrence implant), or as part of initial treatment in conjunction with teletherapy (primary implant). Implanted tumors consisted of malignant gliomas (33), other primary brain tumors (3), and single metastatic lesions (3). All patients were temporarily implanted with Ir-192 using a coaxial catheter afterloading system; two patients were implanted twice. Survival post-implant for glioblastoma multiforme (GBM), 13 patients, was 10 months whether implanted primarily or for recurrence. Mean time to recurrence, measured from initiation of teletherapy to implantation, was 10 months. Twenty patients with anaplastic astrocytoma (AA) had a median survival post-implant of 23 months for primary implants (7 patients) and 11 months for recurrence implants (13 patients). Mean time to recurrence, measured from initiation of teletherapy to implantation, was 19 months. Three patients (9%) of the evaluable group required reoperation for symptomatic mass effect, all with initial diagnosis of AA. Survival for this subgroup was 14, 22, and 32 months post-implantation. Using stereotactic techniques, interstitial brachytherapy of brain tumors was technically feasible with negligible acute morbidity and mortality, and appeared to offer limited prolongation of control for a subset of patients with recurrent malignant gliomas. The role of this modality in primary treatment for malignant gliomas needs to be further defined by prospectively randomized trials.
Adolescent↗
Radiotherapy following radical prostatectomy in patients with adenocarcinoma of the prostate.
From 1973 to 1986, 160 patients with adenocarcinoma localized to the prostate were treated with radical prostatectomy and pelvic lymphadenectomy. In 78 (49%) patients more advanced stage of disease was found at surgery and they received local pelvic irradiation (RT). This consisted of 45 Gy for microscopic and 55 Gy for macroscopic residual disease. RT was given at 1.8 Gy a day, using the four-field "box" technique with the 23 MV X ray beam. Pelvic lymph node metastases were found in 28 (36%) patients who, in addition to RT, received systemic therapy: 20 with cyclophosphamide alone, 4 combined with 5-Fluorouracil, and 4 patients received DES. The 5- and 10-year overall actuarial survival was 95 and 77%, respectively, and the 5- and 10-year disease-free survival was 58 and 43%, respectively. Recurrent tumor was found in 34 (44%) patients. Of these 34 patients, 32 (94%) had distant metastatic tumor and 2 (6%) had local recurrence in the pelvis. The presence of metastatic disease in pelvic lymph nodes had clinical significance since it influenced disease-free survival and the incidence of tumor recurrence. The 10-year disease-free survival for the 50 patients with no lymph node metastases was 51%, as compared to 28% for the 28 patients with such metastases, p = 0.001. Similarly, recurrent tumor was found in 28% of the former and 68% of the latter patients, p = 0.002. Other important parameters predicting recurrence were: clinical stage, p = 0.018, histological grade, p = 0.013, and Gleason's grade, p = 0.002. This treatment program was very well tolerated and of low toxicity. There was no surgical mortality. Surgical complications were seen in 10 (13%) patients including: minor in 5 and major in 5. At 1 year, 77% of the patients remained continent, while 10% had mild stress incontinence. Of the remaining 13% only 3 (4%) patients had severe incontinence (greater than 5 pads daily). RT toxicity was mild with 38% experiencing diarrhea. Severe toxicity was seen in 2 (3%) patients who, early in the study, developed scrotal and lower extremity edema. Severe chemotherapy complications were seen in 1 (4%) patient who had severe neutropenic sepsis. Postoperative radiotherapy is a well tolerated, safe and effective treatment in patients who have microscopic or macroscopic residual tumor following radical prostatectomy.
Adenocarcinoma↗
Management of carcinoma of the esophagus: the role of radiotherapy.
This is an analysis of treatment results over a 23-year period in 241 patients with carcinoma of the esophagus. The treatment for unresectable patients was external beam radiotherapy (EBRT) alone (mean dose 55 Gy) in 137 (57%) combined with brachytherapy (mean dose 50 + 40 Gy) in 46 (19%), and chemotherapy alone in 3 (1%) patients. In the 55 resectable patients, treatment was resection alone in 9 (4%), and combined with radiotherapy (mean dose 43 Gy) in 46 (19%) patients. The 1-, 2-, and 5-year survival for the 241 patients was 36, 15, and 5%, respectively (median 38 weeks). The 5-year survival was 18% for radiotherapy (RT)-surgery (S) patients, 11% for EBRT with brachytherapy, 2% for EBRT alone, and 0% for patients who had S alone, p less than 0.001. Survival correlated well with initial performance status, treatment, stage of disease, tumor size, radiation dose, and degree of response, p less than 0.001, but not with tumor location in the esophagus and patients' race and sex, p = 0.44. Serious complications occurred in 5 (2%) patients treated with RT alone and in 4 (7%) patients treated with S alone or combined with RT. The leading cause of death was persistent or recurrent tumor in the chest found in 39% patients.
Adult↗
Treatment of uterine sarcomas.
During a 21-year period, 66 patients with uterine sarcomas were treated at California Medical Center. Histological diagnoses were mixed mesodermal sarcoma in 32 patients (48%), leiomyosarcoma in 24 (36%), and endometrial stromal sarcoma in 10 (15%) patients. The majority of patients (73%) had Stage I tumors. The treatment consisted of surgery alone in 27 (41%), surgery in combination with radiation therapy in 36 (55%), and radiation therapy alone in three (4%) patients. The overall 1-, 2-, and 5-year actuarial survival was 74%, 57%, and 38%, respectively. The 1-, 2-, and 5-year actuarial survival for the 27 surgery alone patients was 73%, 50%, and 25%, which compared with 75%, 61%, and 44% for the 36 surgery plus radiation therapy patients (P = 0.12). The disease-free survival was better for the surgery plus radiation therapy patients, as compared with the surgery alone group (38% vs. 18% at 5 years, P = 0.081). The 5-year survival by histology was 70% for the 10 endometrial stromal sarcoma patients, 40% for the 24 leiomyosarcoma patients, and 23% for the 32 mesodermal sarcoma patients (P = 0.064). As expected, survival depended on the stage of disease (P less than 0.0001). Treatment failure was observed in 35 (53%) patients, which included 9 (14%) with failure in the pelvis. There was no difference in the incidence of failure among patients in the three treatment groups and also in the three histologic groups. There was, however, a significant difference in the incidence of pelvic failure between surgery alone and surgery plus radiation therapy patients. In the 27 surgery alone patients, nine (33%) relapsed in the pelvis, whereas none of the 36 surgery plus radiation therapy patients had locoregional failure, P less than 0.0001. Adjuvant radiation therapy is an important treatment in the management of patients with sarcoma of the uterus.
Adult↗
Comments on Dosimetric consideration on multiple arc stereotaxic radiotherapy.
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Humans↗
An interactive treatment planning system for ophthalmic plaque radiotherapy.
Brachytherapy using removable episcleral plaques containing sealed radioisotope sources is being studied as an alternative to enucleation in the treatment of choroidal melanoma and other tumors of the eye. Encouraging early results have been reported, but late complications which lead to loss of vision continue to be a problem. A randomized national study, the Collaborative Ocular Melanoma Study (COMS) is currently in progress to evaluate the procedure. The COMS specified isotope is 125I. Precise dosimetric calculations near the plaque may correlate strongly with complications and could also be used to optimize isotope loading patterns in the plaques. A microcomputer based treatment planning system has been developed for ophthalmic plaque brachytherapy. The program incorporates an interactive, 3-dimensional, solid-surface, color-graphic interface. The program currently supports 125I and 192Ir seeds which are treated as anisotropic line sources. Collimation effects related to plaque structure are accounted for, permitting detailed study of shielding effectiveness near the lip of a plaque. A dose distribution matrix may be calculated in any subregion of a transverse, sagittal, or coronal planar cross section of the eye, in any plane transecting the plaque and crossing the eye diametrically, or on a spherical surface within or surrounding the eye. Spherical surfaces may be displayed as 3-dimensional perspective projections or as funduscopic diagrams. Isodose contours are interpolated from the dose matrix. A pointer is also available to explicitly calculate and display dose at any location on the dosimetry surface. An interactive editing capability allows new plaque designs to be rapidly added to the system.
Brachytherapy↗
Measurement of dose rate from exposure-calibrated 125I seeds.
Dose rate in water 1 cm transverse to an 125I seed calibrated for air kerma strength is not well established; 125I dosimetry calculations are, however, based on this constant. The specific dose constant was obtained from a series of dose rate measurements using thermoluminescent dosimetry (TLD) in a rigid geometry, full scatter acrylic phantom for individual model 6711 seeds. With a statistical precision of approximately +/- .5%, the dose rate to an infinitesimal mass of water located in acrylic at a perpendicular distance of 1 cm from the seed was found to be 0.977 cGy/h per microGy-m2/h of air kerma strength. Dose rate in a water phantom was calculated using a model that takes into account differences in both attenuation and scatter between water and acrylic. The specific dose constant in water was determined to be 0.932 (1.184 cGy-cm2/mCi-h, for the conventional exposure rate constant of 1.45 R cm2/mCi-h). This value is 7.5% less than dose rate in water from an unattenuated point source, and 9.7% less than the value commonly used for dosimetry calculations. The results suggest that most clinical 125I dosimetry estimates to date should be reconsidered for a possible reduction by about 10%. Relative scatter attenuation factors at 3 and 5 mm are also presented.
Calibration↗
Episcleral radioactive plaque therapy: initial clinical experience with 56 patients.
Between 1983 and 1987, 56 patients with choroidal melanoma were treated at the University of Southern California with episcleral plaque (RPT). There were 29 female and 27 male patients, with a mean age of 59 years. Tumor stage at diagnosis was T2 in 18 (32%) and T3 in 38 (68%) patients. The tumor height ranged from 2.9 to 15 mm (mean 6.8 mm). Radial dimensions ranged from 5 to 25 mm (mean 13.2 mm), and circumference ranged from 7 to 23 mm (mean 12.3 mm). Most (77%) patients had posteriorly located tumors, including 18% that were juxtapapillary. Custom-designed gold plaques were utilized in this study. Radioactive isotopes used were 125I for 26 procedures or 192Ir for 31 procedures. A total of 56 patients were treated, with one patient having two procedures. Radiation doses at the tumor apex ranged from 29.8 to 165.4 Gy (mean 94.5 Gy), with the dose at 5-mm depth ranging from 70.5 to 430 Gy (mean 161.5 Gy). Follow-up ranged from 29 to 57 months (mean 39 months). The overall 4-year survival was 96%, with a 91% incidence of free-of-disease progression at 4 years. The majority (84%) of patients experienced a decrease in tumor height, with 27 (48%) patients having greater than 50% decrease. Increase in tumor height was noted in 5 (9%) and no change in 4 (7%) patients. Useful vision (greater than 5/200) was observed in 59% of patients, including 21% who had improved vision. Metastatic tumor occurred in 5 (9%) patients, with a mean time to metastases of 14 months. There was a good correlation between radial tumor dimension and metastatic disease, p less than 0.001. Treatment complications were observed in 34 (61%) patients, with cataract and retinopathy being the most common. Enucleation was performed in 11 (20%) patients, with a mean time to enucleation of 14.5 months. Causative factors for enucleation were treatment complications in 6 and tumor progression in 5 patients. Enucleations were required primarily in patients with tumors greater than 8 mm in height (p = 0.009). Improved RPT techniques with three-dimensional dosimetry are needed to reduce the overall incidence of treatment complications. Adjuvant hyperthermia is being investigated in an attempt to improve tumor control in patients with larger tumors.
Adult↗