Gary Luxton

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 < 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 < 0.0001. Adjuvant radiation therapy is an important treatment in the management of patients with sarcoma of the uterus.

A quality assurance program for the on-board imager ®

To develop a quality assurance (QA) program for the On-Board Imager (OBI) system and to summarize the results of these QA tests over extended periods from multiple institutions. Both the radiographic and cone-beam computed tomography (CBCT) mode of operation have been evaluated. The QA programs from four institutions have been combined to generate a series of tests for evaluating the performance of the On-Board Imager. The combined QA program consists of three parts: (1) safety and functionality, (2) geometry, and (3) image quality. Safety and functionality tests evaluate the functionality of safety features and the clinical operation of the entire system during the tube warm-up. Geometry QA verifies the geometric accuracy and stability of the OBI/CBCT hardware/software. Image quality QA monitors spatial resolution and contrast sensitivity of the radiographic images. Image quality QA for CBCT includes tests for Hounsfield Unit (HU) linearity, HU uniformity, spatial linearity, and scan slice geometry, in addition. All safety and functionality tests passed on a daily basis. The average accuracy of the OBI isocenter was better than 1.5mm with a range of variation of less than 1mm over 8 months. The average accuracy of arm positions in the mechanical geometry QA was better than 1mm, with a range of variation of less than 1mm over 8 months. Measurements of other geometry QA tests showed stable results within tolerance throughout the test periods. Radiographic contrast sensitivity ranged between 2.2% and 3.2% and spatial resolution ranged between 1.25 and 1.6lp∕mm. Over four months the CBCT images showed stable spatial linearity, scan slice geometry, contrast resolution (1%; <7mm disk) and spatial resolution (>6lp∕cm). The HU linearity was within ±40HU for all measurements. By combining test methods from multiple institutions, we have developed a comprehensive, yet practical, set of QA tests for the OBI system. Use of the tests over extended periods show that the OBI system has reliable mechanical accuracy and stable image quality. Nevertheless, the tests have been useful in detecting performance deficits in the OBI system that needed recalibration. It is important that all tests are performed on a regular basis.

Gamma Knife Radiosurgery for Metastatic Melanoma: An Analysis of Survival, Outcome, and Complications

OBJECTIVE Although the mainstays for treatment of metastatic brain disease have been surgery and/or external beam radiation therapy, an increasing number of patients are being referred for stereotactic radiosurgery as the primary intervention for their intracranial pathological abnormalities. The lack of efficacy and cognitive and behavioral consequences of whole brain irradiation have prompted clinicians to select patients for alternative therapies. This study analyzes the effectiveness of Leksell gamma unit therapy for metastatic melanoma to the brain. METHODS We present our experience with 59 Leksell gamma unit treatment sessions in 45 consecutive patients who presented with metastatic melanoma to the brain. Five of these procedures were performed as salvage therapy for patients who needed second radiosurgical treatment for new lesions that were remote from the previous targets and were not included in the overall analyses. RESULTS The population included 78% male patients. The mean patient age was 53 years (age range, 24-80 yr). The mean time from diagnosis of primary melanoma to discovery of brain metastasis was 43 months (median, 27.5 mo; range, 1-180 mo). At the time of diagnosis of brain disease, 35.5% of the patients (16 of 45 patients) had neurological symptoms, 77.7% (35 of 45 patients) had known visceral metastases, and 11.1% (5 of 45 patients) had seizure disorders. Eighty-six percent of the lesions (80 of 93 lesions) were cortical, 12% (11 of 93 lesions) were cerebellar, 1% (1 of 93 lesions) were pontine, and 1% (1 of 93 lesions) were thalamic. Fifty-seven percent of the sessions (31 of 54 sessions) were performed for a single lesion, 24.1% (13 of 54 sessions) for two lesions, 9.2% (5 of 54 sessions) for three lesions, 7.4% (4 of 54 sessions) for four lesions, and 1.8% (1 of 54 sessions) for five lesions. The mean treatment volume was 5.6 cc, with a mean prescription of 21.6 Gy to the 56.0% mean isodose line. The median survival time of the patients in our population, using Kaplan-Meier curves, was 43 months from the time of diagnosis of primary melanoma (range, 3-180 mo) and 8 months (range, 1-20 mo) from the time of gamma knife treatment. Complications included seizures within 24 hours of the procedure in four patients, with transient nausea and vomiting in three patients, transient worsening of preprocedure paresis responsive to steroids in three patients, and increased confusion in one patient. All 45 patients were located for follow-up (mean follow-up duration, 1 yr). After gamma knife treatment, 78% of the patients (35 of 45 patients) experienced either improved or stable neurological symptomatology before death or at the time of the latest follow-up examination. There were 26 deaths (58%). The cause of death was determined to be neurological in only 2 of 45 patients (7.7%). Follow-up magnetic resonance images revealed a 97% local tumor control rate of gamma knife-treated lesions, with 28% radiographic disappearance (9 of 32 cases). Six patients developed new lesions remote from radiosurgical targets and underwent second procedures. CONCLUSION Although metastatic melanoma to the brain continues to have a foreboding prognosis for long-term survival, gamma knife radiosurgery seems to be a relatively safe, noninvasive, palliative therapy, halting or reversing neurological progression in 77.8% of treated patients (35 of 45 patients). The survival rate matches or exceeds those previously reported for surgery and other forms of radiotherapy. Only 7.7% of the patients in our study population who died as a result of metastatic melanoma (2 of 26 patients) died as a result of neurological disease. The routine use of therapeutic level antiseizure medication is emphasized, considering the findings of our review.

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)

Image-guided radiosurgery for the spine and pancreas.

A robotic image-guided radiosurgical system has been modified to treat extra-cranial sites using implanted fiducials and skeletal landmarks to locate the treatment targets. The system has been used to treat an artero-venous malformation in the cervical spine, a recurrent schwannoma of the thoracic spine, a metastatic adenocarcinoma of the lumbar spine, and three pancreatic cancers. During each treatment, the image guidance system monitored the position of the target site and relayed the target coordinates to the beam-pointing system at discrete intervals. The pointing system then dynamically aligned the therapy beam with the lesion, automatically compensating for shifts in target position. Breathing-related motion of the pancreas lesions was managed by coordinating beam gating with breath-holding by the patient. The system maintained alignment with the spine lesions to within +/- 0.2 mm on average, and to within +/- 1 mm for the pancreatic tumors. This experience has demonstrated the feasibility of using image-guided robotic radiosurgery outside the cranium.

Carcinoma of the lip and selected sites of head and neck skin. A clinical study of 896 patients

During a period of over 20 years, 896 patients were treated with radiation in Wadsworth Medical Center, Los Angeles, for carcinoma of the lip and selected sites of skin of the head and neck. Basal cell carcinoma (BCC) was found in 467 (52%) patients, squamous cell carcinoma (SCC) in 362 (40%), and the remaining 67 (8%) had tumors with mixed basal and squamous cell features. BCC was the most common tumor (72%) among the 646 skin cancer patients while SCC predominated (99%) among the 250 lip cancer patients. Tumor control correlated well with the size of the lesion, p less than 0.0001. Histology of the lesion also had a significant (p = 0.021) influence on the tumor control rate, which was the highest among the BCC patients when compared with SCC or mixed cell patients. This study has again demonstrated the effectiveness of radiotherapy in controlling small and intermediate size epithelial tumors of the skin and lip. Additionally, irradiation, if administered properly, results in excellent cosmesis and a low incidence of treatment complications. Severe complications of radiotherapy reported in the literature took place at the beginning of this century and are no longer pertinent in the practice of modern radiation oncology. Larger lesions remain a challenge to radiation or surgical dermato-oncologists. A lack of tumor control in such lesions frequently results in a death of patient.

Microwave applicator for transurethral hyperthermia of benign prostatic hyperplasia

An applicator for heating the prostate gland using a transurethral approach is described. This technique uses three microwave antennas and a thermometry sensor attached to the outer surface of a balloon (Foley) type urological catheter. Each microwave antenna also includes a built-in thermistor to control temperature and balance power. The balloon catheter assures rapid and reproducible localization of the antennas in the prostatic urethra. The two-dimensional SAR and steady-state temperature distributions surrounding the applicator in tissue equivalent phantom are reported. Longitudinal temperature distributions measured in situ at the applicator-urethral interface and the longitudinal and radial temperature distributions measured in normal canine prostate are presented and discussed. The technique appears to be capable of elevating temperature to greater than 42 degrees C in a cylindrically symmetrical volume up to 5 cm length and 0.5 cm radial penetration surrounding the applicator.

A new formula for normal tissue complication probability (NTCP) as a function of equivalent uniform dose (EUD)

To facilitate the use of biological outcome modeling for treatment planning, an exponential function is introduced as a simpler equivalent to the Lyman formula for calculating normal tissue complication probability (NTCP). The single parameter of the exponential function is chosen to reproduce the Lyman calculation to within approximately 0.3%, and thus enable easy conversion of data contained in empirical fits of Lyman parameters for organs at risk (OARs). Organ parameters for the new formula are given in terms of Lyman model m and TD(50), and conversely m and TD(50) are expressed in terms of the parameters of the new equation. The role of the Lyman volume-effect parameter n is unchanged from its role in the Lyman model. For a non-homogeneously irradiated OAR, an equation relates d(ref), n, v(eff) and the Niemierko equivalent uniform dose (EUD), where d(ref) and v(eff) are the reference dose and effective fractional volume of the Kutcher-Burman reduction algorithm (i.e. the LKB model). It follows in the LKB model that uniform EUD irradiation of an OAR results in the same NTCP as the original non-homogeneous distribution. The NTCP equation is therefore represented as a function of EUD. The inverse equation expresses EUD as a function of NTCP and is used to generate a table of EUD versus normal tissue complication probability for the Emami-Burman parameter fits as well as for OAR parameter sets from more recent data.

Monitor unit calculation for an intensity modulated photon field by a simple scatter-summation algorithm

An important issue in intensity modulated radiation therapy (IMRT) is the verification of the monitor unit (MU) calculation of the planning system using an independent procedure. Because of the intensity modulation and the dynamic nature of the delivery process, the problem becomes much more involved than that in conventional radiation therapy. In this work, a closed formula for MU calculation is derived. The approach is independent of the specific form of leaf sequence algorithms. It is straightforward to implement the procedure using a simple computer program. The approach is illustrated by a simplified example and is demonstrated by a few CORVUS (NOMOS Corporation, Sewickley, PA) treatment plans. The results indicate that it is robust and suitable for IMRT MU verification.

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.