A prospective, randomized, double-blind, placebo-controlled study of orbital radiotherapy for Graves' ophthalmopathy.

CONTEXT: Although widely used for more than 85 years, the efficacy of radiotherapy for Graves' ophthalmopathy (GO) has not been established convincingly. OBJECTIVE: To evaluate the efficacy of radiotherapy for GO. DESIGN: Prospective, randomized, internally controlled, double-blind clinical trial in a tertiary care academic medical center. PARTICIPANTS: The patients were ethnically diverse males and females over age 30 seen in a referral practice. The patients had moderate, symptomatic Graves' ophthalmopathy (mean clinical activity score, 6.2) but no optic neuropathy, diabetes, recent steroid treatment, previous decompression, or muscle surgery. Forty-two of 53 consecutive patients were enrolled after giving informed consent and fulfilling study entry criteria. Eleven eligible patients declined to participate because of inconvenience, desire for alternative therapy, or concern about radiation. INTERVENTION: One randomly selected orbit was treated with 20 Gy of external beam therapy; sham therapy was given to the other side. Six months later, the therapies were reversed. MAIN OUTCOME MEASURES: Every 3 months for 1 year, we measured the volume of extraocular muscle and fat, proptosis, range of extraocular muscle motion, area of diplopia fields, and lid fissure width. Effective treatment for GO will modify one or more of these parameters. RESULTS: No clinically or statistically significant difference between the treated and untreated orbit was observed in any of the main outcome measures at 6 months. At 12 months, muscle volume and proptosis improved slightly more in the orbit that was treated first. CONCLUSIONS: In this group of patients, representative of those for whom radiotherapy is frequently recommended, we were unable to demonstrate any beneficial therapeutic effect. The slight improvement noted in both orbits at 12 months may be the result of natural remission or of radiotherapy, but the changes are of marginal clinical significance.

The rationale and technique of staged-volume arteriovenous malformation radiosurgery.

PURPOSE: Stereotactic radiosurgery is an effective management strategy for properly selected arteriovenous malformation (AVM) patients. However, the risk of postradiosurgical radiation-related injury generally limits this procedure to patients with AVMs of an average diameter of 3 cm or less. Radiosurgery of large AVMs in a planned staged fashion was undertaken to limit the radiation exposure to the surrounding normal brain. METHODS AND MATERIALS: Between April 1997 and December 1999, 10 patients with a median AVM volume of 17.4 cm(3) (range, 7.4-53.3 cm(3)) underwent staged-volume radiosurgery (23 procedures). At the first radiosurgical procedure, the total volume of the AVM is estimated and a dose plan calculated that covers 10 cm(3)-15 cm(3), or one-half the nidus volume if the AVM is critically located (brainstem, thalamus, or basal ganglia). At 6-month intervals thereafter, radiosurgery was repeated to different portions of the AVM with the previous dose plan(s) being re-created utilizing intracranial landmarks to minimize radiation overlap. Radiosurgical procedures were continued until the entire malformation has been irradiated. RESULTS: The radiation dosimetry of staged-volume AVM radiosurgery was compared to hypothetical single-session procedures for the 10 patients. Staged-volume radiosurgery decreased the 12-Gy volume by an average of 11.1% (range, 4.9-21%) (p < 0.001). The non-AVM 12-Gy volume was reduced by an average of 27.2% (range, 12.5-51.3%) (p < 0.001). DISCUSSION: Staged-volume radiosurgery of large AVMs results in less radiation exposure to the adjacent brain. Further follow-up is needed to determine whether this technique provides a high rate of AVM obliteration while maintaining an acceptable rate of radiation-related complications.

The Mayo Clinic gamma knife experience: indications and initial results.

OBJECTIVE: To review the results and expectations of contemporary stereotactic radiosurgery. MATERIAL AND METHODS: We conducted a retrospective analysis of 1,033 consecutive patients who underwent gamma knife radiosurgery at Mayo Clinic Rochester between January 1990 and January 1998. RESULTS: The number of patients undergoing radiosurgery increased from 57 in 1990 to 216 in 1997. Of 97 patients with arteriovenous malformations who underwent follow-up angiography 2 years or more after a single radiosurgical procedure, 72 (74%) had complete obliteration of the vascular malformation. Of 209 patients who underwent radiosurgery for benign tumors (schwannomas, meningiomas, or pituitary adenomas) and had radiologic studies after 2 years or more of follow-up, tumor growth control was noted in 200 (96%). Tumor growth was also controlled in 90% of brain metastatic lesions at a median of 7 months after radiosurgery. Of 20 patients with trigeminal neuralgia and follow-up for more than 2 months, 14 (70%) were free of pain after radiosurgery. CONCLUSION: Radiosurgery is a safe and effective management strategy for a wide variety of intracranial disorders. Use of radiosurgical treatment should continue to increase as more data become available on the long-term results of this procedure.

Decrease in cranial nerve complications after radiosurgery for acoustic neuromas: a prospective study of dose and volume.

PURPOSE: To determine whether tumor control can be maintained, and cranial nerve complications decreased by reducing the radiosurgical dose to acoustic neuromas. METHODS AND MATERIALS: Forty-two consecutive patients with acoustic neuromas were treated prospectively using an initial standard-dose protocol in which the tumor-margin dose (50% isodose) was 20, 18, and 16 Gy for tumor diameters < or =2 cm, 2.1-3 cm, and 3.1-4 cm, respectively. After analysis of tumor control and complications, the next 40 patients were treated using a reduced-dose protocol in which the tumor-margin dose was 16, 14, and 12 Gy for tumor volumes < or =4.2 cm3, 4.2-14.1 cm3, and > or =14.1 cm3, respectively. RESULTS: Median follow-up was 2.3 years (range 0.1-6) for 80 of 82 patients. The actuarial incidence (Kaplan-Meier) of facial neuropathy at 2 years was 38% (95% confidence interval [CI], 23-53%) for the standard-dose protocol and 8% (95% CI, 0-17%) for the reduced-dose protocol (p = 0.006). Univariate analysis revealed an association between risk of facial neuropathy and use of CT planning, higher radiosurgical dose, and neurofibromatosis, type 2. Multivariate analysis revealed that the only factor associated with increased risk of post-treatment facial neuropathy was a tumor margin dose > or =18 Gy. The incidence of trigeminal neuropathy at 2 years was 29% (95% CI, 15-43%) for the standard-dose protocol and 15% (95% CI, 3-27%) for the reduced-dose protocol (p = 0.17). Univariate analysis revealed an association between maximal tumor diameter and increased risk of trigeminal neuropathy; multivariate analysis revealed no additional statistically significant associations between tumor and dosimetric and patient characteristics and risk of trigeminal neuropathy. Two tumors in the standard-dose protocol required salvage surgery for progression. To date, no tumor in the reduced-dose protocol has shown progression. CONCLUSION: Our analysis suggests that a tumor margin dose of > or =18 Gy is the most significant risk factor for facial nerve complications after acoustic neuroma radiosurgery. Patients receiving a minimal tumor dose of < or =16 Gy are at significantly lower risk for permanent facial neuropathy after radiosurgery. Longer follow-up is required before definitive conclusions can be made about the ultimate rate of tumor control using reduced radiosurgical doses.

Automated seed localization from CT datasets of the prostate.

With the increasing utilization of permanent brachytherapy implants for treating carcinoma of the prostate, the importance of accurate post-treatment dose calculation also increases for assessing patient outcome and planning future treatments. An automatic method for seed localization of permanent brachytherapy implants, using CT datasets of the prostate, has been developed and tested on a phantom using an actual patient planned seed distribution. This method was also compared to results with the three-film technique for three patient datasets. The automatic method is as accurate or more accurate than the three film technique for 1 mm, 3 mm, and 5 mm contiguous CT slices, and eliminates the inter- and intra-observer variability of the manual methods. The automated method improves the localization of brachytherapy seeds while reducing the time required for the user to input information, and is demonstrated to be less operator dependent, less time consuming, and potentially more accurate than the three-film technique.

Impact of beam energy and field margin on penumbra at lung tumor-lung parenchyma interfaces.

PURPOSE: To determine the characteristics of the penumbra in the region of the lung tumor-lung parenchyma interfaces for various radiation beam energies and various field margins. METHODS AND MATERIALS: A phantom simulating the thoracic cavity with a tumor arising within the lung parenchyma was irradiated with opposed 6-, 10-, and 18-MV photon beams. Beam profiles were obtained at the tumor's surface and midplane using radiographic film. The field edge varied from 0.0 to 3.5 cm from the gross tumor volume. The effective penumbra (distance from 80 to 20% dose) and beam fringe (distance from 90 to 50% dose) were measured. Clinically acceptable beam profiles were defined as those in which no point of the planning target volume (gross tumor volume plus a 1-cm margin) received less than 95% of the central tumor dose. RESULTS: Mean effective penumbra and beam fringe were found to differ in a statistically significant manner with respect to energy, but not with distance from field edge to gross tumor volume. With the field edge < or = 1.5 cm from the gross tumor volume, no energy provided an acceptable dose distribution, as defined above. With the field edge 2 cm from the gross tumor volume, 6 and 10 MV provided acceptable dose distributions, but 18 MV did not. With the field edge > or = 2.5 cm from the gross tumor volume, all energies provided acceptable dose distributions. CONCLUSION: For irradiation of lung carcinomas in which the planning target volume includes a margin of normal lung tissue, 6- and 10-MV opposed beams yield a superior dose distribution with respect to penumbra at the tumor's surface and midplane, with the field edge placed 2 cm from the gross tumor volume. To achieve an equivalent distribution with 18-MV photons, a distance of 2.5 cm from field edge to the gross tumor volume is necessary, leading to an increase in normal lung tissue irradiated.

Report of the ad hoc committee of the AAPM radiation therapy committee on 125I sealed source dosimetry.

PURPOSE: Two developments in 125I-sealed source dosimetry have necessitated swift and accurate implementation of TG43 dosimetry in clinic: (a) the dosimetry constants of 125I endorsed by the AAPM Task Group 43 Report result in calculated dose rate that deviates by as much as 15% from currently accepted dose-rate distributions, and (b) The National Institute of Standards and Technology (NIST) has proposed modifying the 125I air-kerma strength standard by approximately 10%. METHODS AND MATERIALS: The ad hoc committee of AAPM Radiation Therapy Committee describes specific procedures to implement these two developments without causing confusion and mistakes. CONCLUSIONS: Confusion and mistakes may be avoided when the following two general steps are taken: 1) STEP I, TG-43 implementation, and 2) STEP II, new air-kerma strength standard implementation when available from NIST.

The role of stereotactic radiosurgery in the treatment of malignant skull base tumors.

PURPOSE: To determine the efficacy and toxicity of stereotactic radiosurgery in the treatment of malignant skull base tumors. METHODS AND MATERIALS: Thirty-two patients with 35 newly diagnosed or recurrent malignant skull base tumors < or = 33.5 cm3 were treated using the Leksell Gamma unit. Tumor histologies included: adenoid cystic carcinoma [12], basal cell carcinoma [1], chondrosarcoma [1], chordoma [8], nasopharyngeal carcinoma [3], osteogenic sarcoma [2], and squamous cell carcinoma [8]. RESULTS: After a median follow-up of 2.3 years, 83% +/- 15% (+/-95% confidence interval) of patients experienced a symptomatic response to treatment. Local control at the skull base was 95 +/- 9% at 2 years and 78 +/- 23% at 3 years. Local-regional control above the clavicles was 75 +/- 15% at 1 year and 51 +/- 20% at 2 years. Overall and cause specific survival were identical, 82 +/- 13% at 1 year, 76 +/- 14% at 2 years, and 72 +/- 16% at 3 years. One patient developed a radiation-induced optic neuropathy 12 months after radiosurgery. CONCLUSION: Stereotactic radiosurgery using the Leksell Gamma Unit can provide durable tumor control and symptomatic relief with acceptable toxicity in the majority of patients with malignant tumors 4 cm or less in size involving the skull base. Further evaluation of more patients with longer follow-up is warranted.

Stereotactic radiosurgery for glomus jugulare tumors: a preliminary report.

PURPOSE: This study was conducted to evaluate the toxicity and efficacy of stereotactic radiosurgery treatment of glomus jugulare tumors. METHODS AND MATERIALS: Between March 1990 and January 1995, nine patients underwent stereotactic radiosurgery with the Leksell Gamma Knife Unit for glomus jugulare tumors. Previous treatment had failed in four patients. The seven female and two male patients had a median age of 67 years. RESULTS: The median time from stereotactic radiosurgery to the most recent clinical follow-up was 20 months (range 7-65 months). Subjectively, 7 of 9 patients noted a decrease in the intensity of their symptoms. Objectively, 8 of 9 tumors remained stable in size by serial magnetic resonance imaging scans and one was smaller. There was no acute or chronic toxicity. CONCLUSION: This early experience suggests that stereotactic radiosurgery is a promising treatment for glomus jugulare tumors.

Treatment planning for adenocarcinoma of the rectum and sigmoid: a patterns of care study. PCS Committee.

PURPOSE: To conduct a study of the process of treatment planning and treatment of adenocarcinoma of the rectum and sigmoid in the United States, and to compare survey results to consensus guidelines. METHODS AND MATERIALS: A consensus committee developed guidelines for the radiotherapeutic management of adenocarcinoma of the rectum and sigmoid, and also developed a survey form that was used to gather data to evaluate the practice patterns for patients treated in 1989 and 1990 against the consensus guidelines. Seventy-three facilities were randomly selected for site visits from the 1321 radiation therapy facilities in the US: 21 academic, 26 hospital based, and 26 free standing. During the site visits, the radiotherapy records were examined by the surveyor physicist and radiation oncologist to extract and record the required data. Data collected included items related to treatment specific parameters, including treatment planning considerations. Analyses included stratification as to the types of institutions, academic, hospital based, or free standing. RESULTS: For many treatment parameters there are discrepancies between the patterns of practice determined by the surveys and the consensus guidelines for radiotherapy treatment of adenocarcinoma of the rectum and sigmoid. Significant differences in practice among the stratified institution types were found in only a few parameters.

Stereotactic radiosurgery using the gamma knife for acoustic neuromas.

PURPOSE: To assess the efficacy and toxicity of stereotactic radiosurgery using the gamma knife for acoustic neuromas. METHODS AND MATERIALS: Between January 1990 and January 1993, 36 patients with acoustic neuromas were treated with stereotactic radiosurgery using the gamma knife. The median maximum tumor diameter was 21 mm (range: 6-32 mm). Tumor volumes encompassed within the prescribed isodose line varied from 266 to 8,667 mm3 (median: 3,135 mm3). Tumors < or = 20 mm in maximum diameter received a dose of 20 Gy to the margin, tumors between 21 and 30 mm received 18 Gy, and tumors > 30 mm received 16 Gy. The dose was prescribed to the 50% isodose line in 31 patients and to the 45%, 55%, 60%, 70%, and 80% isodose line in one patient each. The median number of isocenters per tumor was 5 (range: 1-12). RESULTS: At a median follow-up of 16 months (range: 2.5-36 months), all patients were alive. Thirty-five patients had follow-up imaging studies. Nine tumors (26%) were smaller, and 26 tumors (74%) were unchanged. No tumor had progressed. The 1- and 2-year actuarial incidences of facial neuropathy were 52.2% and 66.5%, respectively. The 1- and 2-year actuarial incidences of trigeminal neuropathy were 33.7% and 58.9%, respectively. The 1- and 2-year actuarial incidence of facial or trigeminal neuropathy (or both) was 60.8% and 81.7%, respectively. Multivariate analysis revealed that the following were associated with the time of onset or worsening of facial weakness or trigeminal neuropathy: (a) patients < age 65 years, (b) dose to the tumor margin, (c) maximum tumor diameter > or = 21 mm, (d) use of the 18 mm collimator, and (e) use of > five isocenters. The 1- and 2-year actuarial rates of preservation of useful hearing (Gardner-Robertson class I or II) were 100% and 41.7% +/- 17.3, respectively. CONCLUSION: Stereotactic radiosurgery using the gamma knife provides short-term control of acoustic neuromas when a dose of 16 to 20 Gy to the tumor margin is used. Preservation of useful hearing can be accomplished in a significant proportion of patients.

Treatment planning structure and process in the United States: a "Patterns of Care" study.

PURPOSE: To conduct a study of the structure and process of treatment planning in the United States. METHODS AND MATERIALS: A Patterns of Care treatment planning consensus committee developed a survey form that was used to gather data for 106 items relating to the structure and process of treatment planning. These questions were general in nature and not specific to any particular disease site. Seventy-three facilities were randomly selected for site visits from the 1321 radiation therapy facilities in the United States: 21 academic, 26 hospital, and 26 free-standing. During the site visit the facility physicist, assisted by the site-visit physicist, completed the form. RESULTS: Twenty-nine percent of facilities have cobalt-60 machines; 25% have 4 MV linacs; 75% have photon energies in the range of 5-8 MV; and less than 10% have energies greater than 20 MV. Academic facilities led hospital and free-standing facilities by about 30 percentage points in the availability of all electron energies (88 vs. 58%, approximately, in the range 4-13 MeV and scaling downward to about 60 vs. 30% at the highest energies). The national averages for the availability of Cs-137, Ir-192, and I-125 were 87, 73, and 44%, respectively. Computerized tomography (CT) scanning is not available or not used in 15% of hospital and free-standing facilities. Ninety-six percent of facilities have treatment planning computers; at 10% of facilities physicians do not participate in treatment planning. The estimated national averages of facilities having formal quality assurance (QA) programs for treatment planning systems, simulators, film processors, and blocking systems are 44, 79, 62, and 55%, respectively. Sixty-three percent of facilities obtain independent machine calibrations. CONCLUSION: This is the first patterns of treatment planning study carried out in the United States and the results reported here will establish a baseline for future studies. The present study has identified some elements that were unexpected, such as the percentage of facilities lacking formal QA programs for treatment planning systems; however, it has not established any impact of such findings. It is recommended that future studies include the availability of new technologies such as multileaf collimation, dynamic wedges, digital portal imaging, and CT simulation. With the increasing nationwide concern with the cost of health care, we must continue to monitor the implementation, use, and impact on treatment outcome of new and expensive technologies.

The use of a radiochromic detector for the determination of stereotactic radiosurgery dose characteristics.

The measurement of absorbed dose as well as dose distributions (profiles and isodose curves) for small radiation fields (as encountered in stereotactic surgery) has been difficult due to the usual large detector size or densitometer aperture (> 1 mm) relative to the radiation field (as small as 4 mm). The radiochromic direct-imaging film, when read with a scanning laser microdensitometer (laser beam diameter 0.1 mm), overcomes this difficulty and has advantages over conventional film in providing improved precision, better tissue equivalence, greater dynamic range, higher spatial resolution, and room light handling. As a demonstration of suitability, the calibrated radiochromic film has been used to measure the dose characteristics for the 18-, 14-, 8-, and 4-mm fields from the gamma-ray stereotactic surgery units at Mayo Clinic and the University of Pittsburgh. Intercomparisons of radiochromic film with conventional methods of dosimetry and vendor-supplied computational dose planning system values indicate agreement to within +/- 2%. The dose, dose profiles, and isodose curves obtained with radiochromic film can provide high-spatial-resolution information of value for acceptance testing and quality control of dose measurement and/or calculation.

Low-versus high-energy photon beams in radiotherapy for lung cancer.

This retrospective study analyzed the outcome of lung cancer patients who were treated with either 4-MV or 10-MV photons. From October 1979 through December 1982, 126 patients with locally advanced, unresectable or medically inoperable, nonmetastatic non-small cell lung cancer were treated in a prospective trial in which they were randomly assigned to one of three chemotherapy combinations and thoracic radiotherapy. The patients were stratified by cell type, extent of operation, age, sex, and status of supraclavicular lymph nodes. All patients were followed until death or for a minimum of 4.8 years. Of the 102 evaluable patients, 98 were treated with either 4-MV or 10-MV photons (49 patients in each group). Outcomes examined included best primary tumor response, time to first local (in-field) recurrence, disease-free survival, and overall survival. No significant differences were detected between the patients treated with 4-MV or 10-MV photons for several important prognostic and treatment factors or for any of the study outcomes, including first local (in-field) recurrence, disease-free survival, and overall survival. For the group of 98 patients treated with either 4-MV or 10-MV photons, the estimated 2-year freedom from first local (in-field) recurrence was 47.7%. The estimated 2-year disease-free and overall survivals were 21.6% and 28.6%, respectively.

Electron beam port films.

Portal localization films are taken in order to assure the accurate placement of the treatment field relative to the patient anatomy. This is routinely done for photon fields and maybe for electron fields. This paper describes a technique which uses the bremsstrahlung component of an electron beam of energy 10 MeV and greater to expose a film to image a treatment port. These films provide verification of the placement of the electron field and document the treatment of a specific area.

Comparison of measured and calculated dose distributions around an iridium-192 wire.

The relative dose distribution around a 5.0-cm-long piece of 192Ir wire has been measured using LiF chips. Measurements were made at distances of 0.25 to 5.0 cm away from the source and distances of 0.0 to 4.0 cm along the source. In addition, measurements were also made at several distances along the axis of the source. Attention was paid to the errors associated with these measurements. A comparison was made between a commercial software program, ISODOS, an analytical solution to the Sievert integral, and the measurements. Good agreement was obtained at distances along and away from the source. Major disagreements were found at points along the source axis.

The generalized geometry of eye plaque therapy.

A calculation is described that enables the rapid assessment of dose rate at various points of interest within the eye (lens, optic nerve, etc.) for the treatment of choroidal melanoma by plaque therapy. 125I seeds are used as the radiation source. The location of the plaque and its associated seeds relative to the eye (in a Cartesian coordinate system) is determined from the description of the tumor, as drawn and dimensioned on a fundus-view diagram by the ophthalmologist. This requires a computer to numerically solve an equation, which is derived in the framework of spherical geometry. Further results of this calculation yield data files that serve as the input to a conventional brachytherapy treatment planning program. This enables the visualization of the dose distribution within a plane that contains the major axis of the tumor in order to assess the adequacy of the treated volume.