A round-robin gamma stereotactic radiosurgery dosimetry interinstitution comparison of calibration protocols.

PURPOSE: Absorbed dose calibration for gamma stereotactic radiosurgery is challenging due to the unique geometric conditions, dosimetry characteristics, and nonstandard field size of these devices. Members of the American Association of Physicists in Medicine (AAPM) Task Group 178 on Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance have participated in a round-robin exchange of calibrated measurement instrumentation and phantoms exploring two approved and two proposed calibration protocols or formalisms on ten gamma radiosurgery units. The objectives of this study were to benchmark and compare new formalisms to existing calibration methods, while maintaining traceability to U.S. primary dosimetry calibration laboratory standards. METHODS: Nine institutions made measurements using ten gamma stereotactic radiosurgery units in three different 160 mm diameter spherical phantoms [acrylonitrile butadiene styrene (ABS) plastic, Solid Water, and liquid water] and in air using a positioning jig. Two calibrated miniature ionization chambers and one calibrated electrometer were circulated for all measurements. Reference dose-rates at the phantom center were determined using the well-established AAPM TG-21 or TG-51 dose calibration protocols and using two proposed dose calibration protocols/formalisms: an in-air protocol and a formalism proposed by the International Atomic Energy Agency (IAEA) working group for small and nonstandard radiation fields. Each institution's results were normalized to the dose-rate determined at that institution using the TG-21 protocol in the ABS phantom. RESULTS: Percentages of dose-rates within 1.5% of the reference dose-rate (TG-21+ABS phantom) for the eight chamber-protocol-phantom combinations were the following: 88% for TG-21, 70% for TG-51, 93% for the new IAEA nonstandard-field formalism, and 65% for the new in-air protocol. Averages and standard deviations for dose-rates over all measurements relative to the TG-21+ABS dose-rate were 0.999±0.009 (TG-21), 0.991±0.013 (TG-51), 1.000±0.009 (IAEA), and 1.009±0.012 (in-air). There were no statistically significant differences (i.e., p>0.05) between the two ionization chambers for the TG-21 protocol applied to all dosimetry phantoms. The mean results using the TG-51 protocol were notably lower than those for the other dosimetry protocols, with a standard deviation 2-3 times larger. The in-air protocol was not statistically different from TG-21 for the A16 chamber in the liquid water or ABS phantoms (p=0.300 and p=0.135) but was statistically different from TG-21 for the PTW chamber in all phantoms (p=0.006 for Solid Water, 0.014 for liquid water, and 0.020 for ABS). Results of IAEA formalism were statistically different from TG-21 results only for the combination of the A16 chamber with the liquid water phantom (p=0.017). In the latter case, dose-rates measured with the two protocols differed by only 0.4%. For other phantom-ionization-chamber combinations, the new IAEA formalism was not statistically different from TG-21. CONCLUSIONS: Although further investigation is needed to validate the new protocols for other ionization chambers, these results can serve as a reference to quantitatively compare different calibration protocols and ionization chambers if a particular method is chosen by a professional society to serve as a standardized calibration protocol.

A noninvasive eye fixation monitoring system for CyberKnife radiotherapy of choroidal and orbital tumors.

A new noninvasive monitoring system for fixing the eye has been developed to treat orbital and choroidal tumors with CyberKnife-based radiotherapy. This device monitors the eye during CT/MRI scanning and during treatment. The results of this study demonstrate the feasibility of the fixation light system for CyberKnife-based treatments of orbital and choroidal tumors and supports the idea that larger choroidal melanomas and choroidal metastases could be treated with CyberKnife without implanting fiducial markers.

Image-guided robotic stereotactic body radiotherapy for benign spinal tumors: theUniversity of California San Francisco preliminary experience.

We evaluate our preliminary experience using the Cyberknife Radiosurgery System in treating benign spinal tumors. A retrospective review of 16 consecutively treated patients, comprising 19 benign spinal tumors, was performed. Histologic types included neurofibroma [11], chordoma [4], hemangioma [2], and meningioma [2]. Three patients had Neurofibromatosis Type 1 (NF1). Only one tumor, recurrent chordoma, had been previously irradiated, and as such not considered in the local failure analysis. Local failure, for the remaining 18 tumors, was based clinically on symptom progression and/or tumor enlargement based on imaging. Indications for spine stereotactic body radiotherapy (SBRT) consisted of either adjuvant to subtotal resection (5/19), primary treatment alone (12/19), boost following external beam radiotherapy (1/19), and salvage following previous radiation (1/19). Median tumor follow-up is 25 months (2-37), and one patient (with NF1) died at 12 months from a stroke. The median total dose, number of fractions, and prescription isodose was 21 Gy (10-30 Gy), 3 fx (1-5 fx), 80% (42-87%). The median tumor volume was 7.6 cc (0.2-274.1 cc). The median V100 (volume V receiving 100% of the prescribed dose) and maximum tumor dose was 95% (77-100%) and 26.7 Gy (15.4-59.7 Gy), respectively. Three tumors progressed at 2, 4, and 36 months post-SR (n=18). Two tumors were neurofibromas (both in NF1 patients), and the third was an intramedullary hemangioblastoma. Based on imaging, two tumors had MRI documented progression, three had regressed, and 13 were unchanged (n=18). With short follow-up, local control following Cyberknife spine SBRT for benign spinal tumors appear acceptable.

Peripheral dose in ocular treatments with CyberKnife and Gamma Knife radiosurgery compared to proton radiotherapy.

Peripheral radiation can have deleterious effects on normal tissues throughout the body, including secondary cancer induction and cataractogenesis. The aim of this study is to evaluate the peripheral dose received by various regions of the body after ocular treatment delivered with the Model C Gamma Knife, proton radiotherapy with a dedicated ocular beam employing no passive-scattering system, or a CyberKnife unit before and after supplemental shielding was introduced. TLDs were used for stray gamma and x-ray dosimetry, whereas CR-39 dosimeters were used to measure neutron contamination in the proton experiments. Doses to the contralateral eye, neck, thorax and abdomen were measured on our anthropomorphic phantom for a 56 Gy treatment to a 588 mm(3) posterior ocular lesion. Gamma Knife (without collimator blocking) delivered the highest dose in the contralateral eye, with 402-2380 mSv, as compared with 118-234 mSv for CyberKnife pre-shielding, 46-255 mSv for CyberKnife post-shielding and 9-12 mSv for proton radiotherapy. Gamma Knife and post-shielding CyberKnife delivered comparable doses proximal to the treatment site, with 190 versus 196 mSv at the thyroid, whereas protons doses at these locations were less than 10 mSv. Gamma Knife doses decreased dramatically with distance from the treatment site, delivering only 13 mSv at the lower pelvis, comparable to the proton result of 4 to 7 mSv in this region. In contrast, CyberKnife delivered between 117 and 132 mSv to the lower pelvis. In conclusion, for ocular melanoma treatments, a proton beam employing no double scattering system delivers the lowest peripheral doses proximally to the contralateral eye and thyroid when compared to radiosurgery with the Model C Gamma Knife or CyberKnife. At distal locations in the pelvis, peripheral doses delivered with proton and Gamma Knife are of an order of magnitude smaller than those delivered with CyberKnife.

[Malignant turn of oral planus in three new cases]. / Transformación maligna del liquen plano oral en tres nuevos casos.

The possible malignant potential of oral lichen planus (OLP) is still controversial. We present three new oral lichen planus (OLP) patients who developed oral squamous-cell carcinoma (OSCC). In all cases, were analyzed variables like sex, age, clinical type, localization, extension, follow-up study and treatment, moreover were considered the patient's habits, localization, stage and treatment of cancer. The average age was 59 years and both of them were non smoker or with no alcohol habits. The follow-up period was greater than two years and the malignant lesion developed after mean of nine years, after the diagnosis of OLP had been established. Oral squamous-cell carcinoma (OSCC) arose on lesions previously diagnosed clinically and histologically as atrophic and erosive oral lichen planus in two of our patients and on a plaque lesion LP in a patient. All of them had been using topical corticoids before the cancer was diagnosed. The appearance of new cases of OLP malignization framed inside the established approaches, suggests the realization of new researches in order to determine the factors involved in this process.

Dose conformity of gamma knife radiosurgery and risk factors for complications.

PURPOSE: To quantitatively evaluate dose conformity achieved using Gamma Knife radiosurgery, compare results with those reported in the literature, and evaluate risk factors for complications. METHODS AND MATERIALS: All lesions treated at our institution with Gamma Knife radiosurgery from May 1993 (when volume criteria were routinely recorded) through December 1998 were reviewed. Lesions were excluded from analysis for reasons listed below. Conformity index (the ratio of prescription volume to target volume) was calculated for all evaluable lesions and for lesions comparable to those reported in the literature on conformity of linac radiosurgery. Univariate Cox regression models were used to test for associations between treatment parameters and toxicity. RESULTS: Of 1612 targets treated in 874 patients, 274 were excluded, most commonly for unavailability of individual prescription volume data because two or more lesions were included within the same dose matrix (176 lesions), intentional partial coverage for staged treatment of large arteriovenous malformations (AVMs) (33 lesions), and missing target volume data (26 lesions). The median conformity indices were 1.67 for all 1338 evaluable lesions and 1.40-1.43 for lesions comparable to two linac radiosurgery series that reported conformity indices of 1.8 and 2.7, respectively. Among all 651 patients evaluable for complications, there were one Grade 5, eight Grade 4, and 27 Grade 3 complications. Increased risk of toxicity was associated with larger target volume, maximum lesion diameter, prescription volume, or volume of nontarget tissue within the prescription volume. CONCLUSIONS: Gamma Knife radiosurgery achieves much more conformal dose distributions than those reported for conventional linac radiosurgery and somewhat more conformal dose distributions than sophisticated linac radiosurgery techniques. Larger target, nontarget, or prescription volumes are associated with increased risk of toxicity.

Insecure attachment and alexithymia in young men with mood symptoms.

According to attachment theorists, affect regulation and quality of attachment are closely linked. As a personality trait associated with deficits in the cognitive processing and regulation of affects, alexithymia has been hypothesized to correlate with insecure attachment. To test this hypothesis, we studied the relationships between alexithymia, adult attachment style, and retrospective memories of separation anxiety symptoms during childhood in 100 young men with clinically significant mood symptoms. The most common DSM-IV diagnosis (N = 72) was adjustment disorder with depressed mood, with anxiety, or with mixed anxiety and depressed mood. Each participant completed the Twenty-Item Toronto Alexithymia Scale (TAS-20), the Beck Depression Inventory (BDI), the state form of the State-Trait Anxiety Index (STAI), the Attachment Style Questionnaire (ASQ), the Relationship Questionnaire (RQ), and the Separation Anxiety Symptom Inventory (SASI). Alexithymic traits were more pronounced in those participants who had patterns of insecure attachment and who reported more severe symptoms of separation anxiety during childhood, independently of the severity of their current anxiety and depressive symptoms. Among the subgroup of participants with insecure attachment styles, those with preoccupied or fearful patterns had a higher prevalence of alexithymia (65% and 73%, respectively) than those with a dismissing pattern (36%). These data suggest a role for early developmental factors in the etiology of alexithymia

Radiosurgery for malignant meningioma: results in 22 patients.

OBJECT: The initial treatment of malignant meningiomas in the past has included surgical removal followed by fractionated external-beam radiotherapy. Radiosurgery has been added to the options for treatment of primary or recurrent tumors over the last 10 years. The authors report their results of using gamma knife radiosurgery (GKS) to treat 22 patients over an 8-year period. METHODS: Twenty-two patients who underwent GKS for malignant meningioma between December 1991 and May 1999 were evaluated. Three patients were treated with GKS as a boost to radiotherapy and 19 for recurrence following radiotherapy. Outcome factors including patient survival, freedom from progression, and complications were analyzed. In addition, in the recurrent group, variables such as patient age, sex, tumor location, target volume, margin dose, and maximum dose were also analyzed. Univariate and multivariate analyses were performed. Overall 5-year survival and progression-free survival estimates were 40% and 26%, respectively. Age (p < or = 0.003) and tumor volume (p < or = 0.05) were significant predictors of time to progression and survival in both univariate and multivariate analyses. Five patients (23%) developed radiation necrosis. Significant relationships between complications and treatment variables or patient characteristics could not be established. CONCLUSIONS: Tumor control following GKS is greater in patients with smaller-sized tumors (< 8 cm3) and in younger patients. Gamma knife radiosurgery can be performed to treat malignant meningioma with acceptable toxicity. The efficacy of GKS relative to other therapies for recurrent malignant meningioma as well as the value of GKS as a boost to radiotherapy will require further evaluation.

An application of GafChromic MD-55 film for 67.5 MeV clinical proton beam dosimetry.

The purpose of this study is to explore the use of GafChromic MD-55 (RC) film for 67.5 MeV clinical proton beam dosimetry at the Crocker Nuclear Laboratory, University of California, Davis. Several strips of RC film 6 cm x 6 cm in dimension were irradiated at a depth of 18.2 mm corresponding to the middle of a 24 mm spread-out Bragg peak (SOBP). The films were irradiated to a proton dose in the range of 0.5 Gy to 100 Gy. The beam profiles were also measured at the middle of the 24 mm SOBP. The Bragg peak was measured by using a wedge shaped phantom made of Lucite. The Bragg peak measured with RC film was compared with diode and ionization chamber measurements. After background subtraction, the calibration of the dose response of RC film showed, to a maximum deviation of 10%, a linear increase of optical density (OD) with dose from 0.5 to 100 Gy. The uniformity of OD over a single sheet of film showed a variation of +/-6%. The distal-fall off between 90% and 20% measured with GafChromic film for the Bragg peak was 1.3 mm as compared to 1.1 mm for a diode measurement and 1.4 mm for an ionization chamber measurement. The FWHM of the Bragg peak was 7.5 mm when measured with GafChromic film, 5.3 mm when measured with a diode and 8.1 mm as measured by an ionization chamber. The peak/plateau ratio with GafChromic film was 3.3 as compared to 3.7 with a diode and 3.2 with an ionization chamber. In conclusion, GafChromic MD-55 film may be a useful and convenient detector for dose measurement and quality assurance programmes of proton beams.

Gamma knife radiosurgery for malignant melanoma brain metastases.

PURPOSE: To evaluate the efficacy and toxicity of gamma knife radiosurgery in the treatment of melanoma metastases to the brain. PATIENTS AND METHODS: We retrospectively reviewed 55 patients with single or multiple intracranial melanoma metastases treated at the University of California, San Francisco, with gamma knife radiosurgery from 1991 through 1995. Sixteen patients were treated with gamma knife radiosurgery for recurrence following previous radiation therapy, 11 received radiosurgery as a boost to whole-brain radiation therapy, and 28 had radiosurgery alone for initial management of brain metastases. The median minimum radiosurgery tumor dose for 140 treated lesions was 19 Gy (range, 10-22 Gy) prescribed at the 35% to 90% isodose contour (median, 50%). The median total target volume per patient was 6.1 cc (range, 0.25-28.3 cc). RESULTS: With a median follow-up of 75 weeks in living patients, the median survival times were 35 weeks overall: 35 weeks for patients with solitary metastases versus 33 weeks for those with multiple metastases. A factor that was significant in univariate analysis of survival was total target volume treated. This parameter remained significant on multivariate analysis. The actuarial median freedom from progression analyzed by lesion for 113 lesions in 46 patients with imaging follow-up was 89 weeks with 6-month and 1-year actuarial freedom from progression rates of 89% (95% confidence interval, 80%-95%) and 77% (95% confidence interval, 62%-87%). In univariate analysis, improved freedom from progression was associated with smaller target volume treated, smaller maximum diameter, or higher prescribed dose. Four patients (7%) developed acute Radiation Therapy Oncology Group grade > or = 2 morbidity, and five patients (9%) developed late grade > or = 2 morbidity. DISCUSSION: Median survival and freedom from progression in patients treated with radiosurgery for melanoma metastatic to the brain are comparable to results in published radiosurgery series of grouped histologies. For melanoma patients, total intracranial tumor volume appears to be of greater prognostic significance than the absolute number of metastases treated. We conclude that gamma knife radiosurgery is effective and should be considered among various management strategies.

15 years experience with helium ion radiotherapy for uveal melanoma.

PURPOSE: To review the long-term experience of helium ion therapy as a therapeutic alternative to enucleation for uveal melanoma, particularly with respect to survival, local control, and morbidity. METHODS AND MATERIALS: 347 patients with uveal melanoma were treated with helium ion RT from 1978-1992. A nonrandomized dose-searching study was undertaken, with doses progressively reduced from 80 GyE in five fractions to 48 GyE in four fractions, given in 3-15 days, mean of 7 days. RESULTS: Local control was achieved in 96% of patients, with no difference in the rate of local control being seen at 80, 70, 60, or 50 GyE in five fractions. At the lowest dose level of 48 GyE in four fractions, the local control rate fell to 87%. Fifteen of 347 patients (4%) had local regrowth in the eye requiring enucleation (12 patients), laser (1 patient) or reirradiation (2 patients). The time of appearance of local regrowth ranged from 4 months to 5 years posttreatment, with 85% occurring within 3 years. Of the 347 patients, 208 are alive as of May 1, 1997. The median follow up of all patients is 8.5 years, range 1-17 years. Kaplan-Maier (K-M) survival is 80% at 5 years, 76% at 10 years, and 72% at 15 years posttreatment. Patients with tumors not involving the ciliary body have a 15-year K-M survival of 80%. The results for patients whose tumors involved the ciliary body are poor, with a 15-year K-M survival of 43%. Seventy-five percent of patients with tumors at least 3.0 mm from the fovea and optic nerve, and initial ultrasound height less than 6.0 mm, retained vision of 20/200 or better posttreatment. Patients with tumors larger than 6 mm in thickness, or with tumors lying close to the optic nerve or fovea, have a reduced chance of retaining useful vision. The enucleation rate is 19%, 3% for local failure and 16% because of complications of the helium RT, particularly neovascular glaucoma, which occurred in 35% of patients. CONCLUSIONS: Local control and retention of the eye are excellent. Complications of therapy reduce vision and eye preservation. Twenty-four percent of patients manifested distant metastases 6 to 146 months posttreatment, mean of 43 months, median of 36 months. Late-appearing distant metastases do not appear to be caused by persistent tumor in the eye. The risk of metastases is high for patients with tumors greater than 7 mm in initial ultrasound height (37%), anterior tumors involving the ciliary body (47%), and in those with local failure (53%). Patients with tumors not involving the ciliary body and initial dimensions less than 10 mm had only an 8% chance of death from melanoma. A search for effective adjuvant therapy is needed for patients at high risk of metastases (large tumors, ciliary body involved, local regrowth in eye).

Anterior segment sparing to reduce charged particle radiotherapy complications in uveal melanoma.

PURPOSE: The purpose of this investigation is to delineate the risk factors in the development of neovascular glaucoma (NVG) after helium-ion irradiation of uveal melanoma patients and to propose treatment technique that may reduce this risk. METHODS AND MATERIALS: 347 uveal melanoma patients were treated with helium-ions using a single-port treatment technique. Using univariate and multivariate statistics, the NVG complication rate was analyzed according to the percent of anterior chamber in the radiation field, tumor size, tumor location, sex, age, dose, and other risk factors. Several University of California San Francisco-Lawrence Berkeley National Laboratory (LBNL) patients in each size category (medium, large, and extralarge) were retrospectively replanned using two ports instead of a single port. By using appropriate polar and azimuthal gaze angles or by treating patients with two ports, the maximum dose to the anterior segment of the eye can often be reduced. Although a larger volume of anterior chamber may receive a lower dose by using two ports than a single port treatment. We hypothesize that this could reduce the level of complications that result from the irradiation of the anterior chamber of the eye. Dose-volume histograms were calculated for the lens, and compared for the single and two-port techniques. RESULTS: NVG developed in 121 (35%) patients. The risk of NVG peaked between 1 and 2.5 years posttreatment. By univariate and multivariate analysis, the percent of lens in the field was strongly correlated with the development of NVG. Other contributing factors were tumor height, history of diabetes, and vitreous hemorrhage. Dose-volume histogram analysis of single-port vs. two-port techniques demonstrate that for some patients in the medium and large category tumor groups, a significant decrease in dose to the structures in the anterior segment of the eye could have been achieved with the use of two ports. CONCLUSION: The development of NVG after helium-ion irradiation is correlated to the amount of lens, anterior chamber in the treatment field, tumor height, proximity to the fovea, history of diabetes, and the development of vitreous hemorrhage. Although the influence of the higher LET deposition of helium-ions is unclear, this study suggests that by reducing the dose to the anterior segment of the eye may reduce the NVG complications. Based on this retrospective analysis of LBNL patients, we have implemented techniques to reduce the amount of the anterior segment receiving a high dose in our new series of patients treated with protons using the cyclotron at the UC Davis Crocker Nuclear Laboratory (CNL).

New compensator design options for charged-particle radiotherapy.

The purpose of this investigation is to propose new compensator design strategies for protons and heavier particles which are based on pencil-beam (PB) dose calculations and which significantly reduce the dose to tissues downstream from the target, yet provide acceptable target coverage under conditions of patient motion. Averaging and expansion operations are provided to improve the target coverage if the patient moves slightly during treatment, and a structure-sparing option is provided to protect critical structures lying downstream from the target. The new compensator design options were evaluated for two patients who had skull-base tumours. When the patient and compensator were perfectly aligned, the new PB compensator designs provided target coverage comparable to, if not better than, standard compensator designs for both patients. Furthermore, the volume of normal tissue distal to the target which received in excess of 95% of the prescription dose was roughly a factor of two lower for the averaged PB compensators than for the expanded standard compensators. In the event of patient motion, on average, the volume of the target receiving 95% or more of the prescribed dose was 3% less for the averaged PB compensators than for the expanded standard compensators. In conclusion, the new compensator design options evaluated in this investigation provide better protection for normal tissues distal to the target volume than standard compensator designs, with only a modest decrease in target volume coverage in the event of patient motion.

Neon heavy charged particle radiotherapy of glioblastoma of the brain.

PURPOSE: High-linear energy transfer (LET) radiation beams have potential applications in the treatment of glioblastoma, but have not yet demonstrated significant improvement in results. However, some patients have had local control of glioblastoma with high-LET irradiations such as neutrons and heavy charged particles. METHODS AND MATERIALS: In this collaborative study, 15 patients were entered into a randomized protocol comparing two dose levels of 20 and 25 Gy in 4 weeks of neon ion irradiation. This trial was intended to determine the optimal neon dose in terms of survival and effects of radiation. RESULTS: Fourteen patients were evaluable with no significant differences in median survival (13 and 14 months; p = NS) or median time to failure (7 and 9 months; p = NS) between the two dose arms. Three patients died of nontumor-related causes, of whom one (who died 19 months posttreatment) had autopsy confirmation of no tumor on pathological exam. The other two patients had stable magnetic resonance imaging scans at 6 and 22 months posttreatment. CONCLUSION: Although the results did not demonstrate the optimal high-LET dose level, there is an intriguing effect in that two patients had control of glioblastoma until death at 19 and 22 months. This suggests that better conformation of the high-LET dose to the tumor with neutron capture therapy or dynamic conformal heavy charged particle therapy might control glioblastoma while minimizing brain damage from radiation.

Radiosurgery for brain metastases: relationship of dose and pattern of enhancement to local control.

PURPOSE: This study aimed to analyze dose, initial pattern of enhancement, and other factors associated with freedom from progression (FFP) of brain metastases after radiosurgery (RS). METHODS AND MATERIALS: All brain metastases treated with gamma-knife RS at the University of California, San Francisco, from 1991 to 1994 were reviewed. Evaluable lesions were those with follow-up magnetic resonance or computed tomographic imaging. Actuarial FFP was calculated using the Kaplan-Meier method, measuring FFP from the date of RS to the first imaging study showing tumor progression. Controlled lesions were censored at the time of the last imaging study. Multivariate analyses were performed using a stepwise Cox proportional hazards model. RESULTS: Of 261 lesions treated in 119 patients, 219 lesions in 100 patients were evaluable. Major histologies included adenocarcinoma (86 lesions), melanoma (77), renal cell carcinoma (21), and carcinoma not otherwise specified (17). The median prescribed RS dose was 18.5 Gy (range, 10-22) and the median tumor volume was 1.3 ml (range, 0.02-30.9). The initial pattern of contrast enhancement was homogeneous in 68% of lesions, heterogeneous in 12%, and ring-enhancing in 19%. The actuarial FFP was 82% at 6 months and 77% at 1 year for all lesions, and 93 and 90%, respectively, for 145 lesions receiving > or = 18 Gy. Multivariate analysis showed that longer FFP was significantly associated with higher prescribed RS dose, a homogeneous pattern of contrast enhancement, and a longer interval between primary diagnosis and RS. Adjusted for these factors, adenocarcinomas had longer FFP than melanomas. No significant differences in FFP were noted among lesions undergoing RS for recurrence after prior radiotherapy (119 lesions), RS alone as initial treatment (45), or RS boost (55). CONCLUSION: A minimum prescribed radiosurgical dose > or = 18 Gy yields excellent local control of brain metastases. The influence of pattern of enhancement on local control, a new finding in this retrospective analysis, needs to be confirmed.

Factors influencing survival after gamma knife radiosurgery for patients with single and multiple brain metastases.

PURPOSE: Radiosurgery has been reported to yield high local control rates for brain metastases. However, further work is needed to define which subgroups of patients may benefit from this treatment modality. PATIENTS AND METHODS: We reviewed 116 patients who underwent stereotactic radiosurgery for initial management or recurrence of solitary or multiple brain metastases from September 1991 through December 1994 at the University of California, San Francisco. Survival time and time to local-regional failure were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards model. RESULTS: Median survival was 40 weeks from radiosurgery. In multivariate analysis, smaller total tumor volume, absence of extracranial metastases, higher Karnofsky score, and age < or = 70 had a positive effect on survival. In patients initially managed for brain metastases, the addition of whole brain radiotherapy to radiosurgery had no significant effect on survival. Although the presence of multiple metastases was associated with a significantly worse survival rate in patients initially managed with radiosurgery in univariate analysis, it was not as a significant factor in multivariate analysis. An analysis of patients within this series treated with radiosurgery who would have been eligible for Patchell's study on the role of surgery in the treatment of solitary brain metastasis revealed a favorable median survival of 70 weeks. CONCLUSIONS: We conclude that radiosurgical treatment of brain metastases results in survival times that compare favorably with the historic experience in patients treated with whole brain radiotherapy alone or with surgical resection. In patients presenting initially with brain metastases, radiosurgery alone may yield survival results equivalent to radiosurgery with whole brain radiotherapy, but intracranial control and quality of life also need to be evaluated. Also, the presence of multiple brain metastases should not be a contraindication for the use of radiosurgery given the good survival achieved with such patients in this series. Each such case should therefore be evaluated based on other factors such as patient's age, Karnofsky score and systemic disease.

Evaluation of a pencil-beam dose calculation technique for charged particle radiotherapy.

PURPOSE: The purpose of this article is to evaluate a pencil-beam dose calculation algorithm for protons and heavier charged particles in complex patient geometries defined by computed tomography (CT) data and to compare isodose distributions calculated with the new technique to those calculated with conventional algorithms in selected patients with skull-base tumors. METHODS AND MATERIALS: Monte Carlo calculations were performed to evaluate the pencil-beam algorithm in patient geometries for a modulated 150-MeV proton beam. A modified version of a Monte Carlo code described in a previous publication (18) was used for these comparisons. Tissue densities were inferred from patient CT data on a voxel-by-voxel basis, and calculations were performed with and without tissue compensators. A dose calculation module using the new algorithm was written, and treatment plans using the new algorithm were compared to plans using standard ray-tracing techniques for 10 patients with clival chordoma and three patients with nasopharyngeal carcinoma who were treated with helium lons at Lawrence Berkeley National Laboratory (LBL). RESULTS: Pencil beam calculations agreed well with Monte Carlo calculations in the patient geometries. The pencil-beam algorithm predicted several multiple-scattering effects that are not modeled by conventional ray-tracing calculations. These include (a) the widening of the penumbra as a function of beam penetration, (b) the degradation in the sharpness of the dose gradient at the end of the particle range in highly heterogeneous regions, and (c) the appearance of hot and cold dose regions in the shadow of complex heterogeneities. In particular, pencil-beam calculations indicated that the dose distribution within the target was not as homogeneous as expected on the basis of ray-tracing calculations. On average, for the 13 patients considered, only about 72% of the conedown target volume received at least 99% of the prescribed dose, whereas, 93% of the conedown volume was contained within the 95% isodose surface. This may be significant because in standard charged particle dose calculations, the dose across the spread-Bragg peak is assumed to be uniform and equal to the maximum or prescribed dose. CONCLUSIONS: Dose distributions computed with the pencil-beam model are more accurate than ray-tracing calculations, providing additional information to clinicians, which may influence the doses they prescribe. In particular, these calculations indicate that for some patients with skull-base tumors, it may be advantageous to prescribe proton doses to a lower isodose level than is commonly done.

Gamma knife radiosurgery in children.

52 pediatric patients were treated with radiosurgery at the University of California, San Francisco. Arteriovenous malformations were treated in 27 patients. Complete obliteration was noted in 4 of 12 patients imaged more than 2 years after radiosurgery. Arteriovenous malformation rebleed was noted in 1 patient. Symptomatic T2 changes were noted in 2 patients. Among 29 neoplasms treated in 25 patients, local control was noted in 5 of 7 low-grade gliomas, 5 of 14 high-grade gliomas, 4 of 5 craniopharyngiomas and 3 of 3 sarcomas. Three patients treated for neoplasms developed necrosis after radiosurgery.

Stereotactic radiosurgery in children.

The role of stereotactic radiosurgery in the treatment of pediatric patients is still being explored. We report the Gamma Knife treatment of 33 patients under the age of 21, at the University of California, San Francisco, between the years 1991 and 1993. Treatment-related toxicity has been low. 10/14 patients treated for arteriovenous malformation (AVM) with follow-up > 1 month have shown partial or complete AVM obliteration. No patient has had a new hemorrhage after AVM treatment. In children with malignant tumors, treatment was well tolerated, although most patients, ultimately, had progressive disease. Stereotactic radiosurgery is logistically possible in the pediatric population. Its use in selected patients with AVMs seems appropriate, although its role in the treatment of malignant brain tumors remains to be defined.

An automated image-registration technique based on multiple structure matching.

A new image-registration technique that matches multiple structures on complementary imaging data sets (e.g., CT and MRI) has been developed and tested with both phantom and patient data. The algorithm assumes a rigid-body transformation and is suitable for correlating structures within the cranium or at the skull base. The basic premise of the new technique is that an optimum transformation is achieved when the relative volume lying outside of the intersection between a structure and its transformed counterpart is a minimum. This relative volume is calculated numerically using a random sampling approach, and a binary searching algorithm was used to step through the nine-dimensional parameter space consisting of three rotation angles, three scaling factors and three components of a translation vector. For the nine tests using phantom data, the automated structure-matching technique was able to predict the correct rotation angles to within +/- 1 degree. The expected clinical performance of the new technique was assessed by comparing results obtained with the new method to those obtained using other techniques for 12 patients who were treated with charged particles at Lawrence Berkeley Laboratory (LBL) and who had image-registration studies performed as part of their treatment plan. For 9 of the 12 patients considered, the new structure-matching technique produced a significantly better registration than the older methods, as measured by the resultant average relative volume lying outside of the intersection between any structure and its transformed counterpart. For the other three patients, results were not significantly different for the new structure-matching method and the older techniques.