Evaluation of ultrasound-based prostate localization for image-guided radiotherapy.

To evaluate the use of the ultrasound-based BAT system for daily prostate alignment. Prostate alignments using the BAT system were compared with alignments using radiographic images of implanted radiopaque markers. The latter alignments were used as a reference. The difference between the BAT and marker alignments represents the displacements that would remain if the alignments were done using ultrasonography. The inter-user variability of the contour alignment process was assessed. On the basis of the marker alignments, the initial displacement of the prostate in the AP, superoinferior, and lateral direction was -0.9 +/- 3.9, 0.1 +/- 3.9, and 0.2 +/- 3.4 mm respectively. The directed differences between the BAT and marker alignments in the respective directions were 0.2 +/- 3.7, 2.7 +/- 3.9, and 1.6 +/- 3.1 mm. The occurrence of displacements >/=5 mm was reduced by a factor of two in the AP direction after the BAT system was used. Among eight users, the average range of couch shifts due to contour alignment variability was 7, 7, and 5 mm in the antero-posterior (AP), superoinferior, and lateral direction, respectively. In our study, the BAT alignments were systematically different from the marker alignments in the superoinferior, and lateral directions. The remaining random variability of the prostate position after the ultrasound-based alignment was similar to the initial variability. However, the occurrence of displacements >/=5 mm was reduced in the AP direction. The inter-user variation of the contour alignment process was significant.

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.

Description and dosimetric verification of the PEREGRINE Monte Carlo dose calculation system for photon beams incident on a water phantom.

PEREGRINE is a three-dimensional Monte Carlo dose calculation system written specifically for radiotherapy. This paper describes the implementation and overall dosimetric accuracy of PEREGRINE physics algorithms, beam model, and beam commissioning procedure. Particle-interaction data, tracking geometries, scoring, variance reduction, and statistical analysis are described. The BEAM code system is used to model the treatment-independent accelerator head, resulting in the identification of primary and scattered photon sources and an electron contaminant source. The magnitude of the electron source is increased to improve agreement with measurements in the buildup region in the largest fields. Published measurements provide an estimate of backscatter on monitor chamber response. Commissioning consists of selecting the electron beam energy, determining the scale factor that defines dose per monitor unit, and describing treatment-dependent beam modifiers. We compare calculations with measurements in a water phantom for open fields, wedges, blocks, and a multileaf collimator for 6 and 18 MV Varian Clinac 2100C photon beams. All calculations are reported as dose per monitor unit. Aside from backscatter estimates, no additional, field-specific normalization is included in comparisons with measurements. Maximum discrepancies were less than either 2% of the maximum dose or 1.2 mm in isodose position for all field sizes and beam modifiers.

Forward or inversely planned segmental multileaf collimator IMRT and sequential tomotherapy to treat multiple dominant intraprostatic lesions of prostate cancer to 90 Gy.

PURPOSE: To investigate the technical feasibility of using forward or inversely planned segmental multileaf collimator (SMLC) intensity-modulated radiotherapy and sequential tomotherapy (ST) to escalate to a dose of 90 Gy to multiple dominant intraprostatic lesions within the prostate gland while delivering a dose of 75.6 Gy to the remaining prostate. METHODS AND MATERIALS: A selected case with one dominant intraprostatic lesion located at the left base and a second dominant intraprostatic lesion at the right apex of the prostate was planned using three different intensity modulation techniques. Two plans were generated with inverse treatment planning, using either SMLC or ST with a special multivane collimator. The third plan also employed SMLC but was generated using forward planning. All three plans were compared based on dose-volume histograms, isodose distributions, and doses to sensitive normal structures. RESULTS: All three plans meet and exceed the desired dose constraints, limiting doses to the rectum and bladder to an estimated RTOG Grade 2 complication rate of <10%. The ST plan achieved the best dose conformality, whereas the inverse SMLC plan gave the lowest dose to the rectal wall, and the forward SMLC plan obtained the best dose homogeneity inside the targets. CONCLUSIONS: Using any of the three intensity-modulated techniques, it is technically feasible to concurrently treat multiple selected high-risk regions within the prostate to 90 Gy and the remaining prostate to 75.6 Gy, while keeping the doses to the rectum and the bladder significantly lower than those associated with a Grade 2 complication rate of 10%.

Delivery systems of intensity-modulated radiotherapy using conventional multileaf collimators.

Intensity-modulated radiotherapy (IMRT) using conventional multileaf collimators (MLCs) has gained much attention in the radiation therapy community. To implement IMRT safely and efficiently, it is essential to understand the characteristics of MLCs, the associated delivery systems, and the limitations of each system when applied to IMRT. In this article, 3 major manufactured MLC collimators are reviewed, including the general descriptions such as the location of the MLC, whether or not it is single focused or double focused, the physical characteristics of leaves, the leaf movement restrictions, and the maximum achievable field size for IMRT delivery. MLC-based static and dynamic mechanisms are reviewed, and the delivery systems for these 3 collimators are described. Machine-related and patient plan-related quality assurance issues are discussed. Our conclusions are that MLC-based IMRT delivery is practical; however, extensive efforts are needed when IMRT is implemented in clinics.

MR-spectroscopy guided target delineation for high-grade gliomas.

PURPOSE: Functional/metabolic information provided by MR-spectroscopy (MRSI) suggests MRI may not be a reliable indicator of active and microscopic disease in malignant brain tumors. We assessed the impact MRSI might have on the target volumes used for radiation therapy treatment planning for high-grade gliomas. METHODS AND MATERIALS: Thirty-four patients (22 Grade III; 12 Grade IV astrocytomas) were evaluated; each had undergone MRI and MRSI studies before surgery. MRI data sets were contoured for T1 region of contrast enhancement (T1), region of necrosis, and T2 region of hyperintensity (T2). The three-dimensional MRSI peak parameters for choline (Cho) and N-acetylaspartate (NAA), acquired by a multivoxel technique, were categorized based on an abnormality index (AI), a quantitative assessment of tissue metabolite levels. The AI data were aligned to the MRI and displayed as three-dimensional contours. AI vs. T conjoint and disjoint volumes were compared. RESULTS: For both grades, although T2 estimated the region at risk of microscopic disease as being as much as 50% greater than by MRSI, metabolically active tumor still extended outside the T2 region in 88% of patients by as many as 28 mm. In addition, T1 suggested a lesser volume and different location of active disease compared to MRSI. CONCLUSION: The use of MRSI to define target volumes for RT treatment planning would increase, and change the location of, the volume receiving a boost dose as well as reduce the volume receiving a standard dose. Incorporation of MRSI into the treatment-planning process may have the potential to improve control while reducing complications.

Three-dimensional intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma: the University of California-San Francisco experience.

PURPOSE: To review our experience with three-dimensional intensity-modulated radiotherapy (IMRT) in the treatment of nasopharyngeal carcinoma. METHODS AND MATERIALS: We reviewed the records of 35 patients who underwent 3D IMRT for nasopharyngeal carcinoma at the University of California-San Francisco between April 1995 and March 1998. According to the 1997 American Joint Committee on Cancer staging classification, 4 (12%) patients had Stage I disease, 6 (17%) had Stage II, 11 (32%) had Stage III, and 14 (40%) had Stage IV disease. IMRT of the primary tumor was delivered using one of the following three techniques: (1) manually cut partial transmission blocks, (2) computer-controlled autosequencing static multileaf collimator (MLC), and (3) Peacock system using a dynamic multivane intensity-modulating collimator (MIMiC). A forward 3D treatment-planning system was used for the first two methods, and an inverse treatment planning system was used for the third method. The neck was irradiated with a conventional technique using lateral opposed fields to the upper neck and an anterior field to the lower neck and supraclavicular fossae. The prescribed dose was 65-70 Gy to the gross tumor volume (GTV) and positive neck nodes, 60 Gy to the clinical target volume (CTV), and 50-60 Gy to the clinically negative neck. Eleven (32%) patients had fractionated high-dose-rate intracavitary brachytherapy boost to the primary tumor 1-2 weeks following external beam radiotherapy. Thirty-two (91%) patients also received cisplatin during, and cisplatin and 5-fluorouracil after, radiotherapy. Acute and late normal tissue effects were graded according to the Radiation Therapy Oncology Group (RTOG) radiation morbidity scoring criteria. Local-regional progression-free, distant metastasis-free survival and overall survival were estimated using the Kaplan-Meier method. RESULTS: With a median follow-up of 21.8 months (range, 5-49 months), the local-regional progression-free rate was 100%. The 4-year overall survival was 94%, and the distant metastasis-free rate was 57%. The worst acute toxicity was Grade 2 in 16 (46%) patients, Grade 3 in 18 (51%) patients and Grade 4 in 1 (3%) patient. The worst late toxicity was Grade 1 in 15 (43%), Grade 2 in 13 (37%), and Grade 3 in 5 (14%) patients. Only 1 patient had a transient Grade 4 soft-tissue necrosis. At 24 months after treatment, 50% of the evaluated patients had Grade 0, 50% had Grade 1, and none had Grade 2 xerostomia. Analysis of the dose-volume histograms (DVHs) showed that the average maximum, mean, and minimum dose delivered were 79.5 Gy, 75.8 Gy, and 56.5 Gy to the GTV, and 78.9 Gy, 71.2 Gy, and 45.4 Gy to the CTV, respectively. An average of only 3% of the GTV and 2% of the CTV received less than 95% of the prescribed dose. The average dose to 5% of the brain stem, optic chiasm, and right and left optic nerves was 48.3 Gy, 23.9 Gy, 15.0 Gy, and 14.9 Gy, respectively. The average dose to 1 cc of the cervical spinal cord was 41.7 Gy. The doses delivered were within the tolerance of these critical normal structures. The average dose to 50% of the right and left parotids, pituitary, right and left T-M joints, and ears was 43. 2 Gy, 41.0 Gy, 46.3 Gy, 60.5 Gy, 58.3 Gy, 52.0 Gy, and 52.2 Gy, respectively. CONCLUSION: 3D intensity-modulated radiotherapy provided improved target volume coverage and increased dose to the gross tumor with significant sparing of the salivary glands and other critical normal structures. Local-regional control rate with combined IMRT and chemotherapy was excellent, although distant metastasis remained unabated.

Comparison of treatment plans involving intensity-modulated radiotherapy for nasopharyngeal carcinoma.

PURPOSE: To compare intensity-modulated radiotherapy (IMRT) treatment plans with conventional treatment plans for a case of locally advanced nasopharyngeal carcinoma. METHODS AND MATERIALS: The study case was planned using two types of IMRT techniques, as well as a three-dimensional conformal radiotherapy technique (3D-CRT), and a traditional treatment method using bilateral opposing fields. These four plans were compared with respect to dose conformality, dose-volume histogram (DVH), dose to the sensitive normal tissue structures, and ease of treatment delivery. RESULTS: The planned dose distributions were more conformal to the tumor target volume in the IMRT plans than those in the conventional plans. With similar dose coverage of the clinical target volume (CTV), defined as delivery of minimum of 60 Gy to >/= 95% of CTV, the IMRT plans achieved better sensitive normal tissue structure sparing, while concomitantly delivering a minimum dose of 68 Gy to >/= 95% of the gross tumor volume (GTV) at a higher dose per fraction. CONCLUSIONS: Compared to conventional techniques, IMRT techniques provide improved tumor target coverage with significantly better sparing of sensitive normal tissue structures in the treatment of locally advanced nasopharyngeal carcinoma. With improvement of the delivery efficiency, IMRT should provide the optimal treatment for all nasopharyngeal carcinoma. Further studies are needed to establish the true clinical advantage of this new modality.

Dose optimization for the treatment of anaplastic thyroid carcinoma: a comparison of treatment planning techniques.

PURPOSE: To evaluate and compare dose optimization for the treatment of anaplastic thyroid carcinoma using a 3D conformal plan, and two 3D intensity-modulated inverse plans. METHODS AND MATERIALS: After patient immobilization using an alpha cradle and head-mask system, a postoperative CT scan was obtained to delineate the gross tumor volume (GTV), the clinical tumor volume (CTV), and adjacent critical structures. Treatment plans were generated using UM-Plan (University of Michigan), PeacockPlan and Corvus (NOMOS Corporation, Sewickley, PA). Isodoses were displayed in the sagittal, coronal, and multiple axial planes, and dose-volume histograms (DVH) were generated for the GTV, CTV, and critical normal tissues. Treatment times were estimated to compare the practicality of delivering each plan in a busy radiotherapy department. RESULTS: All three treatment planning systems were able to deliver a minimum dose of 60 Gy to the GTV while keeping the maximum spinal cord dose at or below 45 Gy. However, there were differences in the doses delivered to 50% and 5% of the cord, the minimum CTV dose, and the overall treatment time. The PeacockPlan best spared the uninvolved tissues of the posterior neck, and provided the lowest dose to the cord without compromising the CTV. CONCLUSIONS: Inverse treatment planning provides superior dose optimization for the treatment of anaplastic thyroid carcinoma. The radiobiologic impact of intensity modulation for this tumor should be further tested clinically.

A dosimetric comparison of fan-beam intensity modulated radiotherapy with Gamma Knife stereotactic radiosurgery for treating intermediate intracranial lesions.

PURPOSE: To compare and evaluate treatment plans for the fan-beam intensity modulated radiotherapy and the Gamma Knife radiosurgery for treating medium-size intracranial lesions (range 4-25 cm3). METHODS AND MATERIALS: Treatment plans were developed for the Leksell Gamma Knife and a fan-beam inverse treatment planning system for intensity modulated radiotherapy. Treatment plan comparisons were carried out using dose-volume histogram (DVH), tissue-volume ratio (TVR), and maximum dose to the prescription dose (MDPD) ratio. The study was carried out for both simulated targets and clinical targets with irregular shapes and at different locations. RESULTS: The MDPD ratio was significantly greater for the Gamma Knife plans than for the fan-beam IMRT plans. The Gamma Knife plans produced equivalent TVR values to the fan-beam IMRT plans. Based on the DVH comparison, the fan-beam IMRT delivered significantly more dose to the normal brain tissue than the Gamma Knife. The results of the comparison were found to be insensitive to the target locations. CONCLUSION: The Gamma Knife is better than the fan-beam IMRT in sparing normal brain tissue while producing equivalent tumor dose conformity for treating medium-size intracranial lesions. However, the target dose homogeneity is significantly better for the fan-beam IMRT than for the Gamma Knife.

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.

Comparison of three-dimensional conformal radiation therapy and intensity-modulated radiation therapy systems.

The use of three-dimensional conformal radiation therapy (3DCRT) has now become common practice in radiation oncology departments around the world. Using beam's eye viewing of volumes defined on a treatment planning computed tomography scan, beam directions and beam shapes can be selected to conform to the shape of the projected target and minimize dose to critical normal structures. Intensity-modulated radiation therapy (IMRT) can yield dose distributions that conform closely to the three-dimensional shape of the target volume while still minimizing dose to normal structures by allowing the beam intensity to vary across those shaped fields. Predicted dose distributions for patients with tumors of the prostate, nasopharynx, and paraspinal region are compared between plans made with 3DCRT programs and those with inverse-planned IMRT programs. The IMRT plans are calculated for either static or dynamic beam delivery methods using multileaf collimators. Results of these comparisons indicate that IMRT can yield significantly better dose distributions in some situations at the expense of additional time and resources. New technologies are being developed that should significantly reduce the time needed to plan, implement, and verify these treatments. Current research should help define the future role of IMRT in clinical practice.

Multileaf collimator leaf sequencing algorithm for intensity modulated beams with multiple static segments.

The "stop and shoot" method of producing intensity modulation using combinations of static multileaf collimator (MLC) segments has a number of advantages including precise dose delivery, easy verification, and general availability. However, due to the potential limitation of prolonged treatment time, it is essential to keep the number of required segments to a reasonable number. We propose an algorithm to minimize the number of segments for an intensity modulated field. In this algorithm, the sequence of delivery intensity is proposed to be a series of powers of 2, depending on the maximum intensity level in the matrix. The MLC leaf position sequence is designed directly on the two-dimensional intensity matrix to irradiate the largest possible area in each segment. The algorithm can be applied directly to MLC systems with different motion constraints. This algorithm has been evaluated by generating 1000 random 15 x 15 cm intensity matrices, each having from 3 to 16 intensity levels. Five clinical intensity modulated fields generated from the NOMOS CORVUS planning system for a complex clinical head and neck case were also tested with this and two other algorithms. The results of both the statistical and clinical studies showed that for all the intensity matrices tested, the proposed algorithm results in the smallest number of segments with a moderately increased monitor units. Thus it is well-suited for use in static MLC intensity modulation beam delivery. For MLC systems with interleaf motion constraint, we prove mathematically that this constraint reduces the tongue and groove effect at the expense of an increase of 25% in the number of segments.

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.

Comparison of radiosurgery treatment modalities based on physical dose distributions.

PURPOSE: As a means of selecting the optimal stereotactic radiosurgery (SRS) treatment modality, a comparison of physical dose distributions to defined targets and nontarget brain tissue has been made for a group of test cases selected to represent a range of treatment-planning situations from small, nearly spherical volumes to large irregular volumes. METHODS AND MATERIALS: Plans were developed for each case using photon beams from the Leksell Gamma Unit (LGU), multiarc bremsstrahlung photon beams from a linear accelerator (linac) and proton beams, with the objective of encompassing the target as closely as possible with the prescription isodose line, and minimizing dosage to normal tissue within the bounds of standard clinical practice. Dose-volume histograms (DVHs) were calculated for target and for nontarget brain tissue and compared for the various modalities. RESULTS: In general, protons delivered less dosage to normal brain than other modalities for large and peripheral lesions and LGU plans were more successful at conforming to highly irregular shapes than conventional linac plans. CONCLUSIONS: Differences were observed to depend on treatment modality, target characteristics (shape, size and location), and the amount of effort expended on treatment planning and the time allotted for treatment implementation.

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).

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.