Absorbed radiation dose of the female breast during diagnostic multidetector chest CT and dose reduction with a tungsten-antimony composite breast shield: preliminary results.

AIM: To determine the absorbed radiation dose to the female breast during chest computed tomography (CT), and whether a custom-designed breast shield can reduce that dose. MATERIALS AND METHODS: Bilateral breast phantoms were combined with an anthropomorphic torso phantom. Each breast phantom contained 20 thermoluminescent dosimeter (TLD) cavities. Eight cavities were used per phantom. Absorbed radiation was measured using TLD 100 s. Three-stacked TLDs comprised a set. Three sets of three TLDs were positioned at eight designated locations and three depths (surface; 1 cm; 4 cm). One set of three TLDs was positioned at eight additional designations, 1cm deep. Each breast was divided anatomically into quadrants. In total, 32 TLD sets/96 TLDs were deployed. The breast-torso phantom was consecutively imaged using a 16-detector array CT machine. Subsequently, 32 new TLD sets were similarly placed, the phantom re-imaged in a likewise manner, but with the application of a tungsten-antimony composite breast shield. TLD readings were averaged and calculated. RESULTS: Average absorbed radiation doses for unshielded right and left breast phantoms ranged from 13.83-19.36 mGy, and 14-20.47 mGy, respectively. The absorbed dose in the shielded right and left breast was reduced to 6.64-8.12 mGy, and 6.7-8.03 mGy, respectively. Average absorbed radiation doses based on the depth for the unshielded breasts ranged from 15.4-18.3 mGy. Shielding reduced this dose to 7-7.9 mGy. Unshielded absorbed radiation doses based on anatomic quadrants ranged from 17.5-18.9 mGy. Shielding reduced this dose to 7-7.5 mGy. CONCLUSIONS: The average absorbed radiation dose to the unshielded female breast phantom is approximately 14-20 mGy. An externally applied shield can reduce this absorbed dose by 56-61%.

Deferiprone, an orally deliverable iron chelator, ameliorates experimental autoimmune encephalomyelitis.

The iron chelator, Desferal, suppressed disease activity of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), and it has been tested in pilot trials for MS. The administration regimen of Desferal is cumbersome and prone to complications. Orally-deliverable, iron chelators have been developed that circumvent these difficulties, and the objective of this study was to test an oral chelator in EAE. SJL mice with active EAE were randomly assigned to receive deferiprone (150 mg/kg) or vehicle (water) 2x/day via gavage. EAE mice given deferiprone had significantly less disease activity and lower levels of inflammatory cell infiltrates (revealed by H&E staining) than EAE mice administered vehicle. T-cell infiltration, assessed by anti-CD3 immunohistochemical staining, also was reduced, although not significantly. Splenocytes cultured from naïve SJL mice were stimulated with anti-CD3 and anti-CD28 with or without 250 microM deferiprone. While approximately 39% of costimulated splenocytes without deferiprone underwent division, only approximately 2.8% of costimulated splenocytes with deferiprone divided and the latter cells were only 53% as viable as the former. Deferiprone had no effect on proliferation or viability of cells that were not costimulated. In summary, deferiprone effectively suppressed active EAE disease and it inhibited T-cell function.

Alternate costimulatory molecules in T cell activation: differential mechanisms for directing the immune response.

T cells are required for an effective immune response against a wide range of pathogens and for the generation of immunological memory. T cell activation can be divided into two phases: an antigen-specific signal delivered through the T cell antigen receptor, and a costimulatory signal delivered through accessory molecules on the T cell surface. Following activation, T cells differentiate to acquire distinct effector functions depending on the costimulatory signal, cytokine environment, and the pathogen itself. Although CD28 has been identified as the dominant costimulatory molecule, several other molecules have been described as having a costimulatory function. This review will focus on recent evidence for the existence of alternate costimulatory molecules, and the differential roles they might play in the activation, development, and survival of T cells.

How should we describe the radioblologic effect of extracranial stereotactic radlosurgery: equivalent uniform dose or tumor control probability?

Extracranial stereotactic radiosurgery (ESR) is now undergoing clinical investigation at numerous institutions as a treatment for solitary malignant lesions. Because there is no standard ESR technique, the same minimum dose might be applied through widely variable target dose-volume histograms. For multicenter trials of ESR or interinstitutional comparisons, a reliable index of radiobiological dose equivalency might facilitate the evaluation of dose-response relationships. Equivalent uniform dose (EUD) and tumor control probability (TCP) were considered for this application. While EUD appears more robust for the prospective description of ESR, TCP is expected to remain more valuable for a post hoc estimation of radiosensitivity parameters.

Training status influences T-cell responses in women following acute resistance exercise.

The purpose of this investigation was to examine white blood cell counts (WBC), immunoglobulin (IgA, IgG, IgM) levels, and T-cell proliferation following acute resistance training in 9 untrained (UT) and 6 trained (TR) women. Resistance training on 7 Universal machines at the subject's 10 repetition maximum (IORM) was performed at 89 +/- 5% for UT and 88 +/- 3% for TR. Blood was analyzed for WBCs and Ig levels pre-exercise, immediately postexercise, and 1.5, 3, and 24 hours postexercise. T-cell proliferation was determined pre-exercise and 3 hours postexercise through response to phytohemagglutanin (PHA). WBCs were significantly elevated in the UT subjects 1.5 and 3 hours postexercise compared with pre- and immediately postexercise; no differences (p < 0.05) were observed in TR subjects. No significant differences were found for Ig levels either between or within groups, although there was a trend for decreased IgG following exercise. T-cell proliferation was significantly decreased in the UT at 3 hours postexercise (0.27 +/- 0.06 units) compared with pre-exercise (0.41 +/- 0.06 units), whereas the proliferative response in TR was not significantly different from pre-exercise (0.48 +/- 0.04 units) to 3 hours postexercise (0.34 +/- 0.06 units). These data indicate that UT subjects experience an increase in WBC counts and a decrease in T-cell proliferative ability after acute resistance training, whereas TR subjects experience no significant change in these parameters.

Cost analysis of erythropoietin versus blood transfusions for cervical cancer patients receiving chemoradiotherapy.

PURPOSE: Red blood cell (RBC) transfusions or erythropoietin (EPO) can be used to evade the detrimental effects of anemia during radiotherapy, but the economic consequences of selecting either intervention are not well defined. The RBC transfusion needs during chemoradiotherapy for cervix cancer were quantified to allow comparison of RBC transfusion costs with the projected cost of EPO in this setting. METHODS AND MATERIALS: For patients receiving pelvic radiotherapy, weekly cisplatin, and brachytherapy, the RBC units transfused during treatment were tallied. RBC transfusion costs per unit included the blood itself, laboratory fees, and expected value (risk multiplied by cost) of transfusion-related viral illness. EPO costs included the drug itself and supplemental RBC transfusions when hemoglobin was not adequately maintained. An EPO dosage based on reported usage in cervix cancer patients was applied. RESULTS: Transfusions were given for hemoglobin <10 g/dL. Among 12 consecutive patients, 10 needed at least 1 U of RBC before or during treatment, most commonly after the fifth week. A total of 37 U was given during treatment, for an average of 3.1 U/patient. The sum total of the projected average transfusion-related costs was $990, compared with the total projected EPO-related costs of $3869. CONCLUSIONS: Because no proven clinical advantage has been documented for EPO compared with RBC transfusions to maintain hemoglobin during cervix cancer treatment, for most patients, transfusions are an appropriate and appealingly less expensive option.

MIP-1alpha induces activation of phosphatidylinositol-3 kinase that associates with Pyk-2 and is necessary for B-cell migration.

The chemokine macrophage inflammatory protein-1 alpha [MIP-1alpha] causes migration of B cells and also induces changes in antibody secretion. However, the signal transduction pathways leading to these phenotypic changes remain undefined. We have identified a signal transduction pathway initiated by MIP-1alpha in B cells. Here we report that stimulation of tonsil B cells with MIP-1alpha induces phosphatidylinositol 3-kinase [PI3-K] activation. Kinase activity was transient with peak induction occurring within 2.5 to 5 min after stimulation and was dose-dependent. In addition stimulation with MIP-1alpha induces tyrosine phosphorylation of the proline-rich tyrosine kinase Pyk-2. Immunoprecipitation analysis showed a constitutive association between Pyk-2 and PI3-K and pretreatment of MIP-1alpha-stimulated B cells with wortmannin, a specific inhibitor of PI3-K, resulted in a loss of PI3-K activity. The PI3-K inhibitor wortmannin prevented B cells from migrating in response to MIP-1alpha. Hence, PI3-K and Pyk-2 seem to be components of a signal transduction pathway induced by stimulation of B cells with MIP-1alpha, and this pathway may play a role in B-cell migration.

Intensity-modulated stereotactic radiosurgery using dynamic micro-multileaf collimation.

PURPOSE: The implementation of dynamic leaf motion on a micro-multileaf collimator system provides the capability for intensity-modulated stereotactic radiosurgery (IMSRS), and the consequent potential for improved dose distributions for irregularly shaped tumor volumes adjacent to critical organs. This study explores the use of IMSRS to provide improved tumor coverage and normal tissue sparing for small cranial tumors relative to plans based on multiple fixed uniform-intensity beams or traditional circular collimator arc-based stereotactic techniques. METHODS AND MATERIALS: Four patient cases involving small brain lesions are presented and analyzed. The cases were chosen to include a representative selection of target shapes, number of targets, and adjacent critical areas. Patient plans generated for these comparisons include standard arcs with multiple circular collimators, and fixed noncoplanar static fields with uniform-intensity beams and IMSRS. Parameters used for evaluation of the plans include the percentage of irradiated volume to tumor volume (PITV), normal tissue dose-volume histograms, and dose-homogeneity ratios. All IMSRS plans were computed using previously established IMRT techniques adapted for use with the BrainLAB M3 micro-multileaf collimator. The algorithms comprising the IMRT system for optimization of intensity distributions and conversion into leaf trajectories of the BrainLab M3 were developed at our institution. The ADAC Pinnacle(3) radiation treatment-planning system was used for dose calculations and for input of contours for target volumes and normal critical structures. RESULTS: For all cases, the IMSRS plans showed a high degree of conformity of the dose distribution with the target shape. The IMSRS plans provided either (1) a smaller volume of normal tissue irradiated to significant dose levels, generally taken as doses greater than 50% of the prescription, or (2) a lower dose to an important adjacent critical organ. The reduction in volume of normal tissue irradiated in the IMSRS plans ranged from 10% to 50% relative to the other arc and uniform fixed-field plans. CONCLUSION: The case studies presented for IMSRS demonstrate significant dosimetric improvements for small, irregularly shaped lesions of the brain when compared to treatments using multiple static fields or standard SRS arc techniques with circular collimators. For all cases, the IMSRS plan yielded a smaller volume of normal tissue irradiated, and/or a reduction in the volume of an adjacent critical organ (i.e., brainstem) irradiated to significant dose levels.

Minimal influence of carbohydrate ingestion on the immune response following acute resistance exercise.

The effect of carbohydrate supplementation (CHO) on the lymphocyte response to acute resistance exercise was examined in 10 resistance-trained males. Subjects completed a randomized double-blind protocol with sessions separated by 14 days. The exercise session consisted of a high intensity, short rest interval squat workout. Subjects consumed 1.0 g á kg body mass(-1) CHO or an equal volume of placebo (PLC) 10 min prior to and 10 min following exercise. Blood was collected at rest (REST), immediately post exercise (POST), and at 1.5 hours and 4.0 hours of recovery, and analyzed for plasma glucose, serum cortisol, leukocyte subsets, and phytohemagglutinin (PHA)-stimulated lymphocyte proliferation. A significant Treatment 3 Time effect was observed for lymphocyte proliferation between CHO and PLC, but post hoc analyses revealed no between-treatment differences at any post-exercise time point. Lymphocyte proliferation was significantly depressed below REST at POST (-39.2% for PLC, -25.7% for CHO). Significant fluctuations in leukocyte subset trafficking were observed for both treatments at POST, 1.5 hours, and 4.0 hours. Plasma glucose was significantly increased POST in CHO compared to PLC. Cortisol was significantly increased from REST to POST in both treatments. These data support a minimal effect of carbohydrate ingestion on the lymphocyte response to high-intensity resistance exercise.

Linear and cyclic LFA-1 and ICAM-1 peptides inhibit T cell adhesion and function.

Short peptides derived from functional proteins have been used in several instances to inhibit activity of the parent proteins. In some cases, stability and efficacy were found to be increased by cyclization of these peptides. Inhibition of interaction of the two cell adhesion counter receptors leukocyte function-associated antigen (LFA)-1 and intercellular adhesion molecule (ICAM)-1 is being studied as a method for modulating autoimmune diseases such as rheumatoid arthritis and for facilitating organ transplantation. Here, several 10-amino acid peptides derived from the contact domains of LFA-1 and ICAM-1 were evaluated for their ability to interfere with intercellular adhesion by T cells and to inhibit a more biologic, mixed lymphocyte reaction. Both linear and cyclic forms of the peptides were effective at inhibiting intercellular adhesion. Cyclic forms were effective at inhibiting T cell activation and proliferation in the mixed lymphocyte reaction.

Muscle damage and resting metabolic rate after acute resistance exercise with an eccentric overload.

PURPOSE: The purpose of this investigation was to determine whether muscle damage caused from acute resistance exercise with an eccentric overload would influence resting metabolic rate (RMR) up to 72 h postexercise in resistance-trained (RT) and untrained (UT) subjects. METHODS: Nine RT and 9 UT male subjects (mean +/- SD; age = 20.7 +/- 2.1 yr; body mass = 79.0 +/- 1.4 kg; height = 178.4 +/- 3.1 cm; and body fat = 10.2 +/- 1.6%) were measured for RMR, creatine kinase concentration ([CK]), and rating of perceived muscle soreness (RPMS) on five consecutive mornings. To induce muscle damage, after the measurements on day 2, each subject performed leg presses that emphasized the eccentric movement for 8 sets at his six-repetition maximum (6-RM). RESULTS: Compared with baseline, the RMR (kJ x d(-1) and kJ x kg FFM(-1) x h(-1) was significantly elevated for RT and UT at 24 h and 48 h postexercise. From 24 h to 48 h to 72 h postexercise, RMR significantly decreased within both groups. The UT group had a significantly higher RMR at 24 h (9,705.4 +/- 204.5 kJ x d(-1)) and 48 h postexercise (8,930.9 +/- 104.4 kJ x d(-1)) when compared with the RT group (9,209.3 +/- 535.3 and 8,601.7 + 353.7 kJ x d(-1)). Both [CK] and RPMS showed a similar time course. CONCLUSION: There was a significantly higher [CK] for the UT group at 24 h postexercise (320.4 +/- 20.1 U x L(-1)) and for both [CK] and RPMS at 48 h (1,140.3 +/- 37.1 U x L(-1) and 4.4 +/- 0.5, respectively) and 72 h postexercise (675.9 +/- 41.7 U x L(-1) and 1.67 +/- 0.5, respectively) when compared with the RT group (24 h, 201.9 +/- 13.4 U x L(-1); 48 h, 845.4 +/- 30.7 U x L(-1) and 3.7 +/- 0.5: and 72 h postexercise, 420.2 +/- 70.2 U x L(-1) and 0.89 +/- 0.3). These data indicate that eccentrically induced muscle damage causes perturbations in RMR up to 48 h postexercise.

Hypofractionated stereotactic radiotherapy as an alternative to radiosurgery for the treatment of patients with brain metastases.

PURPOSE: Modeling studies have demonstrated a potential biologic advantage of fractionated stereotactic radiotherapy for malignant brain tumors as compared to radiosurgery (SRS), even when only a few fractions are utilized. We prospectively evaluated the feasibility, toxicity, efficacy and cost of hypofractionated stereotactic radiotherapy (HSRT) in the treatment of selected radiosurgery-eligible patients with brain metastases. METHODS AND MATERIALS: Patients with a limited number of brain metastases not involving the brainstem or optic chiasm underwent linac-based HSRT delivered in 3 fractions using a relocatable stereotactic frame. Depth-helmet and reference point measurements were recorded to address treatment accuracy. All patients underwent whole brain radiotherapy to a dose of 30 Gy. Toxicity, response, and survival duration were recorded for each patient. Prognostic factors were assessed by Cox regression analysis. Cost comparisons with a cohort of SRS treated patients were performed. RESULTS: Thirty-two patients with 57 brain metastases were treated with HSRT. Twenty-three and 9 patients underwent HSRT for upfront and salvage treatment, respectively. The median dose delivered was 27 Gy, given in 3 fractions of 9 Gy. From 3328 depth-helmet measurements, the absolute median setup deviation in AP, lateral, and vertical orientations was approximately 1.0 mm. No significant acute toxicity was seen. Late toxicities included seizures in four patients, and radionecrosis in two patients. The median survival duration from treatment was 12 months. KPS (p = 0.039) and RTOG-RPA class (p = 0.039) were identified as significant prognostic factors for survival. HSRT was $4119 less costly than SRS. CONCLUSION: HSRT, as delivered in this study, is more comfortable for patients and less costly than SRS in the treatment of selected patients with brain metastases. Proper dose selection and radiobiologic/toxicity trade-offs with SRS await further study.

Induction of PYK-2 phosphorylation during LFA-1/ICAM-1-dependent homotypic adhesion of fresh human B-cells.

Stimulation with the combination of PDB plus ionomycin induced LFA-1/ICAM-1-dependent homotypic adhesion of tonsil B cells. Adhesion of tonsil B cells in our system induced tyrosine phosphorylation of Pyk-2. Disruption of homotypic adhesion and concomitant inhibition of induction of protein tyrosine phosphorylation was achieved by physical separation of the cells and by treatment with methyl-2.5-dihydroxycinnamate (MDHC), an inhibitor of protein tyrosine phosphorylation. These results suggest that protein tyrosine phosphorylation that is associated with homotypic adhesion is mediated by LFA-1/ICAM-1 interactions.

MIP-1alpha induces binding of nuclear factors to the kappaB DNA element in human B cells.

The chemokine macrophage inflammatory protein-1 alpha (MIP-1alpha) stimulates migration of B cells through an unknown mechanism. Furthermore, little is known about signal transduction mechanisms through which MIP-1alpha might signal phenotypic changes in B cells. We are investigating the role of MIP-1alpha in B cell signaling. Here we report that stimulation of the Ramos B cell line or tonsil B or peripheral blood-B (PBL-B) cells with MIP-1alpha caused the transcription factor NF-kappaB to bind to DNA. NF-kappaB induction was dose dependent, and was transient, with peak induction occurring at 30 min. MIP-1alpha treatment stimulated the degradation of IkappaBalpha, a cytoplasmic inhibitor of NF-kappaB. The biological significance of NF-kappaB activation by MIP-1alpha is currently unknown, but it is known that NF-kappaB modulates expression of genes involved in many inflammatory and immune responses. Here we show that NF-kappaB activation is a target of signals sent into B cells by MIP-1alpha.

Peptides derived from ICAM-1 and LFA-1 modulate T cell adhesion and immune function in a mixed lymphocyte culture.

BACKGROUND: The counter receptors intercellular adhesion molecule (ICAM)-1 and lymphocyte function-associated antigen (LFA)-1 are lymphocyte cell surface adhesion proteins the interaction of which can provide signals for T cell activation. This binding event is important in T cell function, migration, and general immune system regulation. The ability to inhibit this interaction with monoclonal antibodies has proved to be therapeutically useful for several allograft rejection and autoimmune disease models. METHODS: Short peptides representing counter-receptor contact domains of LFA-1 and ICAM-1 were examined for their ability to inhibit T cell adhesion and T cell function. RESULTS: Peptides encompassing amino acids Q1-C21 and D26-K50 of ICAM-1, I237-I261 and G441-G466 of the LFA-1 alpha-subunit, and D134-Q159 of the LFA-1 beta-subunit inhibited LFA-1/ICAM-1-dependent adhesion in a phorbol-12,13-dibutyrate-induced model of tonsil T cell homotypic adhesion. This inhibition was specific to the peptide sequence and occurred without stimulation of T cell proliferation. The peptides also were effective in preventing T cell function using a one-way mixed lymphocyte reaction model for bone marrow transplantation. CONCLUSIONS: Our data suggest that these peptides or their derivatives may be useful as therapeutic modulators of LFA-1/ICAM-1 interaction during organ transplants.

Determining the optimal block margin on the planning target volume for extracranial stereotactic radiotherapy.

PURPOSE: To determine the block margin that minimizes normal tissue irradiation outside of the planning target volume (PTV) for body stereotactic radiotherapy (Body-SRT) of lung and liver tumors. METHODS AND MATERIALS: Representative patient cases of lung and liver tumors were chosen for analysis. A PTV was constructed for each case and plans were generated which employed an array of block margins ranging from -2.5 mm to 10 mm at isocenter. Plans were generated for cerrobend blocks and for a multileaf collimator. The prescription isodose coverage was renormalized for each case and dose-volume histograms (DVH) and normal tissue complication probabilities (NTCP) were determined for each plan. RESULTS AND CONCLUSION: For the cases studied, the optimal block margin was in the 0.0 mm range. The ranking of plans was identical for both dose-volume based and biological based criteria. The method of blocking had no significant effect on treatment plans. The use of narrow margins for Body-SRT results in normal tissue sparing and creates significant target dose inhomogeneity which may be beneficial for tumor control.

Triptolide is more effective in preventing T cell proliferation and interferon-gamma production than is FK506.

The Chinese traditional herb Tripterygium wilfordii Hook. F (TWHF) has been reported to be effective in the treatment of a variety of autoimmune disorders. The major active component of this herb is triptolide and most of the efficacy of this herb immunosuppression is attributed to triptolide. FK506 is also a potent immunosuppressive agent and is currently being used clinically. The present studies compare the effectiveness of triptolide and FK506 to suppress certain human T cell functions. Specifically human T cell proliferation, IL-2 and IFNgamma were compared. The results show that, overall, triptolide is more effective at inhibiting T cell proliferation and IFNgamma production than FK506 and the two compounds inhibit IL-2 production in an equivalent manner.

Sequences at the 3' side of the c-fos SRE mediate gene expression via an Sob1-dependent, TCF-independent pathway.

We previously described a 110-kDa tyrosine phosphoprotein, Sob 1, that regulates formation of the DNA binding complex Band A at the c-fos serum response element (SRE) during T cell activation. Using competition and mutant oligonucleotide analysis, we have determined that both the core CArG box of the c-fos SRE and the 3' sequences flanking the CArG box are necessary for stable Band A complex formation. Moreover, using transient transfection and reporter assays, we show that mutations affecting Band A complex formation in vitro also impaired serum induction of c-fos gene expression in vivo. Since mutation at this site has no effect on SRF binding, our results suggest that in combination with SRE/SRF, Sob 1-regulated factor(s) bind at the 3' side of SRE to form Band A, and this confers maximal serum induction of c-fos gene expression via the SRE.

A Ca2+ binding cyclic peptide derived from the alpha-subunit of LFA-1: inhibitor of ICAM-1/LFA-1-mediated T-cell adhesion.

The objective of this work is to study the conformation of cyclic peptide (1), cyclo (1, 12) Pen1-Gly2-Val3-Asp4-Val5-Asp6-Gln7-+ ++Asp8-Gly9-Glu10-Thr11-Cys12, in the presence and absence of calcium. Cyclic peptide 1 is derived from the divalent cation binding sequence of the alpha-subunit of LFA-1. This peptide has been shown to inhibit ICAM-1-LFA-1 mediated T-cell adhesion. In order to understand the structural requirements for this biologically active peptide, its solution structure was studied by nuclear magnetic resonance (NMR), circular dichroism (CD) and molecular dynamics simulations. This cyclic peptide exhibits two types of possible conformations in solution. Structure I is a loop-turn-loop type of structure, which is suitable to bind cations such as EF hand proteins. Structure II is a more extended structure with beta-hairpin bend at Asp4-Val5-Asp6-Gln7. There is evidence that alterations in the conformation of LFA-1 upon binding to divalent cations cause LFA-1 to bind to ICAM-1. To understand this mechanism, the cation-binding properties of the peptide were studied by CD and NMR. CD studies indicated that the peptide binds to calcium and forms a 1 : 1 (peptide: calcium) complex at low calcium concentrations and multiple types of complexes at higher cation concentrations. NMR studies indicated that the conformation of the peptide is not significantly altered upon binding to calcium. The peptide can inhibit T-cell adhesion by directly binding to ICAM-1 or by disrupting the interaction of the alpha and beta-subunits of LFA-1 protein. This study will help us to understand the mechanism(s) of action of this peptide and will improve our ability to design a better inhibitor of T-cell adhesion.

A comparison of three stereotactic radiotherapy techniques; ARCS vs. noncoplanar fixed fields vs. intensity modulation.

PURPOSE: Linac arc based stereotactic radiotherapy is being used with increasing frequency to treat brain tumors. This approach can be used for single or fractionated treatments, and is typically carried out with circular collimators which are optimal for small, spherical targets. Treatment planning using fixed noncoplanar beams or intensity-modulated beams may enhance the ability to conform to irregularly shaped and/or large tumors, especially when combined with stereotactic localization. We compare the dose conformity and normal brain dose characteristics of three stereotactic techniques for various nonspherical target shapes. METHODS AND MATERIALS: Three intracranial test targets were constructed using a 3D treatment planning system after a patient underwent CT simulation. The targets included an ellipsoid with major axis dimensions of 4.0, 2.0, and 2.0 cm, a hemisphere with a diameter of 4.0 cm, and an irregularly shaped patient tumor with a maximum dimension of 5.3 cm. The following stereotactic techniques were compared for each target: a) 5 arcs as used in traditional linac radiosurgery/radiotherapy (noncoplanar arcs [ARCS]), b) 6 fixed noncoplanar custom blocked fields (3D), c) intensity modulation using 6 noncoplanar beams and a mini-multileaf collimator (intensity-modulated radiation therapy [IMRTI). Dose volume histograms were performed for each target/technique combination. RESULTS: For the ellipsoid, dose conformity is similar for all three techniques and normal brain isodose distributions are more favorable with the ARCS plan. For the hemisphere and irregular tumor targets, dose conformity and high/low isodose normal brain volumes are more favorable with the IMRT technique. CONCLUSIONS: For the targets described above, the intensity-modulated technique results in improved dose conformity and decreased dose to nontarget brain in high and low isodose regions as compared to the standard noncoplanar arc technique or noncoplanar fixed fields for the hemisphere and tumor targets. Intensity-modulated treatment delivery may allow for an increase in the therapeutic ratio for treating stereotactically defined large and/or irregularly shaped intracranial targets.