Biomedical subjects

D Yan

Publications and source records attributed to D Yan.

At least 19 recordsLinked to original sources

PubMed2003

Reducing uncertainties in volumetric image based deformable organ registration.

Applying volumetric image feedback in radiotherapy requires image based deformable organ registration. The foundation of this registration is the ability of tracking subvolume displacement in organs of interest. Subvolume displacement can be calculated by applying biomechanics model and the finite element method to human organs manifested on the multiple volumetric images. The calculation accuracy, however, is highly dependent on the determination of the corresponding organ boundary points. Lacking sufficient information for such determination, uncertainties are inevitable-thus diminishing the registration accuracy. In this paper, a method of consuming energy minimization was developed to reduce these uncertainties. Starting from an initial selection of organ boundary point correspondence on volumetric image sets, the subvolume displacement and stress distribution of the whole organ are calculated and the consumed energy due to the subvolume displacements is computed accordingly. The corresponding positions of the initially selected boundary points are then iteratively optimized to minimize the consuming energy under geometry and stress constraints. In this study, a rectal wall delineated from patient CT image was artificially deformed using a computer simulation and utilized to test the optimization. Subvolume displacements calculated based on the optimized boundary point correspondence were compared to the true displacements, and the calculation accuracy was thereby evaluated. Results demonstrate that a significant improvement on the accuracy of the deformable organ registration can be achieved by applying the consuming energy minimization in the organ deformation calculation.

Algorithms↗

PubMed2002

Neural inhibition by c-Jun as a synergizing factor in bone morphogenetic protein 4 signaling.

The transcription factor, activator protein 1 (AP-1) complexes (c-Jun and c-Fos heterodimers) has been shown to interact with transforming growth factor beta signaling in mammalian cells and Drosophila embryo. Here we show that c-Jun alone is involved in the anti-neuralizing activity of bone morphogenetic protein 4, a transforming growth factor beta superfamily member, in Xenopus neurogenesis. Co-injection of mRNAs encoding c-jun and a dominant negative bone morphogenetic protein receptor completely inhibits dominant negative bone morphogenetic protein receptor-induced neuralization and reverses the epidermal fate in the animal cap. Surprisingly, a dominant negative c-Jun does not induce neural tissue in the animal cap, but it synergizes with dominant negative bone morphogenetic protein receptor for neural induction. Temporal analysis using a dexamethasone-inducible c-Jun shows that exogenous c-Jun activity must be turned on before or at stage 11 to fulfill the anti-neuralizing effect. Neural inhibition by c-Jun does not occur until stage 13 suggesting that c-Jun probably acts by suppressing neural maintenance rather than neural initiation. This is also supported by the fact that c-Jun does not inhibit expression of the neural-initializing gene Zic-r1 but the neural cofactor Sox2, and that ectopic expression of Sox2 attenuates the anti-neuralizing effect of c-Jun. Finally, we display that the c-Jun effect is enhanced by an auto-regulatory loop between c-Jun and bone morphogenetic protein. These studies suggest that c-Jun/AP-1 is a converging point in both the fibroblast growth factor and transforming growth factor beta signaling pathways. Based on our findings, we propose that c-Jun synergizes with bone morphogenetic protein 4 signaling to inhibit neural development in Xenopus ectoderm.

Animals↗

PubMed2001

Elevated expression of axin2 and hnkd mRNA provides evidence that Wnt/beta -catenin signaling is activated in human colon tumors.

Genetic studies have identified mutations in key regulators of the Wnt/beta-catenin pathway in a variety of cancers, most frequently in colon cancers. However, whether the pathway is activated in clinical cancer samples is not easily determined, and therefore it is useful to find markers that could be surrogates to show activation of the Wnt/beta-catenin pathway. Gene expression profiles were analyzed in SW620, a colon cancer cell line in which beta-catenin levels are stabilized as a consequence of truncated adenomatous polyposis coli and were compared with profiles of the same cells transfected with antisense oligodeoxynucleotides. Treatment of cells with beta-catenin antisense oligodeoxynucleotides resulted in a decrease in the levels of axin2 and human naked cuticle (hnkd) mRNAs. Interestingly, the proteins encoded by both of these mRNAs are known inhibitors of the beta-catenin pathway. In 30 human cell lines derived from different origins, axin2 and hnkd were expressed only in human colon cancer cell lines that are known to have activating mutations in the Wnt/beta-catenin pathway. Further, levels of both axin2 and hnkd mRNA were also found to be elevated in about 65% of laser microdissected cells from human colon tumors compared with laser microdissected cells of normal morphology from the same patient samples. The increased expression of axin2 and hnkd correlated with truncations in adenomatous polyposis coli in the same patient samples. These results reveal that it is possible to detect activation of a carcinogenic pathway in human cancer samples with specific markers.

Axin Protein↗

PubMed2001

The position and volume of the small bowel during adjuvant radiation therapy for rectal cancer.

PURPOSE: The rate of small bowel toxicity from adjuvant pelvic radiation therapy (RT) for rectal cancer has been reported to be lower for patients treated preoperatively (Preop). This was probably due to a lesser volume of irradiated small bowel; however, studies of postoperative treatment reported that patients with an abdominoperineal resection (APR), who likely have the largest volume of small bowel in the pelvis, had less acute and chronic toxicity than those with a low anterior resection (LAR). In this study, three-dimensional treatment planning techniques were used to characterize the position and volume of small bowel in the pelvis and compare these to repeat studies obtained during the typical 5-week course of treatment to attempt to explain the above observations. METHODS AND MATERIALS: Treatment planning CT scans were obtained in 30 patients with rectal cancer (10 Preop, 10 LAR, 10 APR), including 12 patients with weekly CT scans during RT (65 scans). The position of the small bowel was measured by the distance to the nearest small bowel from the bones of the posterior pelvis and by the volume of small bowel within four anatomically defined regions of the pelvis. The motion of the small bowel was expressed as the standard deviation of the small bowel position measured with both the distance and the volume in the 12 patients with repeat studies. RESULTS: Contrast-containing small bowel was found an average 2.9 cm more anterior than small bowel without contrast below the sacral promontory. The position of the small bowel in Preop patients was significantly more anterior (p < or = 0.01) with less volume (p < or = 0.04) in the pelvis than postoperatively treated patients. The small bowel was also more anterior for patients with an LAR vs. APR (p < or = 0.03) but with similar volume in all pelvic regions. Small bowel motion, expressed as the standard deviation of the distance from the bones of the posterior pelvis to the closest small bowel, was 2.9 cm, 1.4 cm, and 0.2 cm for the Preop, LAR, and APR group, respectively. The LAR group had a considerable degree of motion in the posterior pelvis. Increased bladder volume was associated with reduced small bowel volumes, although this benefit decreased during treatment. CONCLUSION: Because treatment planning CT scans can detect small bowel that does not contain contrast, they may be more accurate than the traditional small bowel series. The Preop patients had significantly less pelvic small bowel supporting the clinical observation of better tolerance to therapy. The higher small bowel toxicity reported for LAR vs. APR patients may be explained by the greater variability of both the position and volume of the small bowel in the posterior pelvis for LAR patients. This finding suggests that a single planning study may not be accurate for the block design used for boost treatment of LAR patients. Bladder-filling techniques were useful for Preop and LAR but not APR patients, and decreased in benefit over time. This study suggested that treatment planning CT scans were more useful than a small bowel series and that more than one treatment planning CT may be obtained in any patient receiving > 45 Gy for rectal cancer. However, further research will be necessary to determine the optimal timing and total number of repeat studies.

Diarrhea↗

PubMed2001

The influence of interpatient and intrapatient rectum variation on external beam treatment of prostate cancer.

PURPOSE: The rectal dose/volume relationship and inherent variations thereof are fundamental parameters to guide dose escalation in prostate cancer treatment. This study evaluates the effect of rectal dose/volume variation on the risk of rectal complication for different planning target volume (PTV) constructions. METHODS AND MATERIALS: Thirty prostate patients with multiple daily CT scans obtained during the treatment course were included in this retrospective study. The dose distribution was calculated based on the pretreatment CT image alone. Treatment plans were generated by applying the four-field-box beam arrangement to each of three different PTVs: PTVs with 0.5-cm and 1.0-cm uniform margins, and a patient-specific PTV constructed using treatment imaging feedback. For each of the 30 patients, the rectal wall as manifested on each of multiple CT images was delineated after image bony registration to the pretreatment CT image, and applied to the corresponding treatment plan to obtain the rectal wall dose-volume histogram (DVH). Interpatient and intrapatient rectal dose/volume variations were quantified accordingly. The corresponding uncertainty and sensitivity of the risk of rectal complication to the variations were evaluated for each of the three PTVs. Finally, the efficacy of using multiple CT images to reduce uncertainty in planning evaluation was examined. RESULTS: Sensitivity of the risk of rectal complication to rectal dose/volume variation strongly depends on the clinical target volume (CTV)-to-PTV margin or prescription dose, or both. Compared to the conventional two-dimensional (2D) prostate cancer treatment, the sensitivity for a conformal treatment can be 3 times higher or more. Due to the interpatient rectal dose/volume variation, the individual normal tissue complication probability (NTCP) was distributed from 10% to 37% when a common prescription dose was applied for all patients. The intrapatient rectal dose/volume variation introduces at least +/- 25% uncertainty in the NTCP calculation for at least 10% or 25% of the patients treated with the PTV of 1.0- or 0.5-cm margin, respectively. These uncertainties were larger for the smaller PTV, with the standard deviation up to 20%. By applying multiple CT image feedback, the NTCP uncertainty could be reduced by a factor of 2. CONCLUSIONS: Shape and position variation of rectum has less influence on treatment planning in the conventional 2D treatment of prostate cancer. However, this influence is quickly growing with high treatment dose or small CTV-to-PTV margins. To reduce the variation and uncertainties in the treatment planning evaluation associated with the inter- and intrapatient rectal dose/volume variation, the iso-NTCP model and treatment image feedback technique can be applied in dose escalation trials of prostate cancer treatment.

Algorithms↗

PubMed2001

Improvement in dose escalation using the process of adaptive radiotherapy combined with three-dimensional conformal or intensity-modulated beams for prostate cancer.

PURPOSE: Advances in technology allow the creation of complex treatment plans with tightly conforming doses. However, variations in positioning of the organ/patient with respect to treatment beams necessitate the use of an appreciable margin, potentially limiting dose escalation in many patients. To (1) reduce this margin and (2) test the hypothesis that the achievable level of dose escalation is patient dependent, a patient-specific, confidence-limited planning target volume (cl-PTV) was constructed using an adaptive radiotherapy (ART) process for prostate cancer treatment developed in-house. The potential dose escalation achievable with this ART process is quantified for both conformal radiotherapy (CRT) delivery and intensity-modulated radiotherapy (IMRT) delivery. MATERIAL AND METHODS: Patients with organ confined prostate cancer were entered prospectively into an ART process developed in-house. This ART process has been designed to improve accuracy and precision of dose delivery, consequently enhancing dose escalation. In this process, a cl-PTV is constructed for each patient in the second week of treatment based upon on-line portal and CT images acquired during the first week of treatment. The treatment prescription dose, defined as the minimum dose to the cl-PTV, is selected based on predefined dose-volume constraints for rectum/bladder and derived from the pretreatment planning CT image. In addition, the treatment modality (CRT or IMRT) is determined based on the level of dose escalation achievable and the risk of inaccurate targeting. The potential for both dose escalation and the application of IMRT was evaluated by comparing the prescription doses delivered using the ART process, with the cl-PTV, to those in the traditional treatment process, with a conventional generic PTV. In addition, the distributions of potential geometric target underdosing and normal tissue overdosing were also calculated to evaluate the quality of the conventional treatment plans. RESULTS: One hundred and fifty patients have been treated with the ART process. When compared to the treatment dose delivered with the conventional treatment process (generic PTV), an average 5% (2.5--10%) more dose could be delivered using the ART process with CRT, and 7.5% (2.5--15%) more dose could be delivered with IMRT. Of the 150 patients, 70% were treated to a minimum cl-PTV dose > or = 77.4 Gy (81.3 Gy ICRU isocenter dose). Dosimetric analysis revealed that 81 Gy to the cl-PTV (or 86.7 Gy ICRU) could be prescribed to at least 50% of patients if IMRT was applied using the ART process. In contrast, IMRT did not yield an obvious dose escalation gain if patients were treated using the generic PTV. Our results also demonstrate that the cl-PTV is significantly smaller than the conventional generic PTV for most patients, with a mean volume reduction of 24% (range, 5--43%). CONCLUSION: These results support our hypothesis that the achievable level of dose escalation using ART is patient dependent. By using the ART process to develop a cl-PTV, one can (1) optimize the dose level, (2) increase the applicability of IMRT, and (3) improve the quality of dose delivery. The ART process provides the foundation to identify a suitable option (CRT or IMRT) for the delivery of a safe treatment and dose escalation. It is now our standard of practice for prostate cancer treatment.

Adenocarcinoma↗

PubMed2001

BeF(3)(-) acts as a phosphate analog in proteins phosphorylated on aspartate: structure of a BeF(3)(-) complex with phosphoserine phosphatase.

Protein phosphoaspartate bonds play a variety of roles. In response regulator proteins of two-component signal transduction systems, phosphorylation of an aspartate residue is coupled to a change from an inactive to an active conformation. In phosphatases and mutases of the haloacid dehalogenase (HAD) superfamily, phosphoaspartate serves as an intermediate in phosphotransfer reactions, and in P-type ATPases, also members of the HAD family, it serves in the conversion of chemical energy to ion gradients. In each case, lability of the phosphoaspartate linkage has hampered a detailed study of the phosphorylated form. For response regulators, this difficulty was recently overcome with a phosphate analog, BeF(3)(-), which yields persistent complexes with the active site aspartate of their receiver domains. We now extend the application of this analog to a HAD superfamily member by solving at 1.5-A resolution the x-ray crystal structure of the complex of BeF(3)(-) with phosphoserine phosphatase (PSP) from Methanococcus jannaschii. The structure is comparable to that of a phosphoenzyme intermediate: BeF(3)(-) is bound to Asp-11 with the tetrahedral geometry of a phosphoryl group, is coordinated to Mg(2+), and is bound to residues surrounding the active site that are conserved in the HAD superfamily. Comparison of the active sites of BeF(3)(-) x PSP and BeF(3)(-) x CeY, a receiver domain/response regulator, reveals striking similarities that provide insights into the function not only of PSP but also of P-type ATPases. Our results indicate that use of BeF(3)(-) for structural studies of proteins that form phosphoaspartate linkages will extend well beyond response regulators.

Aspartic Acid↗

PubMed2001

Cell autonomous regulation of multiple Dishevelled-dependent pathways by mammalian Nkd.

Genetic studies have identified Drosophila Naked Cuticle (Nkd) as an antagonist of the canonical Wnt/beta-catenin signaling pathway, but its mechanism of action remains obscure [Zeng, W., Wharton, K. A., Jr., Mack, J. A., Wang, K., Gadbaw, M., et al. (2000) Nature (London) 403, 789--795]. Here we have cloned a cDNA encoding a mammalian homolog of Drosophila Nkd, mNkd, and demonstrated that mNkd interacts directly with Dishevelled. Dishevelled is an intracellular mediator of both the canonical Wnt pathway and planar cell polarity (PCP) pathway. Activation of the c-Jun-N-terminal kinase has been implicated in the PCP pathway. We showed that mNkd acts in a cell-autonomous manner not only to inhibit the canonical Wnt pathway but also to stimulate c-Jun-N-terminal kinase activity. Expression of mNkd disrupted convergent extension in Xenopus, consistent with a role for mNkd in the PCP pathway. These data suggest that mNkd may act as a switch to direct Dishevelled activity toward the PCP pathway, and away from the canonical Wnt pathway.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Crystal structure of activated CheY. Comparison with other activated receiver domains.

The crystal structure of BeF(3)(-)-activated CheY, with manganese in the magnesium binding site, was determined at 2.4-A resolution. BeF(3)(-) bonds to Asp(57), the normal site of phosphorylation, forming a hydrogen bond and salt bridge with Thr(87) and Lys(109), respectively. The six coordination sites for manganese are satisfied by a fluorine of BeF(3)(-), the side chain oxygens of Asp(13) and Asp(57), the carbonyl oxygen of Asn(59), and two water molecules. All of the active site interactions seen for BeF(3)(-)-CheY are also observed in P-Spo0A(r). Thus, BeF(3)(-) activates CheY as well as other receiver domains by mimicking both the tetrahedral geometry and electrostatic potential of a phosphoryl group. The aromatic ring of Tyr(106) is found buried within a hydrophobic pocket formed by beta-strand beta4 and helix H4. The tyrosine side chain is stabilized in this conformation by a hydrogen bond between the hydroxyl group and the backbone carbonyl oxygen of Glu(89). This hydrogen bond appears to stabilize the active conformation of the beta4/H4 loop. Comparison of the backbone coordinates for the active and inactive states of CheY reveals that only modest changes occur upon activation, except in the loops, with the largest changes occurring in the beta4/H4 loop. This region is known to be conformationally flexible in inactive CheY and is part of the surface used by activated CheY for binding its target, FliM. The pattern of activation-induced backbone coordinate changes is similar to that seen in FixJ(r). A common feature in the active sites of BeF(3)(-)-CheY, P-Spo0A(r), P-FixJ(r), and phosphono-CheY is a salt bridge between Lys(109) Nzeta and the phosphate or its equivalent, beryllofluoride. This suggests that, in addition to the concerted movements of Thr(87) and Tyr(106) (Thr-Tyr coupling), formation of the Lys(109)-PO(3)(-) salt bridge is directly involved in the activation of receiver domains generally.

Bacterial Proteins↗

PubMed2001

Attempt to adsorb N-nitrosamines in solution by use of zeolites.

The strong adsorption of zeolite for N-nitrosamines in solution was first revealed by use of adsorption, and temperature programmed surface reaction (TPSR) techniques. N-nitrosodimethylamine (NDMA) and N-nitrosopyrrolidine (NPYR) as well as N-nitrosohexamethyleneimine (NHMI) can be adsorbed on zeolite Y, ZSM-5 and A in the solution of methylene chloride or water, which will be helpful for removal of the N-nitrosamines pollution in environmental protection. The equilibrium data were fitted to Freundlich-type isotherms, but the adsorption capacity of zeolites mainly depended on their pore size, surface area and acid-basic properties. Molecular size of adsorbate and solute-solvent interaction also strongly affected the adsorption of N-nitrosamines on zeolite in solution. The extraordinary adsorption properties of NaA zeolite for N-nitrosamines in aqueous solution is first reported and discussed.

Adsorption↗

PubMed2001

Phosphoaspartates in bacterial signal transduction.

Bacteria use a strategy referred to as two-component signal transduction to sense a variety of stimuli and initiate an appropriate response. Signal processing begins with proteins referred to as histidine kinases. In most cases, these are membrane-bound receptors that respond to environmental cues. Histidine kinases use ATP as a phosphodonor to phosphorylate a conserved histidine residue. Subsequent transfer of the phosphoryl group to a conserved aspartyl residue in the cognate response regulator results in an appropriate output. Recent structural studies of activated (phosphorylated) response regulators and their aspartate-bearing regulatory domains have provided insight into the links between the chemistry and biology of these ubiquitous regulatory proteins. Chemical aspects of their function appear to generalize broadly to enzymes that adopt a phosphoaspartate intermediate.

Aspartic Acid↗

PubMed2001

Crystal structure of an activated response regulator bound to its target.

The chemotactic regulator CheY controls the direction of flagellar rotation in Escherichia coli. We have determined the crystal structure of BeF3--activated CheY from E. coli in complex with an N-terminal peptide derived from its target, FliM. The structure reveals that the first seven residues of the peptide pack against the beta4-H4 loop and helix H4 of CheY in an extended conformation, whereas residues 8-15 form two turns of helix and pack against the H4-beta5-H5 face. The peptide binds the only region of CheY that undergoes noticeable conformational change upon activation and would most likely be sandwiched between activated CheY and the remainder of FliM to reverse the direction of flagellar rotation.

Amino Acid Sequence↗

PubMed2001

A dimeric two-component receiver domain inhibits the sigma54-dependent ATPase in DctD.

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Adenosine Triphosphatases↗

PubMed2001

Organ/patient geometric variation in external beam radiotherapy and its effects.

Treatment variation in positioning of the organ/patient with respect to the radiation beams causes a temporal dose variation in critical normal tissues adjacent to the treatment target. This temporal variation induces uncertainties in understanding the normal tissue dose response, thereby limiting reliable treatment evaluation and optimization. The aim of this study is to model and analyze the temporal variation of organ dose distribution, and its effect on the biological effective dose. The study mainly focuses on the temporal dose variation caused by intertreatment organ motion/ deformation and daily setup error. Sensitivity of the biological effective dose to organ/patient geometric variation, dose distribution, and treatment fractionation will be investigated. Significant deviation of the biological effective dose could be expected in a critical normal structure, even if the cumulative dose deviation in this structure is negligible. Patients with similar geometric variation characteristics can experience significantly different biological effective dose, and the differences are sensitive to the dose distribution and the total number of treatment fractions.

Humans↗

PubMed2001

Implementing multiple static field delivery for intensity modulated beams.

A clinically oriented two-dimensional intensity-modulated beam delivery method is implemented using multiple static segmented fields, i.e., the "step-and-shoot" approach. Starting with a desired al" intensity distribution, it creates a multiple-level intensity approximation, and then constructs a sequence of segmented fields to deliver the multiple-level intensities using multileaf collimator (MLC) and independent backup jaws. The approach starts with a simple grouping of all the nonzero intensity values into a minimum number of clusters for a user specified deviation tolerance for the ideal plan. The k-means clustering algorithm is then employed to find the optimal levels of intensity that minimize the discrepancies between the ideal and the approximated intensities, without violating the user specified deviation tolerance. The multiple-level intensities are then decomposed into a sequence of machine deliverable segments. Apart from the first segment for each gantry angle, all the other segments are arranged to minimize the total travel distance of the leaves. The first segment covers the entire irradiated area and is used for treatment verification by electronic portal imaging. The implementation issues due to the physical constraints of the MLCs are also addressed.

Algorithms↗

PubMed2001

[Experimental studies on muscle fatigue of human limb motion with FNS].

The basic characteristic of the functional neuromuscular stimulation signals suitable to body is preliminarily determined after the fatigue performance of the biceps, and the physiological reaction to stimulation is investigated using many continuous stimulation signal patterns. The flexion motion of the elbow joint (right hand) of a healthy man was taken as our research objective. The surface electrodes were connected to the biceps and a micro angle sensor was mounted on the elbow joint (right hand). The curves of angular displacement for the elbow joint motion were obtained by using functional neuromuscular stimulation (FNS) limbs motion measurement instruments. The results demonstrate that the biceps are characterized by the non-linear and time-variant no matter what the stimulation patterns are, that continuous slow stimulation signals can reduce the muscle fatigue of the biceps, and that the stimulation frequencies ranging from 30 Hz to 50 Hz are applicable to the neuromuscular system.

Adult↗

PubMed2001

[Purification of conjugated bilirubin from human urine].

OBJECTIVES: To develop a simple, practical method with fine yield and purity for separating conjugated bilirubin(Bc) from a sustainable and facile material in order that it could serve as a calibrator for total and direct bilirubin determination. METHODS: Isolating Bc from urine of patients with obstructive jaundice by CHCl3: CH3CH2OH(1:1, V/V) followed by CNBr activated Sepharose 4B-HAS affinity chromatography, we analyzed the products by the use of Doumas J-G diazo method and HPLC, respectively. RESULTS: Determined by J-G diazo method, the crude product extracted by CHCl3: CH3CH2OH(1:1, V/V) yields 90.2 +/- 5.4%(n = 3) of urine Bc, the ratio of Bc to total dry weight being 67.9 +/- 6.4%(n = 3). The final product purified by affinity chromatography with the ratio of separation of 1.5, 1.737 and analyzed by HPLC has the yield of 46.9% and purity of 94.7%(BDG of 76.2%, BMG of 18.5%). CONCLUSION: The above data demonstrate that urine conjugated bilirubin can be successfully purified by CHCl3: CH3CH2OH extraction followed by Sephrose-HSA affinity chromatography with sufficient purity and output.

Bilirubin↗

PubMed2000

Intensity modulation to improve dose uniformity with tangential breast radiotherapy: initial clinical experience.

PURPOSE: We present a new technique to improve dose uniformity and potentially reduce acute toxicity with tangential whole-breast radiotherapy (RT) using intensity-modulated radiation therapy (IMRT). The technique of multiple static multileaf collimator (sMLC) segments was used to facilitate IMRT. METHODS AND MATERIALS: Ten patients with early-stage breast cancer underwent treatment planning for whole-breast RT using a new method of IMRT. The three-dimensional (3D) dose distribution was first calculated for equally weighted, open tangential fields (i.e., no blocks, no wedges). Dose calculation was corrected for density effects with the pencil-beam superposition algorithm. Separate MLC segments were constructed to conform to the beam's-eye-view projections of the 3D isodose surfaces in 5% increments, ranging from the 120% to 100% isodose surface. Medial and lateral MLC segments that conformed to the lung tissue in the fields were added to reduce transmission. Using the beam-weight optimization utility of the 3D treatment planning system, the sMLC segment weights were then determined to deliver the most uniform dose to 100 reference points that were uniformly distributed throughout the breast. The accuracy of the dose calculation and resultant IMRT delivery was verified with film dosimetry performed on an anthropomorphic phantom. For each patient, the dosimetric uniformity within the breast tissue was evaluated for IMRT and two other treatment techniques. The first technique modeled conventional practice where wedges were derived manually without consideration of inhomogeneity effects (or density correction). A recalculation was performed with density correction to represent the actual dose delivered. In the second technique, the wedges were optimized using the same beam-weight optimization utility as the IMRT plan and included density correction. All dose calculations were based on the pencil-beam superposition algorithm. RESULTS: For the sMLC technique, treatment planning required approximately 60 min. Treatment delivery (including patient setup) required approximately 8-10 min. Film dosimetry measurements performed on an anthropomorphic phantom generally agreed with calculations to within +/- 3%. Compared to the wedge techniques, IMRT with sMLC segments resulted in smaller "hot spots" and a lower maximum dose, while maintaining similar coverage of the treatment volume. A median of only 0.1% of the treatment volume received > or = 110% of the prescribed dose when using IMRT versus 10% with standard wedges. A total of 6-8 segments were required with the majority of the dose delivered via the open segments. The addition of the lung-block segments to IMRT was of significant benefit for patients with a greater proportion of lung parenchyma within the irradiated volume. Since August 1999, 32 patients have been treated in the clinic with the IMRT technique. No patient experienced RTOG grade III or greater acute skin toxicity. CONCLUSION: The use of intensity modulation with an sMLC technique for tangential breast RT is an efficient and effective method for achieving uniform dose throughout the breast. It is dosimetrically superior to the treatment techniques that employ only wedges. Preliminary findings reveal minimal or no acute skin reactions for patients with various breast sizes.

Breast Neoplasms↗