Biomedical subjects

Xiaochun Wang

Publications and source records attributed to Xiaochun Wang.

At least 19 recordsLinked to original sources

PubMed2026

Discovery and evolution of endogenous retroviruses in the genome of crab-eating macaque (Macaca fascicularis).

Endogenous retroviruses (ERVs) are a dynamic and biologically significant component of vertebrate genomes, with integration events spanning deep evolutionary time. The crab-eating macaque (Macaca fascicularis) is an important non-human primate model for biomedical research because of its close phylogenetic relationship to humans and its conservation status as an endangered species. However, the ERV complement of its genome has not been systematically characterized. Using the current highest-quality chromosome-level genome assembly for this species, we performed a genome-wide, homology-based survey of relatively intact ERV proviruses in M. fascicularis. We identified 106 proviral loci distributed across all chromosomes. Phylogenetic reconstruction based on conserved reverse transcriptase domains classified these elements into β-, γ-, and unclassified lineages, with β- and γ-retroviral lineages predominating. LTR divergence-based dating indicated that these proviruses represent multiple waves of historical retroviral activity and span a broad range of integration ages. This curated dataset provides a high-confidence reference set for investigating the evolutionary history and genomic impact of preserved ERV proviruses in an endangered primate model; however, it does not include degraded ERV fragments or solo LTRs.

Animals↗

PubMed2006

Dosimetric verification for intensity-modulated radiotherapy of thoracic cancers using experimental and Monte Carlo approaches.

PURPOSE: To investigate the dosimetric accuracy of commercial treatment planning systems used in intensity-modulated radiotherapy (IMRT) for thoracic cancer. METHODS AND MATERIALS: Clinical IMRT plans for lung and esophageal cancers and mesothelioma were used to investigate the accuracy of dose calculations from two commercial treatment planning systems (Pinnacle and Corvus systems). Dose distributions were measured with ion chambers and thermoluminescent dosimeters for individual IMRT fields and composite treatment plans in water phantoms and anthropomorphic phantoms. A Monte Carlo-based system was established to compute three-dimensional dose distributions to compare with the treatment planning system calculations. RESULTS: Dose calculations from the Pinnacle system were acceptable within 5% of the local dose or a 5-mm distance-to-agreement for 80% of the points measured with ion chambers, 74% of the points measured with thermoluminescent dosimeters, and 96% of the points compared with the Monte Carlo calculations. For the Corvus system, 89% of the points agreed with the measured dose and 98% agreed with the Monte Carlo calculations. Underestimation of the dose from the treatment planning system was found in the low-dose regions (<50% of the prescribed dose), possibly caused by inadequate modeling of the multileaf collimators. CONCLUSION: The Pinnacle and Corvus dose calculations were acceptable for thoracic IMRT in high-dose regions. Beam modeling is likely the most critical factor for the accuracy of IMRT dose calculations.

Algorithms↗

PubMed2006

Expression and characterization of RNA-dependent RNA polymerase of Dendrolimus punctatus tetravirus.

Dendrolimus punctatus tetravirus (DpTV) has been identified as a new member of the genus Omegatetravirus of the family Tetraviridae that may be related serologically to Nudaurelia capensis virus (NomegaV). To establish the function of DpTV RNA genome and to better understand the mechanism of viral replication, the putative RNA-dependent RNA polymerase (RdRp) domain has been cloned and expressed in Escherichia coli. The recombinant protein was purified on a Ni-chelating HisTrap affinity column and demonstrated to initiate viral RNA synthesis in a primer-independent manner but not by terminal nucleotidyle transferase activity in the presence of Mg2+ and RNA template. Mutation of the GDD to GAA interferes with the residues at the polymerase active site and metal ions, and thus renders the polymerase inactive.

Amino Acid Sequence↗

PubMed2006

Rapid separation and determination of structurally related anthraquinones in Rhubarb by pressurized capillary electrochromatography.

A pressurized capillary electrochromatography (pCEC) with monolithic column has been developed for the rapid separation and determination of five structurally related anthraquinones in Rhubarb. The possibility of rapid separation resulted from the unique pore structure with high permeability and favorable mass transfer characteristics of the monolithic stationary phase. The effect factors such as organic modifier, acidity and concentration of running buffer, separation voltage were investigated to acquire the optimum condition. In the 220 nm wavelengths, the five anthraquinones could be baseline-separated rapidly within 5 min with the separation voltage of -20 kV in 10 mmol/L phosphate buffer (pH 6.2) containing 65% acetonitrile. The calibration graphs of rhein, aloe-emodin, emodin chrysophanol and physcion were linear by plotting the peak area against the analytes concentration over the range of 0.2-65, 0.1-30, 0.1-55, 0.5-30 and 0.5-55 microg/mL, respectively. The detection limits of five anthraquinones were ranged from 0.06 to 0.2 microg/mL and the recoveries of Rhubarb samples were about 81.3-86.4% (R.S.D.< or = 5.2%). This proposed method was successfully applied to determination of the five analytes in Rhubarb with satisfactory results.

Anthraquinones↗

PubMed2006

Isolation and RNA1 nucleotide sequence determination of a new insect nodavirus from Pieris rapae larvae in Wuhan city, China.

A new insect nodavirus is isolated from Pieris rapae larvae in Wuhan city, China and tentatively designated Wuhan nodavirus (WhNV). We here report the physicochemical characterization of WhNV and determine the nucleotide sequences of its larger segment of genome, RNA1. The results show that WhNV particles are isometric, non-enveloped, with a diameter of about 29nm. The virus has a major capsid protein and a minor capsid protein with estimated molecular mass of 40 and 44kDa, respectively. WhNV RNA1 is determined to be 3149nt long, containing a 1014-amino-acid open reading frame (ORF) encoding protein A with a calculated molecular mass of 114,608Da. The protein A shows 39 and 27% identity to its homologues in Pariacoto virus (PaV) and Striped jack necrosis nervous virus (SJNNV), respectively, but shows only 24% or less identity to its homologues in other insect Nodaviruses such as Nodamura virus (NoV), Black beetle virus (BBV), Boolarra virus (BoV) and Flock house virus (FHV). Predicted domains for six RNA-dependent RNA polymerase motifs and putative ORFs (protein B) are confirmed by sequence analysis of WhNV RNA1.

Amino Acid Sequence↗

PubMed2006

Beam angle optimization and reduction for intensity-modulated radiation therapy of non-small-cell lung cancers.

PURPOSE: To optimize beam angles and reduce the number of beams used for intensity-modulated radiation therapy (IMRT) of non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: An exhaustive search scheme was used to perform beam angle optimization (BAO) for IMRT of NSCLC. This approach involved intercomparison of all possible beam angle combinations and selection of the best angles based on the scores or costs of the objective functions used in the treatment plan optimization. Ten Stage III NSCLC cases were selected to evaluate the BAO algorithm and dosimetry benefits of IMRT-BAO. IMRT plans using five or seven coplanar beams were optimized and compared with those using nine equal-spaced beams. Results of BAO were also compared between plans using different numbers of beams with or without fluence modulation. RESULTS: Each anatomic structure, e.g., tumor or lung, had its own preferred beam angles. Thus, BAO required appropriate balance of competing objective functions. Plans using fewer angles (five or seven beams) could achieve plan quality similar to those using nine equal-spaced beams, however with reduced monitor units and field segments. The number of beams used for the treatment (five vs. seven) and the fluence modulation (open or IMRT beams) did not have a significant impact on the results of the BAO. CONCLUSIONS: Use of fewer beams (e.g., five) for lung IMRT could result in acceptable plan quality but improved treatment efficiency. A multiresolution search scheme could be developed for BAO using fewer and nonmodulated beams to reduce the computation cost of BAO.

Algorithms↗

PubMed2006

Significant reduction of normal tissue dose by proton radiotherapy compared with three-dimensional conformal or intensity-modulated radiation therapy in Stage I or Stage III non-small-cell lung cancer.

PURPOSE: To compare dose-volume histograms (DVH) in patients with non-small-cell lung cancer (NSCLC) treated by photon or proton radiotherapy. METHODS AND MATERIALS: Dose-volume histograms were compared between photon, including three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), and proton plans at doses of 66 Gy, 87.5 Gy in Stage I (n=10) and 60-63 Gy, and 74 Gy in Stage III (n=15). RESULTS: For Stage I, the mean total lung V5, V10, and V20 were 31.8%, 24.6%, and 15.8%, respectively, for photon 3D-CRT with 66 Gy, whereas they were 13.4%, 12.3%, and 10.9%, respectively, with proton with dose escalation to 87.5 cobalt Gray equivalents (CGE) (p=0.002). For Stage III, the mean total lung V5, V10, and V20 were 54.1%, 46.9%, and 34.8%, respectively, for photon 3D-CRT with 63 Gy, whereas they were 39.7%, 36.6%, and 31.6%, respectively, for proton with dose escalation to 74 CGE (p=0.002). In all cases, the doses to lung, spinal cord, heart, esophagus, and integral dose were lower with proton therapy even compared with IMRT. CONCLUSIONS: Proton treatment appears to reduce dose to normal tissues significantly, even with dose escalation, compared with standard-dose photon therapy, either 3D-CRT or IMRT.

Carcinoma, Non-Small-Cell Lung↗

PubMed2006

The optimization of dose delivery for intraoperative high-dose-rate radiation therapy using curved HAM applicators.

BACKGROUND AND PURPOSE: To determine the effect of the curvature of Harrison-Anderson-Mick applicators on the dose distribution in high-dose-rate intraoperative radiation therapy (HDR-IORT). MATERIAL AND METHODS: Treatment planning was performed with flat applicators using (192)Ir as the radioactive source, and dwell times were optimized using dose-point optimization techniques. These optimized dwell times were then used for the curved applicators, and the dose distributions that would actually be delivered to patients were determined. RESULTS: The dose directly below the central catheter was strongly dependent on the curvature of the applicator. Steep parabolic curves caused underdoses of as much as 19% at a point 1cm from the convex side of the applicator. The rate of dose reduction with increasing distance from the applicator surface was also a function of the curvature of the applicator. CONCLUSIONS: The curvature of the applicator profoundly affects dosimetry and can be exploited to optimize coverage of the target during HDR-IORT procedures. To ensure accurate dose delivery, these dose perturbations must be accounted for in the planning process. We recommend maintaining a dosimetry atlas of various applicator sizes and curvatures in addition to one for flat applicators.

Brachytherapy↗

PubMed2006

Study on pharmacokinetics and tissue distribution of norvancomycin in rats by CE with electrochemical detection.

In this paper, we developed a sensitive and simple method to study the pharmacokinetics and tissue distribution of norvancomycin (NVCM) in experimental animals by using CE with electrochemical detection. Pharmacokinetics investigation was performed by the collection of blood samples at timed intervals following administration of NVCM. Pharmacokinetic parameters were calculated by the 3P87 pharmacokinetic program. The elimination half-life of NVCM was 42.4742 min with a clearance rate of 0.0233 mL x kg(-1) x min(-1). Additionally, drug distribution was studied by measuring the NVCM levels in kidney, lung, stomach, intestine, spleen, heart, liver, and cerebrum. Electrophoresis conditions such as buffer solution, working potential, separation voltage, and sampling time were also discussed. The linear range was from 0.8 to 540 microg/mL with a correlation coefficient of 0.9991. The detection limit was 0.3 microg/mL. This method was for the first time applied to study the pharmacokinetics and tissue distributions of NVCM in experimental animals.

Animals↗

PubMed2006

In vitro and in vivo identification of structural and sequence elements in the 5' untranslated region of Ectropis obliqua picorna-like virus required for internal initiation.

Ectropis obliqua picorna-like virus (EoPV) is a newly described insect virus that is classified as a putative member of the genus Iflavirus. The virus possesses a large, positive-sense RNA genome encoding a single polyprotein that shares physicochemical properties with those of members of the family Picornaviridae. The 5' untranslated region (5' UTR) plays an important role in picornavirus translation initiation, as it contains an internal ribosome entry site (IRES) that mediates cap-independent translation. To investigate translation in EoPV, an extensive range of mutations were engineered within the 5' UTR and the effects of these changes were examined in vitro and in vivo by using a bicistronic construct. Results showed that deletions within the first 63 nt had little impact on IRES activity, whilst core IRES function was contained within stem-loops C and D, as their removal abrogated IRES activity significantly. In contrast to these findings, removal of stem-loop G containing two cryptic AUGs caused a remarkable increase in IRES activity, which was further investigated by site-directed mutagenesis at these two positions. It was also confirmed that initiation of protein synthesis occurs at AUG6 (position 391-394) and not at the AUG immediately downstream of the polypyrimidine tract. Mutation of the polypyrimidine tract (CCTTTC) had a slight effect on EoPV IRES activity. Furthermore, mutations of the RAAA motif led to a decrease in IRES activity of approximately 40 % in vitro, but these results were not supported by in vivo experiments. In conclusion, this study reveals that the EoPV IRES element is unique, although it has features in common with the type II IRESs.

5' Untranslated Regions↗

PubMed2006

A sensitivity-guided algorithm for automated determination of IMRT objective function parameters.

Optimizing intensity-modulated radiotherapy (IMRT) plans involves tradeoffs that balance normal-tissue objectives against each other and against tumor objectives. Adjusting the parameters that determine the appropriate contributions of individual anatomic structures to the objective functions through trial and error is time consuming and may not produce the best achievable plans. We have developed a sensitivity-guided parameter optimization (SGPO) method to assist in the automatic determination of parameters to drive the IMRT optimization to better achieve, or even exceed, specified planning goals. The method is based on the trade-off relationships among multiple objectives: In a globally optimal plan (or within a convex subspace of the plan objectives), any attempt to improve the achievement of goals for a structure will result in sacrificing the goals for at least one other structure. However, different objectives may have different sensitivities to the overall goal of an IMRT plan. For instance, changes in dose distribution, hence the subscore corresponding to an objective for a given normal structure, may minimally impact the target dose distribution. Stated differently, the target coverage is insensitive to the changes in dose distribution of the specific normal structure. A lung cancer treatment plan designed with the SGPO method was used to demonstrate that IMRT plans could be designed to favor a structure with the highest target sensitivity and spare the structures with the least target sensitivity without compromising the target coverage. Using one case each of prostate and paranasal sinus cancers, we also demonstrated that several alternative optimal solutions could be designed with the SGPO algorithm favoring different structures. Finally, we applied the method to eight oropharyngeal cancer cases to obtain objective function parameters that satisfied the Radiation Therapy Oncology Group RTOG-H-0022 protocol. The eight plans optimized using the computer-generated objective function parameters met the protocol's scoring criteria with no or only minor protocol violations. Our preliminary study indicates that the SGPO method may be an effective and practical way to improve IMRT planning.

Artificial Intelligence↗

PubMed2006

[Synthetic and photo-immobilization of photo-active tumor necrosis factor-alpha].

Tumor Necrosis Factor is one of the cell factors with much stronger anti-tumor activity. In this study, photoactive arylazide-4-azidobenzoic acid was modified to Tumor Necrosis Factor-alpha (TNF-alpha). The IR data (2127cm(-1)) was given to confirm the modification. By photo-immobilization, this modified TNF-a was immobilized on cell culture polystyrene. Both the relation between the amount of TNF-alpha in feed and immobilized TNF-alpha and the influence of different UV irradiation time on photo-immobilization are discussed. Microscopic observations of the photo-immobilization TNF-alpha were made by use of scanning electrom microscope and atomic force microscope.

Female↗

PubMed2005

Feasibility of using intensity-modulated radiotherapy to improve lung sparing in treatment planning for distal esophageal cancer.

BACKGROUND AND PURPOSE: To evaluate the feasibility whether intensity-modulated radiotherapy (IMRT) can be used to reduce doses to normal lung than three-dimensional conformal radiotherapy (3 DCRT) in treating distal esophageal malignancies. PATIENTS AND METHODS: Ten patient cases with cancer of the distal esophagus were selected for a retrospective treatment-planning study. IMRT plans using four, seven, and nine beams (4B, 7B, and 9B) were developed for each patient and compared with the 3 DCRT plan used clinically. IMRT and 3 DCRT plans were evaluated with respect to PTV coverage and dose-volumes to irradiated normal structures, with statistical comparison made between the two types of plans using the Wilcoxon matched-pair signed-rank test. RESULTS: IMRT plans (4B, 7B, 9B) reduced total lung volume treated above 10 Gy (V(10)), 20 Gy (V(20)), mean lung dose (MLD), biological effective volume (V(eff)), and lung integral dose (P<0.05). The median absolute improvement with IMRT over 3DCRT was approximately 10% for V(10), 5% for V(20), and 2.5 Gy for MLD. IMRT improved the PTV heterogeneity (P<0.05), yet conformity was better with 7B-9B IMRT plans. No clinically meaningful differences were observed with respect to the irradiated volumes of spinal cord, heart, liver, or total body integral doses. CONCLUSIONS: Dose-volume of exposed normal lung can be reduced with IMRT, though clinical investigations are warranted to assess IMRT treatment outcome of esophagus cancers.

Dose-Response Relationship, Radiation↗

PubMed2005

Effectiveness of noncoplanar IMRT planning using a parallelized multiresolution beam angle optimization method for paranasal sinus carcinoma.

PURPOSE: To determine the effectiveness of noncoplanar beam configurations and the benefit of plans using fewer but optimally placed beams designed by a parallelized multiple-resolution beam angle optimization (PMBAO) approach. METHODS AND MATERIALS: The PMBAO approach uses a combination of coplanar and noncoplanar beam configurations for intensity-modulated radiation therapy (IMRT) treatment planning of paranasal sinus cancers. A smaller number of beams (e.g. 3) are first used to explore the solution space to determine the best and worst beam directions. The results of this exploration are then used as a starting point for determining an optimum beam orientation configuration with more beams (e.g. 5). This process is parallelized using a message passing interface, which greatly reduces the overall computation time for routine clinical practice. To test this approach, treatment for 10 patients with paranasal sinus cancer was planned using a total of 5 beams from a pool of 46 possible beam angles. The PMBAO treatment plans were also compared with IMRT plans designed using 9 equally spaced coplanar beams, which is the standard approach in our clinic. Plans with these two different beam configurations were compared with respect to dose conformity, dose heterogeneity, dose-volume histograms, and doses to organs at risk (i.e., eyes, optic nerve, optic chiasm, and brain). RESULTS: The noncoplanar beam configuration was superior in most paranasal sinus carcinoma cases. The target dose homogeneity was better using a PMBAO 5-beam configuration. However, the dose conformity using PMBAO was not improved and was case dependent. Compared with the 9-beam configuration, the PMBAO configuration significantly reduced the mean dose to the eyes and optic nerves and the maximum dose to the contralateral optical path (e.g. the contralateral eye and optic nerve). The maximum dose to the ipsilateral eye and optic nerve was also lower using the PMBAO configuration than using the 9-beam configuration, although this difference was not significant. The mean doses to the optic chiasm and brain are marginally lower using the PMBAO configuration than using 9-beam configuration. The maximum doses to the optic chiasm and brain are the same with the PMBAO configuration and the 9-beam configuration. CONCLUSION: Parallelized multiple-resolution beam angle optimization with an optimized noncoplanar beam configuration is an effective and practical approach for IMRT treatment planning. Five-beam treatment plans optimized using the PMBAO are at least equivalent to, and overall better than, the plans using 9 equally spaced coplanar beams.

Humans↗

PubMed2005

Use of deformed intensity distributions for on-line modification of image-guided IMRT to account for interfractional anatomic changes.

PURPOSE: Recent imaging studies have demonstrated that there can be significant changes in anatomy from day to day and over the course of radiotherapy as a result of daily positioning uncertainties and physiologic and clinical factors. There are a number of strategies to minimize such changes, reduce their impact, or correct for them. Measures to date have included improved immobilization of external and internal anatomy or adjustment of positions based on portal or ultrasound images. Perhaps the most accurate way is to use CT image-guided radiotherapy, for which the possibilities range from simple correction of setup based on daily CT images to on-line near real-time intensity modulated radiotherapy (IMRT) replanning. In addition, there are numerous intermediate possibilities. In this paper, we report the development of one such intermediate method that takes into account anatomic changes by deforming the intensity distributions of each beam based on deformations of anatomy as seen in the beam's-eye-view. METHODS AND MATERIALS: The intensity distribution deformations are computed based on anatomy deformations discerned from the changes in the current image relative to a reference image (e.g., the pretreatment CT scan). First, a reference IMRT plan is generated based on the reference CT image. A new CT image is acquired using an in-room CT for every fraction. The anatomic structure contours are obtained for the new image. (For this article, these contours were manually drawn. When image guided IMRT methods are implemented, anatomic structure contours on subsequent images will likely be obtained with automatic or semiautomatic means. This could be achieved by, for example, first deforming the original CT image to match today's image, and then using the same deformation transformation to map original contours to today's image.) The reference intensity distributions for each beam are then deformed so that the projected geometric relationship within the beam's-eye-view between the anatomy (both target and normal tissues) extracted from the reference image and the reference intensity distribution is the same as (or as close as possible to) the corresponding relationship between anatomy derived from today's image and the newly deformed intensity distributions. To verify whether the dose distributions calculated using the deformed intensity distributions are acceptable for treatment as compared to the original intensity distributions, the deformed intensities are transformed into leaf sequences, which are then used to compute intensity and dose distributions expected to be delivered. The corresponding dose-volume histograms and dose-volume and dose-response indices are also computed. These data are compared with the corresponding data derived (a) from the original treatment plan applied to the original image, (b) from the original treatment plan applied to today's image, and (c) from a new full-fledged IMRT plan designed based on today's image. RESULTS: Depending on the degree of anatomic changes, the use of an IMRT plan designed based on the original planning CT for the treatment of the current fraction could lead to significant differences compared to the intended dose distributions. CT-guided setup compared to the setup based on skin marks or bony landmarks may improve dose distributions somewhat. Replanning IMRT based on the current fraction's image yields the best physically deliverable plan (the "gold standard"). For the prostate and head-and-neck examples studied as proof of principle, the results of deforming intensities within each beam based on the anatomy seen in the beam's-eye-view are a good approximation of full-fledged replanning compared with other alternatives. CONCLUSIONS: Our preliminary results encourage us to believe that deforming intensities taking into account deformation in the anatomy may be a rapid way to produce new treatment plans on-line in near real-time based on daily CT images. The methods we have developed need to be applied to a group of patients for both prostate and head-and-neck cases to confirm the validity of our approach.

Algorithms↗

PubMed2004

Development of methods for beam angle optimization for IMRT using an accelerated exhaustive search strategy.

PURPOSE: The purpose of this article is to explore the use of the accelerated exhaustive search strategy for developing and validating methods for optimizing beam orientations for intensity-modulated radiation therapy (IMRT). Combining beam-angle optimization (BAO) with intensity distribution optimization is expected to improve the quality of IMRT treatment plans. However, BAO is one of the most difficult problems to solve adequately because of the huge hyperspace of possible beam configurations (e.g., selecting 7 of 36 uniformly spaced coplanar beams would require the intercomparison of 8,347,680 IMRT plans). METHODS AND MATERIALS: An "influence vector" (IV) approximation technique for high-speed estimation of IMRT dose distributions was used in combination with a fast gradient search algorithm (Newton's method) for IMRT optimization. In the IV approximation, it is assumed that the change in intensity of a ray (or bixel) proportionately changes dose along the ray. Evidence is presented that the IV approximation is valid for BAO. The scatter contribution at points away from the ray is accounted for fully in IMRT optimization after the optimum beam orientation has been determined. IVs for all candidate beam angles are generated before the start of optimization. For all subsets of beams selected from a given pool of beams (e.g., 5 of 24 uniformly spaced beams), the distribution of planning scores for the best and the worst plans, optimum angle distributions, dose distributions, and dose-volume histograms (DVH) were analyzed for one prostate and two lung cancer cases. The results of the exhaustive search technique were used to develop a "multiresolution" search strategy. In this approach, a smaller number of beams (e.g., three) is first used to explore the hyperspace of solutions to determine the most preferred and the least preferred directions. The results of such exploration are then used as a starting point for determining an optimum configuration comprising a larger number of beams (e.g., seven). This two-step process is considerably faster than full exhaustive search. The question to be answered was whether the two methods lead to the same or similar solutions. The results of exhaustive search and multiresolution approaches were also compared with a previously published approach that used beam's-eye-view dosimetrics (BEVD). RESULTS: The relative ranks of plans optimized by an accurate dose calculation method were highly correlated with those of the plans optimized by the fast calculation method (i.e., using the IV approximation), which suggests that an approximate dose calculation algorithm can be used effectively for ranking of plans during BAO. We found that dose distributions and DVH of many beam configurations within a specified subset from a given pool of beams (e.g., 5 of 18) may be clinically indistinguishable and acceptable. Their optimized IMRT scores fall in a narrow range, although beam configurations and dose distributions may be different. We used the frequency distributions as a function of beam angles for the best 100 and the worst 100 plans to determine the most and the least preferred beam angles. We found that the most and the least preferred angle distributions for 3 of 18 configurations were very similar to those for 5, 6, 7, or 8 of 18 or 24 configurations, but the size of the search space was much smaller for the 3 of 18 case. Using fewer than three beams was discovered to be inadequate. This information was used to select the most preferred angles and eliminate the least preferred ones before searching for the optimum angles for the remaining beams. For the cases we studies, the multiresolution strategy produced very similar results to the full exhaustive search. Based on the observation that the worst plans had at least one parallel-opposed pair of beams and virtually all of the best plans had none, we were able to further reduce the size of the search space dramatically by using a pool of only nonparallel-opposed equispaced beams (i.e., 7 of 19 instead of 7 of 36). Another observation was that the probability of finding an optimum configuration in a smaller beam pool is substantially lower than in a larger pool (e.g., 5 of 18 vs. 5 of 24). The implication of this BAO is not very important when a large number of beams (nine or more) is used and vice versa. Our results showed that the plans with fewer but optimally placed beams could be as good as or better than plans using a larger number of unoptimized or uniformly placed beams. CONCLUSION: Exhaustive search with fast IMRT algorithms provides a novel and realistic approach to study the characteristics of IMRT dose distributions as a function of beam angles and to design practical BAO strategies for IMRT planning.

Algorithms↗

PubMed2004

Feasibility of sparing lung and other thoracic structures with intensity-modulated radiotherapy for non-small-cell lung cancer.

PURPOSE: To investigate the possibility of using intensity-modulated radiotherapy (IMRT) to reduce the irradiated volumes of the normal lung and other critical structures in the treatment of non-small-cell lung cancer (NSCLC) and to investigate the effect of IMRT on the potential of spreading low doses to large volumes of normal tissues in such treatment. METHODS AND MATERIALS: A retrospective treatment planning study was performed to compare IMRT and conventional three-dimensional conformal radiation therapy (3D-CRT) for 10 NSCLC patients (Stage I-IIIB). In the IMRT plans, three to nine coplanar beams were designed to treat 95% of the planning target volume with 63 Gy and to minimize the volumes of the normal lung, esophagus, heart, and spinal cord irradiated above their tolerance doses. The two types of plans were compared with respect to the planning target volume coverage, dose-volume histograms, and other dosimetric indexes of the normal structures. RESULTS: Comparing the nine-beam IMRT plan with the 3D-CRT plan, the percentage of lung volume that received >20 Gy and the mean lung dose were reduced for all cases, with a median reduction of 8% and 2 Gy, respectively. An additional reduction of the >5-Gy volume and >10-Gy volume for the lung and thoracic tissue was more difficult with IMRT, although still possible using fewer beams in IMRT. The integral dose to the entire thorax was equivalent and even reduced for 8 of 10 cases using IMRT. CONCLUSION: It is possible to reduce the volumes of low doses (such as the >10-Gy volume and >20-Gy volume) for thoracic normal tissues using IMRT. The increased integral dose and low-dose volumes can be avoided for IMRT if such concerns are addressed carefully in the inverse planning process and with optimization of the IMRT beam configuration.

Carcinoma, Non-Small-Cell Lung↗

PubMed2004

Dose and volume reduction for normal lung using intensity-modulated radiotherapy for advanced-stage non-small-cell lung cancer.

PURPOSE: To investigate dosimetric improvements with respect to tumor-dose conformity and normal tissue sparing using intensity-modulated radiotherapy (IMRT) compared with three-dimensional conformal radiotherapy (3D-CRT) for advanced-stage non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: Forty-one patients with Stage III-IV and recurrent NSCLC who previously underwent 3D-CRT were included. IMRT plans were designed to deliver 63 Gy to 95% of the planning target volume using nine equidistant coplanar 6-MV beams. Inverse planning was performed to minimize the volumes of normal lung, heart, esophagus, and spinal cord irradiated above their tolerance doses. Dose distributions and dosimetric indexes for the tumors and critical structures in both plans were computed and compared. RESULTS: Using IMRT, the median absolute reduction in the percentage of lung volume irradiated to >10 and >20 Gy was 7% and 10%, respectively. This corresponded to a decrease of >2 Gy in the total lung mean dose and of 10% in the risk of radiation pneumonitis. The volumes of the heart and esophagus irradiated to >40-50 Gy and normal thoracic tissue volume irradiated to >10-40 Gy were reduced using the IMRT plans. A marginal increase occurred in the spinal cord maximal dose and lung volume >5 Gy in the IMRT plans, which could be have resulted from the significant increase in monitor units and thus leakage dose in IMRT. CONCLUSION: IMRT planning significantly improved target coverage and reduced the volume of normal lung irradiated above low doses. The spread of low doses to normal tissues can be controlled in IMRT with appropriately selected planning parameters. The dosimetric benefits of IMRT for advanced-stage non-small-cell lung cancer must be evaluated further in clinical trials.

Adult↗