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Biomedical subjects

Lili Chen

Publications and source records attributed to Lili Chen.

At least 19 recordsLinked to original sources
PubMed2026

Osimertinib With or Without Chemotherapy in Advanced Non-Small Cell Lung Cancer With EGFR and Concurrent TP53 Mutations: A Randomized Clinical Trial.

IMPORTANCE: Combination therapy has emerged as a promising therapeutic approach for patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). However, its clinical benefit-risk profile remains a focus of ongoing debate. Identifying patients most likely to derive benefit from such regimens remains an unmet clinical need. OBJECTIVE: To prospectively compare the efficacy and safety of first-line osimertinib plus chemotherapy with osimertinib monotherapy for patients with EGFR-mutated advanced NSCLC harboring concurrent TP53 mutations. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, randomized, open-label, phase 3 study conducted at 17 sites in China. Between March 25, 2021, and July 11, 2024, a total of 294 eligible patients with treatment-naive, stage IV or recurrent nonsquamous NSCLC harboring concurrent TP53 and EGFR-sensitizing mutations were enrolled. INTERVENTIONS: Patients were randomized (1:1) to receive osimertinib plus chemotherapy (pemetrexed and carboplatin every 3 weeks for 4 cycles, followed by maintenance therapy of osimertinib plus pemetrexed; n&#x2009;=&#x2009;146) or osimertinib monotherapy (n&#x2009;=&#x2009;148). MAIN OUTCOMES AND MEASURES: The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival, response, safety, and quality of life. RESULTS: Among 294 enrolled patients, the median age was 57 years (range, 26-79 years), and 159 (54.1%) were female. The data cutoff date was November 11, 2025. At a median follow-up of 25.1 months for the osimertinib-chemotherapy group and 26.1 months for the osimertinib monotherapy group, median progression-free survival was significantly longer with osimertinib plus chemotherapy than with osimertinib monotherapy (34.0 vs 15.6 months; difference, 18.4 months [95% CI, 9.9-22.3]; hazard ratio, 0.44 [95% CI, 0.32-0.60]; P&#x2009;<&#x2009;.001). This benefit was consistent across prespecified subgroups, including those with brain metastases and L858R mutations. The overall survival data remained immature (30.6% maturity); however, a trend toward overall survival benefit with combination therapy was observed. The incidence of grade 3 or higher treatment-related adverse events was higher in the combination group, with no new safety signal identified. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, osimertinib plus chemotherapy significantly increased progression-free survival among patients with EGFR-mutated advanced NSCLC harboring concurrent TP53 mutations. These findings provided a clinical rationale for individualized combination strategies in the management of patients with EGFR-mutated NSCLC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04695925.

Adult↗
PubMed2006

Structure-based discovery of inhibitors of the YycG histidine kinase: new chemical leads to combat Staphylococcus epidermidis infections.

BACKGROUND: Coagulase-negative Staphylococcus epidermidis has become a major frequent cause of infections in relation to the use of implanted medical devices. The pathogenicity of S. epidermidis has been attributed to its capacity to form biofilms on surfaces of medical devices, which greatly increases its resistance to many conventional antibiotics and often results in chronic infection. It has an urgent need to design novel antibiotics against staphylococci infections, especially those can kill cells embedded in biofilm. RESULTS: In this report, a series of novel inhibitors of the histidine kinase (HK) YycG protein of S. epidermidis were discovered first using structure-based virtual screening (SBVS) from a small molecular lead-compound library, followed by experimental validation. Of the 76 candidates derived by SBVS targeting of the homolog model of the YycG HATPase_c domain of S. epidermidis, seven compounds displayed significant activity in inhibiting S. epidermidis growth. Furthermore, five of them displayed bactericidal effects on both planktonic and biofilm cells of S. epidermidis. Except for one, the compounds were found to bind to the YycG protein and to inhibit its auto-phosphorylation in vitro, indicating that they are potential inhibitors of the YycG/YycF two-component system (TCS), which is essential in S. epidermidis. Importantly, all these compounds did not affect the stability of mammalian cells nor hemolytic activities at the concentrations used in our study. CONCLUSION: These novel inhibitors of YycG histidine kinase thus are of potential value as leads for developing new antibiotics against infecting staphylococci. The structure-based virtual screening (SBVS) technology can be widely used in screening potential inhibitors of other bacterial TCSs, since it is more rapid and efficacious than traditional screening technology.

Amino Acid Sequence↗
PubMed2006

Discovering severe acute respiratory syndrome coronavirus 3CL protease inhibitors: virtual screening, surface plasmon resonance, and fluorescence resonance energy transfer assays.

An integrated system has been developed for discovering potent inhibitors of severe acute respiratory syndrome coronavirus 3C-like protease (SARS-CoV 3CL(pro)) by virtual screening correlating with surface plasmon resonance (SPR) and fluorescence resonance energy transfer (FRET) technologies-based assays. The authors screened 81,287 small molecular compounds against SPECS database by virtual screening; 256 compounds were subsequently selected for biological evaluation. Through SPR technology-based assay, 52 from these 256 compounds were discovered to show binding to SARS-CoV 3CL(pro). The enzymatic inhibition activities of these 52 SARS-CoV 3CL(pro) binders were further applied to FRET-based assay, and IC(50) values were determined. Based on this integrated assay platform, 8 new SARS-CoV 3CL(pro) inhibitors were discovered. The fact that the obtained IC(50) values for the inhibitors are in good accordance with the discovered dissociation equilibrium constants (K(D)s) assayed by SPR implied the reliability of this platform. Our current work is hoped to supply a powerful approach in the discovery of potent SARS-CoV 3CL(pro) inhibitors, and the determined inhibitors could be used as possible lead compounds for further research.

Binding Sites↗
PubMed2006

Discovery of Helicobacter pylori shikimate kinase inhibitors: bioassay and molecular modeling.

Shikimate kinase (SK) is the fifth enzyme in the shikimate pathway and catalyzes the phosphate transfer from ATP to shikimate in generating shikimate 3-phosphate and ADP. SK has been developed as a promising target for the discovery of antibacterial agents. In this report, two small molecular inhibitors (compound 1, 3-methoxy-4-{[2-({2-methoxy-4-[(4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene)methyl]phenoxy}methyl)benzyl]oxy}benzaldehyde; compound 2, 5-bromo-2-(5-{[1-(3,4-dichlorophenyl)-3,5-dioxo-4-pyrazolidinylidene]methyl}-2-furyl)benzoic acid) against Helicobacter pylori SK (HpSK) were successfully identified with IC(50) values of 5.5+/-1.2 and 6.4+/-0.4 microM, respectively. The inhibition kinetics shows that compound 1 is a noncompetitive inhibitor with respect to both shikimate and MgATP, and compound 2 is a competitive inhibitor toward shikimate and noncompetitive inhibitor with respect to MgATP. The surface plasmon resonance (SPR) technology based analysis reveals that the equilibrium dissociation constants (K(D)s) of compounds 1 and 2 with HpSK enzyme are 4.39 and 3.74 microM, respectively. The molecular modeling and docking of two inhibitors with HpSK reveals that the active site of HpSK is rather roomy and deep, forming an L-shape channel on the surface of the protein, and compound 1 prefers the corner area of L-shape channel, while compound 2 binds the short arm of the channel of SK in the binding interactions. It is expected that our current work might supply useful information for the development of novel SK inhibitors.

Algorithms↗
PubMed2006

Binding interaction of quercetin-3-beta-galactoside and its synthetic derivatives with SARS-CoV 3CL(pro): structure-activity relationship studies reveal salient pharmacophore features.

The 3C-like protease (3CL(pro)) of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is one of the most promising targets for discovery of drugs against SARS, because of its critical role in the viral life cycle. In this study, a natural compound called quercetin-3-beta-galactoside was identified as an inhibitor of the protease by molecular docking, SPR/FRET-based bioassays, and mutagenesis studies. Both molecular modeling and Q189A mutation revealed that Gln189 plays a key role in the binding. Furthermore, experimental evidence showed that the secondary structure and enzymatic activity of SARS-CoV 3CL(pro) were not affected by the Q189A mutation. With the help of molecular modeling, eight new derivatives of the natural product were designed and synthesized. Bioassay results reveal salient features of the structure-activity relationship of the new compounds: (1) removal of the 7-hydroxy group of the quercetin moiety decreases the bioactivity of the derivatives; (2) acetoxylation of the sugar moiety abolishes inhibitor action; (3) introduction of a large sugar substituent on 7-hydroxy of quercetin can be tolerated; (4) replacement of the galactose moiety with other sugars does not affect inhibitor potency. This study not only reveals a new class of compounds as potential drug leads against the SARS virus, but also provides a solid understanding of the mechanism of inhibition against the target enzyme.

Binding Sites↗
PubMed2006

Biochemical characterization and inhibitor discovery of shikimate dehydrogenase from Helicobacter pylori.

Shikimate dehydrogenase (SDH) is the fourth enzyme involved in the shikimate pathway. It catalyzes the NADPH-dependent reduction of 3-dehydroshikimate to shikimate, and has been developed as a promising target for the discovery of antimicrobial agent. In this report, we identified a new aroE gene encoding SDH from Helicobacter pylori strain SS1. The recombinant H. pylori shikimate dehydrogenase (HpSDH) was cloned, expressed, and purified in Escherichia coli system. The enzymatic characterization of HpSDH demonstrates its activity with k(cat) of 7.7 s(-1) and K(m) of 0.148 mm toward shikimate, k(cat) of 7.1 s(-1) and K(m) of 0.182 mm toward NADP, k(cat) of 5.2 s(-1) and K(m) of 2.9 mm toward NAD. The optimum pH of the enzyme activity is between 8.0 and 9.0, and the optimum temperature is around 60 degrees C. Using high throughput screening against our laboratory chemical library, five compounds, curcumin (1), 3-(2-naphthyloxy)-4-oxo-2-(trifluoromethyl)-4H-chromen-7-yl 3-chlorobenzoate (2), butyl 2-{[3-(2-naphthyloxy)-4-oxo-2-(trifluoromethyl)-4H-chromen-7-yl]oxy}propanoate (3), 2-({2-[(2-{[2-(2,3-dimethylanilino)-2-oxoethyl]sulfanyl}-1,3-benzothiazol-6-yl)amino]-2-oxoethyl}sulfanyl)-N-(2-naphthyl)acetamide (4), and maesaquinone diacetate (5) were discovered as HpSDH inhibitors with IC(50) values of 15.4, 3.9, 13.4, 2.9, and 3.5 microm, respectively. Further investigation indicates that compounds 1, 2, 3, and 5 demonstrate noncompetitive inhibition pattern, and compound 4 displays competitive inhibition pattern with respect to shikimate. Compounds 1, 4, and 5 display noncompetitive inhibition mode, and compounds 2 and 3 show competitive inhibition mode with respect to NADP. Antibacterial assays demonstrate that compounds 1, 2, and 5 can inhibit the growth of H. pylori with MIC of 16, 16, and 32 microg.mL(-1), respectively. This current work is expected to favor better understanding the features of SDH and provide useful information for the development of novel antibiotics to treat H. pylori-associated infection.

Alcohol Oxidoreductases↗
PubMed2006

Benefit of three-dimensional image-guided stereotactic localization in the hypofractionated treatment of lung cancer.

PURPOSE: The aim of this study was to investigate the benefit of image-guided stereotactic localization in the hypofractionated treatment for medically inoperable non-small-cell lung cancer. METHODS AND MATERIALS: A stereotactic body localizer (SBL) system was used for patient immobilization, reliable image registration among multiphase computed tomography (CT) scanning, and image-guided stereotactic localization. Three sets of CT scans were taken (free breathing, and breath holding at the end-tidal inspiration and expiration, respectively) to contrast target motion. Target delineation was performed on all 3 sets of images and the combination of the targets forms an internal target volume (ITV). In this retrospective study of treatment dose verification, we performed image fusion between the simulation CT scan and each pretreatment CT scan to obtain the same target and critical structure information. The same treatment plans were reloaded onto each pretreatment CT scan with their respective stereotactic coordinate system. The changes in dose distributions were assessed by dose-volume histograms of the planning target volume (PTV) and the critical structures before and after isocenter corrections which were prompted by image-guided stereotactic localization. We compared D95, D99, and V95 for the PTV and internal target volume, and V20 and V30 for the ipsilateral lung. RESULTS: Our retrospective study for 10 patients with 40 dose reconstructions showed that the average D95, D99, and V95 of the PTVs are 92.1%, 88.1%, and 95.8% of the planned values before isocenter corrections. With the corrections, all of these values are improved to 100% of the planned values. CONCLUSIONS: Three-dimensional image guidance is crucial for stereotactic radiotherapy of lung tumors.

Carcinoma, Non-Small-Cell Lung↗
PubMed2006

Gene families encoding transcription factors expressed in early development of Strongylocentrotus purpuratus.

All genes encoding transcription factors of the bHLH, Nuclear Receptor, Basic Leucine Zipper, T-box, Smad, Sox, and other smaller families were identified in the Strongylocentrotus purpuratus genome by means of a permissive blast search of the genome using a database of known transcription factors. Phylogenetic trees were constructed for the major families, permitting a comparison of the regulatory protein repertoire of the sea urchin and other species. QPCR and whole mount in situ hybridization experiments revealed the temporal and spatial expression patterns of these genes during early development. These regulatory genes are initially expressed at a broad range of time points, and the large majority of genes of all families are expressed within the first 48 h of development. The observations suggest assignment of many regulatory genes to specific developmental sub-networks, including endomesodermal, oral, aboral, and apical.

Animals↗
PubMed2006

Identification and characterization of homeobox transcription factor genes in Strongylocentrotus purpuratus, and their expression in embryonic development.

A set of 96 homeobox transcription factors was identified in the Strongylocentrotus purpuratus genome using permissive blast searches with a large collection of authentic homeodomain sequences from mouse, human and fly. A phylogenetic tree was constructed to compare the sea urchin homeobox gene family to those of vertebrates, with the result that with the only a few exceptions, orthologs of all vertebrate homeodomain genes were uncovered by our search. QPCR time course measurements revealed that 65% of these genes are expressed within the first 48 h of development (late gastrula). For genes displaying sufficiently high levels of transcript during the first 24 h of development (late blastula), whole mount in situ hybridization was carried out up to 48 h to determine spatial patterns of expression. The results demonstrate that homeodomain transcription factors participate in multiple and diverse developmental functions, in that they are used at a range of time points and in every territory of the developing embryo.

Animals↗
PubMed2006

The Amino-terminal domain of tntegrin beta3 functions as a transcriptional activator in yeast.

A deletion mutant encoding the integrin beta3(4I-F56) with an additional Gln at the carboxyl terminus was found occassionally when we were constructing a counterselection yeast two-hybrid assay modle. This mutant exhibited strong transcriptional activation in yeast cells, bearing the Escherichia coli lacZ reporter gene encoding the beta-galactosidase under the transcriptional control of GAL4 promoter and TATA box. Further analysis revealed that the region between the amino acid residues 23C to S77, an acidic domain involved in the function of several transcriptional activators were critical for optimal level of transactivation.

Amino Acid Sequence↗
PubMed2006

Structural and functional characterization of Falcipain-2, a hemoglobinase from the malarial parasite Plasmodium falciparum.

Malaria is caused by protozoan erythrocytic parasites of the Plasmodium genus, with Plasmodium falciparum being the most dangerous and widespread disease-causing species. Falcipain-2 (FP-2) of P. falciparum is a papain-family (C1A) cysteine protease that plays an important role in the parasite life cycle by degrading erythrocyte proteins, most notably hemoglobin. Inhibition of FP-2 and its paralogues prevents parasite maturation, suggesting these proteins may be valuable targets for the design of novel antimalarial drugs, but lack of structural knowledge has impeded progress toward the rational discovery of potent, selective, and efficacious inhibitors. As a first step toward this goal, we present here the crystal structure of mature FP-2 at 3.1 A resolution, revealing novel structural features of the FP-2 subfamily proteases including a dynamic beta-hairpin hemoglobin binding motif, a flexible N-terminal alpha-helical extension, and a unique active-site cleft. We also demonstrate by biochemical methods that mature FP-2 can proteolytically process its own precursor in trans at neutral to weakly alkaline pH, that the binding of hemoglobin to FP-2 is strictly pH-dependent, and that FP-2 preferentially binds methemoglobin over hemoglobin. Because the specificity and proteolytic activity of FP-2 toward its multiple targets appears to be pH-dependent, we suggest that environmental pH may play an important role in orchestrating FP-2 function over the different life stages of the parasite. Moreover, it appears that selectivity of FP-2 for methemoglobin may represent an evolutionary adaptation to oxidative stress conditions within the host cell.

Amino Acid Motifs↗
PubMed2006

Commissioning and quality assurance of a commercial stereotactic treatment-planning system for extracranial IMRT.

A 3D treatment-planning system (TPS) for stereotactic intensity-modulated radiotherapy (IMRT) using a micro-multileaf collimator has been made available by Radionics. In this work, we report our comprehensive quality assurance (QA) procedure for commissioning this TPS. First, the accuracy of stereotaxy established with a body frame was checked to ensure accurate determination of a target position within the planning system. Second, the CT-to-electron density conversion curve used in the TPS was fitted to our site-specific measurement data to ensure the accuracy of dose calculation and measurement verification in a QA phantom. Using the QA phantom, the radiological path lengths were verified against known geometrical depths to ensure the accuracy of the ray-tracing algorithm. We also checked inter- and intraleaf leakage/transmission for adequate jaw settings. Measurements for dose verification were performed in various head/neck and prostate IMRT treatment plans using the patient-specific optimized fluence maps. Both ion chamber and film were used for point dose and isodose distribution verifications. To ensure that adjacent organs at risk receive dose within the expectation, we used the Monte Carlo method to calculate dose distributions and dose-volume histograms (DVHs) for these organs at risk. The dosimetric accuracy satisfied the published acceptability criteria. The Monte Carlo calculations confirmed the measured dose distributions for target volumes. For organs located on the beam boundary or outside the beam, some differences in the DVHs were noticed. However, the plans calculated by both methods met our clinical criteria. We conclude that the accuracy of the XKnifetrade mark RT2 treatment-planning system is adequate for the clinical implementation of stereotactic IMRT.

Brain Neoplasms↗
PubMed2006

Monte Carlo based IMRT dose verification using MLC log files and R/V outputs.

Conventional IMRT dose verification using film and ion chamber measurements is useful but limited with respect to the actual dose distribution received by the patient. The Monte Carlo simulation has been introduced as an independent dose verification tool for IMRT using the patient CT data and MLC leaf sequence files, which validates the dose calculation accuracy but not the plan delivery accuracy. In this work, we propose a Monte Carlo based IMRT dose verification method that reconstructs the patient dose distribution using the patient CT, actual beam data based on the information from the record and verify system (R/V), and the MLC log files obtained during dose delivery that record the MLC leaf positions and MUs delivered. Comparing the Monte Carlo dose calculation with the original IMRT plan using these data simultaneously validates the accuracy of both the IMRT dose calculation and beam delivery. Such log file based Monte Carlo simulations are expected to be employed as a useful and efficient IMRT QA modality to validate the dose delivered to the patient. We have run Monte Carlo simulations for eight IMRT prostate plans using this method and the results for the target dose were consistent with the original CORVUS treatment plans to within 3.0% and 2.0% with and without heterogeneity corrections in the dose calculation. However, significant dose deviations in nearby critical structures have been observed. The results showed that up to 9.0% of the bladder dose and up to 38.0% of the rectum dose, to which leaf position errors were found to contribute <2%, were underestimated by the CORVUS treatment planning system. The concept of average leaf position error has been defined to analyze MLC leaf position errors for an IMRT plan. A linear correlation between the target dose error and the average position error has been found based on log file based Monte Carlo simulations, showing that an average position error of 0.2 mm can result in a target dose error of about 1.0%.

Computer Simulation↗
PubMed2006

An overall picture of SARS coronavirus (SARS-CoV) genome-encoded major proteins: structures, functions and drug development.

A severe atypical pneumonia designated as severe acute respiratory syndrome (SARS) by The World Health Organization broke out in China and menaced to more than other 30 countries between the end of the year 2002 and June of the year 2003. A novel coronavirus called severe acute respiratory syndrome coronavirus (SARS-CoV) has been recently identified as the etiological agent responsible for the infectious SARS disease. Based on extensively scientific cooperation and almost two-year's studies, remarkable achievements have been made in the understanding of the phylogenetic property and the genome organization of SARS-CoV, as well as the detailed characters of the major proteins involved in SARS-CoV life cycle. In this review, we would like to summarize the substantial scientific progress that has been made towards the structural and functional aspects of SARS-CoV associated key proteins. The progress focused on the corresponding key proteins' structure-based drug and vaccine developments has been also highlighted. The concerted and cooperative response for the treatment of the SARS disease has been proved to be a triumph of global public health and provides a new paradigm for the detection and control of future emerging infectious disease threats.

Antiviral Agents↗
PubMed2005

Folding of the SARS coronavirus spike glycoprotein immunological fragment (SARS_S1b): thermodynamic and kinetic investigation correlating with three-dimensional structural modeling.

Spike glycoprotein of SARS coronavirus (S protein) plays a pivotal role in SARS coronavirus (SARS_CoV) infection. The immunological fragment of the S protein (Ala251-His641, SARS_S1b) is believed to be essential for SARS_CoV entering the host cell through S protein-ACE-2 interaction. We have quantitatively characterized the thermally induced and GuHCl-induced unfolding features of SARS_S1b using circular dichroism (CD), tryptophan fluorescence, and stopped-flow spectral techniques. For the thermally induced unfolding at pH 7.4, the apparent activation energy (E(app)) and transition midpoint temperature (Tm) were determined to be 16.3 +/- 0.2 kcal/mol and 52.5 +/- 0.4 degrees C, respectively. The CD spectra are not dependent on temperature, suggesting that the secondary structure of SARS_S1b has a relatively high thermal stability. GuHCl strongly affected SARS_S1b structure. Both the CD and fluorescent spectra resulted in consistent values of the transition middle concentration of the denaturant (Cm, ranging from 2.30 to 2.45 M) and the standard free energy change (deltaG(o), ranging from 2.1 to 2.5 kcal/mol) for the SARS_S1b unfolding reaction. Moreover, the kinetic features of the chemical unfolding and refolding of SARS_S1b were also characterized using a stopped-flow CD spectral technique. The obvious unfolding reaction rates and relaxation times were determined at various GuHCl concentrations, and the Cm value was obtained, which is very close to the data that resulted from CD and fluorescent spectral determinations. Secondary and three-dimensional structural predictions by homology modeling indicated that SARS_S1b folded as a globular-like structure by beta-sheets and loops; two of the four tryptophans are located on the protein surface, which is in agreement with the tryptophan fluorescence result. The three-dimensional model was also used to explain the recently published experimental results of S1-ACE-2 binding and immunizations.

Amino Acid Sequence↗
PubMed2005

Dosimetric advantage and clinical implication of a micro-multileaf collimator in the treatment of prostate with intensity-modulated radiotherapy.

This paper investigates the dosimetric benefits of a micro-multileaf (4-mm leaf width) collimator (mMLC) for intensity-modulated radiation therapy (IMRT) treatment planning of the prostate cancer and its potential application for dose escalation and hypofractionation. We compared treatment plans for IMRT delivery using 2 different multileaf collimator (MLC) leaf widths (4 vs. 10 mm) for 10 patients with prostate cancer. Treatment planning was performed on the XknifeRT2 treatment planning system. All beams and optimization parameters were identical for the mMLC and MLC plans. All of the plans were normalized to ensure that 95% of the planning target volume (PTV) received 100% of the prescribed dose (74 Gy). The differences in dose distribution between the 2 groups of plans using the mMLC and the MLC were assessed by dose-volume histogram (DVH) analysis of the target and critical organs. Significant reductions in the volume of rectum receiving medium to higher doses were achieved using the mMLC. The average decrease in the volume of the rectum receiving 40, 50, and 60 Gy using the mMLC plans was 40.2%, 33.4%, and 17.7%, respectively, with p-values less than 0.0001 for V40 and V50 and 0.012 for V60. The mean dose reductions for D17 and D35 for the rectum were 20.0% (p < 0.0001) and 18.3% (p < 0.0002), respectively, when compared to those with the MLC plans. There were consistent reductions in all dose indices studied for the bladder. The target dose inhomogeneity was improved in the mMLC plans by an average of 32%. In the high-dose range, there was no significant difference in the dose deposited in the "hottest" 1 cc of the rectum between the 2 MLC plans for all cases (p > 0.78). Because of the reduction of rectal volume receiving medium to higher doses, dose to the prostate target can be escalated by about 20 Gy to over 74 Gy, while keeping the rectal dose (either denoted by D17 or D35) the same as those with the use of the MLC. The maximum achievable dose, derived when the rectum is allowed to reach the tolerance level, was found to be in the range of 113-172 Gy (using the tolerance value of D17). We conclude that the use of the mMLC for IMRT of the prostate may facilitate dose hypofractionation due to its dosimetric advantage in significantly improving the DVH parameters of the prostate and critical organs. When used for conventional fractionation scheme, mMLC for IMRT of the prostate may reduce the toxicity to the critical organs.

Equipment Design↗