MOSFET dose measurements for proton SOBP beam.

PURPOSE: The aim of this work was to develop a computational scheme for the correction of the LET dependence on the MOSFET response in water phantom dose measurements for a spread-out Bragg peak (SOBP) proton beam. METHODS: The LET dependence of MOSFET was attributed to the stopping power ratio of SiO2 to H2O and to the fractional hole yield in the SiO2 layer. Using literature values for the stopping powers of the continuous slowing down approximation and measured fractional hole yields vs. electric field and LET, formulas were derived for the computation of a dose-weighted correction factor of a SOBP beam. RESULTS: Dose-weighted correction factors were computed for a clinical 190-MeV proton SOBP beam in a high-density polyethylene phantom. By applying correction factors to the SOBP beam, which consisted of weighted monoenergetic Bragg peaks, the MOSFET outputs were predicted and agreed well with the measured MOSFET responses. CONCLUSION: By applying LET dependent correction factors to MOSFET data, quality assurance of dose verification based on MOSFET measurements becomes possible for proton therapy.

Four direct measurements of the fine-structure constant 13 billion years ago.

Observations of the redshift z = 7.085 quasar J1120+0641 are used to search for variations of the fine structure constant, α, over the redshift range 5.5 to 7.1. Observations at z = 7.1 probe the physics of the universe at only 0.8 billion years old. These are the most distant direct measurements of α to date and the first measurements using a near-IR spectrograph. A new AI analysis method is employed. Four measurements from the x-shooter spectrograph on the Very Large Telescope (VLT) constrain changes in a relative to the terrestrial value (α0). The weighted mean electromagnetic force in this location in the universe deviates from the terrestrial value by Δα/α = (α z - α0)/α0 = (-2.18 ± 7.27) × 10-5, consistent with no temporal change. Combining these measurements with existing data, we find a spatial variation is preferred over a no-variation model at the 3.9σ level.

A novel, potent, and orally bioavailable thiazole HCV NS5A inhibitor for the treatment of hepatitis C virus.

A medicinal chemistry program based on the small-molecule HCV NS5A inhibitor daclatasvir has led to the discovery of dimeric phenylthiazole compound 8, a novel and potent HCV NS5A inhibitor. The subsequent SAR studies and optimization revealed that the cycloalkyl amide derivatives 27a-29a exhibited superior potency against GT1b with GT1b EC50 values at picomolar concentration. Interestingly, high diastereospecificity for HCV inhibition was observed in this class with the (1R,2S,1'R,2'S) diastereomer displaying the highest GT1b inhibitory activity. The best inhibitor 27a was found to be 3-fold more potent (GT1b EC50 = 0.003 nM) than daclatasvir (GT1b EC50 = 0.009 nM) against GT1b, and no detectable in vitro cytotoxicity was observed (CC50 > 50 µM). Pharmacokinetic studies demonstrated that compound 27a had an excellent pharmacokinetic profiles with a superior oral exposure and desired bioavailability after oral administration in both rats and dogs, and therefore it was selected as a developmental candidate for the treatment of HCV infection.

Predictors of Radiation-Induced Liver Disease in Eastern and Western Patients With Hepatocellular Carcinoma Undergoing Proton Beam Therapy.

PURPOSE: To identify predictors of radiation-induced liver disease (RILD) in patients with hepatocellular carcinoma (HCC) treated with proton beam therapy (PBT). METHODS: This multicenter study included 136 patients with HCC (eastern, n = 102; western, n = 34) without evidence of intrahepatic tumor progression after PBT. The RILD was defined as ascites with alkaline-phosphatase abnormality, grade ≥3 hepatic toxicity, or Child-Pugh score worsening by ≥2 within 4 months after PBT completion. The proton doses were converted to equivalent doses in 2-GyE fractions. The unirradiated liver volume (ULV) was defined as the absolute liver volume (LV) receiving <1 GyE; the standard liver volume (SLV) was calculated using body surface area. Possible correlations of clinicodosimetric parameters with RILD were examined. RESULTS: The mean pretreatment LV was 85% of SLV, and patients with a history of hepatectomy (P < .001) or hepatitis B virus infection (P = .035) had significantly smaller LV/SLV. Nineteen (14%) patients developed RILD. Multivariate logistic regression analysis identified ULV/SLV (P = .001), gross tumor volume (P = .001), and Child-Pugh classification (P = .002) as independent RILD predictors, and mean liver dose and target-delivered dose were not associated with RILD occurrence. A "volume-response" relationship between ULV/SLV and RILD was consistently observed in both eastern and western cohorts. In Child-Pugh class-A patients whose ULV/SLV were ≥50%, 49.9%-40%, 39.9%-30% and <30%, the RILD incidences were 0%, 6%, 16%, and 39% (P < .001), respectively. For the Child-Pugh class-B group, the RILD incidences in patients with ≥60%, 59.9%-40%, and <40% of ULV/SLV were 0%, 14%, and 83% (P = .006), respectively. CONCLUSIONS: The ULV/SLV, not mean liver dose, independently predicts RILD in patients with HCC undergoing PBT. The relative and absolute contraindications for Child-Pugh class-A patient's ULV/SLV are <50% and <30%, and <60% and <40% for Child-Pugh class-B patients, respectively. Our results indicate that the likelihood of hepatic complications for PBT is dictated by similar metrics as that for surgery.

A Potent, Selective, and Orally Bioavailable HCV NS5A Inhibitor for Treatment of Hepatitis C Virus: (S)-1-((R)-2-(Cyclopropanecarboxamido)-2-phenylacetyl)-N-(4-phenylthiazol-2-yl)pyrrolidine-2-carboxamide.

Starting from the initial lead 4-phenylthiazole 18, a modest HCV inhibitor (EC50 = 9440 nM), a series of structurally related thiazole derivatives has been identified as a novel chemical class of potent and selective HCV NS5A inhibitors. The introduction of a carboxamide group between the thiazole and pyrrolidine ring (42) of compound 18 resulted in a dramatic increase in activity (EC50 = 0.92 nM). However, 42 showed only moderate pharmacokinetic properties and limited oral bioavalability of 18.7% in rats. Further optimization of the substituents at the 4-position of the thiazole ring and pyrrolidine nitrogen of the lead compound 42 led to the identification of compound 57, a highly potent and selective NS5A inhibitor of HCV (EC50 = 4.6 nM), with greater therapeutic index (CC50/EC50 > 10000). Pharmacokinetic studies revealed that compound 57 had a superior oral exposure and desired bioavailability of 45% after oral administration in rats.

Depth dose characteristics of proton beams within therapeutic energy range using the particle therapy simulation framework (PTSim) Monte Carlo technique.

BACKGROUND: The stopping power and range tables published by the National Institute of Standards and Technology (NIST) were obtained by assuming continuous slowing down approximation (CSDA). This study examined more detail depth dose characteristics of ideal proton beams using the particle therapy simulation framework (PTSim) Monte Carlo technique. METHODS: Simulation for parallel broad field geometry (PBFG) was replaced by the pencil beam geometry (PBG) for improved simulation efficiency. Depth dose distributions (Bragg peak, BP) for beam energies from 69.44 to 230.71 MeV at 5 mm range interval were obtained. This study used seven parameters, Rpeak, R90, R80, R50, full width at half maximum (FWHM), W(80-20), and peak-to-entrance ratio to represent BP characteristics. The resulting energy-range relationships were fitted into third order polynomial formulae. In addition, initial beam energy spreads at 0-1% (1σ) of the mean incident energies at 70, 110, 150, 190, and 230 MeV were added into the simulation to uncover their impact on BP shapes. RESULTS: The study results reveal deeper penetration, broader FWHM and decreased peak-to-entrance dose ratio at increasing beam energy. Study results for beams with initial energy spreads show that R 80 can be a good indicator to characterize initial mean energy. They also suggest FWHM is more sensitive than the width of 80-to-20% distal fall-off in finding initial energy spread. CONCLUSION: Detail depth dose characteristics for monoenergetic proton beams and beams with initial energy spreads within therapeutic energy ranges were reported. These data can serve as a good reference for a clinical practitioner in their daily practice.

MCNPX simulation of proton dose distributions in a water phantom.

BACKGROUND: This study presents the Monte Carlo N-Particles Transport Code, Extension (MCNPX) simulation of proton dose distributions in a water phantom. METHODS: In this study, fluence and dose distributions from an incident proton pencil beam were calculated as a function of depth in a water phantom. Moreover, lateral dose distributions were also studied to understand the deviation among different MC simulations and the pencil beam algorithm. MCNPX codes were used to model the transport and interactions of particles in the water phantom using its built-in "repeated structures" feature. Mesh Tally was used in which the track lengths were distributed in a defined cell and then converted into doses and fluences. Two different scenarios were studied including a proton equilibrium case and a proton disequilibrium case. RESULTS: For the proton equilibrium case, proton fluence and dose in depths beyond the Bragg peak were slightly perturbed by the choice of the simulated particle types. The dose from secondary particles was about three orders smaller, but its simulation consumed significant computing time. This suggests that the simulation of secondary particles may only be necessary for radiation safety issues for proton therapy. For the proton disequilibrium case, the impacts of different multiple Coulomb scattering (MCS) models were studied. Depth dose distributions of a 70 MeV proton pencil beam in a water phantom obtained from MCNPX, Geometry and Track, version 4, and the pencil beam algorithm showed significant deviations between each other, because of different MCS models used. CONCLUSIONS: Careful modelling of MCS is necessary when proton disequilibrium exists.

Pre-radiotherapy PSA level as a predictor for biochemical control in prostate cancer patients receiving radiotherapy after radical prostatectomy.

BACKGROUND: To report the outcome of patients receiving radiotherapy (RT) after radical prostatectomy (RP). METHODS: Between May 2001 and December 2008, 53 consecutive cases of prostate adenocarcinoma treated with RP and RT were reviewed. RESULTS: A total of 49 patients were eligible for this study. After a median follow-up of 53 months, the 4-year overall survival (OS) and biochemical progression-free survival (bPFS) for all patients were 91.0% and 68.9%, respectively. According to univariate and multivariate analysis, pre-RT prostate-specific antigen (PSA) was the most significant factor for bPFS. Patients with pre-RT PSA levels of < 0.2 ng/ml and ≧ 0.2 ng/ml had a 4-year bPFS of 83.1% and 52.6%, respectively (p = 0.013). The incidence of chronic rectal toxicity was low, with no grade 3 toxicity reported and grade 2 toxicity found in only 6 patients (12.2%). However, long-term urinary toxicity of grade 2 or higher was found in 24 patients (49.0%). CONCLUSION: For patients with increasing PSA levels following RP, local RT should be administered prior to biochemical failure (PSA ≧ 0.2), to ensure good bPFS.

The dosimetric impact of dental implants on head-and-neck volumetric modulated arc therapy.

This work aims to investigate the dosimetric impact of dental implants on volumetric modulated arc therapy (VMAT) for head-and-neck patients and to evaluate the effectiveness of using the material's electron-density ratio for the correction. An in-house Monte Carlo (MC) code was utilized for the dose calculation to account for the scattering and attenuation caused by the high-Z implant material. Three different dental implant materials were studied in this work: titanium, Degubond®4 and gold. The dose perturbations caused by the dental implant materials were first investigated in a water phantom with a 1 cm(3) insert. The per cent depth dose distributions of a 3 × 3 cm(2) photon field were compared with the insert material as water and the three selected dental implant materials. To evaluate the impact of the dental implant on VMAT patient dose calculation, four head-and-neck cases were selected. For each case, the VMAT plan was designed based on the artifact-corrected patient geometry using a treatment planning system (TPS) that was typically utilized for routine patient treatment. The plans were re-calculated using the MC code for five situations: uncorrected geometry, artifact-corrected geometry and artifact-corrected geometry with one of the three different implant materials. The isodose distributions and the dose-volume histograms were cross-compared with each other. To evaluate the effectiveness of using the material's electron-density ratio for dental implant correction, the implant region was set as water with the material's electron-density ratio and the calculated dose was compared with the MC simulation with the real material. The main effect of the dental implant was the severe attenuation in the downstream. The 1 cm(3) dental implant can lower the downstream dose by 10% (Ti) to 51% (Au) for a 3 × 3 cm(2) field. The TPS failed to account for the dose perturbation if the dental implant material was not precisely defined. For the VMAT patient dose calculation, the presence of dental implants degrades the PTV coverage significantly. With the material's electron-density ratio applied, the dose calculation accuracy in the water phantom and the VMAT patient was improved to a clinically acceptable level. The effects of the dental implant material can be clinically significant and its impact varies with the density of the dental implant material. We demonstrated that it was effective to use the material's electron-density ratio to account for the dosimetric impact of the dental implant.

Noninvasive monitoring of microvascular changes with partial irradiation using dynamic contrast-enhanced and blood oxygen level-dependent magnetic resonance imaging.

PURPOSE: The microvasculature of a tumor plays an important role in its response to radiation therapy. Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) and blood oxygen level-dependent (BOLD) MRI are both sensitive to vascular characteristics. The present study proposed a partial irradiation approach to a xenograft tumor to investigate the intratumoral response to radiation therapy using DCE and BOLD MRI. METHODS AND MATERIALS: TRAMP-C1 tumors were grown in C57BL/6J mice. Partial irradiation was performed on the distal half of the tumor with a single dose of 15 Gy. DCE MRI was performed to derive the endothelium transfer constant, K(trans), using pharmacokinetic analysis. BOLD MRI was performed using quantitative R2 measurements with carbogen breathing. The histology of the tumor was analyzed using hematoxylin and eosin staining and CD31 staining to detect endothelial cells. The differences between the irradiated and nonirradiated regions of the tumor were assessed using K(trans) values, ΔR2 values in response to carbogen and microvascular density (MVD) measurements. RESULTS: A significantly increased K(trans) and reduced BOLD response to carbogen were found in the irradiated region of the tumor compared with the nonirradiated region (P<.05). Histologic analysis showed a significant aggregation of giant cells and a reduced MVD in the irradiated region of the tumor. The radiation-induced difference in the BOLD response was associated with differences in MVD and K(trans). CONCLUSIONS: We demonstrated that DCE MRI and carbogen-challenge BOLD MRI can detect differential responses within a tumor that may potentially serve as noninvasive imaging biomarkers to detect microvascular changes in response to radiation therapy.

The feasibility study of using multiple partial volumetric-modulated arcs therapy in early stage left-sided breast cancer patients.

The purpose of this study was to assess the feasibility of using a multiple partial volumetric-modulated arcs therapy (MP-VMAT) technique on the left breast irradiation and to evaluate the dosimetry and treatment efficiency. Ten patients with left-sided breast cancer who had been treated by whole breast irradiation were selected for the treatment plan evaluation by using six partial volumetric modulated arcs. Each arc consisted of a 50° gantry rotation. The planning target volumes and the normal organs, including the right breast, the bilateral lungs, left ventricle, heart, and unspecified tissue, were contoured on the CT images. Dose-volume histograms were generated and the delivery time for each arc was recorded. The PTV received greater than 95% of the V(95) for all cases, and the maximum dose was within ± 1% of 110% of the prescription dose. The mean homogeneity index (HI) was 10.61 ± 0.99, and mean conformity index (CI) was 1.21 ± 0.03. The mean dose, V(5), V(10), V(25), and V(30) of the heart were 7.61 ± 1.38 Gy, 59.73% ± 15.87%, 24.39%± 6.82%, 2.52%± 1.11%, and 1.57% ± 0.71%, respectively. The volume of the left ventricle receiving 25 Gy was 5.15% ± 2.23%. The total lung mean dose was 5.57 ± 0.36 Gy, with V(5) of 25.39% ± 3.88% and V(20) of 5.66% ± 0.89%. The right breast received a mean dose of 2.13 ± 0.22 Gy, with V(5) of 1.83% ± 1.22% and V(10) of 0.04% ± 0.12%. The mean dose of unspecified tissue was 5.34 ± 0.37 Gy and V(5) was 22.23% ± 1.57%. The volume of the unspecified tissue receiving 50 Gy was 0.50% ± 0.14%. The mean delivery time for each arc was 13.9 seconds. The average MU among ten patients was 511 MU (range 443 to 594 MUs). The MP-VMAT technique for the left-sided breast cancer patients achieved adequate target dose coverage while maintaining low doses to organs-at-risk, and therefore reduced the potential for induction of second malignancy and side effects. The highly efficient treatment delivery would be beneficial for improving patient throughput, providing patient comfort, and achieving precise treatment with the breathing control system.

Monte Carlo simulations of therapeutic proton beams for relative biological effectiveness of double-strand break.

PURPOSE: The relative biological effectiveness (RBE) values relative to (60)Co for the induction of double-strand breaks (DSB) were calculated for therapeutic proton beams. RBE-weighted absorbed doses were determined at different depths in a water phantom for proton beams. MATERIALS AND METHODS: The depth-dose distributions and the fluence spectra for primary protons and secondary particles were calculated using the FLUKA (FLUktuierende KAskade) MC (Monte Carlo) transport code. These spectra were combined with the MCDS (Monte Carlo damage simulation) code to simulate the spectrum-averaged yields of clustered DNA lesions. RBE for the induction of DSB were then determined at different depths in a water phantom for the unmodulated and modulated proton beams. RESULTS: The maximum RBE for the induction of DSB at 1 Gy absorbed dose was found about 1.5 at 0.5 cm distal to the Bragg peak maximum for an UNMODULATED 160 MeV proton beam. The RBE-weighted absorbed dose extended the biologically effective range of the proton beam by 1.9 mm. The corresponding maximum RBE value was inversely proportional to the proton beam energy, reaching a value of about 1.9 for 70 MeV proton beam. For a modulated 160 MeV proton beam, the RBE weightings were more pronounced near the spread-out Bragg peak (SOBP) distal edge. CONCLUSIONS: It was demonstrated that a fast MCDS code could be used to simulate the DNA damage yield for therapeutic proton beams. Simulated RBE for the induction of DSB were comparable to RBE measured in vitro and in vivo. Depth dependent RBE values in the SOBP region might have to be considered in certain treatment situations.

Vasculatures in tumors growing from preirradiated tissues: formed by vasculogenesis and resistant to radiation and antiangiogenic therapy.

PURPOSE: To investigate vasculatures and microenvironment in tumors growing from preirradiated tissues (pre-IR tumors) and study the vascular responses of pre-IR tumors to radiation and antiangiogenic therapy. METHODS AND MATERIALS: Transgenic adenocarcinoma of the mouse prostate C1 tumors were implanted into unirradiated or preirradiated tissues and examined for vascularity, hypoxia, and tumor-associated macrophage (TAM) infiltrates by immunohistochemistry. The origin of tumor endothelial cells was studied by green fluorescent protein-tagged bone marrow (GFP-BM) transplantation. The response of tumor endothelial cells to radiation and antiangiogenic agent was evaluated by apoptotic assay. RESULTS: The pre-IR tumors had obvious tumor bed effects (TBE), with slower growth rate, lower microvascular density (MVD), and more necrotic and hypoxic fraction compared with control tumors. The vessels were dilated, tightly adhered with pericytes, and incorporated with transplanted GFP-BM cells. In addition, hypoxic regions became aggregated with TAM. As pre-IR tumors developed, the TBE was overcome at the tumor edge where the MVD increased, TAM did not aggregate, and the GFP-BM cells did not incorporate into the vessels. The vessels at tumor edge were more sensitive to the following ionizing radiation and antiangiogenic agent than those in the central low MVD regions. CONCLUSIONS: This study demonstrates that vasculatures in regions with TBE are mainly formed by vasculogenesis and resistant to radiation and antiangiogenic therapy. Tumor bed effects could be overcome at the edge of larger tumors, but where vasculatures are formed by angiogenesis and sensitive to both treatments. Vasculatures formed by vasculogenesis should be the crucial target for the treatment of recurrent tumors after radiotherapy.

Isatin-ß-thiosemicarbazones as potent herpes simplex virus inhibitors.

A series of isatin-ß-thiosemicarbazones have been designed and evaluated for antiviral activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in a plaque reduction assay. Their cytotoxicity was examined using human rhabdomyosarcoma cells (RD cells). Several derivatives of isatin-ß-thiosemicarbazone exhibited significant and selective antiviral activity with low cytotoxicity. It was found that the thiourea group at thiosemicarbazone and the NH functionality at isatin were essential for their antiherpetic activity. The synthesis and structure-activity relationship studies are presented.

Synthesis, activity, and pharmacokinetic properties of a series of conformationally-restricted thiourea analogs as novel hepatitis C virus inhibitors.

A series of novel conformationally-restricted thiourea analogs were designed, synthesized, and evaluated for their anti-HCV activity. Herein we report the synthesis, structure-activity relationships (SARs), and pharmacokinetic properties of this new class of thiourea compounds that showed potent inhibitory activities against HCV in the cell-based subgenomic HCV replicon assay. Among compounds tested, the fluorene compound 4b was found to possess the most potent activity (EC(50)=0.3 microM), lower cytotoxicity (CC(50)>50 microM), and significantly better pharmacokinetic properties compared to its corresponding fluorenone compound 4c.

Midline dose verification with diode in vivo dosimetry for external photon therapy of head and neck and pelvis cancers during initial large-field treatments.

During radiotherapy treatments, quality assurance/control is essential, particularly dose delivery to patients. This study was designed to verify midline doses with diode in vivo dosimetry. Dosimetry was studied for 6-MV bilateral fields in head and neck cancer treatments and 10-MV bilateral and anteroposterior/posteroanterior (AP/PA) fields in pelvic cancer treatments. Calibrations with corrections of diodes were performed using plastic water phantoms; 190 and 100 portals were studied for head and neck and pelvis treatments, respectively. Calculations of midline doses were made using the midline transmission, arithmetic mean, and geometric mean algorithms. These midline doses were compared with the treatment planning system target doses for lateral or AP (PA) portals and paired opposed portals. For head and neck treatments, all 3 algorithms were satisfactory, although the geometric mean algorithm was less accurate and more uncertain. For pelvis treatments, the arithmetic mean algorithm seemed unacceptable, whereas the other algorithms were satisfactory. The random error was reduced by using averaged midline doses of paired opposed portals because the asymmetric effect was averaged out. Considering the simplicity of in vivo dosimetry, the arithmetic mean and geometric mean algorithm should be adopted for head/neck and pelvis treatments, respectively.

Design and efficient synthesis of novel arylthiourea derivatives as potent hepatitis C virus inhibitors.

A novel class of arylthiourea HCV inhibitors bearing various functionalities, such as cyclic urea, cyclic thiourea, urea, and thiourea, on the alkyl linker were designed and synthesized. Herein we report the synthesis and structure-activity relationships (SARs) of this novel class of arylthiourea derivatives that showed potent inhibitory activities against HCV in the cell-based subgenomic HCV replicon assay. Among compounds tested, the new carbazole derivative 64, which has an eight-carbon linkage between the phenyl and carbazole rings and a tolyl group at the N-9 position of carbazole, was found to possess strong anti-HCV activity (EC50=0.031 microM), lower cytotoxicity (CC50 >50 microM), and higher selectivity index (SI >1612) compared to its derivatives.

Design and synthesis of indole, 2,3-dihydro-indole, and 3,4-dihydro-2H-quinoline-1-carbothioic acid amide derivatives as novel HCV inhibitors.

An efficient synthetic methodology to provide indole, 2,3-dihydro-indole, and 3,4-dihydro-2H-quinoline-1-carbothioic acid amide derivatives is described. These conformationally restricted heterobicyclic scaffolds were evaluated as a novel class of HCV inhibitors. Introduction of an acyl group at the NH(2) of the thiourea moiety has been found to enhance inhibitory activity. The chain length and the position of the alkyl group on the indoline aromatic ring markedly influenced anti-HCV activity. The indoline scaffold was more potent than the corresponding indole and tetrahydroquinoline scaffolds and analogue 31 displayed excellent activity (EC(50)=510nM) against HCV without significant cytotoxicity (CC(50) >50microM).

Measurement-based Monte Carlo dose calculation system for IMRT pretreatment and on-line transit dose verifications.

The aim of this study was to develop a dose simulation system based on portal dosimetry measurements and the BEAM Monte Carlo code for intensity-modulated (IM) radiotherapy dose verification. This measurement-based Monte Carlo (MBMC) system can perform, within one systematic calculation, both pretreatment and on-line transit dose verifications. BEAMnrc and DOSXYZnrc 2006 were used to simulate radiation transport from the treatment head, through the patient, to the plane of the aS500 electronic portal imaging device (EPID). In order to represent the nonuniform fluence distribution of an IM field within the MBMC simulation, an EPID-measured efficiency map was used to redistribute particle weightings of the simulated phase space distribution of an open field at a plane above a patient/phantom. This efficiency map was obtained by dividing the measured energy fluence distribution of an IM field to that of an open field at the EPID plane. The simulated dose distribution at the midplane of a homogeneous polystyrene phantom was compared to the corresponding distribution obtained from the Eclipse treatment planning system (TPS) for pretreatment verification. It also generated a simulated transit dose distribution to serve as the on-line verification reference for comparison to that measured by the EPID. Two head-and-neck (NPC1 and NPC2) and one prostate cancer fields were tested in this study. To validate the accuracy of the MBMC system, film dosimetry was performed and served as the dosimetry reference. Excellent agreement between the film dosimetry and the MBMC simulation was obtained for pretreatment verification. For all three cases tested, gamma evaluation with 3%/3 mm criteria showed a high pass percentage (> 99.7%) within the area in which the dose was greater than 30% of the maximum dose. In contrast to the TPS, the MBMC system was able to preserve multileaf collimator delivery effects such as the tongue-and-groove effect and interleaf leakage. In the NPC1 field, the TPS showed 16.5% overdose due to the tongue-and-groove effect and 14.6% overdose due to improper leaf stepping. Similarly, in the NPC2 field, the TPS showed 14.1% overdose due to the tongue-and-groove effect and 8.9% overdose due to improper leaf stepping. In the prostate cancer field, the TPS showed 6.8% overdose due to improper leaf stepping. No tongue-and-groove effect was observed for this field. For transit dose verification, agreements among the EPID measurement, the film dosimetry, and the MBMC system were also excellent with a minimum gamma pass percentage of 99.6%.