Prediction of self-diffusion coefficients of chemically diverse pure liquids by all-atom molecular dynamics simulations.

Molecular self-diffusion coefficients underlie various kinetic properties of the liquids involved in chemistry, physics, and pharmaceutics. In this study, 547 self-diffusion coefficients are calculated based on all-atom molecular dynamics (MD) simulations of 152 diverse pure liquids at various temperatures employing the OPLS4 force field. The calculated coefficients are compared with experimental data (424 extracted from the literature and 123 newly measured by pulsed-field gradient nuclear magnetic resonance). The calculations well agree with the experimental values. The determination coefficient and root mean square error between the observed and calculated logarithmic self-diffusion coefficients of the 547 entries are 0.931 and 0.213, respectively, demonstrating that the MD calculation can be an excellent industrial tool for predicting, for example, molecular transportation in liquids such as the diffusion of active ingredients in biological and pharmaceutical liquids. The self-diffusion coefficients collected in this study are compiled into a database for broad researches including artificial intelligence calculations.

Effect of 5-fluorouracil on cellular response to proton beam in esophageal cancer cell lines according to the position of spread-out Bragg peak.

INTRODUCTION: To investigate enhancement by 5-fluorouracil (5-FU) of the sensitivity of cancer cells to proton beam irradiation and clarify the differences in the responses of the 5-FU-treated cells to proton beam irradiation according to the position of the cells on the spread-out Bragg peak (SOBP). METHODS: OE21 human esophageal squamous cells were irradiated with a 235-MeV proton beam at four different positions on the SOBP. The effects of the irradiation plus 5-FU treatment on the cell survival were assessed by clonogenic assays and determination of the sensitizer enhancement ratio (SER). In addition, DNA double-strand breaks were estimated by measuring phospho-histone H2AX (γH2AX) foci formation in the cells at 0.5 and 24 h after irradiation. RESULTS: The relative biological effectiveness (RBE) of proton beam irradiation against vehicle-control cells tended to increase with an increase in the depth of the cells on the SOBP. On the other hand, the degree of enhancement of the cellular sensitivity to proton beam irradiation by 5-FU was similar across all the positions on the SOBP. Furthermore, a marked increase in the number of residual γH2AX foci at 24 h post-irradiation was observed in the cells at the distal end of the SOBP. CONCLUSIONS: Our data indicated that the degree of enhancement by 5-FU of the sensitivity of OE21 cells to 235-MeV proton beam irradiation did not differ significantly depending on the position of the cells on the SOBP. Furthermore, the degree of increase in the number of γH2AX foci at 24 h after proton beam irradiation with or without 5-FU exposure did not differ significantly according to the position on the SOBP. The effect of 5-FU in enhancing the effect of proton beam irradiation on cancer cells may be constant for all positions on the SOBP.

Usefulness of hybrid deformable image registration algorithms in prostate radiation therapy.

To evaluate the accuracy of commercially available hybrid deformable image registration (DIR) algorithms when using planning CT (pCT) and daily cone-beam computed tomography (CBCT) in radiation therapy for prostate cancer. The hybrid DIR algorithms in RayStation and MIM Maestro were evaluated. Contours of the prostate, bladder, rectum, and seminal vesicles (SVs) were used as region-of-interest (ROIs) to guide image deformation in the hybrid DIR and to compare the DIR accuracy. To evaluate robustness of the hybrid DIR for prostate cancer patients with organs with volume that vary on a daily basis, such as the bladder and rectum, the DIR algorithms were performed on ten pairs of CT volumes from ten patients who underwent prostate intensity-modulated radiation therapy or volumetric modulated arc therapy. In a visual evaluation, MIM caused unrealistic image deformation in soft tissues, organs, and pelvic bones. The mean dice similarity coefficient (DSC) ranged from 0.46 to 0.90 for the prostate, bladder, rectum, and SVs; the SVs had the lowest DSC. Target registration error (TRE) at the centroid of the ROIs was about 2 mm for the prostate and bladder, and about 6 mm for the rectum and SVs. RayStation did not cause unrealistic image deformation, and could maintain the shape of pelvic bones in most cases. The mean DSC and TRE at the centroid of the ROIs were about 0.9 and within 5 mm generally. In both software programs, the use of ROIs to guide image deformation had the possibility to reduce any unrealistic image deformation and might be effective to keep the DIR physically reasonable. The pCT/CBCT DIR for the prostate cancer did not reduce the DIR accuracy because of the use of ROIs to guide the image deformation.

In Silico Predictions of Human Skin Permeability using Nonlinear Quantitative Structure-Property Relationship Models.

PURPOSE: Predicting human skin permeability of chemical compounds accurately and efficiently is useful for developing dermatological medicines and cosmetics. However, previous work have two problems; 1) quality of databases used, and 2) methods for prediction models. In this paper, we attempt to solve these two problems. METHODS: We first compile, by carefully screening from the literature, a novel dataset of chemical compounds with permeability coefficients, measured under consistent experimental conditions. We then apply machine learning techniques such as support vector regression (SVR) and random forest (RF) to our database to develop prediction models. Molecular descriptors are fully computationally obtained, and greedy stepwise selection is employed for descriptor selection. Prediction models are internally and externally validated. RESULTS: We generated an original, new database on human skin permeability of 211 different compounds from aqueous donors. Nonlinear SVR achieved the best performance among linear SVR, nonlinear SVR, and RF. The determination coefficient, root mean square error, and mean absolute error of nonlinear SVR in external validation were 0.910, 0.342, and 0.282, respectively. CONCLUSIONS: We provided one of the largest datasets with purely experimental log kp and developed reliable and accurate prediction models for screening active ingredients and seeking unsynthesized compounds of dermatological medicines and cosmetics.

Modeling and Prediction of Solvent Effect on Human Skin Permeability using Support Vector Regression and Random Forest.

PURPOSE: The solvent effect on skin permeability is important for assessing the effectiveness and toxicological risk of new dermatological formulations in pharmaceuticals and cosmetics development. The solvent effect occurs by diverse mechanisms, which could be elucidated by efficient and reliable prediction models. However, such prediction models have been hampered by the small variety of permeants and mixture components archived in databases and by low predictive performance. Here, we propose a solution to both problems. METHODS: We first compiled a novel large database of 412 samples from 261 structurally diverse permeants and 31 solvents reported in the literature. The data were carefully screened to ensure their collection under consistent experimental conditions. To construct a high-performance predictive model, we then applied support vector regression (SVR) and random forest (RF) with greedy stepwise descriptor selection to our database. The models were internally and externally validated. RESULTS: The SVR achieved higher performance statistics than RF. The (externally validated) determination coefficient, root mean square error, and mean absolute error of SVR were 0.899, 0.351, and 0.268, respectively. Moreover, because all descriptors are fully computational, our method can predict as-yet unsynthesized compounds. CONCLUSION: Our high-performance prediction model offers an attractive alternative to permeability experiments for pharmaceutical and cosmetic candidate screening and optimizing skin-permeable topical formulations.

Regulation of Ca(2+)/calmodulin-dependent protein kinase phosphatase (CaMKP) by oxidation/reduction at Cys-359.

Ca(2+)/calmodulin-dependent protein kinase phosphatase (CaMKP/PPM1F) is a Ser/Thr protein phosphatase that dephosphorylates and regulates multifunctional Ca(2+)/calmodulin-dependent protein kinases. Although CaMKP is known to be activated by phosphorylation with CaMKII and stimulated by the addition of polycations such as poly-l-lysine, detailed mechanisms of regulation of CaMKP in vivo still remain unclear. In the present study, we found that CaMKP is regulated by oxidation/reduction at Cys residue(s). When CaMKP was incubated with H(2)O(2), time- and dose-dependent inactivation of the enzyme was observed. This inactivation was restored when the inactivated CaMKP was treated with a reducing agent such as 2-mercaptoethanol. Since there are three Cys residues (Cys-259, Cys-315, and Cys-359) in human CaMKP (hCaMKP), we produced three point mutants of hCaMKP, CaMKP(C259S), CaMKP(C315S), and CaMKP(C359S), of which the Cys residues were replaced by Ser residues. Among these Cys-substituted mutants, only CaMKP(C359S) exhibited significant tolerance against oxidation by H(2)O(2). Incubation of CaMKP with H(2)O(2) led to formation of disulfide bond between Cys-359 and Cys-259/Cys-315, resulting in the inactivation of the enzyme. These results suggest that hCaMKP activity is reversibly regulated by oxidation/reduction at Cys-359.

Functional processing of nuclear Ca2+/calmodulin-dependent protein kinase phosphatase (CaMKP-N): evidence for a critical role of proteolytic processing in the regulation of its catalytic activity, subcellular localization and substrate targeting in vivo.

Ca(2+)/calmodulin-dependent protein kinase phosphatase (CaMKP) and its nuclear homolog CaMKP-N are Ser/Thr protein phosphatases that belong to the PPM family. These phosphatases are highly specific for multifunctional CaM kinases and negatively regulate their activities. CaMKP-N is only expressed in the brain and specifically localized in the nucleus. In this study, we found that zebrafish CaMKP-N (zCaMKP-N) underwent proteolytic processing in both the zebrafish brain and Neuro2a cells. In Neuro2a cells, the proteolytic processing was effectively inhibited by the proteasome inhibitors MG-132, Epoxomicin, and Lactacystin, suggesting that the ubiquitin-proteasome pathway was involved in this processing. Using MG-132, we found that the proteolytic processing changed the subcellular localization of zCaMKP-N from the nucleus to the cytosol. Accompanying this change, the cellular targets of zCaMKP-N in Neuro2a cells were significantly altered. Furthermore, we obtained evidence that the zCaMKP-N activity was markedly activated when the C-terminal domain was removed by the processing. Thus, the proteolytic processing of zCaMKP-N at the C-terminal region regulates its catalytic activity, subcellular localization and substrate targeting in vivo.

Accidental ingestion of a long dental crown.

It is recommended that a sharp-pointed object, such as a dental crown, in the proximal duodenum be retrieved endoscopically if this can be accomplished safely.

In-gel protein phosphatase assay using fluorogenic substrates.

We developed a method for the detection of phosphatase activity using fluorogenic substrates after polyacrylamide gel electrophoresis. When phosphatases such as Ca2+/calmodulin-dependent protein kinase phosphatase (CaMKP), protein phosphatase 2C (PP2C), protein phosphatase 5 (PP5), and alkaline phosphatase were resolved by polyacrylamide gel electrophoresis in the absence of SDS and the gel was incubated with a fluorogenic substrate such as 4-methylumbelliferyl phosphate (MUP), all of these phosphatase activities could be detected in situ. Although 6,8-difluoro-4-methylumbelliferyl phosphate (DiFMUP) as well as MUP could be used as a fluorogenic substrate for an in-gel assay, MUP exhibited lower background fluorescence. Using this procedure, several fluorescent bands that correspond to endogenous phosphatases were observed after electrophoresis of various crude samples. The in-gel phosphatase assay could also be used to detect protein phosphatases resolved by SDS-polyacrylamide gel electrophoresis. In this case, however, the denaturation/renaturation process of resolved proteins was necessary for the detection of phosphatase activity. This procedure could be used for detection of renaturable protein phosphatases such as CaMKP and some other phosphatases expressed in cell extracts. The present fluorescent in-gel phosphatase assay is very useful, since no radioactive compounds or no special apparatus are required.

Measurement of microdosimetric spectra produced from a 290 MeV/n Spread Out Bragg Peak carbon beam.

This study describes measurements on secondary particles produced by a 290 MeV/n Spread Out Bragg Peak (SOBP) carbon beam. Microdosimetric distributions of secondary fragments from the SOBP carbon beam have been measured by using a new tissue equivalent proportional counter (TEPC) system at the Heavy Ion Medical Accelerator in Chiba of the National Institute of Radiological Sciences. The new TEPC system consists of a TEPC, two solid-state detectors (SSD) and a scintillation counter (FSC: forward scintillation counter). The SSDs and FSC can separately identify charged fragments and secondary neutrons produced by the incident carbon ions. Microdosimetric distributions were measured for secondary particles including neutrons produced by a body-simulated phantom consisting of various PMMA plates (thickness: 0, 34.81, 55.2, 60.95, 64.83, 95.03, 114.79, 124.69, 135.2 and 144.98 mm, respectively) to cover the SOBP (at 60-125 mm depth). The new system can separately determine produced fragments from the incident SOBP carbon beam in a body-simulated phantom.

Dose-Volume and Radiobiological Model-Based Comparative Evaluation of the Gastrointestinal Toxicity Risk of Photon and Proton Irradiation Plans in Localized Pancreatic Cancer Without Distant Metastasis.

Background: Radiobiological model-based studies of photon-modulated radiotherapy for pancreatic cancer have reported reduced gastrointestinal (GI) toxicity, although the risk is still high. The purpose of this study was to investigate the potential of 3D-passive scattering proton beam therapy (3D-PSPBT) in limiting GI organ at risk (OAR) toxicity in localized pancreatic cancer based on dosimetric data and the normal tissue complication probability (NTCP) model. Methods: The data of 24 pancreatic cancer patients were retrospectively analyzed, and these patients were planned with intensity-modulated radiotherapy (IMRT), volume-modulated arc therapy (VMAT), and 3D-PSPBT. The tumor was targeted without elective nodal coverage. All generated plans consisted of a 50.4-GyE (Gray equivalent) dose in 28 fractions with equivalent OAR constraints, and they were normalized to cover 50% of the planning treatment volume (PTV) with 100% of the prescription dose. Physical dose distributions were evaluated. GI-OAR toxicity risk for different endpoints was estimated by using published NTCP Lyman-Kutcher-Burman (LKB) models. Analysis of variance (ANOVA) was performed to compare the dosimetric data, and ΔNTCPIMRT-PSPBT and ΔNTCPVMAT-PSPBT were also computed. Results: Similar homogeneity and conformity for the clinical target volume (CTV) and PTV were exhibited by all three planning techniques (P > 0.05). 3D-PSPBT resulted in a significant dose reduction for GI-OARs in both the low-intermediate dose range (below 30 GyE) and the highest dose region (D max and V 50 GyE) in comparison with IMRT and VMAT (P < 0.05). Based on the NTCP evaluation, the NTCP reduction for GI-OARs by 3D-PSPBT was minimal in comparison with IMRT and VMAT. Conclusion: 3D-PSPBT results in minimal NTCP reduction and has less potential to substantially reduce the toxicity risk of upper GI bleeding, ulceration, obstruction, and perforation endpoints compared to IMRT and VMAT. 3D-PSPBT may have the potential to reduce acute dose-limiting toxicity in the form of nausea, vomiting, and diarrhea by reducing the GI-OAR treated volume in the low-to-intermediate dose range. However, this result needs to be further evaluated in future clinical studies.

Radiobiological model-based approach to determine the potential of dose-escalated robust intensity-modulated proton radiotherapy in reducing gastrointestinal toxicity in the treatment of locally advanced unresectable pancreatic cancer of the head.

BACKGROUND: The purpose of this study was to determine the potential of escalated dose radiation (EDR) robust intensity-modulated proton radiotherapy (ro-IMPT) in reducing GI toxicity risk in locally advanced unresectable pancreatic cancer (LAUPC) of the head in term of normal tissue complication probability (NTCP) predictive model. METHODS: For 9 patients, intensity-modulated radiotherapy (IMRT) was compared with ro-IMPT. For all plans, the prescription dose was 59.4GyE (Gray equivalent) in 33 fractions with an equivalent organ at risk (OAR) constraints. Physical dose distribution was evaluated. GI toxicity risk for different endpoints was estimated using published NTCP Lyman Kutcher Burman (LKB) models for stomach, duodenum, small bowel, and combine stomach and duodenum (Stoduo). A Wilcoxon signed-rank test was used for dosimetry parameters and NTCP values comparison. RESULT: The dosimetric results have shown that, with similar target coverage, ro-IMPT achieves a significant dose-volume reduction in the stomach, small bowel, and stoduo in low to high dose range in comparison to IMRT. NTCP evaluation for the endpoint gastric bleeding of stomach (10.55% vs. 13.97%, P = 0.007), duodenum (1.87% vs. 5.02%, P = 0.004), and stoduo (5.67% vs. 7.81%, P = 0.008) suggest reduced toxicity by ro-IMPT compared to IMRT. ∆NTCP IMRT - ro-IMPT (using parameter from Pan et al. for gastric bleed) of ≥5 to < 10% was seen in 3 patients (33%) for stomach and 2 patients (22%) for stoduo. An overall GI toxicity relative risk (NTCPro-IMPT/NTCPIMRT) reduction was noted (0.16-0.81) for all GI-OARs except for duodenum (> 1) with endpoint grade ≥ 3 GI toxicity (using parameters from Holyoake et al.). CONCLUSION: With similar target coverage and better conformity, ro-IMPT has the potential to substantially reduce the risk of GI toxicity compared to IMRT in EDR of LAUPC of the head. This result needs to be further evaluated in future clinical studies.

Hypofractionated proton beam therapy for centrally located lung cancer.

INTRODUCTION: To clarify the efficacy and safety of hypofractionated proton beam therapy (PBT) for centrally located lung cancer. METHODS: We retrospectively reviewed 39 patients who received hypofractionated [≧3 Gy (relative biological effectiveness: RBE)/fraction] PBT for centrally located cT1-2N0M0 (8th edition) lung cancer between 1999 and 2015. A tumour within 2 cm of the proximal bronchial tree was defined as a centrally located tumour. RESULTS: Twenty-four patients (62%) were treated with 80 Gy (RBE) in 20 fractions (112 Gy10 ), whereas eight (21%) were treated with 66 Gy (RBE) in 10 fractions (109.56 Gy10 ). The median follow-up period for censored patients was 48 months (range: 4-140). The 2-year progression-free survival (PFS) and overall survival (OS) rates were 86 and 100% for T1 disease and 56 and 94% for T2 disease, respectively. Patients who received 110 Gy10 or higher showed significantly better PFS than those who received less than 110 Gy10 , while no significant difference was noted in OS between the two groups. The sites of the first progression were local in six patients (27%), regional in seven (32%), distant in seven (32%), and local and distant in two (9%). Among the 13 patients with loco-regional recurrence, only two (15%) received treatments with curative intent. Dyspnoea of grade 3 was noted in one patient (3%), and pneumonitis of grade 2 was noted in four patients (10%). CONCLUSION: Hypofractionated PBT may be a very safe and effective treatment option for centrally located early lung cancer.

Multi-institutional comparison of computer-based independent dose calculation for intensity modulated radiation therapy and volumetric modulated arc therapy.

PURPOSE: No multi-institutional studies of computer-based independent dose calculation have addressed the discrepancies among radiotherapy treatment planning systems (TPSs) and the verification programs for intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). We conducted a multi-institutional study to investigate whether ±5% is a reasonable action level for independent dose calculation for IMRT/VMAT. METHODS: In total, 477 IMRT/VMAT plans for prostate or head and neck (H&N) malignancies were retrospectively analyzed using a modified Clarkson-based commercial verification program. The doses from the TPSs and verification programs were compared using the mean ±1 standard deviation (SD). RESULTS: In the TPS-calculated dose comparisons for prostate and H&N malignancies, the sliding window (SW) technique (-2.5 ±â€¯1.8% and -5.3 ±â€¯2.6%) showed greater negative systematic differences than the step-and-shoot (S&S) technique (-0.3 ±â€¯2.2% and -0.8 ±â€¯2.2%). The VMAT dose differences for prostate and H&N malignancies were 0.9 ±â€¯1.8% and 1.1 ±â€¯3.3%, respectively. The SDs were larger for the H&N plans than for the prostate plans in both IMRT and VMAT. Such plans including more out-of-field control points showed greater systematic differences and SDs. CONCLUSIONS: This study will help individual institutions to establish an action level for agreement between primary calculations and verification for IMRT/VMAT. A local dose difference of ±5% at a point within the planning target volume (above -350 HU) may be a reasonable action level.

First case of sexually transmitted asymptomatic female genital tuberculosis from spousal epididymal tuberculosis diagnosed by active screening.

Tuberculosis screening was performed for a healthy asymptomatic woman to determine whether she had been infected with active genital tuberculosis via sexual intercourse with her husband who had epididymal tuberculosis. Vaginal swab culture yielded Mycobacterium tuberculosis. Furthermore, whole genome sequencing revealed that the two causative isolates were genetically identical. This appears to be the first report on the sexual transmission of genital tuberculosis from a man to an asymptomatic woman, detected by active screening for genital tuberculosis and molecular analysis, including whole genome sequencing. Active screening for genital tuberculosis in the female partner should be considered soon after diagnosis of male genital tuberculosis, even when the female partner is asymptomatic.

Late radiological changes after passive scattering proton beam therapy for Stage I lung cancer.

This study aimed to examine late radiological changes after proton beam therapy (PBT) for early-stage non-small cell lung cancer (NSCLC) and to clarify correlations between mass-like radiological changes and patient characteristics. CT scans of patients who underwent passive scattering PBT for T1-2N0M0 NSCLC were analyzed retrospectively. Patients were considered eligible if follow-up CT was performed for at least 2 years, with no definite evidence of local recurrence. The following five periods were defined: (i) 6-12 months, (ii) 12-24 months, (iii) 24-36 months, (iv) 36-48 months and (v) 48-60 months after PBT. Late (≥6 months) radiological changes were scored by consensus of three radiation oncologists according to classifications set forth by Koenig (Radiation injury of the lung after three-dimensional conformal radiation therapy. AJR Am J Roentgenol 2002;178:1383-8.). CT scans of 113 patients (median follow-up, 36 months; range, 24-137 months) were evaluated. Late radiological changes during Periods (i), (ii), (iii), (iv) and (v) included modified conventional pattern (80%, 79%, 72%, 58% and 56%, respectively), mass-like changes (8%, 9%, 14%, 22% and 18%, respectively), scar-like changes (4%, 9%, 11%, 17% and 24%, respectively) and no increased density (8%, 3%, 3%, 2% and 2%, respectively). Mass-like changes were observed in 23 patients (20%). Among patients who developed mass-like changes, the median interval between the initiation of PBT and the onset of mass-like changes was 19 months (range, 6-62 months). In multivariate analysis, a peripheral location was found to be a significant factor (P = 0.035; odds ratio: 4.44; 95% confidence interval: 1.12-21.28). In conclusion, mass-like changes were observed in 20% of patients who underwent PBT. Patients with peripheral tumors showed a higher incidence of mass-like changes.

A multi-institutional study of secondary check of treatment planning using Clarkson-based dose calculation for three-dimensional radiotherapy.

PURPOSE: As there have been few reports on quantitative analysis of inter-institutional results for independent monitor unit (MU) verification, we performed a multi-institutional study of verification to show the feasibility of applying the 3-5% action levels used in the U.S. and Europe, and also to show the results of inter-institutional comparisons. METHODS: A total of 5936 fields were collected from 12 institutions. We used commercial software employing the Clarkson algorithm for verification after a validation study of measurement and software comparisons was performed. The doses generated by the treatment planning systems (TPSs) were retrospectively analyzed using the verification software. RESULTS: Mean ±â€¯two standard deviations of all locations were 1.0 ±â€¯3.6%. There were larger differences for breast (4.0 ±â€¯4.0%) and for lung (2.5 ±â€¯5.8%). A total of 80% of the fields with differences over 5% of the action level involved breast and lung targets, with 7.2 ±â€¯5.4%. Inter-institutional comparisons showed various systematic differences for field shape for breast and differences in the fields were attributable to differences in reference point placement for lung. The large differences for breast and lung are partially attributable to differences in the methods used to correct for heterogeneity. CONCLUSIONS: The 5% action level may be feasible for verification; however, an understanding of larger differences in breast and lung plans is important in clinical practice. Based on the inter-institutional comparisons, care must be taken when determining an institution-specific action level from plans with different field shape settings and incorrectly placed reference points.

Quantitative prediction of ionization effect on human skin permeability.

Although skin permeability of an active ingredient can be severely affected by its ionization in a dose solution, most of the existing prediction models cannot predict such impacts. To provide reliable predictors, we curated a novel large dataset of in vitro human skin permeability coefficients for 322 entries comprising chemically diverse permeants whose ionization fractions can be calculated. Subsequently, we generated thousands of computational descriptors, including LogD (octanol-water distribution coefficient at a specific pH), and analyzed the dataset using nonlinear support vector regression (SVR) and Gaussian process regression (GPR) combined with greedy descriptor selection. The SVR model was slightly superior to the GPR model, with externally validated squared correlation coefficient, root mean square error, and mean absolute error values of 0.94, 0.29, and 0.21, respectively. These models indicate that Log D is effective for a comprehensive prediction of ionization effects on skin permeability. In addition, the proposed models satisfied the statistical criteria endorsed in recent model validation studies. These models can evaluate virtually generated compounds at any pH; therefore, they can be used for high-throughput evaluations of numerous active ingredients and optimization of their skin permeability with respect to permeant ionization.

Variation of the prescription dose using the analytical anisotropic algorithm in lung stereotactic body radiation therapy.

PURPOSE: The aim of the present investigation was to evaluate the dosimetric variation regarding the analytical anisotropic algorithm (AAA) relative to other algorithms in lung stereotactic body radiation therapy (SBRT). We conducted a multi-institutional study involving six institutions using a secondary check program and compared the AAA to the Acuros XB (AXB) in two institutions. METHODS: All lung SBRT plans (128 patients) were generated using the AAA, pencil beam convolution with the Batho (PBC-B) and adaptive convolve (AC). All institutions used the same secondary check program (simple MU analysis [SMU]) implemented by a Clarkson-based dose calculation algorithm. Measurement was performed in a heterogeneous phantom to compare doses using the three different algorithms and the SMU for the measurements. A retrospective analysis was performed to compute the confidence limit (CL; mean±2SD) for the dose deviation between the AAA, PBC, AC and SMU. The variations between the AAA and AXB were evaluated in two institutions, then the CL was acquired. RESULTS: In comparing the measurements, the AAA showed the largest systematic dose error (3%). In calculation comparisons, the CLs of the dose deviation were 8.7±9.9% (AAA), 4.2±3.9% (PBC-B) and 5.7±4.9% (AC). The CLs of the dose deviation between the AXB and the AAA were 1.8±1.5% and -0.1±4.4%, respectively, in the two institutions. CONCLUSIONS: The CL of the AAA showed much larger variation than the other algorithms. Relative to the AXB, larger systematic and random deviations still appeared. Thus, care should be taken in the use of AAA for lung SBRT.

Precision in Wedge Off-axis Using Independent Dose Verification.

It is essential for quality assurance to verify the safety of each individual patient's plan in radiation therapy. The tolerance level for independent verification of monitor unit calculations for non-IMRT clinical radiotherapy has been shown in the AAPM TG114. Thus, we investigated the precision of independent MU (dose) verification considering a wedge off-axis calculation and we conducted a study at twelve institutes for independent verification with the wedge off-axis calculation. The results obtained with the wedge off-axis calculation showed better agreement with the treatment planning system calculation results than those without the former calculation in a phantom study and in the patient retrospective study. The confidence limits with the wedge off-axis calculation were 2.2±3.4% and 2.0±4.3% for the plans with a physical wedge and a non-physical wedge in the patient study, respectively. However, the confidence limits were over 5% without the off-axis calculation. From our multi-institutional study, the results suggested that the tolerance level for the wedge off-axis plan would be 5% when considering the wedge off-axis calculation and the level was similar to that of the treatment planning system using other conventional irradiation techniques.