Taweap Sanghangthum

LINE-1 methylation status of endogenous DNA double-strand breaks

DNA methylation and the repair of DNA double-strand breaks (DSBs) are important processes for maintaining genomic integrity. Although DSBs can be produced by numerous agents, they also occur spontaneously as endogenous DSBs (EDSBs). In this study, we evaluated the methylation status of EDSBs to determine if there is a connection between DNA methylation and EDSBs. We utilized interspersed repetitive sequence polymerase chain reaction (PCR), ligation-mediated PCR and combined bisulfite restriction analysis to examine the extent of EDSBs and methylation at long interspersed nuclear element-1 (LINE-1) sequences nearby EDSBs. We tested normal white blood cells and several cell lines derived from epithelial cancers and leukemias. Significant levels of EDSBs were detectable in all cell types. EDSBs were also found in both replicating and non-replicating cells. We found that EDSBs contain higher levels of methylation than the cellular genome. This hypermethylation is replication independent and the methylation was present in the genome at the location prior to the DNA DSB. The differences in methylation levels between EDSBs and the rest of the genome suggests that EDSBs are differentially processed, by production, end-modification, or repair, depending on the DNA methylation status.

Statistical process control analysis for patient-specific IMRT and VMAT QA

This work applied statistical process control to establish the control limits of the % gamma pass of patient-specific intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) quality assurance (QA), and to evaluate the efficiency of the QA process by using the process capability index (Cpml). A total of 278 IMRT QA plans in nasopharyngeal carcinoma were measured with MapCHECK, while 159 VMAT QA plans were undertaken with ArcCHECK. Six megavolts with nine fields were used for the IMRT plan and 2.5 arcs were used to generate the VMAT plans. The gamma (3%/3 mm) criteria were used to evaluate the QA plans. The % gamma passes were plotted on a control chart. The first 50 data points were employed to calculate the control limits. The Cpml was calculated to evaluate the capability of the IMRT/VMAT QA process. The results showed higher systematic errors in IMRT QA than VMAT QA due to the more complicated setup used in IMRT QA. The variation of random errors was also larger in IMRT QA than VMAT QA because the VMAT plan has more continuity of dose distribution. The average % gamma pass was 93.7% ± 3.7% for IMRT and 96.7% ± 2.2% for VMAT. The Cpml value of IMRT QA was 1.60 and VMAT QA was 1.99, which implied that the VMAT QA process was more accurate than the IMRT QA process. Our lower control limit for % gamma pass of IMRT is 85.0%, while the limit for VMAT is 90%. Both the IMRT and VMAT QA processes are good quality because Cpml values are higher than 1.0.

Retrospective analysis of linear accelerator output constancy checks using process control techniques

Shewhart control charts have previously been suggested as a process control tool for use in routine linear accelerator (linac) output verifications. However, a comprehensive approach to process control has not been investigated for linac output verifications. The purpose of this work is to investigate a comprehensive process control approach to linac output constancy quality assurance (QA). The RBA‐3 dose constancy check was used to verify outputs of photon beams and electron beams delivered by a Varian Clinac 21EX linac. The data were collected during 2009 to 2010. Shewhart‐type control charts, exponentially weighted moving average (EWMA) charts, and capability indices were applied to these processes. The Shewhart‐type individuals chart (X‐chart) was used and the number of data points used to calculate the control limits was varied. The parameters tested for the EWMA charts (smoothing parameter (λ) and the control limit width (L)) were λ=0.05, L=2.492; λ=0.10, L=2.703; and λ=0.20, L=2.860, as well as the number of points used to estimate the initial process mean and variation. Lastly, the number of in‐control data points used to determine process capability (Cp) and acceptability (Cpk) were investigated, comparing the first in‐control run to the longest in‐control run of the process data. Cp and Cpk values greater than 1.0 were considered acceptable. The 95% confidence intervals were reported. The X‐charts detected systematic errors (e.g., device setup errors). In‐control run lengths on the X‐charts varied from 5 to 30 output measurements (about one to seven months). EWMA charts showed in‐control runs ranging from 9 to 33 output measurements (about two to eight months). The Cp and Cpk ratios are higher than 1.0 for all energies, except 12 and 20 MeV. However, 10 MV and 6, 9, and 16 MeV were in question when considering the 95% confidence limits. The X‐chart should be calculated using 8–12 data points. For EWMA chart, using 4 data points is sufficient to calculate the initial mean and variance of the process. The EWMA limits should be calculated with λ=0.10, L=2.703. At least 25–30 in‐control data points should be used to calculate the Cp and Cpk indices. PACS number: 89

A method of setting limits for the purpose of quality assurance

The result from any assurance measurement needs to be checked against some limits for acceptability. There are two types of limits; those that define clinical acceptability (action limits) and those that are meant to serve as a warning that the measurement is close to the action limits (tolerance limits). Currently, there is no standard procedure to set these limits. In this work, we propose an operational procedure to set tolerance limits and action limits. The approach to establish the limits is based on techniques of quality engineering using control charts and a process capability index. The method is different for tolerance limits and action limits with action limits being categorized into those that are specified and unspecified. The procedure is to first ensure process control using the I-MR control charts. Then, the tolerance limits are set equal to the control chart limits on the I chart. Action limits are determined using the Cpm process capability index with the requirements that the process must be in-control. The limits from the proposed procedure are compared to an existing or conventional method. Four examples are investigated: two of volumetric modulated arc therapy (VMAT) point dose quality assurance (QA) and two of routine linear accelerator output QA. The tolerance limits range from about 6% larger to 9% smaller than conventional action limits for VMAT QA cases. For the linac output QA, tolerance limits are about 60% smaller than conventional action limits. The operational procedure describe in this work is based on established quality management tools and will provide a systematic guide to set up tolerance and action limits for different equipment and processes.

Evaluation of Deformable Image Registration (DIR) Methods for Dose Accumulation in Nasopharyngeal Cancer Patients during Radiotherapy

Abstract Introduction Deformable image registration (DIR) is used to modify structures according to anatomical changes for observing the dosimetric effect. In this study, megavoltage computed tomography (MVCT) images were used to generate cumulative doses for nasopharyngeal cancer (NPC) patients by various DIR methods. The performance of the multiple DIR methods was analysed, and the impact of dose accumulation was assessed. Patients and methods The study consisted of five NPC patients treated with a helical tomotherapy unit. The weekly MVCT images at the 1st, 6th, 11th, 16th, 21st, 26th, and 31st fractions were used to assess the dose accumulation by the four DIR methods. The cumulative dose deviations from the initial treatment plan were analysed, and correlations of these variations with the anatomic changes and DIR methods were explored. Results The target dose received a slightly different result from the initial plan at the end of the treatment. The organ dose differences increased as the treatment progressed to 6.8% (range: 2.2 to 10.9%), 15.2% (range: -1.7 to 36.3%), and 6.4% (range: -1.6 to 13.2%) for the right parotid, the left parotid, and the spinal cord, respectively. The mean uncertainty values to estimate the accumulated doses for all the DIR methods were 0.21 ± 0.11 Gy (target dose), 1.99 ± 0.76 Gy (right parotid), 1.19 ± 0.24 Gy (left parotid), and 0.41 ± 0.04 Gy (spinal cord). Conclusions Accuracy of the DIR methods affects the estimation of dose accumulation on both the target dose and the organ dose. The DIR methods provide an adequate dose estimation technique for observation as a result of inter-fractional anatomic changes and are beneficial for adaptive treatment strategies.

Accuracy of eight deformable image registration (DIR) methods for tomotherapy megavoltage computed tomography (MVCT) images

The application of deformable image registration (DIR) to megavoltage computed tomography (MVCT) images benefits adaptive radiotherapy. This study aims to quantify the accuracy of DIR for MVCT images when using different deformation methods assessed in a cubic phantom and nasopharyngeal carcinoma (NPC) patients.

Dosimetry of conformal dynamic arc radiotherapy and intensity modulated radiotherapy in unresectable cholangiocarcinoma

Background: Radiotherapy in cholangiocrcinoma has to overcome organ tolerance of the upper abdomen. Hi-technology radiotherapy may improve conformity and reduce dose to those organ. Objective: Quantitatively compare the dosimetry of conformal dynamic arc radiotherapy (CD-arcRT) and intensity modulated radiotherapy (IMRT) in unresectable cholangiocarcinoma. Material and methods: Eleven cases of unresectable cholangiocarcinoma were re-planned with IMRT and CDarcRT at King Chulalongkhorn Memorial Hospital between 20 September 2004 and 31 December 2005. Both the planning techniques were evaluated using the dose volume histogram of the planning target volume and organ at risk. The conformation number and dose to critical normal structures were used to determine the techniques. Results: IMRT technique was significantly conformed to the planning target volume than CD-arcRT in term of conformation number. For critical structure, IMRT significantly reduced the radiation dose to liver in terms of mean liver dose, V30Gy and V20Gy of the right kidney. Conclusion: The advantage of IMRT was more conformity and reduced dose to critical structure compared with CD-arcRT, but there was no difference between these techniques in terms of V20Gy of left kidney and maximum dose to the spinal cord.