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Purpose The purpose of this study was to evaluate the risk of central nervous system (CNS) failure in Korean patients with human epidermal growth factor receptor 2 (HER2)-enriched breast cancer treated with surgery followed by postoperative radiotherapy (RT). Methods A total of 749 patients from eight institutions were enrolled in this study. All of them underwent surgery followed by postoperative RT from 2003 to 2011; 246 (32.8%) received neoadjuvant chemotherapy and 649 (81.7%) received adjuvant chemotherapy. Adjuvant trastuzumab was administered to 386 patients (48.6%). Results The median follow-up duration was 84 (range, 8-171) months. The 7-year disease-free and overall survival rates were 79.0% and 84.2%, respectively. On multivariate analysis, mastectomy, nodal involvement, and presence of lymphatic invasion were correlated with poor overall survival (p = 0.004, 0.022, and 0.011, respectively), whereas T stage and lymphatic invasion were associated with disease-free survival (p = 0.018 and 0.005, respectively). Regarding CNS failures, 30 brain metastases, 2 leptomeningeal metastases, and 8 brain and leptomeningeal metastases were noted. The 7-year CNS relapse-free survival rates in patients receiving and not receiving trastuzumab were 91.2% and 96.9%, respectively (p = 0.005). On multivariate analysis, the administration of adjuvant trastuzumab was the only prognostic factor in predicting a higher CNS failure rate (hazard ratio, 2.260; 95% confidence interval, 1.076-4.746; p = 0.031). Conclusion Adjuvant trastuzumab was associated with higher CNS failure rate in Korean patients with HER2-enriched breast cancer. Close monitoring and reasonable approaches such as CNS penetrating HER2 blockades combined with the current standard therapy could contribute to improving intracranial tumor control and quality of life in patients with CNS metastasis from HER2-enriched breast cancer.

Background/aim To present the variations in the target delineation and the planning results of intensity-modulated radiation therapy (IMRT) for breast cancers. Patients and methods We requested the target volumes and organs at risk delineation for two cases of left breast cancers, and evaluated the IMRT plans including the supraclavicular and internal mammary node irradiation. Results Twenty-one institutions participated in this study. Differences in the planning target volume among institutions reached up to three-times for breast-conserving surgery (BCS) case and five-times for mastectomy case. Mean heart doses ranged from 3.3 to 24.1 Gy for BCS case and from 5.0 to 26.5 Gy for mastectomy case. Ipsilateral lung volumes receiving more than 20 Gy ranged from 4.7 to 57.4% for BCS case and from 16.4 to 55.5% for mastectomy case. Conclusion There were large variations in the target delineation and planning results of IMRT for breast cancers among institutions. Considering the increased use of breast IMRT, more standardized protocols are needed.

Background We investigate the gamma passing rate (GPR) consistency when applying different types of gamma analyses, linacs, and dosimeters for volumetric modulated arc therapy (VMAT). Methods A total of 240 VMAT plans for various treatment sites, which were generated with Trilogy (140 plans) and TrueBeam STx (100 plans), were retrospectively selected. For each VMAT plan, planar dose distributions were measured with both MapCHECK2 and ArcCHECK dosimeters. During the planar dose distribution measurements, the actual multileaf collimator (MLC) positions, gantry angles, and delivered monitor units were recorded and compared to the values in the original VMAT plans to calculate mechanical errors. For each VMAT plan, both the global and local gamma analyses were performed with 3%/3 mm, 2%/2 mm, 2%/1 mm, 1%/2 mm, and 1%/1 mm. The Pearson correlation coefficients (r) were calculated 1) between the global and the local GPRs, 2) between GPRs with the MapCHECK2 and the ArcCHECK dosimeters, 3) and between GPRs and the mechanical errors during the VMAT delivery. Results For the MapCHECK2 measurements, strong correlations between the global and local GPRs were observed only with 1%/2 mm and 1%/1 mm (r > 0.8 with p 0.05), while the local GPRs showed moderate correlations only with 2%/1 mm and 1%/1 mm for TrueBeam STx (r > 0.5 with p

Purpose To implement the DMAIC (Define-Measure-Analyze-Improve-Control) can be used for customizing the patient-specific QA by designing site-specific range tolerances. Methods The DMAIC framework (process flow diagram, cause and effect, Pareto chart, control chart, and capability analysis) were utilized to determine the steps that need focus for improving the patient-specific QA. The patient-specific range QA plans were selected according to seven treatment site groups, a total of 1437 cases. The process capability index, Cpm was used to guide the tolerance design of patient site-specific range. Results For prostate field, our results suggested that the patient range measurements were capable at the current tolerance level of ±1 mm in clinical proton plans. For other site-specific ranges, we analyzed that the tolerance tends to be overdesigned to insufficient process capability calculated by the patient-specific QA data. The customized tolerances were calculated for treatment sites. Control charts were constructed to simulate the patient QA time before and after the new tolerances were implemented. It is found that the total simulation QA time was decreased on average of approximately 20% after establishing new site-specific range tolerances. We simulated the financial impact of this project. The QA failure for whole process in proton therapy would lead up to approximately 30% increase in total cost. Conclusion DMAIC framework can be used to provide an effective QA by setting customized tolerances. When tolerance design is customized, the quality is reasonably balanced with time and cost demands.

The purpose of this study was to evaluate the differential effect of chemotherapy regimen in preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer.The medical records of 279 patients who underwent preoperative CRT followed by surgery for cT3/4 rectal cancer from 2003 to 2010 were retrospectively reviewed. Thirty-four patients were treated with one cycle of i.v. bolus 5-fluorouracil (5-FU) during 1st week (group A), 214 patients with two cycles of i.v. bolus 5-FU during 1st and 5th week (group B), and 31 patients with oral capecitabine on the days with radiotherapy (group C). Propensity score matching was performed between three groups.Median follow-up was 60.1 months. Five-year locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) rates were 91.2, 83.3, 75.0, and 84.5%, respectively. Thirty-one patients per group were allocated to three groups via propensity score matching. On univariate analysis, concurrent chemotherapy regimen was not a significant prognostic factor for survival outcomes in the matched group analysis (OS, p=0.175; DFS, p=0.481; DMFS, p=0.515; LRFS, p=0.456). In addition, there was no significant difference in the sphincter preserving surgery rate, circumferential resection margin status, and pathologic response between three groups (p=0.441, 1.000, 0.818, respectively). As regards to treatment-related toxicity, 9 patients showed grade 3 neutropenia in group B, while there was no grade 3 or higher toxicity in groups A and C.The concurrent chemotherapy regimen (5-FU #1 vs 5-FU #2 vs capecitabine) did not have a significant effect on treatment outcomes in locally advanced rectal cancer patients receiving neoadjuvant CRT.

We investigated changes in PA levels by the treatment of human bone-marrow-derived mesenchymal stem cells (hBM-MSCs) in ischemic stroke in rat brain model and in cultured neuronal SH-SY5Y cells exposed to oxygen-glucose deprivation (OGD). In ischemic rat model, transient middle cerebral artery occlusion (MCAo) was performed for 2 h, followed by intravenous transplantation of hBM-MSCs or phosphate-buffered saline (PBS) the day following MCAo. Metabolic profiling analysis of PAs was examined in brains from three groups: control rats, PBS-treated MCAo rats (MCAo), and hBM-MSCs-treated MCAo rats (MCAo + hBM-MSCs). In ischemic cell model, SH-SY5Y cells were exposed to OGD for 24 h, treated with hBM-MSCs (OGD + hBM-MSCs) prior to continued aerobic incubation, and then samples were collected after coculture for 72 h. In thein vivoMCAo ischemic model, levels of some PAs in brain samples of the MCAo and MCAo + hBM-MSCs groups were significantly different from those of the control group. In particular, putrescine, cadaverine, and spermidine in brain tissues of the MCAo + hBM-MSCs group were significantly reduced in comparison to those in the MCAo group. In thein vitroOGD system,N1-acetylspermidine, spermidine,N1-acetylspermine, and spermine in cells of the OGD + hBM-MSCs group were significantly reduced compared to those of OGD group.

Purpose The purpose of this study was to develop a patient-specific elastic skin applicator and to evaluate its dosimetric characteristics for high-dose-rate (HDR) brachytherapy. Methods and Materials We simulated the treatment of a nonmelanoma skin cancer on the nose. An elastic skin applicator was manufactured by pouring the Dragon Skin (Smooth-On Inc., Easton, PA) with a shore hardness of 10A into an applicator mold. The rigid skin applicator was printed using high-impact polystyrene with a shore hardness of 73D. HDR plans were generated using a Freiburg Flap (FF) applicator and patient-specific rigid and elastic applicators. For dosimetric assessment, dose-volumetric parameters for target volume and normal organs were evaluated. Global gamma evaluations were performed, comparing film measurements and treatment planning system calculations with various gamma criteria. The 10% low-dose threshold was applied. Results The V120% values of the target volume were 56.9%, 70.3%, and 70.2% for HDR plans using FF, rigid, and elastic applicators, respectively. The maximum doses of the right eyeball were 21.7 Gy, 20.5 Gy, and 20.5 Gy for the HDR plans using FF, rigid, and elastic applicators, respectively. The average gamma passing rates were 82.5% ± 1.5%, 91.6% ± 0.8%, and 94.8% ± 0.2% for FF, rigid, and elastic applicators, respectively, with 3%/3 mm criterion. Conclusions Patient-specific elastic skin applicator showed better adhesion to irregular or curved body surfaces, resulting in better agreement between planned and delivered dose distributions. The applicator suggested in this study can be effectively implemented clinically.

This paper is about use cases of congestive heart failure. The purpose of this paper is to know through the use of the congestive heart failure use cases the currently developing smart patch at some stage to apply to patients with congestive heart failure. This smart patch has a total of three sensors. The sensor is an electrocardiogram, acceleration, impedance. We examined definitions, symptoms, causes, diagnosis, and methods of congestive heart failure and we have described the process from the stage where the patient first visited the hospital to the stage where he or she is discharged to the hospital, as a total of ten stages of use cases. The smart patch currently under development can be applied at the stage of confirming the therapeutic effect of congestive heart failure patients.

Adjuvant radiotherapy (RT) is a well-established treatment for breast cancer. However, there is a large degree of variation and controversy in practice patterns. A nationwide survey on the patterns of practice in breast RT was designed by the Division for Breast Cancer of the Korean Radiation Oncology Group. All board-certified members of the Korean Society for Radiation Oncology were sent a questionnaire comprising 39 questions on six domains: hypofractionated whole breast RT, accelerated partial breast RT, postmastectomy RT (PMRT), regional nodal RT, RT for ductal carcinoma in situ, and RT toxicity. Sixty-four radiation oncologists from 54 of 86 (62.8%) hospitals responded. Twenty-three respondents (35.9%) used hypofractionated whole breast RT, and the most common schedule was 43.2 Gy in 16 fractions. Only three (4.7%) used accelerated partial breast RT. Five (7.8%) used hypofractionated PMRT, and 40 (62.5%) had never used boost RT after chest wall irradiation. Indications for regional nodal RT varied; ≥pN2 (n=7) versus ≥pN1 (n=17) versus ≥pN1 with pathologic risk factors (n=40). Selection criteria for internal mammary lymph node (IMN) irradiation also varied; only four (6.3%) always treated IMN when regional nodal RT was administered and 30 (46.9%) treated IMN only if IMN involvement was identified through imaging. Thirty-one (48.4%) considered omission of whole breast RT after breast-conserving surgery for ductal carcinoma in situ based on clinical and pathologic risk factors. Fifty-two (81.3%) used heart-sparing techniques. Overall, there were wide variations in the patterns of practice in breast RT in Korea. Standard guidelines are needed, especially for regional nodal RT and omission of RT for ductal carcinoma in situ.

Purpose We evaluated the glass dosimeter suitability as an external audit program in proton therapy beam. A feasibility test of the glass dosimeter postal dose intercomparison was performed for high-energy proton beam use in radiation oncology with the collaboration of five proton therapy centers (Shizuoka Cancer Center, University of Florida Proton Center, MD Anderson Cancer Center, Loma Linda University Medical Center, and University of Pennsylvania School of Medicine). Material and methods The dosimetric properties of a GD-301 glass dosimeter were investigated for its potential use for postal dosimetry. Measurements were performed in a water phantom using a stair-like holder specially designed for this study. The depth-dose distribution measured with the glass dosimeter was compared to those from GEANT4 Monte-Carlo simulation. The GEANT4 code was also used to simulate the influence of holder material in the absorbed dose by inserting the glass dosimeter in a water phantom within the stair-like holder. We investigated the methodology of the absorbed dose determination with the glass dosimeter system establishing the calibration factor and various correction factors (non-linearity, fading, energy, holder). The participating proton therapy centers were asked to irradiate the glass dosimeter to 2 Gy with similar setup and conditions. Results The repeatability and dose rate dependence is within 1.2% and 1.5%, respectively. Depth-dose distributions in the pristine Bragg curve and the spread-out Bragg curve were estimated to be within 3%, compared with depth-dose measured with the ionization chamber. The difference in absorbed dose between the glass dosimeter and ionization chamber was within ±2% as a function of proton beam quality, residual ranges were between 2.1 and 9.0 cm. The influence of the holder material in absorbed doses of the proton beams is less than 1%. In the accuracy evaluation of the glass dosimeter system established in blind test, we obtained within 2.5% agreements with the ionization chamber dosimetry for the proton beam. In this feasibility study, the results on the proton beam output check are relatively good within ±6% for all participating centers. Conclusion We believe that the glass dosimeter system has considerable potential to be used for a postal dose audit program in proton beam.

To investigate the accuracy of Eclipse treatment planning system (TPS) dose calculations at the surface. It is desirable to know the accuracy of the proton treatment planning system in predicting dose at superficial region. All measurements were performed in a clinical proton beam at the National Cancer Center in Korea. Proton treatment plans were developed for a superficial planning target volume (PTV) contoured on a cylindrical polymethylmethacrylate phantom specially designed for this study. Dose was then measured at the surface and also in the PTV for these treatment plans and compared against the TPS calculations. For our study, a model GD-301 glass dosimeters were used. The proton treatment planning system overestimated the superficial dose without use of bolus as much as by 7–14% when compared to glass dosimeter. On the other hand, with use of bolus to cover the superficial region, surface dose between the calculation from Eclipse and measurement using the glass dosimeter are approximately within 3%.

Metallic eye shields have been widely used for near-eye treatments to protect critical regions, but have never been incorporated into treatment plans because of the unwanted appearance of the metal artifacts on CT images. The purpose of this work was to test the use of an acrylic dummy eye shield as a substitute for a metallic eye shield during CT scans. An acrylic dummy shield of the same size as the tungsten eye shield was machined and CT scanned. The BEAMnrc and the DOSXYZnrc were used for the Monte Carlo (MC) simulation, with the appropriate material information and density for the aluminum cover, steel knob and tungsten body of the eye shield. The Pinnacle adopting the Hogstrom electron pencil-beam algorithm was used for the one-port 6-MeV beam plan after delineation and density override of the metallic parts. The results were confirmed with the metal oxide semiconductor field effect transistor (MOSFET) detectors and the Gafchromic EBT2 film measurements. For both the maximum eyelid dose over the shield and the maximum dose under the shield, the MC results agreed with the EBT2 measurements within 1.7%. For the Pinnacle plan, the maximum dose under the shield agreed with the MC within 0.3%; however, the eyelid dose differed by -19.3%. The adoption of the acrylic dummy eye shield was successful for the treatment plan. However, the Pinnacle pencil-beam algorithm was not sufficient to predict the eyelid dose on the tungsten shield, and more accurate algorithms like MC should be considered for a treatment plan.

Changes in target-induced cold and hot spots may result in significant dose differences to some parts of a target, which might be related to clinical outcome. We suggest a guideline for adaptive planning using megavoltage CT (MVCT) during tomotherapy. Twenty-one head-and-neck cancer patients, including eight who experienced relatively large weight loss during tomotherapy treatment, were evaluated retrospectively with initial and final MVCT images to quantify the greatest weightloss effects. Kilovoltage CTs (KVCTs) of five patients were obtained during radiation therapy (RT), and volumes of targets and organs were delineated on the KVCTs. Direct machine parameter optimization (DMPO) was used to generate intensity-modulated radiotherapy (IMRT) plans. The beam configurations of the initial plans were applied to the second KVCT images. We compared changes in target dose and organs with various parameters. We compared the initial and the final MVCTs of the 21 patients undergoing tomotherapy with the same initial target. We found that the average of the maximum and mean doses delivered to the gross tumor increased. Data on modified targets and organs on KVCT imaging from five patients showed that the maximum and the mean doses delivered to the gross tumor increased and that the minimum dose decreased. Heterogeneity and coverage also decreased similarly when the overall results from the 21 patients were assessed. The relative thicknesses of the five patients were close to 0.9, and therapy for some patients required replanning. When the thickness value was less than 0.85, adaptive planning was recommended during tomotherapy even if the setup variation had also been considered. Attention should be paid to weight loss during tomotherapy treatment, and if a patient shows significant weight loss, an adaptive plan should be considered to achieve prescribed doses to targets and to spare nearby critical structures.

Purpose: To overcome the problem of organ motion in intensity-modulated radiation therapy (IMRT), gated IMRT is often used for the treatment of lung cancer. In this study, the authors investigated the accuracy of the delivered monitor units (MUs) from each segment during gated IMRT using a two-dimensional detector array for user-specific verification purpose. Methods: The authors planned a 6 MV photon, seven-port step-and-shoot lung IMRT delivery. The respiration signals for gated IMRT delivery were obtained from the one-dimensional moving phantom using the real-time position management (RPM) system (Varian Medical Systems, Palo Alto, CA). The beams were delivered using a Clinac iX (Varian Medical Systems, Palo Alto, CA) with the Millennium 120 MLC. The MatriXX (IBA Dosimetry GmbH, Germany) was validated through consistency and reproducibility tests as well as comparison with measurements from a Farmer-type ion chamber. The authors delivered beams with varying dose rates and duty cycles and analyzed the MatriXX data to evaluate MU delivery accuracy. Results: There was quite good agreement between the planned segment MUs and the MUs computed from the MatriXX within {+-}2% error. The beam-on times computed from the MatriXX data were almost identical for all cases, and they matched well with the RPM beam-onmore » and beam-off signals. A slight difference was observed between them, but it was less than 40 ms. The gated IMRT delivery demonstrated an MU delivery accuracy that was equivalent to ungated IMRT, and the delivered MUs with a gating signal agreed with the planned MUs within {+-}0.5 MU regardless of dose rate and duty cycle. Conclusions: The authors can conclude that gated IMRT is able to deliver an accurate dose to a patient during a procedure. The authors believe that the methodology and results can be transferred to other vendors' devices, particularly those that do not provide MLC log data for a verification purpose.« less

The intensity-modulated radiation therapy (IMRT) planning strategies for nasopharyngeal cancer among Korean radiation oncology facilities were investigated. Five institutions with IMRT planning capacity using the same planning system were invited to participate in this study. The institutions were requested to produce the best plan possible for 2 cases that would deliver 70 Gy to the planning target volume of gross tumor (PTV1), 59.4 Gy to the PTV2, and 51.5 Gy to the PTV3 in which elective irradiation was required. The advised fractionation number was 33. The planning parameters, resultant dose distributions, and biological indices were compared. We found 2-3-fold variations in the volume of treatment targets. Similar degree of variation was found in the delineation of normal tissue. The physician-related factors in IMRT planning had more influence on the plan quality. The inhomogeneity index of PTV dose ranged from 4 to 49% in Case 1, and from 5 to 46% in Case 2. Variation in tumor control probabilities for the primary lesion and involved LNs was less marked. Normal tissue complication probabilities for parotid glands and skin showed marked variation. Results from this study suggest that greater efforts in providing training and continuing education in terms of IMRT planning parameters usually set by physician are necessary for the successful implementation of IMRT.

Several studies on the effect of tumor cell killing by dose rate variation have implied that the use of a shorter treatment time is more favorable for intensity modulated radiation therapy (IMRT). Aiming at step-and-shoot IMRT with higher dose rates, the stabilities of beam output and profiles with small monitor unit (MU) settings were investigated for various dose rates. With the use of a Varian 21EX (Varian Medical Systems Inc., Palo Alto, CA), static and step-and-shoot IMRT beam output along with profiles were measured by use of an ion chamber and a two-dimensional diode array detector as a function of monitor units and dose rates. For a static case, as the MU approached 1, the beam output increased up to 2% for 300 MU/min and 4.5% for 600 MU/min, showing a larger overdose as the dose rate increased. Deterioration of the beam symmetry and flatness were also observed as the MU decreased to 1 monitor unit. For the step-and-shoot IMRT case, a large dosimetric error of more than 10% was also detected with the use of a small MU segment. However, no definite correlation with the dose rate was observed due to the combined beam start-up effects by the grid pulse and finite communication time between the machine console and multileaf collimator (MLC) controller. For step-and-shoot IMRT with higher dose rates, beam output and beam profile stability with small MU needs to be checked, and adequate MU limitation where segments are not allowed need to be reflected in the step-and-shoot IMRT planning.

Four novel human leukocyte antigen (HLA)-DQA1 alleles have been characterized by direct DNA sequencing of coding exons 1-4. All the novel alleles exhibited a single nucleotide substitution either in exon 3 or in exon 4 when compared with previously defined alleles. Thus, it is likely that alleles were generated by point mutation from pre-existing alleles in the population. Substitutions resulted in either a silent (DQA1*010203) or an amino acid change (DQA1*0506, DQA1*0507, and DQA1*0508). The substituted sites were both previously known polymorphic and conserved positions. Putative haplotypes associated with the novel alleles were deduced based on the HLA types shared by the individuals carrying a novel allele or from previously reported population data.

To evaluate and improve the reliability of proton quality assurance (QA) processes and, to provide an optimal customized tolerance level using the statistical process control (SPC) methodology.The authors investigated the consistency check of dose per monitor unit (D/MU) and range in proton beams to see whether it was within the tolerance level of the daily QA process. This study analyzed the difference between the measured and calculated ranges along the central axis to improve the patient-specific QA process in proton beams by using process capability indices.The authors established a customized tolerance level of ±2% for D/MU and ±0.5 mm for beam range in the daily proton QA process. In the authors' analysis of the process capability indices, the patient-specific range measurements were capable of a specification limit of ±2% in clinical plans.SPC methodology is a useful tool for customizing the optimal QA tolerance levels and improving the quality of proton machine maintenance, treatment delivery, and ultimately patient safety.

In this paper, we propose a secure, distributed and scaleable infrastructure for a lifelong personal medical record system. We leverage on existing and widely available technologies, like the Web and public-key cryptography, to define an architecture that allows patients to exercise full control over their medical data. This is done without compromising patients' privacy and the ability of other interested parties (e.g. physicians, health-care institutions, public-health researchers) to access the data when appropriately authorized. The system organizes the information as a tree of encrypted plain-text XML files, in order to ensure platform independence and durability, and uses a role-based authorization scheme to assign access privileges. In addition to the basic architecture, we describe tools to populate the patient's record with data from hospital databases and the first testbed applications we are deploying.

Purpose: To evaluate the suitability of the GD-301 glass dosimeter for in vivo dose verification in proton therapy. Methods and Materials: The glass dosimeter was analyzed for its dosimetrics characteristic in proton beam. Dosimeters were calibrated in a water phantom using a stairlike holder specially designed for this study. To determine the accuracy of the glass dosimeter in proton dose measurements, we compared the glass dosimeter and thermoluminescent dosimeter (TLD) dose measurements using a cylindrical phantom. We investigated the feasibility of the glass dosimeter for the measurement of dose distributions near the superficial region for proton therapy plans with a varying separation between the target volume and the surface of 6 patients. Results and Discussion: Uniformity was within 1.5%. The dose-response has good linearity. Dose-rate, fading, and energy dependence were found to be within 3%. The beam profile measured using the glass dosimeter was in good agreement with the profile obtained from the ionization chamber. Depth-dose distributions in nonmodulated and modulated proton beams obtained with the glass dosimeter were estimated to be within 3%, which was lower than those with the ionization chamber. In the phantom study, the difference of isocenter dose between the delivery dose calculated by the treatmentmore » planning system and that measured by the glass dosimeter was within 5%. With in vivo dosimetry, the calculated surface doses overestimated measurements by 4%-16% using glass dosimeter and TLD. Conclusion: It is recommended that bolus be added for these clinical cases. We also believe that the glass dosimeter has considerable potential for use with in vivo patient proton dosimetry.« less

Purpose The GD-301 radiophotoluminescent glass dosimeter system has recently become commercially available. The purpose of this study was to investigate the dosimetric characteristics (reproducibility, linearity, dose rate, fading, angular dependence, and depth–dose distribution) of this system for clinical dosimetry in a high-energy proton beam and to compare it with lithium fluoride TLD-100. Materials and methods The depth–dose distribution measured with the glass dosimeter was compared to those from GEANT4 Monte-Carlo simulation. All measurements were performed in a proton beam (IBA Proton Therapy System-Proteus 235) at the National Cancer Center in Korea. Dosimeters were irradiated in a water phantom using a stair-shaped holder specially designed for this study. Maximum height was 100 mm with 1 mm steps in each of ten-tiers. Results Reproducibility in the 200 MeV proton beam was within 1.5% for the glass dosimeter, and within 1.7% for TLD-chip responses. The glass dosimeter signal was linear as a function of applied dose in the range of 1–10 Gy. The dose rate dependence of both dosimeters was within 1.5%. The fading effect of the glass dosimeter was found to be within 1.6% for 6 months. Angular dependence of the glass dosimeter was measured to be approximately 1.3% for angles that were 80° from the beam axis using a cylindrical phantom. Depth–dose distributions in the non-modulated and modulated proton beams obtained with the glass dosimeter were estimated to be within 3.0% lower than those measured with the ionization chamber and simulation model using GEANT4 code. The Bragg peak depths determined from the ionization chamber, the glass dosimeter and GEANT4 simulation were 84.8 mm, 84.2 mm and 85.0 mm, respectively. For the modulated proton beam, the SOBP width between the 90% proximal and the distal dose levels as obtained from the glass dosimeter was 48.1 mm. The SOBP width measured with the ionization chamber was 52.2 mm. Conclusions Measurements comparing the glass dosimeter and TLD-100 dosimetric characteristics demonstrated the suitability of use of the glass dosimeter for dose measurement in high-energy proton beam therapy.

To overcome the problem of organ motion in intensity-modulated radiation therapy (IMRT), gated IMRT is often used for the treatment of lung cancer. In this study, the authors investigated the accuracy of the delivered monitor units (MUs) from each segment during gated IMRT using a two-dimensional detector array for user-specific verification purpose.The authors planned a 6 MV photon, seven-port step-and-shoot lung IMRT delivery. The respiration signals for gated IMRT delivery were obtained from the one-dimensional moving phantom using the real-time position management (RPM) system (Varian Medical Systems, Palo Alto, CA). The beams were delivered using a Clinac iX (Varian Medical Systems, Palo Alto, CA) with the Millennium 120 MLC. The MatriXX (IBA Dosimetry GmbH, Germany) was validated through consistency and reproducibility tests as well as comparison with measurements from a Farmer-type ion chamber. The authors delivered beams with varying dose rates and duty cycles and analyzed the MatriXX data to evaluate MU delivery accuracy.There was quite good agreement between the planned segment MUs and the MUs computed from the MatriXX within +/- 2% error. The beam-on times computed from the MatriXX data were almost identical for all cases, and they matched well with the RPM beam-on and beam-off signals. A slight difference was observed between them, but it was less than 40 ms. The gated IMRT delivery demonstrated an MU delivery accuracy that was equivalent to ungated IMRT, and the delivered MUs with a gating signal agreed with the planned MUs within +/- 0.5 MU regardless of dose rate and duty cycle.The authors can conclude that gated IMRT is able to deliver an accurate dose to a patient during a procedure. The authors believe that the methodology and results can be transferred to other vendors' devices, particularly those that do not provide MLC log data for a verification purpose.

A commercial radiation treatment planning system, Pinnacle3, has been prepared for the electron arc treatment with a Varian machine. For this purpose, a new physics machine was commissioned for the exclusive electron arc therapy. The electron arc plan was made with multiple static beams with fixed interval. The phantom measurements were executed with a MOSFET and EBT films. The resulting plan shows an impressive dose distribution, however, in-vivo dosimetry for a few representative points should be proceeded before treatment to be sure of the calculation accuracy.

Dose uniformity was estimated depending on the number of control points in forward-planned intensity-modulated radiation therapy for breast cancer.

Several studies on the effect of tumor cell killing by dose rate variation have implied that the use of a shorter treatment time is more favorable for intensity modulated radiation therapy (IMRT). Aiming at step-and-shoot IMRT with higher dose rates, the stabilities of beam output and profiles with small monitor unit (MU) settings were investigated for various dose rates. With the use of a Varian 21EX (Varian Medical Systems Inc., Palo Alto, CA), static and step-and-shoot IMRT beam output along with profiles were measured by use of an ion chamber and a two-dimensional diode array detector as a function of monitor units and dose rates. For a static case, as the MU approached 1, the beam output increased up to 2% for 300 MU/min and 4.5% for 600 MU/min, showing a larger overdose as the dose rate increased. Deterioration of the beam symmetry and flatness were also observed as the MU decreased to 1 monitor unit. For the step-and-shoot IMRT case, a large dosimetric error of more than 10% was also detected with the use of a small MU segment. However, no definite correlation with the dose rate was observed due to the combined beam start-up effects by the grid pulse and finite communication time between the machine console and multileaf collimator (MLC) controller. For step-and-shoot IMRT with higher dose rates, beam output and beam profile stability with small MU needs to be checked, and adequate MU limitation where segments are not allowed need to be reflected in the step-and-shoot IMRT planning.

This chapter focuses on three new studies that used autologous (i.e., when the donor and recipient are the same individual) and heterologous (i.e., when the donor and recipient are different individuals) transplants of adult, bone-marrow-derived stem cells to counteract the behavioral deficits produced by intrastriatal injections of quinolinic acid (QA) in rats, a rodent model for Huntington’s disease (HD). These studies support previous findings that have demonstrated that transplants of adult bone-marrow-derived stem cells can survive and integrate into the host tissue and can counteract functional deficits caused by CNS damage. In the initial study using this HD model, nestin-positive cells were observed 14 d after the transplant and GAD-positive cells were observed at 21 d posttransplant, a finding that supports the contention that adult bone-marrow stem cells possess the plasticity to transdifferentiate into neurons. However, because less than 1% of the cells expressed neuronal phenotypes, and because the functional recovery observed in all three studies occurred within 1 mo after transplantation, it is hypothesized that the ameliorative effects of the transplants were due to the production of neurotrophic factors that facilitated functioning of spared neurons, rather than through the replacement of lost neurons. When compared with transplants of heterologous stem cells, the transplants of autologous stem cells were more efficacious, at least for reducing QA-induced behavioral deficits. Because the use of autologous transplants in HD may prove unfeasible, if the mutant gene becomes expressed in the transplanted autologous stem cells, it may become critically important to find ways to reduce any adverse immunological response or other factors that may be limiting the efficacy of heterologous transplants, if this form of therapy is to become clinically viable for HD. In summary, the findings reported in this chapter support the contention that transplantation of adult, bone-marrow-derived stem cells has significant therapeutic potential as a treatment for HD, but research into how to prevent a possible immune reaction of the heterologous transplant may prove to be critical before this approach has clinical utility.

Genotype of the human leukocyte antigen (HLA)-DQA1 locus was analyzed in Koreans (n= 467) using the 14th International Workshop protocol established to characterize the sequences of exons 1-4 of the gene. Unexpectedly, it appeared that the DQA1 (19 alleles) was more diverse than DQB1 (15 alleles) in the study population. DQA1*010201, DQA1*0303, DQA1*0103, and DQA1*0302 appeared to be major alleles exhibiting more than 10%. Among six allele groups, DQA1*01-*06, DQA1*01 showed highest diversity exhibiting seven different alleles. Analysis using maximum likelihood method showed numerous multi-locus HLA haplotypes. High relative linkage disequilibrium values (RLD) of the two-locus haplotypes and exclusive association of a specific DQA1 allele with a specific DRB1 and/or DQB1 alleles suggested tight linkage of DQA1 to DRB1 and DQB1. In HLA-matching process for hematopoietic stem cell transplantation, however, DQA1 typing would be informative for individuals carrying specific DRB1 allele (DRB1*0802, DRB1*1201, or DRB1*1403) that could be associated with multiple DQA1 alleles in the study population. Information obtained in this study will be useful in medical and forensic areas as well as in anthropology.

Purpose: To evaluate and improve the reliability of proton quality assurance (QA) processes and, to provide an optimal customized tolerance level using the statistical process control (SPC) methodology. Methods: The authors investigated the consistency check of dose per monitor unit (D/MU) and range in proton beams to see whether it was within the tolerance level of the daily QA process. This study analyzed the difference between the measured and calculated ranges along the central axis to improve the patient-specific QA process in proton beams by using process capability indices. Results: The authors established a customized tolerance level of ±2% for D/MU and ±0.5 mm for beam range in the daily proton QA process. In the authors’ analysis of the process capability indices, the patient-specific range measurements were capable of a specification limit of ±2% in clinical plans. Conclusions: SPC methodology is a useful tool for customizing the optimal QA tolerance levels and improving the quality of proton machine maintenance, treatment delivery, and ultimately patient safety.

BACKGROUND At present the addition of thoracic irradiation to combination chemotherapy is a standard treatment for limited staged small cell lung cancer. However, there is still controversy about the optimum timing of chest irradiation. We conducted a phase II study of etoposide (VP-16)-ifosfamide-cisplatin (VIP) combination chemotherapy plus early concurrent thoracic irradiation for the patients with previously untreated limited small cell lung cancer in order to assess if the treatment modality could improve the response rate and the toxicity. METHODS Forty-four patients with limited small cell lung cancer were treated with etoposide-ifosfamide-cisplatin and concurrent thoracic irradiation. Combination chemotherapy consisted of etoposide 100 mg/m2 (on days 1-3), ifosfamide 1000 mg/m2 (on days 1 and 2) and cisplatin 100 mg/m2 (on day 1). Concurrent thoracic irradiation consisted of a total of 4000 cGy over 4 weeks starting on the first day of the first chemotherapy. All patients who showed a complete response were given prophylactic cranial irradiation for 2.5 weeks. RESULTS Forty-four of the 49 patients who entered the study from May 1994 to August 1998 were evaluable. The median age was 59 years and 40 patients had a performance status of 0 or 1. The median survival time was 22.5 months. Twenty-eight patients (62%) showed a complete response and 16 (38%) a partial response. Twenty-four patients (54%) developed grade 3 or 4 neutropenia; there was a 9% RTOG score 3 or 4 esophagitis. CONCLUSION VIP combination chemotherapy and early concurrent thoracic irradiation for patients with limited stage small cell lung cancer revealed excellent antitumor response with tolerable toxicity.

Background A Patterns-of-Care Study (PCS) was conducted to determine the patterns of evaluation and treatment for nonmetastatic non— small-cell lung cancer (NSCLC) in Korea. Patients and Methods A Web-based data system for Korean PCS was developed, and a national survey was conducted. Patients who received thoracic radiation therapy (RT) for clinical or pathologic stage I-III NSCLC without other malignancy in 1998 and 1999 were eligible and randomly selected by power allocation method. Results The records of 446 selected patients from 19 institutions were reviewed, and 10 patients were excluded because of incomplete clinical information. Accordingly, 436 patients were the subjects of this study, with a median age of 62.2 years (range, 33.1–88 years) and male-to-female ratio of 86:14. The histologies were squamous cell carcinoma in 61.2%, adenocarcinoma in 28.4%, large-cell carcinoma in 2.3%, and NSCLC not otherwise specified in 8% of patients, respectively. Bone scan, abdominal ultrasonography or computed tomography (CT), brain CT or magnetic resonsance imaging, and positron emission tomography were examined in 92.5%, 81.5%, 44.8%, and 26.6% of patients, respectively. The clinical stage was I in 8.9%, II in 12.2%, IIIA in 37.4%, and IIIB in 41.5%, respectively. Regarding treatment modalities, RT was used alone in 38.1%; RT combined with operation in 22.9%; RT combined with chemotherapy in 27.1%; and trimodalities including RT, operation, and chemotherapy in 11.9%. The median total dose was 59.4 Gy with daily median fraction size of 1.8 Gy, and the percent delivered dose > 90% was achieved in 87.6%. Most of patients received RT in supine position (99.3%) with beam direction of anterior-posterior/posterior-anterior (95.6%) as their first RT plan and with photon energy of 6 MV (42%) followed by 10 MV (41.7%). The chemotherapy-based planning was used in 2.3 % and 32.6% for their first and second RT plan, respectively. The 3-or-more RT planning was performed in 13.5% of patients. Elective nodal irradiation was used in 87.8% of patients, and the N2 nodal station (48.6%) was most frequently included. The 8% of patients received thoracic RT based on prospective protocol. Conclusion This study is the first PCS for NSCLC conducted in Korea. We confirmed that various types of RT planning were used according to each institution, but beam delivery techniques were not much different between 1998 and 1999. Another PCS is planned to evaluate changing trends in national practice.

It has been speculated that human leukocyte antigen (HLA) alleles are associated with the outcome of hepatitis B virus (HBV) infection although the data obtained from various populations have shown some inconsistencies. A total of 464 HBV-infected Korean individuals (80 spontaneously recovered [SR] and 384 chronically infected [CI]) were selected to investigate the association of HLA class II alleles with the viral clearance and persistence. Our results showed that: 1) multiple HLA class II alleles and haplotypes were associated with viral clearance (DRB1*1302, DRB1*1502, DQB1*0302, DQB1*0609, and related-haplotypes) and persistence (DRB1*0701, DQB1*0301, and related-haplotypes); 2) DRB1*1302 and DQB1* 0609 were more strongly associated with viral clearance. And the association of DQB1*0609 (pc=0.0084; OR, 7.24) with vial clearance was much stronger than previously recognized, DRB1*1302 (pc=0.0038; OR, 4.34); and 3) linkage to a specific DPB1 allele in a haplotype strengthened the association with viral clearance, although DPB1 itself was not associated with the outcome. These results indicate the existence of multiple factors controlling viral clearance in the HLA class II gene region. Further extended investigation on the genetic factors related to the outcome of HBV infection will provide valuable insights into the understanding of the mechanisms involved.

Background The purpose of this study is to evaluate the dosimetric benefits of a proton arc technique for treating tumors of the para-aortic lymph nodes (PALN). Method In nine patients, a proton arc therapy (PAT) technique was compared with intensity modulated radiation therapy (IMRT) and proton beam therapy (PBT) techniques with respect to the planning target volume (PTV) and organs at risk (OAR). PTV coverage, conformity index (CI), homogeneity index (HI) and OAR doses were compared. Organ-specific radiation induced cancer risks were estimated by applying organ equivalent dose (OED) and normal tissue complication probability (NTCP). Results The PAT techniques showed better PTV coverage than IMRT and PBT plans. The CI obtained with PAT was 1.19 ± 0.02, which was significantly better than that for the IMRT techniques. The HI was lowest for the PAT plan and highest for IMRT. The dose to the OARs was always below the acceptable limits and comparable for all three techniques. OED results calculated based on a plateau dose–response model showed that the risk of secondary cancers in organs was much higher when IMRT or PBT were employed than when PAT was used. NTCPs of PAT to the stomach (0.29 %), small bowel (0.69 %) and liver (0.38 %) were substantially lower than those of IMRT and PBT. Conclusion This study demonstrates that there is a potential role for PAT as a commercialized instrument in the future to proton therapy.