Inter-institutional Variation in Intensity-modulated Radiotherapy for Breast Cancer in Korea (KROG 19-01).

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.

Impact of plan parameters and modulation indices on patient-specific QA results for standard and stereotactic VMAT.

PURPOSE: To demonstrate the impact of modulation indices and plan parameters on the gamma passing rates (GPR) of patient-specific quality assurance of standard and stereotactic volumetric modulated arc therapy (VMAT) plans. METHODS: A total of 758 patients' QA plans were utilized, including standard VMAT plans with Trilogy (n = 87, group A) and TreuBeam STx (n = 332, group B), and 339 stereotactic VMAT plans with TrueBeam STx (group C). Modulation indices were obtained considering the speed and acceleration of the multileaf collimator (MLC) (MIs, MIa), and MLC, gantry speed, and dose rate changes (MIt). The mean aperture size (MA), monitor unit (MU), and amount of jaw tracking (%JT) were acquired. Gamma analysis was performed with 2 mm/2% and 1 mm/2% for the standard and stereotactic VMAT plans, respectively. Statistical analyses were performed to investigate the correlation between modulation index/plan parameters and GPR. RESULTS: Spearman's rank correlation to GPRs with MIs, MIa, and MIt, were -0.44, -0.45, and -0.46 for group A; -0.39, -0.37, and -0.38 for group B; and -0.04, -0.11, and -0.10 for group C, respectively. While MU and MA showed significant correlations in all groups, %JT showed a significant correlation only with stereotactic VMAT plans. The most influential parameter combinations were MU-MA (rs = 0.50), MIs-%JT (rs = 0.43), and MU-%JT (rs = 0.38) for groups A, B, and C, respectively. CONCLUSIONS: MLC modulation mostly affected the GPR in the delivery of standard VMAT plans, while MU and %JT showed more importance in stereotactic VMAT plans.

Differential effect of concurrent chemotherapy regimen on clinical outcomes of preoperative chemoradiotherapy for locally advanced rectal cancer.

PURPOSE: The purpose of this study was to evaluate the differential effect of chemotherapy regimen in preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Central Nervous System Failure in Korean Breast Cancer Patients with HER2-Enriched Subtype: Korean Radiation Oncology Group 16-15 Multicenter Retrospective Study.

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.

Development and dosimetric assessment of a patient-specific elastic skin applicator for high-dose-rate brachytherapy.

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.

Patterns of Practice in Radiotherapy for Breast Cancer in Korea.

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.

Reliability of the gamma index analysis as a verification method of volumetric modulated arc therapy plans.

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 < 0.001), while weak or no correlations were observed for the ArcCHECK measurement. Between the MapCHECK2 and ArcCHECK measurements, the global GPRs showed no correlations (all 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 < 0.001). Both the global and local GPRs always showed weak or no correlations with the MLC positional errors except for the GPRs of MapCHECK2 with 1%/2 mm and 1%/1 mm for TrueBeam STx and the GPR of ArcCHECK with 1%/2 mm for Trilogy (r < - 0.5 with p < 0.001). CONCLUSIONS: The GPRs varied according to the types of gamma analyses, dosimeters, and linacs. Therefore, each institution should carefully establish their own gamma analysis protocol by determining the type of gamma index analysis and the gamma criterion with their own linac and their own dosimeter.

Prognostic value of FDG PET/CT during radiotherapy in head and neck cancer patients.

PURPOSE: To evaluate the prognostic value of 18F-fluorodeoxyglucose positron-emission tomography (FDG PET) with computed tomography (CT) before and during radiotherapy (RT) in patients with head and neck cancer. METHODS: Twenty patients with primary head and neck squamous cell carcinoma were enrolled in this study, of whom 6 had oropharyngeal cancer, 10 had hypopharyngeal cancer, and 4 had laryngeal cancer. Fifteen patients received concurrent cisplatin and 2 received concurrent cetuximab chemotherapy. FDG PET/CT was performed before RT and in the 4th week of RT. The parameters of maximum standardized uptake value, metabolic tumor volume, and total lesion glycolysis (TLG) of the primary tumor were measured, and the prognostic significance of each was analyzed with the Cox proportional hazards model. RESULTS: Higher TLG (>19.0) on FDG PET/CT during RT was a poor prognostic factor for overall survival (OS) (p = 0.001) and progression-free survival (PFS) (p = 0.007). In the multivariate analysis, TLG during RT as a continuous variable was significantly associated with OS and PFS rate (p = 0.023 and p = 0.016, respectively). Tumor response worse than partial remission at 1 month after RT was another independent prognostic factor for PFS (p = 0.024). Conclusions: Higher TLG of the primary tumor on FDG PET/CT during RT was a poor prognostic factor for OS and PFS in patients with head and neck cancer.

Tolerance design of patient-specific range QA using the DMAIC framework in proton therapy.

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.

A treatment planning study of proton arc therapy for para-aortic lymph node tumors: dosimetric evaluation of conventional proton therapy, proton arc therapy, and intensity modulated radiotherapy.

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.

Feasibility study of using statistical process control to customized quality assurance in proton therapy.

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.

Application of a dummy eye shield for electron treatment planning.

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.

Dosimetric evaluation of a glass dosimeter for proton beam measurements.

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 100mm with 1mm 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 84.8mm, 84.2mm and 85.0mm, 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 48.1mm. The SOBP width measured with the ionization chamber was 52.2mm. 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.

Feasibility study of glass dosimeter for in vivo measurement: dosimetric characterization and clinical application in proton beams.

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 treatment 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.

Evaluation of delivered monitor unit accuracy of gated step-and-shoot IMRT using a two-dimensional detector array.

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-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. 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.

Multi-institutional comparison of intensity modulated radiation therapy (IMRT) planning strategies and planning results for nasopharyngeal cancer.

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.

Dosimetric characteristics of linear accelerator photon beams with small monitor unit settings.

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.

Human leukocyte antigen class II association with spontaneous recovery from hepatitis B virus infection in Koreans: analysis at the haplotype level.

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 HBVinfected 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.