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Purpose: This study aimed to determine the correlation between protein induced by vitamin K absence or antagonist-II (PIVKA-II) and stereotactic body radiotherapy (SBRT) in patients with hepatocellular carcinoma (HCC). Materials and Methods: Sixty-one patients received SBRT between 2015 and 2020 with a median dose of 48 Gy (range, 39 to 60 Gy) with a median of 4 fractions. Changes in tumor markers before and after SBRT were analyzed. Results: The median follow-up period was 31 months (range, 12 to 64 months). The estimated 2-year in-field failure-free survival, progression-free survival (PFS), and overall survival rates were 82.0%, 39.3%, and 96.7%, respectively. Patients with decreased PIVKA-II levels through SBRT had significantly few in-field failures (p = 0.005). Patients with PIVKA-II levels of ≤25 mAU/mL after SBRT had significantly long PFS (p = 0.004). Conclusion: PIVKA-II could be a useful surrogate marker for response or survival outcomes in patients with localized HCC receiving SBRT.

Purpose To evaluate the efficacy and toxicity of hypofractionated preoperative chemoradiotherapy (HPCRT) combined with oral capecitabine in patients with rectal cancer. Methods HPCRT was delivered by an intensity-modulated radiotherapy of either 33 Gy to the whole pelvis or 35 Gy in 10 fractions to the primary tumor and 33 Gy to the surrounding pelvis. Surgery was performed 4–8 weeks after HPCRT completion. Oral capecitabine was administered concurrently. Tumor response, toxicity, and survival were analyzed. Results Seventy-six patients were eligible for this study. Patients number of clinical stage I, II, III, and IVA were 5, 29, 36, and 6, respectively. Nine patients (11.8%) achieved a pathological complete response. Sphincter preservation was achieved in 23/32 (71.9%) and 44/44 (100%) of patients with a distal extent from anal verge of ≤ 5 cm and > 5 cm, respectively. Twenty-eight patients (36.8%) achieved T-downstaging, and 25 (32.9%) achieved N-downstaging. Five-year disease-free survival (DFS) was 73.6% and overall survival was 90.6%. In the multivariate analysis for DFS, significant prognostic factors were pathologic nodal stage and lymphovascular space invasion. Six patients with stage IVA underwent salvage treatments after HPCRT completion, and all survived to the final follow-up. Three patients experienced grade 3 postoperative complications. No grade 4 toxicities were observed. Conclusion HPCRT of 33 Gy or 35 Gy in 10 fractions showed similar results to those of long-course fractionation. This fractionation scheme could be beneficial for patients with early stage disease, locally advanced rectal cancer, simultaneous distant metastasis requiring early intervention, or for patients who wish to avoid multiple hospital visits.

In this study, the effect of Cl activation treatment on performance indicators of CdS/CdTe solar cells was investigated. We improved the performance of CdTe solar cells by applying a novel double treatment method that combines the CdCl2 dipping treatment and Freon (difluoro chloromethane) treatment methods that were previously studied. Conventional CdCl2 methanol dipping treatment (CdCl2 dipping treatment), Freon gas treatment that includes chlorine (Freon treatment), and CdCl2 dipping treatment + Freon treatment (double treatment) were performed, and the efficiencies, open circuit voltage (V OC ), and short circuit current (J SC ) for all three processes were observed. Although the efficiencies of the CdCl2 dipping treatment and Freon treatment were similar, there was a trade-off between the V OC and J SC in both processes. The double treatment sample shows an efficiency of 14.3%, which was higher than that of a single-treated sample. To investigate the characteristic change of each part of the solar cell, an equivalent circuit model in which the device was divided into a main junction and a back contact was used. In addition to electrical measurements, secondary ion mass spectroscopy (SIMS) and time of flight (TOF) analysis were performed. Through TOF measurement, drift mobility values for three treatment samples were calculated to be 1.1 cm 2/Vs, 1.8 cm 2/Vs, and 1.9 cm 2/Vs, respectively. With TOF measurement, it was proved that the double treatment had a significant influence on the efficiency of the sample.

The internal target volume (ITV)-based IMRT method can be used to reduce the effect of respiratory tumor motion. In this study, the effect of tumor motion on the dosimetric accuracy during ITV-based IMRT was investigated. ITV-based IMRT plans for a total of ten cases of liver cancer were prepared in TomoTherapy (Tomo) and volumetric modulated arc therapy (VMAT). Delivery quality assurance (DQA) plans were created using Delta4 phantom for the verification of dosimetric accuracy of the established Tomo and VMAT plans. DQA measurements were performed in both the static mode and the Hexa-Motion mode by using the Delta4 Hexa-Motion system in Tomo and VMAT. In the static mode, the average gamma passing rate (GPR) using a 3% dose difference/3 mm distance-to-agreement criteria was 99.61% in Tomo and 99.35% in VMAT, which confirmed sufficient dosimetric accuracy in both IMRT methods. For the Hexa-Motion measurement, the average GRP result of 90.93% in Tomo was higher than the result of 82.58% obtained in VMAT. In addition, the difference in the GPR results between the static and the Hexa-motion modes in Tomo was 8.68%, which is approximately 8% less than the 16.77% difference in VMAT. This study verifies that the dosimetric error of ITV-based IMRT due to the tumor motion was larger in VMAT than in Tomo. Also, Tomo can be considered to be more suitable than the conventional LINAC-based VMAT method in terms of the dosimetric accuracy of ITV-based IMRT for the treatment of a moving tumor.

The postoperative hypofractionated intensity-modulated radiation therapy (POHIM-RT) trial is a phase II study to evaluate toxicity following hypofractionated intensity modulated radiation therapy (IMRT) for cervical cancer. This study describes the results of a benchmark procedure for RT quality assurance of the POHIM-RT trial. Six participating institutions were provided computed tomography for RT planning and an IMRT plan for a sample and were instructed to delineate volumes, create a treatment plan and quality assurance (QA) plan, and submit the results of all procedures. The inter-institutional agreements on RT volume and plan results were evaluated using the kappa value and dice similarity coefficients. The simultaneous truth and performance level estimation (STAPLE) method was employed to generate a consensus target volume. The treatment volumes, organs-at-risk volumes, and results of the RT plan and QA reported by the institutions were acceptable and adhered well to the protocol. In terms of clinical target volume (CTV) delineation, there were differences between the institutions, particularly in vaginal cuff and paracolpium subsites. Consensus CTV was generated from the collected CTVs with the STAPLE method. The participating institutions showed considerable agreement regarding volume, dose and QA results. To improve CTV agreement in CTV, we provided feedback with images of the consensus target volume and detailed written guidelines for specific subsites that were the most heterogeneous.

Background and purpose Charcot-Marie-Tooth (CMT) disease is the most common hereditary peripheral neuropathy. CMT type 1A (CMT1A) accounts for approximately 50% of CMT patients and is linked to PMP22 gene duplication. Histone deacetylase-6 (HDAC6) has pleiotropic effects, such as regulating lipid homeostasis and cellular stress. Although HDAC6 has been regarded as a promising drug target for neurodegenerative diseases, its inhibition has not yet been tested in CMT1A. Here we have tested the therapeutic potential of CKD-504, a clinical stage HDAC6 inhibitor, in a mouse model of CMT1A EXPERIMENTAL APPROACH: The potency and selectivity of CKD-504 was evaluated, using a HDAC enzyme panel assay and western blots. The therapeutic potential of CKD-504 was evaluated using behavioural testing and electrophysiological assessments in the C22 mouse model of CMT1A. PMP22 protein expression and aggregation were analysed in mesenchymal stem cell-derived Schwann cells from CMT1A patients and sciatic nerves from C22 mice. Key results The HDAC6 inhibitor, CKD-504, modulated molecular chaperon proteins such as HSP90 and HSP70, which are involved in the folding/refolding of proteins such as PMP22. CKD-504 treatment restored myelination in both mesenchymal stem cell-derived Schwann cells from CMT1A patients and sciatic nerves of C22 mice and improved the axonal integrity of the sciatic nerve, leading to behavioural, electrophysiological, and histological improvements in C22 mice. Conclusion and implications A novel HDAC6 inhibitor, CKD-504, has potent therapeutic efficacy for CMT1A.

Most two-dimensional (2D) detector arrays used for the verification of the intensity-modulated radiotherapy (IMRT) dose distribution comprise diode detectors or ion chamber detectors. These detectors show different sensitivities depending on the angle of incidence of the IMRT beam on the detector. In this study, the effect of the radiation beam’s angle of incidence onto the detector was analyzed in order to find an optimal 2D detector array setup position for delivery quality assurance in breast IMRT. For breast IMRT plans, comprising mostly tangential fields, the dose distribution produced with true composite beams was measured by arranging 2D detector array devices at various angles. The change in dosimetric accuracy was then assessed as a function of the radiation beam’s angle of incidence. A total of 72 dose distributions were measured and analyzed for 12 breast IMRT plans. Both the diode detector array and the ion chamber array showed a higher gamma passing ratio in the sagittal dose distribution measurement, where the beam’s angle of incidence was relatively larger. This study indicates that using a 2D detector array placed at a relatively large angle of incidence offers a more accurate verification of the IMRT dose distribution.

Purpose To investigate the differences in treatment outcomes between two radiation techniques, intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3DCRT). Materials and methods We retrospectively analyzed 160 (IMRT = 23, 3DCRT = 137) patients with stage I glottic cancer treated from January 2005 through December 2016. The IMRT was performed with TomoTherapy (16 patients), volumetric-modulated arc therapy (6 patients), and step-and-shoot technique (1 patient), respectively. The 3DCRT was performed with bilateral parallel opposing fields. The median follow-up duration was 30 months (range, 31 to 42 months) in the IMRT group and 65 months (range, 20 to 143 months) in the 3DCRT group. Results The 5-year overall survival and 3-year local control rates of the 160 patients were 95.7% and 91.4%, respectively. There was no significant difference in 3-year local control rates between the IMRT and 3DCRT groups (94.4% vs. 91.0%; p = 0.587). Thirteen of 137 patients in the 3DCRT group had recurrences. In the IMRT group, one patient had a recurrence at the true vocal cord. Patients treated with IMRT had less grade 2 skin reaction than the 3DCRT group, but this had no statistical significance (4.3% vs. 21.2%; p = 0.080). Conclusion IMRT had comparable outcomes with 3DCRT, and a trend of less acute skin reaction in stage I glottic cancer patients.

Charcot-Marie-Tooth disease type 2D (CMT2D), is a hereditary peripheral neuropathy caused by mutations in the gene encoding glycyl-tRNA synthetase (GARS1). Here, human induced pluripotent stem cell (hiPSC)-based models of CMT2D bearing mutations in GARS1 and their use for the identification of predictive biomarkers amenable to therapeutic efficacy screening is described. Cultures containing spinal cord motor neurons generated from this line exhibited network activity marked by significant deficiencies in spontaneous action potential firing and burst fire behavior. This result matched clinical data collected from a patient bearing a GARS1(P724H) mutation and was coupled with significant decreases in acetylated α-tubulin levels and mitochondrial movement within axons. Treatment with HDAC6 inhibitors, tubastatin A and CKD504, improved mitochondrial movement and α-tubulin acetylation in these cells. Furthermore, CKD504 treatment enhanced population-level electrophysiological activity, highlighting its potential as an effective treatment for CMT2D.

PURPOSE To determine prognostic significance of lymphovascular invasion (LVI) in prostate cancer patients who underwent adjuvant or salvage postoperative radiotherapy (PORT) after radical prostatectomy (RP). MATERIALS AND METHODS A total of 168 patients with prostate cancer received PORT after RP, with a follow-up of ≥12 months. Biochemical failure after PORT was defined as prostate-specific antigen (PSA) ≥0.2 ng/mL after PORT or initiation of androgen deprivation therapy (ADT) for increasing PSA levels regardless of the value. We analyzed the clinical outcomes including survivals, failure patterns, and prognostic factors affecting the outcomes. RESULTS In total, 120 patients (71.4%) received salvage PORT after PSA levels were >0.2 ng/mL or owing to clinical failure. The 5-year biochemical failure-free survival (BCFFS), clinical failure-free survival (CFFS), distant metastasis-free survival (DMFS), overall survival, and cause-specific survival rates were 78.3%, 94.3%, 95.0%, 95.8%, and 97.3%, respectively, during a follow-up range of 12-157 months (median: 64 months) after PORT. On multivariate analysis, PSA level of ≤1.0 ng/mL at the time of receiving PORT predicted favorable BCFFS, CFFS, and DMFS. LVI predicted worse CFFS (p = 0.004) and DMFS (p = 0.015). Concurrent and/or adjuvant ADT resulted in favorable prognosis for BCFFS (p < 0.001) and CFFS (p = 0.017). CONCLUSION For patients with adverse pathologic findings, PORT should be initiated as early as possible after continence recovery after RP. Even after administering PORT, LVI was an unfavorable predictive factor, and further intensive adjuvant therapy should be considered for these patients.

Objectives. To investigate the prognostic factors and treatment outcomes of primary parotid carcinoma treated with surgery and postoperative radiotherapy (PORT).Methods. We reviewed retrospectively 57 patients with primary parotid carcinoma who were treated with surgery and PORT between 2005 and 2014. Superficial parotidectomy was performed in 19 patients, total parotidectomy in 10 patients, and total parotidectomy with lymph node dissection in 28 patients PORT on the tumor bed was performed in 41 patients, while PORT on tumor bed and ipsilateral cervical lymph nodes was performed in 16 patients.Results. With a median follow-up of 66 months, the 5-year overall survival, disease-free survival, locoregional control, and distant control rates were 77.0%, 60.2%, 77.6%, and 72.8%, respectively. The 5-year overall survival by stage was 100%, 100%, 80.0%, and 46.4% in stage I, II, III, and IV, respectively. Recurrences at primary lesions were found in seven patients, while at cervical nodes in six patients. Distant recurrences were developed in 12 patients. No patient with the low and intermediate histologic grade developed distant failure. As prognostic factors, the histologic grade for overall survival (P=0.005), pathological T-stage (P=0.009) and differentiation grade (P=0.009) for disease-free survival, pathological T-stage for locoregional control (P=0.007), and lympho-vascular invasion (P=0.023) for distant recurrence were significant on multivariate analysis.Conclusion. This study revealed that differentiation grade, histologic grade, pathological T-stage, and lympho-vascular invasion were significant independent prognostic factors on clinical outcomes.

Introduction To determine the prognostic significance of long-term adjuvant androgen deprivation therapy (A-ADT) over 1 year in achieving undetectable levels of prostate-specific antigen (PSA) less than 0.001 ng/mL in prostate cancer patients with high- or very high-risk prostate cancer who underwent radiotherapy (RT). Materials and methods A total of 197 patients with prostate cancer received RT, with a follow-up of ≥12 months. Biochemical failure was defined as PSA ≥nadir + 2 ng/mL after RT. We analyzed clinical outcomes, including survival, failure patterns, and prognostic factors affecting outcomes. Results Biochemical failure-free survival (BCFFS), clinical failure-free survival, distant metastasis-free survival, cancer-specific survival, and overall survival (OS) rates at 5 years were 91.1%, 95.4%, 96.9%, 99.5%, and 89.1%, respectively. Administration of long-term A-ADT significantly predicted favorable BCFFS (p = 0.027) and OS (p < 0.001) in multivariate analysis. Nadir PSA ≤0.001 ng/mL was an independent prognostic factor for BCFFS (p = 0.006) and OS (p = 0.021). The use of long-term A-ADT significantly affected nadir PSA ≤0.001 ng/mL (p < 0.001). The patients with A-ADT for 1 year or longer had better BCFFS or OS than those for less than 1 year or those without A-ADT (p < 0.001). The best prognosis was demonstrated in patients treated with long-term A-ADT and nadir PSA ≤0.001 ng/mL in BCFFS (p < 0.001). Conclusion The addition of long-term A-ADT over 1 year to RT demonstrated good treatment outcomes in patients with locally advanced prostate cancer. Achieving a nadir PSA value ≤0.001 ng/mL using combination therapy with RT and A-ADT is a powerful clinical predictor of treatment outcomes.

Irradiation enhances the adhesion between natural killer (NK) cells and target cells by up-regulating intercellular adhesion molecule-1 (ICAM-1) on target cells. Therefore, we investigated the effect of irradiation-induced ICAM-1 expression on human cancer cells on NK cell-mediated cytotoxicity.Expression levels of ICAM-1 on the target cell surface before and after irradiation of six human cancer cell lines (HL60, SKBR-3, T47D, HCT-116, U937 and U251) were analyzed by flow cytometry. Ex vivo expansion of NK cells from human peripheral blood mononuclear cells was performed by co-culture with irradiated K562 cells. The related adhesion molecule lymphocyte function-associated antigen 1 (LFA-1) on NK cells was analyzed by flow cytometry. An enzyme-linked immunosorbent assay was used to detect interferon-γ (IFN-γ), and WST-8 assays were performed to check NK cell cytotoxicity. Finally, blocking assays were performed using monoclonal antibodies against ICAM-1 or LFA-1.LFA-1 expression increased on NK cells after expansion (P 0.001). The expression of ICAM-1 was significantly upregulated by irradiation after 24 h in various cell lines, including HL60 (P 0.001), SKBR-3 (P 0.001), T47D (P 0.001) and U937 (P 0.001), although the level of expression depended on the cell line. ICAM-1 expression was extremely low before and after irradiation in U251 cells. NK cell-mediated cytotoxicity increased after irradiation of HL60 (P 0.001), SKBR-3 (P 0.001), T47D (P = 0.003), and U937 (P = 0.004) cells, in which ICAM-1 expression was significantly increased after irradiation. IFN-γ production by NK cells in response to HL60 (P 0.001) and T47D (P = 0.011) cells significantly increased after irradiation. NK cell-mediated cytotoxicity against irradiated SKBR-3 (P 0.001) and irradiated T47D cells (P = 0.035) significantly decreased after blocking of ICAM-1. Blocking of LFA-1 on NK cells resulted in reduced cytotoxicity against irradiated HL60 (P 0.001) and irradiated SKBR-3 (P 0.001).Irradiation upregulates ICAM-1 expression on the surface of human cancer cells and enhances activated NK cell-mediated cytotoxicity. Therefore, irradiation combined with NK cell therapy may improve the antitumor effects of NK cells.

Purpose This study evaluated outcomes of radiotherapy (RT) after chemotherapy in limited-stage head-and-neck diffuse large B-cell lymphoma (DLBCL). Materials and Methods Eighty patients who were treated for limited-stage head-and-neck DLBCL with CHOP (n = 43) or R-CHOP (n = 37), were analyzed. After chemotherapy, RT was administered to the extended field (n = 60) or the involved field (n = 16), or the involved site (n = 4). The median dose of RT ranged from 36 Gy in case of those with a complete response, to 45–60 Gy in those with a partial response. Results In all patients, the 5-year overall survival (OS) and disease-free survival (DFS) rates were 83.9% and 80.1%, respectively. In comparison with the CHOP regimen, the R-CHOP regimen showed a better 5-year DFS (86.5% vs. 73.9%, p = 0.027) and a lower rate of treatment failures (25.6% vs. 8.1%, p = 0.040). The volume (p = 0.047) and dose of RT (p < 0.001) were significantly reduced in patients treated with R-CHOP compared to that in those treated with CHOP. Conclusion The outcomes of RT after chemotherapy with R-CHOP were better than those of CHOP regimen for limited-stage head-and-neck DLBCL. In patients treated with R-CHOP, a reduced RT dose and volume might be feasible without increasing treatment failures.

We evaluated the durability of cadmium telluride (CdTe) solar cells upon proton beam irradiation as well as the possibility of achieving a dosimeter usable in proton beam therapy by applying 100 MeV of pencil beam scanning (PBS) irradiation. Specifically, a 100 MeV proton PBS beam was applied at irradiation doses of 0, 1012, 1013, 1014, and 1015 cm-2. According to the results, the remaining factors (defined as the ratio of the degraded value to the initial value) of open-circuit voltage (Voc), short-circuit current (Jsc), fill-factor (FF), and efficiency (ƞ) which are solar cell performance parameters, were approximately 89%, 44%, 69%, and 30%, respectively, compared to those of the reference cell (without irradiation) at the highest dose of 1×1015 cm-2. In particular, the conversion efficiency, which is the main factor, was approximately 70% of that of the reference cell even at a high fluence of 1×1014 cm-2. In addition, we observed the projected range of the hydrogen atoms based on the PBS beam energy using the Tool for Particle Simulation software and assessed the amount of fluence accumulated in a CdTe cell. As the energy increased, the fluence accumulated inside the cell tended to decrease owing to the characteristics of the Bragg peak of the proton. Thus, the radiation damage to the cell induced by the proton beam was reduced. The results of this study are expected to provide valuable reference information for research on dosimetry sensors composed of thin-film solar cells, serving as the basis for future application in proton beam therapy with CdTe solar cells.

Oligodendrocyte precursor cells (OPCs), also known as NG2 cells or polydendrocytes, are distributed widely throughout the developing and mature central nervous system. They remain proliferative throughout life and are an important source of myelinating cells in normal and demyelinating brain as well as a source of glioma, the most common type of primary brain tumor with a poor prognosis. OPC proliferation is dependent on signaling mediated by platelet-derived growth factor (PDGF) AA binding to its alpha receptor (PDGFRα). Here, we describe a group of structurally related compounds characterized by the presence of a basic guanidine group appended to an aromatic core that is effective in specifically repressing the transcription of Pdgfra but not the related beta receptor (Pdgfrb) in OPCs. These compounds specifically and dramatically reduced proliferation of OPCs but not that of astrocytes and did not affect signal transduction by PDGFRα. These findings suggest that the compounds could be further developed for potential use in combinatorial treatment strategies for neoplasms with dysregulated PDGFRα function.

A practical method was designed to verify the accuracy of dose distributions calculated using Compass, which can reconstruct the dose distribution inside a patient's body during intensity-modulated radiation therapy (IMRT). Twelve virtual IMRT treatment plans were developed using an ArcCHECK diode detector array, and then the recalculated and reconstructed doses in Compass were compared with the actual measurements to assess the dosimetric accuracy. Based on the results of gamma evaluation for the 12 plans, Compass achieved average pass rates higher than 98%, which confirmed proper dosimetric accuracy in the IMRT quality assurance process. The validity of Compass for clinical applications was also confirmed through an additional comparison with the results calculated using 3DVH, another dose reconstruction program. It is necessary to verify the accuracy of the dose calculated using the program in advance before the commercialized dose reconstruction program is applied in clinical practice. This study has limitations in that it did not provide a real scientific contribution such as an introduction of new algorithm for dose calculation and the development of new measurement tools. However, the method based on the comparative analysis with the actual measured dose values as devised in this study seems to be useful in that it can be applied effectively to verify the dosimetric accuracy of the dose reconstruction program before first using it in the clinical cases.

This study aims to investigate tolerance levels for patient‐specific IMRT dose QA (DQA) using the confidence limits (CL) determined by a multi‐institutional study. Eleven institutions participated in the multi‐institutional study in Korea. A total of 155 DQA measurements, consisting of point‐dose differences (high‐ and low‐dose regions) and gamma passing rates (composite and per‐field) for IMRT patients with brain, head and neck (H&N), abdomen, and prostate cancers were examined. The Shapiro‐Wilk test was used to evaluate the normality of data grouped by the treatment sites and the DQA methods. The confidence limit coefficients in cases of the normal distribution, and the two‐sided Student's t‐distribution were applied to determine the confidence limits for the grouped data. The Spearman's test was applied to assess the sensitivity of DQA results within the limited groups. The differences in CLs between the two confidence coefficients based on the normal and t‐distributions were negligible for the point‐dose data and the gamma passing rates with 3%/3 criteria. However, with 2%/2 criteria, the difference in CLs were 1.6% and 2.2% for composite and per‐field measurements, respectively. This resulted from the large standard deviation and the more sensitive criteria of 2%/2. There was no noticeable correlation among the different QA methods. Our multi‐institutional study suggested that the CL was not a suitable metric for defining the tolerance level when the statistics of the sample group did not follow the normality and had a large standard deviation. PACS number: 87.55.Qr

Purpose To evaluate treatment outcomes and determine prognostic factors in patients with esophageal cancer treated with esophagectomy after neoadjuvant chemoradiotherapy (NCRT). Materials and methods We retrospectively evaluated 39 patients with esophageal cancer who underwent concurrent chemoradiotherapy followed by esophagectomy between 2002 and 2012. Initial clinical stages of patients were stage IB in 1 patient (2.6%), stage II in 5 patients (12.9%), and stage III in 33 patients (84.6%). Results The median age of all the patients was 62 years, and the median follow-up period was 17 months. The 3-year overall survival (OS) rate was 33.6% in all the patients. The 3-year locoregional recurrence-free survival (LRFS) rate was 33.7%. In multivariate analysis with covariates of age, the Eastern Cooperative Oncology Group performance status, hypertension, diabetes mellitus, tumor length, clinical response, clinical stage, pathological response, pathological stage, lymphovascular invasion, surgical type, and radiotherapy to surgery interval, only pathological stage was an independent significant prognostic factor affecting both OS and LRFS. The complications in postoperative day 90 were pneumonia in 9 patients, anastomotic site leakage in 3 patients, and anastomotic site stricture in 2 patients. Postoperative 30-day mortality rate was 10.3% (4/39); the cause of death among these 4 patients was respiratory failure in 3 patients and myocardial infarction in one patient. Conclusion Only pathological stage was an independent prognostic factor for both OS and LRFS in patients with esophageal cancer treated with esophagectomy after NCRT. We could confirm the significant role of NCRT in downstaging the initial tumor bulk and thus resulting in better survival of patients who gained earlier pathological stage after NCRT.

Purpose: This study was conducted to investigate the effect of postural education in preventive educational aspects on physical satisfaction and life habit related to posture in elementary school students. Methods: Participants were 974 4th-grade elementary school students in 9 schools of U city (boy 50.2%, girl 49.8%). Postural education was conducted from May through November 2011, once each semester, each class was conducted two times. Results: Results of this study showed that physical satisfaction and life habit related to posture were significantly improved after postural education (p

Backgrounds Stereotactic ablative radiotherapy (SABR) is one of the newly developed innovative radiotherapy and of which optimal dose prescription needs to be standardized. We aimed to investigate the dose-response relationship for patients with SABR. Methods Fifty-three patients with Stage I non-small cell lung cancer patients, who underwent SABR between November 2006 and January 2015, were evaluated retrospectively. Thirteen patients (24.5%), who refused the surgery were included and 40 patients (75.5%) were medically inoperable at diagnosis. The median age was 74 years. The median SABR dose was 50 Gy in 3-8 fractions and the median biologically effective dose (BED;α/β = 10) was 105.6 Gy (range: 60-160.53 Gy). Results The median follow-up was 37.1 months. The 1 and 3 year local control rates were 91.7% and 85.1%. The 3 year overall and progression-free survival rate were 63.3% and 47.5%, respectively, and freedom from progression was 62.2%. Local control rate and 3-year overall survival according to tumor size was 100% and 79.4% in T1 tumors in a while 61.8% and 45% in T2a tumors. The 3-year local and regional control by BED10 was 79.4% and 69.4% in ≤100 Gy vs. 89.1% and 100% in >100 Gy (P = 0.526, 0.004). Dyspnea more than Grade 3 was reported in six (11.3%) patients and Grade 1 chest pain was shown in five (9.4%) patients. Conclusions The excellent regional control was conferred with a prescription of more than BED10 of 100 Gy, which also might be needed to achieve better local tumor control in T2a patients with tolerable lung function.

Based on per-field data, 3 dose-volume histogram (DVH) is designed to calculate 3-dimensional (3D) dose using patient-computed tomography (CT) for an intensity-modulated radiation therapy (IMRT) delivery quality assurance (DQA) process measured with diode detector arrays. In this study, the characteristics and suitability of 3DVH for an IMRT DQA process were evaluated by assessment of clinically applied results. The DQA plans were prepared with a 2D diode detector array (MapCHECK 2) for 20 IMRT patients (10 with head and neck cancer and 10 with prostate cancer), and the matching rate between the calculated dose and the measured dose was analyzed. The relative dose differences between the original IMRT plan and the recalculated plan by 3DVH were evaluated for tumor target and organs at risk (OARs). Confidence limits (CLs) were determined for quantification of the degree of agreement that should be expected in each DQA method. The individual CLs for DQA accuracy of 3D dosimetric evaluation in the tumor target and OARs were also calculated to evaluate the differences compared with conventional 2D-based DQA results. The matching rates were sufficient to validate the accuracy of IMRT DQA analyses and the calculated CL values were reasonable values considering the normal criteria of our institution. The 3DVH analysis generally had better matching rate than per-field measurement analysis and the CL values for OARs were better than those for the planning target volume (PTV). The usefulness of the 3DVH tool was verified for IMRT DQA from the point of view of dose evaluation in the corresponding patient's CT data. It also enables dosimetric evaluation in each important structure (PTV and OARs), which can promote more effective evaluation of DQA error in terms of tumor treatment and side effects.

The purpose of this study was to suggest tolerance levels for IMRT DQA measurements using confidence limits determined by a multi‐institutional study in Korea. Ten institutions were grouped into LINAC (seven linear accelerators) and TOMO (three tomotherapy machines). The DQA processes consisted of point (high‐ and low‐dose regions) and planar (per‐field and composite‐field) dose measurements using an ion chamber and films (or 2D detector array) inserted into a custom‐made acryl phantom (LINAC) or a cheese phantom (TOMO). The five mock structures developed by AAPM TG‐119 were employed, but the prostate as well as the H&N structures were modified according to Korean patients' anatomy. The point measurements were evaluated in a ratio of measured and planned doses, while the planar dose distributions were assessed using two gamma criteria of 2 mm/2% and 3 mm/3%. The confidence limit (|mean + 1.96 σ|) for point measurements was determined to be 3.0% in high‐dose regions and 5.0% in low‐dose regions. The average percentage of points passing the gamma criteria of 2 mm/2% and 3 mm/3% for per‐field measurements was 92.7 ±6.5% and 98.2 ±2.8%, respectively. Thus, the corresponding confidence limit was 79.1% and 92.7%, respectively. The gamma passing rate averaged over all mock tests and institutions for composite‐field measurements was 86.1 ±6.5% at 2 mm/2% and 95.3 ±3.8% at 3 mm/3%, leading to the confidence limit of 73.3% and 87.9%, respectively. There was no significant difference in the tolerance levels of point dose measurements between LINAC and TOMO groups. In spite of the differences in mock structures and dosimetry tools, our tolerance levels were comparable to those of AAPM and ESTRO guidelines. PACS number: 87.55.Qr

Background: Advances of tissue microarray (TMA) technology have enabled simultaneous in situ analysis of biomarker expression in a large number of archived pathology specimens. However, the relatively high cost of TMA construction may hamper many researchers from using this essential tool of modern pathology research. We discuss methods for making TMA kits and recipient blocks for manual construction of high-density TMAs at low cost. Methods: Ordinary cannula piercing needles, hypodermic needles, bone marrow biopsy needles, metallic ink cartridges of ballpoint pens, and disposable skin biopsy punches were used to construct self-made manual TMA kits. The recipient blocks were manufactured by boring holes in the conventional bare paraffin blocks. A mini electric hand drill and a microcompound table assembled on a drill stand were used to maximize the capacity of the recipient blocks. Results: By using TMA kits made from cannula piercing needles (16- and 18-gauge), it was possible to construct TMAs with 1 mm × 140 cores, 0.6 mm × 320 cores, 2 mm × 70 cores, 3 mm × 35 cores, and 5 mm × 12 cores. The capacity of the recipient blocks could be dramatically increased by drilling holes. Conclusions: Construction of TMAs using self-made TMA kits is an inexpensive alternative to construction of TMAs using commercial devices.

Background After local excision of early rectal cancer, revision radical resection is recommended for patients with high-risk pathologic stage T1 (pT1) or pT2 cancer, but the revision procedure has high morbidity rates. We evaluated the efficacy of adjuvant concurrent chemoradiotherapy (CCRT) for reducing recurrence after local excision in these patients. Methods Eighty-three patients with high-risk pT1 or pT2 rectal cancer underwent postoperative adjuvant CCRT after local excision. We defined high-risk features as pT1 having tumor size ≤3 cm, and/or resection margin (RM) ≤3 mm, and/or lymphovascular invasion (LVI), and/or non-full thickness excision such as endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD), or unknown records regarding those features, or pT2 cancer. Radiotherapy was administered with a median dose of 50.4 Gy in 1.8 Gy fraction size over 5–7 weeks. Concurrent 5-fluorouracil and leucovorin were administered for 4 days in the first and fifth weeks of radiotherapy. Results The median interval between local excision and radiotherapy was 34 (range, 11–104) days. Fifteen patients (18.1 %) had stage pT2 tumors, 22 (26.5 %) had RM of ≥3 mm, and 21 (25.3 %) had tumors of ≥3 cm in size. Thirteen patients (15.7 %) had LVI. Transanal excision was performed in 58 patients (69.9 %) and 25 patients (30.1 %) underwent EMR or ESD. The median follow-up was 61 months. The 5-year overall survival (OS), locoregional relapse-free survival (LRFS), and disease-free survival (DFS) rates for all patients were 94.9, 91.0, and 89.8 %, respectively. Multivariate analysis did not identify any significant factors for OS or LRFS, but the only significant factor affecting DFS was the pT stage (p = 0.027). Conclusions In patients with high-risk pT1 rectal cancer, adjuvant CCRT after local excision could be an effective alternative treatment instead of revision radical resection. However, patients with pT2 stage showed inferior DFS compared to pT1.

To evaluate the metabolic response of uterine cervix and pelvic lymph nodes (LNs) using consecutive 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT) immediately after RT and to correlate survival outcome with the metabolic response.We retrospectively reviewed 48 patients with cervical cancer who had positive pelvic LNs by preradiation therapy (pre-RT) PET/CT. All patients underwent PET/CT scans immediately after RT (inter-RT PET/CT) after median 63 Gy to the gross LNs. The metabolic response of the LNs was assessed quantitatively and semiquantitatively by measurement of the maximal standardized uptake value (SUVmax).Classifying the metabolic response of all nodal lesions, 37 patients (77%) had LNs with complete metabolic response on the inter-RT PET/CT (LNCMRi), and 11 patients had a non-LNCMRi, including 4 patients with progressive metabolic disease. The overall 3-year survival rates were 83% for the patients with LNCMRi and 73% for the non-LNCMRi group (P=.038). The disease-free survival for patients with LNCMRi were significantly better than that for the non-LNCMRi group (71% vs 18%, respectively, P.001). The 3-year distant metastasis-free survival rates were 79% for the patients with LNCMRi and 27% for the non-LNCMRi group (P.001). There were no statistically significant differences in overall survival (76% vs 86%, respectively, P=.954) and disease-free survival rates (58% vs 61%, respectively, P=.818) between the CMR of primary cervical tumor and the non-CMR groups.The results showed a significant correlation between survival outcome and the interim metabolic response of pelvic LNs. CMR of nodal lesion on inter-RT PET/CT had excellent overall survival, disease-free survival and distant metastasis-free survival rates. This suggested that PET/CT immediately after RT can be a useful tool for the evaluation of the interim response of the LNs and identify a subset of patients with a high risk of recurrence and poor survival in patients with cervical cancer with initial positive LNs.

The effect of the accuracy in the application of the image value-to-density table (IVDT) from kilovoltage computed tomography (kVCT) and mega-voltage computed tomography (MVCT) images on the delivery quality assurance (DQA) in helical tomotherapy (HT) was analyzed. The DQA plans were prepared with a kVCT image of a cheese phantom for 10 HT patients, and the difference in absolute dose equivalence between the planned and real measurement was evaluated according to the accuracy of IVDT application. The difference between the calculated dose distribution and real dose distribution measured with MapCHECK (SunNuclear, Melbourne, FL) was analyzed through the DQA process with a kVCT MapCHECK image and the same analysis was performed with an MVCT MapCHECK image. The IVDT for kVCT was applied to MVCT and the variation in error between the planned and real measurement caused by improper application of IVDT was evaluated. The accuracy of the IVDT application in the homogeneous water-equivalent cheese phantom had only a minor influence on the dose calculation. Although the overall accuracy of the calculated dose was increased when the proper IVDT was applied, this result had no statistical significance. The MVCT image of MapCHECK contained less error between the calculated dose and delivered dose with a high pass rate. The proper IVDT application to the MVCT image of MapCHECK increased the accuracy of dose calculation, and this result had a statistical significance. Application of the correct IVDT is important in HT DQA and its significance is increased when using phantoms consisting of inhomogeneous density materials.

The purpose of this study was to investigate the effects of learning style on blended learning. Subjects were 102 college students(grade 1, department of physical therapy) who enrolled in `neuroanatomy` course. Blended learning was composed of 13 weeks-3 hour/1week in offline and 16 chapters-24 lessons in online. According to Kolb`s learning style, assimilator was the most common. There were no significant differences between the learning style but, they were most preferred blended learning(92.1% of subjects), improved participation and excitation in learning(each 55.5%, 58.8% of subjects), and blended learning was helpful in learning(85.1% of subjects). In student`s satisfaction, there was significant difference between the learning style. Statistical difference was found in satisfaction between assimilator(80.7%) and accommodator(67.5%).

Background and purpose To predict tumor regression in pre-operative chemoradiotherapy (CRT) using 18 F-fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT) and serum carcinoembryonic antigen (CEA) in patients with rectal cancer. Materials and methods The metabolic response of the tumor was assessed by determining the maximal standardized uptake value (SUV max ), absolute difference (ΔSUV max ), and SUV reduction ratio (SRR) on pre- and post-CRT PET/CT scans. The serum CEA, absolute difference (ΔCEA), and the CEA reduction ratio (CRR) were also determined. A receiver-operating characteristic (ROC) curve was generated. Results Of all seventy two patients, mean pre- and post-CRT SUV max was 14.9 and 5.8, respectively. The mean pre- and post-CRT CEA level was 15.5ng/ml and 5.4ng/ml, respectively. Forty-three patients (59.8%) were classified as responders (Dworak's tumor regression grade 3–4) and 36 patients (50%) achieved tumor down-staging. ROC analysis showed that both post-CRT SUV max and SRR were predictive factors for responders ( p =0.03 and p =0.02, respectively). A threshold of post-CRT SUV max was 5.4 and that of SRR was 53.1%. Pre-CRT SUV max , ΔSUV max , and all parameters in regard to CEA were not significant in ROC analysis. Conclusions The post-CRT SUV max and SRR are potential factors for predicting tumor response in pre-operative CRT. The patients with lower post-CRT SUV max and higher SRR could be expected to achieve maximum tumor regression after pre-operative CRT in this study.

Acrolein is an alpha, beta-unsaturated aldehyde present in cigarette smoke, and is also a product of lipid peroxidation. Heme oxygenase-1 (HO-1) plays critical roles in preventing oxidative stress and other cellular functions, and induces viability and proliferation of tumor cells. Acrolein is well-known to induce HO-1, although the signal pathway has not been fully elucidated. This study elucidated the involved signaling and acrolein’s cytoprotective effects in human hepatocellular carcinoma (HepG2) cells. Cells were treated with acrolein to induce HO-1, whose expression was measured by Western blot, RT-PCR and immunofluorescence staining analyses. Low concentrations of acrolein remarkably increased HO-1 mRNA and protein levels. Acrolein-mediated HO-1 induction was notably decreased by rottlerin and SB203580, selective inhibitors of PKC-δ and p38 MAPK, respectively. Furthermore, the cells displayed an increased arrest at the G0/G1 phase of the cell-cycle. The data indicates that acrolein enhances HO-1 expression via PKC-δ and p38 MAPK signaling. Acrolein may provide a cytoprotective effect via the expression of HO-1 in HepG2 cells.

The cone-beam CT (CBCT), which is acquired using an on-board imager (OBI) attached to a linear accelerator, is used effectively in the verification of setup accuracy for lung radiation surgery. In this study, the respiratory organ motional effect on the CBCT was evaluated with a properly devised phantom system, and the level of possible error in conditions of a real clinical process was assessed. In a comparison study between the CBCT in static status and CBCT images acquired in 20 different motional cases, we confirmed that the image quality and information of CBCT were degraded, with an increase of motional ranges in the region of inhomogeneous structures. The 4D-CT MIP (50 approximately 55%) for the planning of lung radiation surgery and the 4D-CT MIP (full phase) were compared with CBCT in the various motional cases for the evaluation of the influence of the motional effect on CBCT in the process of the setup error correction. The average ratio of relative difference between plan CT: 4D-CT MIP (50% approximately 55%) and CBCT was 5.79% and between plan CT: 4D-CT MIP (50% approximately 55%) and 4D-CT MIP (full phase) was 42.95% in the phantom study. In the analysis of clinical cases of lung radiation surgery, the gross tumor volumes were compared in each CT image. The average ratio of relative difference between plan CT: 4D-CT MIP (50 approximately 55%) and CBCT was 10.72% and between plan CT: 4D-CT MIP (50 approximately 55%) and 4D-CT MIP (full phase) was 28.19%. These results showed that, although a respiratory organ motional effect on CBCT introduced variation in image quality, the error as a result of this variation could be estimated relatively low in the setup error correction for a gated-lung radiation surgery when the planning was performed in 4D-CT MIP (50 approximately 55%), which already included a related signal of motional effect.

The present study evaluated the pretreatment expression patterns of hMLH1, MDM2, p53, and pRb protein to determine whether these could predict the outcome of definitive concurrent chemoradiotherapy (CCRT) in 51 patients with stage I-IVa esophageal squamous cell carcinoma. High immunoreactivies of hMLH1, MDM2, p53, and pRb were detected in 90.2%, 19.6%, 27.5%, and 66.7% of entire patients, respectively. High hMLH1 expression was found to favor earlier stage, less locoregional failure, and longer cause-specific survival, and all were with significance. However, the expressions of MDM2, p53, and pRb were not found to be clinically significant. Thirty-three patients with high hMLH1 and pRb expression tended to survive longer than four patients with low hMLH1 and pRb expression. We suggest that the expression of hMLH1 is a potential marker of tumor response and survival. Determinations of this protein expression might be useful for selecting esophageal squamous cell carcinoma patients for definitive CCRT.

The concurrent administration of cisplatin and fluorouracil (CCRT) during radiotherapy after induction chemotherapy had better results than induction chemotherapy followed by radiotherapy alone (CT+RT) for overall survival, laryngeal preservation, and locoregional control in patients with locally advanced hyopharyngeal cancer.To report treatment results comparing CCRT with CT+RT in locally advanced hypopharyngeal cancer.Sixty-six consecutive patients treated with curative intent were analyzed retrospectively. Thirty-eight patients were treated with induction chemotherapy followed by definitive RT, and 28 patients with induction chemotherapy followed by concurrent chemoradiotherapy. All patients had more than three cycles of continuous infusion of cisplatin and 5-fluorouracil every 3 weeks. The median dose of irradiation was 70 Gy in the CT+RT group and 68.4 Gy in the CCRT group, respectively.The overall 5-year survival rates were 24% for the CT+RT group and 42% for the CCRT group (p=0.031). The 3-year pharyngolaryngectomy-free survival rates were 32% for the CT+RT group and 63% for the CCRT group (p=0.032). The 3-year locoregional control rate for CCRT was significantly better than that for the CT+RT (52% vs 23%, p=0.004). Acute hematologic toxicity appeared in 39% of the CT+RT patients and 75% of the CCRT patients.