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Conventional non-local total variation (NLTV) approaches use the weight of a non-local means (NLM) filter, which degrades performance in low-dose cone-beam computed tomography (CBCT) images generated with a low milliampere-seconds (mAs) parameter value because a local patch used to determine the pixel weights comprises noisy-damaged pixels that reduce the similarity between corresponding patches. In this paper, we propose a novel type of NLTV based on a combination of mutual information (MI): MI-NLTV. It is based on a statistical measure for a similarity calculation between the corresponding bins of non-local patches vs. a reference patch. The weight is determined in terms of a statistical measure comprising the MI value between corresponding non-local patches and the reference-patch entropy. The MI-NLTV denoising process is applied to CBCT images generated by the analytical reconstruction algorithm using a ray-driven backprojector (RDB). The MI-NLTV objective function is minimized based on the steepest gradient descent optimization to augment the difference between a real structure and noise, cleaning noisy pixels without significant loss of the fine structure and details that remain in the reconstructed images. The proposed method was evaluated using patient data and actual phantom measurement data acquired with lower mAs. The results show that integrating the RDB further enhances the MI-NLTV denoising-based analytical reconstruction algorithm to achieve a higher CBCT image quality when compared with those generated by NLTV denoising-based approach, with an average of 15.97% higher contrast-to-noise ratio, 2.67% lower root mean square error, 0.12% lower spatial non-uniformity, 1.14% higher correlation, and an average of 18.11% higher detectability index. These quantitative results indicate that the incorporation of MI makes the NLTV more stable and robust than the conventional NLM filter for low-dose CBCT imaging. In addition, achieving clinically acceptable CBCT image quality despite low-mAs projection acquisition can reduce the burden on common online CBCT imaging, improving patient safety throughout the course of radiotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lee, Sung, Choi, Kim and Lee.)

Purpose: Studies on de-escalation in radiation therapy (RT) for human papillomavirus-related (HPV(+)) oropharyngeal cancer (OPC) are currently ongoing. This study investigated the current practice regarding the radiation dose and field in the treatment of HPV(+) OPC., Materials and Methods: The Korean Society for Head and Neck Oncology conducted a questionnaire on the primary treatment policy. Among them, for HPV(+) OPC scenarios, radiation oncologists were questioned regarding the field and dose of RT., Results: Forty-two radiation oncologists responded to the survey. In definitive concurrent chemoradiotherapy (CCRT) treatment for stage T2N1M0 OPC, most respondents prescribed a dose of >60 Gy to the primary tonsil and involved ipsilateral lymph nodes. However, eight of the respondents prescribed a relatively low dose of ≤54 Gy. For stage T2N1M0 OPC, postoperative adjuvant RT was prescribed by eight and nine respondents with a lower dose of ≤50 Gy for the ipsilateral tonsil and involved neck, respectively. In definitive CCRT in complete remission after induction chemotherapy for initial stage T2N3M0 OPC, de-escalation of the tonsil and involved neck were performed by eight and seven respondents, respectively. Regarding whether de-escalation is applied in radiotherapy for HPV(+) OPC, 27 (64.3%) did not do it at present, and 15 (35.7%) were doing or considering it., Conclusion: The field and dose of prescribed treatment varied between institutions in Korea. Among them, dose de-escalation of RT in HPV(+) OPC was observed in approximately 20% of the respondents. Consensus guidelines will be set in the near future after the completion of ongoing prospective trials.

Objective: The aim of this study was to identify the comprehensive risk factors for lymphedema, thereby enabling a more informed multidisciplinary treatment decision-making., Summary Background Data: Lymphedema is a serious long-term complication in breast cancer patients post-surgery; however, the influence of multimodal therapy on its occurrence remains unclear., Methods: We retrospectively collected treatment-related data from 5549 breast cancer patients who underwent surgery between 2007 and 2015 at our institution. Individual radiotherapy plans were reviewed for regional nodal irradiation (RNI) field design and fractionation type. We identified lymphedema risk factors and used them to construct nomograms to predict individual risk of lymphedema. Nomograms were validated internally using 100 bootstrap samples and externally using 2 separate datasets of 1877 Asian and 191 Western patients., Results: Six hundred thirty-nine patients developed lymphedema during a median follow-up of 60 months. The 3-year lymphedema incidence was 10.5%; this rate increased with larger irradiation volumes (no RNI vs RNI excluding axilla I-II vs RNI including axilla I-II: 5.7% vs 16.8% vs 24.1%) and when using conventional fractionation instead of hypofractionation (13.5% vs 6.8%). On multivariate analysis, higher body mass index, larger number of dissected nodes, taxane-based regimen, total mastectomy, larger irradiation field, and conventional fractionation were strongly associated with lymphedema (all P < 0.001). Nomograms constructed based on these variables showed good calibration and discrimination internally (concordance index: 0.774) and externally (0.832 for Asian and 0.820 for Western patients)., Conclusions: Trimodality breast cancer treatment factors interact to promote lymphedema. Lymphedema risk can be decreased by deintensifying node dissection, chemotherapy regimen, and field and dose of radiotherapy. Deescalation strategies on a multidisciplinary basis might minimize lymphedema risk., Competing Interests: The authors report no conflicts of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Attention-deficit/hyperactivity disorder (ADHD) leads to functional decline in academic performance, interpersonal relationships, and development in school-aged children. Early diagnosis and appropriate intervention can significantly reduce the functional decline caused by ADHD. Currently, there is no established biological marker for ADHD. Some studies have suggested that various indicators from the quantitative electroencephalogram (QEEG) may be useful biological markers for the diagnosis of ADHD. Until the 2010s, theta/beta ratio (TBR) was a biomarker candidate for ADHD that consistently showed high diagnostic value. However, limitations of TBR have recently been reported. Studies have demonstrated that phase-amplitude coupling, especially theta phase-gamma amplitude coupling, are related to cognitive dysfunction and may assist in the diagnosis of ADHD. As yet, the underlying mechanism is not clearly established, and the clinical efficacy of these biomarkers needs to be proven through well-controlled studies. Based on the heterogeneous characteristics of ADHD, subgrouping through QEEG plays a key role in diagnosis and treatment planning. Sophisticated, well-designed studies and meta-analyses are necessary to confirm these findings., Competing Interests: Conflicts of Interest The authors have no potential conflicts of interest to disclose., (Copyright © 2021 Korean Academy of Child and Adolescent Psychiatry.)

This study aims to confirm the usefulness of patient-specific quality assurance (PSQA) using three-dimensional (3D)-printed phantoms in ensuring the stability of IORT and the precision of the treatment administered. In this study, five patient-specific chest phantoms were fabricated using a 3D printer such that they were dosimetrically equivalent to the chests of actual patients in terms of organ density and shape around the given target, where a spherical applicator was inserted for breast IORT treatment via the INTRABEAM™ system. Models of lungs and soft tissue were fabricated by applying infill ratios corresponding to the mean Hounsfield unit (HU) values calculated from CT scans of the patients. The two models were then assembled into one. A 3D-printed water-equivalent phantom was also fabricated to verify the vendor-provided depth dose curve. Pieces of an EBT3 film were inserted into the 3D-printed customized phantoms to measure the doses. A 10 Gy prescription dose based on the surface of the spherical applicator was delivered and measured through EBT3 films parallel and perpendicular to the axis of the beam. The shapes of the phantoms, CT values, and absorbed doses were compared between the expected and printed ones. The morphological agreement among the five patient-specific 3D chest phantoms was assessed. The mean differences in terms of HU between the patients and the phantoms was 2.2 HU for soft tissue and -26.2 HU for the lungs. The dose irradiated on the surface of the spherical applicator yielded a percent error of -2.16% ± 3.91% between the measured and prescribed doses. In a depth dose comparison using a 3D-printed water phantom, the uncertainty in the measurements based on the EBT3 film decreased as the depth increased beyond 5 mm, and a good agreement in terms of the absolute dose was noted between the EBT3 film and the vendor data. These results demonstrate the applicability of the 3D-printed chest phantom for PSQA in breast IORT. This enhanced precision offers new opportunities for advancements in IORT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Choi, Lee, Park, Park, Cho, Kim and Lee.)

Vaccines and therapeutics are urgently needed for the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we screen human monoclonal antibodies (mAb) targeting the receptor binding domain (RBD) of the viral spike protein via antibody library constructed from peripheral blood mononuclear cells of a convalescent patient. The CT-P59 mAb potently neutralizes SARS-CoV-2 isolates including the D614G variant without antibody-dependent enhancement effect. Complex crystal structure of CT-P59 Fab/RBD shows that CT-P59 blocks interaction regions of RBD for angiotensin converting enzyme 2 (ACE2) receptor with an orientation that is notably different from previously reported RBD-targeting mAbs. Furthermore, therapeutic effects of CT-P59 are evaluated in three animal models (ferret, hamster, and rhesus monkey), demonstrating a substantial reduction in viral titer along with alleviation of clinical symptoms. Therefore, CT-P59 may be a promising therapeutic candidate for COVID-19.

Objective: Approximately half of patients with cancer have comorbidities, such as adjustment disorder, major depressive disorder, and delirium. Radiotherapy can cause psychological problems, e.g., the fear of treatment and its side effects, anxiety, depression, and social isolation. Health-related quality of life (QoL) must be determined to evaluate the effectiveness of cancer treatment. We analyzed the clinical, psychological, and sociodemographic factors influencing the QoL of patients with cancer who were undergoing radiotherapy., Methods: Twenty-six patients undergoing radiotherapy (10 male, 16 female) were included. Sociodemographic and clinical data were collected prior to radiotherapy. Psychosocial factors were assessed by self-reported questionnaires before, immediately after, and 3 months after radiotherapy. A multivariate regression analysis identified factors affecting QoL at each time point., Results: Patients' diagnoses were breast, cervical, prostate, endometrial, rectal, hypopharyngeal, laryngeal, liver, gallbladder, esophageal, ovarian, lung, and skin cancers. Before radiotherapy, better resilience was significantly associated with a higher QoL score (R2=0.199, p=0.033). Immediately after radiotherapy, financial difficulty was significantly associated with a lower QoL score (R2=0.274, p=0.010). Three months after radiotherapy, the presence of chronic disease (R2=0.398, p=0.002) and the severity of nausea and vomiting were significantly associated with a lower QoL score (R2=0.278, p=0.014)., Conclusion: Resilience, financial difficulty, the presence of chronic diseases, and the severity of nausea and vomiting significantly influenced the QoL of patients with cancer who were undergoing radiotherapy. Factors affecting QoL varied at each time point. Thus, patients with cancer should undergo regular mental health assessments, including assessments of QoL. Multidimensional (physical, psychological, and social) approaches and individualized time-based interventions are needed to improve the QoL of cancer patients undergoing radiotherapy.

Background and Objectives: Diet and smartphone use are daily routines that can affect adolescents' mental health. This study investigated whether the frequency of the consumption of certain foods is associated with the duration of smartphone use and problems caused by smartphone overuse in adolescents., Methods and Study Design: Food consumption and smartphone use were investigated in 62,276 Korean adolescents aged 12-18 years by using a nationwide self-report survey. Food intake was assessed on a seven-point scale ("never" to "1, 2, and 3 or more times per day") for nine items: fruits, vegetables, milk, soda, energy drinks, sweetened beverages, fast food, instant noodles, and snacks. The durations of smartphone use and problematic use were determined using self-report items., Results: Most respondents (66.5%) used smartphones over 2 hours per day. Higher consumption levels of fruits (F=151.8; p<0.001), vegetables (F=119.9; p<0.001), and milk (F=33.0; p<0.001) were associated with significantly lower smartphone usage, whereas higher consumption levels of soda (F=292.5; p<0.001), energy drinks (F=24.0; p<0.001), sweetened beverages (F=224.8; p<0.001), fast food (F=192.1; p<0.001), instant noodles (F=196.2; p<0.001), and snacks (F=131.6; p<0.001) were positively associated with higher smartphone usage., Conclusions: Our findings provide useful clinical information regarding the association between dietary habits and smartphone use in adolescents. Future studies should investigate underlying mechanisms and examine the efficacy of dietary interventions for adolescents with excessive smartphone use.

Purpose: To optimize and validate a current (NRG [a newly constituted National Clinical Trials Network group through National Surgical Adjuvant Breast and Bowel Project [NSABP], the Radiation Therapy Oncology Group [RTOG] and the Gynecologic Oncology Group (GOG)]) nomogram for glioblastoma patients as part of continuous validation., Methods: We identified patients newly diagnosed with glioblastoma who were treated with temozolomide-based chemoradiotherapy between 2006 and 2016 at three large-volume hospitals. The extent of resection was determined via postoperative MRI. The discrimination and calibration abilities of the prediction algorithm were assessed; if additional factors were identified as independent prognostic factors, updated models were developed using the data from two hospitals and were externally validated using the third hospital. Models were internally validated using cross-validation and bootstrapping., Results: A total of 837 patients met the eligibility criteria. The median overall survival (OS) was 20.0 (95% CI 18.5-21.5) months. The original nomogram was able to estimate the 6‑, 12-, and 24-month OS probabilities, but it slightly underestimated the OS values. In multivariable Cox regression analysis, MRI-defined total resection had a greater impact on OS than that shown by the original nomogram, and two additional factors-IDH1 mutation and tumor contacting subventricular zone-were newly identified as independent prognostic values. An updated nomogram incorporating these new variables outperformed the original nomogram (C-index at 6, 12, 24, and 36 months: 0.728, 0.688, 0.688, and 0.685, respectively) and was well calibrated. External validation using an independent cohort showed C‑indices of 0.787, 0.751, 0.719, and 0.702 at 6, 12, 24, and 36 months, respectively, and was well calibrated., Conclusion: An updated and validated nomogram incorporating the contemporary parameters can estimate individual survival outcomes in patients with glioblastoma with better accuracy.

Background: Intraoperative radiotherapy (IORT) with a 50-kV x-ray is used for a tumor bed boost during breast-conserving surgery. This study evaluated the anatomicosurgical factors associated with cancellation of planned IORT., Methods: Patient eligibility for the study included age of 20 years or older, compatibility for lumpectomy, and ductal carcinoma in situ or stages 1-3 invasive carcinoma. All the patients underwent magnetic resonance imaging (MRI) and multidisciplinary team evaluations. Resection margins were assessed by frozen pathology. Pre- and intraoperative variables were compared between the IORT and IORT-cancellation groups., Results: A total of 434 patients underwent surgeries for IORT between August 2014 and December 2017. For 90 of these patients, IORT was canceled because of repeated positive margins leading to a large cavity or total mastectomy (n = 27), insufficient cavity-skin distance (n = 14), satellite lesions leading to a large cavity or total mastectomy (n = 12), MRI findings of a large primary tumor or uncertain margins leading to a large cavity (n = 6), cavity geometry unsuitable for IORT (n = 6), subareolar tumor extension (n = 6), tumor abutting the pectoralis muscle (n = 3), patient refusal (n = 5), intraoperative confirmation of bilateral breast cancer (n = 3) or benign pathology (n = 3), device malfunction (n = 3), or scheduling difficulty (n = 2). A tumor larger than 2 cm (P = 0.014) and the presence of satellite lesions (P = 0.014) were independent predictors of IORT cancellation., Conclusions: Surgical procedures resulting in large cavities were the leading cause of IORT cancellation. Multidisciplinary evaluations using MRI were critical for completion of IORT procedures.

Background and Purpose: Based on the 6th edition of the American Joint Commission on Cancer (AJCC) staging system for esophageal squamous cell carcinoma (ESCC), M1a node involvement was classified as regional node involvement in the revised 7th/8th edition. However, the clinical significance of M1a node involvement is unclear. Thus, we analyzed the prognostic value of M1a node involvement in patients with ESCC after definitive concurrent chemoradiotherapy (CCRT)., Materials and Methods: In total, 188 patients with ESCC had M0 disease according to the 7th/8th edition AJCC. We reclassified 31 (16.5%) of these patients as having M1a disease according to the 6th edition. After definitive CCRT, we compared baseline characteristics between the two groups and analyzed the rates of responders and recurrence. Finally, we compared prognoses according to overall survival (OS), disease-specific OS, and disease-free survival (DFS)., Results: Among 31 patients reclassified to have M1a disease, 21 (67.7%) had supraclavicular lymph node metastasis and 10 (32.3%) had celiac lymph node metastasis. The number of responders was significantly lower for M1a disease based on univariate (p = 0.004) and multivariate (p = 0.011) analyses. Significantly lower survival rates were observed in individuals with M1a disease (median OS, 16.4 vs. 42.7 months; 5-year OS, 10.8% vs. 41.2%)., Conclusions: M1a node involvement should be differentiated from regional node involvement., (Copyright © 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: To report the results of a phase I/II study of helical IMRT-based stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC)., Methods: Eligibility included Child-Turcotte-Pugh class A or B, ≤3 lesions, and cumulative tumor diameter ≤6 cm. Dose was escalated from 36 Gy to 60 Gy delivered in 4 fractions. Grade ≥3 gastrointestinal toxicities (CTCAE v3.0) or radiation-induced liver disease defined dose-limiting toxicity (DLT)., Results: Thirty-two patients were enrolled: seven in dose levels 1-2 (36-44 Gy) and 25 in levels 3-4 (42-60 Gy). Failures included 1 local, 14 outfield intrahepatic, 2 distant, 1 concurrent local and outfield, 1 concurrent outfield and distant, and 1 concurrent local, outfield, and distant. Nine had grade 3 hematologic toxicities and 5 had grade 2 hepatic toxicities; no patient experienced DLT. Two-year local control (LFFS), outfield intrahepatic control (OutFFS), and overall survival (OS) rates were 80.9%, 46.7%, and 81.3%, respectively. Dose levels 3-4 and pre-radiotherapy multi-segment recurrence were independent prognostic factors for LFFS and OutFFS, respectively. Two-year LFFS, OutFFS, and OS were significantly higher for patients who were treated with dose-levels 3/4 for tumor(s) involving single segment compared with the rest of the patients., Conclusions: Helical IMRT-based SBRT was safe and effective, and patients with multi-segment recurrences prior to SBRT need to be closely followed., (Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: There are concerns regarding local toxicity when IORT is applied in Asian women with a smaller breast volume than that of Western women. Trials are required to develop safety profiles for this technique. The aim of this trial was to evaluate acute toxicity after intra-operative radiotherapy (IORT) with low-energy X-ray plus whole breast irradiation (WBI) in Asian patients with breast cancer., Methods: This single-arm, single-institute, phase II trial investigated acute toxicity after completion of radiotherapy (targeted IORT followed by WBI) in Korean patients treated with breast-conserving surgery (BCS). In the conventional WBI arm from the TARGIT-A trial, the incidence of acute toxicity within 6 months was 15%. To prove the non-inferiority of the acute toxicity rate, 215 patients were required. This trial is registered with ClinicalTrials.gov (NCT02213991)., Results: Two-hundred and fifteen women were enrolled, and 198 underwent IORT. In 33 patients, clinically significant complications during the acute period were noted. The incidence of acute toxicity was 16.7% (95% CI 11.5-21.9%). There were 29 patients with seroma needing more than 3 aspirations, 4 with wound infection, and 2 with skin breakdown. There was no difference in the rate of complications according to the tumor volume or the tumor-breast volume ratio. Advanced age and high BMI were risk factors for acute complications., Conclusions: Targeted intra-operative radiotherapy using Intrabeam® is a safe procedure for Korean patients with breast cancer with an acceptable toxicity profile in the acute period.

Background: The aim of this study was to assess the outcomes of patients with de novo stage IV breast cancer after locoregional treatment (LRT) of primary site., Patients and Methods: We studied 245 patients diagnosed with de novo stage IV breast cancer. LRT of the primary tumor (+ systemic therapy) was performed in 82 (34%) patients (surgery, 27; surgery + radiotherapy (RT), 46; and RT, 9). Among those undergoing surgery, 64 (88%) patients underwent mastectomy, and 9 (12%) patients underwent breast-conserving surgery (BCS). Local recurrence-free survival (LRFS) and overall survival (OS) were investigated, and propensity score matching was used to balance patient distributions., Results: The 5-year LRFS and OS rates were 27% and 50%, respectively. Advanced T stage (T4), liver or brain metastasis, ≥ 5 metastatic sites, and absence of hormone therapy were significant adverse factors for LRFS, whereas T4 stage and absence of hormone therapy were significant for OS. The LRT group demonstrated significantly more favorable outcomes (5-year LRFS, 61%; 5-year OS, 71%), especially after surgery. After matching, survival rates remained significantly higher for patients who received LRT (5-year LRFS, 62% vs. 20%; P < .001; 5-year OS, 73% vs. 45%; P = .02). BCS + RT was superior to mastectomy ± RT, which can be attributed to more patients with a low tumor burden undergoing BCS + RT. Outcomes were better with post-mastectomy RT in selected patients (≥ N2, ≥ T3, or T2N1)., Conclusions: Upfront LRT including RT is an important option together with systemic therapies for de novo stage IV breast cancer., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Theta-phase gamma-amplitude coupling (TGC) was used as an evidence-based tool to reflect the dysfunctional cortico-thalamic interaction in patients with schizophrenia. The aim of the present study was to evaluate the diagnostic utility of TGC. The subjects included 90 patients with schizophrenia and 90 healthy controls. We compared the TGC results between the groups using an analysis of covariance (ANCOVA) to adjust for age and sex and receiver operator characteristic (ROC) curve analyses to examine the discrimination ability of delta to gamma frequency bands and TGC. Patients with schizophrenia showed a significant increase in the resting-state TGC at all 19 electrodes. The analysis of the ROC curves for each frequency band exhibited relatively low classification accuracies for the delta, theta, slow alpha, fast alpha, and beta power. The TGC generated the most accurate results among the electroencephalography (EEG) measures, with an overall classification accuracy of 92.5%. The resting-state TGC value was increased in patients with schizophrenia compared to that in healthy controls and had a higher discriminating ability than the other parameters. These findings may be related to the compensatory hyper-arousal patterns of the dysfunctional default-mode network (DMN) in schizophrenia. Therefore, resting-state TGC is a promising neurophysiological marker of schizophrenia., (Copyright © 2017 Elsevier B.V. All rights reserved.)

We evaluated the efficacy of dose de-escalation to the normal larynx using conformal radiotherapy (CRT) for T1/T2 glottic cancer. For conventional RT (2DRT, n = 38), the laryngeal box received a median equivalent dose in 2 Gy fractions (EQD2) of 66 Gy. For CRT (n = 42; 3D-CRT, 20; intensity-modulated RT, 22), clinical target volume (CTV)1 (gross tumor with a 3-mm margin) and CTV2 (laryngeal box) received median EQD2s of 66.6 Gy and 52.2 Gy, respectively. With a 71-month median follow-up, five-year local control and overall survival rates for 2DRT vs. CRT were 88.1% vs. 95.1% (p = 0.405) and 94.7% vs. 90.7% (p = 0.102), respectively. Grade 2 and 3 pharyngitis rates were 52.6% and 5.3% for 2DRT vs. 35.7% and 2.4% for CRT (p = 0.121). Grade 2 and 3 dermatitis rates were 42.1% and 2.6% for 2DRT vs. 35.7% and 0% for CRT (p = 0.013). The maximum phonation time increased from 12.1 ± 7.1 to 14.0 ± 6.6 seconds after 2DRT (p = 0.375) and from 12.0 ± 5.5 to 13.8 ± 10.1 seconds after CRT (p = 0.313). Fundamental frequency decreased from 150.6 ± 40.3 to 121.9 ± 30.2 Hz after 2DRT (p = 0.039) and from 138.5 ± 31.9 to 126.1 ± 23.7 Hz after CRT (p = 0.058). CRT can effectively de-escalate the normal larynx dose while maintaining oncologic outcome and voice quality.

Background: Local recurrence is common after surgical resection of clivus chordoma. We report the results of maximum surgical resection followed by intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB)., Methods: We reviewed 14 consecutive clivus chordoma cases undergoing postoperative IMRT-SIB using the institutional protocol between 2005 and 2013. Total and near-total resections were achieved in 11 patients (78.6 %), partial in 2 patients (14.3 %), and 1 patient (7.1 %) received RT for recurrent tumor after total resection. Gross residual or the high-risk area defined the planning target volume (PTV)1; PTV2 was the postoperative tumor bed plus a 3-5-mm margin, and PTV3 was PTV2 plus a 5-10 mm margin. A moderate hypofractionation schedule was used: doses to PTV1, PTV2 and PTV3 were 3.9 Gy, 3.15 Gy and 2.8 Gy through 15 fractions for the first two patients, and the rest received 2.5 Gy, 2.2 Gy and 1.8 Gy through 25 fractions. The biologically equivalent dose in 2-Gy fractions (EQD2) was 65-68 Gy for PTV1, 52-56 Gy for PTV2, and 44.3-44.8 Gy for PTV3., Results: Median follow-up was 41 months. Eight patients were free of disease for median 42.5 months (range 23-91 months), four patients had stable disease for median 60.5 months (range 39-113 months), and 1 patient showed partial response for 38 months after RT. Local progression was seen in one patient who received EQD2 67.8 Gy after partial resection. Estimated 5-year progression-free and overall survival rates were 92.9 %. Surgery improved the neurologic deficit in six patients, and IMRT-SIB was well tolerated without lasting toxicity., Conclusion: Our experience suggests that maximum resection and high-dose IMRT-SIB can achieve local control without significant morbidities.

The 3D-printed boluses were used during the radiation therapy of the chest wall in six patients with breast cancer after modified radical mastectomy (MRM). We measured the in-vivo skin doses while both conventional and 3D-printed boluses were placed on the chest wall and compared the mean doses delivered to the ipsilateral lung and the heart. The homogeneity and conformity of the dose distribution in the chest wall for both types of boluses were also evaluated. The uniformity index on the chest skin was improved when the 3D-printed boluses were used, with the overall average skin dose being closer to the prescribed one in the former case (-0.47% versus -4.43%). On comparing the dose-volume histogram (DVH), it was found that the 3D-printed boluses resulted in a reduction in the mean dose to the ipsilateral lung by up to 20%. The precision of dose delivery was improved by 3% with the 3D-printed boluses; in contrast, the conventional step bolus resulted in a precision level of 5%. In conclusion, the use of the 3D-printed boluses resulted in better dose homogeneity and conformity to the chest wall as well as the sparing of the normal organs, especially the lung. This suggested that their routine use on the chest wall as a therapeutic approach during post-mastectomy radiation therapy offers numerous advantages over conventional step boluses.

Guillain-Barre syndrome (GBS)-associated achalasia is a very rare disease of uncertain cause. We report the case of a patient diagnosed with GBS-associated type I achalasia who was successfully treated with peroral endoscopic myotomy (POEM). A 30-year-old man who was diagnosed with GBS 3 mo before was referred to our department with dysphagia and meal-related regurgitation. The results of esophagography, endoscopy, and high-resolution manometry (HRM) revealed type I achalasia. POEM that utilized a submucosal tunneling technique was performed to treat the GBS-associated type I achalasia. After POEM, smooth passage of a contrast agent into the stomach was shown in follow-up esophagography, and follow-up HRM revealed a decrease in the mean integrated relaxation pressure 22.9 mmHg to 9.6 mmHg. The patient remained without dysphagia for 7 mo, even though the patient's neurological problems were not fully resolved. POEM may be a safe and effective treatment for GBS-associated type I achalasia., Competing Interests: Conflict-of-interest statement: Authors have no conflict of interest to disclose.

Purpose: There has been increasing use of external beam radiotherapy for localized treatment of hepatocellular carcinoma (HCC) with both palliative and curative intent. Quality control of target delineation in primary HCC is essential to deliver adequate doses of radiation to the primary tumor while preserving adjacent healthy organs. We analyzed interobserver variability in gross tumor volume (GTV) delineation for HCC., Patients and Methods: Twelve radiation oncologists specializing in liver malignancy participated in a multi-institutional contouring dummy-run study of nine HCC cases and independently delineated GTV on the same set of provided computed tomography images. Quantitative analysis was performed using an expectation maximization algorithm for simultaneous truth and performance level estimation (STAPLE) with kappa statistics calculating agreement between physicians. To quantify the interobserver variability of GTV delineations, the ratio of the actual delineated volume to the estimated consensus volume (STAPLE), the ratio of the common and encompassing volumes, and the coefficient of variation were calculated., Results: The median kappa agreement level was 0.71 (range 0.28-0.86). The ratio of the actual delineated volume to the estimated consensus volume ranged from 0.19 to 1.93 (median 0.94) for all cases. The ratio of the common and encompassing volumes ranged from 0.001 to 0.56 (median 0.25). The coefficient of variation for GTV delineation ranged from 8 to 57 % (median 26 %)., Conclusion: The interobserver variability in target delineation of HCC GTV in this study is noteworthy. Multi-institution studies involving radiotherapy for HCC require appropriate quality assurance programs for target delineation.

Aim: To investigate the risk factors causing structural sequelae after anastomotic leakage in patients with mid to low rectal cancer., Methods: Prospectively collected data of consecutive subjects who had anastomotic leakage after surgical resection for rectal cancer from March 2006 to May 2013 at Korea University Anam Hospital were retrospectively analyzed. Two subgroup analyses were performed. The patients were initially divided into the sequelae (stricture, fistula, or sinus) and no sequelae groups and then divided into the permanent stoma (PS) and no PS groups. Univariate and multivariate analyses were performed to identify the risk factors of structural sequelae after anastomotic leakage., Results: Structural sequelae after anastomotic leakage were identified in 29 patients (39.7%). Multivariate analysis revealed that diversion ileostomy at the first operation increases the risk of structural sequelae [odds ratio (OR) = 6.741; P = 0.017]. Fourteen patients (17.7%) had permanent stoma during the follow-up period (median, 37 mo). Multivariate analysis showed that the tumor level from the dentate line was associated with the risk of permanent stoma (OR = 0.751; P = 0.045)., Conclusion: Diversion ileostomy at the first operation increased the risk of structural sequelae of the anastomosis, while lower tumor location was associated with the risk of permanent stoma in the management of anastomotic leakage.

Aim: To evaluate the efficacy of stents in treating patients with anastomotic site obstructions due to cancer recurrence following colorectal surgery., Methods: The medical records of patients who underwent endoscopic self-expanding metal stents (SEMS) insertion for colorectal obstructions between February 2004 and January 2014 were retrospectively reviewed. During the study period, a total of 218 patients underwent endoscopic stenting for colorectal obstructions. We identified and examined the patients who underwent endoscopic stenting for obstructions caused by cancer recurrence at the anastomotic site following colorectal surgeries for primary colorectal cancer., Results: Five consecutive patients [mean age, 56.4 years (range: 39-82 years); 4 women, 1 man] underwent endoscopic stenting for obstructions caused by cancer recurrence at the anastomotic site following colorectal surgeries for primary colorectal cancer. Technical and clinical success was achieved in all 5 patients, without any early complications. During follow-up, 3 patients did not need further intervention, prior to their death, after the first stent insertion; thus, the overall success rate was 3/5 (60%). Perforations occurred in 2 patients who required a second SEMS insertion due to re-obstruction; none of the patients experienced stent migration., Conclusion: SEMS placement is a promising treatment option for patients who develop obstructions of their colonic anastomosis sites due to cancer recurrence.

Aim: To elucidate the endoscopic features that predict the cancer following endoscopic submucosal dissection (ESD) in patients with high-grade neoplasia (HGN)., Methods: We retrospectively analyzed the medical records of patients who underwent ESD of gastric neoplasms from January 2007 to September 2010. ESD was performed in 555 cases involving 550 patients. A total of 112 lesions from 110 consecutive patients were initially diagnosed as HGN without cancer by forceps biopsy, and later underwent ESD. We classified lesions into two groups according to histologic discrepancies between the biopsy and ESD diagnosis. Gastric adenoma in the final diagnosis by ESD specimens were defined as adenoma group. Lesions with coexisting cancer after ESD were defined as cancer group., Results: The mean age was 65.3 years, and 81 patients were male. There was no significant difference in the age or gender distribution between the adenoma (n = 52) and cancer (n = 60) groups. Thirty-six of these lesions (32.1%) showed histologic concordance between the forceps biopsy and ESD specimens, 16 (14.3%) showed a downgraded histology (low-grade neoplasia), and 60 (53.6%) showed an upgraded histology (cancer). A red color change of the mucosal surface on endoscopy was found in 27/52 (51.9%) of cases in the adenoma group and in 46/60 (76.7%) of cases in the cancer group (P = 0.006). Ulceration of the mucosal surface on endoscopy was found in 5 (9.6%) of 52 lesions in the adenoma group and in 17 (28.3%) of 60 lesions in the cancer group (P = 0.013). In the multivariate analysis, a reddish surface color change and mucosal ulceration were significant predictive factors correlated with cancer after ESD of the HGN by forceps biopsy., Conclusion: HGN with a red color change or mucosal ulceration correlated with the presence of gastric cancer. These finding may help to guide the diagnosis and treatment.

Aim: To identify risk factors for surgical failure after colonic stenting as a bridge to surgery in left-sided malignant colonic obstruction., Methods: The medical records of patients who underwent stent insertion for malignant colonic obstruction between February 2004 and August 2012 were retrospectively reviewed. Patients with malignant colonic obstruction had overt clinical symptoms and signs of obstruction. Malignant colonic obstruction was diagnosed by computed tomography and colonoscopy. A total of 181 patients underwent stent insertion during the study period; of these, 68 consecutive patients were included in our study when they had undergone stent placement as a bridge to surgery in acute left-sided malignant colonic obstruction due to primary colon cancer., Results: Out of 68 patients, forty-eight (70.6%) were male, and the mean age was 64.9 (range, 38-89) years. The technical and clinical success rates were 97.1% (66/68) and 88.2% (60/68), respectively. Overall, 85.3% (58/68) of patients underwent primary tumor resection and primary anastomosis. Surgically successful preoperative colonic stenting was achieved in 77.9% (53/68). The mean duration, defined as the time between the SEMS attempt and surgery, was 11.3 d (range, 0-26 d). The mean hospital stay after surgery was 12.5 d (range, 6-55 d). On multivariate analysis, the use of multiple self-expanding metal stents (OR = 28.872; 95%CI: 1.939-429.956, P = 0.015) was a significant independent risk factor for surgical failure of preoperative stenting as a bridge to surgery. Morbidity and mortality rates in surgery after stent insertion were 4.4% (3/68) and 1.5% (1/68), respectively., Conclusion: The use of multiple self-expanding metal stents appears to be a risk factor for surgical failure.

Objective: The purpose of this study was to examine the influence of temperament and character on resilience., Methods: A total of 4355 participants completed two questionnaires: the Conner-Davison Resilience Scale (CD-RISC) and the Temperament and Character Inventory-Revised Short (TCI-RS). We used Pearson's correlations to evaluate the correlation between the dimensions of the TCI and the CD-RISC. To determine the most influential TCI dimension with respect to the CD-RISC, a backward multiple regression analysis was performed., Results: The resilience of both men and women was positively correlated with persistence, self-directedness, and cooperativeness. Conversely, harm avoidance was negatively correlated with resilience. In addition, reward dependence in men and self-transcendence in women were positively correlated with resilience. In the multiple regression analysis, persistence, self-directedness, and harm avoidance significantly predicted resilience after adjusting for age and gender., Conclusion: This results show that social support is affected by personality, which consists of both temperament and character. High persistence and self-directedness as well as low harm avoidance are found to contribute to a better stress response., (Copyright © 2013 Elsevier Inc. All rights reserved.)