Search

Purpose We aimed to investigate manifestations and patterns of care for patients with brain metastasis (BM) from breast cancer (BC) and compared their overall survival (OS) from 2005 through 2014 in Korea.Materials and Methods We retrospectively reviewed 600 BC patients with BM diagnosed between 2005 and 2014. The median follow-up duration was 12.5 months. We categorized the patients into three groups according to the year when BM was initially diagnosed (group I [2005-2008], 98 patients; group II [2009-2011], 200 patients; and group III [2012-2014], 302 patients).Results Over time, the median age at BM diagnosis increased by 2.2 years (group I, 49.0 years; group II, 48.3 years; and group III, 51.2 years; p=0.008). The percentage of patients with extracranial metastasis was 73.5%, 83.5%, and 86.4% for group I, II, and III, respectively (p=0.011). The time interval between BC and BM was prolonged in patients with stage III primary BC (median, 2.4 to 3 years; p=0.029). As an initial brain-directed treatment, whole-brain radiotherapy alone decreased from 80.0% in 2005 to 41.1% in 2014. Meanwhile, stereotactic radiosurgery or fractionated stereotactic radiotherapy alone increased from 13.3% to 34.7% during the same period (p=0.005). The median OS for group I, II, and III was 15.6, 17.9, and 15.0 months, respectively, with no statistical significance.Conclusion The manifestations of BM from BC and the pattern of care have changed from 2005 to 2014 in Korea. However, the OS has remained relatively unchanged over the 10 years.

Background: We analyzed the treatment outcome of breast cancer patients with brain metastases (BM) in Korea to identify the prognostic factors and the role of whole brain radiation therapy (WBRT). Methods: Seven hundred thirty patients of breast cancer with BM treated at 17 institutions in Korea from 2000 to 2014 were analyzed. The median follow-up duration was 12 months. The analysis consisted of three cohorts: in cohort A, a total of 730 patients were included; in cohort B, 538 patients with available follow-up imaging after initial brain-directed treatment; and in cohort C, 54 patients receiving salvage WBRT due to recurrent BM after initial Stereotactic radiosurgery or WBRT. Overall survival (OS) was calculated from BM diagnosis in cohort A or from the last day of salvage WBRT in cohort C. Results: Median OS of cohort A was 15 months. In multivariate analysis, histologic grade 3, extracranial metastasis, number of BM >4, hormone receptor (HR) or HER2 negativity, and shorter time interval to diagnosis of BM were associated with inferior OS. Among 538 patients in cohort B, 201 showed subsequent development of new BM at a median of 11 months after stereotactic radiosurgery or WBRT for the management of initial BM (at 1 year, HR+/HER2- 51.9%, HER2+ 44.0%, and TNBC 69.6%, respectively; p=0.008). Upfront WBRT reduced subsequent development of new BM, which showed the significant difference among molecular subtypes (HR+/HER2-, 42% reduction at 1 year, p4, and involvement of both tentoria increased subsequent development of new BM. Anti-HER2 therapy for HER2+ patients and upfront WBRT significantly reduced risk of new BM. In cohort C, upfront WBRT prolonged the salvage WBRT-free duration (median 6.9 vs. 8.7 months, p=0.058). Median OS was 6.8 months after salvage WBRT. Longer interval to salvage WBRT, controlled primary tumor, high dose of salvage WBRT (BED10 >37.5 Gy), and systemic treatment after salvage WBRT showed better OS. Uncontrolled extracranial systemic disease and salvage WBRT due to local progression without distant intracranial failure showed worse OS. Conclusions: The rates of new BM showed the significant differences among molecular subtypes. Upfront WBRT decreased subsequent development of new BM and this effect was dependent on the molecular subtype as well. Anti-HER2 therapy for HER2+ patients significantly decreased the subsequent development of new BM. On salvage WBRT setting, the patients having high dose of salvage WBRT, stable extracranial systemic disease and subsequent systemic therapy showed better OS. Citation Format: Jae Sik Kim, Kyubo Kim, Wonguen Jung, Kyung Hwan Shin, Seock-Ah Im, Hee-Jun Kim, Yong Bae Kim, Jee Suk Chang, Jee Hyun Kim, Doo Ho Choi, Yeon Hee Park, Dae Yong Kim, Tae Hyun Kim, Byung Ock Choi, Sea-Won Lee, Suzy Kim, Jeanny Kwon, Ki Mun Kang, Woong-Ki Chung, Kyung Su Kim, Won Sup Yoon, Jin Hee Kim, Jihye Cha, Yoon Kyeong Oh, In Ah Kim. Multicenter study for brain metastasis from breast cancer in Korea: The significance of molecular subtype (KROG 1612) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-21-01.

We previously constructed a nomogram for predicting the risk of arm lymphedema following contemporary breast cancer treatment. This nomogram should be validated in patients with different background characteristics before use. Therefore, we aimed to externally validate the nomogram in a large multi-institutional cohort.Overall, 8835 patients who underwent breast cancer surgery during 2007-2017 were identified. Data of variables in the nomogram and arm lymphedema were collected. The nomogram was validated externally using C-index and integrated area under the curve (iAUC) with 1000 bootstrap samples and by calibration plots.Overall, 1377 patients (15.6%) developed lymphedema. The median time from surgery to lymphedema development was 11.4 months. Lymphedema rates at 2, 3, and 5 years were 11.2%, 13.1%, and 15.6%, respectively. Patients with lymphedema had significantly higher body mass index (median, 24.1 kg/mThis nomogram, which was developed using factors related to multimodal breast cancer treatment and was validated in a large multi-institutional cohort, can well predict the risk of breast cancer-related lymphedema.

Background To investigate outcomes of salvage whole-brain radiotherapy (WBRT) for recurrent brain metastases (BM) from breast cancer (BC), to identify prognostic factors of overall survival (OS), and to propose a novel prognostic classification for OS in these patients. Materials and methods We identified 54 patients who had received salvage WBRT as the second brain-focused treatment for recurrent BM from BC (2000–2014). The median follow-up duration was 4.9 months. A recursive partitioning analysis (RPA) was conducted to develop a model to predict OS at the time of salvage WBRT. Results The median OS was 6.8 months. OS according to BC-specific graded prognostic assessment (breast-GPA), modified breast-GPA, and updated breast-GPA did not represent our cohort. In the multivariate analysis, a long time before salvage WBRT (≥16 months), control of primary BC or extracranial metastases, systemic treatment after salvage WBRT, and administration of a biologically effective dose for an α/β of 10 Gy (BED10) of salvage WBRT >37.5 Gy showed superior OS. We proposed three RPA classes based on the control of both primary BC and extracranial metastasis and BED10 of salvage WBRT: class I, class II, and class III. In this model, patients with class I experienced the best OS (34.6 months; class II, 5.0 months; class III, 2.4 months; P, Highlights • Multicenter retrospective study of salvage WBRT for recurrent brain metastasis. • Subsequent use of systemic treatment after salvage WBRT showing better OS. • Limitations of previous graded prognostic assessments for recurrent brain metastasis. • Novel RPA classification consisting of four simple clinical factors predicts OS.

Cardiac radioablation is emerging as an alternative option for refractory ventricular arrhythmias. However, the immediate acute effect of high-dose irradiation on human cardiomyocytes remains poorly known. We measured the electrical activities of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) upon irradiation with 0, 20, 25, 30, 40, and 50 Gy using a multi-electrode array, and cardiomyocyte function gene levels were evaluated. iPSC-CMs showed to recover their electrophysiological activities (total active electrode, spike amplitude and slope, and corrected field potential duration) within 3–6 h from the acute effects of high-dose irradiation. The beat rate immediately increased until 3 h after irradiation, but it steadily decreased afterward. Conduction velocity slowed in cells irradiated with ≥25 Gy until 6–12 h and recovered within 24 h; notably, 20 and 25 Gy-treated groups showed subsequent continuous increase. At day 7 post-irradiation, except for cTnT, cardiomyocyte function gene levels increased with increasing irradiation dose, but uniquely peaked at 25–30 Gy. Altogether, high-dose irradiation immediately and reversibly modifies the electrical conduction of cardiomyocytes. Thus, compensatory mechanisms at the cellular level may be activated after the high-dose irradiation acute effects, thereby, contributing to the immediate antiarrhythmic outcome of cardiac radioablation for refractory ventricular arrhythmias.

PurposeIn the present study, we aimed to establish a liquid biopsy-based monitoring method using peripheral blood cell-free DNA (cfDNA) for patients with cervical cancer who underwent radical radiotherapy (RT).Materials and MethodsTwenty-five patients with cervical cancer were prospectively recruited and treated with external beam RT and brachytherapy. In all patients, except one, chemotherapy was administered concurrently during RT. Whole peripheral blood samples were obtained at least twice from each patient. We performed next-generation sequencing (NGS) for the target-captured libraries (67 oncogenes and human papillomavirus [HPV] type 16/18) using 64 plasma cfDNA samples from the 25 participants. The ratio of HPV cfDNA and the variant allele frequency (VAF) in cfDNA was calculated, and their dynamic changes were monitored. The median follow-up duration was 25.4 months.ResultsIn total, we identified 21,866 cfDNA variants. ARID1A and frameshift variants occupied the largest portion of altered genes and HIGH-grade variant types, respectively. In most cases, tumor shrinkage was followed by a decrease in the HPV ratio; however, an increase in HPV ratio indicated distant metastasis, despite the reduced tumor size. The initial HPV ratio reflecting the tumor burden was likely associated with treatment outcomes (p = 0.16). We did not determine a role for serial changes in the VAF in cfDNA.ConclusionOur findings suggest that the HPV cfDNA ratio, calculated after targeted NGS, may be valuable for monitoring and predicting treatment responses. Accordingly, further validation of these findings is warranted.

New powertrain technologies, such as those used in Hybrid Electric Vehicles, have a price premium which is often offset by lower running costs. Total Cost of Ownership (TCO) combines these purchase and operating expenses to identify the most economical vehicles overall. This is a valuable assessment for both private and fleet purchasers. To date, no studies have compared Total Cost of Ownership across more than two vehicle markets or analysed historic costs. To address this gap, this research provides a more extensive assessment of TCO in three industrialized countries — the U.S.A. (California specifically), the UK, and Republic of Korea — for the time period from 2015 ∼ 2019. As an early analysis of the regional characteristics of TCO, this study aims to examine how TCO varies across different geographic regions and develop an analysis methodology for future analysis of environmental vehicles. To analyze the TCO under identical conditions for each region, the TCO result is calculated using data from conventional vehicles by utilizing sufficient statistical data. The TCO model includes registration and road taxes as well as insurance, fuel, financial interest, depreciation, and maintenance costs. To represent the local features, the research considers four vehicles from different manufacturers. Using the proposed TCO model, the regional characteristic is analyzed and a sensitivity analysis is performed with the parameters constituting the TCO model. This research has implications for both fleet purchasers and private owners considering new vehicles. The findings are also relevant for carmakers aiming to develop vehicle sales strategies optimized for specific regions.

Exogenous epidermal growth factor (EGF) causes apoptosis in EGF receptor (EGFR)-overexpressing cell lines. The apoptosis-inducing factors could be a therapeutic target. We aimed to determine the mechanism of EGF-induced apoptosis using a genome-wide clustered regularly interspaced short palindromic repeat (CRISPR)-based knockout screen.Two-vector system of the human genome-scale CRISPR knockout library v2 was used to target 19,050 genes using 123,411 single guide RNAs (sgRNAs). Recombinant human EGF (100 nM) or distilled water four times was administered to the experimental and control groups, respectively. The read counts of each sgRNA obtained from next-generation sequencing were analyzed using the edgeR algorithm. We used another EGFR-overexpressing cell line (A549) and short hairpin RNAs (shRNAs) targeting five EGF-resistance genes for validation. DUSP1 expression in A431, A549, and HEK293FT cells was calculated using reverse transcription-quantitative polymerase chain reaction.We found 77 enriched and 189 depleted genes in the experimental group using the CRISPR-based knockout screen and identified the top five EGF-resistance genes: DDX20, LHFP, REPS1, DUSP1, and KRTAP10-12. Transfecting shRNAs targeting these genes into A549 cells significantly increased the surviving fractions after EGF treatment, compared with those observed in the control shRNA-transfected cells. The expression ratio of DUSP1 (inhibits ERK signaling) increased in A431 and A549 cells after EGF treatment. However, DUSP1 expression remained unchanged in HEK293FT cells after EGF treatment.The CRISPR-based knockout screen revealed 266 genes possibly responsible for EGF-induced apoptosis. DUSP1 might be a critical component of EGF-induced apoptosis and a novel target for EGFR-overexpressing cancers.

To assess treatment outcomes in patients with stage I/II extranodal NK-/Between 1992 and 2018, 76 patients with early-stage ENKTCL-NT who achieved CR or partial response (PR) after induction chemotherapy received adjuvant RT. RT doses (using biologically equivalent doses in 2 Gy fractions [EQD2]) and rates of local recurrence-free survival (LRFS), locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and cancer-specific survival (CSS) were determined.Median follow-up was 5.1 years (range, 0.5-20.8). The median RT dose was 45 Gy (range, 20-54). The 5-year LRFS, LRRFS, DMFS, PFS, and CSS rates were 82.7 %, 78.2 %, 81.1 %, 68.7 %, and 84.4 %, respectively. CR after induction chemotherapy was notably linked to better survival outcomes across each endpoint. Survival outcomes were not affected either by the administration of l-ASP or EQD2 40 Gy in patients displaying CR after l-ASP. Adverse events (AEs) ≥ Grade 2 were significantly reduced with EQD2 40 Gy, compared with EQD2 ≥ 40 Gy.Achieving CR after chemotherapy was the most predictive factor of survival outcomes in early-stage ENKTCL-NT. Decreasing RT doses in patients with CR after l-ASP appeared to minimize the occurrence of AE without compromising LRR risk; however, longer follow-ups and cautious application are warranted.

During the braking process, frictional heat generated between a disc and a pad can lead to high temperatures. The location of friction blocks on the brake pad can lead directly to differences in friction contact time and friction speed at each point on the brake disc surface, this can lead to non-uniform temperature distribution on the brake disc surface. In this paper, the optimum design for friction blocks on a brake pad is investigated using the design of experiments (DOE) of Taguchi approach and response surface method (RSM) with an aim to minimize the deviation in the rate of friction heating in each area along the radial direction of brake disc. 18 design variables on 2 levels are adjusted. A table of orthogonal arrays, L32 (218), is used. Finite element analysis (FEA) is performed to analyze the mean squared error (MSE) values in the temperature deviations from frictional heat, the disc’s thermo-mechanical characteristics are taken into account. Analysis of variance (ANOVA) is carried out using the data gathered from the DOE stage, we find 7 significant factors among the design variables. A meta-model using RSM is proposed for reduction of temperature deviations over the brake disc. An optimized brake pad is analyzed in terms of the temperature and thermal stress imparted on the brake disc, this optimized pad is then compared with the original pad. The maximum temperatures of the optimized pad and original pad were 399.8 °C and 480.6 °C, respectively. The thermal stress of the optimized pad and original pad were 640.4 MPa and 721.4 MPa, respectively. In the optimized model, the size of the hot band on the disc is larger than that from the original model, so the thermal stress distribution on the disc is smaller. Finally, the optimized pad was found to give significant performance benefits with a 16.8 % decrease in maximum temperature and 11.2 % decrease in thermal stress.

Purpose Spontaneous rib fractures (SRFs) are defined as fractures without apparent blunt force trauma. This study evaluated the incidence and risk factors of SRFs after treatment of breast cancer patients based on bone scans. In addition, we analyzed radiation-associated SRFs and identified radiotherapy (RT) factors related to SRF. Methods We retrospectively reviewed 1,265 patients with breast cancer who underwent surgery in 2015 at our institution, and were followed-up with at least three bone scans. Bone scans were conducted approximately every 12 months after breast cancer treatment. The endpoint was SRF detected by bone scan. In this study, 754 (60%) patients were treated with chemotherapy, 867 (69%) with RT, and 946 (75%) with anti-hormone therapy. Results The median follow-up duration was 37.5 months. A total of 209 (16.5%) patients experienced SRFs during follow-up. The incidence of SRFs increased sharply during the 3-year follow-up period after completion of treatment. In multivariate analyses, abnormal bone density, chemotherapy, and RT were significant risk factors for SRFs. In patients treated with RT (n = 867), 159 (18%) rib fractures occurred: 127 (80%) in the ipsilateral breast and 32 (20%) in the contralateral breast. Among the ipsilateral SRF patients who received tumor bed boost (n = 84), the SRF occurred inside the boost field in 80 (95%) cases. Multivariate analysis of RT subgroups showed that hypofractionated RT increased the rate of SRFs (p = 0.002). Conclusions Most of the rib fractures that occurred after treatment were spontaneous. Hypofractionated RT increased the risk of ipsilateral rib fractures in RT-treated patients.

612 Background: The radiotherapy (RT) planning process for patients with gastrointestinal tract cancers is regarded as a time-consuming and complicated task due to proximity of multiple organs at risk (OARs). Dose prediction model based on deep learning might be a solution to increase efficiency by reducing the time required to find the optimal plan. Dose distribution model was developed using a three-dimensional (3D) U-Net deep learning. Methods: Altogether RT plan of patients with liver cancer (N=40) and pancreatic cancer (N=26) were acquired from the MRIdian (Viewray Technologies, Oakwood Village, OH) treatment planning system from 2016 to 2018. Magnetic resonance (MR) images for RT, planning dose, and contoured RT structures were retrospectively collected. The 3D U-Net was employed, and transfer-learning was performed on the training set (N=60, 91.3%). The initial learning rate was 0.1, decreasing by 10% every 5 epochs, for a total of 200 epochs. A developed model was evaluated by the testing set (N=5, 7.7%). The difference between ground truth and predicted dose was compared by calculating normalized minimum, maximum, and mean doses of the planning target volume (PTV) and OARs. Results: Root-mean-square error (RMSE) of voxels between ground truth and predictive dose was 3.04 (range 2.29-3.79). Percentage of mean dose difference and standard deviation between clinical and prediction models were 1.75 ± 2.84%, 0.08 ± 0.11%, 0.13 ± 0.08%, 0.05 ± 0.03%, 0.07 ± 0.05% for PTV, duodenum, liver, kidney, and stomach, respectively. And the percentage of max dose difference between the two were 0.91 ± 0.01%, 0.34 ± 0.43%, 0.63 ± 0.39%, 0.25 ± 0.18%, 0.33 ± 0.30%, respectively. Overall, the predicted normalized target DVH metrics were within 2% of the ground truth plans. Conclusions: We developed a deep learning model for dose prediction in liver and pancreatic cancer using MR images acquired from MRIdian system. Larger-scale training and validation are required to prove the efficacy of the dose prediction model by the 3D U-Net.

To identify the risk factors leading to new brain metastases (BM) following brain-directed treatment for initial BM resulting from breast cancer (BC). In this multi-institutional study, 538 BC patients with available follow-up imaging after brain-directed treatment for initial BM were analyzed. Tumor molecular subtypes were classified as follows: hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−, n = 136), HER2-positive (HER2+, n = 253), or triple-negative BC (TNBC, n = 149). In 37.4% of patients, new BM emerged at a median of 10.5 months after brain-directed treatment for initial BM. The 1-year actuarial rate of new BM for HR+/HER2−, HER2+, and TNBC were 51.9%, 44.0%, and 69.6%, respectively (p = 0.008). Initial whole-brain radiotherapy (WBRT) reduced new BM rates (22.5% reduction at 1 year, p 4) (p

Introduction We evaluated the incidence of cardiac events after chemoradiotherapy in patients with stage III non-small cell lung cancer (NSCLC) based on baseline cardiovascular risk and the heart substructures’ radiation dose. Methods From 2008 to 2018, the cardiac events of 258 patients with stage III NSCLC who received definitive chemoradiotherapy were reviewed. The 10-year cardiovascular risk was calculated using the Atherosclerotic Cardiovascular Disease (ASCVD) scoring system. Dose-volume histograms were estimated for each cardiac chamber. A multivariate competing-risk regression analysis was conducted to assess each cardiac event’s subhazard function (SHR). Results The median follow-up was 27.5 months overall and 38.9 months for survivors. Among the 179 deaths, none was definitely related to cardiac conditions. Altogether, 32 cardiovascular events affected 27 patients (10.5%) after chemoradiotherapy. Ten were major cardiac adverse events, including heart failure (N = 6) and acute coronary syndrome (ACS, N = 4). Most cardiovascular events were related to well-known risk factors. However, the volume percentage of the left ventricle (LV) receiving 60 Gy (LV V60) > 0 was significantly associated with ACS (SHR = 9.49, 95% CI = 1.28–70.53, P = 0.028). In patients with high cardiovascular risk (ASCVD score > 7.5%), LV V60 > 0% remained a negative ACS prognostic factor (P = 0.003). Meanwhile, in patients with low cardiovascular risk, the LV radiation dose was not associated with ACS events (P = 0.242). Conclusions A high LV radiation dose could increase ACS events in patients with stage III NSCLC and high cardiovascular risk. Pre-treatment cardiac risk evaluation and individualized surveillance may help prevent cardiac events after chemoradiotherapy.

Spontaneous rib fracture (SRF) is a common late complication in treated breast cancer patients. This study evaluated the incidence and risk factors of ipsilateral SRF after radiotherapy (RT) in breast cancer patients. In addition, we identified dosimetric parameters that were significantly associated with ipsilateral SRF.We retrospectively reviewed 2204 patients with breast cancer who underwent RT between 2014 and 2016, and were followed up with bone scans. We evaluated clinical risk factors for ipsilateral SRF. Dose-volume histogram analysis was also performed for patients (n = 538) whose dosimetric data were available. All ipsilateral ribs were manually delineated, and dosimetric parameters of the ribs were converted into the equivalent dose in 2 Gy fractions (EQD2).Most of the patients with SRF (87.3%) were asymptomatic, and the remaining symptomatic patients complained of mild tenderness or chest wall discomfort; these symptoms all resolved within 6 months without any treatment. Ipsilateral SRF occurred in 14.5% of patients 3 years after RT. The median time to develop ipsilateral SRF was 15 months. In dosimetric analysis, near-maximum rib dose (D2cc) best predicted ipsilateral SRF. The cut-off value of D2cc was EQD2 52 Gy, as determined by receiver operating characteristic analysis. In multivariate analysis including dosimetric variables, D2cc EQD2 ≥ 52 Gy was the only significant risk factor for ipsilateral SRF.Our data demonstrated that near-maximum rib dose was the best dosimetric parameter to predict ipsilateral SRF in RT-treated breast cancer patients. In addition, our results suggest that patients who received RT with exceeding rib dose cut-off value and had ipsilateral SRF on bone scan be recommended routine follow-up without additional imaging tests.

Purpose We aimed to analyze the treatment outcomes of ipsilateral cervical lymph node (CLN)-positive breast cancer without other distant metastasis and compare the outcomes with those of supraclavicular lymph node (SCL)-positive breast cancer. Methods Seventy-eight patients with breast cancer and ipsilateral CLN metastasis above the supraclavicular fossa (CLN[+] group) were treated at 7 institutions (2000-2014). Seventy-four patients received systemic chemotherapy and breast surgery followed by locoregional radiotherapy. Outcomes of the CLN(+) group were compared with those of the SCL(+) group, which included 183 patients with SCL involvement. Results The median follow-up duration was 55.9 months. Twenty-two regional failures were found in 15 patients-axillary lymph node (LN) in 8, SCL in 6, internal mammary LN in 3, previously involved CLN in 4, and previously uninvolved ipsilateral CLN in one patient. The 5-year overall survival (OS), disease-free survival (DFS), locoregional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS) rates were 68.6%, 46.7%, 68.4%, and 57.0%, respectively. Neck dissection did not improve LRRFS and DFS (p = 0.86 and p = 0.26, respectively). Multivariate analysis showed that hormone receptor negativity and the presence of extracapsular extension were prognostic factors for poor DFS. On comparison with stage IIIC using propensity score matching, survival outcomes of the CLN(+) and SCL(+) groups were not different (5-year OS, p = 0.75; DFS, p = 0.88; LRRFS, p = 0.86; and DMFS, p = 0.45). Conclusion The comparable clinical outcomes indicate that patients with breast cancer who have ipsilateral CLN metastasis without other distant metastasis may benefit from locoregional treatment of the ipsilateral breast and systemic therapies, as do those with N3c disease.

Pleuropulmonary blastoma (PPB) is a rare intrathoracic neoplasm in children. Although surgery with or without chemotherapy mainly conducted, the response of radiotherapy (RT) has not been evaluated yet. For unresectable tumor, RT might be considered as one option to decrease tumor extent to relieve obstructing symptoms or to facilitate successive treatment. We report one child in whom PPB with DICER1 mutation recurred after surgery and lead to respiratory distress. She emergently received palliative RT with a relatively low dose (20 Gy), and symptoms sufficiently relieved. Even she showed an 84.3% reduction in diameter and maintained the remission status for 1 year. These might reflect possible radiosensitivity of PPB, and further investigations of RT might be necessary for unresectable PPB.

Purpose We first analyzed the prognostic power of albumin-to-alkaline phosphatase ratio (AAPR) before radical radiotherapy (RT) in non-metastatic nasopharyngeal carcinoma (NPC) patients. Materials and methods The records of 170 patients with biopsy-proven, non-metastatic NPC treated by radical RT between 1998 and 2016 at our institution were retrospectively reviewed. Median follow-up duration was 50.6 months. All patients received intensity-modulated RT and cisplatin based chemotherapy before, during, or after RT. The major treatment of patients was based on concurrent chemoradiotherapy (92.4%). The AAPR was calculated by the last value of both albumin and alkaline phosphatase within 1 month immediately preceding RT. The optimal cut-off level of AAPR was determined by using Cutoff Finder, a web-based system. Propensity score matching (PSM) analysis was performed. Results The optimal cut-off level of AAPR was 0.4876. After PSM analysis of whole cohort, an AAPR was not related to survival outcomes. In PSM analysis for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC), an AAPR ≥ 0.4876 was related to better overall survival (OS), progression-free survival (PFS), and locoregional relapse-free survival (LRRFS) (OS: hazard ratio [HR], 0.341; 95% confidence interval [CI], 0.144 to 0.805; p=0.014; PFS: HR, 0.416; 95% CI, 0.189 to 0.914; p=0.029; and LRRFS: HR, 0.243; 95% CI, 0.077 to 0.769; p=0.016, respectively). Conclusion The AAPR, inexpensive and readily derived from a routine blood test, could be an independent prognostic factor for patients with LA-NPC. And it might help physicians determine treatment plans by identifying the patient's current status. Future prospective clinical trials to validate its prognostic value are needed.

Prevention emerges as a powerful approach in minimizing the risk of deleterious lifestyle diseases because therapies do not necessarily guarantee a permanent cure. Accordingly, consumers’ growing preference for natural and health-promoting dietary options that are rich in antioxidants has become widespread. Grape (Vitis vinifera) is an antioxidant-rich fruit extensively grown for fresh or processed consumption. The long-term consumption of its polyphenolic antioxidants may promote multiple health benefits. However, grape pomace (GP), consisting of peel, seed, stem, and pulp, is discarded during grape processing, including juice extraction and winemaking, despite its substantial antioxidant content. Polyphenolic extraction techniques have been widely explored to date, but the consolidation of reported physiological impacts of GP-derived polyphenolic constituents is limited. Thus, this review highlights current studies of the potential applications of GP extract in disease prevention and treatment, emphasizing the major influence of polyphenolic compositions and origins of different grape varieties.

Considering the anti-photoaging effect of antioxidant compounds, we investigated the protective capacity of grape peel extract (GPE) and resveratrol on ultraviolet (UV)-induced skin wrinkle formation. Total phenolic, total anthocyanin, and total flavonoid content in GPE prepared from peel of Campbell Early variety were 23.96 ± 0.09, 3.27 ± 0.40, and 1.24 ± 0.09 mg/g dry weight, respectively. Additionally, trans-resveratrol and piceid content of the resulting GPE were 117.14 ± 19.97 and 85.23 ± 8.89 µg/g dry weight, respectively. Oral administration of either 2 g GPE or 2 mg resveratrol per kg body weight in mice attenuated UVB-induced epidermal thickening (the thickness was reduced by about 63% and 55% with GPE and resveratrol consumption prior to exposure to UVB, respectively, compared to only UVB-treated condition) and had marginally protective effect on wrinkle formation of skin exposed to UVB. As introduction of either GPE or resveratrol induced Nrf2-dependent antioxidant enzymes including heme oxygenase-1 (HO-1) in liver and skin as well as inhibited metalloproteinases, it is highly probable that the extract or resveratrol mitigated UVB-induced photoaging through activation of Nrf2/HO-1 signaling pathway. PRACTICAL APPLICATION: This study proved that resveratrol and the extract of grape peel, a common by-product of grape juice processing, provide effective protection from UV-induced skin wrinkle formation. Therefore, grape peel extract, which contains an appreciable amount of bioactive compound resveratrol, can be utilized as functional food ingredient for the manufacture of inner beauty products.

Purpose To identify prognostic factors influencing progression-free survival (PFS) of aggressive fibromatosis (AF) after postoperative radiotherapy (PORT) and assess correlations between immunohistochemistry (IHC) features of β-catenin/smooth muscle actin (SMA) and PFS. Materials and Methods Records of 37 patients with AF treated by PORT from 1984 to 2015 were retrospectively reviewed. Fifteen patients underwent wide excision for AF and 22 patients received debulking operation. The median total dose of PORT was 59.4 Gy. IHC staining results of β-catenin and SMA were available for 11 and 12 patients, respectively. Results The median follow-up duration was 105.9 months. Five-year PFS rate was 70.9%. Tumor size or margin status was not related to PFS in univariate analysis (p = 0.197 and p = 0.716, respectively). Multivariate analysis showed that increased interval from surgery to PORT (>5.7 weeks) was a marginal risk factor for PFS (p = 0.054). Administration of PORT at the initial diagnosis resulted in significantly improved PFS compared to deferring PORT after recurrence (p = 0.045). Patient with both risk factors of deferring PORT after recurrence and interval from surgery to PORT >5.7 weeks had significantly lower 5-year PFS than patients without risk factor (34.1% vs. 100.0%; p = 0.012). Nuclear β-catenin intensity tended to inversely correlate with 5-year PFS, although it did not reach statistical significance (62.5% at low vs. 100.0% at high; p = 0.260). SMA intensity was not related to PFS (p = 0.700). Conclusion PORT should be performed immediately after surgery irrespective of margin status or tumor size especially in recurrent case. Nuclear β-catenin staining intensity of IHC might correlate with local recurrence.

Al2O3/Cu composite films, useful for film resistors, were successfully fabricated at room temperature via aerosol deposition (AD). Microstructures of the Al2O3/Cu composite films were analyzed to understand the correlations between the surface morphologies and Al2O3/Cu ratio. A scratch test was carried out by gradually increasing the load applied to the Al2O3/Cu composite films. We also evaluated the adhesion ability by measuring the tensile strength between Al2O3/Cu composite films and Al2O3 substrate. The results confirmed that the adhesive properties of Al2O3/Cu composite films were strongly influenced by two adhesive mechanisms: mechanical interlocking and anchoring bonds between the films and Al2O3 substrate. When a powder mixture containing 50 wt% of Al2O3 and Cu was deposited on the substrate, high mechanical properties and suitable resistivity were simultaneously achieved at approximately 8.02 MPa and 85.2 mΩ cm, respectively due to effective mechanical interlocking and anchoring bonds. The results further suggest that room-temperature AD method is highly favorable to fabricate heterogeneous composite films for application to film resistors.

To identify the risk factors leading to new brain metastases (BM) following brain-directed treatment for initial BM resulting from breast cancer (BC).In this multi-institutional study, 538 BC patients with available follow-up imaging after brain-directed treatment for initial BM were analyzed. Tumor molecular subtypes were classified as follows: hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-, n = 136), HER2-positive (HER2+, n = 253), or triple-negative BC (TNBC, n = 149).In 37.4% of patients, new BM emerged at a median of 10.5 months after brain-directed treatment for initial BM. The 1-year actuarial rate of new BM for HR+/HER2-, HER2+, and TNBC were 51.9%, 44.0%, and 69.6%, respectively (p = 0.008). Initial whole-brain radiotherapy (WBRT) reduced new BM rates (22.5% reduction at 1 year, p 0.001) according to molecular subtype (HR+/HER2-, 42% reduction at 1 year, p 0.001; HER2+, 18.5%, p = 0.004; TNBC, 16.9%, p = 0.071). Multivariate analysis revealed an increased risk of new BM for the following factors: shorter intervals between primary BC diagnoses and BM (p = 0.031); TNBC (relative to HR+/HER2-) (p = 0.016); presence of extracranial metastases (p = 0.019); number of BM (4) (p 0.001); and BM in both tentorial regions (p = 0.045). Anti-HER2 therapy in HER2+ patients (p = 0.013) and initial use of WBRT (p 0.001) significantly lowered new BM development.Tumor molecular subtypes were associated with both rates of new BM development and the effectiveness of initial WBRT. Anti-HER2 therapy in HER2+ patients significantly lowered new BM occurrence.

e14008 Background: We analyzed the treatment outcome of breast cancer patients with brain metastases (BM) in Korea to identify the prognostic factors and the role of whole brain radiation therapy (WBRT). Methods: Seven hundred thirty patients of breast cancer with BM treated at 17 institutions in Korea from 2000 to 2014 were analyzed. The median follow-up duration was 12 months. The analysis consisted of three cohorts: in cohort A, a total of 730 patients were included; in cohort B, 538 patients with available follow-up imaging after initial brain-directed treatment; and in cohort C, 54 patients receiving salvage WBRT due to recurrent BM after initial Stereotactic radiosurgery or WBRT. Overall survival (OS) was calculated from BM diagnosis in cohort A or from the last day of salvage WBRT in cohort C. Results: Median OS of cohort A was 15 months. In multivariate analysis, histologic grade 3, extracranial metastasis, number of BM > 4, hormone receptor (HR) or HER2 negativity, and shorter time interval to diagnosis of BM were associated with inferior OS. Among 538 patients in cohort B, 201 showed subsequent development of new BM at a median of 11 months after stereotactic radiosurgery or WBRT for the management of initial BM (at 1 year, HR+/HER2- 51.9%, HER2+ 44.0%, and TNBC 69.6%, respectively; p = 0.008). Upfront WBRT reduced subsequent development of new BM, which showed the significant difference among molecular subtypes (HR+/HER2-, 42% reduction at 1 year, p < 0.001; HER2+, 18.5%, p = 0.004; TNBC, 16.9%, p = 0.071). Multivariate analysis showed that shorter time interval to BM, TNBC subtype, extracranial systemic disease, number of BM > 4, and involvement of both tentoria increased subsequent development of new BM. Anti-HER2 therapy for HER2+ patients and upfront WBRT significantly reduced risk of new BM. In cohort C, upfront WBRT prolonged the salvage WBRT-free duration (median 6.9 vs. 8.7 months, p = 0.058). Median OS was 6.8 months after salvage WBRT. Longer interval to salvage WBRT, controlled primary tumor, high dose of salvage WBRT (BED10 > 37.5 Gy), and systemic treatment after salvage WBRT showed better OS. Uncontrolled extracranial systemic disease and salvage WBRT due to local progression without distant intracranial failure showed worse OS. Conclusions: The rates of new BM showed the significant differences among molecular subtypes. Upfront WBRT decreased subsequent development of new BM and this effect was dependent on the molecular subtype as well. Anti-HER2 therapy for HER2+ patients significantly decreased the subsequent development of new BM. On salvage WBRT setting, the patients having high dose of salvage WBRT, stable extracranial systemic disease and subsequent systemic therapy showed better OS.

In this study, the authors analyse the effects of the design parameters of a high-power bipolar short-pulsed array antenna on a beamwidth and a sidelobe of a transient radiation pattern. The analysed results can provide guidelines for synthesising a desired transient radiation performance of high-power bipolar short pulsed-array antennas. The analysis is performed using a formulation that consists of an element pattern and an array factor of a transient radiation pattern. To verify the validation of the studies, the analysed results of various array configurations (1 × 3, 1 × 4, 3 × 1, 4 × 1 and 2 × 2 arrays) are compared to the full-wave simulated and measured results.

A multiple scattering points generator for multi-target (MSPG-MT) is proposed to simulate multi-target engagement of a high-resolution radar (HRR) at an indoor testing. A multi-target signal generator provides to the MSPG-MT with multi-target signals generated by multiple direct-digital synthesizers (DDSs). The MSPG-MT provides to antennas with individual multiple scattering points of the multi-target generated by multiple divider blocks. The HRR receives the radiated signals from antennas and displays the multiple scattering points in the beat frequency domain. The validation of the proposed MSPG-MT was verified through a measurement using a Ku-band HRR and the MSPG-MT.

This paper presents a compact monopulse antenna which can be fitted inside of a small diameter radome. The monopulse antenna is composed of four antenna elements and each antenna consists of a square open-ended waveguide(OEWG), a stepped impedance matching structure, and a conformal aperture. Because of the compactness and the conformal aperture of the element that can be mounted on the inner surface of the radome, the center space of the radome can be secured, which can provide a space for other sensors or devices. To verify the monopulse performance of the designed antenna, its sum (Σ) and difference (Δ) patterns are calculated. The Σ pattern gains of the antenna are 15.3 dB, 15.1 dB, and 15.4 dB for f l GHz, f c GHz, and f h GHz, respectively. The normalized null depths of the Δ patterns are under -40 dB within the operational frequency.

In this paper, the BaTiO3/Ni composite films of 10 μm were fabricated by Aerosol deposition. We investigate the dielectric behavior of BaTiO3/Ni composite films with various Ni contents. The BaTiO3/Ni composite film with Ni content of 9.1 vol% has high dielectric constant at 1 kHz (476) due to the percolation effect. This high dielectric constant was attributed to the microcapacitor structures and Maxwell–Wagner polarization. Although the BaTiO3/Ni composite film was fabricated at room temperature, it had a high dielectric constant of 8 times higher than that of raw BaTiO3 film, and showed a very low leakage current. Therefore, BaTiO3/Ni composite films fabricated by Aerosol deposition can potentially be used as embedded capacitors.