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PurposeWe aimed to assess the real-world efficacy of nab-paclitaxel in metastatic breast cancer patients.Materials and MethodsThis is a retrospective study performed in two tertiary referral hospitals in Korea. Patients with metastatic breast cancer treated with nab-paclitaxel (Abraxane®) between March 2016 and March 2020 were enrolled.ResultsA total of 102 patients with metastatic breast cancer were included. Patients were heavily pre-treated with a median of four prior lines of chemotherapy (5 lines when including endocrine therapy in hormone-receptor-positive patients), and 66 patients (64.7%) were exposed to taxanes in the metastatic setting. According to St. Gallen molecular subtypes, 36 patients (35.3%) were luminal A, 28 (27.5%) were luminal B, 18 (17.7%) were human epidermal growth factor receptor 2–positive and 20 (19.6%) had triple-negative disease. Fifty patients (49.0%) were treated with a 3-weekly regimen (260 mg/m2 on day 1 every 3 weeks), and 52 (51.0%) were treated with a weekly regimen (100 mg/m2 every week). Objective response rate was 22.9%. After a median follow-up of 22.0 months, median progression-free survival (PFS) was 4.0 months (95% confidence interval [CI], 2.6 to 4.8) and median overall survival was 8.7 months (95% CI, 7.5 to 11.2). Patients treated with weekly regimen had longer PFS compared to 3-weekly regimen (5.5 vs. 2.3 months, p < 0.001). Multivariate analysis revealed the treatment regimen as an independent prognostic factor for PFS. There was no grade 3 or 4 hypersensitivity reaction.ConclusionThis real-world data shows that nab-paclitaxel is a reasonable treatment option in heavily pre-treated and/or taxane-exposed metastatic breast cancer patients.

The aim of this study was to compare the current fall prevention nursing practices with the evidence-based practices recommended in clinical practice guidelines according to the risk of falling and specific risk factors.The standardized nursing statements of 12,277 patients were extracted from electronic nursing records and classified into groups according to the risk of falling and individual patients' specific risk factors. The mean frequencies of the fall prevention practices in 10 categories derived from clinical practice guidelines were compared among the groups. We additionally analyzed the differences in the mean frequencies of tailored fall prevention practices according to individual patients' specific risk factors.The nurses documented more fall prevention practices for patients at a high risk of falling and nonfallers than for patients at a low risk of falling and fallers. Specifically, the difference in nursing practices related to environmental modifications was largest between patients at a high risk of falling and those at a low risk of falling. There were also large differences in the nursing practices related to mental status, dizziness/vertigo, and mobility limitations between fallers and nonfallers. There was more documentation of tailored fall prevention practices related to mobility limitations for patient with mild lower limb weakness than for those with good power and balance. In contrast, patients with severe lower limb weakness had received fewer fall prevention practices related to mobility limitations.The present findings emphasize that individual risk-specific nursing interventions in addition to universal precautions are crucial for preventing falls among patients.

Women with endometriosis may experience uncertainty owing to the characteristics of the disease, including vague symptom patterns, delayed diagnosis, and long-term management with no cure. However, women use various coping strategies to adapt to the uncertainty caused by their endometriosis. This descriptive qualitative study explored the coping experiences of women with endometriosis to reduce their uncertainty about the disease and to achieve successful adaptation to their lives with endometriosis. By using convenience and purposive sampling methods, qualitative data were collected from 14 women in South Korea (mean age = 37.7 years, age range = 27-54 years), who were diagnosed with endometriosis through laparoscopy or open surgery. All interview data were thematically analyzed. Four themes were identified as adaptive coping experiences: (1) gaining self-control over the ambiguous disease; (2) regaining the daily routines destroyed by the disease; (3) being emotionally supported and expressing oneself when feeling unsupported by society; and (4) taking an active role in one's treatment plan by being self-directed. Patients' sense of self-control and self-directedness regarding the disease and the treatment process were important to adapt to life with endometriosis. In addition, regaining stable daily routines as well as being emotionally supported were critical for decreasing their uncertainty. This paper has widespread implications, including the need for training or a continuing education program for health professionals to enhance their competencies when caring for women with endometriosis and the need for social efforts to increase awareness of the disease.

Introduction Breast cancer co-occurred with thyroid cancer might be associated with thyroid hormone receptor (TR) and estrogen receptor (ER), but few have been reported. We aimed to investigate the expression and prognostic significance of ERs and TRs in such settings. Material and methods Tissue microarrays were constructed from 75 patients with breast and thyroid cancer (BC + TC) who were retrospectively recruited between 1999 and 2012 and 147 with breast cancer only (BC controls). The ERα, ERβ, TRα, and TRβ expression levels were analyzed by immunohistochemistry. Results TRα expression was more frequently observed in the BC + TC group than the BC control group both in the normal (51.5% vs 23.3%, respectively, p = 0.009) and cancer tissues (21.6% vs 6.8%, respectively, p = 0.001). The BC + TC group showed greater ERα-positivity in the cancer tissues (79.7% vs 58.7%, respectively, p = 0.002) than the BC control group. The degree of ERα- and TRα-positivity was unchanged by radioactive treatment or serum thyroid stimulating hormone levels. In the BC + TC group, ERα-positivity was associated with earlier disease stage I/IIA (81.0% vs 50.0%; p = 0.031) and lower recurrence rates (8.5% vs 40.0%; p = 0.002). TRα-positivity alone was not associated with any recurrence-free survival-related differences, and ERα- and TRα-negativity were associated with significantly shorter recurrence-free survival (p Conclusion Enhanced ERα and TRα expression in breast cancer is associated with thyroid cancer occurrence, and the observed association with prognosis suggests the possible role of ERs and TRs in the link between breast cancer and thyroid cancer.

BACKGROUND Liver fibrosis is characterized by the excessive accumulation of extracellular matrix proteins. Electrical conductivity imaging at low frequency can provide novel contrast because the contrast mechanisms originate from the changes in the concentration and mobility of ions in the extracellular space. PURPOSE To evaluate the feasibility of an MR-based electrical conductivity imaging that can detect the changes in a tissue condition associated with the progression of liver fibrosis. STUDY TYPE Prospective phantom and animal study. ANIMAL MODEL Fibrosis was induced by weekly intraperitoneal injection of dimethylnitrosamine (DMN) in 45 male Sprague-Dawley rats. FIELD STRENGTH/SEQUENCE 3T MRI with a multispin-echo pulse sequence. ASSESSMENT The percentage change of conductivity (Δσ, %) in the same region-of-interest (ROI) was calculated from the DMN-treated rats based on the values of the normal control rats. The percentage change was also calculated between the ROIs in each DMN-treated group. STATISTICAL TESTS One-way analysis of variance (ANOVA) and a two-sample t-test were performed. RESULTS Liver tissues in normal control rats showed a uniform conductivity distribution of 56.6 ± 4.4 (mS/m). In rats more than 5 weeks after induction, the fibrous region showed an increased conductivity of ≥12% compared to that of the corresponding normal control rats. From regional comparisons in the same liver, the fibrous region showed an increased conductivity of ≥11% compared to the opposite, less induced region of rats more than 5 weeks after induction. Liver samples from the fibrous region represent tissue damages such as diffuse centrilobular congestion with marked dilatation of central veins from the histological findings. Immunohistochemistry revealed significant levels of attenuated fibrosis and increased inflammatory response. DATA CONCLUSION The increased conductivity in the fibrous region is related to the changes of the extracellular space. The correlation between the collagen deposition and conductivity changes is essential for future clinical studies. Level of Evidence 2 Technical Efficacy Stage 2 J. MAGN. RESON. IMAGING 2021;53:554-563.

Accurate prediction of pathologic complete response (pCR) in breast cancer using magnetic resonance imaging (MRI) and ultrasound (US)-guided biopsy may aid in selecting patients who forego surgery for breast cancer. We evaluated the accuracy of US-guided biopsy aided by MRI in predicting pCR in the breast after neoadjuvant chemotherapy (NAC). After completion of NAC, 40 patients with near pCR (either tumor size ≤ 0.5 cm or lesion-to-background signal enhancement ratio (L-to-B SER) ≤ 1.6 on MRI) and no diffused residual microcalcifications were prospectively enrolled at a single institution. US-guided multiple core needle biopsy (CNB) or vacuum-assisted biopsy (VAB) of the tumor bed, followed by standard surgical excision, was performed. Matched biopsy and surgical specimens were compared to assess pCR. The negative predictive value (NPV), accuracy, and false-negative rate (FNR) were analyzed. pCR was confirmed in 27 (67.5%) surgical specimens. Preoperative biopsy had an NPV, accuracy, and FNR of 87.1%, 90.0%, and 30.8%, respectively. NPV for hormone receptor-negative and hormone receptor-positive tumors were 83.3% and 100%, respectively. Obtaining at least 5 biopsy cores based on tumor size ≤ 0.5 cm and an L-to-B SER of ≤ 1.6 on MRI (27 patients) resulted in 100% NPV and accuracy. No differences in accuracy were noted between CNB and VAB (90% vs. 90%). Investigation using stringent MRI criteria and ultrasound-guided biopsy could accurately predict patients with pCR after NAC. A larger prospective clinical trial evaluating the clinical safety of breast surgery omission after NAC in selected patients will be conducted based on these findings.

Objective Early detection and proper management of mental illness can help to prevent severe deterioration. However, with limited financial and human resources of community mental health services, it is not practical to carry out all conventional screening tools simultaneously. In this study, we aimed to develop and validate a brief but comprehensive screening questionnaire for four common mental illnesses of the elderly.Methods The brief screening for four mental illnesses of elderly (BS4MI-elderly) is a 14-item binary response questionnaire that covers dementia, depressive disorder, sleep disorder, and hwa-byung. To test validity, we compared conventional scale scores for three groups of participants classified using the BS4MI-elderly. The sensitivity, specificity, predictive value of positive test, likelihood ratio of positive test and internal consistency of the BS4MI-elderly were assessed. Finally, a correlation analysis between the BS4MI-elderly and general mental health scales was conducted.Results A total of 254 participants aged over 65 years were recruited. The BS4MI-elderly showed moderate to high sensitivity for the test that distinguishes the normal group from the risk and disorder groups (dementia: 0.61, depressive disorder: 0.88, sleep disorder: 0.85, hwa-byung: 0.94) and high specificity for the test that distinguishes the disorder group from the normal and risk groups (dementia: 0.91, depressive disorder: 0.93, hwa-byung: 0.84, sleep disorder: 0.84). The BS4MI-elderly also exhibited good internal consistency and significant correlations with general mental health scales.Conclusion The BS4MI-elderly, a brief but comprehensive screening tool, could be a useful instrument for screening the elderly in community mental health services.

Gadolinium neutron capture therapy (GdNCT) is considered as a new promising cancer therapeutic technique. Nevertheless, limited GdNCT applications have been reported so far. In this study, surface-modified ultrasmall gadolinium oxide nanoparticles (UGNPs) with cancer-targeting ability (davg = 1.8 nm) were for the first time applied to the in vivo GdNCT of cancer using nude model mice with cancer, primarily because each nanoparticle can deliver hundreds of Gd to the cancer site. For applications, the UGNPs were grafted with polyacrylic acid (PAA) for biocompatibility and colloidal stability, which was then conjugated with cancer-targeting arginylglycylaspartic acid (RGD) (shortly, RGD-PAA-UGNPs). The solution sample was intravenously administered into the tails of nude model mice with cancer. At the time of the maximum accumulation of the RGD-PAA-UGNPs at the cancer site, which was monitored using magnetic resonance imaging, the thermal neutron beam was locally irradiated onto the cancer site and the cancer growth was monitored for 25 days. The cancer growth suppression was observed due to the GdNCT effects of the RGD-PAA-UGNPs, indicating that the surface-modified UGNPs with cancer-targeting ability are potential materials applicable to the in vivo GdNCT of cancer.

Rationale: Steroid receptor activator (SRA), a long non-coding RNA, serves as a critical regulator of gynecologic cancer. The objective of this study was to determine biological function and clinical significance of SRA expression in endometrial cancer. Method: We investigated whether SRA was involved in the development of endometrial cancer via binding to eukaryotic translation initiation factor 4E-binding protein 1 (EIF4E-BP1) as a transcription factor to enhance Wnt/ β-catenin signaling pathway. Results: Expression levels of SRA were upregulated in endometrial cancer tissues compared to those in adjacent control tissues. We also found high expression of SRA in EC cells. The relationship between SRA and EIF4E-BP1 was corroborated by transfection of a luciferase reporter plasmid. In addition, SRA knockdown inhibited the expression of EIF4E-BP1 known to play a critical role in the control of protein synthesis, cell growth, and cell survival, thus promoting tumourigenesis and epithelial-mesenchymal transition (EMT) important for cell motility and metastasis. Consistently, immunostaining and western blotting analysis showed that expression levels of β-catenin and 4EBP1 in the nucleus were significantly decreased by SRA knockdown but increased by SRA over-expression. Conclusions: These results suggest that SRA is involved in proliferation, migration, and invasion of endometrial cancer cells by increasing the expression of EIF4E-BP1 and activity of Wnt/ β-catenin signaling. These findings indicate that SRA might be a novel biomarker for predicting recurrence and prognosis. It might also serve as a promising therapeutic target in endometrial cancer.

Seoul Metropolitan Seobuk Hospital is a hospital which is directly managed by the Seoul Metropolitan Government and has mainly been used for homeless people and tuberculosis patients...

Long non-coding RNA (lncRNA) is a newly identified regulator of tumor formation and tumor progression. The function and expression of lncRNAs remain to be fully elucidated, but recent studies have begun to address their importance in human health and disease. The lncRNA, SRA, known as steroid receptor activator, acts as an important modulator of gynecological cancer, and its expression may affect biological functions including proliferation, apoptosis, steroid formation, and muscle development. However, it is still not well known whether SRA is involved in the regulation of ovarian cancer. The present study investigated the molecular function and association between SRA expression and clinicopathological factors. In ovarian cancer cell lines, SRA knockdown and overexpression regulated cell migration, proliferation, and invasion. Both in vivo and in vitro experiments using knockdown and overexpression showed that SRA potently regulated epithelial–mesenchymal transition (EMT) and NOTCH pathway components. Further, clinical data confirmed that SRA was a significant predictor of overall survival (OS) and progression-free survival and patients with ovarian cancer exhibiting high expression of SRA exhibited higher recurrence rates than patients with low SRA expression. In conclusion, the present study indicates that SRA has clinical significance as its expression can predict the prognosis of ovarian cancer patients. High expression of the lncRNA SRA is strongly correlated with recurrence-free survival of ovarian cancer patients.

Background /aims Although the epidemiology of pyogenic liver abscess (PLA) continues to change, only a few population-based studies have been conducted in Korea. This study investigated the epidemiology and clinical outcomes of PLA patients during a period of 10 years. Methods We analyzed the Health Insurance Review and Assessment Service data between 2007 and 2017. The data included annual incidence rates, demographic data, underlying diseases, complications, and mortality of PLA patients. Results The annual incidence of PLA for all age groups was 10.9 per 100,000 population. The incidence was gradually increased from 5.7 per 100,000 in 2007 to 14.4 per 100,000 in 2017. In patients with liver abscess, the prevalence of diabetes and malignancy were 37.24% and 26.5%, respectively. Metastatic infection was reported in 1.74% of the patients, and endophthalmitis was most common. The mean in-hospital mortality was 9.6%, and there was no significant difference in mortality by year during the observation period. Mortality increased with age and was greatly affected by the underlying diseases, especially cancer. Based on the multivariate analysis results, the mortality of PLA patients was associated with older age, female sex, diabetes, malignancy, and chronic kidney disease. Conclusion The PLA incidence is rapidly increasing in Korea, especially in people with comorbidities. In addition, the causes and risk factors of PLA infections are changing and thus further research on epidemiology, different diagnosis, and management approaches is required.

Background/Aims: Palbociclib is a cyclin dependent kinase 4 and 6 inhibitor which shows promising effect in hormone receptor positive breast cancer. The purpose of this study is to evaluate the real-world efficacy and toxicity of palbociclib plus endocrine therapy. Methods: This is a retrospective study performed in two tertiary referral hospitals in Korea. Advanced breast cancer patients who were treated with 1st line palbociclib plus endocrine therapy were enrolled.Results: A total of 216 patients were included between August 2016 and May 2019. Median age was 56 (29-89) years old and 75 patients (34.7%) were premenopausal. Median progression-free survival (PFS) was 33.0 months (95% confidence interval [CI] 24.7 to 41.3) and objective response rate was 59.3%. Luminal B patients had shorter PFS (Not reached vs. 33.0 months, p = 0.019) and tendency of lower ORR (58.3 vs. 62.0%, p = 0.19) compared to luminal A patients. Multivariate analysis revealed luminal B (adjusted hazard ratio 1.90, p = 0.038) and germline BRCA mutation (adjusted hazard ratio 5.57, p = 0.002) as an independent poor prognostic factor for PFS. The most common grade 3 or 4 adverse event was neutropenia (86.7%).Conclusions: The efficacy and toxicity of palbociclib in the real-world was comparable to those of clinical trials. In addition, palbociclib with endocrine therapy was an effective treatment option for young patients. Luminal B and germline BRCA mutation was associated with inferior outcome.

Persistent HPV (Human Papillomavirus) infection is the primary cause of cervical cancer. Despite the development of the HPV vaccine to prevent infections, cervical cancer is still a fatal malignant tumor and metastatic disease, and it is often difficult to treat, so a new treatment strategy is needed. The FDA-approved drug Bazedoxifene is a novel inhibitor of protein–protein interactions between IL-6 and GP130. Multiple ligand simultaneous docking and drug repositioning approaches have demonstrated that an IL-6/GP130 inhibitor can act as a selective estrogen modulator. However, the molecular basis for GP130 activation in cervical cancer remains unclear. In this study, we investigated the anticancer properties of Bazedoxifene in HPV-positive cervical cancer cells. In vitro and in vivo experiments showed that Bazedoxifene inhibited cell invasion, migration, colony formation, and tumor growth in cervical cancer cells. We also confirmed that Bazedoxifene inhibits the GP130/STAT3 pathway and suppresses the EMT (Epithelial-mesenchymal transition) sub-signal. Thus, these data not only suggest a molecular mechanism by which the GP130/STAT3 pathway may promote cancer, but also may provide a basis for cervical cancer replacement therapy.

Purpose Recognition of cardiogenic syncope caused by acute myocarditis masquerading as febrile seizures (FS) in children can be difficult in the emergency department (ED) before a cardiac work-up. We aimed to identify clinical and laboratory characteristics of children with seizure-like activity and fever caused by myocarditis that would enable their condition to be distinguished from benign FS. Methods We identified seven children who visited the ED for paroxysmal seizure-like activity with fever and were diagnosed with acute myocarditis between 2012 and 2015, as well as 204 children who were diagnosed with benign FS during the same period. A detailed retrospective review of the medical charts of both groups was conducted. Results Age at onset of seizure-like activity was much higher in the myocarditis group than in the FS group (4.4±1.9 years vs. 2.4±1.1 years, P=0.033). Body temperature at seizure-like activity onset was significantly lower in the myocarditis group than in the FS group (37.9°C±0.2°C vs. 38.7°C±0.6°C, P

The clinical diagnosis of pulmonary involvement in individuals with systemic AL amyloidosis remains challenging. [18F]florbetapir imaging has previously identified AL amyloid deposits in the heart and extra-cardiac organs. The aim of this study is to determine quantitative [18F]florbetapir pulmonary kinetics to identify pulmonary involvement in individuals with systemic AL amyloidosis. We prospectively enrolled 58 subjects with biopsy-proven AL amyloidosis and 9 control subjects (5 without amyloidosis and 4 with ATTR cardiac amyloidosis). Pulmonary [18F]florbetapir uptake was evaluated visually and quantified as distribution volume of specific binding (Vs) derived from compartmental analysis and simpler semiquantitative metrics of maximum standardized uptake values (SUVmax), retention index (RI), and target-to-blood ratio (TBR). On visual analysis, pulmonary tracer uptake was absent in most AL subjects (40/58, 69%); 12% (7/58) of AL subjects demonstrated intense bilateral homogeneous tracer uptake. In this group, compared to the control group, Vs (median Vs 30-fold higher, 9.79 vs. 0.26, p 3-fold higher Vs compared to the control group (median 0.99 vs. 0.26, p < 0.001). Vs was independently related to left ventricular SUVmax, a marker of cardiac AL deposition, but not to ejection fraction, a marker of cardiac dysfunction. Also, intense [18F]florbetapir lung uptake was not related to [11C]acetate lung uptake, suggesting that intense [18F]florbetapir lung uptake represents AL amyloidosis rather than heart failure. [18F]florbetapir PET/CT offers the potential to noninvasively identify pulmonary AL amyloidosis, and its clinical relevance warrants further study.

Objectives The current study sought to evaluate whether nursing narratives can be used to predict postoperative length of hospital stay (LOS) following curative surgery for ovarian cancer. Methods A total of 33 patients, aged over 65 years, underwent curative surgery for newly diagnosed ovarian cancer between 2008 and 2012. Based on the median postoperative LOS, patients were divided into two groups: long-stay (>12 days; n = 13) and short-stay (≤12 days; n = 20). Patterns in nursing narratives were examined and compared through a quantitative analysis. Specifically, the total number (TN) of narratives pertaining to care and the standardized number (SN), which was calculated by dividing the TN by the LOS, were compared. Experts evaluated the relevance of the phrases extracted. LOS was then predicted using machine learning techniques. Results The median postoperative LOS was 18 days (interquartile range [IQR]: 16–24 days) in the long-stay group and 9.5 days (IQR: 8–11.25 days) in the short-stay group. In the long-stay group, surgery duration was longer. Overall, patients in the long-stay group showed a higher volume of nursing narratives compared with patients in the short-stay group (SN: 68 vs. 46, p = 0.021). Thirty-two of the most frequently used nursing narratives were selected from 998 uniquely defined nursing narratives. Multiple t-tests were used to compare the TN and real standardized number (RSN; minimum p Conclusions Statistical tests showed that nursing narratives that utilized the words “urination,” “food supply,” “bowel mobility,” or “pain” were related to hospital stay in elderly females with ovarian cancer. Additionally, machine learning effectively predicted LOS. Summary The current study sought to determine whether elements of nursing narratives could be used to predict postoperative LOS among elderly ovarian cancer patients. Results indicated that nursing narratives that used the words “urination,” “food supply,” “bowel mobility,” and “pain” significantly predicted postoperative LOS in the study population. Additionally, it was found that machine learning could effectively predict LOS based on quantitative characteristics of nursing narratives.

Advances in targeted medications have improved the survival rate of breast cancer patients with molecular marker-positive tumors. To date, immunohistochemistry (IHC) has remained as the standard method for quantifying the markers including HER2, ER, and PR. Nevertheless, IHC-based grading is subjective, because the results depend on trained individuals' eye rather than numerical quantities. Thus, alternative methods that can account for quantitative levels of markers are gaining popularity, including targeted proteomics by mass spectrometry (MS). However, technical limitations have impeded the application of MS-based protein quantification to pathological FFPE slides that contain low amounts of cross-linked proteins. To challenge this, we developed a parallel reaction monitoring-mass spectrometry (PRM-MS) method to measure the expression levels of breast cancer markers. After developing the method using cell lines, we performed PRM-MS using 51 individuals' FFPE samples. As a result, we obtained numerical measures of targets, quantifying 13 peptides of 4 markers in a single analysis per sample. The results correlated well with the IHC readings of experienced pathologists. Moreover, the results distinguished a gray zone in HER2 classification, which IHC alone failed to do. This proof-of-concept study demonstrates the application of targeted proteomics in pathologic slides, further supporting the applicability of MS-based approaches in precision medicine.

Background Immune cells in the tumour microenvironment play an essential role in tumorigenesis. This study aimed to evaluate the immunoregulatory protein expression of breast cancer and reveal their prognostic role. Methods Expression of 10 immune markers (PD-1/PD-L1/PD-L2/IDO/TIM-3/OX40/OX40L/B7-H2/ B7-H3/B7-H4) with known/possible clinical relevance was identified in stromal tumour-infiltrating lymphocytes or tumour tissue of stage I–III breast cancer patients. Results A total of 392 patients, including 271(69.1%) luminal A, 36(9.2%) luminal B, 32(8.2%) HER2-positive and 53(13.5%) triple negative disease, were included. Expression of PD-1 and PD-L1 was higher in HER2-positive and triple negative disease. By contrast, expression of TIM-3, OX40 and OX40L were higher in luminal disease. We devised an immune recurrence score (IRS) using seven markers with prognostic value (B7-H2/B7-H3/B7-H4/OX40/OX40L/PD-L1/PD-L2). Patients were classified as high-risk (7.9%), intermediate-risk (67.6%), or low-risk (24.5%). In the multivariate analysis, IRS low-risk (adjusted HR 0.14, p = 0.001) and intermediate-risk (adjusted HR 0.32, p = 0.002) had significantly lower risk of recurrence compared with high-risk. The prognostic role of IRS was maintained in both luminal A and non-luminal A patients. Conclusions This study identified immunoregulatory protein expression of breast cancer patients using 10 immune markers. In addition, we devised an IRS which may predict recurrence in stage I-III breast cancer patients.

This study sought to test whether relative apical sparing (RELAPS) of left ventricular (LV) longitudinal strain (LS) in cardiac amyloidosis (CA) is explained by regional differences in markers of amyloid burden (Further knowledge of the pathophysiological basis for RELAPS can help understand the adverse outcomes associated with apical LS impairment.This was a prospective study of 32 subjects (age 62 ± 7 years; 50% males) with light chain CA. All subjects underwent two-dimensional echocardiography for LS estimation andThere was a significant base-to-apex gradient in LS (-7.4 ± 3.2% vs. -8.6 ± 4.0% vs. -20.8 ± 6.6%; p 0.0001), maximal LV wall thickness (15.7 ± 1.9 cm vs. 15.4 ± 2.9 cm vs. 10.1 ± 2.4 cm; p 0.0001), and LV mass (74.8 ± 21.2 g vs. 60.8 ± 17.3 g vs. 23.4 ± 6.2 g; p 0.0001). In contrast, florbetapir RI (0.089 ± 0.03 μmol/min/g vs. 0.097 ± 0.03 μmol/min/g vs. 0.085 ± 0.03 μmol/min/g; p = 0.45) and ECV (0.53 ± 0.08 vs. 0.49 ± 0.08 vs. 0.49 ± 0.07; p = 0.15) showed no significant base-to-apex gradient in the tissue concentration or proportion of amyloid infiltration, whereas markers of total amyloid load, such as total florbetapir binding (3.4 ± 1.7 μmol/min vs. 2.8 ± 1.5 μmol/min vs. 0.93 ± 0.49 μmol/min; p 0.0001) and extracellular LV mass (40.0 ± 15.6 g vs. 30.2 ± 10.9 g vs. 11.6 ± 3.9 g; p 0.0001), did show a marked base-to-apex gradient.Segmental differences in the distribution of the total amyloid mass, rather than the proportion of amyloid deposits, appear to explain the marked regional differences in LS in CA. Although these 2 matrices are clearly related concepts, they should not be used interchangeably.

BACKGROUND: Gallium-68 Dotatate binds preferentially to somatostatin receptor (sstr) subtype-2 (sstr-2) on inflammatory cells. We aimed at investigating the potential clinical use of sstr-targeted imaging for the detection of myocardial inflammation. METHODS: 13 patients with suspected cardiac sarcoidosis (CS) based on clinical history and myocardial uptake on recent fluorine-18 fluorodeoxyglucose (FDG) PET, were enrolled to undergo Dotatate PET after FDG PET (median time 37 days [IQR 25 – 55]). Additionally, we investigated ex-vivo the immunohistochemistry expression of sstr-2 in 3 explanted sarcoid hearts. RESULTS: All FDG scans showed cardiac uptake (focal/multifocal = 6, focal on diffuse/heterogeneous = 7), and 46% (n=6) extra-cardiac uptake (mediastinal/hilar). In comparison, Dotatate scans showed definite abnormal cardiac uptake (focal/multifocal) in 4 patients, probably abnormal (heterogenous/patchy) in 3, and negative uptake in 6 cases. Similarly, 6 patients had increased mediastinal/hilar Dotatate uptake. Overall concordance of FDG and Dotatate uptake was 54% in the heart and 100% for thoracic nodal activity. Quantitatively, FDG maximum standardized uptake value was 5.0 times [3.8 – 7.1] higher in the heart, but only 2.25 times [1.7 – 3.0; P=0.019] higher in thoracic nodes relative to Dotatate. Ex-vivo, sstr-2 immunostaining was weakly seen within well-formed granulomas in all 3 examined sarcoid heart specimens with no significant staining of background myocardium or normal myocardium. CONCLUSION: Our preliminary data suggests that, compared to FDG imaging, somatostatin receptor-targeted imaging may be less sensitive for the detection of myocardial inflammation, but comparable for detecting extra-cardiac inflammation.

Although controversial, obesity and underweight may have a negative impact on breast cancer outcome. However, the relationship between body mass index (BMI) and breast cancer outcomes according to tumor subtype and menopausal status remains unclear. This study investigated the association between BMI and breast cancer outcome in stage I–III breast cancer patients. The relationships were further evaluated according to tumor subtype and menopausal status. A total of 5919 patients, 3475 (58.7%) hormone receptor (HR)(+) human epidermal growth factor receptor 2 (HER2)(–), 608 (10.3%) HR(+)HER2(+), 621 (10.5%) HR(–)HER2(+), and 1079 (18.2%) HR(–)HER2(–) were included. Underweight and obesity had a negative impact on relapse-free survival but did not affect overall survival. Importantly, the prognostic role of BMI was different according to tumor subtype and menopausal status. In HR(+)HER2(–) patients, underweight was associated with poor relapse-free survival and overall survival in pre-menopausal women. In contrast, obesity had negative impact on relapse-free survival and overall survival in HR(+)HER2(–) post-menopausal patients. Underweight may have a negative prognostic role in HR(+)HER2(+) patients. However, BMI did not impact the outcome of HR(–)HER2(+) and HR(–)HER2(–) patients. The impact of BMI on breast cancer outcome was dependent on tumor subtype and menopausal status. In HR(+)HER2(–) patients, underweight and obesity had a negative prognostic role in pre-menopausal and post-menopausal women, respectively. These findings in Asian population should be further evaluated and compared in Western population.

Primary cardiac tumors are rare, with a prevalence of 0.001-0.2%. Among such tumors, cardiac hemangioendotheliomas are some of the most uncommon. In Korea, there have been no reports of hemangioendothelioma occurring in the heart of infants. We herein report a case of an infant that was admitted to our medical center and presented with cough and a runny nose. The initial diagnosis was acute bronchiolitis. Cardiomegaly was observed on chest radiography. Echocardiography revealed a tumor measuring 3.5×4.0 cm in the right atrium. The infant was transferred to a tertiary medical center for tumor excision. The excised lesion was 3.8×3×3.2 cm in size, and biopsy confirmed a diagnosis of hemangioendothelioma. In this case report, we describe our experience with a rare case involving cardiac tumor in an infant with an upper respiratory tract infection.

Varicella zoster virus (VZV) is a neurotropic and lymphotropic alpha herpesvirus that causes varicella and herpes zoster (HZ). At a primary infection, VZV causes varicella in young children. Reactivation of latent VZV in sensory ganglia causes painful HZ in elderly people, occasionally leading to a serious complication, postherpetic neuralgia (PHN). A live attenuated VZV vaccine, the first vaccine licensed for the prevention of HZ and PHN is not very effective, while a recombinant subunit vaccine provides higher and longer protection against HZ. In the present study, we developed a new adjuvant system CIA09A, which is composed of cationic liposomes, the Toll-like receptor 4 (TLR4) agonist de-O-acylated lipooligosaccharide, and Quillaja saponin fraction QS-21. We then determined its adjuvant activity for recombinant VZV glycoprotein E (gE) in mice. Co-lyophilization of the liposomal adjuvant formulation with gE did not abolish the immune-stimulating activity. In fact, the CIA09A-adjuvanted gE vaccine was highly effective in eliciting both humoral and cellular immune responses to the recombinant gE protein and VZV in a VZV-primed mouse model. Furthermore, the frequency of gE-specific polyfunctional CD4+ T cells expressing interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-2 was significantly increased in mice immunized with the adjuvanted vaccine. These data indicate that co-lyophilization of protein antigens with CIA09A enables development of a liposome-adjuvanted vaccine in a single vial to induce strong cell-mediated immunity required for vaccine efficacy. Thus, the CIA09A-adjuvanted gE vaccine warrants further development as a new prophylactic vaccine against HZ.

Background:Increasing quantities of stromal TILs (sTILs) are associated with higher pathologic complete response (pCR) rates with conventional chemo in early-stage TNBC. We evaluated the association between sTILs and PD-L1 expression with response to pembro+chemo as NAT for TNBC in the KEYNOTE-173 trial (NCT02622074). Methods: sTILs were quantified using light microscopy of H&E-stained slides from pretreatment and on-treatment (during first 3 weeks of pembro monotherapy) tumor biopsies by a pathologist blind to response data. Pretreatment PD-L1 expression was assessed using the PD-L1 IHC 22C3 pharmDx assay and reported as combined positive score (CPS). Endpoints were pCR rate by ypT0 ypN0 and ypT0/Tis ypN0 and objective response rate (ORR; RECIST v1.1) after the first 4 cycles of NAT (taxane±carboplatin+pembro) by MRI. sTILs and PD-L1 CPS were evaluated as continuous variables. Association between sTILs and PD-L1 CPS with response was assessed using logistic regression and area under the reciever operating curve (AUROC) analyses, with a 1-sided alpha level of 0.10. Correlation between PD-L1 and sTILs was assessed by Spearman's rank correlation coefficient. Multivariate analysis included sTILs (pretreatment and on-treatment) and PD-L1 CPS. Likelihood ratio tests were used to evaluate the added value of factors in predicting pCR rate. Results: Of 60 total pts, 34 had tumors evaluated for pretreatment sTILs, 52 for PD-L1 CPS, and 33 for both sTILs and CPS. On-treatment sTILs were evaluated in 31 pts. Overall pCR rates were 56.7% and 60% by ypT0 ypN0 and ypT0/Tis ypN0, respectively; ORR was 78.3%. In pts evaluated for sTILs and CPS (individually), pCR rates and ORR were comparable with overall pCR rates and ORR. There was a significant correlation between pretreatment sTILs and PD-L1 CPS (ρ=0.65, P Conclusions:Higher quantities of pretreatment sTILs and PD-L1 CPS and on-treatment sTILs were significantly associated with higher pCR rates and ORR in primary TNBC treated with pembro and NAT. Citation Format: Loi S, Schmid P, Cortés J, Park YH, Muñoz-Couselo E, Kim S-B, Sohn J, Im S-A, Holgado E, Foukakis T, Kuemmel S, Dent R, Wang A, Aktan G, Karantza V, Salgado R. Relationship between tumor infiltrating lymphocytes (TILs) and response to pembrolizumab (Pembro)+chemotherapy (Chemo) as neoadjuvant treatment (NAT) for triple-negative breast cancer (TNBC): phase Ib KEYNOTE-173 trial [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-10-09.

Background: Anthracycline-containing regimens and taxane have been standard as the first-line chemotherapy for metastatic breast cancer (MBC). We conducted SELECT BC (randomized phase 3 study of taxane versus S-1 as first-line treatment for MBC) for evaluating the efficacy of S-1 for patients with HER2-negative MBC from 2006 to 2010 in Japan. This study demonstrated non-inferiority of S-1 in overall survival (OS) (median OS was 37.2 months in taxes group and 35.0 months in S-1 group (HR 1.05, 95% CI 0.86–1.27, p=0.015)), and superiority in health-related quality of life (HRQOL) to taxanes. S-1 was also shown as less toxic than taxane (Lancet Oncol 2016; 17: 90-98). S-1 might provide clinical benefit as first-line treatment for patients with HER2-negative MBC. To confirm this suggestion, we have conducted further study (randomized phase 3 study of anthracycline-containing regimens versus S-1 as first-line treatment for HER2-negative MBC: SELECT BC-CONFIRM) from 2011 to present, and a combined analysis of two randomized studies (SELECT-BC CONFIRM and SELECT-BC). Methods: In SELECT BC-CONFIRM, 230 patients receiving first-line treatment for MBC were randomly assigned to either anthracycline group (n=115) or S-1 group (n=115). Anthracycline group patients received anthracycline-containing regimens (AC, EC, FAC, FEC, q3w) at the discretion of the treating physician. S-1 group patients received S-1 40–60 mg twice daily based on the patient's body surface area for 28 days on, 14-day off. The primary endpoint was OS, and secondary endpoints were progression-free survival (PFS), time to treatment failure (TTF), adverse events, HRQOL, and cost-effectiveness. The results were combined with SELECT-BC, to confirm the hypothesis that S-1 treatment is not inferior to the standard therapy (taxanes / anthracycline) for HER2-negative MBC. Results: A combined analysis of the two studies showed that HR was 1.06, 95%CI 0.90-1.253, and p=0.0071 between the standard therapy group and S-1 group. In addition, the Bayesian posterior probability for which HR would be less than 1.333 was about 99.6%. Conclusions: A combined analysis of SELECT BC-CONFIRM and SELECT BC clearly demonstrated that OS with S-1 was not inferior to that with the standard therapy in patients receiving first-line treatment for HER2-negative MBC. S-1 could become a standard therapy for this patient population. Citation Format: Park Y, Akabane H, Watanabe T, Takahashi M, Sagara Y, Nishimura R, Tsurutani J, Takashima T, Fujisawa T, Hozumi Y, Uemura Y, Mukai H. Randomized phase 3 study of anthracycline-containing regimens versus S-1 as first-line treatment for metastatic breast cancer (SELECT BC-CONFIRM)–A combined analysis of two randomized phase 3 studies (SELECT BC-CONFIRM and SELECT BC)– [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-14-07.

Introduction: PIK3CA mutation is one of the most frequent genomic alterations in breast cancer. We evaluated PIK3CA mutational status including spatial and temporal heterogeneity, clinical characteristics and prognostic impact focused on ER+/HER2- subtype. Methods: We performed targeted ultra-deep sequencing (CancerSCAN™) of breast cancer tissue in a prospective cohort. Burden of disease was assessed by metabolic tumor volume(MTV) in 18F-FDG-PET scan. Association with clinical characteristics or survival were tested in ER+/HER2- subtype, using Chi square test or Kaplan-Meier method. Results: PIK3CA analyses were performed in 1274 breast cancer specimens from 1091 patients. 957 patients had early breast cancer. PIK3CA alterations were found in 397 patients(36.3%), and frequency of PIK3CA mutation was significantly lower in triple negative breast cancer(19.0%), compared with 40.4% in ER+/HER2-, 40.9% in ER+/HER2+, and 45.2% in ER-/HER2+ subtype(p Conclusion: We observed variations in PIK3CA mutational status in more than 10% of patients with >1 repeated biopsy. In stage IV ER+/HER2- disease, PIK3CA hotspot mutation seemed to be associated with longer PFS and OS, however metabolic tumor burden was not associated with PIK3CA alterations. Citation Format: Ahn HK, Park S, Hyun SH, Park K, Lee E, Kim J-Y, Nam SJ, Kim SW, Lee JE, Lee SK, Yu JH, Ahn JS, Im Y-H, Park YH. PIK3CA mutations in breast cancer: Mutational landscape and clinical implications in ER+/HER2- subtype [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-08-12.

Background The continuum of anti-HER2 agents is regarded as a standard strategy for HER2 positive metastatic breast cancer patients who had progressed disease with anti-HER2 agent- containing treatments. However, there has been lack of data on which agents should be continued and how long continuous anti-HER2 therapies would be effective. This study was aimed to evaluate the efficacy of lapatinib plus vinorelbine in HER2 positive metastatic breast cancer patients who had progressed on both trastuzumab and lapatinib treatments. Methods A total of 149 patients were randomly assigned to lapatinib with vinorelbine (LV) (n=75; laptinib, 1000mg daily ; vinorelbine 20mg/m2 D1,D8 q3w) or vinorelbine alone (V) (n=74; 30mg/m2 D1,D8 q3w). The stratification factors were followings; 1) visceral metastasis, 2) previous response to lapatinib treatment, CR+PR vs. SD ≥ 12 weeks. The primary endpoint was progression free survival (PFS) rate at 18 weeks. The secondary endpoints were objective response rate (ORR), PFS, and overall survival (OS). Results : Both arms were well balanced in various clinical factors. The median number of previous anti-HER2 therapies were 2 (range 2-5). There was no significant difference in PFS rate at 18 weeks between LV and V arms (44.0% vs 36.5%, p=0.44). ORR was 19.7% in LV arm and 16.9% in V arm (p=0.881). PFS and OS did not differ between two arms (LV vs V; median PFS, 16weeks vs 12 weeks, HR= 0.86, 95% CI 0.61-1.22, p=0.41; median OS, 15.0 months vs 18.9 months, HR= 1.07, 95% CI 0.72-1.58, p=0.72). In subgroup analysis, there was no difference in PFS and OS between two arms according to previous response to lapatinib (median PFS, CR+PR vs. SD ≥ 12 weeks, 12.1weeks vs.17.4 weeks; HR= 1.242, 95% CI 0.881-1.751, p=0.215; median OS, 14.9 months vs. 19.4 months; HR= 1.179, 95% CI 0.797-1.744, p=0.41). Most common adverse events in both arms were neutropenia which was more often observed in V arm (55% vs 73%, p=0.03). Overall, the profiles of adverse events were similar in both arms and all were manageable. Conclusion Lapatinib plus vinorelbine treatment was tolerable, however, it did not demonstrate the clinical benefits compared to vinorelbine alone in HER2 positive metastatic breast cancer patients after progression on both trastuzumab and lapatinib. Citation Format: Sim SH, Park IH, Jung KH, Kim S-B, Ahn J-H, Lee K-H, Im S-A, Im Y-H, Park YH, Sohn JH, Kim YJ, Lee S, Kim H-J, Chae YS, Park K-H, Nam B-H, Lee KS, Ro J. Randomized phase II study of lapatinib plus vinorelbine versus vinorelbine in patients with HER2 positive metastatic breast cancer progressed after lapatinib and trastuzumab treatment [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-17-23.

Introduction: Genetic alteration of Estrogen Receptor 1(ESR1) gene have been associated with acquired endocrine resistance and occurred in about 20% of endocrine resistant estrogen receptor(ER)-positive metastatic breast cancer(MBC). Mutations in ligand binding domain of ESR1 lead to constitutive activity of the ER without ligand estrogen and stimulated down stream cell growth signal. Therefore, ESR1 ligand binding domain alteration is known resistant mechanism of aromatase inhibitor. Among these ESR1 mutations, Y537S, one of the ligand binding domain mutations, caused ER antagonist, fulvestrant resistance. Therefore, assessment of ESR1 mutation in ER-positive MBC had significant benefit to further precision medicine for MBCs. In this study, we explored to identify the frequency and type of ESR1 genetic alterations of ER-positive MBC. Methods: We performed targeted ultra-deep sequencing (CancerSCAN™) using BC tissue specimens. This sequencing was covered entire coding area of ESR1 gene and also detected copy number alteration and translocation of ESR1. Results: Targeted ultra-deep sequencing of ESR1 was performed using 990 BC tissues. Of 990 tissue samples, 341(34.5%) were MBCs. Of MBCs, 112(11.3%) were ER-positive and human epidermal growth factor receptor 2(HER2)-negative BCs. In ER-positive HER2-negative MBCs (N=112), 21 ESR1 genetic alterations were identified in 19 BCs (17.0%). Nineteen were single nucleotide variats (SNVs) and three were copy number (CN) amplification. Most commonly detected single nucleotide variant (SNV) was D538G (6 of 19, 31.6%) followed by Y537N, Y537S, V382I (4, 2 and 2 cases, respectively). Three mutations occurred in non-ligand binding domain (G415V, V392I and P79A). Two BC samples harbored two ESR1 mutations, respectively (Y537S and D538G, L536P and Y537N). In terms of treatment, 11 of 12 patients with ER-positive MBC harboring ESR1 mutation received palliative endocrine therapies. Eight patients received aromatase inhibitor and two patients received tamoxifen. One patient received letrozole plus palbociclib. In 2 MBCs with Y537S mutation, progression free survival (PFS) of endocrine therapy was 1.4 and 5.3 months. MBCs with D538G had 12.3months of PFS (range, 5.3-23.7(months)) and BCs harboring another ligand binding domain mutations (Y537N, L536H and L536P) had 15.7months of PFS of endocrine therapy (range, 8.4-17.3(months)). BC with mutation observed in non-lignand binding domain had short PFS (1.8 (V392I) and 2.7 (P79A) months, respectively). In terms of ESR1 CN amplification, patients could not receive endocrine therapy because their BCs rapidly progressed and extensive distant metastases were occurred within 3 months after curative surgery. Conclusion: In this exploratory study, ESR1 genetic alterations were detected in about 20% of ER-positive MBC. The type of genetic alterations varied including SNVs, CNAs. Each locus of ESR1 mutation predicted endocrine resistance. In addition, we might suggest that ESR1 CN amplification is prognostic marker of ER-positive BCs. Citation Format: Kim J-Y, Park KH, Park W-Y, Nam SJ, Kim SW, Lee JE, Lee SK, Yu JH, Ahn JS, Im Y-H, Park YH. Prognostication of genetic alterations of ESR 1 in estrogen receptor positive metastatic breast cancers using targeted ultra-deep sequencing data analysis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-09-11.

Introduction : A phase II, multicenter, randomized clinical trial of the comparison between eribulin plus gemcitabine (EG) and paclitaxel plus gemcitabine (PG) as first-line chemotherapy for patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) found EG was less neurotoxic, but had similar efficacy of PG. In this study, we performed exploratory biomarker analysis of the impact of genetic alterations on the efficacy according to EG and PG chemotherapy. Methods : This biomarker study was conducted using tumor samples from 40patients. When tissue collection was possible after disease progression, we performed paired sample analysis. Tumor DNA and RNA were extracted from formalin-fixed, paraffin-embedded tissues. To perform targeted deep sequencing, we used CancerScanTM, a 375 cancer gene panel. And we performed an nCounter expression assay for gene expression analysis using 730 PanCancer panel and 730 Immune panel. Results: In total, we obtained 44 tissue samples from 40 patients. Twenty two patients were assigned in EG arm and 18 patients were in PG arm. Thirty-eight were at baseline and six after disease progression. Gene expression assay were performed in 44 tissue samples but only 31 samples were possible to be targeted deep sequencing. We performed differently expressed gene(DEG) analysis for detecting the association between level of gene expression and disease progression. In this analysis, high expression of CCNE1, TGFB4 and BAMBI and low expression of DDB2, CD14 and SHC3 were associated with disease progression among 730 PanCancer panel genes (p In targeted deep sequencing, FAT3 (42.3%) was most frequently mutated gene followed by PKHD1, PIK3CA and TP53. Among mutated genes, EWSR1 mutation and upstream mutation of ETV1 were associated with disease progression, respectively (p Conclusion: In gene expression analysis, high expression of TGF-B signaling pathway related genes was associated with disease progression while high expression of immune related genes were related to prolonged disease free survival. In mutation analysis, EWSR1 and ETV1 mutations indicated short disease free interval and HRD mutation signature was also related to poor prognosis. Citation Format: Kim J-Y, Lee EJ, Park KH, Im S-A, Kim S-B, Sohn SH, Lee KS, Chae YS, Lee KH, Kim JH, Im Y-H, Kim T-Y, Lee K-H, Ahn J-H, Kim GM, Park IH, Lee SJ, Han HS, Kim SH, Jung KH, Park YH. Exploratory biomarker analysis from a phase II, multicenter, randomized trial of eribulin plus gemcitabine(EG) versus paclitaxel plus gemcitabine(PG) as first-line chemotherapy for human epidermal growth factor receptor 2 (HER2)- negative metastatic breast cancer(MBC): Korean cancer study group trial (KCSG BR13-11) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-11-07.

Breast cancer (BC) is so-called “systemic disease”, because disseminated cancer cells in bone marrow and blood are detected even in early BC patients. Despite adjuvant therapy and postoperative radiation therapy, patients with triple negative BC and Luminal B-like BC often relapse early and systemic therapy is the only way to control disease progression. On the other hand, some BC patients relapse several years later. In such patients, oligometastases are occasionally diagnosed, because metastatic cancer cells are slowly growing and indolent. Oligometastatic BC is defined as low volume metastatic disease with limited number and size of metastatic lesions (up to five and not necessarily in the same organ). This definition is proposed in the Advanced Breast Cancer guidelines that are developed as a joint effort from European School of Oncology and European Society of Medical Oncology. Several retrospective studies demonstrated survival benefit of locoregional therapy in addition to systemic therapy. Locoregional therapy consisted of surgical resection, radiation therapy, ablation therapy, etc. However, it remains unclear about survival benefit of combined therapy in oligometastatic BC. To improve the standard of cancer treatment through the cooperate studies on more effective therapeutic strategies based on drugs, surgery and/or radiotherapy, Federation of Asian Clinical Oncology (FACO) was established in 2012 by Chinese Society of Clinical Oncology (CSCO), Korean Society of Medical Oncology (KSMO) and Japan Society of Clinical Oncology (JSCO). Thus, FACO conducted a retrospective cohort study on oligometastatic BC. The primary endpoint is to compare the estimated 5-year overall survival (OS) of oligometastatic BC patients treated with combined therapy and systemic therapy alone. To hypothesize that combined therapy has more advantage of OS in oligometastatic BC, the 5-year OS rates are expected to be 50% and 40%, respectively. The estimated sample size is calculated to be the number of 698 cases (349 cases in each group) needed to prove the superiority of survival with a two-sided type I error rate of 5% and a statistical power of 80%. Case registry opened in February 2018 and will close in January 2019. We planned to register 700 cases, i.e., 234 cases each from investigators of CSCO, KSMO and JSCO. Update information will be discussed. Citation Format: Imoto S, Futamura M, Toi M, Fujiwara Y, Ueno T, Im Y-H, Im S-A, Ahn SG, Lee JE, Park YH, Wang K, Kitagawa Y, Nishiyama M. International retrospective cohort study of locoregional and systemic therapy in oligometastatic breast cancer (OLIGO-BC1) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT2-05-02.

Glaucoma is a leading cause of irreversible blindness, a progressive optic neuropathy with retinal ganglion cell (RGC) death beginning in the optic nerve head (ONH). A primary risk factor for developing glaucoma is elevated intraocular pressure (IOP). Reducing IOP is the only treatment proven to be effective at delaying disease progression. Nevertheless, even when patients have their IOP reduced, the majority of them continue to lose vision. There are, in both humans and dogs, significant interindividual variabilities in susceptibilities to IOP-induced optic nerve damage. Vision loss progresses much more slowly in Beagles with open-angle glaucoma (OAG) caused by ADAMTS10 mutation. This can be attributed to the mutation-related altered ocular biomechanical properties. The principal site of optic nerve (ON) damage in glaucoma is the ONH. It is suggested that the biomechanical properties of the ONH and the surrounding peripapillary sclera (PPS) contribute to glaucoma development and progression. As far as the beneficial biomechanical properties of the ONH and PPS for a decreased susceptibility and slow progression of glaucoma, data are inconsistent and conflicting. Recent biomechanical studies on beagles with ADAMTS10 mutation demonstrated that the mutant dogs have mechanically weak posterior sclera. This weakness was associated with a reduced collagen density and a lower proportion of insoluble collagen. These changes, observed before glaucoma development, were considered intrinsic characteristics caused by the mutation rather than a secondary effect of IOP elevation. Further studies of ADAMTS10-OAG may elucidate the effects of altered biomechanical properties of ONH and PPS in determining the glaucoma progression.

[Image: see text] The aim of this work was to evaluate a tumor-targeting porphyrin-based gadolinium complex (Gd-TDAP) for use as an MR/optical imaging agent and potential therapeutic agent. Gd-TDAP had higher longitudinal relaxivity (11.8 mM(–1) s(–1)) than a commercial MRI contrast agent (Omniscan; 3.7 mM(–1) s(–1)) in HSA solution (0.67 mM) at 3 T. The tumor-targeting characteristics were confirmed by T(1)-weighted MR imaging and optical imaging using an orthotopic brain tumor mouse model, which showed 1.3-fold higher uptake in tumor compared to normal brain tissues. The cell fraction data using U87MG glioblastoma cells indicated the potential for gadolinium neutron capture therapy (Gd-NCT), which requires gadolinium to be inside the cell nucleus. In addition, porphyrin derivatives can be used for photodynamic therapy (PDT), and the results demonstrated that Gd-TDAP has great potential not only as a bimodal imaging agent but also for treatment.

Glaucoma is a complex group of optic neuropathies that affects both humans and animals. Intraocular pressure (IOP) elevation is a major risk factor that results in the loss of retinal ganglion cells (RGCs) and their axons. Currently, lowering IOP by medical and surgical methods is the only approved treatment for primary glaucoma, but there is no cure, and vision loss often progresses despite therapy. Recent technologic advances provide us with a better understanding of disease mechanisms and risk factors; this will permit earlier diagnosis of glaucoma and initiation of therapy sooner and more effectively. Gene and cell therapies are well suited to target these mechanisms specifically with the potential to achieve a lasting therapeutic effect. Much progress has been made in laboratory settings to develop these novel therapies for the eye. Gene and cell therapies have already been translated into clinical application for some inherited retinal dystrophies and age-related macular degeneration (AMD). Except for the intravitreal application of ciliary neurotrophic factor (CNTF) by encapsulated cell technology for RGC neuroprotection, there has been no other clinical translation of gene and cell therapies for glaucoma so far. Possible application of gene and cell therapies consists of long-term IOP control via increased aqueous humor drainage, including inhibition of fibrosis following filtration surgery, RGC neuroprotection and neuroregeneration, modification of ocular biomechanics for improved IOP tolerance, and inhibition of inflammation and neovascularization to prevent the development of some forms of secondary glaucoma.

Background Patients with liver cirrhosis have an increased risk of in-hospital mortality or postoperative complication after surgery. However, large-scale studies on the prognosis of these patients after surgery are lacking. The aim of the study was to investigate the adverse outcomes of patients with liver cirrhosis after surgery over five years. Methods and findings We used the Health Insurance Review and Assessment Service-National Inpatient Samples (HIRA-NIS) between 2012 and 2016. In-hospital mortality and hospital stay were analyzed using the data. Mortality rates according to the surgical department were also analyzed. Of the 1,662,887 patients who underwent surgery, 16,174 (1.0%) patients had cirrhosis. The in-hospital mortality (8.0% vs. 1.0%) and postoperative complications such as respiratory (6.0% vs. 5.3%) or infections (2.8% vs. 2.4%) was significantly higher in patients with cirrhosis than in those without cirrhosis. In addition, the total hospitalization period and use of the intensive care unit were significantly higher in patients with liver cirrhosis. In propensity score matching analysis, liver cirrhosis increased the risk of adverse outcome significantly [adjusted OR (aOR) 1.67, 95% CI 1.56–1.79, P Conclusion The adverse outcomes of patients with cirrhosis is significantly high after surgery, despite advances in cirrhosis treatment.

Background Despite the advances in neonatology, the incidence of bronchopulmonary dysplasia (BPD) is increasing. It is important to prevent the development of BPD in the first place. The online BPD outcome estimator from National Institute of Children Health and Human Development and Neonatal Research Network is available. However, it is not applicable for Asians. Moreover, limits are set for birth weight and gestational weeks excluding those who may still have BPD. The aim of this study was to develop a prediction model for BPD using first hour perinatal and neonatal factors in Korean very low birth weight infants (VLBWIs). Methods Data were collected for 8,022 VLBWIs with gestational age (GA) ≥ 22 weeks who were born between January 1, 2013 and December 31, 2016, and admitted to the neonatal intensive care units of the KNN. Multiple logistic regression models reanalyzed by stepwise selection with significant clinical indicators for BPD. PROC package was used to calculate the area under curve (AUC) and corresponding 95% confidence intervals. Moreover, it was used to search the best cut-off value. External validation was performed with the 2017 Korean neonatal network (KNN) data. Results After all missing data were excluded, 4,600 VLBWIs were included in the training dataset of the prediction model. Predictability of presence of BPD was 90.8% and prediction P value cut off was 0.550. Five-minute Apgar score, birth weight, GA, sex, surfactant use were significant indicators. Predictability of severe BPD was 81.5% and prediction P value cut off was 0.160. Five-minute Apgar score, birth weight, maternal PIH, chronic maternal hypertension, GA, sex, respiratory distress syndrome, need of resuscitation at birth were significant indicators. After external validation, sensitivity and specificity did not change significantly. Conclusion From this study, high predictability was obtained using clinical parameters obtained within one hour of life. P value for prediction of each grade of BPD and equation for calculation was presented. It can be helpful for the early prediction of BPD in Korean VLBWI. This study will contribute to the prediction of BPD in Asians especially Korean VLBWIs, not currently included in the NICHD BPD online BPD predictor. In addition, the predictive power may be continuously increased with the cumulative data of KNN., Graphical Abstract

Background Preterm infants are prone to sepsis owing to their immature innate immunity and prolonged hospitalization. We aimed to evaluate the association between late-onset sepsis (LOS) during hospitalization and neurodevelopmental delay at 18–24 months of corrected age in very low birth weight infants (VLBWIs), and to ascertain this association when adjusted for perinatal risk factors. Methods This is a population-based study of VLBWIs born at 23–32 weeks of gestation between January 2014 and December 2017 who were enrolled in the Korean Neonatal Network. Bayley scales of infant development were evaluated at 18–24 months of corrected age in 2,098 infants. To test for LOS as a risk factor for neurodevelopmental delay, multiple logistic regression was used and adjusted for parental education status and clinical variables. Results Blood culture positive LOS was identified in 419 (20.0%) infants. Cognitive and motor delays were found in 392 (18.7%) and 347 (16.5%) infants, respectively. When multivariate analysis was performed, LOS had a significant association with cognitive delay (odds ratio, 1.48; 95% confidence interval, 1.02–2.16), but no association with motor delay in VLBWIs. Both delays were significantly more frequent in cases of intraventricular hemorrhage (IVH) ≥ grade 3, periventricular leukomalacia (PVL), and intrauterine growth restriction (IUGR) and duration of mechanical ventilation. Male sex and necrotizing enterocolitis ≥ grade 2 had an effect on motor delay, whereas paternal college graduation affected cognitive delay. Conclusion In VLBWIs with LOS, there is a heightened risk of cognitive delays at 18–24 months of corrected age. Brain injury, such as severe IVH and PVL, duration of mechanical ventilation, and IUGR, were also associated with cognitive and motor delays., Graphical Abstract

Background COVID-19 has officially been declared as a pandemic, and the spread of the virus is placing sustained demands on public health systems. There are speculations that the COVID-19 mortality differences between regions are due to the disparities in the availability of medical resources. Therefore, the selection of patients for diagnosis and treatment is essential in this situation. Military personnel are especially at risk for infectious diseases; thus, patient selection with an evidence-based prognostic model is critical for them. Objective This study aims to assess the usability of a novel platform used in the military hospitals in Korea to gather data and deploy patient selection solutions for COVID-19. Methods The platform’s structure was developed to provide users with prediction results and to use the data to enhance the prediction models. Two applications were developed: a patient’s application and a physician’s application. The primary outcome was requiring an oxygen supplement. The outcome prediction model was developed with patients from four centers. A Cox proportional hazards model was developed. The outcome of the model for the patient’s application was the length of time from the date of hospitalization to the date of the first oxygen supplement use. The demographic characteristics, past history, patient symptoms, social history, and body temperature were considered as risk factors. A usability study with the Post-Study System Usability Questionnaire (PSSUQ) was conducted on the physician’s application on 50 physicians. Results The patient’s application and physician’s application were deployed on the web for wider availability. A total of 246 patients from four centers were used to develop the outcome prediction model. A small percentage (n=18, 7.32%) of the patients needed professional care. The variables included in the developed prediction model were age; body temperature; predisease physical status; history of cardiovascular disease; hypertension; visit to a region with an outbreak; and symptoms of chills, feverishness, dyspnea, and lethargy. The overall C statistic was 0.963 (95% CI 0.936-0.99), and the time-dependent area under the receiver operating characteristic curve ranged from 0.976 at day 3 to 0.979 at day 9. The usability of the physician’s application was good, with an overall average of the responses to the PSSUQ being 2.2 (SD 1.1). Conclusions The platform introduced in this study enables evidence-based patient selection in an effortless and timely manner, which is critical in the military. With a well-designed user experience and an accurate prediction model, this platform may help save lives and contain the spread of the novel virus, COVID-19.

Background Antibodies to the aquaporin-4 (AQP4) water channel in neuromyelitis optica spectrum disorder (NMOSD) are reported to trigger the complement cascade, which is implicated in astrocyte damage and subsequent neuronal injury. The PREVENT study demonstrated that the terminal complement inhibitor eculizumab reduces adjudicated relapse risk in patients with anti-AQP4 immunoglobulin G-positive (AQP4+) NMOSD. The objective of this analysis was to evaluate the efficacy of eculizumab in reducing relapse risk and its safety in AQP4+ NMOSD across clinically relevant subgroups in PREVENT. Methods In the randomized, double-blind, time-to-event, phase 3 PREVENT trial, 143 adults received eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo (2:1), with stable-dose concomitant immunosuppressive therapy (IST) permitted (except rituximab and mitoxantrone). Post hoc analyses of relapses and adverse events were performed for prespecified and post hoc subgroups based on concomitant IST and prior rituximab use, demographic and disease characteristics, and autoimmune comorbidity. Results The significant reduction in relapse risk observed for eculizumab versus placebo in the overall PREVENT population was consistently maintained across subgroups based on concomitant IST and previous rituximab use, age, sex, region, race, time since clinical onset of NMOSD, historical annualized relapse rate, baseline Expanded Disability Status Scale score, and history of another autoimmune disorder. The serious infection rate was lower with eculizumab than placebo regardless of rituximab use in the previous year, concomitant IST use, or history of another autoimmune disorder. Conclusion Across a wide range of clinically relevant AQP4+ NMOSD patient subgroups in PREVENT, eculizumab therapy was consistently effective versus placebo in reducing relapse risk, with no apparent increase in serious infection rate. Trial registration NCT01892345 (ClinicalTrials.gov).

COVID‐19 remains a global pandemic with more than ten million cases and half a million deaths worldwide. The disease manifestations in patients with chronic kidney disease and especially those on haemodialysis are still being understood, with only a few overseas case series, and small observational trials thus far. It appears the disease is more severe in this patient cohort. 1 (1) 1 1 Part of the pathophysiology of severe COVID‐19 is related to accompanying cytokine release syndrome. Tocilizumab, an interleukin‐6 inhibitor, has been trialled for treatment of cytokine release syndrome in COVID‐19, but not yet approved. We present a case of an Australian patient on long‐term haemodialysis with severe COVID‐19 who was successfully treated with Tocilizumab. The peak of her illness was on day 7, with a C‐reactive protein of 624 mg/L (reference

Cancer survivors suffer from emotional distress, which varies depending on several factors. However, existing emotion management programs are insufficient and do not take into consideration all of the factors. Social media provides a platform for understanding the emotions of the public. The aim of this study was to explore the relationship between the public&rsquo, s emotions about cancer and factors affecting emotions using social media data. We used 321,339 posts on cancer and emotions relating to cancer extracted from 22 social media channels between 1 January 2014, and 30 June 2017. The factors affecting emotions were analyzed using association rule mining and social network analysis. Hope/gratitude was the most frequently mentioned emotion group on social media followed by fear/anxiety/overwhelmed, sadness/depression/loneliness/guilt, and anger/denial. Acute survival stage, treatment method, and breast cancer were associated with hope/gratitude. Early stage, gastrointestinal problems, fatigue/pain/fever, and pancreatic cancer were associated with fear/anxiety/overwhelmed. Surgery, hair loss/skin problems, and fatigue/pain/fever were associated with sadness/depression/loneliness/guilt. Acute survival stage and hair loss/skin problems were associated with anger/denial. We found that emotions concerning cancer differed depending on the cancer type, cancer stage, survival stage, treatment, and symptoms. These findings could guide the development of tailored emotional management programs for cancer survivors that meet the public&rsquo, s needs more effectively.

Background: Despite the recent research implicating E2F8 (E2F Transcription Factor 8) in cancer, the role of E2F8 in the progression of ovarian cancer has remained unclear. Hence, we explored the bio-functional effects of E2F8 knockdown on ovarian cancer cell lines in vitro and in vivo. Methods: The expression of E2F8 was compared between ovarian cancer and noncancer tissues, and its association with the progression-free survival of ovarian cancer patients was analyzed. To demonstrate the function of E2F8 in cell proliferation, migration, and invasion, we employed RNA interference to suppress E2F8 expression in ovarian cancer cell lines. Finally, the effect of E2F8 knockdown was investigated in a xenograft mouse model of ovarian cancer. Results: Ovarian cancer tissue exhibited significantly higher E2F8 expression compared to that of normal ovarian tissue. Clinical data showed that E2F8 was a significant predictor of progression-free survival. Moreover, the prognosis of the ovarian cancer patients with high E2F8 expression was poorer than that of the patients with low E2F8 expression. In vitro experiments using E2F8-knockdown ovarian cancer cell lines demonstrated that E2F8 knockdown inhibited cell proliferation, migration, and tumor invasion. Additionally, E2F8 was a potent inducer and modulator of the expression of epithelial&ndash, mesenchymal transition and Notch signaling pathway-related markers. We confirmed the function of E2F8 in vivo, signifying that E2F8 knockdown was significantly correlated with reduced tumor size and weight. Conclusions: Our findings indicate that E2F8 is highly correlated with ovarian cancer progression. Hence, E2F8 can be utilized as a prognostic marker and therapeutic target against ovarian malignancy.

Purpose:Multigene assays provide useful prognostic information regarding hormone receptor (HR)-positive breast cancer. Next-generation sequencing (NGS)-based platforms have numerous advantages including reproducibility and adaptability in local laboratories. This study aimed to develop and validate an NGS-based multigene assay to predict the distant recurrence risk.Experimental Design:In total, 179 genes including 30 reference genes highly correlated with the 21-gene recurrence score (RS) algorithm were selected from public databases. Targeted RNA-sequencing was performed using 250 and 93 archived breast cancer samples with a known RS in the training and verification sets, respectively, to develop the algorithm and NGS–Prognostic Score (NGS-PS). The assay was validated in 413 independent samples with long-term follow-up data on distant metastasis.Results:In the verification set, the NGS-PS and 21-gene RS displayed 91.4% concurrence (85/93 samples). In the validation cohort of 413 samples, area under the receiver operating characteristic curve plotted using NGS-PS values classified for distant recurrence was 0.76. The best NGS-PS cut-off value predicting distant metastasis was 20. Furthermore, 269 and 144 patients were classified as low- and high-risk patients in accordance with the cut-off. Five- and 10-year estimates of distant metastasis–free survival (DMFS) for low- versus high-risk groups were 97.0% versus 77.8% and 93.2% versus 64.4%, respectively. The age-related HR for distant recurrence without chemotherapy was 9.73 (95% CI, 3.59–26.40) and 3.19 (95% CI, 1.40–7.29) for patients aged ≤50 and >50 years, respectively.Conclusions:The newly developed and validated NGS-based multigene assay can predict the distant recurrence risk in ER-positive, HER2-negative breast cancer.