Purpose: This study aimed to assess the real-world clinical outcomes of consolidative durvalumab in patients with unresectable locally advanced non–small cell lung cancer (LA-NSCLC) and to explore the role of radiotherapy in the era of immunotherapy. Materials and Methods: This retrospective study assessed 171 patients with unresectable LA-NSCLC who underwent concurrent chemoradiotherapy (CCRT) with or without consolidative durvalumab at Asan Medical Center between May 2018 and May 2021. Primary outcomes included freedom from locoregional failure (FFLRF), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS). Results: Durvalumab following CCRT demonstrated a prolonged median PFS of 20.9 months (p=0.048) and a 3-year FFLRF rate of 57.3% (p=0.008), compared to 13.7 months and 38.8%, respectively, with CCRT alone. Furthermore, the incidence of in-field recurrence was significantly greater in the CCRT-alone group compared to the durvalumab group (26.8% vs. 12.4%, p=0.027). While median OS was not reached with durvalumab, it was 35.4 months in patients receiving CCRT alone (p=0.010). Patients positive for programmed cell death ligand 1 (PD-L1) expression showed notably better outcomes, including FFLRF, DMFS, PFS, and OS. Adherence to PACIFIC trial eligibility criteria identified 100 patients (58.5%) as ineligible. The use of durvalumab demonstrated better survival regardless of eligibility criteria. Conclusion The use of durvalumab consolidation following CCRT significantly enhanced locoregional control and OS in patients with unresectable LA-NSCLC, especially in those with PD-L1–positive tumors, thereby validating the role of durvalumab in standard care.

BACKGROUND: Psoriasis is an immune-mediated, chronic inflammatory disease affecting multiple aspects of patients' lives. Its epidemiology varies regionally; however, nationwide epidemiologic data on psoriasis depicting profile of Korean patients has not been available to date. OBJECTIVE: To understand nationwide epidemiologic characteristics and clinical features of adult patients with psoriasis visited university hospitals in Korea. METHODS: This multicenter, non-interventional, cross-sectional study recruited 1,278 adult patients with psoriasis across 25 centers in Korea in 2013. Various clinical data including PASI, BSA, DLQI, SF-36 and PASE were collected. RESULTS: A total of 1,260 patients completed the study (male:female=1.47:1). The mean age was 47.0 years with a distribution mostly in the 50s (24.9%). Early onset (<40 years) of psoriasis accounted for 53.9% of patients. The mean disease duration was 109.2 months; mean body mass index was 23.9 kg/m²; and 12.7% of patients had a family history of psoriasis. Plaque and guttate types of psoriasis accounted for 85.8% and 8.4%, respectively. Patients with PASI ≥10 accounted for 24.9%; patients with body surface area ≥10 were 45.9%. Patients with DLQI ≥6 accounted for 78.8%. Between PASI <10 and PASI ≥10 groups, significant difference was noted in age at diagnosis, disease duration, blood pressure, waist circumference of female, and treatment experiences with phototherapy, systemic agents, and biologics. CONCLUSION: This was the first nationwide epidemiologic study of patients with psoriasis in Korea and provides an overview of the epidemiologic characteristics and clinical profiles of this patient population.
Adult ; Biological Products ; Blood Pressure ; Body Mass Index ; Body Surface Area ; Cross-Sectional Studies* ; Diagnosis ; Epidemiologic Studies ; Epidemiology ; Female ; Hospitals, University ; Humans ; Korea* ; Phototherapy ; Psoriasis* ; Waist Circumference

PURPOSE: To determine failure patterns and survival outcomes of T4N0-1 non-small cell lung cancer (NSCLC) treated with definitive radiotherapy. MATERIALS AND METHODS: Ninety-five patients with T4N0-1 NSCLC who received definitive radiotherapy with or without chemotherapy from May 2003 to October 2014 were retrospectively reviewed. The standard radiotherapy scheme was 66 Gy in 30 fractions. The main concurrent chemotherapy regimen was 50 mg/m2 weekly paclitaxel combined with 20 mg/m2 cisplatin or AUC 2 carboplatin. The primary outcome was overall survival (OS). Secondary outcomes were failure patterns and toxicities. RESULTS: The median age was 64 years (range, 34 to 90 years). Eighty-eight percent of patients (n = 84) had an Eastern Cooperative Oncology Group performance status of 0-1, and 42% (n = 40) experienced pretreatment weight loss. Sixty percent of patients (n = 57) had no metastatic regional lymph nodes. The median radiation dose was EQD2 67.1 Gy (range, 56.9 to 83.3 Gy). Seventy-one patients (75%) were treated with concurrent chemotherapy; of these, 13 were also administered neoadjuvant chemotherapy. At a median follow-up of 21 months (range, 1 to 102 months), 3-year OS was 44%. The 3-year cumulative incidences of local recurrence and distant recurrence were 48.8% and 36.3%, respectively. Pretreatment weight loss and combined chemotherapy were significant factors for OS. Acute esophagitis over grade 3 occurred in three patients and grade 3 chronic esophagitis occurred in one patient. There was no grade 3-4 radiation pneumonitis. CONCLUSION: Definitive radiotherapy for T4N0-1 NSCLC results in favorable survival with acceptable toxicity rates. Local recurrence is the major recurrence pattern. Intensity modulated radiotherapy and radio-sensitizing agents would be needed to improve local tumor control.
Area Under Curve ; Carboplatin ; Carcinoma, Non-Small-Cell Lung* ; Cisplatin ; Drug Therapy* ; Esophagitis ; Follow-Up Studies ; Humans ; Incidence ; Lymph Nodes ; Paclitaxel ; Radiation Pneumonitis ; Radiotherapy* ; Recurrence ; Retrospective Studies ; Weight Loss

BACKGROUND: It is important to educate families of pediatric patients with atopic dermatitis (AD) so that they have a correct understanding of AD. OBJECTIVE: The purpose of this study is to introduce, evaluate, and improve our family-engaged educational program. METHODS: Children suffering from AD and their families have participated in a half-day educational program called "AD school" with catchy slogans such as "Enjoy with AD Families!" every year since 2005. Educational lectures were conducted for parents. For children with AD, various entertaining programs were provided. A feedback survey about AD school was administered for the purpose of evaluation. RESULTS: A total of 827 people (376 patients and 451 family members) participated in this program over 7 years. On-site surveys showed a positive response (i.e., "excellent" or "good") for the prick test (95.1%), emollient education (78.4%), educational lecture (97.0%), drawing contest and games (90.2%), and recreation (magic show; 99.0%) respectively. Telephone surveys one year later also elicited a positive response. CONCLUSION: We herein introduce the experience of a half-day, family-engaged educational program for AD. Family-engaged education programs for AD such as this AD school encourage and validate family participation in the treatment of their children's AD.
Child ; Dermatitis, Atopic* ; Education ; Humans ; Korea* ; Lectures ; Parents ; Recreation ; Telephone

PURPOSE: This study was conducted to evaluate the efficacy and safety of azasetron compared to ondansetron in the prevention of delayed chemotherapy-induced nausea and vomiting. MATERIALS AND METHODS: This study was a multi-center, prospective, randomized, double-dummy, double-blind and parallel-group trial involving 12 institutions in Korea between May 2005 and December 2005. A total of 265 patients with moderately and highly emetogenic chemotherapy were included and randomly assigned to either the azasetron or ondansetron group. All patients received azasetron (10 mg intravenously) and dexamethasone (20 mg intravenously) on day 1 and dexamethasone (4 mg orally every 12 hours) on days 2-4. The azasetron group received azasetron (10 mg orally) with placebo of ondansetron (orally every 12 hours), and the ondansetron group received ondansetron (8 mg orally every 12 hours) with placebo of azasetron (orally) on days 2-6. RESULTS: Over days 2-6, the effective ratio of complete response in the azasetron and ondansetron groups was 45% and 54.5%, respectively (95% confidence interval, -21.4 to 2.5%). Thus, the non-inferiority of azasetron compared with ondansetron in delayed chemotherapy-induced nausea and vomiting was not proven in the present study. All treatments were well tolerated and no unexpected drug-related adverse events were reported. The most common adverse events related to the treatment were constipation and hiccups, and there were no differences in the overall incidence of adverse events. CONCLUSION: In the present study, azasetron showed inferiority in the control of delayed chemotherapy-induced nausea and vomiting compared with ondansetron whereas safety profiles were similar between the two groups.
Antineoplastic Agents ; Constipation ; Dexamethasone ; Drug Therapy* ; Hiccup ; Humans ; Incidence ; Korea ; Nausea* ; Ondansetron* ; Prospective Studies ; Serotonin Antagonists ; Vomiting*

PURPOSE: To review the results of postoperative radiation therapy (PORT) for residual non-small cell lung cancer (NSCLC) following surgical resection and evaluate multiple clinicopathologic prognostic factors. MATERIALS AND METHODS: A total of 58 patients, who completed scheduled PORT for positive resection margin, among 658 patients treated with PORT from January 2001 to November 2011 were retrospectively analyzed. Radiation therapy was started at 4 to 6 weeks after surgery. Chemotherapy was also administered to 35 patients, either sequentially or concurrently with PORT. RESULTS: The median age of patients was 63 years (range, 40 to 82 years). The postoperative pathological stage I NSCLC was diagnosed in 10 (17.2%), stage II in 18 (31.0%), and stage III in 30 patients (51.7%). Squamous cell carcinoma was identified in 43, adenocarcinoma in 10, large cell in 1, others in 4 patients. Microscopic residual disease (R1) was diagnosed in 55 patients (94.8%), and the remaining three patients were diagnosed with gross residual disease (R2). The median dose of PORT was 59.4 Gy (range, 50.0 to 64.8 Gy). Chemotherapy was administered to 35 patients (60%), and the median follow-up time was 22.0 months (range, 6.0 to 84.0 months). The 3-year locoregional relapse-free survival and distant metastasis-free survival rates were 82.1% and 52.9%, respectively. The median overall survival was 23.8 months (range, 6.0 to 84.1 months), and the 3-year overall survival rate was 58.2%. Chemotherapy did not influence the failure pattern or survival outcome. CONCLUSION: PORT is an effective modality for improving local tumor control in incompletely resected NSCLC patients. Major failure pattern was distant metastasis despite chemotherapy.
Adenocarcinoma ; Carcinoma, Non-Small-Cell Lung* ; Carcinoma, Squamous Cell ; Drug Therapy ; Follow-Up Studies ; Humans ; Neoplasm Metastasis ; Retrospective Studies ; Survival Rate

The potential role of topical valproate (VPA) in hair regrowth has been recently suggested. However, safety reports of VPA as a topical formulation are lacking. Therefore, in the present study, we investigated whether VPA causes skin irritation in humans. We first performed a cell viability test and showed that VPA did not exhibit toxicity toward HaCaT keratinocytes, fibroblasts, and RBL-3H mast cells. We then performed clinical patch test and skin irritation test through transdermal drug delivery with the help of microneedle rollers. No significant findings were obtained in the clinical patch test. In the skin irritation test, only 1 patient showed erythema at 1 hr, but the irritation reaction faded away within a few hours. Erythema and edema were not observed at 24 hr. We concluded that VPA has minimal potential to elicit skin irritation. Therefore, we consider that VPA can safely be applied to human skin.
Cell Survival ; Edema ; Erythema ; Fibroblasts ; Hair ; Humans ; Keratinocytes ; Mast Cells ; Patch Tests ; Skin ; Valproic Acid

BACKGROUNDThere is a significant association between obesity and breast cancer, which is possibly due to the expression of leptin. Therefore, it is important to clarify the role of leptin/ObR (leptin receptor) signaling during the progression of human breast cancer.

METHODSNude mice with xenografts of MCF-7 human breast cancer cells were administered recombinant human leptin subcutaneous via injection around the tumor site. Mice in the experimental group were intratumorally injected with ObR-RNAi-lentivirus, while negative control group mice were injected with the same dose of negative-lentivirus. Tumor size was blindly measured every other day, and mRNA and protein expression levels of ObR, estrogen receptor a (ERa), and vascular endothelial growth factor (VEGF) for each group were determined.

RESULTSKnockdown of ObR-treated xenografted nude mice with a high leptin microenvironment was successfully established. Local injection of ObR-RNAi-lentivirus significantly suppressed the established tumor growth in nude mice. ObR level was significantly lower in the experimental group than in the negative control group, while the amounts of ERa and VEGF expression were significantly lower in the leptin group than in the control group (P < 0.01 for all).

CONCLUSIONSInhibition of leptin/ObR signaling is essential to breast cancer proliferation and possible crosstalk between ObR and ERa, and VEGF, and may lead to novel therapeutic treatments aiming at targeting ObR in breast cancers.

Animals ; Breast Neoplasms ; genetics ; metabolism ; therapy ; Estrogen Receptor alpha ; genetics ; metabolism ; Female ; Humans ; Lentivirus ; genetics ; MCF-7 Cells ; Mice ; Mice, Nude ; RNA Interference ; physiology ; Receptors, Leptin ; genetics ; metabolism ; Vascular Endothelial Growth Factor A ; genetics ; metabolism ; Xenograft Model Antitumor Assays

Objective To numerically simulate the propagation of pulse wave in human arterial tree by proposing a novel calculation method which combines a transmission line model and a recursive algorithm of input impedance, and to study the effects of individual differences and arterial tree parameters on pulse wave so as to provide references for the analysis on physiologic and pathologic characteristics of human arterial tree. MethodsThe transmission line model of human arterial tree was constructed, which consisted of 55-segment large and medium sized arteries. The recursive algorithm was applied to compute the input impedance of arterial tree at each point. The blood pressures and flows of 55 arteries were calculated and showed in the distribution graphs. Based on this method, the effects of height, heart rate, stroke volume, internal radius and wall thickness on pulse wave propagation and blood pressure distribution were compared. Results The simulation results were in good agreement with the general rules of pulse wave propagation. The propagation of pulse wave in arterial tree showed significantly different characteristics for different parameters. Conclusions The proposed method can effectively simulate the propagation of pulse wave in arterial tree and accurately reflect the effects of individual differences and hemodynamics parameters on pulse wave propagation, and it is an important assistant means for the pathophysiologic analysis and diagnosis of human arterial tree.

OBJECTIVEGlycogen storage disease type III (GSD III) is an autosomal recessive disease caused by glycogen debranching enzyme (GDE) gene (AGL gene) mutation resulting in hepatomegaly, hypoglycemia, short stature and hyperlipidemia. GSD IIIA, involves both liver and muscle, and accounts for up to 80% of GSD III. The definitive diagnosis depends on either mutation analysis or liver and muscle glycogen debranching enzyme activity tests. This study aimed to establish enzymologic diagnostic method for GSD IIIA firstly in China by detecting muscular GDE activity, glycogen content and structure and to determine the normal range of muscular GDE activity, glycogen content and structure in Chinese children.

METHODMuscle samples were collected from normal controls (male 15, female 20; 12-78 years old), molecularly confirmed GSD III A patients (male 8, female 4, 2-27 years old) and other myopathy patients (male 9, 2-19 years old). Glycogen in the muscle homogenate was degraded into glucose by amyloglucosidase and phosphorylase respectively. The glycogen content and structure were identified by glucose yield determination. The debranching enzyme activity was determined using limit dextrin as substrate. Independent samples Kruskal-Wallis H test, Nemenyi-Wilcoxson-Wilcox test, and Chi-square test were used for statistical analyses by SPSS 11.5.

RESULT(1) GSD III A patients' glycogen content were higher, but G1P/G ratio and GDE activity were lower than those of the other two groups (P < 0.01). In all of the three parameters, there were no significant difference between normal controls and other myopathy patients. (2) The range of normal values: glycogen content 0.31%-0.43%, G1P/G ratio 22.37%- 26.43%, GDE activity 0.234-0.284 micromol/(g. min). (3) Enzymologic diagnostic method had a power similar to that of gene analysis in diagnosis of GSD-IIIA patients. The sensitivity and specificity of enzymologic diagnostic method and mutation detection were 91.7% and 100% respectively.

CONCLUSIONEnzymologic diagnostic method of GSD IIIA was firstly established in China. The range of normal values was determined. This method could be used in diagnosing suspected GSD IIIA patients in the clinic.

Adolescent ; Adult ; Aged ; Biopsy ; Case-Control Studies ; Child ; Child, Preschool ; China ; Female ; Glycogen ; analysis ; Glycogen Debranching Enzyme System ; analysis ; Glycogen Storage Disease Type III ; diagnosis ; enzymology ; pathology ; Humans ; Male ; Middle Aged ; Muscles ; chemistry ; pathology ; Young Adult