Automated lung tumor segmentation robust to various tumor sizes using a consistency learning-based multi-scale dual-attention network.

BACKGROUND: It is often difficult to automatically segment lung tumors due to the large tumor size variation ranging from less than 1 cm to greater than 7 cm depending on the T-stage. OBJECTIVE: This study aims to accurately segment lung tumors of various sizes using a consistency learning-based multi-scale dual-attention network (CL-MSDA-Net). METHODS: To avoid under- and over-segmentation caused by different ratios of lung tumors and surrounding structures in the input patch according to the size of the lung tumor, a size-invariant patch is generated by normalizing the ratio to the average size of the lung tumors used for the training. Two input patches, a size-invariant patch and size-variant patch are trained on a consistency learning-based network consisting of dual branches that share weights to generate a similar output for each branch with consistency loss. The network of each branch has a multi-scale dual-attention module that learns image features of different scales and uses channel and spatial attention to enhance the scale-attention ability to segment lung tumors of different sizes. RESULTS: In experiments with hospital datasets, CL-MSDA-Net showed an F1-score of 80.49%, recall of 79.06%, and precision of 86.78%. This resulted in 3.91%, 3.38%, and 2.95% higher F1-scores than the results of U-Net, U-Net with a multi-scale module, and U-Net with a multi-scale dual-attention module, respectively. In experiments with the NSCLC-Radiomics datasets, CL-MSDA-Net showed an F1-score of 71.7%, recall of 68.24%, and precision of 79.33%. This resulted in 3.66%, 3.38%, and 3.13% higher F1-scores than the results of U-Net, U-Net with a multi-scale module, and U-Net with a multi-scale dual-attention module, respectively. CONCLUSIONS: CL-MSDA-Net improves the segmentation performance on average for tumors of all sizes with significant improvements especially for small sized tumors.

Prevalence of and Gender Differences in Psychiatric Disorders among Juvenile Detainees in South Korea: A Comparative Study.

Background and Objectives: High rates of psychiatric disorders and comorbidities have been reported in juvenile detainees, which have been associated with repeat offenses. However, research into this topic has been limited to Asian countries. This study aimed to examine the prevalence of psychiatric disorders and sexual differences among juvenile detainees in a detention center in South Korea. Materials and Methods: The participants comprised 54 males and 46 females, with a minimum intelligence score of 80. Psychiatric diagnosis was determined using the Mini-International Neuropsychiatric Interview for Children and Adolescents (MINI-KID). The Massachusetts Youth Screening Instrument-Version 2 (MAYSI-2) was used to investigate gender differences. Results: Using the MINI-KID, the most frequent diseases were conduct disorder (CD), alcohol dependence, suicidal tendency, and attention-deficit/hyperactivity disorder (ADHD), with statistically significant differences between men and women. Only alcohol abuse was higher in males, while the rest were higher in females. The items with a statistically significant gender difference in MAYSI-2 were alcohol/drug use, feeling depressed/anxious, somatic complaints, suicidal ideation, and traumatic experiences. All items for which gender difference was statistically significant were higher in the proportion of women. Conclusions: Juvenile detainees exhibit high rates of psychiatric disorders and comorbidities. CDs, alcohol dependence, and ADHD are the most common psychiatric disorders among juvenile detainees in South Korea. Assessment of and intervention in psychiatric disorders may help prevent further offenses. These findings highlight the importance of diagnosing and intervening in psychiatric disorders within juvenile detention systems.

Lung tumor segmentation using dual-coupling net with shape prior based on lung and mediastinal window images from chest CT images.

BACKGROUND: Volumetric lung tumor segmentation is difficult due to the diversity of the sizes, locations and shapes of lung tumors, as well as the similarity in the intensity with surrounding tissue structures. OBJECTIVE: We propose a dual-coupling net for accurate lung tumor segmentation in chest CT images regardless of sizes, locations and shapes of lung tumors.METHODSTo extract shape information from lung tumors and use it as shape prior, three-planar images including axial, coronal, and sagittal planes are trained on 2D-Nets. Two types of window images, lung and mediastinal window images, are trained on 2D-Nets to distinguish lung tumors from the thoracic region and to better separate the boundaries of lung tumors from adjacent tissue structures. To prevent false-positive outliers to adjacent structures and to consider the spatial information of lung tumors, pairs of tumor volume-of-interest (VOI) and tumor shape prior are trained on 3D-Net.RESULTSIn the first experiment, the dual-coupling net had the highest Dice Similarity Coefficient (DSC) of 75.7%, considering the shape prior as well as mediastinal window images to prevent the leakage of adjacent structures while maintaining the shape of the lung tumor, with 18.23% p, 3.7% p, 1.1% p, and 1.77% p higher DSCs than in the 2D-Net, 2.5D-Net, 3D-Net, and single-coupling net results, respectively. In the second experiment with annotations for two clinicians, the dual-coupling net showed outcomes of 67.73% and 65.07% regarding the DSC for each annotation. In the third experiment, the dual-coupling net showed 70.97% for the DSC.CONCLUSIONSThe dual-coupling net enables accurate segmentation by distinguishing lung tumors from surrounding tissue structures and thus yields the highest DSC value.

A randomised phase 2b study comparing the efficacy and safety of belotecan vs. topotecan as monotherapy for sensitive-relapsed small-cell lung cancer.

BACKGROUND: This study compared the efficacy/safety of the camptothecin analogues belotecan and topotecan for sensitive-relapsed small-cell lung cancer (SCLC). METHODS: One-hundred-and-sixty-four patients were randomised (1:1) to receive five consecutive daily intravenous infusions of topotecan (1.5 mg/m2) or belotecan (0.5 mg/m2), every 3 weeks, for six cycles. Main outcomes were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), tolerability and toxicity. The study statistical plan was non-inferiority design with ORR as the endpoint. RESULTS: In the belotecan vs. topotecan groups, ORR (primary endpoint) was 33% vs. 21% (p = 0.09) and DCR was 85% vs. 70% (p = 0.030). PFS was not different between groups. Median OS was significantly longer with belotecan than with topotecan (13.2 vs. 8.2 months, HR = 0.69, 95% CI: 0.48-0.99), particularly in patients aged <65 years, with more advanced disease (i.e., extensive-stage disease, time to relapse: 3-6 months), or Eastern Cooperative Oncology Group performance status 1 or 2. More belotecan recipients completed all treatment cycles (53% vs. 35%; p = 0.022). CONCLUSIONS: The efficacy/safety of belotecan warrants further evaluation in Phase 3 trials. Belotecan potentially offers an alternative to topotecan for sensitive-relapsed SCLC, particularly in patients aged <65 years, with more advanced disease, or poor performance.

Interference with daily functioning by breakthrough pain in patients with cancer.

PURPOSE: To investigate the association between quality of life (QOL) and breakthrough cancer pain (BTCP) intensity in patients who met the commonly accepted definition of BTCP. METHODS: This study was a subset analysis of a South Korean multicenter, non-interventional, cross-sectional, nationwide survey. Participants were recruited from March 2016 to December 2017. BTCP was defined as a controlled background pain of less than a numeric rating scale (NRS) of 3 and any flare-up pain intensity. Pain intensity data were collected using the Brief Pain Inventory (BPI), which includes an interference assessment of the affective and physical domains. Patients were categorized by BTCP intensity into mild (NRS 1-3), moderate (4-6), and severe (7-10) groups. RESULTS: Of the 969 screened patients with cancer, 679 had ≤ NRS 3 background pain, of whom 438 completed the BPI. Of these 438 patients, 40, 204, and 194 were in the mild, moderate, and severe BTCP groups, respectively. The median NRS of BTCP was 6.0 (interquartile range = 5.0-8.0). Patients with moderate-severe BTCP had significantly higher interference with daily functioning (IDF) scores than did mild BTCP patients (3.3 vs. 5.7; p < 0.01). Both domains of IDF were significantly hampered proportionally by increased BTCP intensity (p < 0.001). The median total IDF scores of the no, moderate, and severe BTCP groups were 3.3, 5.0, and 6.9, respectively. Furthermore, IDF depended on BTCP intensity, duration, and frequency (p < 0.01) but not on pain type and cause. CONCLUSION: An increase in BTCP intensity is likely to result in IDF, regardless of the cause or type of BTCP.

Pazopanib maintenance after first-line etoposide and platinum chemotherapy in patients with extensive disease small-cell lung cancer: a multicentre, randomised, placebo-controlled Phase II study (KCSG-LU12-07).

BACKGROUND: We investigated whether pazopanib maintenance following first-line chemotherapy would improve survival in patients with extensive disease small-cell lung cancer (ED-SCLC). METHODS: This study is a randomised, placebo-controlled, phase II study that enroled ED-SCLC patients who had not progressed after four cycles of etoposide plus platinum therapy. Eligible patients were randomly assigned (1 : 1 ratio) to either placebo or pazopanib 800 mg per day until progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). RESULTS: 97 patients were enroled and randomly assigned; 2 patients did not receive study drugs. In total, 95 patients received maintenance therapy (pazopanib, n=48; placebo, n=47) and were included in the analyses. Grade 3 toxicities for pazopanib maintenance were thrombocytopenia (10.4%, including one case with grade 4 toxicity), liver enzyme elevation (10.4%), fatigue (6.3%), and hypertension (6.3%). Median PFS was 3.7 months for pazopanib maintenance and 1.8 months for placebo (hazard ratio 0.44, 95% confidence interval: 0.29-0.69, P<0.0001). CONCLUSIONS: Pazopanib maintenance significantly prolonged PFS in patients with ED-SCLC. Given the toxicity profiles, however, relevant biomarkers to select patients for benefit from pazopanib should be further investigated.

Prescription Trends of Psychotropics in Children and Adolescents with Autism Based on Nationwide Health Insurance Data.

Children with autism are often medicated to manage emotional and behavioral symptoms; yet, data on such pharmacotherapy is insufficient. In this study, we investigated the Korean National Health Insurance Claims Database (NHICD) information related to autism incidence and psychotropic medication use. From the 2010-2012 NHICD, we selected a total of 31,919,732 subjects under 19 years old. To examine the diagnostic incidence, we selected patients who had at least one medical claim containing an 10th revision of International Statistical Classification of Diseases and Related Health Problems (ICD-10) code for pervasive developmental disorder, F84, not diagnosed in the previous 360 days. Psychotropics were categorized into seven classes. Then, we analyzed the data to determine the mean annual diagnostic incidence and psychotropic prescription trends. Diagnostic incidence was 17,606 for the 3 years, with a mean annual incidence per 10,000 population of 5.52. Among them, 5,348 patients were prescribed psychotropics. Atypical antipsychotics were the most commonly used, followed by antidepressants. An older age, male sex, and the availability of medical aid were associated with a higher rate of prescription than observed for a younger age, female sex, and the availability of health insurance. Psychotropic drugs were used for less than one-third of patients newly diagnosed with autism, and prescription differed by sex and age. Increased diagnostic incidence is associated with an increased prescription of psychotropic drugs. Therefore, medication-related safety data and policies for psychotropic drugs in autism should be prepared.

Type of childhood maltreatment and the risk of criminal recidivism in adult probationers: a cross-sectional study.

BACKGROUND: Childhood maltreatment is strongly associated with delinquency and the repeated crime. Specific types of childhood maltreatment have been found to have differential effects on recidivism in juvenile offenders, but studies of adult probationers have not been performed. This study investigated the relationship between having a history of childhood maltreatment and mental-health problems and the independent contribution of specific types of maltreatment and mental-health problems to the criminal recidivism of adult probationers. METHOD: This study included 183 adult probationers (107 males and 76 females) with a mean age of 40.1 (SD = 11.8) years. Type of childhood maltreatment was assessed using the Childhood Trauma Questionnaire, which consists of five subscales (emotional neglect and abuse, physical neglect and abuse, and sexual abuse). Additionally, we used the Mini International Neuropsychiatric Interview to assess participants for the presence of psychiatric disorders and assessed levels of emotional dysregulation and resilience. Hierarchical logistic regression analysis was performed to determine whether the types of childhood maltreatment were independently associated with repeated crime, after adjusting for demographic factors and mental-health problems. RESULTS: The overall prevalence of mental illness in the childhood maltreatment group was significantly higher than in the no childhood maltreatment group (56.1 % vs. 38.2 %, p = 0.017). The maltreated group had a higher rate of major depressive disorder, a higher level of emotional dysregulation, and a lower level of resilience than the group that was not maltreated. Recidivism was uniquely associated with physical neglect (Adjusted Odds Ratio [AOR], 2.862; 95 % Confidence Interval [95 % CI], 1.213-6.752) and the presence of at least one psychiatric disorder (AOR, 3.791; 95 % CI, 1.703-8.443). CONCLUSIONS: Childhood maltreatment deserves further attention in adult probationers because it is potentially associated with higher rates of psychiatric morbidity and recidivism. In particular, physical neglect during childhood plays a critical role in repeated crime, independent of mental-health problems for high-risk adults involved with the criminal justice system. Rigorous evaluations of the relevance of childhood maltreatment in the assessment and treatment of criminal offenders are needed.

Utilization of Western and Traditional Korean Medicine for Children and Adolescents with Mental Disorders: a Nationwide Population-based Study from 2010 to 2012.

When in need of medical treatment, Korean citizens have a choice of practitioners of western medicine (WM) or Traditional Korean Medicine (TKM). However, the two branches frequently conflict with one another, particularly with regard to mental disorders. This study was designed to compare the utilization of WM and TKM, focusing on child/adolescent patients with mental disorders. We analyzed F-code (Mental and behavioral disorders) claims from the Korean Health Insurance Review and Assessment Service, including data from 0-18-year-old patients from 2010 to 2012. Slightly more men than women utilized WM, while TKM use was almost evenly balanced. WM claims increased with advancing age, whereas utilization of TKM was common for the 0-6 age group. In WM and TKM, the total number of claims relying on the National Health Insurance Service (NHIS) was 331,154 (92.78%) and 73,282 (97.85%), respectively, and the number of claims relying on medical aid was 25,753 (7.22%) and 1,610 (2.15%), respectively. The most frequent F-coded claim in WM was F90 (Hyperkinetic disorders), with 64,088 claims (17.96%), and that in TKM was F45 (Somatoform disorders), with 28,852 claims (38.52%). The prevalence of a single disorder without comorbidities was 168,764 (47.29%) in WM and 52,615 (70.25%) in TKM. From these data, we conclude that WM takes prevalence over TKM in cases of attention deficit/hyperactivity disorder (ADHD), as well as in psychological problems such as depression and anxiety. On the other hand, patients utilizing TKM more commonly present with physical health problems including somatoform problems, sleep, and eating disorders.

Naturalistic Pharmacotherapy Compliance among Pediatric Patients with Attention Deficit/Hyperactivity Disorder: a Study Based on Three-Year Nationwide Data.

We examined short- and long-term medication compliance among youth with attention-deficit hyperactivity disorder (ADHD), using data from the National Health Insurance database in Korea. Of the 5,699,202 6-14-year-old youth in 2008, we chose those with at least 1 medical claim containing an ICD-10 code for diagnosis of ADHD (F90.0) and no prescription for ADHD within the previous 365 days. We tracked the data every 6 months between 2008 and 2011, to determine treatment compliance among newly diagnosed, medicated patients. Further, we checked every 1 month of the 6 months after treatment commencement. Treatment continuity for each patient was calculated by sequentially counting the continuous prescriptions. For measuring compliance, we applied the medication possession ratio (MPR) as 0.6, 0.7, and 0.8, and the gap method as 15- and 30-days' intervals. There were 15,133 subjects; 11,934 (78.86%) were boys. Overall 6-month treatment compliance was 59.0%, 47.3%, 39.9%, 34.1%, 28.6%, and 23.1%. Monthly drop-out rates within the first 6 months were 20.6%, 6.5%, 4.7%, 3.7%, 3.0%, and 2.5%, respectively. When applying MPR more strictly or shorter gap days, treatment compliance lessened. This is the first nationwide report on 36-month treatment compliance of the whole population of 6-14-year-olds with ADHD. We found the beginning of the treatment, especially the first month, to be a critical period in pharmacotherapy. These results also suggest the importance of setting appropriate treatment adherence standards for patients with ADHD, considering the chronic course of ADHD.

Differences in Utilization Patterns among Medications in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: a 36-Month Retrospective Study Using the Korean Health Insurance Review and Assessment Claims Database.

We evaluated the differences in utilization patterns including persistence and adherence among medications in children and adolescents with attention deficit hyperactivity disorder (ADHD). The current study was performed using data from the Korean Health Insurance Review and Assessment claims database from January 1, 2009 to December 31, 2013. Our study sample consisted of 10,343 children and adolescents with ADHD who were not given their newly prescribed medication in 360 days before the initial claim in 2010. Data were followed up from the initiation of treatment with ADHD medications in 2010 to December 31, 2013. Discontinuation rates for 4 ADHD medications in our sample ranged from 97.7% for immediate-release methylphenidate to 99.4% for atomoxetine using refill gap more than 30 days and from 56.7% for immediate-release methylphenidate to 62.3% for extended-release methylphenidate using refill gap more than 60 days. In the number of discontinued, we found significant differences among medications using refill gap more than 30 days. Among 4 ADHD medications, extended-release methylphenidate and atomoxetine had more days than immediate-release methylphenidate and osmotic-controlled oral delivery system methylphenidate. In logistic regression analyses, extended-release methylphenidate, osmotic-controlled oral delivery system methylphenidate, and atomoxetine showed less discontinuation compared to immediate-release methylphenidate group when a refill gap more than 30 days was used. In logistic regression analysis of adherence, we could not find any differences among 4 medication types. We suggest that the utilization patterns should be assessed regularly in order to improve future outcomes in children and adolescents with ADHD.

A survey study of the satisfaction and attitude of the Korean psychiatrists toward antipsychotic polypharmacy.

BACKGROUND: Antipsychotic polypharmacy (AP) to treat patients with schizophrenia and schizoaffective disorder is commonly prescribed in clinical practice; however, evidence supporting its use is scarce. This study surveyed South Korean psychiatrists' rationale for AP. METHODS: Psychiatrists were interviewed using a newly developed, semi-structured questionnaire inquiring about AP attitudes and behaviors, including frequency of use, rationale, concerns, and preferred combinations. RESULTS: Compared with the high-prescribing AP group (≥10 patients a day; HAP group), the low-prescribing AP group (≤9 patients a day; LAP group) tended to work in a university general hospital, publish more research papers a year, attend more psychiatric conferences, prescribe more 2-antipsychotic combinations, and have more satisfaction with AP. Psychiatrists were satisfied with the therapeutic response with AP (rating 6.4±1.5). Psychiatrists felt concern about AP (rating 4.7±1.6), mostly because of its higher risk of chronic adverse effects. CONCLUSIONS: In South Korean psychiatric practices, the LAP group seems to pay closer attention to AP than the HAP group does. However, both the HAP and LAP groups share similar attitudes toward satisfaction, concerns, and preferred combinations of AP.

Parental quality of life and depressive mood following methylphenidate treatment of children with attention-deficit hyperactivity disorder.

AIM: This naturalistic study investigated the associations between quality of life and depressive mood in parents and symptom changes in attention-deficit hyperactivity disorder (ADHD) children. METHODS: At baseline and at weeks 4 and 8, the parents evaluated their children, who were receiving treatment with osmotic-release oral system methylphenidate (mean dosage 36.3 ± 15.5 mg/day), using the Swanson, Nolan, and Pelham - Fourth Edition (SNAP-IV-18) scale. The parents evaluated themselves using the Beck Depression Inventory (BDI) and the World Health Organization Quality of Life Assessment, Brief Version (WHOQOL-BREF). RESULTS: A significant reduction in SNAP-IV-18 scores and improvements in parental BDI scores and parental WHOQOL-BREF scores were observed. The decrease in BDI scores from baseline to 8 weeks was significantly associated with increases in WHOQOL-BREF sub-domain scores from baseline to 8 weeks, with a greater decrease at 4 weeks and after. The decrease in the SNAP-IV-18 hyperactivity-impulsivity score was significantly associated with increases in WHOQOL social sub-domain scores from baseline to 8 weeks. For those patients who showed a 25% or greater decrease in the SNAP-IV-18 total scores from baseline to 8 weeks, the decreases in the SNAP-IV-18 total score and in the inattention and hyperactivity-impulsivity scores were significantly associated with a decrease in BDI scores from baseline to 8 weeks. CONCLUSION: Methylphenidate treatment for ADHD was associated with both symptom alleviation in children with ADHD and improvement in parental depressive mood and quality of life, suggesting that the effects of treatment could go beyond symptom improvement in ADHD.

Effectiveness of paliperidone extended-release for patients with schizophrenia: focus on subjective improvement.

OBJECTIVE: This study assessed whether the subjective experience of patients with schizophrenia improved after switching from an oral antipsychotic to flexibly-dosed paliperidone extended-release. METHODS: We conducted a 24-week, multicenter, non-comparative, open-label trial. A total of 387 patients with schizophrenia participated the study. The primary study outcome was the change in subjective symptoms measured by the Symptom Checklist-90-Revised version (SCL-90-R) from baseline. Visual analogue scales were used for sleep and daytime somnolence as secondary subjective assessments. The clinical global impression-schizophrenia-severity scale was used to assess overall symptom severity. Social functioning was evaluated by the personal and social performance scale. Adverse events were also evaluated. RESULTS: All subjective symptoms measured by the SCL-90-R improved significantly. The early responders, who achieved >20% reduction in the SCL-90-R within 1 week, maintained significantly lower severity through the 24 weeks. The clinical global impression-schizophrenia-severity scale and personal and social performance scores also improved significantly. The visual analogue scales revealed that daytime somnolence improved significantly, whereas nocturnal sleep quality was unaltered. CONCLUSION: Our results suggest that switching to paliperidone extended-release was associated with improvements in various subjective symptoms, decreased overall symptom severity, and increased social functioning. The results also suggest that early detection and reduction of subjective symptoms are important for treatment outcome.

Methylphenidate-osmotic-controlled release oral delivery system treatment reduces parenting stress in parents of children and adolescents with attention-deficit/hyperactivity disorder.

OBJECTIVE: The aim of the current study was to investigate the effect of methylphenidate-osmotic release oral delivery system (MPH-OROS) treatment on parenting stress in parents of children and adolescents with attention-deficit/hyperactivity disorder (ADHD). METHODS: Four hundred and ninety-five children and adolescents (391 boys and 104 girls), aged 7 to 18 years who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria for ADHD, were recruited at 48 psychiatric outpatient clinics across South Korea. Children's symptoms, parenting stress, and parental depression were assessed at baseline, week 4, and week 8 of MPH-OROS treatment using the Korean version of the DuPaul's ADHD Rating Scale (ARS), the Beck's Depression Inventory (BDI), and the Parenting Stress Index, Short Form (PSI-SF). RESULTS: We found significantly decreased scores of ARS, parental BDI, and PSI-SF from baseline to week 4 and from week 4 to week 8. Also, there were positive correlations among baseline PSI-SF, ARS, and BDI scores. The changes in BDI and ARS scores were significantly associated with the PSI score changes, accounting for 20.1% and 10.0%, respectively. CONCLUSIONS: We suggest that the increased parenting stress and depression in parents of children and adolescents with ADHD can be improved following the treatment with MPH-OROS.

Beyond Attention-Deficit Hyperactivity Disorder: Exploring Psychiatric Comorbidities and Their Neuropsychological Consequences in Adults.

Objectives: This study aimed to identify the psychiatric comorbidity status of adult patients diagnosed with attention-deficit hyperactivity disorder (ADHD) and determine the impact of comorbidities on neuropsychological outcomes in ADHD. Methods: The study participants were 124 adult patients with ADHD. Clinical psychiatric assessments were performed by two boardcertified psychiatrists in accordance with the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. All participants were assessed using the Mini-International Neuropsychiatric Interview Plus version 5.0.0 to evaluate comorbidities. After screening, neuropsychological outcomes were assessed using the Comprehensive Attention Test (CAT) and the Korean version of the Wechsler Adult Intelligence Scale, Fourth Edition (K-WAIS-IV). Results: Mood disorders (38.7%) were the most common comorbidity of ADHD, followed by anxiety (18.5%) and substance use disorders (13.7%). The ADHD with comorbidities group showed worse results on the Perceptual Organization Index and Working Memory Index sections of the K-WAIS than the ADHD-alone group (p=0.015 and p=0.024, respectively). In addition, the presence of comorbidities was associated with worse performance on simple visual commission errors in the CAT tests (p=0.024). Conclusion: These findings suggest that psychiatric comorbidities are associated with poor neuropsychological outcomes in adult patients with ADHD, highlighting the need to identify comorbidities in these patients.

A combination of BR101801 and venetoclax enhances antitumor effect in DLBCL cells via c-Myc/Bcl-2/Mcl-1 triple targeting.

Double hit diffuse large B-cell lymphoma (DLBCL) with rearrangement and overexpression of both c-Myc and Bcl-2 responds poorly to standard R-CHOP therapy. In a recent phase I study, Venetoclax (ABT-199) targeting Bcl-2 also exhibited disappointing response rates in patients with relapsed/refractory DLBCL, suggesting that targeting only Bcl-2 is not sufficient for achieving successful efficacy due to the concurrent oncogenic function of c-Myc expression and drug resistance following an increase in Mcl-1. Therefore, co-targeting c-Myc and Mcl-1 could be a key combinatorial strategy to enhance the efficacy of Venetoclax. In this study, BR101801 a novel drug for DLBCL, effectively inhibited DLBCL cell growth/proliferation, induced cell cycle arrest, and markedly inhibited G0/G1 arrest. The apoptotic effect of BR101801 was also observed by increased Cytochrome C, cleaved PARP, and Annexin V-positive cell populations. This anti-cancer effect of BR101801 was confirmed in animal models, where it effectively inhibited tumor growth by reducing the expression of both c-Myc and Mcl-1. Furthermore, BR101801 exhibited a significant synergistic antitumor effect even in late xenograft models when combined with Venetoclax. Our data strongly suggest that c-Myc/Bcl-2/Mcl-1 triple targeting through a combination of BR101801 and Venetoclax could be a potential clinical option for double-hit DLBCL.

Gefitinib versus pemetrexed as second-line treatment in patients with nonsmall cell lung cancer previously treated with platinum-based chemotherapy (KCSG-LU08-01): an open-label, phase 3 trial.

BACKGROUND: Gefitinib was compared with pemetrexed as second-line therapy in a clinically selected population previously treated with platinum-based chemotherapy. METHODS: A phase 3 trial of gefitinib (250 mg/day) versus pemetrexed (500 mg/m(2) on day 1, every 3 weeks) was conducted in patients who had never smoked and who had advanced pulmonary adenocarcinoma treated with 1 previous platinum-based regimen. The primary endpoint was progression-free survival (PFS). RESULTS: A total of 135 patients were analyzed. The gefitinib group had significantly longer PFS compared with the pemetrexed group, with a median PFS time of 9.0 versus 3.0 months (P = .0006). The objective response rates were 58.8% and 22.4% for gefitinib and pemetrexed, respectively (P < .001). However, there was no statistically significant difference in overall survival between the 2 groups (22.2 vs 18.9 months; P = .37). The difference of PFS was increased in a subgroup analysis of 33 patients with activating epidermal growth factor receptor mutation (15.7 vs 2.9 months; hazard ratio, 0.3; 95% confidence interval, 0.13-0.72; P = .005), with numerical superiority of gefitinib in the 38 patients testing negative for epidermal growth factor receptor mutation (5.9 vs 2.7 months; P = .099). Both regimens were well tolerated. There were no significantly different changes in quality of life between the 2 groups, except that symptom scores for dyspnea and diarrhea favored the gefitinib and pemetrexed arms, respectively. CONCLUSIONS: Gefitinib showed superior efficacy to pemetrexed as second-line therapy in Korean never-smokers with pulmonary adenocarcinoma.

A phase II trial of erlotinib in combination with gemcitabine and capecitabine in previously untreated metastatic/recurrent pancreatic cancer: combined analysis with translational research.

BACKGROUND: To confirm the efficacy and toxicity of Erlotinib in combination with Gemcitabine and Capecitabine when used as a first-line therapy in metastatic/recurrent pancreatic cancer (PC). METHODS: Locally advanced PC was excluded. Erlotinib was given at a dose of 100 mg daily from D1 to D28. 1000 mg/m(2) of gemcitabine was given on D1,8,15 and 1660 mg/m(2)/day of capecitabine was given from D1 to 21, repeated every 4 weeks. Response was assessed every 8 weeks. RESULTS: A total of 47 patients were enrolled. Response rate and disease control rate was 32.6% (95% CI, 18.6-46.6%) and 83.7% (95% CI, 72.7-94.7%) respectively. The PFS was 6.5 months (95% CI, 3.4-9.7) and OS was 12.0 months (95% CI, 8.6-15.9). The Gr 3/4 toxicities were: neutropenia (6.8%), thrombocytopenia (3.2%), anemia (1.6%). nausea (1.6%), vomiting (1.6%), anorexia (5.3%), rash (2.4%). The EGFR expression was associated with shorter OS and ERCC2 expression was associated with longer PFS and OS. PFS and OS were not different according to K-RAS mutation or polymorphism of RRM1 and CDA. CONCLUSIONS: Erlotinib, gemcitabine and capecitabine combination showed promising efficacy and good tolerability in metastatic PC. This efficacy was observed irrespective of K-RAS mutation, and EGFR expression was poor prognostic factor for OS.

Prediction of Two-Year Recurrence-Free Survival in Operable NSCLC Patients Using Radiomic Features from Intra- and Size-Variant Peri-Tumoral Regions on Chest CT Images.

To predict the two-year recurrence-free survival of patients with non-small cell lung cancer (NSCLC), we propose a prediction model using radiomic features of the inner and outer regions of the tumor. The intratumoral region and the peritumoral regions from the boundary to 3 cm were used to extract the radiomic features based on the intensity, texture, and shape features. Feature selection was performed to identify significant radiomic features to predict two-year recurrence-free survival, and patient classification was performed into recurrence and non-recurrence groups using SVM and random forest classifiers. The probability of two-year recurrence-free survival was estimated with the Kaplan-Meier curve. In the experiment, CT images of 217 non-small-cell lung cancer patients at stages I-IIIA who underwent surgical resection at the Veterans Health Service Medical Center (VHSMC) were used. Regarding the classification performance on whole tumors, the combined radiomic features for intratumoral and peritumoral regions of 6 mm and 9 mm showed improved performance (AUC 0.66, 0.66) compared to T stage and N stage (AUC 0.60), intratumoral (AUC 0.64) and peritumoral 6 mm and 9 mm classifiers (AUC 0.59, 0.62). In the assessment of the classification performance according to the tumor size, combined regions of 21 mm and 3 mm were significant when predicting outcomes compared to other regions of tumors under 3 cm (AUC 0.70) and 3 cm~5 cm (AUC 0.75), respectively. For tumors larger than 5 cm, the combined 3 mm region was significant in predictions compared to the other features (AUC 0.71). Through this experiment, it was confirmed that peritumoral and combined regions showed higher performance than the intratumoral region for tumors less than 5 cm in size and that intratumoral and combined regions showed more stable performance than the peritumoral region in tumors larger than 5 cm.