Purpose: This study evaluated whether combination therapy is more effective than monotherapy in elderly patients with metastatic or recurrent gastric cancer (MRGC) as first-line chemotherapy. Materials and Methods: Elderly (≥ 70 years) chemo-naïve patients with MRGC were allocated to receive either combination therapy (group A: 5-fluorouracil [5-FU]/oxaliplatin, capecitabine/oxaliplatin, capecitabine/cisplatin, or S-1/cisplatin) or monotherapy (group B: 5-FU, capecitabine, or S-1). In group A, starting doses were 80% of standard doses, and they could be escalated to 100% at the discretion of the investigator. Primary endpoint was to confirm superior overall survival (OS) of combination therapy vs. monotherapy. Results: After 111 of the planned 238 patients were randomized, enrollment was terminated due to poor accrual. In the full-analysis population (group A [n=53] and group B [n=51]), median OS of combination therapy vs. monotherapy was 11.5 vs. 7.5 months (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.56 to 1.30; p=0.231). Median progression-free survival (PFS) was 5.6 vs. 3.7 months (HR, 0.53; 95% CI, 0.34 to 0.83; p=0.005). In subgroup analyses, patients aged 70-74 years tended to have superior OS with combination therapy (15.9 vs. 7.2 months, p=0.056). Treatment-related adverse events (TRAEs) occurred more frequently in group A vs. group B. However, among severe TRAEs (≥ grade 3), there were no TRAEs with a frequency difference of > 5%. Conclusion Combination therapy was associated with numerically improved OS, although statistically insignificant, and a significant PFS benefit compared with monotherapy. Although combination therapy showed more frequent TRAEs, there was no difference in the frequency of severe TRAEs.

Purpose: Renal tumors account for approximately 7% of all childhood cancers. These include Wilms tumor (WT), clear cell sarcoma of the kidney (CCSK), malignant rhabdoid tumor of the kidney (MRTK), renal cell carcinoma (RCC), congenital mesoblastic nephroma (CMN) and other rare tumors. We investigated the epidemiology of pediatric renal tumors in Korea. Materials and Methods: From January 2001 to December 2015, data of pediatric patients (0–18 years) newly-diagnosed with renal tumors at 26 hospitals were retrospectively analyzed. Results: Among 439 patients (male, 240), the most common tumor was WT (n=342, 77.9%), followed by RCC (n=36, 8.2%), CCSK (n=24, 5.5%), MRTK (n=16, 3.6%), CMN (n=12, 2.7%), and others (n=9, 2.1%). Median age at diagnosis was 27.1 months (range 0-225.5) and median follow-up duration was 88.5 months (range 0-211.6). Overall, 32 patients died, of whom 17, 11, 1, and 3 died of relapse, progressive disease, second malignant neoplasm, and treatment-related mortality. Five-year overall survival and event free survival were 97.2% and 84.8% in WT, 90.6% and 82.1% in RCC, 81.1% and 63.6% in CCSK, 60.3% and 56.2% in MRTK, and 100% and 91.7% in CMN, respectively (p < 0.001). Conclusion The pediatric renal tumor types in Korea are similar to those previously reported in other countries. WT accounted for a large proportion and survival was excellent. Non-Wilms renal tumors included a variety of tumors and showed inferior outcome, especially MRTK. Further efforts are necessary to optimize the treatment and analyze the genetic characteristics of pediatric renal tumors in Korea.

Purpose: Acute promyelocytic leukemia (APL) is a rare disease in children and there are some different characteristics between children and adult. We aimed to evaluate incidence, clinical characteristics and treatment outcomes of pediatric APL in Korea. Materials and Methods: Seventy-nine pediatric APL patients diagnosed from January 2009 to December 2016 in 16 tertiary medical centers in Korea were reviewed retrospectively. Results: Of 801 acute myeloid leukemia children, 79 (9.9%) were diagnosed with APL. The median age at diagnosis was 10.6 years (range, 1.3 to 18.0). Male and female ratio was 1:0.93. Thirty patients (38.0%) had white blood cell (WBC) count greater than 10×109/L at diagnosis. All patients received induction therapy consisting of all-trans retinoic acid and chemotherapy. Five patients (6.6%) died during induction chemotherapy and 66 patients (86.8%) achieved complete remission (CR) after induction chemotherapy. The causes of death were three intracranial hemorrhage, one cerebral infarction, and one sepsis. Five patients (7.1%) suffered a relapse during or after maintenance chemotherapy. The estimated 4-year event-free survival and overall survival (OS) rates were 82.1%±4.4%, 89.7%±5.1%, respectively. The 4-year OS was significantly higher in patients with initial WBC < 10×109/L than in those with initial WBC ≥ 10×109/L (p=0.020). Conclusion This study showed that the CR rates and survival outcomes in Korean pediatric APL patients were relatively good. The initial WBC count was the most important prognostic factor and most causes of death were related to serious bleeding in the early stage of treatment.

Background/Aims: Because weight control is important in treatment of type 2 diabetes, it is essential to understand the associations between weight change and the risk of microvascular complications among patients with type 2 diabetes. We examined whether weight changes early after new-onset diabetes have an impact on the clinical outcomes of diabetic nephropathy and retinopathy. Methods: Using the Korean National Health Insurance Service-National Health Screening Cohort database, 181,872 patients newly diagnosed with type 2 diabetes who were free of end-stage renal disease (ESRD) and proliferative diabetic retinopathy (PDR) during 2007 to 2012 were followed to the end of 2016. Weight change was defined as the difference in body weight from the time of diabetes diagnosis to 2 years later. Results: We identified 180 cases of ESRD and 780 cases of PDR followed up for a median of 5.5 years from the index year at 2 years after diagnosis. Those with 5% to 10% weight gain showed a significantly higher hazard ratio (HR) for ESRD, compared with those with ≤ 5% weight change after adjusting for several confounding factors, including the baseline estimated glomerular filtration rate (HR, 1.75; 95% confidence interval [CI], 1.14 to 2.70). Those with ≥ 10% weight loss showed the lowest HR for PDR (HR, 0.52; 95% CI, 0.33 to 0.83), whereas those with ≥ 10% weight gain showed the highest HR for PDR (HR, 3.20; 95% CI, 2.51 to 4.08). Conclusions Weight gain after new-onset diabetes was associated with increased risk of ESRD and PDR whereas weight loss with decreased risk of PDR, but not ESRD.

Background: Recently, a metabolic syndrome severity score (MS score) using a dataset of the Korea National Health and Nutrition Examination Surveys has been developed. We aimed to determine whether the newly developed score is a significant predictor of cardiovascular (CV) events among the Korean population. Methods: From the Korean National Health Insurance System, 2,541,364 (aged 40 to 59 years) subjects with no history of CV events (ischemic stroke or myocardial infarction [MI]), who underwent health examinations from 2009 to 2011 and were followed up until 2014 to 2017, were identified. Cox proportional hazard model was employed to investigate the association between MS score and CV events. Model performance of MS score for predicting CV events was compared to that of conventional metabolic syndrome diagnostic criteria (Adult Treatment Program III [ATP-III]) using the Akaike information criterion and the area under the receiver operating characteristic curve. Results: Over a median follow-up of 6 years, 15,762 cases of CV events were reported. MS score at baseline showed a linear association with incident CV events. In the multivariable-adjusted model, the hazard ratios (95% confidence intervals) comparing the highest versus lowest quartiles of MS score were 1.48 (1.36 to 1.60) for MI and 1.89 (1.74 to 2.05) for stroke. Model fitness and performance of the MS score in predicting CV events were superior to those of ATP-III. Conclusion The newly developed age- and sex-specific continuous MS score for the Korean population is an independent predictor of ischemic stroke and MI in Korean middle-aged adults even after adjusting for confounding factors.

Purpose: The incidence of human papillomavirus (HPV)-related oropharyngeal cancer (OPC) has increased, and staging and optimal therapeutic approaches are challenging. A questionnaire survey was conducted to investigate the controversial treatment policy of stage T2 OPC according to the N category and determine the opinions of multidisciplinary experts in Korea. Materials and Methods: Five OPC scenarios were developed by the Subcommittee on Oropharyngeal Treatment Guidelines of the Korean Society for Head and Neck Oncology and distributed to experts of multidisciplinary treatment hospitals. Results: Sixty-five experts from 45 institutions responded. For the HPV-positive T2N0M0 scenario, 67.7% of respondents selected surgery followed by definitive concurrent chemoradiotherapy (CCRT) or radiotherapy alone. For the T2N1M0 HPV-positive scenario, there was a notable difference in the selection of primary treatment by expert specialty; 53.9% of respondents selected surgery and 39.8% selected definitive CCRT as the primary treatment. For the T2N3M0 advanced HPV-positive scenario, 50.0% of respondents selected CCRT and 33.3% considered induction chemotherapy (IC) as the primary treatment. CCRT and IC were significantly more frequently selected for the HPV-related OPC cases (p=0.010). The interdepartmental variability showed that the head and neck surgeons and medical oncologists favored surgery, whereas the radiation oncologists preferably selected definitive CCRT (p < 0.001). Conclusion In this study, surgery was preferred for lymph node-negative OPC, and as lymph node metastasis progressed, CCRT tended to be preferred, and IC was administered. Clinical practice patterns by stage and HPV status showed differences according to expert specialty. Multidisciplinary consensus guidelines will be essential in the future.

Background/Aims: Because weight control is important in treatment of type 2 diabetes, it is essential to understand the associations between weight change and the risk of microvascular complications among patients with type 2 diabetes. We examined whether weight changes early after new-onset diabetes have an impact on the clinical outcomes of diabetic nephropathy and retinopathy. Methods: Using the Korean National Health Insurance Service-National Health Screening Cohort database, 181,872 patients newly diagnosed with type 2 diabetes who were free of end-stage renal disease (ESRD) and proliferative diabetic retinopathy (PDR) during 2007 to 2012 were followed to the end of 2016. Weight change was defined as the difference in body weight from the time of diabetes diagnosis to 2 years later. Results: We identified 180 cases of ESRD and 780 cases of PDR followed up for a median of 5.5 years from the index year at 2 years after diagnosis. Those with 5% to 10% weight gain showed a significantly higher hazard ratio (HR) for ESRD, compared with those with ≤ 5% weight change after adjusting for several confounding factors, including the baseline estimated glomerular filtration rate (HR, 1.75; 95% confidence interval [CI], 1.14 to 2.70). Those with ≥ 10% weight loss showed the lowest HR for PDR (HR, 0.52; 95% CI, 0.33 to 0.83), whereas those with ≥ 10% weight gain showed the highest HR for PDR (HR, 3.20; 95% CI, 2.51 to 4.08). Conclusions Weight gain after new-onset diabetes was associated with increased risk of ESRD and PDR whereas weight loss with decreased risk of PDR, but not ESRD.

Background: Recently, a metabolic syndrome severity score (MS score) using a dataset of the Korea National Health and Nutrition Examination Surveys has been developed. We aimed to determine whether the newly developed score is a significant predictor of cardiovascular (CV) events among the Korean population. Methods: From the Korean National Health Insurance System, 2,541,364 (aged 40 to 59 years) subjects with no history of CV events (ischemic stroke or myocardial infarction [MI]), who underwent health examinations from 2009 to 2011 and were followed up until 2014 to 2017, were identified. Cox proportional hazard model was employed to investigate the association between MS score and CV events. Model performance of MS score for predicting CV events was compared to that of conventional metabolic syndrome diagnostic criteria (Adult Treatment Program III [ATP-III]) using the Akaike information criterion and the area under the receiver operating characteristic curve. Results: Over a median follow-up of 6 years, 15,762 cases of CV events were reported. MS score at baseline showed a linear association with incident CV events. In the multivariable-adjusted model, the hazard ratios (95% confidence intervals) comparing the highest versus lowest quartiles of MS score were 1.48 (1.36 to 1.60) for MI and 1.89 (1.74 to 2.05) for stroke. Model fitness and performance of the MS score in predicting CV events were superior to those of ATP-III. Conclusion The newly developed age- and sex-specific continuous MS score for the Korean population is an independent predictor of ischemic stroke and MI in Korean middle-aged adults even after adjusting for confounding factors.

Many previous studies have shown reduced glucose uptake in the ischemic brain. In contrast, in a permanent unilateral common carotid artery occlusion (UCCAO) mouse model, our pilot experiments using 18F-fluorodeoxyglucose positron emission tomography (FDG PET) revealed that a subset of mice exhibited conspicuously high uptake of glucose in the ipsilateral hemisphere at 1 week post-occlusion (asymmetric group), whereas other mice showed symmetric uptake in both hemispheres (symmetric group). Thus, we aimed to understand the discrepancy between the two groups. Cerebral blood flow and histological/metabolic changes were analyzed using laser Doppler flowmetry and immunohistochemistry/Western blotting, respectively. Contrary to the increased glucose uptake observed in the ischemic cerebral hemisphere on FDG PET (p<0.001), cerebral blood flow tended to be lower in the asymmetric group than in the symmetric group (right to left ratio [%], 36.4±21.8 vs. 58.0±24.8, p=0.059). Neuronal death was observed only in the ischemic hemisphere of the asymmetric group. In contrast, astrocytes were more activated in the asymmetric group than in the symmetric group (p<0.05). Glucose transporter-1, and monocarboxylate transporter-1 were also upregulated in the asymmetric group, compared with the symmetric group (p<0.05, respectively). These results suggest that the increased FDG uptake was associated with relatively severe ischemia, and glucose transporter-1 upregulation and astrocyte activation. Glucose metabolism may thus be a compensatory mechanism in the moderately severe ischemic brain.