Radiological safety assessment for transportation of reactor pressure vessel during decommissioning of a nuclear power plant in Korea.

In Korea, decommissioning of nuclear power plants and transportation of the decommissioning waste are expected to expand in the near future. It is necessary to confirm that radiological risks to the public and workers are not significant through radiological safety assessment. The objective of this study is to assess the radiological safety for transportation of RPV waste, which is a major decommissioning waste with relatively high level of radioactivity. It was assumed that the waste would be transported to the Gyeongju disposal facility by land transportation. First, the source term and transportation method of the RPV waste were determined, and the external dose rates from the waste were calculated using MCNP. Then, transportation scenarios were assumed under both normal and accident conditions. Under the scenarios, radiation doses were calculated using the RADTRAN. Under normal operation scenarios without a transportation accident, assuming 40 shipments per year, the average individual doses for the public ranged from 6.56×10-6to 2.18×10-2mSv yr-1. The maximum individual doses for only a single shipment ranged from 2.43×10-6to 3.14×10-1mSv. For cargo handlers and vehicle crew members, the average doses were 2.26×101mSv yr-1and 2.95 mSv yr-1, respectively. Under transportation accident scenarios, average individual radiological risks which are product of the radiation doses and the annual accident rates ranged from 1.14×10-11to 1.61×10-10mSv yr-1by transportation route segment when considering the transportation accident rate. Average individual doses assuming transportation accident occurrence ranged from 2.62×10-4to 1.42×10-3mSv. The maximum individual dose under accident conditions was 7.99×10-2mSv. The calculated doses were below the regulatory limits in Korea. However, relatively high doses were observed for cargo handlers and vehicle crew members because of conservative assumptions. This study results can be used as basic data for the radiological safety assessment for the decommissioning waste transportation in the future.

Completion rate of physician orders for life-sustaining treatment for patients with metastatic or recurrent cancer: a preliminary, cross-sectional study.

BACKGROUND: "End of life" is a difficult topic of conversation in East Asian cultures, even among patients and doctors who share a good rapport. In 2016, the Hospice, Palliative Care, and Life-Sustaining Treatment Decision-Making Act, which took the form of "Physician Orders for Life-Sustaining Treatment," was introduced in South Korea. This study was conducted to investigate the completion rate of Physician Orders for Life-Sustaining Treatment in patients with advanced cancer on the active recommendation of physicians, as well as patients' general attitudes toward end-of-life care. METHODS: We conducted a preliminary, cross-sectional descriptive survey on patients with advanced cancer. A total of 101 patients with advanced solid cancer agreed to participate in the study. The primary endpoint was the rate of completion of Physician Orders for Life-Sustaining Treatment based on a doctor's suggestion. Written interviews were conducted to understand the perceptions and factors influencing patients' decisions. RESULTS: Of the 101 patients, 72 (71.3%) agreed to prepare Physician Orders for Life-Sustaining Treatment. Patients who had an educational level of high school or higher were more likely to agree to complete Physician Orders for Life-Sustaining Treatment documentation as compared to the lower educational status group. More than half of the respondents who completed Physician Orders for Life-Sustaining Treatment documentation reported that they had more than a fair understanding of "life-sustaining care" or "Physician Orders for Life-Sustaining Treatment." Participants' reasons for Physician Orders for Life-Sustaining Treatment completion were diverse. CONCLUSIONS: We found that highly educated patients, who understood the concept behind the policy well, tended to accept Physician Orders for Life-Sustaining Treatment without hesitation. Better education, information shared through the media, and conversations with health care providers might improve understanding of Physician Orders for Life-Sustaining Treatment in patients with cancer.

Multicenter, cross-sectional observational study of the impact of neuropathic pain on quality of life in cancer patients.

PURPOSE: Neuropathic cancer pain (NCP) is a common and potentially debilitating symptom in cancer patients. We investigated the prevalence of NCP, as well as its management and association with QOL. METHODS: Cancer patients with pain ≥1 on the visual analogue scale (VAS) were surveyed with the Douleur Neuropathique (DN4) questionnaire, the Brief Pain Inventory-Short Form (BPI-SF), and the EuroQOL five dimensions (EQ-5D) questionnaire. The associations between NCP and pain severity or NCP and QOL, while controlling for variables relevant to QOL, were then analyzed. RESULTS: A total of 2003 patients were enrolled in this survey; the prevalence of NCP was 36.0% (n = 722, 95% CI, 32.5-39.5). We found that NCP in cancer patients was closely correlated to a higher pain severity (BPI-SF; 4.96 ± 1.94 versus 4.24 ± 2.02, p < 0.001), and in patients with NCP, pain more severely interfered with daily living, as compared to those without NCP (BPI-SF; 4.86 ± 2.71 versus 4.41 ± 2.87, p < 0.001). Patients with NCP also had worse QOL than those without NCP, as measured by EQ-5D index score (0.47 ± 0.30 vs. 0.51 ± 0.30, p = 0.005), and this was confirmed using multivariate analysis (p < 0.001), even after controlling for other variables such as age, sex, disease stage, cancer duration, radiotherapy, chemotherapy, and comorbidities. Importantly, adjuvant analgesics were used in less than half of patients with NCP (n = 358, 46.4%). CONCLUSIONS: We found that NCP in cancer patients was significantly associated with a worsened QOL, and current management is inadequate. Therefore, future research aimed at developing improved strategies for management of NCP is required.

Red meat and chicken consumption and its association with high blood pressure and obesity in South Korean children and adolescents: a cross-sectional analysis of KSHES, 2011-2015.

BACKGROUND: The impact of meat consumption on high blood pressure (HBP) and obesity in children and adolescents is a subject of debate. The aim of this study was thus to evaluate the association between meat consumption and both HBP and obesity in this group. METHODS: We performed a cross-sectional analysis using nationally representative samples of children and adolescents aged 9, 12, and 15 years old (n = 136,739) who were included in the Korea School Health Examination Survey (KSHES) for the 2011-2015 period. Multiple linear and logistic regression analysis was used to determine the factors influencing systolic blood pressure (SBP), diastolic blood pressure (DBP), and body mass index (BMI, kg/m2) levels, and to test the strength of these relationships. RESULTS: Adjusted for covariates, 6.3% of those subjects who consumed >5 servings of meat (including beef, pork, and chicken) per week were obese, compared with 9.1% of the subjects who consumed <1 serving of meat/wk (obesity adjusted odds ratio [OR]: 1.44; 95% confidence interval [CI]: 1.21-1.70; P ≤0.001). Those who consumed <1 serving of meat/wk had an HBP prevalence of 8.2%, compared with 7.2% for subjects who consumed >5 servings of meat/wk (systolic HBP adjusted OR: 1.30; 95% CI: 1.05-1.62; P ≤0.01, diastolic HBP adjusted OR: 1.25; 95% CI: 1.02-1.54; P <0.05). Obese subjects were estimated to have a higher SBP (ß = 7.497, P < 0.001) and DBP (ß = 4.123, P <0.001) than subjects who had no excess weight. Compared to subjects who consumed >5 servings of meat/wk, those who consumed <3 servings of meat/wk had a higher SBP (ß = 0.574, P <0.001) and DBP (ß = 0.376, P = 0.003) after adjusting for BMI. The intake of milk, fruit, and vegetables was not associated with either SBP or DBP (P >0.05). In contrast, BMI was significantly associated with milk, fruits, and vegetables (P <0.01). CONCLUSIONS: Among children and adolescents, a higher level of meat consumption was associated with lower SBP, DBP, and BMI, and greater height, suggesting that consuming an appropriate amount of meat is important for healthy growth at a young age.

Incidence and Predictors of Febrile Neutropenia among Early-Stage Breast Cancer Patients Receiving Anthracycline-Based Chemotherapy in Korea.

OBJECTIVE: This retrospective study was undertaken to assess the incidence of and risk factors for febrile neutropenia (FN) during adjuvant chemotherapy for early-stage breast cancer (ESBC). METHODS: A multicenter survey of three tertiary hospitals was conducted, with data extracted from the records of ESBC patients treated with adjuvant chemotherapy containing AC (doxorubicin, 60 mg/m2 and cyclophosphamide, 600 mg/m2 every 21 days). Assessments included clinical characteristics, chemotherapy dose modifications, and incidence of FN. RESULTS: A total of 610 patients were included for analysis. The incidence of grade 4 neutropenia and FN was 44.6 and 8.5%, respectively. Reduced relative dose intensity (RDI) less than 85% occurred in 11.0% of patients, and there were treatment delays in 12.6% of patients. Multivariate analysis identified several independent predictors for FN, including the presence of grade 4 neutropenia and pretreatment calculated estimated glomerular filtration rate less than 60 ml/min. CONCLUSION: Patients with ESBC are at substantial risk for FN and reduced RDI when treated with adjuvant AC chemotherapy. Predictive models based on risk factors identified in this study should enable the selective application of supportive measures in an effort to deliver the full dose of chemotherapy.

A Prognostic Index to Identify Patients With Intrahepatic Cholangiocarcinoma Who Could Benefit From Gemcitabine Plus Cisplatin.

Biliary tract cancer is a heterogenous group. Gemcitabine plus cisplatin has been the standard chemotherapy for advanced biliary tract cancer, but there is lack of evidence on treatment in patients with intrahepatic cholangiocarcinoma (IHC). We analyzed 29 patients with only IHC who received gemcitabine plus cisplatin between June 2010 and February 2013. The median age was 63 years (range, 40-78 years), and Eastern Cooperative Oncology Group performance status of all patients was <2. The median progression-free survival and median overall survival (OS) were 4.3 and 7.3 months, respectively. Multivariate analysis showed that platelet count (≤180 × 10 per liter), metastatic site of more than 2, and albumin level (≤3.5 g/dL) were independent prognostic factors for decreased OS. OS was estimated based on the number of adverse prognostic factors: zero or 1 (good prognostic group), 2 (intermediate group), or 3 (poor prognostic group). The median OS for good (n = 15), intermediate (n = 10), and poor (n = 4) prognostic group was 10.5, 6.1, and 1.6 months, respectively (P < 0.005). Relatively better prognosis of the good prognosis group comparing to other prognosis groups can be expected from the prognostic model established in this study by analyzing patients with IHC treated with gemcitabine.

A Randomized, Multicenter, Phase II Study of Cetuximab With Docetaxel and Cisplatin as Induction Chemotherapy in Unresectable, Locally Advanced Head and Neck Cancer.

BACKGROUND: We investigated the efficacy of cetuximab when added to induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) in patients with locally advanced head and neck squamous cell carcinoma. METHODS: Patients were randomized to receive three cycles of docetaxel and cisplatin (TP regimen) with or without cetuximab (TP plus cetuximab [CTP] vs. TP) as induction chemotherapy. Patients in the CTP arm received CCRT with cetuximab and cisplatin, whereas patients in the TP arm received cisplatin alone. The primary endpoint was the objective response rate (ORR) after induction chemotherapy. RESULTS: Overall, 92 patients were enrolled. The ORRs for induction chemotherapy in the CTP and TP arms were not different (81% vs. 82%). Adding cetuximab lowered the completion rate of induction chemotherapy and CCRT and resulted in more frequent dose reductions of the induction chemotherapy, although this did not reach statistical significance. In the CTP and TP arms, respectively, the 3-year progression-free survival (PFS) rates were 70% and 56% (p = .359), and the overall survival (OS) rates were 88% and 74% (p = .313). When limited to patients who completed induction chemotherapy, 3-year PFS rates of 78% and 59% (p = .085) and OS rates of 94% and 73% (p = .045) were observed in the CTP and TP arms, respectively. CONCLUSION: Adding cetuximab to sequential treatment did not increase the treatment efficacy and resulted in greater toxicity. In the intent-to-treat population, neither PFS nor OS was improved by the addition of cetuximab to sequential treatment; however, a suggestion of improved survival outcomes was observed in patients completing cetuximab-containing induction chemotherapy.

Ramosetron Versus Ondansetron in Combination With Aprepitant and Dexamethasone for the Prevention of Highly Emetogenic Chemotherapy-Induced Nausea and Vomiting: A Multicenter, Randomized Phase III Trial, KCSG PC10-21.

BACKGROUND: A combination of serotonin receptor (5-hydroxytryptamine receptor type 3) antagonists, NK-1 receptor antagonist, and steroid improves the complete response (CR) of chemotherapy-induced nausea and vomiting (CINV) in cancer patients. Ramosetron's efficacy in this triple combination regimen has not been investigated. This prospective, multicenter, single-blind, randomized, phase III study compares a combination of ramosetron, aprepitant, and dexamethasone (RAD) with a combination of ondansetron, aprepitant, and dexamethasone (OAD) to prove the noninferiority of RAD in controlling highly emetogenic CINV. METHODS: Aprepitant and dexamethasone were orally administered for both arms. Ramosetron and ondansetron were intravenously given to the RAD and OAD groups. The primary endpoint was no vomiting and retching and no need for rescue medication during the acute period (day 1); the noninferiority margin was -15%. RESULTS: A total of 299 modified intention-to-treat cancer patients who received RAD (144 patients) and OAD (155 patients) were eligible for the efficacy analysis. The CR rates of RAD versus OAD were 97.2% versus 93.6% during the acute period, 77.8% versus 73.6% during the delayed period (day 2-5), and 77.1% versus 71.6% during the overall period. Furthermore, RAD was noninferior to OAD in subgroups stratified by age, cancer type, chemotherapeutic agents, and schedule. Repeated measures analysis showed that in male patients, RAD was superior to OAD. Profiles of adverse events were similar in both groups. CONCLUSION: RAD is as effective and tolerable as OAD for CINV prevention in patients receiving highly emetogenic chemotherapy. Ramosetron could be considered one of the best partners for aprepitant.

Predictors of mortality attributable to Clostridium difficile infection in patients with underlying malignancy.

PURPOSE: This study aimed at evaluating the clinical severity and treatment outcomes of Clostridium difficile infections (CDI) and identifying predictors associated with mortality in patients with malignancy. METHODS: A retrospective study was conducted in a teaching hospital from January 2004 to June 2013. The subjects included adult patients (aged ≥ 18 years) receiving treatment for malignancy whose conditions were complicated by CDI. Clinical severity was determined using the guidelines from the Society for Healthcare Epidemiology of America and the Infectious Diseases Society of America (SHEA/IDSA). Multivariate logistic regression analysis was performed to identify predictors independently associated with CDI-related mortality. RESULTS: Of the 5,594 patients treated for malignancy at the Division of Hematology/Oncology during the study period, 61 (1.1%) had CDI complications. CDI-related mortality was 19.7% (12/61). Twenty-seven (44.3%) patients were diagnosed with neutropenia (ANC ≤ 500/mm(3)) at initial CDI presentation. Forty-one patients (67.2%) received antimicrobial therapy for CDI. Based on the SHEA/IDSA guidelines, only 12 patients (19.7%) presented with severe CDI, but 25 (61.0%) patients experienced treatment failure. Multiple logistic regression modeling showed neutropenia to be an independent risk factor for CDI-related mortality (odds ratio, 5.17; 95% confidence interval, 1.24-21.59). CONCLUSIONS: This study tracked poor CDI treatment outcomes in patients with malignancy and identified neutropenia as a previously unrecognized risk factor of CDI-related mortality. Alternative definitions of severe CDI that include neutropenia might be necessary to more accurately determine clinical severity.

Pediatric Finger Warts Treated Using Taeeumjowi-tang: a case report.

Warts caused by the human papillomavirus (HPV) are generally treated with cryotherapy, CO2 laser ablation, interferon injections, and bleomycin injections. However, it is sometimes difficult to treat children because the treatment can be painful. In addition, recurrence may occur after treatment. In this study, warts completely disappeared following the administration of herbal medicine in two children, with warts in multiple parts of the hands and around the nails. Two pediatric patients visited the hospital for treatment of warts around their fingers and nails. Both patients received Taeeumjowi-tang (TJT) as a decoction for 60 days. TJT was performed twice per day for the 11-year-old patient and once per day for the 7-year-old patient. Patient progress was observed monthly, and the visual condition of the warts was photographed during the visits. After approximately two months of treatment, the warts disappeared from the fingers and nails of both patients. This case study suggests that the oral administration of TJT may be effective for pediatric patients with warts. Further studies are required to determine the efficacy and safety of these therapies.

Lazertinib versus Gefitinib as First-Line Treatment for EGFR-mutated Locally Advanced or Metastatic NSCLC: LASER301 Korean Subset.

PURPOSE: This subgroup analysis of the Korean subset of patients in the phase 3 LASER301 trial evaluated the efficacy and safety of lazertinib versus gefitinib as first-line therapy for epidermal growth factor receptor mutated (EGFRm) non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Patients with locally advanced or metastatic EGFRm NSCLC were randomized 1:1 to lazertinib (240 mg/day) or gefitinib (250 mg/day). The primary endpoint was investigator-assessed progression-free survival (PFS). RESULTS: In total, 172 Korean patients were enrolled (lazertinib, n=87; gefitinib, n=85). Baseline characteristics were balanced between the treatment groups. One-third of patients had brain metastases (BM) at baseline. Median PFS was 20.8 months (95% confidence interval [CI], 16.7 to 26.1) for lazertinib and 9.6 months (95% CI, 8.2 to 12.3) for gefitinib (hazard ratio [HR], 0.41; 95% CI, 0.28 to 0.60). This was supported by PFS analysis based on blinded independent central review. Significant PFS benefit with lazertinib was consistently observed across predefined subgroups, including patients with BM (HR, 0.28; 95% CI, 0.15 to 0.53) and those with L858R mutations (HR, 0.36; 95% CI, 0.20 to 0.63). Lazertinib safety data were consistent with its previously reported safety profile. Common adverse events (AEs) in both groups included rash, pruritus, and diarrhoea. Numerically fewer severe AEs and severe treatment-related AEs occurred with lazertinib than gefitinib. CONCLUSION: Consistent with results for the overall LASER301 population, this analysis showed significant PFS benefit with lazertinib versus gefitinib with comparable safety in Korean patients with untreated EGFRm NSCLC, supporting lazertinib as a new potential treatment option for this patient population.

Randomized Trial of Tepotinib Plus Gefitinib versus Chemotherapy in EGFR-Mutant NSCLC with EGFR Inhibitor Resistance Due to MET Amplification: INSIGHT Final Analysis.

PURPOSE: The final analyses of the INSIGHT phase II study evaluating tepotinib (a selective MET inhibitor) plus gefitinib versus chemotherapy in patients with MET-altered EGFR-mutant NSCLC (data cut-off: September 3, 2021). PATIENTS AND METHODS: Adults with advanced/metastatic EGFR-mutant NSCLC, acquired resistance to first-/second-generation EGFR inhibitors, and MET gene copy number (GCN) ≥5, MET:CEP7 ≥2, or MET IHC 2+/3+ were randomized to tepotinib 500 mg (450 mg active moiety) plus gefitinib 250 mg once daily, or chemotherapy. Primary endpoint was investigator-assessed progression-free survival (PFS). MET-amplified subgroup analysis was preplanned. RESULTS: Overall (N = 55), median PFS was 4.9 months versus 4.4 months [stratified HR, 0.67; 90% CI, 0.35-1.28] with tepotinib plus gefitinib versus chemotherapy. In 19 patients with MET amplification (median age 60.4 years; 68.4% never-smokers; median GCN 8.8; median MET/CEP7 2.8; 89.5% with MET IHC 3+), tepotinib plus gefitinib improved PFS (HR, 0.13; 90% CI, 0.04-0.43) and overall survival (OS; HR, 0.10; 90% CI, 0.02-0.36) versus chemotherapy. Objective response rate was 66.7% with tepotinib plus gefitinib versus 42.9% with chemotherapy; median duration of response was 19.9 months versus 2.8 months. Median duration of tepotinib plus gefitinib was 11.3 months (range, 1.1-56.5), with treatment >1 year in six (50.0%) and >4 years in three patients (25.0%). Seven patients (58.3%) had treatment-related grade ≥3 adverse events with tepotinib plus gefitinib and five (71.4%) had chemotherapy. CONCLUSIONS: Final analysis of INSIGHT suggests improved PFS and OS with tepotinib plus gefitinib versus chemotherapy in a subgroup of patients with MET-amplified EGFR-mutant NSCLC, after progression on EGFR inhibitors.

Varicella zoster virus infection during chemotherapy in solid cancer patients.

BACKGROUND: Varicella zoster virus (VZV) infection is a representative opportunistic infection in patients with hematological malignancies, with a high incidence of 30-50%. Many studies on the risk factors of VZV infection in this patient group have been conducted. However, few data have been reported exploring VZV infection during systemic chemotherapy in solid cancer patients. PATIENTS AND METHODS: We retrospectively analyzed 92 patients diagnosed with VZV infection between April 2001 and July 2010 during systemic chemotherapy for solid tumors. All patients had received antiviral prophylaxis for VZV. RESULTS: The median age at the time of diagnosis of VZV infection was 60.8 years (range 30.1-83.0) and the majority of patients (79.3%) did not have comorbidities. Eighty-one patients (88%) received chemotherapy for locally advanced or metastatic/recurrent disease and 11 (12.0%) had adjuvant chemotherapy after curative resection. Of 92 patients, 14 (15.2%) had non-small cell lung cancer and 10 (10.9%) breast cancer. All patients had a median of 2 metastatic lesions (range 0-4). At the time of diagnosis, 55 patients (59.8%) were receiving first-line chemotherapy and 15 (16.3%) more than third-line chemotherapy. The mean white blood cell, platelet and albumin level was 5,736/µl, 205.7 × 10(3) and 3.8 mg/dl, respectively. On analysis for disease evaluation at the time nearest to diagnosis of VZV infection, only 14 patients (15.2%) revealed tumor response to chemotherapy. After the diagnosis of VZV infection, all patients were treated with antiviral agents. None of the patients experienced failure of therapy for VZV. CONCLUSION: We reported VZV infection during systemic chemotherapy in solid cancer patients. Patients may have a relatively poor tumor response to chemotherapy at the time nearest to diagnosis of VZV infection. A prospective or matched controlled trial is needed to confirm this finding.

How does inhibition of the renin-angiotensin system affect the prognosis of advanced gastric cancer patients receiving platinum-based chemotherapy?.

BACKGROUND: The renin-angiotensin system (RAS) is related to the regulation of cell proliferation, angiogenesis, and tumor progression. PATIENTS AND METHODS: We retrospectively analyzed the effect of angiotensin I-converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs) in 63 patients with advanced gastric cancer (AGC) with platinum-based chemotherapy. All patients analyzed had received medications for hypertension at the diagnosis of AGC. Patients were divided into two groups: an ACEI/ARB group (n = 30) and a non-ACEI/ARB group (n = 33). RESULTS: Patient characteristics were not different between patients with and without ACEI/ARB. The response rate for all patients was 25.4% and the disease control rate was 77.8%. The median progression-free survival (PFS) for first-line chemotherapy was 5.5 months (95% CI 3.71-7.29) in the ACEI/ARB group and 4.3 months (95% CI 2.39-6.21) in the non-ACEI/ARB group (p = 0.506). There was a significant difference in overall survival (OS) in the ACEI/ARB group compared to the non-ACEI/ARB group (median OS: 8.2 vs. 13.9, p = 0.0095). In multivariate analysis, the use of ACEI/ARB was a significant independent prognostic factor for OS (p = 0.039) but not for PFS. CONCLUSION: ACEI/ARB in combination with standard chemotherapy might improve survival in patients with AGC and hypertension. These results support further investigation into the anticancer effects of ACEL/ARB.

Comparison of the Data of a Next-Generation Sequencing Panel from K-MASTER Project with That of Orthogonal Methods for Detecting Targetable Genetic Alterations.

PURPOSE: K-MASTER project is a Korean national precision medicine platform that screened actionable mutations by analyzing next-generation sequencing (NGS) of solid tumor patients. We compared gene analyses between NGS panel from the K-MASTER project and orthogonal methods. MATERIALS AND METHODS: Colorectal, breast, non-small cell lung, and gastric cancer patients were included. We compared NGS results from K-MASTER projects with those of non-NGS orthogonal methods (KRAS, NRAS, and BRAF mutations in colorectal cancer [CRC]; epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK] fusion, and reactive oxygen species 1 [ROS1] fusion in non-small cell lung cancer [NSCLC], and Erb-B2 receptor tyrosine kinase 2 (ERBB2) positivity in breast and gastric cancers). RESULTS: In the CRC cohort (n=225), the sensitivity and specificity of NGS were 87.4% and 79.3% (KRAS); 88.9% and 98.9% (NRAS); and 77.8% and 100.0% (BRAF), respectively. In the NSCLC cohort (n=109), the sensitivity and specificity of NGS for EGFR were 86.2% and 97.5%, respectively. The concordance rate for ALK fusion was 100%, but ROS1 fusion was positive in only one of three cases that were positive in orthogonal tests. In the breast cancer cohort (n=260), ERBB2 amplification was detected in 45 by NGS. Compared with orthogonal methods that integrated immunohistochemistry and in situ hybridization, sensitivity and specificity were 53.7% and 99.4%, respectively. In the gastric cancer cohort (n=64), ERBB2 amplification was detected in six by NGS. Compared with orthogonal methods, sensitivity and specificity were 62.5% and 98.2%, respectively. CONCLUSION: The results of the K-MASTER NGS panel and orthogonal methods showed a different degree of agreement for each genetic alteration, but generally showed a high agreement rate.

Epidermal growth factor receptor mutations as a prognostic factor in Korean patients with advanced lung adenocarcinoma who had not been treated with received epidermal growth factor receptor tyrosine kinase inhibitors.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations as prognostic marker in patients with non-small cell lung cancers remain controversial. In particular, there is only a limited amount of data on the subject in Asian patients with advanced lung adenocarcinomas. PATIENTS AND METHODS: We analyzed 50 patients with advanced lung adenocarcinoma, who received best supportive care with and without cytotoxic chemotherapy, between March 2006 and December 2008. The patients had never been treated with EGFR tyrosine kinase inhibitors. Tumor tissues of all 50 patients were analyzed for the status of EGFR gene mutations. RESULTS: The median age of patients was 64 years (range 32-84) at diagnosis, and the male/female ratio was 2.6/1.0. Thirty-two patients were current or ever smokers. EGFR gene mutations were detected in 11 patients (22%). Seven of them had in-frame deletion within exon 19, resulting in the loss of codon 746 through 750 (delE746-A750), 2 patients had L858R in exon 21, and 2 patients had point mutation at codon 709 in exon 18, resulting in the substitution of glycine either with glutamic acid or alanine. The status of EGFR mutations was not significantly associated with gender, smoking status, ages, metastatic sites and number of metastasized sites. Seventeen patients received best supportive care without cytotoxic chemotherapy and 33 patients received the standard platinum-based doublet chemotherapy. The median overall survival was 8.90 months (95% CI 4.01-13.79). There were no significant differences in overall survival (p = 0.282) according to the status of EGFR mutations. CONCLUSION: These results suggest that EGFR mutation is not a prognostic marker in Korean patients with advanced lung adenocarcinoma who had not been treated with EGFR tyrosine kinase inhibitors.

Development and Validation of Targeted Gene Sequencing Panel Based Companion Diagnostic for Korean Patients with Solid Tumors.

Recently, several panels using two representative targeting methods have been developed but they do not reflect racial specificity, especially for Asians. We have developed and analytically validated the Korean Pan-cancer Companion Diagnostic (CDX) Panel to apply targeted anticancer drugs to Korean patients based on the molecular characteristics of tumors using tumor samples without matched patient normal samples. The panel included 31 genes with reported single nucleotide variants, 9 genes with reported copy number variations, and 15 genes with predictive responses to targeted drugs under clinical testing, enabling the panel to be analyzed for the targets of 30 targeted anticancer drugs. It is cost-effective and optimized for cancer type-specific therapy in Korean cancer patients across solid cancer types while minimizing the limitations of existing approaches. In addition, the optimized filtering protocol for somatic variants from tumor-only samples enables researchers to use this panel without matched normal samples. To verify the panel, 241 frozen tumor tissues and 71 formalin-fixed paraffin-embedded (FFPE) samples from several institutes were registered. This gene screening method is expected to reduce test turnaround time and cost, making it a balanced approach to investigate solid cancer-related gene regions.

Significance of descriptive symptoms and signs and clinical parameters as predictors of neuropathic cancer pain.

PURPOSE: Evaluation of symptoms and signs for the management of neuropathic cancer pain (NCP) is challenging. This study aimed to identify clinical predictors of NCP and symptoms and signs most relevant of those in Korean patients. METHODS: This nationwide, descriptive, cross-sectional, multicenter, observational study included 2,003 cancer patients aged ≥20 years who reported a visual analog scale (VAS) score ≥1 for pain and provided informed consent for participation. The Douleur Neuropathic (DN4) questionnaire (score ≥4) was used to determine symptoms and signs as well as the presence of NCP. RESULTS: The prevalence of NCP was associated with age <65 years [OR, 1.57; 95% CI, 1.270-1.934], disease duration >6 months (OR, 1.57; 95% CI, 1.232-2.012), stage IV cancer (OR, 0.75; 95% CI, 0.593-0.955), history of chemotherapy (OR, 1.74; 95% CI, 1.225-2.472), and moderate-to-severe cancer pain (OR, 2.05; 95% CI, 1.671-2.524) after multivariate analysis. The most common descriptive symptoms of NCP were tingling, electric shock, and pins and needles. For NCP patients in the presence or absence of the clinical predictors, pins and needles (p = 0.001) and painful cold (p<0.001) symptoms were significantly frequent in patients with moderate-to-severe pain. Tingling, numbness, and touch hypoesthesia (p = 0.022, 0.033, 0.024, respectively) were more frequent in those with longer cancer duration and hyperesthesia (p = 0.024) was more frequent in young patients. CONCLUSION: Age <65 years, disease duration >6 months, stage IV cancer, history of chemotherapy, and moderate-to-severe cancer pain, were identified as predictors of NCP. Some symptoms and signs of NCP were associated with these predictors. Further studies are warranted on the pathogenesis and management of NCP with respect to the symptoms and signs, and factors associated with pain severity in Korean patients.