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Background: Immune checkpoint inhibitor (ICI) or irinotecan-based chemotherapy is frequently used after failure of second-line paclitaxel plus ramucirumab treatment for patients with locally advanced unresectable or metastatic advanced gastric cancer (AGC). This study aimed to compare the efficacy between ICI and irinotecan-based chemotherapy as third-line treatment in patients with AGC., Methods: We retrospectively reviewed patients with AGC, whose third-line treatment started between July 2019 and June 2021 at 17 institutions in Korea. The ICI group included patients who received nivolumab or pembrolizumab, and the irinotecan-based chemotherapy group included patients who received irinotecan or FOLFIRI (5-fluorouracil, leucovorin and irinotecan)., Results: A total of 363 patients [n = 129 (ICI) and n = 234 (irinotecan-based chemotherapy)] were analyzed. The median progression-free survival was 2.3 and 2.9 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.802). The median overall survival (OS) was 5.5 and 6.0 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.786). For all patients included in this study, multivariable analysis showed that weight loss, peritoneal metastasis, low serum sodium or albumin, and short duration of second-line treatment were associated with inferior OS (p < 0.05). ICI showed significantly longer OS than irinotecan-based chemotherapy in patients without peritoneal metastasis. Whereas ICI showed significantly shorter OS in patients without PD-L1 expression than irinotecan-based chemotherapy., Conclusions: No significant difference in survival outcome was observed between ICI and irinotecan-based chemotherapy as third-line treatment for AGC patients. ICI might be preferred for patients without peritoneal metastasis and irinotecan-based chemotherapy for patients with tumors without PD-L1 expression., Trial Registration: This study was registered in the Clinical Trial Registry of Korea ( https://cris.nih.go.kr : KCT 0007732)., (© 2024. The Author(s).)

Purpose: Adolescents and young adults (AYAs) with cancer have special care needs that are different from those of children and older adults with cancer. This study assessed the perspective and experience of AYAs with cancer in South Korea to identify their care needs. Methods: This study used a convergent mixed-methods design. From July 2020 to November 2021, AYAs with cancer ( N  = 77; 15-39 years of age) participated in a quantitative cross-sectional study, using a tool developed by our study team. In May 2021, a qualitative focus group was conducted with 10 AYAs with cancer. Integrated analyses were conducted concurrently by reporting the quantitative and qualitative findings together. Results: Quantitative findings revealed that the highest care need domains were communication and information, whereas the highest care priority item was the management of pain and symptoms occurring during the treatment. Qualitative findings revealed 12 themes across 5 domains. Comparing and merging of the quantitative and qualitative data resulted in eight confirmed themes and four expanded findings, including knowing people who overcame similar illnesses, fear of death, dedicated space, and a program for AYAs with cancer. Conclusion: When developing and implementing programs and health care services, especially in countries with no established program or cancer specialty unit for AYAs with cancer, it is important to consider the special care needs and priorities of AYAs with cancer. This mixed methods study provided empirical evidence to help understand and prioritize the needs of AYAs with cancer undergoing active treatment in South Korea.

Purpose: An increasing number of patients with cancers are interested in complementary and alternative medicine (CAM), which lacks scientific evidence. This study aimed to determine how CAM was used and how media affected patients in online cancer support groups (OCSG)., Materials and Methods: Between August 18 and September 12, 2021, an online survey was conducted among the members of OCSG. The survey consisted of five parts: baseline characteristics, attitudes toward and experience with CAM, source of information and reliabilities, experience with anthelmintics, and online health information literacy and usage., Results: Among the 644 responders, a total of 221 patients with cancer completed the survey, and 78.2% (173/221) used CAM. The users' median age was 52 years; 46.8% were males, and 43.9% had metastatic disease. Fifty-three CAM users (30.6%) discussed their physicians about CAM. In addition, 16.2% (28/173) of CAM users had the experience of anthelmintics. The use of anthelmintics in patients with cancers was associated with younger age (odds ratio [OR], 0.89; 95% confidence interval [CI], 0.84 to 0.95), metastatic disease (OR, 10.88; 95% CI, 3.39 to 34.86), previous exposure to CAM information (OR, 5.57; 95% CI, 1.01 to 30.72), experience with more types of CAM (OR, 1.98; 95% CI, 1.29 to 3.05), and side effects (OR, 5.10; 95% CI 1.46 to 17.75)., Conclusion: Use of anthelmintics, a CAM of which information is widespread online, is affected by several factors. This study will provide essential information for developing a CAM management strategy in this digital age.

Objective: Previous studies have comprehensively investigated the prevalence and various potential risk factors for delirium among patients with advanced cancer admitted to the acute palliative care unit (APCU). Our objective was to evaluate the comprehensive association between delirium and various risk factors among patients with advanced cancer in an acute palliative care setting using a patient-based multicenter registry cohort., Patients and Methods: We performed a multicenter, patient-based registry cohort study collected in South Korea between January 1, 2019, and December 31, 2020. Delirium was identified using a medical record review based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition., Results: In total, 2,124 eligible patients with advanced cancer in the APCU met the inclusion criteria. There were 127 out of 2,124 patients (prevalence, 6.0%; 95% CI, 5.0 to 7.1) with delirium during admission. Delirium in patients with advanced cancer was associated with age >70 years (OR, 1.793; 95% CI, 1.246 to 2.581), male sex (OR, 1.675; 95% CI, 1.131 to 2.479), no chemotherapy during hospitalization (OR, 2.019; 95% CI, 1.236 to 3.298), hearing impairment (OR, 3.566; 95% CI, 1.176 to 10.810), underweight (OR, 1.826; 95% CI, 1.067 to 3.124), current use of opioid medication (OR, 1.942; 95% CI, 1.264 to 2.982), previous history of delirium (OR, 12.497; 95% CI, 6.920 to 22.568), and mental illness (OR, 2.333; 95% CI, 1.251 to 4.352)., Conclusions: In a large-scale multicenter patient-based registry cohort, delirium was associated with old age, male sex, no chemotherapy during hospitalization, hearing impairment, underweight, current use of opioid medication, and a history of delirium and mental illness. Our findings suggest physicians should pay attention to delirium in patients with advanced cancer admitted to the APCU with the above risk factors.

Background: A subgroup analysis of data from a nationwide study (KCSG-ST19-16) was performed to evaluate the efficacy and safety of second-line ramucirumab plus paclitaxel treatment in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric or gastro-esophageal junction (GEJ) adenocarcinoma., Methods: The KCSG-ST19-16 study enrolled a total of 1063 patients from 56 hospitals in South Korea with advanced gastric or GEJ adenocarcinoma, who had received second-line treatment with ramucirumab plus paclitaxel. HER2 status was known for 994 (93.5%) of these patients, who were thus included in the subgroup analysis., Results: In total, 163 of 994 patients (16.4%), had HER2-positive gastric or GEJ adenocarcinoma. The objective response rate to ramucirumab plus paclitaxel treatment was significantly higher in patients with HER2-positive disease compared to those with HER2-negative disease (23.0% [95% confidence interval (CI), 15.9-30.1] vs. 15.1% [95% CI, 12.3-17.9], p = 0.025). The median progression-free survival was longer in patients with HER2-positive versus HER2-negative disease, but the difference was not statistically significant (4.3 months [95% CI, 3.7-5.3] vs 3.7 months [95% CI, 3.4-4.0], p = 0.054). There was no statistically significant difference in median overall survival (OS) between the groups (9.8 months [95% CI, 8.9-12.3] vs 10.1 months [95% CI, 9.2-10.9], p = 0.564)., Conclusions: In patients with HER2-positive gastric or GEJ adenocarcinoma, the objective response rate to second-line treatment with ramucirumab plus paclitaxel was significantly higher compared to patients with HER2-negative disease. However, an increased response to treatment was not associated with an improvement in OS., (© 2022. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Purpose: Adjuvant chemotherapy after D2 gastrectomy is standard for resectable locally advanced gastric cancer (LAGC) in Asia. Based on positive findings for perioperative chemotherapy in European phase III studies, the phase III PRODIGY study (ClinicalTrials.gov identifier: NCT01515748) investigated whether neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) followed by surgery and adjuvant S-1 could improve outcomes versus standard treatment in Korean patients with resectable LAGC., Patients and Methods: Patients 20-75 years of age, with Eastern Cooperative Oncology Group performance status 0-1, and with histologically confirmed primary gastric or gastroesophageal junction adenocarcinoma (clinical TNM staging: T2-3N+ or T4Nany) were randomly assigned to D2 surgery followed by adjuvant S-1 (40-60 mg orally twice a day, days 1-28 every 6 weeks for eight cycles; SC group) or neoadjuvant DOS (docetaxel 50 mg/m 2 , oxaliplatin 100 mg/m 2 intravenously day 1, S-1 40 mg/m 2 orally twice a day, days 1-14 every 3 weeks for three cycles) before D2 surgery, followed by adjuvant S-1 (CSC group). The primary objective was progression-free survival (PFS) with CSC versus SC. Two sensitivity analyses were performed: intent-to-treat and landmark PFS analysis., Results: Between January 18, 2012, and January 2, 2017, 266 patients were randomly assigned to CSC and 264 to SC at 18 Korean study sites; 238 and 246 patients, respectively, were treated (full analysis set). Follow-up was ongoing in 176 patients at data cutoff (January 21, 2019; median follow-up 38.6 months [interquartile range, 23.5-62.1]). CSC improved PFS versus SC (adjusted hazard ratio, 0.70; 95% CI, 0.52 to 0.95; stratified log-rank P = .023). Sensitivity analyses confirmed these findings. Treatments were well tolerated. Two grade 5 adverse events (febrile neutropenia and dyspnea) occurred during neoadjuvant treatment., Conclusion: PRODIGY showed that neoadjuvant DOS chemotherapy, as part of perioperative chemotherapy, is effective and tolerable in Korean patients with LAGC., Competing Interests: Yoon-Koo KangConsulting or Advisory Role: DAEHWA Pharmaceutical, Bristol-Myers Squibb, Zymeworks, ALX Oncology, Amgen, Novartis, MacroGenics, Surface Oncology Min-Hee RyuHonoraria: DAEHWA Pharmaceutical, Bristol-Myers Squibb, Lilly, Ono Pharmaceutical, MSD, Taiho Pharmaceutical, Novartis, Daiichi Sankyo, AstraZenecaConsulting or Advisory Role: DAEHWA Pharmaceutical, Bristol-Myers Squibb, Lilly, Ono Pharmaceutical, MSD, Taiho Pharmaceutical, Novartis, Daiichi Sankyo, AstraZeneca Sun Young RhaConsulting or Advisory Role: MSD Oncology, Ipsen, Daiichi Sankyo, Eisai, Amgen, IndivumedSpeakers' Bureau: Lilly, EisaiResearch Funding: MSD Oncology, Bristol-Myers Squibb, Eisai, Roche/Genentech, MedPacto, ASLAN Pharmaceuticals, SillaJen, Bayer, Immunomet Gyunji KimEmployment: Sanofi, NovartisStock and Other Ownership Interests: Sanofi YeonJu LeeEmployment: SanofiStock and Other Ownership Interests: Sanofi Jee Hyun LeeEmployment: SanofiNo other potential conflicts of interest were reported.

Objective: An unmet need exists for a non-invasive biomarker assay to aid gastric cancer diagnosis. We aimed to develop a serum microRNA (miRNA) panel for identifying patients with all stages of gastric cancer from a high-risk population., Design: We conducted a three-phase, multicentre study comprising 5248 subjects from Singapore and Korea. Biomarker discovery and verification phases were done through comprehensive serum miRNA profiling and multivariant analysis of 578 miRNA candidates in retrospective cohorts of 682 subjects. A clinical assay was developed and validated in a prospective cohort of 4566 symptomatic subjects who underwent endoscopy. Assay performance was confirmed with histological diagnosis and compared with Helicobacter pylori (HP) serology, serum pepsinogens (PGs), 'ABC' method, carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA19-9). Cost-effectiveness was analysed using a Markov decision model., Results: We developed a clinical assay for detection of gastric cancer based on a 12-miRNA biomarker panel. The 12-miRNA panel had area under the curve (AUC)=0.93 (95% CI 0.90 to 0.95) and AUC=0.92 (95% CI 0.88 to 0.96) in the discovery and verification cohorts, respectively. In the prospective study, overall sensitivity was 87.0% (95% CI 79.4% to 92.5%) at specificity of 68.4% (95% CI 67.0% to 69.8%). AUC was 0.848 (95% CI 0.81 to 0.88), higher than HP serology (0.635), PG 1/2 ratio (0.641), PG index (0.576), ABC method (0.647), CEA (0.576) and CA19-9 (0.595). The number needed to screen is 489 annually. It is cost-effective for mass screening relative to current practice (incremental cost-effectiveness ratio=US$44 531/quality-of-life year)., Conclusion: We developed and validated a serum 12-miRNA biomarker assay, which may be a cost-effective risk assessment for gastric cancer., Trial Registration Number: This study is registered with ClinicalTrials.gov (Registration number: NCT04329299)., Competing Interests: Competing interests: KGY, JBYS, WPY, HPT, LZ, RZ and FZ were coinventors in the patent application 'Serum MicroRNA Biomarker for the Diagnosis of Gastric Cancer'. HPT, LZ and RZ are founders and shareholders of MiRXES. LZ, RZ and YCT are employees of MiRXES. HCC received grants from Lilly, GSK, MSD. Merck-Serono, BMS-Ono, Taiho outside the submitted work. The rest of authors declare no competing interests., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The effect of long-term surveillance for asymptomatic patients after curative resection of gastric cancer is being debated. We compared the prognosis of Korean patients with recurrent gastric cancer according to the presence or absence of cancer-related symptoms at the time of recurrence detection., Methods: We retrospectively reviewed the medical records of 305 Korean patients who experienced recurrence after curative resection of primary gastric cancer between March 2002 and February 2017 at Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea., Results: The median follow-up duration was 169.8 months (1-267.2), and the median age at first recurrence was 58.1 years (23.4-81.9). Among 305 patients with recurrence, 97 of 231 (42.0%) patients with early recurrence (≤5 years after curative surgical resection) and 47 of 74 (63.5%) patients with late recurrence (>5 years after curative surgical resection) had cancer-related symptoms at recurrence (p = 0.001). For survival after recurrence, detection of asymptomatic recurrence was an independent favorable factor (hazard ratio, 0.527; 95% confidence interval, 0.409-0.681; p < 0.001) accompanied with the possibility of subsequent treatment, targeted-, or immunotherapy for recurrent disease, and locoregional recurrence only. In the late-recurrence group, the patients with asymptomatic detection of recurrence showed favorable post-recurrence survival (median, 33.3 months vs. 14.7 months; p = 0.002), overall survival (median, 136.3 months vs. 106.1 months; p = 0.010), and cancer-specific survival (median, 177.5 months vs. 106.1 months; p = 0.005) than the patients with symptomatic detection., Conclusion: The detection of gastric cancer recurrence in patients without cancer-related symptoms may be related to improved survival, suggesting the potential benefit of long-term surveillance., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

At the end of 2019, the cause of pneumonia outbreaks in Wuhan, China, was identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In February 2020, the World Health Organization named the disease cause by SARS-CoV-2 as coronavirus disease 2019 (COVID-19). In response to the pandemic, the Korean Cancer Association formed the COVID-19 task force to develop practice guidelines. This special article introduces the clinical practice guidelines for cancer patients which will help oncologists best manage cancer patients during the COVID-19 pandemic.

Purpose: Temsirolimus is effective in the treatment for metastatic non-clear cell renal cell carcinoma (nccRCC) with poor prognosis. We aim to investigate the efficacy and tolerability of temsirolimus in treatment of naïve Asian patients with metastatic/recurrent nccRCC., Materials and Methods: From January 2008 to July 2017, data of treatment-naïve, metastatic/recurrent nccRCC patients, who were treated with temsirolimus according to the standard protocol, were collected. The primary end-point was progression-free survival (PFS). Secondary end points were overall survival (OS), objective response rate (ORR), and tolerability of temsirolimus., Results: Forty-four metastatic/recurrent nccRCC patients, 10 from prospective and 34 from retrospective groups, were enrolled; 24 patients (54%) were papillary type, and other histology subtypes included 11 chromophobes (25%), two collecting ducts (5%), one Xp11.2 translocation (2%), and six others (14%). The median PFS and OS were 7.6 months and 17.6 months, res-pectively. ORR was 11% and disease control rate was 83%. Patients with prior nephrectomy had longer PFS (hazard ratio [HR], 0.16; 95% confidence interval [CI], 0.06 to 0.42; p < 0.001) and OS (HR, 0.15; 95% CI, 0.05 to 0.45; p < 0.001). Compared to favorable/intermediate prognosis group, poor prognosis group had shorter median PFS (4.7 months vs. 7.6 months [HR, 2.91; 95% CI, 1.39 to 6.12; p=0.005]) and median OS (9.2 months vs. 17.6 months [HR, 2.84; 95% CI, 1.23 to 6.56; p=0.015])., Conclusion: Temsirolimus not only benefits poor-risk nccRCC patients, but it is also effective in favorable or intermediate-risk group in Asians. Temsirolimus was well-tolerated with manageable adverse events.

Purpose: A soft tissue sarcoma (STS) is a rare type of cancer, accounting for 1% of adult solid cancers. The aim of the present study is to determine the incidence of localized and advanced STS in Korean patients, their treatment patterns, and the survival of patients by disease status., Materials and Methods: The STS patient cohort was defined using National Health Insurance Service medical data from 2002 to 2015. Incidence, distribution, anatomical location of tumors, survival rates (Kaplan-Meyer survival function) and treatment patterns were analyzed by applying different algorithms to the STS cohort containing localized and advanced STS cases., Results: A total of 7,813 patients were diagnosed with STS from 2007 to 2014, 4,307 were localized STS and 3,506 advanced STS cases. The total incidence of STS was 2.49 per 100,000 person- years: 1.37 per 100,000 person-years for localized STS and 1.12 per 100,000 person-years for advanced STS. The 5-year survival rate after diagnosis was 56.4% for all STS, 82.4% for localized, and 27.2% for advanced STS. Half of the advanced STS patients (49.98%) received anthracycline-containing chemotherapy as initial treatment after diagnosis., Conclusion: This study provides insights into localized and advanced STS epidemiology, treatment patterns and outcomes in Korea, which could be used as fundamental data in improving clinical outcomes of STS patients in the future.

Purpose: A cross-sectional survey was conducted to explore the current awareness and use of complementary and alternative medicine (CAM), as well as attitudes toward CAM, in patients with cancer and their family members in South Korea., Materials and Methods: Between September 21 and October 31, 2017, a 25-item questionnaire regarding CAM experiences among cancer patients and their family members was conducted in 10 oncology clinics in South Korea after institutional review board approval at each institution., Results: In total, 283/310 patients were analyzed. The median age was 60 years, and 60% were male. Most of the patients were actively receiving anticancer treatment at the time of the survey. A total of 106 patients (37%) had experienced a median of two types (interquartile range, 1 to 3) of CAM. Belief in CAM (odds ratio [OR], 3.015; 95% confidence interval [CI], 1.611 to 5.640) and duration of disease (OR, 1.012; 95% CI, 1.004 to 1.020) were independent factors for using CAM in multivariable analysis. Belief in CAM was significantly associated with current use of CAM (OR, 3.633; 95% CI, 1.567 to 8.424). Lay referral was the most common reason for deciding to use CAM, and only 25% of patients (72/283) discussed CAM with their physicians., Conclusion: Patient attitudes toward and confidence in CAM modalities were strongly associated with their CAM experiences, and only a small number of patients had an open discussion about CAM with their physicians. A patient education program for CAM is needed.

Background: 10-20% of patients with gastric cancer (GC) have HER2+ tumors. Addition of trastuzumab (T) to cisplatin/fluoropyrimidine-based chemotherapy (CT) improved survival in metastatic, HER2+ GC. When pertuzumab (P) was added to neoadjuvant T and CT, a significant increase in histopathological complete response rate was observed in HER2+ breast cancer. This study aims to investigate the added benefit of using both HER2 targeting drugs (T alone or the combination of T + P), in combination with perioperative CT for localized HER2+ GC., Methods: This is a prospective, randomized, open-label, phase II trial. HER2 status from patients with resectable GC (UICC TNM7 tumor stage Ib-III) will be centrally determined. Two hundred and-fifteen patients from 52 sites in 14 countries will be centrally randomized (1:2:2 ratio) to one of the following treatment arms: 1. Standard: CT alone. CT regimens will be FLOT (5-FU, leucovorin, oxaliplatin, taxotere) CapOx (capecitabine, oxaliplatin) or FOLFOX (5-FU, leucovorin, oxaliplatin) according to investigator's choice in Europe, and cisplatin/capecitabine in Asia. 2. Experimental arm 1: CT as in control group, plus T (8 mg/kg loading dose, followed by 6 mg/kg every 3 weeks) at day 1, independent of CT chosen for 3 cycles of 3 weeks before and after surgery. 3. Experimental arm 2: CT plus T as in experimental arm 1, plus P (840 mg every 3 weeks) on day 1. Adjuvant treatment with T or T + P will continue for 17 cycles in total. Stratification factors are: histology (intestinal/non-intestinal); region (Asia vs Europe); location (GEJ vs non-GEJ); HER2 immunohistochemistry score (IHC 3+ vs IHC 2+/FISH+) and chemotherapy regimen. Primary objective is to detect an increase in the major pathological response rate from 25 to 45% either with CT plus T alone, or with CT plus the combination of T and P., Discussion: Depending on the results of the INNOVATION trial, the addition of HER2 targeted treatment with either T or T and P to CT may inform future study designs or become a standard in the perioperative management HER2+ GC., Trial Registration: This article reports a health care intervention on human participants and was registered on July 10, 2014 under ClinicalTrials.gov identifier: NCT02205047 ; EudraCT: 2014-000722-38.

Purpose: We conducted a randomized, multicenter, phase III trial to compare S-1 plus docetaxel (DS) with S-1 plus cisplatin (SP) as adjuvant chemotherapy for stage III gastric cancer patients., Materials and Methods: Stage III gastric cancer patients who had received curative gastrectomy with D2 lymphadenectomy were randomized into equal groups to receive adjuvant chemotherapy of eight cycles of DS (S-1 70 mg/m2 /day on days 1-14 plus docetaxel 35 mg/m2 on days 1 and 8) every 3 weeks or SP (S-1 70 mg/m2 /day on days 1-14 plus cisplatin 60 mg/m2 on day 1) every 3 weeks. The primary endpoint was 3-year disease-free survival (DFS) rate., Results: Between November 2010 and July 2013, 153 patients (75 patients to DS and 78 patients to SP) were enrolled from 8 institutions in Korea. After the capecitabine plus oxaliplatin was approved based on the CLASSIC study, itwas decided to close the study early. With a median follow-up duration of 56.9 months, the 3-year DFS rate between two groups was not significantly different (49.14% in DS group vs. 52.5% in SP group). The most common grade 3-4 adverse event was neutropenia (42.7% in DS and 38.5% in SP, p=0.351). SP group had more grade 3-4 anemia (1.3% vs. 11.5%, p=0.037), whereas grade 3-4 hand-foot syndrome (4.1% vs. 0%, p=0.025) and mucositis (10.7% vs. 2.6%, p=0.001) were more common in DS group. Fifty-one patients (68%) in DS group and 52 (66.7%) in SP group finished planned treatment., Conclusion: Our findings suggest that SP or DS is an effective and tolerable option for patients with curatively resected stage III gastric cancer.

Purpose: With the emergence of next-generation sequencing (NGS) technology, profiling a wide range of genomic alterations has become a possibility resulting in improved implementation of targeted cancer therapy. In Asian populations, the prevalence and spectrum of clinically actionable genetic alterations has not yet been determined because of a lack of studies examining high-throughput cancer genomic data., Materials and Methods: To address this issue, 1,071 tumor samples were collected from five major cancer institutes in Korea and analyzed using targeted NGS at a centralized laboratory. Samples were either fresh frozen or formalin-fixed, paraffin embedded (FFPE) and the quality and yield of extracted genomic DNA was assessed. In order to estimate the effect of sample condition on the quality of sequencing results, tissue preparation method, specimen type (resected or biopsied) and tissue storage time were compared., Results: We detected 7,360 non-synonymous point mutations, 1,164 small insertions and deletions, 3,173 copy number alterations, and 462 structural variants. Fifty-four percent of tumors had one or more clinically relevant genetic mutation. The distribution of actionable variants was variable among different genes. Fresh frozen tissues, surgically resected specimens, and recently obtained specimens generated superior sequencing results over FFPE tissues, biopsied specimens, and tissues with long storage duration., Conclusion: In order to overcome, challenges involved in bringing NGS testing into routine clinical use, a centralized laboratory model was designed that could improve the NGS workflows, provide appropriate turnaround times and control costs with goal of enabling precision medicine.

Purpose: Melanoma is a highly heterogeneous neoplasm, composed of subpopulations of tumor cells with distinct molecular and biological phenotypes and genotypes. In this study, to determine the genetic heterogeneity between primary and metastatic melanoma in Korean melanoma patients, we evaluated several well-known genetic alterations of melanoma. In addition, to elucidate the clinical relevance of each genetic alteration and heterogeneity between primary and metastatic lesions, clinical features and patient outcome were collected., Materials and Methods: In addition to clinical data, BRAF, NRAS, GNAQ/11 mutation and KIT amplification data was acquired from an archived primary Korean melanoma cohort (KMC) of 188 patients. Among these patients, 43 patients were included for investigation of tumor heterogeneity between primary melanoma and its corresponding metastatic lesions., Results: Overall incidence of genetic aberrations of the primary melanomas in KMC was 17.6% of BRAF V600, 12.6% of NRAS mutation, and 28.6% of KIT amplification. GNAQ/11 mutation was seen in 66.6% of the uveal melanoma patients. Patients with BRAF mutation were associated with advanced stage and correlated to poor prognosis (p < 0.01). Among 43 patients, 55.8% showed heterogeneity between primary and metastatic lesion. The frequency of BRAF mutation and KIT amplification significantly increased in the metastatic lesions compared to primary melanomas.

Purpose: The role of family caregivers in cancer care continues to expand, and it has been suggested that the caregiving influences health-promoting behaviors. The purpose was to describe the caregiving burden and health-promoting behaviors of the family caregivers of cancer patients and to determine the relationship between caregiving burden and health-promoting behaviors., Method: A cross-sectional descriptive study was conducted involving 227 family caregivers of adult cancer patients. Caregiving burden was measured using the Korean version of the Zarit Burden Interview (K-ZBI), and health-promoting behaviors were determined using structured questionnaires., Results: Considerable burden was experienced by the caregivers of cancer patients (K-ZBI score of 36.51 ± 12.54, mean ± SD). However, caregiving burden did not influence caregivers' physical activity, diet, smoking, alcohol consumption, or adherence to cancer screening tests. When the caregivers were compared to controls from the Korea National Health and Nutrition Examination Survey V utilizing adjusted proportions, caregivers were less likely to perform physical activities (16.0% vs. 29.1%, p < 0.001), but more likely to adhere to alcohol consumption recommendations (76.3% vs. 35.0%, p < 0.001) and receive cancer screening services for stomach (68.5% vs. 56.8%, p < 0.011), breast (81.4% vs. 58.8%, p < 0.001), and cervical cancer (75.3% vs. 55.0%, p < 0.001)., Conclusions: The caregivers of cancer patients reported considerable caregiving burden. However the burden was not associated with health-promoting behaviors. Physical inactivity among caregivers may require interventions to promote health of caregivers., Implications for Practice: Relieving caregiving burden and improving caregivers' physical activities need to be considered as separate care issues in planning interventions for caregivers of cancer patients., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: The main aim of this study was to evaluate the antitumor activity and safety of vinorelbine and gemcitabine combination chemotherapy in patients with primary refractory or recurrent platinum-resistant epithelial ovarian and primary peritoneal cancers., Methods: Patients with platinum-resistant or primary refractory disease were eligible. Patients were allowed one prior chemotherapy for the treatment of platinum-resistant or refractory disease. Vinorelbine 25mg/m(2), followed by gemcitabine 1000mg/m(2), was administered intravenously on days 1 and 8 every 3weeks. Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 and cancer antigen 125 test (CA-125 criteria) were adopted to classify responses., Results: 44 patients received the median of 4 (range, 1-24) treatments with fifteen (34.1%) receiving six or more cycles. The overall objective response rate was 22.7%. One patient (2.3%) had complete while 9 patients (20.4%) had partial responses with median duration of response of 5.9months. 17 patients (38.6%) had stable disease for a median of 3.3months. Median progression-free survival (PFS) was 3.4months and overall survival (OS) was 14.5months. Four (9.1%) patients were not assessable. Neutropenia was the most frequently encountered toxicity, with grade 3 or 4 observed in 22 patients (50.0%). Fifteen patients (34.1%) needed immediate dose reduction. No treatment related death was reported., Conclusions: The combination chemotherapy with gemcitabine and vinorelbine achieved the primary end point of our clinical trial in management of platinum resistant recurrent ovarian cancer. However, further sophisticated dosing and scheduling of combination chemotherapy are needed because of a significant proportion of dose reduction., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: Few studies have investigated the effects of everolimus therapy in Asian populations. This study evaluates the safety and efficacy of everolimus in Korean patients with metastatic renal cell carcinoma (mRCC)., Methods: We retrospectively reviewed records of Korean patients with mRCC (n = 22) who received everolimus between January 2009 and July 2010 and evaluated them for efficacy and safety., Results: One patient achieved a partial response, and 16 patients had stable disease, corresponding to an overall response rate of 4.5 % and a disease control rate of 77.3 %. Median progression-free survival was 5.4 months (95 % CI 0.9-9.8). Median overall survival was not reached. Univariate analysis showed that Memorial Sloan-Kettering Cancer Center risk (P = .004), thrombocytopenia (P = .018), hyperglycemia (P = .007) and hypertriglyceridemia (P = .041) were associated with disease progression. The most common adverse events (AEs) were hypertriglyceridemia and anemia, similar to Western patients. Creatinine and aspartate aminotransferase levels were higher than those reported for Western patients. The most common grade ≥3 AEs in this study were hypertriglyceridemia and anemia, compared with lymphopenia (14 %) in Western patients., Conclusions: Safety of everolimus in Korean mRCC patients differed from that reported in Western patients. Therefore, liver function enzymes, hemoglobin levels, lipid profile and chest CT scans should be monitored more closely in Asian mRCC patients receiving everolimus.

Purpose: The aim of this study was to investigate the pharmacogenetic determinants of sunitinib-related toxicity and ethnic difference in metastatic renal cell carcinoma (mRCC) among Korean patients., Methods: A pharmacogenetic study was performed in 65 patients with mRCC treated with the standard schedule of sunitinib (50 mg orally once daily for 4 weeks-on/2 weeks-off). Detailed data regarding the toxicity of sunitinib, including thrombocytopenia, neutropenia, anemia, and hand-foot syndrome (HFS), were prospectively collected in a clinical trial program (n = 38) or standard oncology practice (n = 27). Total of 12 genetic polymorphisms in 8 candidate genes (CYP1A1, CYP3A5, ABCB1, ABCG2, PDGFRα, VEGFR2, RET, and FLT3) were analyzed for an association with treatment-related toxicity from sunitinib using Pearson χ (2) test., Results: Common grade 3 or grade 4 treatment-related toxicities were thrombocytopenia (36.9 %, 24/65), neutropenia (18.4 %, 12/65), anemia (7.7 %, 5/65), and HFS (12.3 %, 8/65). Patients carrying an ABCG2 421 AA genotype developed significantly more grade 3 or grade 4 thrombocytopenia, neutropenia, and HFS adjusted for age, sex, and Eastern Cooperative Oncology Group performance status, and body surface area (odds ratio compared with AC/CC genotypes [OR] 9.90, P = 0.04, thrombocytopenia; OR 18.20, P = 0.02, neutropenia; and OR 28.46, P = 0.01, HFS). In addition, total and surface protein ABCG2 protein expression was decreased in ABCG2 421 AA mutant cells compared to wild type., Conclusion: Among 12 genetic polymorphisms, polymorphism in the ABCG2 421C>A gene may be mostly associated with the risk of sunitinib-related toxicity in mRCC patients. Considering the high frequency of 421C>A SNP in Asian, this may be related to differential toxicities among ethnic groups.

Background: This study aimed to apply the International mRCC Database Consortium (IMDC) prognostic model in metastatic non-clear cell renal cell carcinoma (nccRCC). In addition, the survival outcome of metastatic nccRCC patients was characterized., Methods: Data on 2215 patients (1963 with clear-cell RCC [ccRCC] and 252 with nccRCC) treated with first-line VEGF- and mTOR-targeted therapies were collected from the IMDC. Time to treatment failure (TTF) and overall survival (OS) were compared in groups with favorable, intermediate, and poor prognoses according to IMDC prognostic criteria, Results: The median OS of the entire cohort was 20.9 months. nccRCC patients were younger (P < .0001) and more often presented with low hemoglobin (P = .014) and elevated neutrophils (P = .0001), but otherwise had clinicopathological features similar to those of ccRCC patients. OS (12.8 vs 22.3 months; P < .0001) and TTF (4.2 vs 7.8 months; P < .0001) were worse in nccRCC patients compared with ccRCC patients. The hazard ratio for death and TTF when adjusted for the prognostic factors was 1.41 (95% CI, 1.19-1.67; P < .0001) and 1.54 (95% CI, 1.33-1.79; P < .0001), respectively. The IMDC prognostic model reliably discriminated 3 risk groups to predict OS and TTF in nccRCC; the median OS of the favorable, intermediate, and poor prognosis groups was 31.4, 16.1, and 5.1 months, respectively (P < .0001), and the median TTF was 9.6, 4.9, and 2.1 months, respectively (P < .0001)., Conclusions: Although targeted agents have significantly improved the outcome of patients with nccRCC, for the majority survival is still inferior compared with patients with ccRCC. The IMDC prognostic model reliably predicts OS and TTF in nccRCC and ccRCC patients., (Copyright © 2013 American Cancer Society.)

Background: Adjuvant! Online (AOL) is a Web-accessible risk-assessment model that predicts the mortality and the benefits of adjuvant therapy for breast cancer., Methods: Using the Yonsei Tumor Registry database, patients with T1-3, N0-3, M0 breast cancer who were treated at the Yonsei Cancer Center between 1986 and 1999 were entered into AOL version 8.0 to calculate survival., Results: The median age of the study population was 45 years (range, 23-76 years) and the median follow-up duration was 10.8 years (range, 0.1-25.9 years) for all 699 patients. AOL significantly overestimated overall survival (OS) (by 11.1 %, P < 0.001), breast cancer-specific survival (BCSS) (by 11.6 %, P < 0.001), and event free-free survival (EFS) (by 9.25 %, P < 0.001) in Korean patients. Therefore, we developed a Korean version of AOL (KAOL), which is a new model for prognosis based on AOL's parameters. The observed 10-year OS (61.4 %), BCSS (62.3 %), and EFS (59.1 %) and the KAOL predicted OS (61.5 %), BCSS (63.5 %) and EFS (57.6 %) were not different (P = 0.976, P = 0.771, and P = 0.674, respectively)., Conclusions: AOL was not found to be suitable in Korean patients with breast cancer. The newly developed KAOL accurately predicted 10-year outcomes in Korean breast cancer patients.

Purpose: Phosphatidylinositol 3-kinases/AKT pathway plays a pivotal role in hepatocellular carcinoma (HCC). Mutant PIK3CA, encoding the p110a catalytic subunit, stimulates the AKT pathway and promotes cell growth in various cancers. PIK3CA mutation rate has been usually reported as low frequency (<5%) in HCC except one report from Korea with 35.6%. Therefore, we investigated the frequency of PIK3CA mutations in Korean HCC patients., Materials and Methods: We sequenced exons1, 3, 4, 6, 7, 8, 9, 19 and 20 of PIK3CA in 268 HCC tumor tissue samples by Sanger method and pyrosequencing assay., Results: In this study, the mutations were not detected in exons3, 6, 8, and 19, and detected 1 at unknown SNP in exon1 and exon4, 2 at unknown SNP in exon7, 2 at unknown SNP in exon20. However, 1 at unknown SNP, 1 at G1635T and surprisingly all samples at A1634Cin exon9 were detected by Sanger method. Additional experiments with normal tissue, cloning experiments and a pyrosequencing assay revealed that the double peak at A1634C of exon9 is a pseudogene, not true mutation. The mutations found in this study were all different and small numbers, therefore, we cannot conclude specific relationship between clinical characteristics of HCC and mutation of PIK3CA., Conclusion: Our study suggests that the rate of PIK3CA mutation in the Korea population is in fact similar to the rates seen elsewhere in the world.

Background: We conducted a Phase I clinical trial to evaluate the safety, tolerability, and pharmacokinetics (PK) of CKD-732 [6-O-(4-dimethylaminoethoxy) cinnamoyl fumagillol hemioxalate] in combination with capecitabine and oxaliplatin (XELOX) in nine metastatic colorectal cancer patients who had progressed on irinotecan-based chemotherapy., Methods: Using a dose-escalation schedule, CKD-732 doses of 2, 5, or 10 mg/m(2)/d were administered twice weekly for 2 weeks, followed by a 1-week rest. Oxaliplatin (130 mg/m(2)) was administered on day 1, and capecitabine (1,000 mg/m(2) twice a day) was orally administered for 14 days of a 3-week cycle., Results: In the group given the 10 mg/m(2)/d dose, two patients experienced dose limiting toxicities (one had grade 3 nausea, insomnia, and fatigue; the other had grade 3 insomnia). The maximum tolerated dose was 10 mg/m(2)/d, and the clinically recommended dose was 5 mg/m(2)/d for CKD-732 in combination with XELOX. Frequently encountered non-hematological grade 3/4 adverse events included insomnia (22.2%), fatigue (11.1%), sensory neuropathy (11.1%), hyperbilirubinemia (11.1%), and dyspnea (11.1%). The area under the concentration-time curve and maximum concentration of CKD-732 increased in a dose-dependent manner. There were no notable effects of CKD-732 on the PK of capecitabine and oxaliplatin-derived platinum., Conclusion: The Phase II recommended dose of CKD-732 was determined to be 5 mg/m(2)/d, and this dose was safely combined with a conventional dose of capecitabine and oxaliplatin in this patient population. Further studies on the effects of CKD-732 in combination with XELOX and other chemotherapies using a larger study population are warranted.

Background: Although its efficacy is unproven, 5-fluorouracil plus cisplatin (FP) is used to prevent postoperative relapse in gastric cancer. We investigated the safety and feasibility of S-1 plus cisplatin (SP) vs. FP for stage IIIB-IV (M0) gastric cancer., Methods: Following curative resection, 41 stage IIIB-IV (M0) gastric cancer patients were assigned to SP (eight 14-day cycles of S-1 [40 mg/m(2) twice daily] plus cisplatin [60 mg/m(2) day 1] administered every 3 weeks) or FP (six 3-day cycles of FU [1 g/m(2) per day] plus cisplatin [80 mg/m(2) day 1] every 4 weeks). Doses were reduced based on predefined criteria., Results: Patient characteristics were balanced between the two arms. In total, 124 cycles of SP (N = 20, median = 7, range 1-8) and 113 cycles of FP (N = 21, median 6, range 1-6) were administered. The median relative dose intensity per patient was 75% (49.99-100%) for S-1, 100% (75-100%) for cisplatin in SP, and 100% (64-100%) for 5-FU, 100% (60-100%) for cisplatin in FP. The relative dose intensity of FP was stable, while that of SP decreased during treatment. After median follow-up of 7.9 months (3.8-14.55), the median RFS was not reached. Relapse occurred in two (10%) patients on SP and five (23.8%) in the FP arm (P = 0.24). The incidence of grade 3-4 granulocytopenia was 36.8% with SP and 14.3% with FP. Grade 3-4 non-hematologic toxicities included fatigue (5.2% with SP vs. 4.8% with FP), vomiting (10.5% with SP vs. 0% with FP), and infection (5.2% with SP vs. 0% FP)., Conclusion: S-1 plus cisplatin was feasible and tolerable as adjuvant treatment for stage IIIB-IV (M0) gastric cancer. However, because of decreased relative dose intensity during treatment, further study is warranted to determine optimal dosage and combination.

Objective: To establish a comprehensive cancer treatment and prevention policy, data collection should be performed in a timely manner, and survival analysis needs to reflect changes in treatment strategy. Therefore, we introduced the concept of period analysis for gastric cancer, the most prevalent cancer in Korea. We estimated 5- and 10-year survival trend of gastric cancer, based on data from the Yonsei Cancer Center Tumor Registry between 1990 and 2004., Methods: We compared the differences in survival between cohort, complete and period analyses for two different periods, 1995-99 and 2000-04., Results: A total of 11 724 cases were included. The median age of cancer diagnosis gradually increased over time, and more patients were diagnosed with Stage I disease in recent years. In the basic comparison of three estimated analytic methods (cohort, complete and period), period analysis (45.8%) was most similar to the actual 5-year observed survival rate (48.5%), when compared with cohort (43.6%) and complete (44.8%) analyses. When we compared survival between different 10-year periods (1990-99 and 1995-2004), period analysis demonstrated a greater difference than complete analysis (9.0 versus 3.9%). Subgroup analysis indicated that the survival improvement was determined by period analysis, and it was more pronounced for the age group <74 years and in Stages III-IV patients., Conclusions: We observed that period analysis demonstrates the most similar results to the actual observed survival and is, therefore, a useful method to derive precise cancer survival in gastric cancer. This information is useful to understand survival differences that are influenced by changing treatment strategy.

Purpose: This study aims to compare the economic- and patient-reported outcomes between outpatient home-based and inpatient hospital-based chemotherapy in advanced colorectal cancer patients., Methods: A total of 80 patients from Severance Hospital in Seoul, Korea, who had stage III colorectal cancer and underwent home-based (n = 40) or hospital-based chemotherapy (n = 40) with a FOLFOX regimen between January 2007 and April 2008 were enrolled. Patient satisfaction data were collected by a self-administered questionnaire survey. Based on hospital charge records, average cost (in 2008 Korean won (KW)) per chemotherapy session was estimated and compared between home- and hospital-based chemotherapy from a societal perspective., Results: Patients receiving chemotherapy at home showed higher satisfaction with their treatment (mean satisfaction score 3.58 ± 0.15, 5-point Likert-type scale, with a higher score indicating higher satisfaction) than did those treated at the hospital (3.23 ± 0.21; p < 0.01). After adjusting for differences in baseline characteristics between the two groups using multivariate analysis, those receiving home-based chemotherapy still showed significantly higher satisfaction than those undergoing hospital-based therapy (β = 0.271, p < 0.001). Additionally, home-based therapy reduced the cost per chemotherapy session by 16.6%, compared with hospital-based treatment (1,694,216 versus 2,030,383 KW, 1,200 KW ≈ 1 US dollar). The largest cost reduction was attributable to medical costs (-201,122 KW), followed by caregiver's opportunity costs (-135,000 KW)., Conclusions: Higher satisfaction and lower economic cost for home-based chemotherapy suggests that home-based chemotherapy could be a popular and cost-effective treatment option for colorectal cancer patients who are eligible for home-based chemotherapy.

Objectives: This study primarily aimed to investigate the prevalence and associated factors of psychological distress among Korean cancer patients. Its secondary objective was to classify mental illnesses among cancer patients with significant psychological distress., Methods: We administered the Modified Distress Thermometer (MDT), Hospital Anxiety and Depression Scale (HADS), and Center for Epidemiologic Studies-Depression Scale (CES-D) to consecutive, newly diagnosed cancer patients and conducted subsequent psychiatric interviews. A multiple logistic regression produced a discriminate profile of individuals with psychological distress., Results: Among 295 participants, 85 (28.8%) were identified as patients with psychological distress. Female gender [odds ratio (OR)=1.97], low educational level (OR=2.25) and low performance status (OR=4.10) were significantly associated with this condition. Among the 38 patients with psychological distress who received psychiatric assessment, the most common mental illness was adjustment disorder (n=23, 69.7%)., Conclusion: The results of this study showed that approximately one-third of the cancer patients suffered from psychological distress. We recommend that physicians focus on the psychological status of female cancer patients with low levels of education and poor performance status., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: We aimed to describe the efficacy and safety of sunitinib in unselected Korean advanced renal cell carcinoma (RCC) patients., Patients and Methods: From November 2005 to August 2008, 132 histologically confirmed advanced RCC patients (100 in the global expanded access program) were enrolled. Response and toxicity were assessed regularly according to the protocol., Results: Within this population, 82.6% had clear cell RCC, and 28.8% were treatment naïve. Patients received a median of 5 cycles of sunitinib (range 1-30), and the mean relative dose intensity was 82.0 ± 14.20 (SD). The progression-free survival (PFS) and overall survival rates were 8.2 and 23.1 months, respectively. For the 130 evaluable patients, the objective response rate was 34.1% (n = 45); 44.7% (n = 59) exhibited stable disease. Reasons for discontinuation were disease progression (75.0%) and toxicity (7.6%). The most frequent adverse events were thrombocytopenia (75.0%), neutropenia (70.5%), and anemia (69.7%). Low body surface area (OR = 4.2, 95% CI 1.2-13.8, p = 0.02) and previously treated status (OR = 3.1, 95% CI 1.3-7.4, p = 0.01) were highly predictive of grade 3-4 toxicities. Based on these findings, a nomogram predicting the probability of 12-month PFS was constructed, giving a concordance index of 0.675., Conclusions: Despite the different toxicity profiles, maintaining adequate dose modifications and a careful follow-up enables comparable treatment outcomes for unselected Korean advanced RCC patients., (Copyright © 2011 S. Karger AG, Basel.)