Development and validation of a serum microRNA biomarker panel for detecting gastric cancer in a high-risk population.

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).

Unmet needs in the physical and daily living domain mediates the influence of symptom experience on the quality of life of gastric cancer patients.

PURPOSE: Gastric cancer patients are expected to have considerable supportive care needs; however, few studies have been conducted. This study aimed to understand the unmet needs of gastric cancer patients at different phases of the cancer journey, identify factors contributing to their unmet needs and quality of life (QOL) and explore the relationships among unmet needs, symptom experience, anxiety, depression, and QOL. METHODS: A correlational study was conducted using data from 223 gastric cancer patients. The instruments include the SCNS-SF 34, HADS, MDASI, and EORTC QLQ-C 30 (Korean version). Descriptive statistics, t test/ANOVA, Pearson's correlation, multiple regression, and path analyses were used to analyze the data. RESULTS: Unmet needs in the health system and information domain were the highest. The phase of the cancer journey had a significant association only with physical and daily living unmet needs (p = 0.027). Physical and daily living unmet needs, symptom severity, symptom interference, and depression demonstrated direct effects on QOL. The physical and daily living unmet needs mediated the association between symptom experience (symptom severity and interference with daily living caused by symptoms) and QOL. The overall paths explained 51.6% of the variance in the QOL of gastric cancer patients (p < 0.001). CONCLUSION: The health system and information unmet needs of gastric cancer patients should be fulfilled by reinforcing the continuity of care, professional counseling, and self-care education. Unmet needs in the physical and daily living domain have to be appraised to facilitate improved symptom management to minimize the negative influence on QOL. Factors contributing to the unmet needs and QOL of gastric cancer patients need to be reflected in supportive care planning.

Assessment of Adrenal Function and Health-Related Quality of Life in Advanced Gastric Cancer Patients Who Received First-Line Chemotherapy.

OBJECTIVE: We performed this prospective study to identify both the incidence of adrenal insufficiency (AI) and health-related quality of life (HRQOL) in advanced gastric cancer (AGC) patients who were treated with the S-1 plus cisplatin (SP) regimen as a first-line palliative chemotherapy. METHODS: We assessed adverse events (AEs) observed in 52 patients who received the SP regimen for AGC between January 2009 and June 2010 using the Common Toxicity Criteria Adverse Events (CTCAE) version 3.0. Adrenal function was assessed at baseline and 12 weeks after chemotherapy using the low-dose adrenocorticotropic hormone stimulation test. HRQOL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire version 3.0 (EORTC-QLQ C30). RESULTS: The incidence of AI was 30.8% (n = 16) and of AE observed 55% (n = 29) among 52 patients after 12 weeks of chemotherapy. Of 29 patients with AE, 34.4% (n = 10) were diagnosed with AI, and of 23 patients without AE, 26.1% (n = 6) were diagnosed with AI. CONCLUSION: The incidence of secondary AI in AGC patients was not rare and was not correlated with the presence of nonspecific AEs. Although patients diagnosed with AI did not show any related symptoms, they are at risk of potentially life-threatening consequences. Thus, the evaluation of AI could be suggested for patients who received chemotherapy.

Caregiving burden and health-promoting behaviors among the family caregivers of cancer patients.

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.

Pharmacogenomic assessment of outcomes of pemetrexed-treated patients with adenocarcinoma of the lung.

PURPOSE: The main objective of this study was to evaluate the association between polymorphisms of the target genes of pemetrexed and clinical outcomes in non-small cell lung cancer (NSCLC) patients treated with pemetrexed. MATERIALS AND METHODS: We assessed polymorphisms at 8 sites in 4 genes [thymidylate synthase (TS), dihydrofolate reductase (DHFR; 1610, 680, 317, intron 1), methylenetetrahydrofolate reductase (MTHFR; 677, 1298), glycinamide ribonucleotide formyl transferase (GARFT; 2255)] associated with pemetrexed metabolism using polymerase chain reaction, gene scanning, and restriction fragment length polymorphism analysis in 90 patients with adenocarcinoma of the lung. RESULTS: Survival was significantly longer with pemetrexed in patients with TS 3RGCC/3RGCC or 3RGGC/3RGGC compared with the other groups (PFS; 5.2 months vs. 3.7 months, p=0.03: OS; 31.8 months vs. 18.5 months, p=0.001). Patients with DHFR 680CC experienced fatigue more frequently (50% vs. 8.6%, p=0.008). Polymorphisms of MTHFR and GARFT were not significantly associated with clinical outcomes of pemetrexed. CONCLUSION: The TS genotype was associated with survival and one DHFR polymorphism was associated with fatigue in NSCLC patients treated with pemetrexed. Further large prospective studies are required to identify other biomarkers that affect patients being treated with pemetrexed for adenocarcinoma of the lung.

Application of the adjuvant! Online model to Korean breast cancer patients: an assessment of prognostic accuracy and development of an alternative prognostic tool.

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.

Economic and patient-reported outcomes of outpatient home-based versus inpatient hospital-based chemotherapy for patients with colorectal cancer.

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 (ß = 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.

Postoperative adjuvant chemotherapy of gastric cancer: scrutiny into the clinical evidence based on quality assessment of medical literature of randomized controlled trials.

The aim of this study was to scrutinize the evidence of adjuvant chemotherapy of gastric cancer by assessing the quality of the medical literature of randomized controlled trials (RCTs). A quality assessment (QA) scoring system was devised with the three parameters-control of bias, quality of report, and quality of design-which consisted 19 items. We searched for all the publications of the RCTs, from 1969 to 2007, with surgery-only arm, and their associated meta-analyses to score. Among the 26 RCTs, quality of three articles were graded as (2+), 10 articles as (1+), and 13 articles as (-). Recently published studies had overall better quality of report, but not necessarily better quality of design. Three studies demonstrating a positive survival benefit of adjuvant chemotherapy had a grade (1+). Hierarchical clustering revealed that the 26 articles were grouped into three major branches associated with study quality and a multi-institutional setting. We also obtained a statistically significant set of ten items (P < 0.001) that could differentiate articles of good (1-2+) and low quality (-) through supervised two-way hierarchical clustering. Finally, the level of recommendation for adjuvant chemotherapy in gastric cancer was to be a "B" according to the Scottish Intercollegiate Guidelines Network (SIGN) System. QA of medical literature should be an essential consideration for medical-related decision-making and the formation of evidence-based guidelines. Multidisciplinary discussion to develop and refine trial design is important for procuring better quality of RCTs of adjuvant chemotherapy of gastric cancer.