Validation of an assessment tool: Estimation of Postoperative Overall Survival for Gastric Cancer.

BACKGROUND: Benchmarking of long-term surgical outcomes has rarely been attempted. We previously devised a prediction model for assessing the outcome of late survival after surgery, termed the Estimation of Postoperative Overall Survival for Gastric Cancer (EPOS-GC). This study was undertaken to validate EPOS-GC in an external data set. METHODS: A retrospective cohort study was conducted in 11 cancer care hospitals in Japan, analyzing a consecutive series of patients who underwent elective gastric cancer resection between April 2007 and March 2009. EPOS-GC consists of three tumor-related variables and three physiological variables. The primary endpoint was postoperative overall survival. The observed-to-expected (O/E) ratio of 5-year survival rates was defined as a metric of quality of care. The sample size for O/E was determined as 42. RESULTS: We included 2045 patients for analysis. The median (95% confidence interval) follow-up time was 5.1 (1.2-6.8) years for censored patients. Although EPOS-GC demonstrated a good discriminative power (Harrell's C-index, 95% confidence interval: 0.80, 0.79-0.83), the calibration plot revealed that EPOS-GC underestimated 5-year survival rates in the high-risk group. Therefore, we recalibrated the model with Cox's regression analysis. The recalibrated EPOS-GC showed a good calibration, preserving the high discriminative power (C-index, 95% confidence interval: 0.80, 0.78-0.82). The O/E among hospitals according to the recalibrated EPOS-GC ranged between 0.87 and 1.27. The O/E correlated with hospital volumes (Spearman's correlation = 0.76, n = 11, p = .006). CONCLUSION: EPOS-GC with recalibration can convey risk-adjusted quality assurance regarding late survival following gastric cancer resection.

Validity of the Japanese version of functional assessment of cancer therapy-gastric (FACT-Ga) and its sensitivity to ascites volume change: a retrospective analysis of Japanese clinical trial participants.

PURPOSE: The functional assessment of cancer therapy-gastric (FACT-Ga) questionnaire was designed to evaluate quality of life (QOL) in patients with gastric cancer. We aimed to explore the reliability and validity of FACT-Ga in Japanese patients, and assess the sensitivity of the gastric cancer subscale for detecting changes in cancer-related variables over time. METHODS: The Japanese version of FACT-Ga was used, and data were obtained from Japanese patients who participated in either of two clinical trials: treatment for advanced or recurrent gastric cancer with ascites (advanced-GC group), or adjuvant chemotherapy after curative resection of gastric cancer (adjuvant group). Psychometric data including data used to determine reliability, internal consistency, and clinical validity were analyzed. Clinical validity was evaluated by comparing subscale scores for patients in the two groups, and by comparing subscale scores for patients with different performance status scores. Correlation between gastric cancer subscale scores and gastric cancer-related variables was also examined. In addition, sensitivity of the gastric cancer subscale to changes in ascites volume, abdominal girth, and Eastern Cooperative Oncology Group (ECOG) performance status (PS) was examined by evaluating their correlation in the advanced-GC group. RESULTS: We collected data on 156 patients (62 advanced-GC group patients and 94 adjuvant group patients). Response rates for the subscales were over 80 % at most time points for both the groups. Cronbach's coefficient alpha revealed good internal consistency for each subscale. At baseline, the adjuvant group had higher QOL scores than the advanced-GC group (P < 0.05), and QOL scores for patients with different performance status scores differed significantly. Changes in gastric cancer subscale scores showed statistically significant correlation with changes in ascites volume (Spearman's rank correlation coefficient, 0.5; P < 0.05). CONCLUSIONS: FACT-Ga is reliable and clinically valid for Japanese patients with gastric cancer. Detection of QOL changes that correlate with ascites volume changes suggests that it could be used more broadly; FACT-Ga scores could be used as an endpoint for patients with gastric cancer-related ascites.

Technical reproducibility of single-nucleotide and size-based DNA biomarker assessment using DNA extracted from formalin-fixed, paraffin-embedded tissues.

DNA extracted from formalin-fixed, paraffin-embedded (FFPE) tissues has been used in the past to analyze genetic polymorphisms. We evaluated the technical reproducibility of different types of assays for gene polymorphisms using DNA extracted from FFPE material. By using the MassARRAY iPLEX system, we investigated polymorphisms in DPYD (rs1801159 and rs3918290), UMPS (rs1801019), ERCC1 (rs11615), ERCC1 (rs3212986), and ERCC2 (rs13181) in 56 FFPE DNA samples. By using PCR, followed by size-based gel electrophoresis, we also examined TYMS 5' untranslated region 2R/3R repeats and GSTT1 deletions in 50 FFPE DNA samples and 34 DNAs extracted from fresh-frozen tissues and cell lines. Each polymorphism was analyzed by two independent runs. We found that iPLEX biomarker assays measuring single-nucleotide polymorphisms provided consistent concordant results. However, by using FFPE DNA, size-based PCR biomarkers (GSTT1 and TYMS 5' untranslated region) were discrepant in 32.7% (16/49, with exact 95% CI, 19.9%-47.5%; exact binomial confidence limit test) and 4.2% (2/48, with exact 95% CI, 0.5%-14.3%) of cases, respectively, whereas no discrepancies were observed using intact genomic DNA. Our findings suggest that DNA from FFPE material can be used to reliably test single-nucleotide polymorphisms. However, results based on size-based PCR biomarkers, and particularly GSTT1 deletions, using FFPE DNA need to be interpreted with caution. Independent repeated assays should be performed on all cases to assess potential discrepancies.

Validity of response assessment criteria in neoadjuvant chemotherapy for gastric cancer (JCOG0507-A).

BACKGROUND: Neoadjuvant chemotherapy may improve outcomes in gastric cancer. Tumor responses can be evaluated with RECIST, Japanese Classification of Gastric Carcinoma (JCGC), and histological criteria. These approaches have not yet been compared. METHODS: We analyzed two phase II trials of neoadjuvant chemotherapy using S-1 plus cisplatin. JCOG0210 included patients with linitis plastica and large ulcero-invasive tumors, whereas JCOG0405 comprised those with para-aortic or bulky lymph node metastases. Radiologic evaluations were conducted using RECIST in JCOG0405 and JCGC criteria in JCOG0210, because the latter included many patients without measurable lesions. A histological responder was defined as a patient in whom one third or more of the tumor was affected. The hazard ratios (HR) for death between responders and non-responders and response rate differences between short- and long-term survivors were estimated. RESULTS: In JCOG0210 (n = 49), HR was 0.54 in JCGC responders (P = 0.059) and 0.40 in histological responders (P = 0.005). The difference in response rates between short- and long-term survivors using histological criteria (34 %, P = 0.023) was greater than that using JCGC criteria (24 %, P = 0.15). In JCOG0405 (n = 51), HR was 0.67 in RECIST responders (P = 0.35) and 0.39 in histological responders (P = 0.030). In short- and long-term survivors, respectively, RECIST response rates were 62  and 67 % (P = 0.77), whereas histological response rates were 33  and 63 % (P = 0.048). CONCLUSIONS: Histological criteria showed higher response assessment validity than RECIST or JCGC criteria and yielded the best surrogate endpoint for overall survival.

[Assessment of the cost of laparoscopy-assisted gastrectomy].

BACKGROUND: The cost of laparoscopic gastrectomy (LG) has not been fully clarified yet. PATIENTS AND METHODS: The actual cost for the instruments used for surgery was examined between LG and conventional open gastrectomy( OG) by separating distant (l D-) and total (l T-) gastrectomy in a total of 20 patients(5 for each)during Oct 2010 and Feb 2011. The profit was defined as the difference of the actual cost and the operation fee including the instruments determined by the insurance and compared. RESULTS: The fee for D-OG, T-OG, D-LG, and T-LG were 708, 700 yen, 856 , 400 yen, 783 , 600 yen and 922 , 300 yen, respectively. The mean profits of D-OG, T-OG, D-LG, and T-LG were 408 , 297 yen, 475 , 812 yen, 308, 681 yen and 269 , 478 yen, respectively. CONCLUSION: Appropriate surgical and instrumental fees should be determined considering the actual cost.

Assessment and data analysis of health-related quality of life in clinical trials for gastric cancer treatments.

This review contains a practical guide as well as a number of design and analytical methods for conducting health-related quality of life assessments in clinical trials for gastric cancer treatment. Although we address issues specific to the assessment of gastric cancer, many are applicable to clinical trials for different cancer types.