Assessment of epidermal growth factor receptor (EGFR) expression in primary colorectal carcinomas and their related metastases on tissue sections and tissue microarray

Metastatic colorectal carcinomas (CRC) resistant to chemotherapy may benefit from targeting monoclonal therapy cetuximab when they express the epidermal growth factor receptor (EGFR). Because of its clinical implications, we studied EGFR expression by immunohistochemistry on tissue sections of primary CRC (n=32) and their related metastases (n=53). A tissue microarray (TMA) was generated from the same paraffin blocks to determine whether this technique could be used for EGFR screening in CRC. On tissue sections, 84% of the primary CRC and 94% of the metastases were EGFR-positive. When matched, they showed a concordant EGFR-positive status in 78% of the cases. Moreover, staining intensity and extent of EGFR-positive cells in the primary CRC correlated with those observed in the synchronous metastases. On TMA, 65% of the primary CRC, 66% of the metastases, and 43% of the matched primary CRC metastases were EGFR-positive. There was no concordant EGFR status between the primary and the metastatic sites. A strong discrepancy of EGFR status was noted between TMA and tissue sections. In conclusion, EGFR expression measured in tissue sections from primary CRC and their related metastases was found to be similar and frequent, but it was significantly underestimated by the TMA technique

Guidelines for time-to-event end point definitions in breast cancer trials: Results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)

Background: Using surrogate end points for overall survival, such as disease-free survival, is increasingly common in randomized controlled trials. However, the definitions of several of these time-to-event (TTE) end points are imprecisely which limits interpretation and cross-trial comparisons. The estimation of treatment effects may be directly affected by the definitions of end points. The DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials) aims to provide recommendations for definitions of TTE end points. We report guidelines for randomized cancer clinical trials (RCTs) in breast cancer. Patients and methods: A literature review was carried out to identify TTE end points (primary or secondary) reported in publications of randomized trials or guidelines. An international multidisciplinary panel of experts proposed recommendations for the definitions of these end points based on a validated consensus method that formalize the degree of agreement among experts. Results: Recommended guidelines for the definitions of TTE end points commonly used in RCTs for breast cancer are provided for non-metastatic and metastatic settings. Conclusion: The use of standardized definitions should facilitate comparisons of trial results and improve the quality of trial design and reporting. These guidelines could be of particular interest to those involved in the design, conducting, reporting, or assessment of RCT.0SCOPUS: re.jinfo:eu-repo/semantics/publishe

Response to FOLFIRINOX by gender in patients with metastatic pancreatic cancer: Results from the PRODIGE 4/ ACCORD 11 randomized trial.

Hohla et al. suggested that female gender could positively predict response to FOLFIRINOX in patients with advanced pancreatic cancer. In this study, we explored the response to the FOLFIRINOX regimen by gender within the trial PRODIGE4/ACCORD 11.Data were described by gender, both in FOLFIRINOX group and in the intention-to-treat population of the trial. The relative effect of gender (females in comparison to males) on overall survival (OS) and progression-free survival was estimated by using a Cox proportional hazard model and was presented with the Hazard Ratio and their 95% confidence interval. The analysis of prognostic factors of OS included also: age (older than 65 years), ECOG performance status, primary tumor location, synchronous metastases, number of metastatic sites, hepatic metastasis, pulmonary metastases, lymph node metastases, level of Albumin and level of serum carbohydrate antigen 19-9 and three domains from the EORTC Quality of Life QLQC-30 questionnaire.The FOLFIRINOX group (N = 171 patients) included 106 women (62%) and 65 men. No significant differences were observed between genders regarding demographic and clinical parameters, excepted for lymph nodes metastasis (17% and 35% in women and men respectively; p = 0.012). Median OS was longer for females as compared to males in FOLFIRINOX group (13.1 versus 10.3 months respectively; HR = 0.73; 95% CI, 0.51-1.06). Similarly, median PFS was superior (7.2 versus 5.9 months; HR = 0.79; 95% CI, 0.57-1.10). Nevertheless, in both cases, the differences were not statistically significant (p = 0.10 et p = 0.169, respectively).In this study, the overall survival and progression-free survival rates were not significantly higher for females than for males in FOLFIRINOX group (HR = 0.73; 95% CI, 0.51-1.06 and HR = 0.79; 95% CI, 0.57-1.10 respectively). Even if the percentage of patients with lymph node metastasis is higher for males than for females, the interaction between gender and lymph node metastasis was non-significant. Our exploratory analysis did not permit to definitively conclude about a possible effect of gender on the prognosis of patients under FOLFIRINOX. This subject deserves further evaluation.ClinicalTrials.gov number: NCT00112658.Our analysis suggests that FOLFIRINOX, as first-line option for patients with metastatic pancreatic cancer who are younger than 76 years and who have a good performance status (ECOG 0 or 1), no cardiac ischemia and normal or nearly normal bilirubin levels, is beneficial, but not particularly in female patients

EORTC QLQ-C30 descriptive analysis with the qlqc30 command

Health-related quality of life is often an endpoint in oncology clinical trials. The European Organization for Research and Treatment of Cancer (EORTC) developed the cancer-specific quality of life questionnaire (QLQ-C30), which includes five functions, nine symptoms, and a global health status. These questionnaires are completed by the patients themselves throughout the process of care. The recommended approaches for processing EORTC QLQ-C30 data are usually descriptive and graphic

Partial credit model with random effects for longitudinal analysis of quality of life in oncology

PosterInternational audienceThe health-related quality of life (HRQoL) has become one of priority objectives of clinical trials in cancer research to evaluate efficiency of care. The EORTC has developed the cancer-specific QLQ-C30 self-questionnaire evaluating five functional scales, nine symptom scales and global health-status/QoL scale. Commonly used models have statistical and practical limitations. The aim of this study was to propose an alternative method for longitudinal analysis of HRQoL, without data modification. Built on the modern Item Response Theory (IRT), our approach considers the HRQoL as a latent variable directly estimated from raw data. For polytomous items, we extended the partial credit model to a longitudinal analysis (LPCM), thereby modeling the latent variable as a function of time and other covariates. LPCM can be seen as a generalized linear mixed model with a multinomial logit link. The main objective is to apply LPCM and then to compare results with the usual methods. We propose an alternative approach to the commonly used linear mixed model. Our model directly takes into account the ordinal data coming from self-reported questionnaires. LPCM was used to analyze the 15 HRQoL scales and to compare the impact of both treatments. LPCM allowed a more precise analysis of each scale or each item, which could be easily plotted for a clearer interpretation