Predictors of disease-free survival in colorectal cancer with microsatellite instability: An AGEO multicentre study.

BACKGROUND: A microsatellite instability (MSI) phenotype is found in about 12% of colorectal cancers (CRCs) and is associated with a low recurrence rate after curative surgery. Several studies have identified clinical and pathological factors predictive of recurrence in resected CRC, but not in the MSI subgroup. PATIENTS AND METHODS: This multicentre retrospective study included patients with stage I, II or III MSI CRCs. Disease-free survival (DFS) was calculated with the Kaplan-Meier method. Factors associated with DFS were identified in univariate and multivariate Cox analyses. RESULTS: We studied 521 patients with MSI CRC. Respectively 11%, 51% and 38% of patients were at stage I, II and III. Mean age was 68.7years and 36% of the patients received adjuvant chemotherapy. Median follow-up was 32.8months. The disease recurrence rates were 6% and 21% in stage II and III patients, respectively. The 3-year DFS rate was 77%. In univariate analysis, age, bowel obstruction, lymph node invasion, stage T4, vascular emboli, lymphatic invasion and perinervous invasion were associated with poorer DFS (P<0.05). Three relevant independent predictors of poor DFS were identified in multivariate analysis, namely bowel obstruction (HR=2.46; 95%CI 1.31-4.62, P=0.005), vascular emboli (HR=2.79; 95%CI 1.74-4.47, P<0.001) and stage T4 (HR=2.16; 95%CI 1.31-3.56, P=0.002). CONCLUSIONS: Bowel obstruction, vascular emboli and stage T4 are independently associated with MSI CRC recurrence, suggesting that screening for vascular emboli in routine clinical practice may assist with adjuvant chemotherapy decision-making.

[Neoadjuvant before surgery treatments: state of the art in prostate cancer]. / Traitements néoadjuvants préopératoires : mise au point dans le cancer de la prostate.

GOAL: To study the impact of systemic treatment in neoadjuvant strategy before surgery in prostate cancer. MATERIALS: Literature reviews with data analysis from PubMed search using the keywords "neoadjuvant", "chemotherapy", "hormonal therapy", "prostate surgery", "radical prostatectomy", but also reports from ASCO and ESMO conferences. The articles on neoadjuvant treatment before radiotherapy were excluded. RESULTS: First studies with former therapy are more than 15-years-old and with questionable methodology: lack of power to have a clear idea of the impact on survival criteria such as overall survival or relapse-free survival. However, the impact of neoadjuvant hormone therapy on the classic risk factors for relapse (positive margins, intraprostatic disease, positive lymph nodes) was demonstrated by these studies and a Cochrane meta-analysis. The association with hormone therapy seems mandatory in comparison to treatment based solely on chemotherapy and/or targeted therapy. Promising data on the use of new drugs and their combinations arise: abiraterone acetate combined with LHRH analogue showed a fast PSA decrease and higher rates of pathologic complete response. Other results are promising with hormonal blockages at various key points. CONCLUSION: Studies with 2nd generation anti-androgene agents or enzyme inhibitors seem to show very promising results. To provide answers about the effectiveness of current neoadjuvant strategy in terms of survival, other studies are needed: randomized phase III or phase II exploring predictive biomarkers. The design of such trials requires a multidisciplinary approach with urologists, oncologists, radiologists and methodologists.

Impact of everolimus blood concentration on its anti-cancer activity in patients with metastatic renal cell carcinoma.

PURPOSE: Everolimus has demonstrated its efficacy in metastatic renal cell carcinoma (mRCC). Preliminary studies have shown high variability of everolimus blood concentrations (EBC). In other settings, its activity was correlated with EBC. We therefore decided to monitor EBC in patients treated with mRCC to assess its influence on oncologic outcomes. PATIENTS AND METHODS: Our study analyzed first 3 months' trough EBC levels in 42 patients treated in 4 French oncologic centers between March 2010 and August 2013. Patients presented a histologically confirmed diagnosis of mRCC and have failed prior anti-angiogenic (AA) therapies. RESULTS: Median follow-up was 25.9 months. A total of 113 EBC were analyzed. The median trough concentration was 14.1 µg/L (range 2.6-91.5). Fourteen patients (67 %) versus 8 (38 %) patients with median EBC above or below 14.1 µg/L were free from progression at 6 months (p = 0.06). Median progression-free survival was 13.3 versus 3.9 months (HR 0.66 95 % CI 0.33-1.31; p = 0.23), and the median overall survival was 26.2 versus 9.9 months (HR 0.62 95 % CI 0.28-1.37; p = 0.24), for patients above or below the median value of trough concentrations, respectively. CONCLUSION: Impact of drug exposure for AA tyrosine kinase inhibitors activity has been demonstrated in mRCC setting. Interpatients EBC variability was confirmed in the present study, and the results suggest a relationship between initial EBC within the first 3 months and the drug activity. It underlines the need to prospectively include EBC monitoring in future clinical trials to determine the need of its implementation in routine use.

Estimate of total salt intake in two regions of Belgium through analysis of sodium in 24-h urine samples.

OBJECTIVES: To evaluate total salt intake in the adult population through an analysis of sodium in 24-h urine samples in two regions of Belgium. METHODS: Urine samples were collected over 24 h from participants and they had to complete a specific questionnaire about salt intake afterwards. Sodium and creatinine concentrations were analysed in these samples. SUBJECTS: The target population comprised adults aged 45-65 years in the region of Ghent and Liege. A total of 123 and 157 volunteers from Ghent and Liege, respectively, were included in the study. RESULTS: The mean creatinine level in Flanders (n=114) amounted to 0.173±0.035 mmol/kg/day, whereas in the Walloon region (n=135) it amounted to 0.161±0.036 mmol/kg/day, after the exclusion of subjects with incomplete urine collection. Intake of sodium in Flanders (n=114) was 4.29±1.29 g/day, whereas in the Walloon region (n=135) it was 3.94±1.44 g/day. In both regions, sodium intake in men was higher than in women. CONCLUSION: Salt intake was more or less twice as high as the recommended intake. Salt intake as estimated from 24-h urine collections is substantially higher than that previously calculated on the basis of food consumption data. A salt reduction programme for Belgium is primordial.