Motivational Interviewing to Increase Physical Activity Behavior in Cancer Patients: A Pilot Randomized Controlled Trials.

OBJECTIVE: This pilot randomized controlled trial (RCT) aimed at evaluating the feasibility and potential efficacy of a motivational interviewing (MI) intervention to increase physical activity (PA) behavior in cancer patients. METHODS: Participants were randomly assigned to an experimental group with standard care plus 12 MI sessions within 12 weeks or a control group with standard care only. The number of recruited participants and the modality of recruitment were recorded to describe the reach of the study. The acceptability of the study was estimated using the attrition rate during the intervention phase. The potential efficacy of the intervention was evaluated by analyzing the PA behavior. RESULTS: Twenty-five participants were recruited within the 16-month recruitment period (1.6 participants per month). Five participants (38.5%) from the experimental group (n = 13) and one participant (8.3%) from the control group (n = 12) dropped out of the study before the end of the intervention phase. No group by time interaction effect for PA behavior was observed at the end of the intervention. CONCLUSION: Due to the low recruitment rate and compliance, no conclusion can be drawn regarding the efficacy of MI to increase PA behavior in cancer patients. Moreover, the current literature cannot provide any evidence on the effectiveness of MI to increase PA in cancer survivors. Future RCTs should consider that the percentage of uninterested patients to join the study may be as high as 60%. Overrecruitment (30% to 40%) is also recommended to accommodate the elevated attrition rate.

Recurrence dynamics of breast cancer according to baseline body mass index.

BACKGROUND: In cancer follow-up, in addition to the evaluation of survival probabilities, there is a fundamental need of assessing recurrence dynamics for optimal disease management. Although the time-dependent effect of the oestrogen receptor (ER) status of the tumour has already been described, so far no factor has proven to disentangle the multi-peak behaviour observed for breast cancer recurrences. Here, we aimed at investigating whether adiposity at diagnosis, reflected by increased patient's body mass index (BMI), could be associated with breast cancer recurrence patterns over time after primary cancer therapy. METHODS: We retrieved BMI from 734 of 777 patients with node-positive breast cancer from a phase III randomised clinical trial, which compared different chemotherapy regimens and had a median follow-up of 15.4 years. Cumulative incidence estimation as well as piecewise exponential models were carried out to estimate the distant recurrence dynamics, in all patients, as well as in subgroups based on the ER status, with the ER-positive group being further split according to the menopausal status. RESULTS: In patients with ER-negative breast cancer, time-dependent analyses revealed that the hazard of late relapses could mainly be attributed to the overweight and obese patients. Within the subgroup of premenopausal patients with ER-positive tumours, obesity was associated with an early high narrow peak of distant recurrences followed by another main peak after 5 years of follow-up. The risk for overweight patients was intermediate between obese and normal-weight patients. In the postmenopausal subgroup of patients with ER-positive tumours, the distant recurrence rate was significantly more elevated in the overweight patients compared to the other BMI categories, and a second late peak of recurrences was also observed for the obese patients. CONCLUSION: These results demonstrate that the patient's BMI at diagnosis is associated with cancer recurrence dynamics. Patient adiposity should therefore be central to the exploration of late adjuvant treatment modalities.

Emerging new anticancer biological therapies in 2013 (haematological malignancies).

PURPOSE OF REVIEW: Although some haematologic diseases such as Hodgkin lymphoma and aggressive lymphoma yield high response rates and acceptable overall survival in first-line treatment, relapse is still a challenge particularly in those patients not eligible for transplant. In acute leukaemias, the prognosis remains poor in general with standard chemotherapy, thus stressing the need for efficient alternate therapies. RECENT FINDINGS: In recent years, biological anticancer agents comprising mAbs, small targeted molecules or more recently bispecific T-cell engaging molecules or chimeric antigen receptors have been developed in haematologic diseases. This review examines the recent advances in biotherapies in the fields of acute leukaemias, aggressive lymphoma, Hodgkin lymphoma and chronic lymphatic leukaemia. SUMMARY: Most biological anticancer agents are currently developed in the setting of relapsed or refractory disease. Some of them however are under development or are already used in first-line therapy wherein they have improved the prognosis of haematology patients.

Determination of genes and microRNAs involved in the resistance to fludarabine in vivo in chronic lymphocytic leukemia.

BACKGROUND: Chronic lymphocytic leukemia (CLL) cells are often affected by genomic aberrations targeting key regulatory genes. Although fludarabine is the standard first line therapy to treat CLL, only few data are available about the resistance of B cells to this purine nucleoside analog in vivo. Here we sought to increase our understanding of fludarabine action and describe the mechanisms leading to resistance in vivo. We performed an analysis of genomic aberrations, gene expression profiles, and microRNAs expression in CLL blood B lymphocytes isolated during the course of patients' treatment with fludarabine. RESULTS: In sensitive patients, the differentially expressed genes we identified were mainly involved in p53 signaling, DNA damage response, cell cycle and cell death. In resistant patients, uncommon genomic abnormalities were observed and the resistance toward fludarabine could be characterized based on the expression profiles of genes implicated in lymphocyte proliferation, DNA repair, and cell growth and survival. Of particular interest in some patients was the amplification of MYC (8q) observed both at the gene and transcript levels, together with alterations of myc-transcriptional targets, including genes and miRNAs involved in the regulation of cell cycle and proliferation. Differential expression of the sulfatase SULF2 and of miR-29a, -181a, and -221 was also observed between resistant and sensitive patients before treatment. These observations were further confirmed on a validation cohort of CLL patients treated with fludarabine in vitro. CONCLUSION: In the present study we identified genes and miRNAs that may predict clinical resistance of CLL to fludarabine, and describe an interesting oncogenic mechanism in CLL patients resistant to fludarabine by which the complete MYC-specific regulatory network was altered (DNA and RNA levels, and transcriptional targets). These results should prove useful for understanding and overcoming refractoriness to fludarabine and also for predicting the clinical outcome of CLL patients before or early during their treatment.

Long-term benefit of high-dose epirubicin in adjuvant chemotherapy for node-positive breast cancer: 15-year efficacy results of the Belgian multicentre study.

PURPOSE: The 4-year results of this trial demonstrated that a higher dose of epirubicin with cyclophosphamide (HEC) is superior to a lower dose of epirubicin, 60 mg/m(2) (EC), for event-free survival (EFS; 27% reduction), but is not superior to classical oral cyclophosphamide, methotrexate, and fluorouracil (CMF) in the adjuvant treatment of node-positive breast cancer. Herein we report the 15-year data on efficacy and long-term toxicity of this three-arm Belgian multicenter trial. PATIENTS AND METHODS: Between March 1988 and December 1996, 777 eligible patients were randomly assigned to six cycles of CMF, eight cycles of EC, or eight cycles HEC. RESULTS: The 15-year EFS was 45% for patients who received CMF, 39% for patients who received EC, and 50% for patients who received HEC. The hazard ratios (HR) were 0.77 for HEC versus EC (95% CI, 0.60 to 0.98; P = .03), 0.90 for HEC versus CMF (P = .39), and 0.86 for EC versus CMF (P = .21). No difference in overall survival (OS) was seen. Cardiac toxicity was more frequent with HEC than with CMF (11 patients v 1 patient; P = .006), but no more than with EC (P = .21). CONCLUSION: Treatment with HEC demonstrated superior EFS when compared with lower-dose epirubicin. However, we do not recommend the use of HEC regimen in daily clinical practice, mainly because of the higher risk of cardiotoxicity related to the cumulative doses of epirubicin and the lack of superiority of anthracyclines over CMF in our study.

[Ongoing medical problems in the anti-doping fight]. / Problèmes médicaux actuels de la lutte antidopage.

Over the last 20 years systematic doping has become a major threat for elite sport. So far, there is no clear information about the daily practice of doping. Repeated scandals and recent personal statements have added to our knowledge. Several more recent doping agents like Erythropoietin (EPO) and, probably, growth hormone (GH) enhance performance in a highly effective way and, together with the well known anabolic steroids (AAS), belong to the major doping categories. The introduction of EPO has really changed the paradigm in endurance sports allowing a good middle class athlete to become a champion. It is evident that doping practices are influenced by the possibilities of the anti-doping control system. Unethical, criminal medical doctors play a decisive role in the ongoing practice of major doping. Apart from the already mentioned substances AAS, EPO and GH several novel drugs appear on the horizon. They are highly effective and there is no doubt that they will be used in attempts to improve performance. During the last years, doping control systems have also been improved: EPO can now be detected in urine samples and the detection of AAS has also become much more sensitive. However GH hormone detection is not possible at the moment and this remains a major weakness of doping control. Other problems are the control procedures which are far from being optimal. In the future the quality of doping controls will be decisive and not only the quantity; controls will have to be "intelligent". The effective fight against doping in the next years will decide about the survival of elite sport.