Idarubicin-loaded beads for chemoembolisation of hepatocellular carcinoma: results of the IDASPHERE phase I trial

SummaryBackground A phase I dose-escalation trial of transarterial chemoembolisation (TACE) with idarubicin-loaded beads was performed in cirrhotic patients with hepatocellular carcinoma (HCC). Aim To estimate the maximum-tolerated dose (MTD) and to assess safety, efficacy, pharmacokinetics and quality of life. Methods Patients received a single TACE session with injection of 2 mL drug-eluting beads (DEBs; DC Bead 300–500 μm) loaded with idarubicin. The idarubicin dose was escalated according to a modified continuous reassessment method. MTD was defined as the dose level closest to that causing dose-limiting toxicity (DLT) in 20% of patients. Results Twenty-one patients were enrolled, inclu…

Erratum to: Development and validation of the FRAGIRE tool for assessment an older person’s risk for frailty

Background Frailty is highly prevalent in elderly people. While significant progress has been made to understand its pathogenesis process, few validated questionnaire exist to assess the multidimensional concept of frailty and to detect people frail or at risk to become frail. The objectives of this study were to construct and validate a new frailty-screening instrument named Frailty Groupe Iso-Ressource Evaluation (FRAGIRE) that accurately predicts the risk for frailty in older adults. Methods A prospective multicenter recruitment of the elderly patients was undertaken in France. The subjects were classified into financially-helped group (FH, with financial assistance) and non-financially …

Pertinence et méthodes pour la conduite d'un essai de supériorité médico-économique en cancérologie

L’existence de ressources economiques limitees et le souci d’allouer, au mieux, a la collectivite, les budgets disponibles, incitent a mener des essais dont le critere de jugement principal pourrait etre un critere medico-economique. Dans le champ de la cancerologie, l’institution de pauses therapeutiques et/ou la diminution de la frequence d’administration des chimiotherapies induit au prealable de s’assurer de la non-inferiorite de l’efficacite de tels schemas. Un autre objectif sous-jacent pourrait etre la demonstration de leur superiorite medico-economique. Dans ce contexte, les essais medico-economiques dont le critere de jugement principal est un critere composite, base sur le cout et…

Critères de substitution: méthodes de validation et état des lieux en cancérologie digestive

In oncology, overall survival is often referred to as the gold standard for the evaluation of a novel therapy in phase III clinical trials. The use of an earlier endpoint (intermediate endpoint) would allow to reduce the duration, the number of patients and/or the cost of the studies. Before being used as primary endpoint, it has to be validated as surrogate for overall survival. Two main statistical methods have been developed. The first evaluates the proportion of treatment effect on overall survival that can be attributable to the effect on the surrogate endpoint. The second, the meta-analytic approach, estimates the correlation between the treatment effect on the surrogate and its effec…

Population-based study of breast cancer survival in Cote d'Or (France): prognostic factors and relative survival.

Abstract Background Few population-based studies have reported jointly analyses of relative survival according to the following prognostic factors: tumour–node–metastasis (TNM) stage, age, number of examined and positive nodes, hormonal status, histological Scarff, Bloom and Richardson (SBR) grade, tumour extension, hormone receptor status and tumour multifocal status. Patients and methods Data on female invasive breast cancer were provided by the Cote d’Or breast cancer registry. The Kaplan–Meier method and log-rank test were used to estimate and compare the survival probability at 1, 5, 10 and 15 years. The effect of prognostic factors on survival was assessed with crude and relative mult…

Time to Deterioration in Quality of Life Score as a Modality of Longitudinal Analysis in Patients with Breast Cancer

Abstract Purpose. This prospective multicenter study explored different definitions of time to deterioration (TTD) in quality of life (QoL) scores, according to different cutoffs of the minimal clinically important difference (MCID) as a modality for longitudinal QoL assessment in breast cancer patients. Methods. QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 and BR-23 before surgery, after surgery, and 6 and 12 months later. The global health score, arm symptoms score (BRAS), and breast symptoms score were analyzed. For a given baseline score, QoL was considered to have deteriorated if this score decreased by ≥5 point…

Effect of dietary polyunsaturated fatty acids on the expression of peroxisomal ABC transporters

Abstract Peroxisomal ABC transporters encoded by the ABCD genes are thought to participate in the import of specific fatty acids in the peroxisomal matrix. ABCD1 deficiency is associated with X-linked adrenoleukodystrophy (X-ALD), the most frequent peroxisomal disorder which is characterized by the accumulation of saturated very-long-chain fatty acids (VLCFA). ABCD2 (the closest homolog of ABCD1) and ABCD3 have been shown to have partial functional redundancy with ABCD1; only when overexpressed, they can compensate for VLCFA accumulation. Other lipids, for instance polyunsaturated fatty acids (PUFA), should be possible candidate substrates for the ABCD2 and ABCD3 gene products, ALDRP and PM…

Population-based study of ovarian cancer in Côte d'Or: prognostic factors and trends in relative survival rates over the last 20 years

Abstract Background The aim of this population-based study was to assess independent prognostic factors in ovarian cancer using relative survival (RS) and to investigate changes in RS rates from 1982 to 2005. Methods Data on 748 patients with ovarian cancer were provided by the Côte d'Or gynaecologic cancer registry. The RS was estimated using a generalized linear model with a Poisson error structure. Relative survival and its 95% confidence interval (CI) were described at the following specific time points 1, 3 and 5 years. The effect of prognostic factors on survival was assessed with multivariate analyses of RS. Results The median follow-up was 12 years. The RS rates at 1, 3 and 5 years …

Factors Associated With Fatigue After Surgery in Women With Early-Stage Invasive Breast Cancer

Abstract Learning Objectives Describe the effect of worsening fatigue after breast cancer surgery on physical functioning and psychological distress. Better identify women at risk for developing cancer-related fatigue. Direct target interventions to patients most in need. Purpose. Fatigue is one of the most frequent symptoms in patients with cancer. However, the precise determinants of fatigue are still unknown. This study was conducted to investigate factors correlated with cancer-related fatigue before surgery and just before subsequent adjuvant therapy. Methods. Patients completed the Multidimensional Fatigue Inventory (MFI-20), the European Organization for Research and Treatment of Can…

The heterogeneity of changes in incidence and survival among lymphoid malignancies in a 30-year French population-based registry.

Our specialized population-based registry has allowed us to explore changes in incidence and survival by subtype over the last 30 years. Between 1980 and 2009, 4790 cases of lymphoid malignancies were registered using the International Classification of Diseases for Oncology. The incidence rate of lymphoid malignancies was 20.5 per 100,000 inhabitants per year, and ranged from 0.1 to 4 according to subtype. Five-year net survival was 65%, and ranged from 41% to 93% according to subtype. We observed an increase in 5-year net survival between the periods 1980-1989 and 2000-2009 (58% vs. 70%). This was observed in most but not all subtypes. Our long-standing population-based registry allowed u…

Evaluation of efficacy and efficiency of a pragmatic intervention by a social worker to support informal caregivers of elderly patients (The ICE Study): study protocol for a randomized controlled trial

Medical progress and the lifestyle modification have prolonged life expectancy, despite the development of chronic diseases. Support and care for older subjects are often provided by a network of informal caregivers composed of family, friends and neighbors, who are essential in helping older persons to continue living at home. It has been shown that the extent and diversity of informal tasks may jeopardize the physical, mental and social wellbeing of caregivers. The aim of the Informal Carers of Elderly cohort is to define, through a longitudinal study, profiles of caregivers of older patients with a diagnosis of one of the following diseases: cancer (breast, prostate, colorectal), neurode…

Randomised controlled trial of lipiodol transarterial chemoembolisation with or without amiodarone for unresectable hepatocellular carcinoma.

Abstract Background There is no consensus about the most effective method for transarterial chemoembolisation of hepatocellular carcinoma. Aim The aim of this phase II trial was to compare the efficacy and toxicity of lipiodol transarterial chemoembolisation with amiodarone in association with pirarubicin or doxorubicin versus lipiodol transarterial chemoembolisation with anthracycline alone in a control group. Methods Patients with unresectable hepatocellular carcinoma and Child-Pugh A/B7 were considered eligible for the trial. transarterial chemoembolisation was repeated every 6 weeks for a maximum of 4 sessions. Results Thirteen patients were randomised in the amiodarone group, and 14 we…

A multicenter cohort study to compare quality of life in breast cancer patients according to sentinel lymph node biopsy or axillary lymph node dissection.

Background: This prospective multicenter study assessed and compared the impact of different surgical procedures on quality of life (QoL) in breast cancer patients. Patients and methods: The EORTC QLQ-C30 and the EORTC QLQ-BR-23 questionnaires were used to assess global health status (GHS), arm (BRAS) and breast (BRBS) symptom scales, before surgery, just after surgery and 6 and 12 months later. The Kruskal–Wallis test with the Bonferroni correction was used to compare scores. A mixed model analysis of variance for repeated measurements was then applied to assess the longitudinal effect of surgical modalities on QoL. Results: Before surgery, GHS (P = 0.7807) and BRAS (P = 0.7688) QoL scores…

Impact of socio-economic and surveillance characteristics on survival in patients with primary invasive breast cancer. A French population-based study.

Visceral fat area as a new independent predictive factor of survival in patients with metastatic renal cell carcinoma treated with antiangiogenic agents.

Abstract Purpose. A better identification of patients who are more likely to benefit from vascular endothelial growth factor–targeted therapy is warranted in metastatic renal cell carcinoma (mRCC). As adipose tissue releases angiogenic factors, we determined whether parameters such as visceral fat area (VFA) were associated with outcome in these patients. Experimental Design. In 113 patients with mRCC who received antiangiogenic agents (bevacizumab, sunitinib, or sorafenib) (n = 64) or cytokines (n = 49) as first-line treatment, we used computed tomography to measure VFA and subcutaneous fat area (SFA). We evaluated associations linking body mass index (BMI), SFA, and VFA to time to progres…

The influence of socio-economic and surveillance characteristics on breast cancer survival: a French population-based study.

International audience; Survival data on female invasive breast cancer with 9-year follow-up from five French cancer registries were analysed by logistic regression for prognostic factors of cancer stage. The Kaplan-Meier method and log-rank test were used to estimate and compare the overall survival probability at 5 and 7 years, and at the endpoint. The Cox regression model was used for multivariate analysis. County of residence, age group, occupational status, mammographic surveillance, gynaecological prevention consultations and the diagnosis mammography, whether within a screening framework or not, were independent prognostic factors of survival. Moreover, for the same age group, and on…

Correlation between clinical prognostic factors and MR spectroscopy-based biomarkers determined at 3.0 T without endorectal coils for patients with localised prostate cancer

International audience

An explorative study to assess the association between health-related quality of life and the recommended phase II dose in a phase I trial: idarubicin-loaded beads for chemoembolisation of hepatocellular carcinoma

Objectives The objective of this study was to explore the association between health-related quality of life (HRQoL) and the recommended phase 2 dose in a phase I clinical trial according to the Time to HRQoL deterioration approach (TTD). Setting This is a phase I dose-escalation trial of transarterial chemoembolisation (TACE) with idarubicin-loaded beads performed in cirrhotic patients with hepatocellular carcinoma. Patients had to complete the EORTC QLQ-C30 HRQoL questionnaire at baseline and at days 15, 30 and 60 after TACE. Participants Patients aged ≥18 years with HCC unsuitable for curative treatments were evaluated for the study (N=21). Primary and secondary outcome measurements The …

Nomograms for predicting local recurrence, distant metastases, and overall survival for patients with locally advanced rectal cancer on the basis of European randomized clinical trials.

Purpose The purpose of this study was to develop accurate models and nomograms to predict local recurrence, distant metastases, and survival for patients with locally advanced rectal cancer treated with long-course chemoradiotherapy (CRT) followed by surgery and to allow for a selection of patients who may benefit most from postoperative adjuvant chemotherapy and close follow-up. Patients and Methods All data (N = 2,795) from five major European clinical trials for rectal cancer were pooled and used to perform an extensive survival analysis and to develop multivariate nomograms based on Cox regression. Data from one trial was used as an external validation set. The variables used in the ana…

EARLY CHOLINE LEVELS FROM 3-TESLA MR SPECTROSCOPY AFTER EXCLUSIVE RADIATION THERAPY IN PATIENTS WITH CLINICALLY LOCALIZED PROSTATE CANCER ARE PREDICTIVE OF PLASMATIC LEVELS OF PSA AT 1 YEAR

International audience; Abstract: Purpose: To investigate the time course response of prostate metabolism to irradiation using magnetic resonance spectroscopy (MRS) at 3-month intervals and its impact on biochemical control. Methods and Materials: Between January 2008 and April 2010, 24 patients with localized prostate cancer were prospectively enrolled in the Evaluation of the Response to Irradiation with MR Spectroscopy (ERIS) trial. All the patients had been treated with intensity-modulated radiation therapy with or without long-term adjuvant hormonal therapy (LTHT) and underwent 3-T MRS and prostate-specific antigen (PSA) assays at baseline and every 3 months thereafter up to 12 months.…

Adjuvant Fluorouracil, Leucovorin, and Oxaliplatin in Stage II to III Colon Cancer: Updated 10-Year Survival and Outcomes According to BRAF Mutation and Mismatch Repair Status of the MOSAIC Study

Purpose The MOSAIC (Multicenter International Study of Oxaliplatin/Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer) study has demonstrated 3-year disease-free survival (DFS) and 6-year overall survival (OS) benefit of adjuvant oxaliplatin in stage II to III resected colon cancer. This update presents 10-year OS and OS and DFS by mismatch repair (MMR) status and BRAF mutation. Methods Survival actualization after 10-year follow-up was performed in 2,246 patients with resected stage II to III colon cancer. We assessed MMR status and BRAF mutation in 1,008 formalin-fixed paraffin-embedded specimens. Results After a median follow-up of 9.5 years, 10-year OS rates in the bolus/…

Surrogate endpoints for overall survival in digestive oncology trials: which candidates? A questionnaires survey among clinicians and methodologists

Abstract Background Overall survival (OS) is the gold standard for the demonstration of a clinical benefit in cancer trials. Replacement of OS by a surrogate endpoint allows to reduce trial duration. To date, few surrogate endpoints have been validated in digestive oncology. The aim of this study was to draw up an ordered list of potential surrogate endpoints for OS in digestive cancer trials, by way of a survey among clinicians and methodologists. Secondary objective was to obtain their opinion on surrogacy and quality of life (QoL). Methods In 2007 and 2008, self administered sequential questionnaires were sent to a panel of French clinicians and methodologists involved in the conduct of …

Development and validation of the FRAGIRE tool for assessment an older person’s risk for frailty

International audience; Background: Frailty is highly prevalent in elderly people. While significant progress has been made to understand its pathogenesis process, few validated questionnaire exist to assess the multidimensional concept of frailty and to detect people frail or at risk to become frail. The objectives of this study were to construct and validate a new frailty-screening instrument named Frailty Groupe Iso-Ressource Evaluation (FRAGIRE) that accurately predicts the risk for frailty in older adults.Methods: A prospective multicenter recruitment of the elderly patients was undertaken in France. The subjects were classified into financially-helped group (FH, with financial assista…