Surveillance des cancers coliques opérés à visée curative : faut-il revoir les recommandations de la conférence de consensus ?

Resume Le cancer colorectal se situe au premier rang des cancers. Le traitement initial reste la resection chirurgicale a visee curative mais pres de la moitie des patients operes presenteront une recidive locoregionale ou a distance. Ce risque eleve de rechute et les possibilites therapeutiques avaient fait recommander une strategie de surveillance lors de la conference de consensus (Paris, 1998) avec un niveau de preuve faible. La question de la strategie de surveillance afin de detecter les recidives plus precocement et a un stade curable n’est toujours pas resolue et les modalites de suivi font toujours l’objet d’un important debat. Les etudes controlees et les meta-analyses publies dep…

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…

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…

Surrogate end points for overall survival and local control in neoadjuvant rectal cancer trials: statistical evaluation based on the FFCD 9203 trial.

Abstract Background In resectable rectal cancer trials, pathological parameters are early preoperative treatment efficacy measures. Their validation as surrogate end points for long-term clinical outcomes would allow to reduce trial duration. The aim was to evaluate potential surrogates for overall survival (OS) and local control (LC) in preoperative T3/T4 rectal cancer trials. Candidate variables included ypT and ypN stages, T downstaging, tumor regression grade (TRG), and circumferential resection margin (CRM) status. Patients and methods In the Federation Francophone de Cancerologie Digestive (FFCD) 9203 trial, 742 eligible patients were randomly assigned to receive preoperative radiothe…

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…

TH-302 + Gemcitabine (G + T) vs Gemcitabine (G) in Patients with Previously Untreated advanced Pancreatic Cancer (PAC)

ABSTRACT Background TH-302 is a hypoxia targeted prodrug with a hypoxia-triggered 2-nitroimidazole component designed to release the DNA alkylator, bromo-isophosphoramide mustard (Br-IPM), when reduced in severe hypoxia. A randomized Phase 2B study (NCT01144455) was conducted to assess the benefit of G + T to standard dose G as first-line therapy of PAC. Materials and methods An open-label multi-center study of two dose levels of TH-302 (240 mg/m2 or 340 mg/m2) in combination with G versus G alone (randomized 1:1:1). G (1000 mg/m2) and T were administered IV over 30-60 minutes on Days 1, 8 and 15 of a 28-day cycle. Patients on the G could crossover after progression and be randomized to a G…

Factors influencing inclusion in digestive cancer clinical trials: A population-based study

Inclusion in a randomized therapeutic trial represents an optimal therapeutic strategy.To determine the influence of demographic characteristics and deprivation on the enrolment of patients in digestive cancer clinical trials.Between 2004 and 2010, 4632 patients were recorded by the Burgundy Digestive Cancer Registry. According to a balancing score, the 136 patients included in a clinical trial were matched with 272 patients who met the eligibility criteria for trials. Deprivation was measured by the ecological European deprivation index. A conditional multivariate logistic regression was performed.Patients aged over 75 years were significantly less likely to be included in clinical trials …

Impact économique de la chimioembolisation avec microsphères chargées dans le traitement du carcinome hépatocellulaire

Resume La chimioembolisation est le traitement de premiere ligne pour les patients atteints d’un carcinome hepatocellulaire (CHC) non resecable, non metastatique. Les microspheres chargees d’anticancereux recemment commercialisees ont pour objectif d’augmenter l’efficacite de la chimioembolisation en permettant un relargage controle et prolonge de l’anticancereux au plus proche de la tumeur. Notre etude monocentrique compare selon deux methodes de valorisation, les couts medicaux hospitaliers directs d’une premiere cure de chimioembolisation conventionnelle et d’une premiere cure de chimioembolisation avec microspheres chez 30 patients atteints de CHC. Le cout moyen valorise par la comptabi…

Adjuvant treatments for gastric cancer: From practice guidelines to clinical practice

Abstract Background For gastric cancers, the benefits of adjuvant radiochemotherapy and of perioperative chemotherapy have been demonstrated since 2001 and 2006 respectively. The aim of this study was to evaluate the diffusion of adjuvant treatments in a French population. Methods 334 incident gastric cancers UICC Stage IB, II, III or IVM0 resected for cure and recorded in the Burgundy digestive cancer registry were retrospectively included. Patients were classified as having received an effective adjuvant treatment if they had been treated by adjuvant radiochemotherapy since 2001 or perioperative chemotherapy since 2006. Results The proportion of patients treated with an effective adjuvant…

Predictive factors of transarterial chemoembolisation toxicity in unresectable hepatocellular carcinoma

Abstract Background Transarterial chemoembolisation (TACE) is an effective treatment for unresectable hepatocellular carcinoma (HCC), but can cause severe toxicity. Aim To identify predictive factors of severe TACE-related toxicity in patients with unresectable HCC. Methods All HCC patients who underwent TACE at the Dijon University Hospital between 2008 and 2011 were included in this retrospective study. Severe TACE-related toxicity was defined as the occurrence of any adverse event grade ≥4, or any adverse event that caused a prolongation of hospitalisation of >8 days, or any additional hospitalisation within 1 month after TACE. Factors predicting toxicity were identified using a logistic…

Cancer du pancréas localement évolué non resécable : chimioradiothérapie d’induction suivie de chimiothérapie par gemcitabine contre chimiothérapie exclusive par gemcitabine : résultats définitifs de l’étude de phase III 2000–2001de la FFCD et de la SFRO

Resume Objectif de l’etude Etudier l’apport de la chimioradiotherapie concomitante suivie de chimiotherapie dans le cancer pancreatique localement evolue, par rapport a la chimiotherapie seule. Patients et methodes Cent dix-neuf patients atteints d’un cancer pancreatique localement evolue, avec indice de performance de 0 a 2 selon l’Organisation mondiale de la sante, ont ete randomises entre une chimioradiotherapie concomitante d’induction (60 Gy, 2 Gy/fraction ; perfusion concomitante de 5-fluoro-uracile de 300 mg/m2 par jour, de j1 a j5 pendant six semaines ; cisplatine, 20 mg/m2 par jour, de j1 a j5 pendant la premiere et la cinquieme semaines) et une chimiotherapie d’induction par gemci…

Editorial: IDASPHERE phase I trial for chemoembolisation for HCC - authors' reply: a necessary step for treatment optimisation and standardisation

Trends in the incidence and management of biliary tract cancer: a French population-based study.

The trends in incidence and management of biliary tract cancer (BTC) were investigated in a well-defined French population over a 30-year period (1976-2005).Data were obtained from the Burgundy digestive cancer registry. Age-standardised incidence rates and trends in incidence were determined. Treatment and stage at diagnosis were also investigated. Five-year survival rates were calculated.Six hundred and fifteen cases of BTC were recorded. There was no significant change in BTC incidence over the 30-year period. For extrahepatic BTC age-standardised incidence rates were 1.1/100,000 for 1976-80 and 2001-2005. These rates were respectively 0.3 and 0.2/100,000 for intrahepatic BTC. The propor…

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 …

Prospective validation of a lymphocyte infiltration prognostic test in stage III colon cancer patients treated with adjuvant FOLFOX.

IF 6.029; International audience; BackgroundThe prognostic value of lymphocyte infiltration (LI) of colorectal carcinoma (CC) has been demonstrated by several groups. However, no validated test is currently available for clinical practice. We previously described an automated and reproducible method for testing LI and aimed to validate it for clinical use.Patients and methodsAccording to National Institutes of Health criteria, we designed a prospective validation of this biomarker in patients included in the PETACC8 phase III study. Primary objective was to compare percentage of patients alive and without recurrence at 2 years in patients with high versus low LI (#NCT02364024). Associations…

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 …

How do gastroenterologists follow patients with colorectal cancer after curative surgical resection? A three-year population-based study

Summary Objectives To assess the contribution of gastroenterologists (GEs) to the surveillance of colorectal cancer after curative surgery. Patients and methods This registry-based study included 407 patients residing in two French administrative areas diagnosed with newly diagnosed colorectal cancer in 1998 and free of disease six months after curative surgery. All surveillance examinations performed either in the three years after surgery or until death or recurrence were collected retrospectively. Results One hundred nine patients (27%) had a regular clinical check-up with a GE at least once a year. Factors independently associated with GE follow-up were young age (P=0.004), use of adjuv…