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Molecular factors influence relapse patterns in glioblastoma. The hotspot mutation located at position 289 of the extracellular domain of the epidermal growth factor receptor (EGFRAn ancillary study from a prospective cohort of patients suffering from glioblastoma was conducted. All patients received radiotherapy and concomitant temozolomide. The population was divided into two groups according to EGFROne hundred twenty-eight patients were included and analyzed: 11% had EGFRWe highlighted a link between the EGFR

Resume La pandemie due au COVID-19 modifie l’organisation des soins et change la realisation de la chirurgie digestive. Les priorites sanitaires et les circuits de soins sont modifies. La chirurgie d’urgence reste prioritaire. Les interventions pour chirurgie fonctionnelles sont a reporter. La chirurgie par laparoscopie doit suivre des regles strictes pour ne pas exposer les professionnels a un surrisque. Le questionnement principal concerne la chirurgie oncologique, operer ou reporter ? Il existe probablement un sur risque operatoire induit par la pandemie qui doit etre mis en balance avec le retard de prise en charge chirurgical. Pour chaque type de cancer, colon, pancreas, œsogastrique, hepatocarcinome, la morbi-mortalite est rappelee et mise en parallele avec le risque oncologique lie au retard a la chirurgie et/ou au temps de doublement de la tumeur. Cette comparaison permet de proposer des strategies, ainsi pour les cancers coliques (T1-2, N0), il est souhaitable de retarder la chirurgie. Pour les lesions coliques avancees, il semble prudent de recommander une chimiotherapie neo adjuvante et d’attendre. Pour les cancers du rectum T3-4 et/ou N+, une radio-chimiotherapie est indiquee, une radiotherapie courte devra etre discutee (suivie d’une periode d’attente) afin de reduire le temps d’exposition a l’hopital et d’eviter les infections. La majorite des chirurgies complexes a forte morbi-mortalite, œsogastrique, hepatique ou pancreatique doivent sans doute le plus souvent etre reportee.

Molecular documentation at relapse of high-grade glioma is an urgent need for patient care. A prospective pilot study was conducted to assess the rate of mutation detection using targeted deep sequencing on circulating tumor DNA from cerebrospinal fluid (CSF) after chemo-radiotherapy based treatment. Fifteen patients were included: 13 patients with glioblastoma, 1 patient with gliosarcoma and 1 patient with anaplastic astrocytoma. At progression, 10/15 patients (67%) had detectable mutations in the CSF. Among them, 5/10 patients harbored at least one common mutation between initial tumor and ctDNA. CSF protein level and cfDNA concentration were higher, although not significant, in the ctDNA positive group versus ctDNA negative group (1.17g/L vs. 0.79g/L). Molecular documentation obtained from ctDNA in CSF at the time of relapse is informative in around two-thirds of the patients.

The pāhoehoe—‘a‘ā morphological transition involves a change in the rheological response of the magmatic suspension from pure viscous to complex rheological behavior, resulting in the development of tear-apart features. Here, we present a suite of concentric cylinder experiments aimed at studying the effects of cooling and shear rates on the rheology of a phonotephrite melt in response to crystallization. Experiments were conducted at: (a) isothermal subliquidus temperatures of 1,167–1,189°C and shear rates of 1–3s−1; (b) constant cooling rates of 1–10°C/min and shear rates of 1–20s−1. We defined the viscosity-temperature-time window of lava solidification, as well as the transition from coherent flow to shear localization and physical separation (i.e., viscous rupture). Through this approach, we mapped the processes and timescales affecting pāhoehoe—‘a‘ā transition in natural lavas at variable cooling and shear rates. Under disequilibrium conditions, as the cooling rate increases, both crystallization onset and viscous rupture occur at lower temperature and earlier in time. Moreover, the time to reach the crystallization onset and viscous rupture also decreases with increasing shear rate. Both increasing cooling and shear rate reduces the critical crystallinity required for viscous rupture, a consequence of the non-linear interplay between temperature, crystallization kinetics, and melt viscosity. This outcome expands our knowledge on compositional, thermal, and rheological changes in phonotephritic systems. In addition to shear rate and apparent viscosity, comparison with previous measurements on basaltic systems indicates that the pāhoehoe—‘a‘ā transition is sensitive to the composition and cooling path of lavas.

Objectif : Notre objectif etait de construire, a partir du Programme de medicalisation des systemes d’information (PMSI), un indicateur de suivi des delais d’initiation de la chimiotherapie (CT) adjuvante pour cancer du colon et de l’evaluer. Materiel et methodes : A partir du PMSI au CHU de Rouen, nous avons calcule le delai entre la colectomie pour cancer du colon et la CT, chez des patients hospitalises entre 2009 et 2015. Par comparaison au dossier medical, nous avons identifie les vrais et les faux positifs, et nous avons calcule la valeur predictive positive (VPP) de notre methode. Resultats : Parmi les 102 patients selectionnes, la VPP etait de 91 % (IC 95 % : [86–97]). Conclusion : La qualite de l’indicateur meriterait d’etre confirmee dans d’autres etablissements. Applique aux bases PMSI nationales, il pourrait servir d’outil de pilotage au sein des agences regionales de sante et de l’Institut national du cancer.

The main objective of the French GETUG/AFU V05 VESPER randomized phase III study was to assess the efficacy of dd-MVAC and GC in term of progression-free survival in patients for whom chemotherapy has been decided, before or after surgery.A total of 500 patients have been randomized in 28 reference centers. Inclusion criteria were urothelial carcinoma without neuro-endocrine variant, disease defined by a T2, T3 or T4a N0 (pelvic lymph node ≤ 10 mm on CT scan) M0 staging for patients receiving neoadjuvant chemotherapy or pT3 or pT4 or pN+ and M0 for patients receiving adjuvant chemotherapy. Secondary endpoints include overall survival, safety, response rate. The peri-operative chemotherapy schedule was experimental arm dd-MVAC for a total of 6 cycles versus standard arm GC 4 cycles. The toxicity was evaluated according to NCI CTCAE (v 4.0). The progression-free survival rate will be estimated at 3 years by the Kaplan-Meier method. All the patients will be followed for 5 years.The last patient was randomized in March 2018 and the primary endpoint results are expected for mid-2021. As the dd-MVAC schedule is associated with higher response rates in metastatic disease, the real question today is to confirm such benefit in the peri-operative setting, taking also in consideration the chemotherapy toxicity. Tomorrow, the challenge may be the best chemotherapy and immunotherapy association, the authors hope that final Vesper Trial results will help to determine the gold standard chemotherapy. Keywords: Bladder cancer, Peri-operative chemotherapy

To evaluate the frequency of use, modalities and potential interest of locoregional irradiation (LRT) in patients with upfront metastatic head and neck squamous cell carcinoma (HNSCC).Retrospective multicentric study. Were included all patients presenting an upfront metastatic HNSCC treated by platin-5FU- cetuximab based regimen, from 2008 to 2016. Patients with past history of cervical irradiation or HNSCC within the 5 years before metastasis diagnosis were excluded.65 patients were included. 25 patients (38%) presented a response or stable disease with chemotherapy. Forty-one patients (63%) underwent a locoregional irradiation: 5 patients before chemotherapy (upfront RT), 13 patients with stable disease or response after chemotherapy (consolidation RT), and 23 patients with progressive disease. Median overall survival (OS) was 11.6 months, median progression free survival was 7.9 months. OS was significantly improved for patients who underwent LRT (median OS 16.1 vs 7.5 months, p 0.01). Among patients who received LRT, OS trended to be better if LRT was performed as consolidation RT compared to upfront RT (median OS of 22.1 vs 15.5 months, p = 0.11). Among patients with stable disease or response after chemotherapy, there was a non-significant better OS for the 13 patients treated by LRT (median OS 22.1 vs 11.8 months, p = 0.21)). Radical dose was not associated with better locoregional control compared to palliative dose (p = 0.37).LRT is frequently performed during management of upfront metastatic HNSCC and associated with better OS. Non-progressive disease after firs-line chemotherapy seems a good way to select patients who would benefit from radical LRT.

Resume Objectif Evaluer l’interet pronostique des variables clinico-biologiques chez les patients traites en deuxieme ligne de therapie ciblee (TC) pour un cancer du rein metastatique (CRM). Materiel et methodes Une etude retrospective a ete realisee chez 60 patients traites en deuxieme ligne de TC entre 2006 et 2013. Les variables clinico-biologiques ont ete incluses, notamment la toxicite induite, le score de Heng, le MSKCC et la fonction renale. La survie globale (SG) et la survie sans progression (SSP) ont ete etudiees en analyses univariee et multivariee. Resultats L’âge median etait de 61 ans [39–81]. Les scores du MSKCC et de Heng etaient significativement pronostiques pour la SG et la SSP ( p p p = 0,003) et une meilleure SSP (5 mois vs 4 mois, p = 0,047). De meme, une fonction renale alteree a l’initiation de la 2 e ligne etait associee a une meilleure survie (SG = 24 mois vs 9 mois, p = 0,035 et SSP = 7 mois vs 4 mois, p = 0,043). En analyse multivariee, la toxicite induite etait retrouvee comme un facteur independant de bon pronostic pour la SG (HR = 0,36 ; p = 0,01). Conclusion Nos resultats suggeraient qu’une alteration de la fonction renale et une toxicite induite en 2 e ligne de TC auraient un potentiel interet pronostique, comme cela a deja ete rapporte pour la premiere ligne de traitement. Niveau de preuve 5.

International audience; The Covid-19 pandemic is changing the organization of healthcare and has a direct impact on digestive surgery. Healthcare priorities and circuits are being modified. Emergency surgery is still a priority. Functional surgery is to be deferred. Laparoscopic surgery must follow strict rules so as not to expose healthcare professionals (HCPs) to added risk. The question looms large in cancer surgery-go ahead or defer? There is probably an added risk due to the pandemic that must be balanced against the risk incurred by deferring surgery. For each type of cancer-colon, pancreas, oesogastric, hepatocellular carcinoma-morbidity and mortality rates are stated and compared with the oncological risk incurred by deferring surgery and/or the tumour doubling time. Strategies can be proposed based on this comparison. For colonic cancers T1-2, N0, it is advisable to defer surgery. For advanced colonic lesions, it seems judicious to undertake neoadjuvant chemotherapy and then wait. For rectal cancers T3-4 and/or N+, chemoradiotherapy is indicated, short radiotherapy must be discussed (followed by a waiting ଝ NB: French speakers are advised to use the TNCD updates. Propositions alternatives de prise en charge des cancers digestifs en fonction de la situation épidémique au COVID 19, selon les données de la littérature et de l'expérience chinoise. ଝଝ The objectif of this paper is to allow the surgeons to adapt their practices during the first phase of the epidemic until the peak is reached. When the peak is over our systems will have to adapt, but patient maganement will have to become optimal again.

Aim of the study The optimal therapeutic strategy in patients with rectal cancer and synchronous unresectable metastases remains unknown. We evaluated the efficacy of FOLFIRINOX induction therapy in this setting. Patients and methods Chemotherapy-naive patients received at least 8 cycles of FOLFIRINOX. The primary end-point was the 4-month disease control (4 m DC) rate. Tumour responses were centrally reviewed and assessed by computed tomography scan for metastases (Response Evaluation Criteria in Solid Tumours criteria) and magnetic resonance imaging for rectal tumorus. With a Simon 2-stage design and a targeted (H1) 4 m DC > 75%, 65 patients were enrolled from July 2012 to February 2015: male, 78%; median age, 61 years; performance status, 0–1, 98%; liver metastases, 92%; ≥2 metastatic sites, 63%. Results Fifty-six (85%) of the 65 patients received the 8 planned FOLFIRINOX cycles. The primary objective was achieved (4 m DC rate: 94%; 95% confidence interval [CI], 86.3–97.8). Primary tumour symptoms decreased from 72% at baseline to 10% at 4 months. Response rate was 86%, and a >70% primary tumour volume decrease was seen in 63% of patients. Forty-four patients (68%) had at least one grade 3 side-effect; no toxic deaths occurred. Median follow-up was 35.0 months (95% CI, 31.3–43.7). Median progression-free survival and overall survival were 10.9 m (95% CI, 8.8–12.9) and 33.4 m (95% CI, 22.6–38.2), respectively. Conclusion Upfront FOLFIRINOX is feasible and allows good local and distant control. It therefore offers the opportunity to choose the best therapeutic strategy for each patient and to personalise treatment according to the local and distant efficacy results of this induction step. Trial registration Clinicaltrials.gov, NCT01674309 .

IF 7.191 (2017); International audience; BACKGROUND:Previous studies showed that high and low body mass index (BMI) was associated with worse prognosis in early-stage colorectal cancer (CRC), and low BMI was associated with worse prognosis in metastatic CRC (mCRC). We aimed to assess efficacy outcomes according to BMI.PATIENTS AND METHODS:A pooled analysis of individual data from 2085 patients enrolled in eight FFCD first-line mCRC trials from 1991 to 2013 was performed. Comparisons were made according to the BMI cut-off: Obese (BMI ≥30), overweight patients (BMI ≥ 25), normal BMI patients (BMI: 18.5-24) and thin patients (BMI

IF 11.855; International audience

International audience

Resume Objectif Etudier la valeur pronostique potentielle des variables clinico-biologiques, en particulier la toxicite induite par les therapies ciblees (TC), chez des patients traites pour un carcinome renal metastatique (CRM). Patients et methodes Une etude retrospective monocentrique a ete realisee chez les patients traites en premiere ligne de TC entre 2006 et 2012. Les variables clinico-biologiques et de toxicite ont ete recueillies. Les survies etaient calculees selon la methode de Kaplan-Meier et comparees par le test du Log-Rank. Une analyse multivariee a ete realisee selon le modele de Cox. Resultats Cent-deux patients ont ete inclus, avec un suivi median de 20 mois. La mediane de survie globale (SG) etait de 21 mois et de 6 mois pour la survie sans progression (SSP). Comme attendu, les variables regroupees dans le score pronostique du MSKCC avaient un impact significatif sur la SG (p Conclusion Une toxicite severe induite par les therapies ciblees etait un facteur significatif de bon pronostic. Des etudes ulterieures sont necessaires afin d’evaluer le veritable interet de ce facteur dans le developpement des strategies multilignes du traitement du CRM. Niveau de preuve Niveau 5.

Objectifs Le lien entre toxicite, alteration de la fonction renale et efficacite des traitement par therapies ciblees du cancer du rein metastatique a ete rapporte par differentes etudes. Cependant, cet impact a ete plus rarement etudie selon le type de molecule utilisee. Notre objectif etait d’etudier l’influence de l’alteration de la fonction renale et de la toxicite sur l’efficacite du traitement selon le type de molecule. Methodes Une etude retrospective monocentrique a ete realisee chez 163 patients traites par au moins une ligne de TKI pour un cancer du rein metastatique entre 2006 et 2017. Les caracteristiques clinicobiologiques ont ete recueillies, en particulier la fonction renale avant chaque ligne : un debit de filtration glomerulaire (DFG) Resultats Un total de 213 lignes de TKI ont ete realise dans la population. L’âge median etait de 64 ans, pour un suivi median de 39 mois. La mediane de survie globale etait de 30 mois. La mediane de survie sans progression (SSP) etait de 11 et 6 mois selon la presence ou non d’IR, respectivement (p = 0,011). Les patients ayant presente une ts avaient une meilleure SSP (12 vs 5 mois ; p = 0,006). Parmi les 145 patients traites par une ligne de sunitinib, une IR etait associee a une meilleure SSP (13 vs 8 mois ; p = 0,05). De plus, une ts etait associee a une meilleure SSP chez ces patients (12 vs 6 mois ; p = 0,03). Enfin, il n’existait aucune difference de SSP selon la fonction renale et la ts, pour les ligne therapeutiques par sorafenib (n = 53) et axitinib (n = 15) ( Fig. 1 , Tableau 1 ). Conclusion Une IR et une toxicite severe etaient associees a une meilleure efficacite des inhibiteurs de tyrosine kinase, pour le traitement d’un CRM. Cependant, cette difference n’etait retrouvee que pour le traitement par sunitinib parmi les differentes molecules etudiees, renforcant l’interet de son utilisation en cas de patient ayant une alteration de la fonction renale.

Background Half of patients newly diagnosed with esophagus squamous cell cancer (ESCC) has a metastatic ESCC (mESCC) and half of patients with initial loco-regional disease presents disease recurrence after surgery and/or chemoradiation. Although not validated by a phase III trial, first-line palliative chemotherapy combines fluoropyrimidine with platinum salt. Patients with disease progression after platinum-based chemotherapy and good performance status may benefit from a second-line chemotherapy. Based on phase I/II trials or retrospective studies, the most commonly used regimens in second-line setting of mESCC are paclitaxel monotherapy or irinotecan monotherapy or combined with 5FU (FOLFIRI). Up to now, there is no randomized trial available. Trial design OESIRI is a multicenter, open-label, randomized phase II trial designed to evaluate efficacy and safety of nanoliposomal irinotecan (NalIRI) plus 5FU versus paclitaxel as second-line therapy in mESCC. Main inclusion criteria are histologically proven mESCC after failure of first-line platinum-based chemotherapy and WHO performance status ≤ 2. Patients initially treated by surgery and chemotherapy or definitive chemoradiation are eligible if relapse occurred less than 6 months after the end of the treatment. In the experimental arm, patients will receive, every 14 days, intravenous (IV) infusion of NalIRI (80 mg/m2) followed by 5FU (2400 mg/m2 over 46 h). In the control arm, patients will receive at days 1, 8 and 14 of a 28 days-cycle, an IV infusion of paclitaxel (80 mg/m2). The primary objective is to evaluate the percentage of patients alive 9 months after randomisation. The clinical hypotheses are to extent the 9-months survival rate from 40% to 60%. With a one-sided type one error α of 5%, a power of 85%, a 5% rate of patients lost to follow-up, 53 patients per arm (n = 106) will be randomized. Secondary endpoints are progression-free survival, overall survival, response rate, safety and quality of life. Circulating tumor DNA will be monitored to assess its predictive value of response to treatment. Inclusions started in January 2019 and theoretical end of recruitment is January 2022. Legal entity responsible for the study Federation Francaise de Cancerologie Digestive. Funding Servier. Disclosure All authors have declared no conflicts of interest.

Background Both peripherally inserted central catheters (PICC) and implanted port catheters (PORT) are used for adjuvant chemotherapy (ACT) administration in early breast cancer (EBC) patients. We evaluated the safety of the two devices in ACT setting. Methods This monocentric phase II randomized trial (NCT02095743) included patients with an EBC and eligible to an ACT. Patients with curative anticoagulation were excluded. The primary endpoint was to identify the device with the less probability of occurrence of a significant adverse event related to the central venous device (SAERCVD) during the 37 weeks following device implantation. A SAERCVD was defined as: CTCAE grade ≥3, inducing a delay in CT administration >7 days, or requiring a replacement of the implanted device. PICC were removed the day of last CT administration; PORT were removed within 4 weeks after the last CT administration. Based on our previous study (Support Care Cancer. 2016; 24(3):1397-403), 256 patients were needed to meet the primary endpoint. Results From February 2014 to April 2018, 256 patients were included; 248 (97%) were analyzed (PICC, n = 125; PORT, n = 123). Overall, 25 patients (10%) had a SAERCVD: thrombosis (n = 13), local infection (n = 6), systemic infection (n = 3) and mechanical complication (n = 3). Probability of occurrence of a SAERCVD within 37 weeks was 4.9% (6 SAERCVD) in PORT vs 15.2% (19 SAERCVD) in PICC (HR = 3.2 [1.3-8.1], p = 0.007). Regarding baseline characteristics, patients experiencing a SAERCVD had a trend toward a higher body mass index (p = 0.08) and a history of thrombo-embolic disease (p = 0.08) compared to patients without SAERCVD. Among the 223 patients without SAERCVD, probability of occurrence of a non-significant adverse event related to the device was 20.8% (22/106) in PICC vs 17.1% (20/117) in PORT (HR = 1.2 [0.7-2.2], p = 0.5), mainly grade 1 local pruritus. Grade≥3 adverse events not related to the implanted device were observed for 48 patients in each group (HR = 1 [0.7-1.5], p = 0.9), mainly CT induced neutropenia. Conclusions Although side effects related to central venous devices are rare during ACT in EBC patients, SAERCVD are more frequently observed with PICC rather than PORT. Clinical trial identification 2012-A01440-43 NCT02095743. Legal entity responsible for the study Florian Clatot. Funding La Ligue contre le cancer. Disclosure F. Clatot: Honoraria (self), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Lilly; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Research grant / Funding (institution): AstraZeneca; Travel / Accommodation / Expenses: Roche. All other authors have declared no conflicts of interest.

Le bilan pretherapeutique d’un patient porteur d’un cancer de la jonction oesogastrique comporte l’evaluation de son etat physiologique et une estimation du stade tumoral. L’etat nutritionnel est un facteur pronostique et predictif de reponse au traitement, son evaluation associe le calcul de la perte de poids et le dosage de l’albumine serique. En l’absence d’antecedent particulier, les fonctions renale, cardiaque et respiratoire sont evaluees de maniere simple (uree, creatinine, calcul de la clairance, bilan hepatique, electrocardiogramme, exploration fonctionnelle respiratoire [EFR]). L’index d’activite quotidienne (Karnofsky ou OMS) est un important facteur pronostique. L’evaluation du stade tumoral associe l’endoscopie et l’echoendoscopie (EE) digestive, la tomodensitometrie (TDM) thoracoabdominopelvienne avec injection, la tomographie a emission de positron (PET) au 18fluorodeoxyglucose (FDG) et, en cas de doute d’envahissement peritoneal, la laparoscopie.

International audience; BACKGROUND:Metastatic colorectal cancer (mCRC) frequently occurs in elderly patients. However, data from a geriatric tailored randomized trial about tolerance to and the efficacy of doublet chemotherapy (CT) with irinotecan in the elderly are lacking. The benefit of first-line CT intensification remains an issue in elderly patients.PATIENTS AND METHODS:Elderly patients (75+) with previously untreated mCRC were randomly assigned in a 2 × 2 factorial design (four arms) to receive 5-FU (5-fluorouracil)-based CT, either alone (FU: LV5FU2 or simplified LV5FU2) or in combination with irinotecan [IRI: LV5FU2-irinotecan or simplified LV5FU2-irinotecan (FOLFIRI)]. The CLASSIC arm was defined as LV5FU2 or LV5FU2-irinotecan and the SIMPLIFIED arm as simplified LV5FU2 or FOLFIRI. The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), safety and objective response rate (ORR).RESULTS:From June 2003 to May 2010, 71 patients were randomly assigned to LV5FU2, 71 to simplified LV5FU2, 70 to LV5FU2-irinotecan and 70 to FOLFIRI. The median age was 80 years (range 75-92 years). No significant difference was observed for the median PFS: FU 5.2 months versus IRI 7.3 months, hazard ratio (HR) = 0.84 (0.66-1.07), P = 0.15 and CLASSIC 6.5 months versus SIMPLIFIED 6.0 months, HR = 0.85 (0.67-1.09), P = 0.19. The ORR was superior in IRI (P = 0.0003): FU 21.1% versus IRI 41.7% and in CLASSIC (P = 0.04): CLASSIC 37.1% versus SIMPLIFIED 25.6%. Median OS was 14.2 months in FU versus 13.3 months in IRI, HR = 0.96 (0.75-1.24) and 15.2 months in CLASSIC versus 11.4 months in SIMPLIFIED, HR = 0.71 (0.55-0.92). More patients presented grade 3-4 toxicities in IRI (52.2% versus 76.3%).CONCLUSION:In this elderly population, adding irinotecan to an infusional 5-FU-based CT did not significantly increase either PFS or OS. Classic LV5FU2 was associated with an improved OS compared with simplified LV5FU2.CLINICALTRIALSGOV:NCT00303771.

Chemotherapy does not increase the survival time of patients treated for rectal cancer. Chemotherapy given concomitantly to radiotherapy and combined before or after radiation significantly reduces the risk of local recurrence. The sterilization of the tumour (complete pathological response) by chemotherapy is a favourable prognostic factor. New trials on optimisation of pathological complete response rates are based on using drugs effective on metastatic colorectal cancer, given prior to chemoradiotherapy and followed by a resection at least 8 weeks after the end of the radiotherapy. The level of evidence for postoperative chemotherapy is low due to lack of specific study. The indication of postoperative chemotherapy depends on the disease extent after preoperative treatment.

Resume En Europe comme aux USA, le cancer colorectal est la seconde cause de deces par cancer. Plus de 50 % des patients avec un cancer colorectal developpent au decours de leur maladie des metastases hepatiques. La resection chirurgicale des metastases hepatiques est le seul traitement a visee curative assurant une survie prolongee. Actuellement, les progres de la chirurgie hepatique ainsi que le developpement de nouvelles strategies ont permis d’envisager des exereses plus larges et plus complexes. La prise en charge des metastases hepatiques necessite une approche multidisciplinaire (chirurgien, oncologue, radiologue, gastroenterologue), elaborant une strategie therapeutique par etapes successives avec des reevaluations regulieres, permettant a terme d’assurer une resection complete a un maximum de patients.

To date, Lugol chromo-endoscopy is the reference technique to detect an esophageal neoplasia in patients with prior esophageal squamous-cell carcinoma (ESCC), but is not easy to perform without general anesthesia, which can limit its use in routine practice. The objective of this study were to compare the accuracy of white light, narrow band imaging (NBI), and Lugol to detect esophageal neoplasia in patients with a history of cured ESCC, in a prospective study. Thirty patients were prospectively included between June 2006 and June 2009. They all had a history of cured ESCC. Esophageal mucosa was examined first using white light, second NBI, and third after Lugol staining. Histology was obtained in all abnormalities detected by white light, NBI, and/or Lugol. Five neoplastic lesions in five different patients were identified at histology, four cancers, and one high-grade dysplasia. NBI and Lugol both detected all esophageal neoplastic lesions, whereas white light detected the four cancers but missed the high-grade dysplasia. In this feasibility study, NBI and Lugol both detected all identified esophageal neoplasia in very high-risk patients of ESCC. This result suggests that NBI could be used instead of Lugol to detect an esophageal neoplasia in patients with high risk of ESCC, but needs to be confirmed in a larger study.

Since 2004, the clinical impact of monoclonal antibodies (mAbs) targeting the epidermal growth factor receptor (EGFR) on patients with metastatic colorectal cancer (MCRC) has been clearly established. The combination of these biological agents with conventional chemotherapy has led to a significant improvement in response rate, progression-free survival and overall survival in first-line as well as in second- or third-line treatment of MCRC. However, the high variability of response and outcome in MCRC patients treated with these anti-EGFR mAbs has highlighted the need of identifying clinical and/or molecular predictive markers to ensure appropriate use of targeted therapies. The presence of somatic KRAS mutations has been clearly identified as a predictive marker of resistance to anti-EGFR in MCRC, and the use of anti-EGFR mAbs is now restricted to patients with no detectable KRAS mutation. Several studies have indicated that amplification of EGFR, overexpression of the EGFR ligands and inactivation of the anti-oncogene TP53 are associated with sensitivity to anti-EGFR mAbs, whereas mutations of BRAF and PIK3CA and loss of PTEN expression are associated with resistance. Besides these somatic variations, germline polymorphisms such as those affecting genes involved in the EGFR pathway or within the immunoglobulin receptors may also modulate response to anti-EGFR mAbs. Until now, all these markers are not completely validated and only KRAS genotyping is mandatory in routine practice for use of the anti-EGFR mAbs in MCRC.

The management of patients with advanced or localized colorectal cancer (CRC) remains to date exclusively based on clinical, radiological and pathologic data. In CCR, KRAS mutations are detected in approximately 30-40% of tumours. In patients with a localized CRC, the prognostic role of KRAS mutation is not yet demonstrated with contradictory results in literature. For patients with metastatic CCR, KRAS mutations are a prognosis value for patients treated by anti-EGFR antibody. Indeed, despite the use of monoclonal antibodies against epidermal growth factor receptor (EGFR) in metastatic CRC, the detection of molecular alterations in tumours is not integrated in the routine practice for patient decision-making. In patients treated with anti-EGFR Abs for a metastatic CRC, the detection of KRAS mutations on tumour DNA is now mandatory since several recent studies have clearly demonstrated that the presence of KRAS mutations confer a resistance to these therapies. Considering the lack of sufficient data, the detection of KRAS mutations is not recommended in other clinical setting.

The optimal treatment strategy for rectal cancer (RC) with synchronous metastases remains an issue of debate. The aim of this study was to evaluate the impact of surgery and radiation on the control of pelvic symptoms in this setting.Consecutive patients with RC and synchronous metastases were retrospectively assessed and divided into four treatment groups: surgical resection of rectal tumor (S); radiotherapy with/without chemotherapy followed by surgery (CRTS); chemoradiotherapy (CRT); and chemotherapy only (CT). Each group was evaluated in terms of duration of pelvic symptom-free periods (relative to overall survival).A total of 96 patients were evaluated: S: n=30; CRTS: n=21; CRT: n=27; and CT: n=18. After treatment, pelvic symptoms persisted in 14.7% patients (S=0%, CRTS=7.1%, CRT=31.8%, CT=25%; P=0.01). The relative pelvic symptom-free periods were 93.0% in the S group, 83.1% in the CRTS group, 53.0% in the CRT group and 53.2% in the CT group (P0.01). On multivariate analysis, only surgical treatment correlated with a significant relative pelvic symptom-free period (P0.01), with an adjusted hazards ratio of 2.80 [95% CI: 1.79-4.39].Our results suggest that rectal resection was the most effective therapeutic procedure in selected patients with RC and synchronous metastases, offering the patients the longest pelvic symptom-free periods.

Les anticorps monoclonaux inhibant la voie du vascular endothelial growth factor ou VEGF et la voie de l’epidermal growth factor receptor ou EGFR sont les biotherapies validees dans le traitement du cancer colorectal metastatique. La mediane de survie des patients est actuellement superieure a 25 mois, avec l’utilisation des biotherapies associees aux chimiotherapies conventionnelles avec une tolerance globalement correcte, sous reserve du respect des contre-indications et d’une prise en charge precoce et adaptee des toxicites. Si les biotherapies peuvent actuellement etre utilisees a toutes les etapes de traitement, aucun arbre decisionnel consensuel n’a, pour l’instant, ete clairement etabli concernant l’utilisation pratique des differents protocoles. Concernant le ciblage therapeutique, il n’existe aucun marqueur predictif valide pour le bevacizumab, alors que, depuis 2008, l’utilisation des anticorps anti-EGFR est restreinte aux patients ne presentant pas de mutation KRAS au sein de la tumeur.

Les difficultes alimentaires secondaires a la chimiotherapie sont principalement la consequence des toxicites digestives chimio-induites. Ainsi, les effets secondaires tels que les nausees-vomissements, les mucites, mais egalement les troubles du gout et de l’odorat ou bien encore l’asthenie peuvent induire des difficultes alimentaires dont l’incidence et l’intensite sont dependantes des caracteristiques du traitement carcinologique, mais aussi de celles du patient. Les difficultes alimentaires se caracterisent ainsi par un large spectre de symptomes qui peuvent avoir un impact sur la qualite de vie des patients. A l’heure actuelle, ces differents troubles restent encore trop souvent sous-estimes par les cliniciens, et leurs consequences tant nutritionnelles que psychologiques, sociales et culturelles ne sont pas clairement evaluees. Une meilleure connaissance des effets secondaires lies a la chimiotherapie et de leurs symptomes associes est donc indispensable, car elle peut permettre d’instaurer une prise en charge preventive et therapeutique adaptee.