o 013safety and efficacy of trifluridine tipiracil in previously treated metastatic colorectal cancer mcrc preliminary results from the phase iiib international open label early access preconnect study

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Incidence and management of malignant digestive endocrine tumours in a well defined French population

Background and aims: Little is known about the epidemiology of malignant digestive endocrine tumours. The aim of this study was to report on their incidence and management in a well defined population. Methods: Data were obtained from the population based Digestive Cancer Registry of Burgundy (France) over a 24 year period. Incidence rates were calculated by sex, age groups, and period of diagnosis. Treatment and stage at diagnosis were also investigated. Prognosis was determined using crude and relative survival rates. A multivariate relative survival analysis was performed. Results: Between 1976 and 1999, 229 cases were recorded. Age standardised incidence rates were 0.76/100 000 for men and 0.50/100 000 for women. They increased over time in both sexes. The resectability rate was 74.1%. Among recorded cases, 26.6% did not extend beyond the organ, 20% had lymph node metastases, and 53.3% had visceral metastases or were unresectable. There was no improvement in the resection rate or in the stage at diagnosis over the study period. The overall relative survival rate was 66.9% at one year, 50.4% at five years, and 40.6% at 10 years. Stage at diagnosis, age at diagnosis, and subsite were independent significant prognostic factors. Conclusions: Although their incidence is increasing, malignant digestive endocrine tumours remain a rare cancer, representing 1% of digestive cancers. Stage at diagnosis and prognosis at a population level are worse than those reported in hospital series. In the short term, new therapeutic possibilities represent the best way to improve their prognosis

Colon cancer in France: Evidence for improvement in management and survival

Background: Cancer registries recording all cases diagnosed in a well defined population represent the only way to assess real changes in the management of colon cancer at the population level. Aims: To determine trends over a 23 year period in treatment, stage at diagnosis, and prognosis of colon cancer in the Côte-d'Or region, France. Patients: A total of 3389 patients with colon cancer diagnosed between 1976 and 1998. Methods: Time trends in clinical presentation, surgical treatment, chemotherapy treatment, stage at diagnosis, postoperative mortality, and survival were studied. A non-conditional logistic regression was performed to obtain an odds ratio for each period adjusted for the other variables. To estimate the independent effect of the period on prognosis, a relative survival analysis was performed. Results: Between 1976 and 1991, the resection rate increased from 69.3% to 91.9% and then remained stable. This increase was particularly marked in the older age group (56.4% to 90.5%). The proportion of stage III patients treated with adjuvant chemotherapy rose from 4.1% for the 1989–1990 period to 45.7% for the 1997–1998 period. Over the 23 years of the study the proportion of stage I and II patients increased from 39.6% to 56.6%, associated with a corresponding decrease in the proportion of patients with advanced stages. Postoperative mortality decreased from 19.5% to 7.3%. This led to an improvement in five year relative survival (from 33.0% for the 1976–1979 period to 55.3% for the 1992–1995 period). Conclusions: Advances in the management of colon cancer have resulted in improving the prognosis of this disease. However, progress is still possible, particularly in the older age group

Gemcitabine/nab-paclitaxel versus folfirinox in locally advanced pancreatic cancer: A European multicenter study

Background: Gemcitabine/nab-paclitaxel (GN) and FOLFIRINOX (FFX) are two standard first-line therapies for metastatic pancreatic cancer (PC) but have rarely been compared, especially in patients with locally advanced PC (LAPC). Methods: This is a retrospective European multicenter study including patients with LAPC treated with either GN or FFX as the first-line therapy between 2010 and 2019. Coprimary objectives were progression-free survival (PFS) and overall survival (OS), both estimated using the Kaplan–Meier method. Results: A total of 147 patients (GN: n = 60; FFX: n = 87) were included. Tumor resection rates were similar between the two groups (16.7% vs. 16.1%; p = 1), with similar R0 resection rates (88.9%). Median PFS rates were not statistically different: 9 months (95% CI: 8–13.5) vs. 12.1 months (95% CI: 10.1–14.6; p = 0.8), respectively. Median OS rates were 15.7 months (95% CI: 12.6–20.2) and 16.7 months (95% CI: 14.8–20.4; p = 0.7), respectively. Abdominal pain at the baseline (HR = 2.03, p = 0.03), tumors located in the tail of the pancreas (HR = 4.35, p = 0.01), CA19-9 > 200 UI/L (HR = 2.03, p = 0.004) and tumor resection (HR = 0.37, p = 0.007) were independent prognostic factors for PFS, similarly to OS. CA19-9 ≤ 200 UI/L (OR = 2.6, p = 0.047) was predictive of the tumor response. Consolidation chemoradiotherapy, more often used in the FFX group (11.7% vs. 50.6%; p < 0.001), was not predictive. Conclusion: This retrospective study did not show any difference between GN and FFX as the first-line treatment in patients with LAPC

A population-based study of adjuvant chemotherapy for stage-II and -III colon cancers.

International audienceBACKGROUND: Although clinical trials have demonstrated that adjuvant chemotherapy improves survival for stage-III colon cancer, the benefits remain controversial for stage-II lesions. The objective of the present study was to determine the extent to which adjuvant chemotherapy is used for patients with stage-II and -III colon cancers. METHODS: The study population comprised 1074 patients with stage-II and -III colon cancers diagnosed in 2000 in 12 French administrative districts and recorded in population-based cancer registries. Data were collected using a standardized procedure. RESULTS: Overall, 20.4% of patients with stage II and 61.9% with stage III received adjuvant chemotherapy. Age at diagnosis was the strongest determinant of chemotherapy. Among stage-II patients, those receiving chemotherapy decreased from 57.6% in patients aged or=85. The corresponding percentages with stage III were 93.6% and 1.4%. In multivariate analyses, other factors found to be independently and significantly associated with administration of adjuvant chemotherapy for stage II were extension of the cancer (stage IIA vs. stage IIB), clinical presentation (obstruction or perforation vs. uncomplicated cancer) and discussion of the case at a multidisciplinary case-review meeting. For stage III, apart from age, discussion of the case at a multidisciplinary meeting was the only factor independently associated with administration of chemotherapy. CONCLUSION: Adjuvant chemotherapy for stage-III colon cancer is used extensively for patients under 75 years of age. However, many elderly patients do not receive such treatment. On the other hand, a substantial percentage of stage-II colon cancer patients receive adjuvant chemotherapy despite its uncertain benefits

Safety and efficacy of trifluridine/tipiracil in previously treated metastatic colorectal cancer (mCRC): Preliminary results from the phase IIIb, international, open-label, early-access PRECONNECT study.

status: publishe

Azathioprine dose reduction in inflammatory bowel disease patients on combination therapy: an open-label, prospective and randomised clinical trial

International audienceBACKGROUND: Infliximab (IFX) combined with azathioprine (AZA) is more effective than IFX monotherapy in inflammatory bowel disease (IBD). AIM: To identify the AZA optimal dose that is required for efficacy when receiving combination therapy. METHODS: Patients with IBD in durable remission on combination therapy were enrolled in a 1-year, open-label, prospective trial after randomisation into three groups: AZA steady (2-2.5~mg/kg/day, n=28) vs AZA down (dose was halved 1-1.25~mg/kg/day, n=27) vs AZA stopped (n=26). Primary endpoint was failure defined as occurrence of a clinical relapse and/or any change in IBD therapy. RESULTS: Eighty-one patients were included. Five (17.9%), 3 (11.1%), and 8 (30.8%) patients experienced failure at 1~year in groups AZA steady, AZA down and AZA stopped, respectively (P=.1 across the groups). The median trough levels of IFX at inclusion were close to those measured at the end of follow-up in group AZA steady (3.65 vs 3.45~μg/mL, P=.9) and in group AZA down (3.95 vs 3.60~μg/mL, P=.5), whereas these levels dropped from 4.25 to 2.15~μg/mL (P=.02) in group AZA stopped. Four (14.3%), four (14.8%) and 11 (42.3%) patients experienced an unfavourable evolution of IFX pharmacokinetics in groups AZA steady, AZA down and AZA stopped, respectively. A threshold of 6-TGN \textless105~pmoles/8.108 RBC was associated with an unfavourable evolution of IFX pharmacokinetics. CONCLUSIONS: Under combination therapy, AZA dose reduction, but not withdrawal, appears to be as effective as continuation of AZA at full dose

Improvements in simulation tools to be developed within the framework of the ASTRID project

International audienceThe ASTRID design comprises innovative features compared to past designs. The simulation tools being very important to support the ASTRID design option selection and to assist a robust Safety demonstration, the CEA and its industrial partners have launched a large program for developing a new generation of simulation tools. Within the framework of the ASTRID project, the strategy for simulation is to continuously improve the simulation tools and their verification and validation (VetV). Furthermore, this new generation of tools is implemented for the basic design of ASTRID in compliance with the regulatory and schedule requirements. Several examples of computation tool developments in the fields of neutronics, fuel behavior, core mechanics, thermal-hydraulics and severe accident analyses are given. The VetV process, described here for the core studies, is also carried out for others domains by the industrial partners.The approach is closely linked to the realization of the RandD experimental programs, aimed to complete the existing experimental data base and so to validate the new model developments and to decrease the calculation uncertainties. The development program of new simulation tools is ambitious in order to meet the challenges which arise from the innovative design options implemented in ASTRID and for the will to comply with the objectives of the 4th generation reactors

Association of Anti-glycan Antibodies and Inflammatory Bowel Disease Course

International audienceBACKGROUND AND AIMS: The usefulness of anti-glycan antibodies alone or combined with anti-Saccharomyces cerevisiae [ASCA] or perinuclear antineutrophil cytoplasmic [pANCA] antibodies for diagnosis of inflammatory bowel disease [IBD], differentiation between Crohn's disease [CD] and ulcerative colitis [UC], disease stratification including IBD phenotype, and also for determination of the course of the disease, remain unclear. METHODS: A large panel of serological anti-glycan carbohydrate antibodies, including anti-mannobioside IgG antibodies [AMCA], anti-chitobioside IgA [ACCA], anti-laminaribioside IgG antibodies [ALCA], anti-laminarin [anti-L] and anti-chitine [anti-C] were measured in the serum from a cohort of 195 patients with IBD] [107 CD and 88 UC]. The respective accuracy of isolated or combined markers for diagnosis, disease differentiation, stratification disease phenotype, and severity of the disease course, defined by a wide panel of criteria obtained from the past medical history, was assessed. RESULTS: The positivity of at least one anti-glycan antibody was detected in a significant higher proportion of CD and UC compared with healthy controls [p \textless 0.0001 and p \textless 0.0007, respectively]. Whereas ASCA and ANCA antibody status had the highest efficacy to be associated with CD in comparison with UC (area under receiver operating characteristic curve [AUROC] = 0.70 for each], the adjunction of anti-laminarin antibody substantially improved the differentiation between CD and UC [AUROC = 0.77]. Titres of ACCA [\textgreater 51U/ml] and anti-laminarin [\textgreater 31U/ml] were significantly linked with a higher association with steroid dependency (odds ratio [OR] =2.0 [1.0-4.0], p = 0.03 and OR = 2.4 [1.1-5.2], p = 0.02, respectively]. We further defined the respective performance of anti-glycan antibodies to discriminate between patients with severe or not severe CD and UC course and determined the associated optimal cut-off values: severe CD course was significantly more likely in case of AMCA \textgreater 77U/ml [OR = 4.3; p = 0.002], ASCA \textgreater 63U/ml [OR = 3.5; p \textless 0.009] and at a lesser degree ACCA \textgreater 50U/ml [OR = 2.8; p \textless 0.02] and severe UC course was significantly associated with AMCA \textgreater 52U/ml [OR = 3.4; p = 0.04] and ACCA \textgreater 25U/ml [OR = 3.0; p \textless 0.04]. CONCLUSIONS: Anti-glycan antibodies are valuable serological markers, especially AMCA antibodies that may help clinicians to promptly classify patients into high risk for severe disease