Pancreatic cancer: Best supportive care

International audienc

O-positive blood type is associated with prolonged recurrence-free survival following curative resection of pancreatic neuroendocrine tumors

International audienceBackground: The ABO blood group may influence the development and progression of cancer. In particular, the prognosis of patients with blood type O is better for pancreatic adenocarcinoma, although this has not been extensively explored in pancreatic neuroendocrine tumors (PanNET).Objective: To assess the influence of the ABO and Rhesus blood types on the risk of recurrence in patients who underwent curative intent PanNET surgical resection.Methods: All consecutive patients operated on for well-differentiated panNET in an expert center from 2003 to 2018 were retrospectively included. Blood group, Rhesus system, demographic and clinical data were collected. The primary endpoint was recurrence free survival (RFS). Factors associated with RFS were explored using Cox proportional hazard models.Results: Overall, 300 patients (male 43%) were included, median age 54 years old (IQR 45-64). The ABO blood group distribution was similar to that of the French population. There was no association between blood group and tumor features. The median postoperative follow-up was 43.9 months (17.0-77.8). The 5- and 10-year RFS rates were 85 ± 4% and 71 ± 13% in O RhD + patients, versus 72 ± 4% and 63 ± 6% otherwise, respectively (p = 0.035). The O RhD + blood group was associated with a decreased risk of recurrence (HR 0.34, 95% CI [0.15-0.75]), p = 0.007 in multivariable analysis adjusted for age, ki67, functioning syndrome, resection margins, tumor size, lymph node status, oncogenetic syndrome.Conclusions: After curative-intent surgical resection for PanNET, patients with a non-O RhD + blood group may have an increased risk of recurrence and could benefit from closer follow-up

Competitive interactions in plant-parasitic nematode communities affecting organic vegetable cropping systems

Plant-parasitic nematodes (PPN) are detected everywhere as mixed-species communities. Most non-chemical control strategies of PPN only target some species, thus raising questions about the consequences that this specificity may have on the residual community. In this respect, the long-term ecological sustainability of such strategies is challenged. In order to evaluate the impacts of agronomical practices on PPN communities, two four-year experiments that differed by the presence or absence of root-knot nematodes (RKN - Meloidogyne spp.) were carried out under cold shelters in the south of France, under native field conditions of vegetable cropping systems that included a nematicidal sorghum green manure and a pepper variety carrying a RKN resistance gene. At the site with RKN, RKN populations developed on susceptible vegetables. They were controlled by the green manure but not by the R-pepper, and were also vulnerable to low soil temperatures. At the site without RKN, Paratylenchidae populations developed on susceptible vegetables, but were controlled by both the green manure and the R-pepper, and not by low temperatures. At each site, populations of Telotylenchidae exhibited dynamics suggesting competition with RKN or Paratylenchidae. Hypotheses about competition models are discussed according to the specific life traits of the PPN involved, including ecto- vs. endoparasitism and sedentary vs. free-living behaviour, and to the antagonist mechanisms of the cover and resistant crops that must be introduced in vegetable cropping systems

Combinations of varietal and technical innovations for the sustainable and integrated management or root-knot nematodes: the gedumen project

National audienc

Évaluer l’acceptabilité par les agriculteurs d’innovations variétales et agronomiques pour maîtriser les nématodes à galles en maraîchage sous abri (le projet GEDUNEM)

National audienceRoot-knot nematodes (RKN, Meloidogyne spp.) is a major disease in sheltered vegetable crops, present on about 40% of the southern France farms (survey 2007 -2010). As most chemical nematicide products are now banned, it is necessary to find alternative solutions using agronomical techniques. New prototypes of cropping systems have been built previously in a participatory research involving scientists and technical advisors. They are based on RKN varietal resistances and on crop rotations alternating host, non-host species, soil solarisation and nematicide green manure. The Gedunem project aims at assessing the agronomical and nematological effects of these cropping systems (Caporalino et al 2014, same symposium), their mid-term sustainability, and their acceptability by farmers. The oral presentation illustrates this latter question. We compared the 3 cropping systems currently under trial and the actual cropping systems of 28 market-gardeners (Furnion 2014). Farmers were asked to explain if the 3 prototypes were acceptable or not depending on their own farm constraints and strategy. The major bottlenecks that were identified are the cost and time required for some practices (such as the use of resistant pepper as a trap-crop), and the availability of free land in summer on some crop rotations. Moreover the nature and intensity of the bottlenecks depend on the type of farm and the farmers’ motivation to innovate. This study enables to highlight how to adapt the present prototypes in order they may be implemented more easily on commercial farms.La gestion des nématodes à galles (Meloidogyne spp.) est un problème majeur en maraîchage sous abri, notamment dans le Sud-Est de la France où plus de 40 % des exploitations sont touchées par ce ravageur (enquête 2007-2010). Suite aux restrictions d’utilisation des nématicides chimiques et afin de conforter la durabilité des moyens de lutte alternatifs, il est nécessaire d’élaborer de nouvelles stratégies de gestion des cultures et des populations de nématodes. Des prototypes de systèmes de culture ont été construits en partenariat avec des conseillers techniques. Ils intègrent des résistances génétiques, des rotations de cultures alternant plantes hôtes et non-hôtes et l’utilisation d'engrais verts à action nématicides pendant l’interculture. Le projet Gedunem vise à évaluer ces stratégies du point de vue de leur efficacité agronomique, de la durabilité de la protection des cultures et d’un point de vue sociotechnique. Cette communication porte sur l’évaluation de l’acceptabilité des stratégies par les agriculteurs. L’étude repose sur une comparaison des systèmes de culture actuels des agriculteurs et des prototypes en cours de test. Il s’agit de recueillir les avis des agriculteurs sur la faisabilité en exploitation pour chacun des 3 prototypes élaborés (Furnion 2014). Les principaux problèmes déjà identifiés dans la mise en œuvre de ces prototypes sont le coût et le temps nécessaire à la mise en place de certaines pratiques (engrais verts nématicides) ainsi que la disponibilité des parcelles suivant les successions de cultures. Il s’agit aussi d’analyser dans quelle mesure l’importance des différentes contraintes varie suivant les types d’exploitation. Cette étude permettra de repérer les adaptations de ces prototypes de systèmes de culture à prévoir pour les rendre plus faciles à mettre en œuvre dans les exploitations sur le plan agronomique, économique et social

Le projet GEDUNEM : Innovations techniques et variétales pour une gestion durable & intégrée des nématodes à galles dans les systèmes maraîchers sous abris

National audienc

Conception et évaluation d’innovations variétales et agronomiques pour maîtriser les nématodes à galles en maraîchage sous abri (le projet GEDUNEM)

National audienc

Telomere length is key to hepatocellular carcinoma diversity and telomerase addiction is an actionable therapeutic target

International audienceBackground & Aims: Telomerase activation is the earliest event in hepatocellular carcinoma (HCC) development. Thus, we aimed to elucidate the role of telomere length maintenance during liver carcinogenesis.Methods: Telomere length was measured in the tumor and non-tumor liver tissues of 1,502 patients (978 with HCC) and integrated with TERT alterations and expression, as well as clinical and molecular (analyzed by genome, exome, targeted and/or RNA-sequencing) features of HCC. The preclinical efficacy of anti-TERT antisense oligonucleotides (ASO) was assessed in vitro in 26 cell lines and in vivo in a xenograft mouse model.Results: Aging, liver fibrosis, male sex and excessive alcohol consumption were independent determinants of liver telomere attrition. HCC that developed in livers with long telomeres frequently had wild-type TERT with progenitor features and BAP1 mutations. In contrast, HCC that developed on livers with short telomeres were enriched in the non-proliferative HCC class and frequently had somatic TERT promoter mutations. In HCCs, telomere length is stabilized in a narrow biological range around 5.7 kb, similar to non-tumor livers, by various mechanisms that activate TERT expression. Long telomeres are characteristic of very aggressive HCCs, associated with the G3 transcriptomic subclass, TP53 alterations and poor prognosis. In HCC cell lines, TERT silencing with ASO was efficient in highly proliferative and poorly differentiated cells. Treatment for 3 to 16 weeks induced cell proliferation arrest in 12 cell lines through telomere shortening, DNA damage and activation of apoptosis. The therapeutic effect was also obtained in a xenograft mouse model.Conclusions: Telomere maintenance in HCC carcinogenesis is diverse, and is associated with tumor progression and aggressiveness. The efficacy of anti-TERT ASO treatment in cell lines revealed the oncogenic addiction to TERT in HCC, providing a preclinical rationale for anti-TERT ASO treatment in HCC clinical trials.Lay summary: Telomeres are repeated DNA sequences that protect chromosomes and naturally shorten in most adult cells because of the inactivation of the TERT gene, coding for the telomerase enzyme. Here we show that telomere attrition in the liver, modulated by aging, sex, fibrosis and alcohol, associates with specific clinical and molecular features of hepatocellular carcinoma, the most frequent primary liver cancer. We also show that liver cancer is dependent on TERT reactivation and telomere maintenance, which could be targeted through a novel therapeutic approach called antisense oligonucleotides

Varietal and technical innovations for the sustainable and integrated management of root-knot nematodes

International audienceThe current restrictions on the use of chemical nematicides have contributed to increased root-knot nematodes (Meloidogyne spp.) problems in horticultural crops. In this context, plant resistance (R) appears as the most effective method of control, but the restricted number of cultivated vegetable species with root-knot nematode R-genes available (tomato, pepper), and the possible occurrence of virulent nematodes able to reproduce on R-plants may constitute a severe threat to this control strategy. To increase the sustainability of the protection, a scientific challenge exists in building cropping strategies based on the combination of genetic resistance with cultivation practices. Our projects aimed at assessing such innovative strategies in a multi-site device in research stations and commercial farms. First, we looked at three components of crop protection, i.e., R-efficiency, R-durability, and sustainability of rotating cultivation. Overall, a constant hierarchy of management strategies was observed, with Pyramyding > Alternating > Mixture of R-genes > Sequential use of a single R-gene introgressed in a susceptible background. We are currently analysing (1) the impact of agronomic practices on the parasite pressure in the soil and on ecological diversity including other nematode species, (2) the linkage between reduction of Meloidogyne populations in the soil and increase of R-genes durability, and (3) the sustainability assessment of such varietal and technical innovations. Multidisciplinary approaches were combined to foster synergistic and long-term goals. The diversity of partners and associated forces brought all the complementary expertise needed for answering specific short-term questions as well as generic mid- to long-term expectations

Nutrition and physical activity: French intergroup clinical practice guidelines for diagnosis, treatment and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, AFC, SFP-APA, SFNCM, AFSOS)

International audienceThis document is a summary of the French intergroup guidelines regarding the nutrition and physical activity (PA) management in digestive oncology. This collaborative work was produced under the auspices of all French medical and surgical societies involved in digestive oncology, nutrition and supportive care. It is based on published guidelines, recent literature review and expert opinions. Recommendations are graded according to the level of evidence. Malnutrition affects more than half of patients with digestive cancers and is often underdiagnosed. It has multiple negative consequences on survival, quality of life and risk of treatment complications. Consequently, in addition to anticancer treatments, supportive care including nutritional support and PA plays a central role in the management of digestive cancers. It is crucial to detect malnutrition (diagnostic criteria updated in 2019) early, to prevent it and to act against it at all stages of the cancer and at all times of the care pathway. In this context, we proposed recommendations for the evaluation and management in nutrition and PA in digestive oncology for each stage of the disease (perioperative setting, during radiation therapy, during systemic treatments, at the palliative phase, after cancer). Guidelines for nutrition and PA management aim at increasing awareness about malnutrition in oncology. They are continuously evolving and need to be regularly updated