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1. Staphylococcus aureus CC30 Lineage and Absence of sed,j,r-Harboring Plasmid Predict Embolism in Infective Endocarditis

Author: Jean-Philippe Rasigade, Amélie Leclère, François Alla, Adrien Tessier, Michèle Bes, Catherine Lechiche, Véronique Vernet-Garnier, Cédric Laouénan, François Vandenesch, Catherine Leport, The AEPEI Study Group, B. Hoen, X. Duval, F. Alla, A. Bouvet, S. Briancxon, E. Cambau, M. Celard, C. Chirouze, N. Danchin, T. Doco-Lecompte, F. Delahaye, J. Etienne, B. Iung, V. Le Moing, J. F. Obadia, C. Leport, C. Poyart, M. Revest, C. Selton-Suty, C. Strady, P. Tattevin, F. Vandenesch, Y. Bernard, S. Chocron, P. Plesiat, I. Abouliatim, C. De Place, P. Y. Donnio, J. P. Carteaux, C. Lion, N. Aissa, B. Baehrel, R. Jaussaud, P. Nazeyrollas, V. Vernet, P. Nataf, C. Chidiac, H. Aumaître, J. M. Frappier, E. Oziol, A. Sotto, C. Sportouch, M. Bes, P. Abassade, E. Abrial, C. Acar, J. F. Alexandra, N. Amireche, D. Amrein, P. Andre, M. Appriou, M. A. Arnould, P. Assayag, A. Atoui, F. Aziza, N. Baille, N. Bajolle, P. Battistella, S. Baumard, A. Ben Ali, J. Bertrand, S. Bialek, M. Bois Grosse, M. Boixados, F. Borlot, A. Bouchachi, O. Bouche, S. Bouchemal, J. L. Bourdon, L. Brasme, F. Bricaire, E. Brochet, F. J. Bruntz, A. Cady, J. Cailhol, M. P. Caplan, B. Carette, O. Cartry, C. Cazorla, H. Chamagne, H. Champagne, G. Chanques, J. Chastre, B. Chevalier, F. Chometon, C. Christophe, A. Cohen, N. Colin de Verdiere, V. Daneluzzi, L. David, P. De Lentdecker, V. Delcey, P. Deleuze, E. Donal, B. Deroure, V. Descotes-Genon, K. Didier Petit, A. Dinh, V. Doat, F. Duchene, F. Duhoux, M. Dupont, S. Ederhy, O. Epaulard, M. Evest, J. F. Faucher, B. Fantin, E. Fauveau, T. Ferry, M. Fillod, T. Floch, T. Fraisse, J. M. Frapier, L. Freysz, B. Fumery, B. Gachot, S. Gallien, I. Gandjbach, P. Garcon, A. Gaubert, J. L. Genoud, S. Ghiglione, C. Godreuil, A. Grentzinger, L. Groben, D. Gherissi, P. Gue'ret, A. Hagege, N. Hammoudi, F. Heliot, P. Henry, S. Herson, P. Houriez, L. Hustache-Mathieu, O. Huttin, S. Imbert, S. Jaureguiberry, M. Kaaki, A. Konate, J. M. Kuhn, S. Kural Menasche, A. Lafitte, B. Lafon, F. Lanternier, V. Le Chenault, C. Lechiche, S. Lefèvre-Thibaut, A. Lefort, A. Leguerrier, J. Lemoine, L. Lepage, C. Lepouse', J. Leroy, P. Lesprit, L. Letranchant, D. Loisance, G. Loncar, C. Lorentz, P. Mabo, I. Magnin-Poull, T. May, A. Makinson, H. Man, M. Mansouri, O. Marcxon, J. P. Maroni, V. Masse, F. Maurier, M. C. Meyohas, P. L. Michel, C. Michelet, F. Mechaï, O. Merceron, D. Messika-Zeitoun, Z. Metref, V. Meyssonnier, C. Mezher, S. Micheli, M. Monsigny, S. Mouly, B. Mourvillier, O. Nallet, V. Noel, T. Papo, B. Payet, A. Pelletier, P. Perez, J. S. Petit, F. Philippart, E. Piet, C. Plainvert, B. Popovic, J. M. Porte, P. Pradier, R. Ramadan, J. Richemond, M. Rodermann, M. Roncato, I. Roigt, O. Ruyer, M. Saada, J. Schwartz, M. Simon, B. Simorre, S. Skalli, F. Spatz, J. Sudrial, L. Tartiere, A. Terrier De La Chaise, M. C. Thiercelin, D. Thomas, M. Thomas, L. Toko, F. Tournoux, A. Tristan, J. L. Trouillet, L. Tual, A. Vahanian, F. Verdier, V. Vernet Garnier, V. Vidal, P. Weyne, M. Wolff, A. Wynckel, N. Zannad, and P. Y. Zinzius
Subjects: S. aureus, MRSA, infective endocarditis, stroke, CC30, enterotoxin, Microbiology, QR1-502
Abstract: Staphylococcus aureus induces severe infective endocarditis (IE) where embolic complications are a major cause of death. Risk factors for embolism have been reported such as a younger age or larger IE vegetations, while methicillin resistance conferred by the mecA gene appeared as a protective factor. It is unclear, however, whether embolism is influenced by other S. aureus characteristics such as clonal complex (CC) or virulence pattern. We examined clinical and microbiological predictors of embolism in a prospective multicentric cohort of 98 French patients with monomicrobial S. aureus IE. The genomic contents of causative isolates were characterized using DNA array. To preserve statistical power, genotypic predictors were restricted to CC, secreted virulence factors and virulence regulators. Multivariate regularized logistic regression identified three independent predictors of embolism. Patients at higher risk were younger than the cohort median age of 62.5 y (adjusted odds ratio [OR] 0.14; 95% confidence interval [CI] 0.05–0.36). S. aureus characteristics predicting embolism were a CC30 genetic background (adjusted OR 9.734; 95% CI 1.53–192.8) and the absence of pIB485-like plasmid-borne enterotoxin-encoding genes sed, sej, and ser (sedjr; adjusted OR 0.07; 95% CI 0.004–0.457). CC30 S. aureus has been repeatedly reported to exhibit enhanced fitness in bloodstream infections, which might impact its ability to cause embolism. sedjr-encoded enterotoxins, whose superantigenic activity is unlikely to protect against embolism, possibly acted as a proxy to others genes of the pIB485-like plasmid found in genetically unrelated isolates from mostly embolism-free patients. mecA did not independently predict embolism but was strongly associated with sedjr. This mecA-sedjr association might have driven previous reports of a negative association of mecA and embolism. Collectively, our results suggest that the influence of S. aureus genotypic features on the risk of embolism may be stronger than previously suspected and independent of clinical risk factors.
Published: 2018
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2. The importance of an informed choice of CO2-equivalence metrics for contrail avoidance

Author: A. Borella, O. Boucher, K. P. Shine, M. Stettler, K. Tanaka, R. Teoh, and N. Bellouin
Subjects: Physics, QC1-999, Chemistry, QD1-999
Abstract: One of the proposed ways to reduce the climate impact of civil aviation is rerouting aircraft to minimise the formation of warming contrails. As this strategy may increase fuel consumption, it would only be beneficial if the climate impact reduction from the avoided contrails exceeds the negative impact of any additional carbon dioxide (CO2) emitted by the rerouted flight. In this study, we calculate the surface temperature response of almost half a million flights that crossed the North Atlantic sector in 2019 and compare it to the temperature response of hypothetical rerouted flights. The climate impacts of contrails and CO2 are assessed through the perspective of CO2-equivalence metrics, represented here as nine combinations of different definitions and time horizons. We estimate that the total emitted CO2 and the persistent contrails formed will have warmed the climate by 17.2 µK in 2039, 13.7 µK in 2069, and 14.1 µK in 2119. Under an idealised scenario where 1 % additional carbon dioxide is enough to reroute all contrail-forming flights and avoid contrail formation completely, total warming would decrease by 4.9 (−28 %), 2.6 (−19 %), and 1.9 (−13 %) µK in 2039, 2069, and 2119, respectively. In most rerouting cases, the results based on the nine different CO2-equivalence metrics agree that rerouting leads to a climate benefit, assuming that contrails are avoided as predicted. But the size of that benefit is very dependent on the choice of CO2-equivalence metrics, contrail efficacy and CO2 penalty. Sources of uncertainty not considered here could also heavily influence the perceived benefit. In about 10 % of rerouting cases, the climate damage resulting from contrail avoidance indicated by CO2-equivalence metrics integrated over a 100-year time horizon is not predicted by metrics integrated over a 20-year time horizon. This study highlights, using North Atlantic flights as a case study, the implications of the choice of CO2-equivalence metrics for contrail avoidance, but the choice of metric implies a focus on a specific climate objective, which is ultimately a political decision.
Published: 2024
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3. LBA23 Avelumab versus standard second-line treatment chemotherapy in metastatic colorectal cancer (mCRC) patients with microsatellite instability (MSI): The SAMCO-PRODIGE 54 randomised phase II trial

Author: J. Taieb, O. Bouche, T. André, E. Barbier, P. Laurent-Puig, J. Bez, C. Toullec, C. Borg, V. Randrian, L. Evesque, S. Corbinais, B. Buecher, H. Perrier, F. Di Fiore, C. Gallois, C. Lepage, F. El Hajbi, and D. Tougeron
Subjects: Oncology, Hematology
Published: 2022
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4. 1204MO PRODIGE 59 - DURIGAST trial: A randomised phase II study evaluating FOLFIRI plus durvalumab and FOLFIRI plus durvalumab plus tremelimumab in second-line treatment of patients with advanced gastric or gastro-oesophageal junction adenocarcinoma

Author: D. Tougeron, L. Dahan, F. El Hajbi, K. Le Malicot, L. Evesque, T. Aparicio, O. Bouche, N. Bonichon Lamichhane, B. Chibaudel, A. Angelergues, null A. bodere, J.M. Phelip, M. Mabro, P. Artru, and C. Louvet
Subjects: Oncology, Hematology
Published: 2022
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5. 387P Maintenance treatment with cetuximab versus observation in RAS wild-type metastatic colorectal cancer: Final results of the randomized phase II TIME-PRODIGE 28 UNICANCER study

Author: V. Boige, E. Francois, H. Blons, M. Ben Abdelghani, J.M. Phelip, V. Ly Lebrun, L. Mineur, M.P. Galais, A-L. Villing, V. Hautefeuille, L. Miglianico, C. de la Fouchardiere, D. Genet, N. Levasseur, N. Lachaux, S. Gourgou, F. Castan, and O. Bouche
Subjects: Oncology, Hematology
Published: 2022
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6. A perspective on the next generation of Earth system model scenarios: towards representative emission pathways (REPs)

Author: M. Meinshausen, C.-F. Schleussner, K. Beyer, G. Bodeker, O. Boucher, J. G. Canadell, J. S. Daniel, A. Diongue-Niang, F. Driouech, E. Fischer, P. Forster, M. Grose, G. Hansen, Z. Hausfather, T. Ilyina, J. S. Kikstra, J. Kimutai, A. D. King, J.-Y. Lee, C. Lennard, T. Lissner, A. Nauels, G. P. Peters, A. Pirani, G.-K. Plattner, H. Pörtner, J. Rogelj, M. Rojas, J. Roy, B. H. Samset, B. M. Sanderson, R. Séférian, S. Seneviratne, C. J. Smith, S. Szopa, A. Thomas, D. Urge-Vorsatz, G. J. M. Velders, T. Yokohata, T. Ziehn, and Z. Nicholls
Subjects: Geology, QE1-996.5
Abstract: In every Intergovernmental Panel on Climate Change (IPCC) Assessment cycle, a multitude of scenarios are assessed, with different scope and emphasis throughout the various Working Group reports and special reports, as well as their respective chapters. Within the reports, the ambition is to integrate knowledge on possible climate futures across the Working Groups and scientific research domains based on a small set of “framing pathways” such as the so-called representative concentration pathways (RCPs) in the Fifth IPCC Assessment Report (AR5) and the shared socioeconomic pathway (SSP) scenarios in the Sixth Assessment Report (AR6). This perspective, initiated by discussions at the IPCC Bangkok workshop in April 2023 on the “Use of Scenarios in AR6 and Subsequent Assessments”, is intended to serve as one of the community contributions to highlight the needs for the next generation of framing pathways that is being advanced under the Coupled Model Intercomparison Project (CMIP) umbrella, which will influence or even predicate the IPCC AR7 consideration of framing pathways. Here we suggest several policy research objectives that such a set of framing pathways should ideally fulfil, including mitigation needs for meeting the Paris Agreement objectives, the risks associated with carbon removal strategies, the consequences of delay in enacting that mitigation, guidance for adaptation needs, loss and damage, and for achieving mitigation in the wider context of societal development goals. Based on this context, we suggest that the next generation of climate scenarios for Earth system models should evolve towards representative emission pathways (REPs) and suggest key categories for such pathways. These framing pathways should address the most critical mitigation policy and adaptation plans that need to be implemented over the next 10 years. In our view, the most important categories are those relevant in the context of the Paris Agreement long-term goal, specifically an immediate action (low overshoot) 1.5 °C pathway and a delayed action (high overshoot) 1.5 °C pathway. Two other key categories are a pathway category approximately in line with current (as expressed by 2023) near- and long-term policy objectives, as well as a higher-emission category that is approximately in line with “current policies” (as expressed by 2023). We also argue for the scientific and policy relevance in exploring two “worlds that could have been”. One of these categories has high-emission trajectories well above what is implied by current policies and the other has very-low-emission trajectories which assume that global mitigation action in line with limiting warming to 1.5 °C without overshoot had begun in 2015. Finally, we note that the timely provision of new scientific information on pathways is critical to inform the development and implementation of climate policy. Under the Paris Agreement, for the second global stocktake, which will occur in 2028, and to inform subsequent development of nationally determined contributions (NDCs) up to 2040, scientific inputs are required by 2027. These needs should be carefully considered in the development timeline of community modelling activities, including those under CMIP7.
Published: 2024
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7. Variability in the properties of the distribution of the relative humidity with respect to ice: implications for contrail formation

Author: S. Sanogo, O. Boucher, N. Bellouin, A. Borella, K. Wolf, and S. Rohs
Subjects: Physics, QC1-999, Chemistry, QD1-999
Abstract: Relative humidity with respect to ice (RHi) is a key variable in the formation of cirrus clouds and contrails. We document its probability density function (PDF) using long-term Measurements of Ozone, Water Vapour, Carbon Monoxide and Nitrogen Oxides by In-Service Airbus Aircraft (MOZAIC) and the In-service Aircraft for a Global Observing System (IAGOS) observations over the period 1995–2022 in the upper troposphere (UT) and the lower stratosphere (LS) between 325 and 175 hPa. The characteristics of the RHi PDF differ in the UT and in the LS of the high-latitude regions (HLs) and mid-latitude regions (MLs) of the Northern Hemisphere. In the LS, this PDF decreases exponentially with increasing RHi. In the UT, it first increases exponentially in subsaturated conditions and then decreases exponentially in supersaturated conditions. Because of these different behaviors, the PDF for the combined UT and LS is bimodal. In contrast to the HLs and the MLs, the RHi PDF in the tropical troposphere decreases exponentially with increasing RHi. The different forms of PDF, in the tropics and in the higher-latitude regions, lead to a global PDF of RHi in subsaturated tropospheric conditions that is almost uniform. These findings invite caution when using MOZAIC and IAGOS measurements to calibrate large-scale simulations of RHi. The variability in RHi properties associated with that of temperature also has implications for the formation of contrails. We examined the impact of switching fuel (from kerosene to bioethanol or liquid hydrogen) on the frequency of contrail formation using the Schmidt–Appleman criterion. We show that bioethanol and, to a larger extent, liquid hydrogen would produce more contrails. The impact of a potential change from kerosene to these alternative fuels decreases with decreasing pressure but increases when moving from the higher latitudes of the Northern Hemisphere to the tropics. Finally, we emphasize that investigations of the impact on contrail occurrence frequency as a result of switching from fossil kerosene to more sustainable fuels must be carried out in various meteorological conditions.
Published: 2024
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8. Distribution and morphology of non-persistent contrail and persistent contrail formation areas in ERA5

Author: K. Wolf, N. Bellouin, and O. Boucher
Subjects: Physics, QC1-999, Chemistry, QD1-999
Abstract: The contrail formation potential as well as its temporal and spatial distribution is estimated using meteorological conditions of temperature and relative humidity from the ERA5 re-analysis provided by the European Centre for Medium-Range Weather Forecasts. Contrail formation is estimated with the Schmidt–Appleman criterion (SAc), solely considering thermodynamic effects. The focus is on a region ranging from the Eastern United States (110–65° W) to central Europe (5° W–30° E). Around 18 000 flight trajectories from the In-service Aircraft for a Global Observing System (IAGOS) are used as a representative subset of transatlantic, commercial flights. The typical crossing distance through a contrail-prone area is determined based on IAGOS measurements of temperature T and relative humidity r and then based on co-located ERA5 simulations of the same quantities. Differences in spatial resolution between IAGOS and ERA5 are addressed from an aircraft-centered perspective, using 1 km segments, and a model-centered perspective, using 19 km flight sections. Using the aircraft-centered approach, 50 % of the crossings of persistent contrail (PC) regions based on IAGOS are shorter than 9 km, while in ERA5 the median is 155 km. Time-averaged IAGOS data lead to a median crossing length of 66 km. The difference between the two data sets is attributed to the higher variability of r in IAGOS compared to ERA5. The model-centered approach yields similar results, but typical crossing lengths are larger by only up to 10 %. Binary masks of PC formation are created by applying the SAc on the two-dimensional fields of T and r from ERA5. In a second step the morphology of PC regions is also assessed. Half of the PC regions in ERA5 are found to be smaller than ≈ 35 000 km2 (at 200 hPa), and the median of the maximum dimension is shorter than 760 km (at 200 hPa). Furthermore, PC regions tend to be of near-circular shape with a tendency to a slight oval shape and a preferred alignment along the dominant westerly flow. Seasonal, vertical distributions of PC formation potential 𝒫 are characterized by a maximum between 250 and 200 hPa. 𝒫 is subject to seasonal variations with a maximum in magnitude and extension during the winter months and a minimum during summer. The horizontal distribution of PC regions suggests that PC regions are likely to appear in the same location on adjacent pressure levels. Climatologies of T, r, wind speed U, and resulting PC formation potential are calculated to identify the constraining effects of T and r on 𝒫. PC formation is primarily limited by conditions that are too warm below and conditions that are too dry above the formation region. The distribution of PCs is slanted towards lower altitudes from 30 to 70° N, following lines of constant T and r. For an observed co-location of high U and 𝒫, it remains unclear whether PC formation and the jet stream are favored by the same meteorological conditions or if the jet stream itself favors PC occurrence. This analysis suggests that some PC regions will be difficult to avoid by rerouting aircraft because of their large vertical and horizontal extents.
Published: 2024
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9. G6-1.5K-SAI: a new Geoengineering Model Intercomparison Project (GeoMIP) experiment integrating recent advances in solar radiation modification studies

Author: D. Visioni, A. Robock, J. Haywood, M. Henry, S. Tilmes, D. G. MacMartin, B. Kravitz, S. J. Doherty, J. Moore, C. Lennard, S. Watanabe, H. Muri, U. Niemeier, O. Boucher, A. Syed, T. S. Egbebiyi, R. Séférian, and I. Quaglia
Subjects: Geology, QE1-996.5
Abstract: The Geoengineering Model Intercomparison Project (GeoMIP) has proposed multiple model experiments during phases 5 and 6 of the Climate Model Intercomparison Project (CMIP), with the latest set of model experiments proposed in 2015. With phase 7 of CMIP in preparation and with multiple efforts ongoing to better explore the potential space of outcomes for different solar radiation modifications (SRMs) both in terms of deployment strategies and scenarios and in terms of potential impacts, the GeoMIP community has identified the need to propose and conduct a new experiment that could serve as a bridge between past iterations and future CMIP7 experiments. Here we report the details of such a proposed experiment, named G6-1.5K-SAI, to be conducted with the current generation of scenarios and models from CMIP6 and clarify the reasoning behind many of the new choices introduced. Namely, compared to the CMIP6 GeoMIP scenario G6sulfur, we decided on (1) an intermediate emission scenario as a baseline (the Shared Socioeconomic Pathway 2-4.5), (2) a start date set in the future that includes both considerations for the likelihood of exceeding 1.5 °C above preindustrial levels and some considerations for a likely start date for an SRM implementation, and (3) a deployment strategy for stratospheric aerosol injection that does not inject in the tropical pipe in order to obtain a more latitudinally uniform aerosol distribution. We also offer more details regarding the preferred experiment length and number of ensemble members and include potential options for second-tier experiments that some modeling groups might want to run. The specifics of the proposed experiment will further allow for a more direct comparison between results obtained from CMIP6 models and those obtained from future scenarios for CMIP7.
Published: 2024
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10. 1296MO PRODIGE 29-UCGI 26(NEOPAN): A phase III randomised trial comparing chemotherapy with folfirinox or gemcitabine in locally advanced pancreatic carcinoma (LAPC)

Author: M.P. Ducreux, R. Desgrippes, Y. Rinaldi, F. Di Fiore, R. Guimbaud, P. Follana, J-B. Bachet, P. Vanelslander, T. Lecomte, O. Capitain, A. Parzy, M. Bolliet, P-L. Etienne, J. Forestier, F. El Hajbi, A.L. Bignon Bretagne, V. Ly Lebrun, N. De Sousa Carvalho, M. Texier, and O. Bouche
Subjects: Oncology, Hematology
Published: 2022
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11. LBA60 Evaluation of gemcitabine and paclitaxel versus gemcitabine alone after FOLFIRINOX failure or intolerance in metastatic pancreatic ductal adenocarcinoma: Results of the randomized phase III PRODIGE 65 - UCGI 36 - GEMPAX UNICANCER study

Author: C. de la Fouchardiere, D. Malka, S. Chabaud, J. Raimbourg, D. Botsen, S. Launay, L. Evesque, A. Vienot, H. Perrier, M. Jary, Y. Rinaldi, C. Coutzac Bergouignan, J-B. Bachet, C. Neuzillet, N. Williet, R. Desgrippes, G. Brard, N. Lachaux, O. Bouche, and F. Ghiringhelli
Subjects: Oncology, Hematology
Published: 2022
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12. LBA28 Prognostic effect of imaging and CEA follow-up in resected colorectal cancer (CRC): Final results and relapse free survival (RFS) - PRODIGE 13 a FFCD phase III trial

Author: C. Lepage, J.M. Phelip, L. Cany, E. Barbier, S. Manfredi, P. Deguiral, R. Faroux, M. Baconnier, D. Pezet, E. Terrebonne, A. Adenis, M. Ben Abdelghani, J.F. Ain, G. Breysacher, I. Boillot Benedetto, A. Pelaquier, A. Lievre, P. Laurent Puig, F. Bibeau, and O. Bouche
Subjects: Oncology, Hematology
Published: 2022
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13. 429P Maintenance treatment with cetuximab versus observation in RAS wild-type metastatic colorectal cancer: First results of the randomized phase II TIME-PRODIGE28 UNICANCER study according to RAS/BRAF status

Author: E. Francois, Hélène Blons, M. Ben Abdelghani, V. Lebrun-Ly, M.P. Galais, Valérie Boige, Sophie Gourgou, L. Mineur, O. Bouche, Florence Castan, Vincent Hautefeuille, Nicolas Lachaux, Anne-Laure Villing, Dominique Genet, J.M. Phelip, Laurent Miglianico, C. de la Fouchardiere, and N. Levasseur
Subjects: Oncology, medicine.medical_specialty, Cetuximab, Colorectal cancer, business.industry, Internal medicine, medicine, Wild type, Hematology, medicine.disease, business, medicine.drug
Published: 2021
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14. 387MO Tumour mutation profiles and circulating tumour cells in metastatic colorectal cancer patients treated with FOLFIRI + cetuximab: A prospective ancillary study of the UNICANCER PRODIGE-28 trial

Author: Sophie Gourgou, E. Francois, Françoise Farace, Valérie Boige, S. Garinet, Nicolas Lachaux, V. Lebrun-Ly, L. Mineur, J.M. Phelip, Hélène Blons, M. Ben Abdelghani, V. Polivka, and O. Bouche
Subjects: Oncology, medicine.medical_specialty, Cetuximab, business.industry, Colorectal cancer, Ancillary Study, Hematology, medicine.disease, Internal medicine, Mutation (genetic algorithm), medicine, FOLFIRI, business, medicine.drug
Published: 2021
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15. 508TiP PRODIGE 68 - UCGI 38 - SOREGATT: A randomized phase II study comparing the sequences of regorafenib (reg) and trifluridine/tipiracil (t/t) after failure of standard therapies in patients (pts) with metastatic colorectal cancer (mCRC)

Author: D. Pannier, Julien Taieb, Anne-Laure Villing, Damien Botsen, H. Alexandre, J-B. Bachet, M. Ben Abdelghani, M-L. Tanguy, Jerome Martin-Babau, F. Garic, A. Parzy, David Tougeron, A. Peytier, O. Bouche, Michel Ducreux, Faiza Khemissa, and J. Viaud
Subjects: Oncology, medicine.medical_specialty, business.industry, Colorectal cancer, Phases of clinical research, Hematology, medicine.disease, chemistry.chemical_compound, chemistry, Internal medicine, Regorafenib, medicine, In patient, business
Published: 2021
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16. 1673MO The GCO-002 CACOVID-19 cohort: A French nationwide multicenter study of COVID-19 infected cancer patients and consequences on cancer management

Author: Didier Debieuvre, Raphael Colle, Anne-Claire Hardy-Bessard, Juliette Thariat, Gérard Zalcman, I.L. Ray-Coquard, Astrid Lièvre, A. Idbaih Ahmed, R. Mathieu, Anthony Turpin, Laura Mansi, Renata Ursu, Guido Ahle, M. L. Garcia-Larnicol, P. Gorphe, K. Le Malicot, V. Sebbagh, Jean Bourhis, O. Bouche, and A. Canellas
Subjects: 0301 basic medicine, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), European community, business.industry, Health authority, Hematology, Article, Cancer treatment, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Multicenter study, Oncology, 030220 oncology & carcinogenesis, Family medicine, Honorarium, Cancer management, Medicine, business, Head and neck
Abstract: Background: The novel COVID-19 outbreak spread rapidly around the world Cancer patients (pts) consist of a highly vulnerable group due to underlying malignancy and/or treatment-induced immunosuppression A high mortality rate from COVID-19 in cancer pts was previously reported France is the fourth most affected country, with more than 150,000 infected individuals and over 28,000 deaths GCO-002 CACOVID-19 study is a large French nationwide cohort of COVID-19 pts with solid tumors with the aim to identify risk factors of COVID-19 severity and evaluate impact on cancer treatment Methods: Bispective multicenter cohort set up by the French Cooperative Groups in solid cancers: ANOCEF-IGCNO (CNS tumors), ARCAGY-GINECO (gynecological and breast cancers), FFCD (digestive cancers), GERCOR (digestive and other solid cancers), GORTEC/intergroupe ORL (head and neck cancers (HNAmgen, Pierre Fabre;Sandoz;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Bayer;Novartis;Honoraria (self): Celgene;HalioDx;Lilly;Honoraria (self), Travel/Accommodation/Expenses: BMS;Roche;Honoraria (self), Research grant/Funding (self): Incyte;Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen;Merck;Servier;Research grant/Funding (self): Integragen;Travel/Accommodation/Expenses: AAA;Pfizer A Turpin: Honoraria (self): Servier;Advisory/Consultancy: Mylan;Merck Serono;Amgen;Travel/Accommodation/Expenses: Merck;Sanofi;Pfizer;AstraZeneca I L Ray-Coquard: Honoraria (self), Advisory/Consultancy: Abbvie;Agenus;Advaxis;Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): BMS;MSD;Honoraria (self), Advisory/Consultancy: PharmaMar;Genmab;Pfizer;Deciphera;Mersena;Amgen;Tesaro;Clovis;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck Serono;Novartis;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca;Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche;Honoraria (self), Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: GSK;Non-remunerated activity/ies: GINECO;ENGOT;GCIG;European community;ESMO;ASCO;ESGO;IGSC;Inca;Swiss and German Health Authorities;Italian Health Authority;Belgium Health Authority J Thariat: Honoraria (self): BMS;Honoraria (institution), Travel/Accommodation/Expenses, Full/Part-time employment: Centre Francois Baclesse;Leadership role: President of the French Head and Neck Intergroup, GORTEC secretary;Non-remunerated activity/ies: Director of Easy-CRF society;Research grant/Funding (institution): Nanobiotix G Ahle: Travel/Accommodation/Expenses: Abbvie;Biogen;Novartis;Roche;Sanofi;Non-remunerated activity/ies: ANOCEF;NENO;AlSacEP R Mathieu: Honoraria (self), Research grant/Funding (self): Astellas;Honoraria (self): AstraZeneca;Ferring;Ipsen;Janssen;MSD;Pfizer;Sanofi;Takeda D Debieuvre: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer;Roche;Novartis;BMS;MSD;Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca;Honoraria (self), Research grant/Funding (institution): Chugai;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Boerhinger-Ingelheim;Research grant/Funding (institution): Chiesi;Sandoz;Takeda;GSK;Research grant/Funding (self): Lilly A Canellas: Honoraria (self), Advisory/Consultancy: BMS;Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca;Travel/Accommodation/Expenses: Oxyvie;LVL Medical;Boerhinger Ingelheim A-C Hardy-Bessard: Advisory/Consultancy: Clovis;Novartis;Roche;MSD;AstraZeneca;GSK L Mansi: Honoraria (institution), Advisory/Consultancy: Sandoz;Advisory/Consultancy: Roche;Eisai;Pfizer;Novartis;Speaker Bureau/Expert testimony: Exact Sciences;Travel/Accommodation/Expenses: Lilly P Gorphe: Honoraria (self): Intuitive Surgical;Non-remunerated activity/ies: Chair, scientific board, French Head and Neck Intergroup;Research grant/Funding (institution): MSD A IDBAIH Ahmed: Research grant/Funding (institution): Transgene;Sanofi;Air Liquide;Travel/Accommodation/Expenses: Carthera;Leo Pharma G Zalcman: Honoraria (self), Honoraria (institution), Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS;Honoraria (self), Honoraria (institution), Travel/Accommodation/Expenses: AstraZeneca;Honoraria (institution), Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche;Honoraria (institution): Takeda;Travel/Accommodation/Expenses: Pfizer;AbbVie;MSD O Bouche: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche;Honoraria (self), Advisory/Consultancy: Merck KgaA;Bayer;AstraZeneca;Grunenthal;MSD;Honoraria (self), Speaker Bureau/Expert testimony: Amgen;Pierre Fabre;Honoraria (self), Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Servier All other authors have declared no conflicts of interest
Published: 2020
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17. Sensitivity of cirrus and contrail radiative effect on cloud microphysical and environmental parameters

Author: K. Wolf, N. Bellouin, and O. Boucher
Subjects: Physics, QC1-999, Chemistry, QD1-999
Abstract: Natural cirrus clouds and contrails cover about 30 % of the Earth's mid-latitudes and up to 70 % of the tropics. Due to their widespread occurrence, cirrus clouds have a considerable impact on the Earth energy budget, which, on average, leads to a warming net radiative effect (solar + thermal infrared). However, whether the instantaneous radiative effect (RE), which in some cases corresponds to a radiative forcing, of natural cirrus or contrails is positive or negative depends on their microphysical, macrophysical, and optical properties, as well as the radiative properties of the environment. This is further complicated by the fact that the actual ice crystal shape is often unknown, and thus, ice clouds remain one of the components that are least understood in the Earth's radiative budget. The present study aims to investigate the dependency of the effect on cirrus RE on eight parameters, namely solar zenith angle, ice water content, ice crystal effective radius, cirrus temperature, surface albedo, surface temperature, cloud optical thickness of an underlying liquid water cloud, and three ice crystal shapes. In total, 283 500 plane-parallel radiative transfer simulations have been performed, not including three-dimensional scattering effects. Parameter ranges are selected that are typically associated with natural cirrus and contrails. In addition, the effect of variations in the relative humidity profile and the ice cloud geometric thickness have been investigated for a sub-set of the simulations. The multi-dimensionality and complexity of the eight-dimensional parameter space makes it impractical to discuss all potential configurations in detail. Therefore, specific cases are selected and discussed. For a given parameter combination, the largest impact on solar, thermal-infrared (TIR), and net RE is related to the ice crystal effective radius. The second most important parameter is ice water content, which equally impacts the solar and terrestrial RE. The solar RE of cirrus is also determined by solar zenith angle, surface albedo, liquid cloud optical thickness, and ice crystal shape (in descending priority). RE in the TIR spectrum is dominated by surface temperature, ice cloud temperature, liquid water cloud optical thickness, and ice crystal shape. Net RE is controlled by surface albedo, solar zenith angle, and surface temperature in decreasing importance. The relative importance of the studied parameters differs, depending on the ambient conditions. Furthermore, and during nighttime the net RE is equal to the TIR RE. The data set generated in this work is publicly available. It can be used as a lookup table to extract the RE of cirrus clouds, contrails, and contrail cirrus instead of full radiative transfer calculations.
Published: 2023
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18. 394P Preliminary tolerance analysis of adjuvant chemotherapy in older patients after resection of stage III colon adenocarcinoma from PRODIGE 34-FFCD 1402-ADAGE randomized phase III trial

Author: Thomas Aparicio, Sandrine Hiret, P.L. Etienne, R. Desgrippes, V. Lebrun-Ly, Y. Rinaldi, F. Hocine, L. Mineur, M. Pauwels, M. Van den Eynde, J.J. Martin, J. Cretin, Jérôme Desramé, Eric Terrebonne, L. Cany, Anthony Turpin, Emilie Barbier, Claire Falandry, O. Bouche, L. Mosser, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (SLuc) Service d'oncologie médicale, and UCL - (SLuc) Service d'hépato-gastro-entérologie
Subjects: Oncology, medicine.medical_specialty, business.industry, Adjuvant chemotherapy, Hematology, Resection, Older patients, Internal medicine, Medicine, Colon adenocarcinoma, Stage (cooking), business
Abstract: Background Colon adenocarcinoma occurs mainly in older patients (pts). Oxaliplatin based adjuvant chemotherapy has demonstrated an improvement on disease-free survival (DFS) after a stage III colon cancer resection in young pts. Nevertheless, the benefit of adjuvant chemotherapy is matter of debate in old pts. Methods The purpose of ADAGE trial is to compare the DFS obtain with oxaliplatin combined with fluoropyrimidine (F) to F alone in fit pts over 70 years (group 1) and F to observation in frail pts (group 2) after resection of a stage III colon cancer. We here report a preliminary tolerance analysis on 50% of the first pts enrolled in the study. Results The analysis was performed on 491 pts (378 in group 1 and 113 in group 2). Main pts characteristics were respectively for the group 1 and 2: male in 57% and 50%, median age of 76 and 83 years, ECOG=0 in 59% and 29%, abnormal IADL in 23% and 62%, no caregiver in 26% and 28%, fall ≤6 months in 9% and 14%, depression possible 28% and 40%, fail of one-leg balance in 20% and 59%, impaired cognition in 21% and 38%, G8 score
Published: 2021
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19. 481P Evaluation of serum mid-infrared spectroscopy as new prognostic marker for bevacizumab-based chemotherapy in first-line treatment of metastatic colorectal cancer

Author: C.J. Pobel, Aurélie Ferru, O. Sire, William Raoul, J.-Y. Douillard, M. Caulet, Olivier Capitain, Thierry Lecomte, Sylvain Manfredi, Maxime Guéguinou, Christophe Borg, O. Hérault, E. Terrebonne, Romain Chautard, Julie Léger, J-P. Spano, and O. Bouche
Subjects: Oncology, medicine.medical_specialty, Chemotherapy, Bevacizumab, Colorectal cancer, business.industry, medicine.medical_treatment, Hematology, medicine.disease, Mid infrared spectroscopy, First line treatment, Internal medicine, medicine, business, medicine.drug
Published: 2021
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20. LBA57 Unicancer PRODIGE 24/CCTG PA6 trial: Updated results of a multicenter international randomized phase III trial of adjuvant mFOLFIRINOX (mFFX) versus gemcitabine (gem) in patients (pts) with resected pancreatic ductal adenocarcinomas (PDAC)

Author: A. Lambert, E. Francois, Anthony Turpin, L. Monard, Marc Ychou, James Joseph Biagi, Thierry Lecomte, A. Lopez, Roger Faroux, Alice C. Wei, J-B. Bachet, Florence Castan, C. Belletier, Patrick Rat, O. Bouche, Pascal Hammel, Eric Assenat, T. Conroy, Pascal Artru, and Emmanuel Mitry
Subjects: Oncology, medicine.medical_specialty, business.industry, medicine.medical_treatment, Hematology, Gemcitabine, Internal medicine, Medicine, In patient, Pancreatic carcinoma, business, Adjuvant, medicine.drug
Published: 2021
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21. Health-related quality of life results from the PRODIGE 5/ACCORD 17 randomised trial of FOLFOX versus fluorouracil–cisplatin regimen in oesophageal cancer

Author: M.P. Galais, Antoine Adenis, J.-Y. Douillard, P.L. Etienne, O. Bouche, Sophie Gourgou, Thierry Conroy, C. Bascoul-Mollevi, Beata Juzyna, Laurent Bedenne, Jean-Luc Raoul, UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM), CRLCC Val d'Aurelle - Paul Lamarque, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'hépato-gastro-entérologie et cancérologie digestive [CHU de Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), CRLCC René Gauducheau, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, UNICANCER [Paris], Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Département d’Oncologie Médicale [Vandoeuvre Les Nancy], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER-UNICANCER, Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), and Université de Lille-UNICANCER
Subjects: Male, Oncology, Cancer Research, Time Factors, Esophageal Neoplasms, Organoplatinum Compounds, Leucovorin, 0302 clinical medicine, Quality of life, FOLFOX, Risk Factors, Surveys and Questionnaires, Antineoplastic Combined Chemotherapy Protocols, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Oesophageal cancer, Chemoradiotherapy, Middle Aged, Dysphagia, 3. Good health, Oxaliplatin, Treatment Outcome, Fluorouracil, 030220 oncology & carcinogenesis, Carcinoma, Squamous Cell, Female, Esophageal Squamous Cell Carcinoma, France, medicine.symptom, medicine.drug, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Adenocarcinoma, Prognostic factors, Disease-Free Survival, Carcinoma, Adenosquamous, 03 medical and health sciences, Internal medicine, medicine, Humans, Neoplasm Staging, business.industry, Regimen, Multivariate Analysis, Linear Models, Quality of Life, Dose Fractionation, Radiation, Cisplatin, business
Abstract: IF 6.029; International audience; BackgroundA recent prospective randomised trial did not reveal significant differences in median progression-free survival between two chemoradiotherapy (CRT) regimens for inoperable non-metastatic oesophageal cancer patients. This secondary analysis aimed to describe the impact of CRT on health-related quality of life (HRQOL), physical functioning, dysphagia, fatigue and pain and to evaluate whether baseline HRQOL domains can predict overall survival.Patients and methodsA total of 267 patients were randomly assigned to receive with 50 Gy of radiotherapy in 25 fractions six cycles of FOLFOX or four cycles of fluorouracil and cisplatin on day 1. HRQOL was prospectively assessed using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire version 3.0 with the oesophageal cancer module (QLQ-OES18).ResultsBoth groups showed high baseline compliance. Subsequently, compliance reduced to 41% at the 6-month follow-up. Baseline HRQOL scores showed no statistical differences between treatment arms. During treatment, both groups exhibited lower physical and social functioning and increased fatigue and dyspnoea, although dysphagia moderately improved in the fluorouracil–cisplatin arm only (p = 0.047).During follow-up, HRQOL scores revealed no significant differences between chemotherapy regimens. Linear mixed model exhibited a treatment-by-time interaction effect for dysphagia (p = 0.017) with a greater decrease in dysphagia in the fluorouracil–cisplatin group. Time until definitive deterioration analysis showed no significant differences in global HRQOL, functional or main symptom domains. However, time until definitive deterioration was significantly longer for the fluorouracil and cisplatin arm compared with FOLFOX for appetite loss (p = 0.002), QLQ-OES-18 pain (p = 0.008), trouble swallowing saliva (p = 0.011) and trouble talking (p = 0.020).ConclusionAnalyses of HRQOL scores revealed no statistically significant differences between patients with inoperable non-metastatic oesophageal cancer treated by FOLFOX versus those treated with a fluorouracil–cisplatin regimen as part of definitive CRT.
Published: 2017
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22. 1454P PARAFIRIGAST: Paclitaxel/ramucirumab versus FOLFIRI as second line chemotherapy of metastatic gastric cancer: An AGEO multicenter comparative study with a propensity score analysis

Author: A. Pellat, C. Toullec, M. Kroemer, David Tougeron, J. Vivier-Chicoteau, J. Lavole, B. De Rauglaudre, Astrid Pozet, Gael Goujon, David Sefrioui, Yann Touchefeu, Vincent Hautefeuille, A.L. Bignon Bretagne, Carole Vitellius, J. Wasselin, Anthony Turpin, O. Bouche, A. Zaanan, S. Racine Doat, and Cristina Smolenschi
Subjects: Oncology, medicine.medical_specialty, business.industry, Hematology, Second line chemotherapy, Metastatic gastric cancer, Ramucirumab, chemistry.chemical_compound, Paclitaxel, chemistry, Internal medicine, Propensity score matching, medicine, FOLFIRI, business
Published: 2020
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23. Why do guidelines supersede the conference consensus?: New French recommendations for metastatic colorectal cancer management

Author: J M, Phelip, O, Bouche, T, Aparicio, and C, Lepage
Subjects: Consensus, Rectal Neoplasms, Colonic Neoplasms, Humans, Intestine, Large, Follow-Up Studies
Published: 2019

24. Perioperative FOLFOX 4 Versus FOLFOX 4 Plus Cetuximab Versus Immediate Surgery for High-Risk Stage II and III Colon Cancers: A Phase II Multicenter Randomized Controlled Trial (PRODIGE 22)

Author: Mehdi Karoui, Cedric Lecaille, C. de Chaisemartin, Johannes Hartwig, Julien Taieb, O. Bouche, Guillaume Piessen, Emilie Barbier, G. Portier, Jean-Marc Regimbeau, Olivier Glehen, Hanifa Ammarguellat, Côme Lepage, Michel Prudhomme, for Prodige investigators, Astrid Lièvre, Gael Goujon, Francesco Brunetti, Jean-Louis Legoux, Anne Rullier, and Benoit Romain
Subjects: Adult, Male, medicine.medical_specialty, Organoplatinum Compounds, Colorectal cancer, medicine.medical_treatment, Population, Leucovorin, Cetuximab, 03 medical and health sciences, 0302 clinical medicine, FOLFOX, Antineoplastic Combined Chemotherapy Protocols, Medicine, Humans, education, Colectomy, Aged, Neoplasm Staging, Tumor Regression Grade, education.field_of_study, business.industry, Perioperative, Middle Aged, medicine.disease, Interim analysis, digestive system diseases, Neoadjuvant Therapy, 3. Good health, Surgery, Tolerability, 030220 oncology & carcinogenesis, Colonic Neoplasms, 030211 gastroenterology & hepatology, Female, Fluorouracil, France, business, Tomography, X-Ray Computed, medicine.drug
Abstract: BACKGROUND Perioperative chemotherapy has proven valuable in several tumors, but not in colon cancer (CC). OBJECTIVE The aim of this study was to evaluate the efficacy and safety of perioperative chemotherapy in patients with locally advanced nonmetastatic CC. METHODS This is a French multicenter randomized phase II trial in patients with resectable high-risk T3, T4, and/or N2 CC on baseline computed tomography (CT) scan. Patients were randomized to receive either 6 months of adjuvant FOLFOX after colectomy (control) or perioperative FOLFOX for 4 cycles before surgery and 8 cycles after (FOLFOX peri-op). In RAS wild-type patients, a third arm testing perioperative FOLFOX-cetuximab was added. Tumor Regression Grade (TRG1) of Ryan et al was the primary endpoint. Secondary endpoints were toxicity, perioperative morbidity, and quality of surgery. RESULTS A total of 120 patients were enrolled. At interim analysis, the FOLFOX-cetuximab arm was stopped (lack of efficacy). The remaining 104 patients (control, n = 52; FOLFOX preop n = 52) represented our intention-to-treat population. In the FOLFOX perioperative group, 96% received the scheduled 4 cycles before surgery. R0 resection and complete mesocolic excision rate were 94% and 93%, respectively. Overall mortality and morbidity rates were similar in both groups. Perioperative FOLFOX chemotherapy did not improve major pathological response rate (TRG1 = 8%) but was associated with a significant pathological regression (TRG1-2 = 44% vs 8%, P < 0.001) and a trend to tumor downstaging as compared to the control group. CT scan criteria were associated with a 33% rate of overstaging in control group. CONCLUSIONS Perioperative FOLFOX for locally advanced resectable CC is feasible with an acceptable tolerability but is not associated with an increased major pathological response rate as expected. However, perioperative FOLFOX induces pathological regression and downstaging. Better preoperative staging tools are needed to decrease the risk of overtreating patients.
Published: 2019

25. 435P Bevacizumab (bev) continuation with FOLFIRI or switch to aflibercept (afli) with FOLFIRI as second-line treatment (L2) after first line of FOLFOX-bev (L1) for metastatic colorectal cancer (mCRC): An AGEO multicenter study

Author: Anthony Turpin, Edouard Auclin, Christophe Locher, C. Torregrosa, L-J. Palmieri, E. Nassif, S. Racine Doat, A. Perret, Simon Pernot, Thierry Lecomte, B. Auberger, M. Jaffrelot, Cindy Neuzillet, T. Godet, Julien Taieb, Cedric Lecaille, Violaine Randrian, O. Bouche, Olivier Dubreuil, and David Sefrioui
Subjects: Oncology, medicine.medical_specialty, Second line treatment, Bevacizumab, business.industry, Colorectal cancer, First line, Hematology, medicine.disease, FOLFOX, Multicenter study, Internal medicine, FOLFIRI, Medicine, business, medicine.drug, Aflibercept
Published: 2020
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26. 526O High activity of nivolumab in patients with pathogenic exonucleasic domain POLE (edPOLE) mutated Mismatch Repair proficient (MMRp) advanced tumours

Author: F. Legrand, N. Hoog-Labouret, Frederic Rolland, P. Augereau, O. Bouche, Romain Cohen, Julien Masliah-Planchon, Ivan Bièche, B.J-C. Rousseau, C. Simon, N. Hamzaoui, Eric Pasmant, Sylvie Chevret, J.-J. Grob, A. Lamrani-Ghaouti, Esma Saada-Bouzid, D. Pouessel, V. Simmet, Aurélien Marabelle, and A. Bruyas
Subjects: Oncology, business.industry, Cancer research, High activity, Medicine, In patient, DNA mismatch repair, Hematology, Nivolumab, business, Domain (software engineering)
Published: 2020
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27. LBA21 Neoadjuvant mFOLFIRINOX and preoperative chemoradiation (CRT) versus preoperative CRT in patients with T3-4 rectal cancer: Surgical and quality of life results of PRODIGE 23 phase III trial

Author: Christophe Borg, E. Francois, Eric Rullier, Frédéric Marchal, C. Louvet, Valérie Boige, Caroline Mollevi, Emmanuel Rio, Véronique Vendrely, Xavier Artignan, Nathalie Bonichon-Lamichhane, Dany Gargot, P.L. Etienne, O. Bouche, Clotilde Morand, Nathalie Mesgouez-Nebout, C. de la Fouchardiere, Beata Juzyna, T. Conroy, and Florence Castan
Subjects: medicine.medical_specialty, Preoperative chemoradiotherapy, Oncology, Quality of life, Colorectal cancer, business.industry, medicine, In patient, Hematology, Radiology, medicine.disease, business
Published: 2020
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28. 398O Effect of 5 years of imaging and CEA follow-up to detect recurrence of colorectal cancer (CRC) - PRODIGE 13 a FFCD phase III trial

Author: M. Baconnier, Astrid Lièvre, I. Boillot-Benedetto, Sylvain Manfredi, Emilie Barbier, Philippe Deguiral, Eric Terrebonne, L. Cany, M. Benabdelghani, C. Lepage, Denis Pezet, J. Ain, Antoine Adenis, Roger Faroux, O. Bouche, P. Prost, J.-C. Duchmann, Gilles Breysacher, J.M. Phelip, and A. Pelaquier
Subjects: Oncology, medicine.medical_specialty, Colorectal cancer, business.industry, Internal medicine, medicine, Hematology, medicine.disease, business
Published: 2020
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29. RAS mutation analysis in circulating tumor DNA from patients with metastatic colorectal cancer: the AGEO RASANC prospective multicenter study

Author: Julien Taieb, Romain Coriat, Thomas Aparicio, David Tougeron, J.-M. Gornet, Pierre Laurent-Puig, Valérie Taly, Aurélia Meurisse, Pascal Artru, Olivier Dubreuil, Jean-Baptiste Bachet, Samy Louafi, Hélène Blons, Lysiane Marthey, F. Bonnetain, Thierry Lecomte, Corinne Normand, Anne Thirot-Bidault, Dewi Vernerey, O. Bouche, Magali Garcia, Florence Mary, I. Baumgaertner, Centre Hospitalier Universitaire de Reims (CHU Reims), Unité de Méthodologie et de Qualité de Vie en Cancérologie (UMQVC), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Pôle cancérologie (CHU Besançon), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Institut Régional Fédératif du Cancer (IRFC), Centre Scientifique et Technique du Bâtiment (CSTB), Service de Gastroentérologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Clinique Jean-Mermoz, Hôpital privé Jean Mermoz, Amélioration génétique et adaptation des plantes méditerranéennes et tropicales (UMR AGAP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Hôpital Bicêtre, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours, Tri ionique par les Systèmes Moléculaires auto-assemblés (LTSM), Institut de Chimie Séparative de Marcoule (ICSM - UMR 5257), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM), Service d'hépato-gastro-entérologie [Hôpital Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Bases moléculaires de la réponse aux xénobiotiques (U775 (IFR95)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Association des Gastroentérologues Oncologues [Paris] (AGEO), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Department of Digestive Oncology, Hopital Europeen Georges Pompidou, Paris, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Pôle cancérologie (CHRU Besançon), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut Régional Fédératif du Cancer (IRFC), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'oncologie [Hôpital Sud Francilien, Corbeil Essonnes], Hôpital Sud Francilien Corbeil-Essonnes, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service de Gastro-entérologie [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), TALY, Valerie, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Pôle cancérologie (CHRU Besançon), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut Régional Fédératif du Cancer (IRFC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC)-Pôle cancérologie (CHU Besançon), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro), Inserm UMR 1098, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Pôle cancérologie (CHU Besançon), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de la Recherche Agronomique (INRA)
Subjects: 0301 basic medicine, Oncology, Adult, Male, medicine.medical_specialty, Colorectal cancer, Concordance, [SDV]Life Sciences [q-bio], DNA Mutational Analysis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Circulating Tumor DNA, 03 medical and health sciences, Young Adult, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Predictive Value of Tests, Internal medicine, medicine, Biomarkers, Tumor, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Prospective Studies, Lung cancer, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, Aged, Randomized Controlled Trials as Topic, Aged, 80 and over, business.industry, Patient Selection, Liver Neoplasms, Hematology, Odds ratio, Middle Aged, medicine.disease, 3. Good health, Clinical trial, [SDV] Life Sciences [q-bio], 030104 developmental biology, 030220 oncology & carcinogenesis, Predictive value of tests, ras Proteins, Biomarker (medicine), Female, business, Colorectal Neoplasms
Abstract: International audience; Background:RAS mutations are currently sought for in tumor samples, which takes a median of almost 3 weeks in western European countries. This creates problems in clinical situations that require urgent treatment and for inclusion in therapeutic trials that need RAS status for randomization. Analysis of circulating tumor DNA might help to shorten the time required to determine RAS mutational status before anti-epidermal growth factor receptor antibody therapy for metastatic colorectal cancer. Here we compared plasma with tissue RAS analysis in a large prospective multicenter cohort.Patients and methods:Plasma samples were collected prospectively from chemotherapy-naive patients and analyzed centrally by next-generation sequencing (NGS) with the colon lung cancer V2 Ampliseq panel and by methylation digital PCR (WIF1 and NPY genes). Tumoral RAS status was determined locally, in parallel, according to routine practice. For a minimal κ coefficient of 0.7, reflecting acceptable concordance (precision ± 0.07), with an estimated 5% of non-exploitable data, 425 subjects were necessary.Results:From July 2015 to December 2016, 425 patients were enrolled. For the 412 patients with available paired plasma and tumor samples, the κ coefficient was 0.71 [95% confidence interval (CI), 0.64-0.77] and accuracy was 85.2% (95% CI, 81.4% to 88.5%). In the 329 patients with detectable ctDNA (at least one mutation or one methylated biomarker), the κ coefficient was 0.89 (95% CI, 0.84-0.94) and accuracy was 94.8% (95% CI, 91.9% to 97.0%). The absence of liver metastases was the main clinical factor associated with inconclusive circulating tumor DNA results [odds ratio = 0.11 (95% CI, 0.06-0.21)]. In patients with liver metastases, accuracy was 93.5% with NGS alone and 97% with NGS plus the methylated biomarkers.Conclusion:This prospective trial demonstrates excellent concordance between RAS status in plasma and tumor tissue from patients with colorectal cancer and liver metastases, thus validating plasma testing for routine RAS mutation analysis in these patients.Clinical Trial registration:Clinicaltrials.gov, NCT02502656.
Published: 2018
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30. OC-0284: First results of the French cohort ANABASE : treatment and outcome in non-metastatic anal cancer

Author: C. Lemanski, David Tougeron, A. de la Rochefordière, M. Saliou, Véronique Vendrely, Eric Francois, Côme Lepage, O. Bouche, J. Cretin, N. Bonichon-Lamichhane, Emilie Barbier, P. Pommier, O. Diaz, Laurent Quero, P. Ronchin, N. Baba Hamed, CHU Bordeaux [Bordeaux], UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM), CRLCC Val d'Aurelle - Paul Lamarque, Service d'oncologie médicale (Centre Antoine Lacassagne, Nice), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA)-UNICANCER, Fédération Francophone de la Cancérologie Digestive, FFCD, Centre hospitalier Saint-Joseph [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Clinique Tivoli Ducos [Bordeaux], Institut Curie [Paris], Centre Hospitalier Universitaire de Reims (CHU Reims), Service d’hépato-gastro-entérologie et assistance nutritive [CHU de Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut Daniel Hollard [Grenoble], Centre Léon Bérard [Lyon], Centre Azureen de cancérologie, Clinique Mutualiste de l'Estuaire (Saint Nazaire), Institut de Cancérologie du GARD ICG - CHU Nîmes (Instit Cancéro - GARD), Service d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), université de Bourgogne, LNC, UNICANCER - Institut régional du Cancer [Montpellier] (ICM), Centre Antoine Lacassagne de Nice, Groupe hospitalier Paris Saint-Joseph - Hôpital, Clinique Tivoli-Ducos, Institut Curie, Institut de Cancérologie du GARD (Instit Cancéro - GARD), and Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
Subjects: Oncology, medicine.medical_specialty, business.industry, [SDV.CAN]Life Sciences [q-bio]/Cancer, 02 engineering and technology, Hematology, 021001 nanoscience & nanotechnology, medicine.disease, Outcome (game theory), 3. Good health, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Internal medicine, Cohort, 0202 electrical engineering, electronic engineering, information engineering, medicine, Non metastatic, Anal cancer, 020201 artificial intelligence & image processing, Radiology, Nuclear Medicine and imaging, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 0210 nano-technology, business
Abstract: IF 4.942 (2017); International audience
Published: 2018

31. Bevacizumab+chemotherapy versus chemotherapy alone in elderly patients with untreated metastatic colorectal cancer: a randomized phase II trial-PRODIGE 20 study results

Author: Julien Taieb, Roger Faroux, M. Baconnier, Laurent Bedenne, Alice Oden-Gangloff, Elena Paillaud, F. Khemissa Akouz, F. Retornaz, Sandrine Lavau-Denes, F. El Hajbi, P.L. Etienne, Christophe Locher, O. Bouche, S. Kirscher, E. Maillard, Yves Rinaldi, Thomas Aparicio, Dominique Genet, E. Francois, Thierry Lecomte, Service d'hépato-gastro-entérologie [Hôpital Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Sorbonne Paris Cité ( USPC ), Service d'hépato-gastro-entérologie et cancérologie digestive [CHU de Reims], Centre Hospitalier Universitaire de Reims ( CHU de Reims ), Service de chirurgie digestive, générale et cancérologique [Hôpital européen Georges-Pompidou], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Fédération Francophone de la Cancérologie Digestive, FFCD, Institut Sainte Catherine [Avignon], Service de hépato-gastro-entérologie - cancérologie digestive [CH de Perpignan], Centre Hospitalier Saint Jean de Perpignan, CRLCC Oscar Lambret, Service des maladies de l'appareil digestif (CH Meaux), CH Meaux, Service de gastro-entérologie (Hôpital Européen de Marseille), Hôpital Européen [Fondation Ambroise Paré - Marseille], Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], CHU Trousseau [APHP]-Centre Hospitalier Régional Universitaire de Tours ( CHRU TOURS ), CHU Dupuytren, Service d'hépato-gastro-entérologie et endoscopies (CH Annecy), CH Annecy Genevois, CHU Rouen, Polyclinique de Limoges - site François Chénieux [Limoges], Unité de médecine gériatrique ( Gériatrie - Henri Mondor ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Laboratoire de Physique Atmosphérique et Planétaire ( LPAP ), Université de Liège, CRLCC Antoine Lacassagne, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Service d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Sorbonne Paris Cité (USPC), Centre Hospitalier Universitaire de Reims (CHU Reims), Service de chirurgie digestive, générale et cancérologique [CHU HEGP], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Normandie Université (NU), Unité de médecine gériatrique (Gériatrie - Henri Mondor), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Laboratoire de Physique Atmosphérique et Planétaire (LPAP), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], Université de Lille-UNICANCER, and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: Male, Organoplatinum Compounds, Colorectal cancer, Leucovorin, law.invention, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, Randomized controlled trial, FOLFOX, law, Antineoplastic Combined Chemotherapy Protocols, randomized trial, Neoplasm Metastasis, Aged, 80 and over, education.field_of_study, Standard treatment, Age Factors, Hematology, Corrigenda, 3. Good health, Bevacizumab, Survival Rate, Oncology, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, Fluorouracil, Colorectal Neoplasms, medicine.drug, medicine.medical_specialty, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, colorectal cancer, elderly, 03 medical and health sciences, Internal medicine, Gastrointestinal Tumors, medicine, FOLFIRI Regimen, Humans, education, Survival rate, Aged, business.industry, antiangiogenic, Original Articles, medicine.disease, composite criteria, Camptothecin, business
Abstract: IF 11.855; International audience; Background :Metastatic colorectal cancer frequently occurs in elderly patients. Bevacizumab in combination with front line chemotherapy (CT) is a standard treatment but some concern raised about tolerance of bevacizumab for these patients. The purpose of PRODIGE 20 was to evaluate tolerance and efficacy of bevacizumab according to specific end points in this population.Patients and methods :Patients aged 75 years and over were randomly assigned to bevacizumab + CT (BEV) versus CT. LV5FU2, FOLFOX and FOLFIRI regimen were prescribed according to investigator’s choice. The composite co-primary end point, assessed 4 months after randomization, was based on efficacy (tumor control and absence of decrease of the Spitzer QoL index) and safety (absence of severe cardiovascular toxicities and unexpected hospitalization). For each arm, the treatment will be consider as inefficient if 20% or less of the patients met the efficacy criteria and not safe if 40% or less met the safety criteria.Results :About 102 patients were randomized (51 BEV and 51 CT), median age was 80 years (range 75–91). Primary end point was met for efficacy in 50% and 58% and for safety in 61% and 71% of patients in BEV and CT, respectively. Median progression-free survival was 9.7 months in BEV and 7.8 months in CT. Median overall survival was 21.7 months in BEV and 19.8 months in CT. The 36-month overall survival rate was 27% in BEV and 10.1% in CT. Severe toxicities grade 3/4 were mainly non-hematologic toxicities (80.4% in BEV, 63.3% in CT).Conclusion :Bevacizumab combined with CT was safe and efficient. Both arms met the primary safety and efficacy criteria.
Published: 2018
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32. Hydrological modelling on atmospheric grids: using graphs of sub-grid elements to transport energy and water

Author: J. Polcher, A. Schrapffer, E. Dupont, L. Rinchiuso, X. Zhou, O. Boucher, E. Mouche, C. Ottlé, and J. Servonnat
Subjects: Geology, QE1-996.5
Abstract: Land surface models (LSMs) use the atmospheric grid as their basic spatial decomposition because their main objective is to provide the lower boundary conditions to the atmosphere. Lateral water flows at the surface on the other hand require a much higher spatial discretization as they are closely linked to topographic details. We propose here a methodology to automatically tile the atmospheric grid into hydrological coherent units which are connected through a graph. As water is transported on sub-grids of the LSM, land variables can easily be transferred to the routing network and advected if needed. This is demonstrated here for temperature. The quality of the river networks generated, as represented by the connected hydrological transfer units, are compared to the original data in order to quantify the degradation introduced by the discretization method. The conditions the sub-grid elements impose on the time step of the water transport scheme are evaluated, and a methodology is proposed to find an optimal value. Finally the scheme is applied in an off-line version of the ORCHIDEE (Organising Carbon and Hydrology In Dynamic Ecosystems) LSM over Europe to show that realistic river discharge and temperatures are predicted over the major catchments of the region. The simulated solutions are largely independent of the atmospheric grid used thanks to the proposed sub-grid approach.
Published: 2023
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33. Opinion: The scientific and community-building roles of the Geoengineering Model Intercomparison Project (GeoMIP) – past, present, and future

Author: D. Visioni, B. Kravitz, A. Robock, S. Tilmes, J. Haywood, O. Boucher, M. Lawrence, P. Irvine, U. Niemeier, L. Xia, G. Chiodo, C. Lennard, S. Watanabe, J. C. Moore, and H. Muri
Subjects: Physics, QC1-999, Chemistry, QD1-999
Abstract: The Geoengineering Model Intercomparison Project (GeoMIP) is a coordinating framework, started in 2010, that includes a series of standardized climate model experiments aimed at understanding the physical processes and projected impacts of solar geoengineering. Numerous experiments have been conducted, and numerous more have been proposed as “test-bed” experiments, spanning a variety of geoengineering techniques aimed at modifying the planetary radiation budget: stratospheric aerosol injection, marine cloud brightening, surface albedo modification, cirrus cloud thinning, and sunshade mirrors. To date, more than 100 studies have been published that used results from GeoMIP simulations. Here we provide a critical assessment of GeoMIP and its experiments. We discuss its successes and missed opportunities, for instance in terms of which experiments elicited more interest from the scientific community and which did not, and the potential reasons why that happened. We also discuss the knowledge that GeoMIP has contributed to the field of geoengineering research and climate science as a whole: what have we learned in terms of intermodel differences, robustness of the projected outcomes for specific geoengineering methods, and future areas of model development that would be necessary in the future? We also offer multiple examples of cases where GeoMIP experiments were fundamental for international assessments of climate change. Finally, we provide a series of recommendations, regarding both future experiments and more general activities, with the goal of continuously deepening our understanding of the effects of potential geoengineering approaches and reducing uncertainties in climate outcomes, important for assessing wider impacts on societies and ecosystems. In doing so, we refine the purpose of GeoMIP and outline a series of criteria whereby GeoMIP can best serve its participants, stakeholders, and the broader science community.
Published: 2023
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34. Bevacizumab (Bev) or cetuximab (Cet) plus chemotherapy after progression with bevacizumab plus chemotherapy in patients with wild-type (WT) KRAS metastatic colorectal cancer (mCRC): Final analysis of a French randomized, multicenter, phase II study (PRODIGE 18)

Author: G. Des Guetz, O. Bouche, Trevor Stanbury, S. Charpentier, F. Ghiringhelli, E. Francois, Marc G. Denis, Antoine Adenis, Pascal Artru, J. Bennouna, Sandrine Hiret, Christophe Borg, Gael Deplanque, T. Conroy, J.F. Seitz, Aurélie Bertaut, Service d'hépato-gastro-entérologie, cancérologie digestive et assistance nutritionnelle [CHU de Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service Biostatistiques et Informatique Médicale (CHU de Dijon) (DIM), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'oncologie médicale (Centre Antoine Lacassagne, Nice), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Département d’Oncologie Médicale [Vandoeuvre Les Nancy], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER-UNICANCER, Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Service d'Oncologie médicale [CHU Limoges], CHU Limoges, Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], Clinique Jean-Mermoz, Hôpital privé Jean Mermoz, R&D UNICANCER, Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCL/UNICANCER), AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, and Université de Lille-UNICANCER
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, Bevacizumab, Colorectal cancer, medicine.medical_treatment, Phases of clinical research, [SDV.CAN]Life Sciences [q-bio]/Cancer, bevacizumab, medicine.disease_cause, phase 2 clinical trials, kras2 gene, chemotherapy regimen, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, cetuximab, medicine, Chemotherapy, Cetuximab, business.industry, Wild type, Hematology, medicine.disease, Chemotherapy regimen, 3. Good health, k-ras oncogene, 030104 developmental biology, 030220 oncology & carcinogenesis, colorectal cancer metastatic, KRAS, business, medicine.drug
Abstract: IF 11.855; International audience
Published: 2017
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35. Predictive factors for early progression during induction chemotherapy (IC) and chemotherapy-free interval (CFI): Analysis from PRODIGE 9 trial

Author: E. Francois, Oana Cojocarasu, Joëlle Egreteau, Côme Lepage, Julien Taieb, K. Le Malicot, Thomas Aparicio, Veronique Guerin-Meyer, François Ghiringhelli, O. Bouche, Jaafar Bennouna, J-B. Bachet, Laetitia Dahan, M-C. Kaminsky-Forrett, Christian Borel, J.M. Phelip, Roger Faroux, Mohamed Gasmi, J.-M. Gornet, Valérie Boige, Service d'hépato-gastro-entérologie, cancérologie digestive et assistance nutritionnelle [CHU de Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Fédération Francophone de la Cancérologie Digestive, FFCD, Service Biostatistiques et Informatique Médicale (CHU de Dijon) (DIM), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'Hépato-Gastro Entérologie et Oncologie Digestive, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), département d'oncologie médicale (CHU Robert Debré, Reims), Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'oncologie médicale (Centre Antoine Lacassagne, Nice), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Service de gastroentérologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre Paul Strauss de Lutte contre le Cancer (Strasbourg), Service de gastroentérologie (CHD Vendee - Hopital Les Oudairies, La Roche Sur Yon), CHD Vendee (La Roche Sur Yon), Service d'oncologie digestive et hépato-gastro-entérologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'Oncologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'oncologie medicale (CH Bretagne Sud, Lorient), CH Bretagne Sud, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hémato-oncologie (CH du Mans), Centre Hospitalier du Mans, Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], Service d'Oncologie Médicale [Angers], Centre Paul Papin, Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Service d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes ( CHU Nantes ), Service Biostatistiques et Informatique Médicale (CHU de Dijon) ( DIM ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Centre Hospitalier Universitaire de Reims ( CHU Reims ), Centre Antoine Lacassagne de Nice, Centre Hospitalier Universitaire de Saint-Etienne ( CHU de Saint-Etienne ), Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Service d'oncologie médicale [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Institut de Cancérologie de Lorraine - Alexis Vautrin ( ICL ), Aix Marseille Université ( AMU ) -Hôpital Saint-Joseph [Marseille], Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Gastro-entérologie et Hépatologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement
Subjects: Oncology, 0303 health sciences, Chemotherapy, medicine.medical_specialty, business.industry, medicine.medical_treatment, Induction chemotherapy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematology, 3. Good health, Free interval, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, Predictor variable, business, 030304 developmental biology
Abstract: IF 11.855; International audience
Published: 2017
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36. Clinical utility of circulating DNA analysis for rapid detection of actionable mutations to select metastatic colorectal patients for anti-EGFR treatment

Author: S. El Messaoudi, Romain Meddeb, Eric Assenat, Rosine Guimbaud, Céline Gavoille, Pascal Artru, B. Auzemery, Jean-Luc Raoul, Muriel Mathonnet, Christophe Borg, Denis Pezet, O. Bouche, Catherine Fiess, Caroline Mollevi, C. de la Fouchardiere, A.R. Thierry, Evelyne Lopez-Crapez, Brice Pastor, M. Ychou, Cynthia Sanchez, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), CHU Toulouse [Toulouse], Service Chirurgie Digestive, CHU Clermont-Ferrand, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de la Recherche Agronomique (INRA), Clinique Jean-Mermoz, Hôpital privé Jean Mermoz, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de Chirurgie digestive, endocrinienne et générale [CHU Limoges], CHU Limoges, Centre Léon Bérard [Lyon], Centre Hospitalier Universitaire de Reims (CHU Reims), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, CRLCC Val d'Aurelle - Paul Lamarque, Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Clermont-Ferrand, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC), Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: 0301 basic medicine, Oncology, Neuroblastoma RAS viral oncogene homolog, Adult, Male, Proto-Oncogene Proteins B-raf, medicine.medical_specialty, Colorectal cancer, Concordance, Population, Antineoplastic Agents, Bioinformatics, medicine.disease_cause, Genetic analysis, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Internal medicine, Biopsy, medicine, Humans, Point Mutation, Prospective Studies, Neoplasm Metastasis, education, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, education.field_of_study, medicine.diagnostic_test, business.industry, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Hematology, DNA, Neoplasm, Middle Aged, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, ErbB Receptors, 030104 developmental biology, Genes, ras, Treatment Outcome, 030220 oncology & carcinogenesis, Female, Personalized medicine, KRAS, business, Colorectal Neoplasms
Abstract: Background While tumor-tissue remains the ‘gold standard’ for genetic analysis in cancer patients, it is challenged with the advent of circulating cell-free tumor DNA (ctDNA) analysis from blood samples. Here, we broaden our previous study on the clinical validation of plasma DNA in metastatic colorectal cancer patients, by evaluating its clinical utility under standard management care. Patients and methods Concordance and data turnaround-time of ctDNA when compared with tumor-tissue analysis were studied in a real-time blinded prospective multicenter clinical study (n = 140 metastatic colorectal patients). Results are presented according to STARD criteria and were discussed in regard with clinical outcomes of patients. Results Much more mutations were found by ctDNA analysis: 59%, 11.8% and 14.4% of the patients were found KRAS, NRAS and BRAF mutant by ctDNA analysis instead of 44%, 8.8% and 7.2% by tumor-tissue analysis. Median tumor-tissue data turnaround-time was 16 days while 2 days for ctDNA analysis. Discordant samples analysis revealed that use of biopsy, long delay between tumor-tissue and blood collection and resection of the tumor at time of blood draw, tumor site, or type of tissue analyzed seem to affect concordance. Altogether, the clinical data with respect to the anti-epidermal growth factor receptor response (RAS status) and the prognosis (BRAF status) of those discordant patients do not appear contradictory to the mutational status as determined by plasma analysis. Lastly, we present the first distribution profile of the RAS and BRAF hotspot mutations as determined by ctDNA analysis (n = 119), revealing a high proportion of patients with multiple mutations (45% of the population and up to 5 mutations) and only 24% of WT scored patients for both genes. Mutation profile as determined from ctDNA analysis with using various detection thresholds highlights the importance of the test sensitivity. Conclusion Our study showed that ctDNA could replace tumor-tissue analysis, and also clinical utility of ctDNA analysis by considerably reducing data turnaround time.
Published: 2017
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37. CMIP6 simulations with the compact Earth system model OSCAR v3.1

Author: Y. Quilcaille, T. Gasser, P. Ciais, and O. Boucher
Subjects: Geology, QE1-996.5
Abstract: Reduced-complexity models, also called simple climate models or compact models, provide an alternative to Earth system models (ESMs) with lower computational costs, although at the expense of spatial and temporal information. It remains important to evaluate and validate these reduced-complexity models. Here, we evaluate a recent version (v3.1) of the OSCAR model using observations and results from ESMs from the current Coupled Model Intercomparison Project 6 (CMIP6). The results follow the same post-processing used for the contribution of OSCAR to the Reduced Complexity Model Intercomparison Project (RCMIP) Phase 2 regarding the identification of stable configurations and the use of observational constraints. These constraints succeed in decreasing the overestimation of global surface air temperature over 2000–2019 with reference to 1961–1900 from 0.60±0.11 to 0.55±0.04 K (the constraint being 0.54±0.05 K). The equilibrium climate sensitivity (ECS) of the unconstrained OSCAR is 3.17±0.63 K, while CMIP5 and CMIP6 models have ECSs of 3.2±0.7 and 3.7±1.1 K, respectively. Applying observational constraints to OSCAR reduces the ECS to 2.78±0.47 K. Overall, the model qualitatively reproduces the responses of complex ESMs, although some differences remain due to the impact of observational constraints on the weighting of parametrizations. Specific features of OSCAR also contribute to these differences, such as its fully interactive atmospheric chemistry and endogenous calculations of biomass burning, wetlands CH4 and permafrost CH4 and CO2 emissions. Identified main points of needed improvements of the OSCAR model include a low sensitivity of the land carbon cycle to climate change, an instability of the ocean carbon cycle, the climate module that is seemingly too simple, and the climate feedback involving short-lived species that is too strong. Beyond providing a key diagnosis of the OSCAR model in the context of the reduced-complexity models, this work is also meant to help with the upcoming calibration of OSCAR on CMIP6 results and to provide a large group of CMIP6 simulations run consistently within a probabilistic framework.
Published: 2023
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38. Northern-high-latitude permafrost and terrestrial carbon response to two solar geoengineering scenarios

Author: Y. Chen, D. Ji, Q. Zhang, J. C. Moore, O. Boucher, A. Jones, T. Lurton, M. J. Mills, U. Niemeier, R. Séférian, and S. Tilmes
Subjects: Science, Geology, QE1-996.5, Dynamic and structural geology, QE500-639.5
Abstract: The northern-high-latitude permafrost contains almost twice the carbon content of the atmosphere, and it is widely considered to be a non-linear and tipping element in the earth's climate system under global warming. Solar geoengineering is a means of mitigating temperature rise and reduces some of the associated climate impacts by increasing the planetary albedo; the permafrost thaw is expected to be moderated under slower temperature rise. We analyze the permafrost response as simulated by five fully coupled earth system models (ESMs) and one offline land surface model under four future scenarios; two solar geoengineering scenarios (G6solar and G6sulfur) based on the high-emission scenario (ssp585) restore the global temperature from the ssp585 levels to the moderate-mitigation scenario (ssp245) levels via solar dimming and stratospheric aerosol injection. G6solar and G6sulfur can slow the northern-high-latitude permafrost degradation but cannot restore the permafrost states from ssp585 to those under ssp245. G6solar and G6sulfur tend to produce a deeper active layer than ssp245 and expose more thawed soil organic carbon (SOC) due to robust residual high-latitude warming, especially over northern Eurasia. G6solar and G6sulfur preserve more SOC of 4.6 ± 4.6 and 3.4 ± 4.8 Pg C (coupled ESM simulations) or 16.4 ± 4.7 and 12.3 ± 7.9 Pg C (offline land surface model simulations), respectively, than ssp585 in the northern near-surface permafrost region. The turnover times of SOC decline slower under G6solar and G6sulfur than ssp585 but faster than ssp245. The permafrost carbon–climate feedback is expected to be weaker under solar geoengineering.
Published: 2023
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39. Long-term upper-troposphere climatology of potential contrail occurrence over the Paris area derived from radiosonde observations

Author: K. Wolf, N. Bellouin, and O. Boucher
Subjects: Physics, QC1-999, Chemistry, QD1-999
Abstract: Condensations trails (or contrails) that form behind aircraft have been of climatic interest for many years; yet, their radiative forcing is still uncertain. A number of studies estimate the radiative impact of contrails to be similar to, or even larger than, that of CO2 emitted by aviation. Hence, contrail mitigation may represent a significant opportunity to reduce the overall climate effect of aviation. Here we analyze an 8-year data set of radiosonde observations from Trappes, France, in terms of the potential for contrail and induced cirrus formation. We focus on the contrail vertical and temporal distribution and test mitigation opportunities by changing flight altitudes and fuel type. Potential contrail formation is identified with the Schmidt–Appleman criterion (SAc). The uncertainty of the SAc, due to variations in aircraft type and age, is estimated by a sensitivity study and is found to be larger than the radiosonde measurement uncertainties. Linkages between potential contrail formation layers and the thermal tropopause, as well as with the altitude of the jet stream maximum, are determined. While non-persistent contrails form at the tropopause level and around 1.5 km above the jet stream, persistent contrails are located approximately 1.5 km below the thermal tropopause and at the altitude of the jet stream. The correlation between contrail formation layers and the thermal tropopause and jet stream maximum allows to use these quantities as proxies to identify potential contrail formation in numerical weather prediction models. The contrail mitigation potential is tested by varying today's flight altitude distribution. It is found that flying 0.8 km higher during winter and lowering flight altitude in summer reduces the probability for contrail formation. Furthermore, the effect of prospective jet engine developments and their influence on contrail formation are tested. An increase in propulsion efficiency leads to a general increase in the potential occurrence of non-persistent and persistent contrails. Finally, the impact of alternative fuels (ethanol, methane, and hydrogen) is estimated and found to generally increase the likelihood of non-persistent contrails and, to a more limited extent, persistent contrails.
Published: 2023
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40. Sorafenib and irinotecan (NEXIRI) as second- or later-line treatment for patients with metastatic colorectal cancer and KRAS-mutated tumours: a multicentre Phase I/II trial

Author: Pierre Laurent-Puig, Sylvain Poujol, Françoise Desseigne, S. Thezenas, Thibault Mazard, Evelyne Crapez, Emmanuelle Samalin, E. Francois, Antoine Adenis, T. Conroy, J.F. Seitz, Julien Taieb, M.P. Galais, Jaafar Bennouna, F. Boissière, Marc Ychou, Eric Assenat, O. Bouche, Frédéric Bibeau, CRLCC Val d'Aurelle - Paul Lamarque, Hôpital universitaire Robert Debré [Reims], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Léon Bérard [Lyon], Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CRLC Val d'Aurelle-Paul Lamarque, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Lille Nord de France (COMUE)-UNICANCER, UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, CRLCC Oscar Lambret, Institut de Cancérologie de l'Ouest, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), and Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
Subjects: Male, Cancer Research, Colorectal cancer, medicine.medical_treatment, Camptothecin/administration & dosage/analogs & derivatives, Gastroenterology, tyrosine kinase inhibitor, Antineoplastic Combined Chemotherapy Protocols, Clinical endpoint, 80 and over, clinic, Aged, 80 and over, education.field_of_study, metastatic colorectal cancer, ras Proteins/*genetics, Mutation, Middle Aged, Sorafenib, 3. Good health, Oncology, Disease Progression, Female, Colorectal Neoplasms, medicine.drug, Adult, Niacinamide, medicine.medical_specialty, Niacinamide/administration & dosage/analogs & derivatives, Population, Colorectal Neoplasms/*drug therapy/genetics, [SDV.CAN]Life Sciences [q-bio]/Cancer, Neutropenia, Irinotecan, Disease-Free Survival, Proto-Oncogene Proteins p21(ras), Internal medicine, Proto-Oncogene Proteins, medicine, Humans, Antineoplastic Combined Chemotherapy Protocols/*therapeutic use, education, neoplasms, Aged, Chemotherapy, business.industry, Phenylurea Compounds, medicine.disease, digestive system diseases, Surgery, KRAS gene mutation, Regimen, Phenylurea Compounds/administration & dosage, Clinical Study, ras Proteins, Proto-Oncogene Proteins/*genetics, Camptothecin, business
Abstract: IMPACT: 5.922; International audience; BACKGROUND: This trial evaluated the feasibility and efficacy of combined sorafenib and irinotecan (NEXIRI) as second- or later-line treatment of patients with KRAS-mutated metastatic colorectal cancer (mCRC), who had progressed after irinotecan-based chemotherapy. METHODS: In Phase I, in a 3+3 dose escalation schedule, patients received irinotecan (125, 150 or 180 mg m(-2) every 2 weeks), in combination with 400 mg sorafenib b.d. The primary end point was the maximum-tolerated dose of irinotecan. In Phase II, the primary end point was disease control rate (DCR). Secondary end points were progression-free survival (PFS), overall survival (OS) and toxicity. RESULTS: Phase I included 10 patients (median age 63 (49-73)); no dose-limiting toxicity was seen. In Phase II, 54 patients (median age 60 (43-80) years) received irinotecan 180 mg m(-)(2) every 2 weeks with sorafenib 400 mg b.d. Nine patients (17%) remained on full-dose sorafenib. The DCR was 64.9% (95% CI, 51-77). Median PFS and OS were 3.7 (95% CI, 3.2-4.7) and 8.0 (95% CI, 4.8-9.7) months, respectively. Toxicities included Grade 3 diarrhoea (37%), neutropenia (18%), hand-foot syndrome (13%) and Grade 4 neutropenia (17%). CONCLUSION: The NEXIRI regimen showed promising activity as second- or later-line treatment in this heavily pretreated mCRC population (ClinicalTrials.gov NCT00989469).
Published: 2014
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41. Analysis of circulating tumour DNA (ctDNA) from patients enrolled in the IDEA-FRANCE phase III trial: Prognostic and predictive value for adjuvant treatment duration

Author: May Mabro, C. Lepere, A. de Gramont, Christophe Borg, T. Andre, O. Bouche, C. Louvet, Dewi Vernerey, Pierre Laurent-Puig, Julien Taieb, Joëlle Egreteau, Marc Ychou, Valérie Taly, Claire Mulot, Jérôme Desramé, J. Bennouna, Roger Faroux, Gael Deplanque, L. Mineur, and Camille Bourreau
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, Colorectal cancer, business.industry, medicine.medical_treatment, Perforation (oil well), Cancer, Hematology, medicine.disease, Minimal residual disease, Oxaliplatin, Clinical trial, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, T-stage, business, Adjuvant, medicine.drug
Abstract: Background ctDNA has been recently suggested as a major prognostic factor in resected stage II and III colon cancer patients (pts)1,2. Its predictive value for adjuvant treatment intensity or duration is currently unknown. We have analyzed here ctDNA from pts enrolled in the IDEA-FRANCE trial3, its prognostic value and its predictive value for treatment duration (3 or 6 months). Methods ctDNA was tested by using the detection of 2 methylated markers (WIF1 and NPY) by digital droplet PCR accordingly to a method developed and validated for colorectal cancer 4-6. Comparisons for pts and tumour characteristics and DFS will be done between the ctDNA tested pts and the full study population and between ctDNA positive and negative pts. DFS has been analyzed in the 6 and 3M treatment arms according to ctDNA results. Subgroup analyses for high- and low-risk pts were pre-planned. Results Of the 1345/2010 pts that consented to the IDEA translational research program, with available blood sample for ctDNA testing, 805 have been sampled before chemotherapy start and fully analyzed. More PS 0 (77% vs 71%) and more T4 and/or N2 (28% vs 23%) were observed in the 805 pts studied here than in the 1205 pts left. 696 pts were found ctDNA- and 109 ctDNA + (13.5%). ctDNA+ pts were more often T4, poorly differentiated and with tumour perforation. 2-year DFS was 64% vs 82% in ctDNA+ and – pts, respectively (HR :1.75 (95%CI 1.25-2.45) p = 0.001). In multivariate analysis including Age, Gender, MSI, perforation, T stage, N stage and treatment arm, ctDNA was confirmed as an independent prognostic marker (adj.HR: 1.85 (95%CI 1.31 to 2.61) p Conclusions In this first ctDNA assessment on a large series coming from a phase III clinical trial we found 13.5% of pts with ctDNA post-surgery. ctDNA was confirmed as an independent prognostic marker. In this series, 6 months of treatment seems better in both ctDNA+ and- pts. [1]Tie J, et al. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer.Sci Transl Med. 2016 Jul 6;8(346):346ra92. [2]Scholer LV, et al. Clinical Implications of Monitoring Circulating Tumor DNA in Patients with Colorectal Cancer. Clin Cancer Res. 2017 Sep 15;23(18):5437-5445. [3] Andre T, et al.Three Versus 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Patients With Stage III Colon Cancer: Disease-Free Survival Results From a Randomized, Open-Label, International Duration Evaluation of Adjuvant (IDEA) France, phase III Trial.J Clin Oncol. 2018 May 20;36(15):1469-1477. [4] Garrigou S, et al. A Study of Hypermethylated Circulating Tumor DNA as a Universal Colorectal Cancer Biomarker. Clin Chem. 2016;62:1129-1139. [5] Garlan F, et al. Early Evaluation of Circulating Tumor DNA as Marker of Therapeutic Efficacy in Metastatic Colorectal Cancer Patients (PLACOL Study). Clin Cancer Res.2017;23:5416-5425. [6] Bachet JB, et al. RAS mutation analysis in circulating tumor DNA from patients with metastatic colorectal cancer: the AGEO RASANC prospective multicenter study. Ann Oncol. 2018May 1;29(5):1211-1219. Clinical trial identification NCT00958737. Legal entity responsible for the study Gercor-Prodige. Funding Clinical trial: INCa, GERCOR; Translational project: ARC (Association de Recherche contre le Cancer, Paris, France). Disclosure J. Taieb: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: merck; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: amgen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Servier; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: pierre fabre; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Sanofi. D. Vernerey: Honoraria (self), Advisory / Consultancy: HalioDX; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Janssen. J. Bennouna: Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim. All other authors have declared no conflicts of interest.
Published: 2019
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42. Regorafenib combined with irinotecan as second-line treatment in patients with metastatic gastro-oesophageal adenocarcinomas: A randomized phase 2 trial (PRODIGE 58 – UCGI 35 – REGIRI)

Author: C. de la Fouchardiere, Sophie Gourgou, Laetitia Dahan, Marine Gilabert, M. Benabdelghani, David Sefrioui, Anthony Turpin, L. Monard, A. Hennequin, Hélène Senellart, A. Lopez, Emmanuelle Samalin, A. Zaanan, Faiza Khemissa, Ludovic Evesque, and O. Bouche
Subjects: medicine.medical_specialty, Second line treatment, business.industry, Hematology, medicine.disease, Gastroenterology, Irinotecan, chemistry.chemical_compound, Oncology, chemistry, Gastro, Regorafenib, Internal medicine, medicine, Adenocarcinoma, In patient, business, medicine.drug
Published: 2019
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43. Circulating tumor cells in locally advanced pancreatic adenocarcinoma: the ancillary CirCe 07 study to the LAP 07 trial

Author: Florence Huguet, J-Y Pierga, Françoise Desseigne, O. Bouche, Jean-Baptiste Bachet, Benoist Chibaudel, Claire Mathiot, C. Louvet, François-Clément Bidard, Pascal Hammel, Laurent Mineur, and Pascal Artru
Subjects: Adult, Male, Oncology, Antimetabolites, Antineoplastic, medicine.medical_specialty, Survival, Anemia, medicine.medical_treatment, Adenocarcinoma, Deoxycytidine, Disease-Free Survival, law.invention, Cohort Studies, Young Adult, Circulating tumor cell, Randomized controlled trial, law, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, medicine, Humans, Prospective Studies, Neoplasm Metastasis, Prospective cohort study, Chemotherapy, business.industry, Cancer, Chemoradiotherapy, Hematology, Middle Aged, Neoplastic Cells, Circulating, medicine.disease, Gemcitabine, Pancreatic Neoplasms, Female, business
Abstract: Background Pancreatic carcinoma is one of the leading causes of cancer-related mortality. At the time of diagnosis, 30% of patients present with a locally advanced pancreatic carcinoma (LAPC). As circulating tumor cells (CTCs) count may be a surrogate of the cancer metastatic abilities, CTC detection rates and prognostic value were studied in a prospective cohort of LAPC patients. Patients and methods An LAP07 international multicenter randomized study assesses in patients whose LAPC is controlled after 4 months of chemotherapy whether chemoradiotherapy could increase survival versus continuation of chemotherapy. A subgroup of patients included in the LAP07 trial was screened for CTCs (CellSearch®) before the start of the chemotherapy and after 2 months of treatment. Patient characteristics and survival were obtained prospectively and were correlated with CTC detection. Results Seventy-nine patients were included. One or more CTCs/7.5 ml were detected in 5% of patients before treatment and in 9% of patients after 2 months of treatment (overall detection rate: 11% of patients). CTC positivity was associated with poor tumor differentiation (P = 0.04), and with shorter overall survival (OS) in multivariable analysis (RR = 2.5, P = 0.01), together with anemia. Conclusions The evaluation of micrometastatic disease using CTC detection appears as a promising prognostic tool in LAPC patients.
Published: 2013
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44. Taking into account successive treatment lines in the analysis of a colorectal cancer randomised trial

Author: Ph. Rougier, Dominique Auby, J.P. Pignon, P.L. Etienne, J. Pénichoux, Stefan Michiels, Michel Ducreux, O. Bouche, and Patrick Texereau
Subjects: Male, Oncology, Cancer Research, medicine.medical_specialty, Organoplatinum Compounds, Colorectal cancer, medicine.medical_treatment, Leucovorin, Irinotecan, Disease-Free Survival, Drug Administration Schedule, Advanced colorectal cancer, FOLFOX, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Outcome Assessment, Health Care, medicine, Humans, Aged, Proportional Hazards Models, Randomized Controlled Trials as Topic, Chemotherapy, business.industry, Proportional hazards model, Hazard ratio, Middle Aged, Prognosis, medicine.disease, Oxaliplatin, Disease Progression, FOLFIRI, Camptothecin, Female, Fluorouracil, Colorectal Neoplasms, business, medicine.drug
Abstract: The FFCD 2000–05 randomised trial included 410 patients with advanced colorectal cancer and compared a sequential arm S treated with 5-fluorouracil and leucovorin (LV5FU2) followed by FOLFOX (LV5FU2 + oxaliplatin) and then FOLFIRI (LV5FU2 + irinotecan) and a combination arm C that begins directly with FOLFOX followed by FOLFIRI. The first aim of this study was to analyse the prognostic effects on overall survival of disease progression, and of toxicities under first-line therapy. We also studied the benefit of introducing irinotecan in each arm. Finally, we compared the effect of treatment on repeated progression and toxicities. For this purpose, we used Cox regression models with time-dependent variables and shared gamma frailty regression models. We found that early on during follow-up, the prognostic effect on survival of progression under first-line therapy was greater in C (hazard ratio [HR] = 18.0 [7.9–41.2]) than in S (HR = 7.7 [3.9–17.4]). This difference was significant, but it decreased over time. The prognostic effect of severe toxicities was greater in S (HR = 2.0 [1.4–2.9]) than in C (HR = 1.3 [0.9–1.9]). Introducing irinotecan was significantly more beneficial in S (HR = 0.2 [0.1–0.4]) than in C (HR = 0.3 [0.2–1.5]). The risk of repeated progression was not significantly different between the two groups (HR = 0.9 [0.8–1.1]) whereas the risk of toxicities was greater in C (HR = 1.7 [1.4–2.1]). Overall, this study suggests that starting with less toxic first-line treatment is a valid option since it does not exert a deleterious effect on the risk of overall progression or death.
Published: 2013
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45. Impact of primary tumour resection on survival of patients with colorectal cancer and synchronous metastases treated by chemotherapy: Results from the multicenter, randomised trial Fédération Francophone de Cancérologie Digestive 9601

Author: S. Louafi, J.P. Pignon, C. Allonier, Michel Ducreux, Valérie Boige, Laurent Bedenne, O. Bouche, P. Deguiral, David Malka, B. Leduc, Jean-Luc Raoul, F.R. Ferrand, Abderrahmane Bourredjem, Matthieu Faron, and Mireille Mousseau
Subjects: Male, Oncology, Cancer Research, Prognostic variable, medicine.medical_specialty, Colorectal cancer, Antineoplastic Agents, Kaplan-Meier Estimate, Disease-Free Survival, Internal medicine, medicine, Humans, Progression-free survival, Digestive System Surgical Procedures, Aged, Proportional Hazards Models, Performance status, business.industry, Proportional hazards model, Hazard ratio, Middle Aged, medicine.disease, Log-rank test, Treatment Outcome, Female, Prior Primary, France, Colorectal Neoplasms, business
Abstract: To assess the impact of primary tumour resection on overall survival (OS) of patients diagnosed with stage IV colorectal cancer (CRC).Among the 294 patients with non-resectable colorectal metastases enrolled in the Fédération Francophone de Cancérologie Digestive (FFCD) 9601 phase III trial, which compared different first-line single-agent chemotherapy regimens, 216 patients (73%) presented with synchronous metastases at study entry and constituted the present study population. Potential baseline prognostic variables including prior primary tumour resection were assessed by univariate and multivariate Cox analyses. Progression-free survival (PFS) and OS curves were compared with the logrank test.Among the 216 patients with stage IV CRC (median follow-up, 33 months), 156 patients (72%) had undergone resection of their primary tumour prior to study entry. The resection and non-resection groups did not differ for baseline characteristics except for primary tumour location (rectum, 14% versus 35%; p=0.0006). In multivariate analysis, resection of the primary was the strongest independent prognostic factor for PFS (hazard ratio (HR), 0.5; 95% confidence interval [CI], 0.4-0.8; p=0.0002) and OS (HR, 0.4; CI, 0.3-0.6; p0.0001). Both median PFS (5.1 [4.6-5.6] versus 2.9 [2.2-4.1] months; p=0.001) and OS (16.3 [13.7-19.2] versus 9.6 [7.4-12.5]; p0.0001) were significantly higher in the resection group. These differences in patient survival were maintained after exclusion of patients with rectal primary (n=43).Resection of the primary tumour may be associated with longer PFS and OS in patients with stage IV CRC starting first-line, single-agent chemotherapy.
Published: 2013
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46. Prognostic factor analysis for elderly patients treated for metastatic colorectal cancer in the randomized phase II trial PRODIGE 20

Author: F. Retornaz, Julien Taieb, E. Francois, S. Kirscher, Thomas Aparicio, Thierry Lecomte, O. Bouche, F. Khemissa Akouz, Dominique Genet, Alice Oden-Gangloff, Laurent Bedenne, F. El Hajbi, Sandrine Lavau-Denes, Elena Paillaud, M. Baconnier, Christophe Locher, E. Maillard, P.L. Etienne, Roger Faroux, Y. Rinaldi, Service de Gastro-entérologie [Avicenne], Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Centre Hospitalier Universitaire de Reims ( CHU Reims ), Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, Fédération Francophone de la Cancérologie Digestive, FFCD, Institut Sainte Catherine [Avignon], Service de gastroenterologie [CHU Georges Pompidou], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Hôpital Privé des Côtes d'Armor ( HPCA ), Centre Hospitalier Départemental Les Oudairies, Service de hépato-gastro-entérologie - cancérologie digestive [CH de Perpignan], Centre Hospitalier Saint Jean de Perpignan, CRLCC Oscar Lambret, Centre Hospitalier de Meaux, Hôpital Européen [Fondation Ambroise Paré - Marseille], CHU Trousseau [Tours], CHRU Tours, CHU Limoges, CH Annecy, Département de Gastroentérologie et hépatologie, Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-Hôpital Michallon, CHU Rouen, Polyclinique de Limoges - site François Chénieux [Limoges], Unité de médecine gériatrique ( Gériatrie - Henri Mondor ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Programme Hospitalier de Recherche Clinique, Laboratoires Roche, Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Service de gastroenterologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital Privé des Côtes d'Armor (HPCA), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Normandie Université (NU), Unité de médecine gériatrique (Gériatrie - Henri Mondor), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, and Université de Lille-UNICANCER
Subjects: 0301 basic medicine, Oncology, Prognostic factor, medicine.medical_specialty, Colorectal cancer, business.industry, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematology, medicine.disease, 3. Good health, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, business, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2016
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47. Effect of 5 years of imaging and CEA follow-up to detect recurrence of colorectal cancer - PRODIGE 13 a FFCD and Unicancer phase III trial: baseline characteristics

Author: E. Maillard, D. Pere-Verge, T. Chatellier, Côme Lepage, J. Ezenfis, J.-C. Duchmann, Antoine Adenis, Gilles Breysacher, Astrid Lièvre, M. Ben Abdelghani, Roger Faroux, Ariane Darut-Jouve, Y. Rinaldi, M. Duluc, J.M. Phelip, O. Bouche, A. Pelaquier, D. Pillon, P. Geoffroy, L. Cany, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Service d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), CHU Saint-Etienne, Polyclinique Francheville, Fédération Francophone de la Cancérologie Digestive, FFCD, Pontchaillou. Service des maladies de l'appareil digestif, Centre Hospitalier Universitaire de Rennes, Centre Hospitalier Départemental Les Oudairies, Centre Hospitalier de Compiègne, CHU, Service d'oncologie médicale [CHU Strasbourg], CHU Strasbourg, Hôpitaux Civils Colmar, Institut de Chimie de Strasbourg, Centre National de la Recherche Scientifique ( CNRS ) -Université de Strasbourg ( UNISTRA ), Centre hospitalier Saint Joseph - Saint Luc [Lyon], CH Montélimar, Centre Hospitalier Fleyriat [Bourg en Bresse], Clinique Drévon, Service d'oncologie digestive et hépato-gastro-entérologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Center Oscar Lambret, CRLCC Oscar Lambret, Centre Hospitalier Universitaire de Reims ( CHU Reims ), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Service des Maladies de l'Appareil Digestif [CHU Rennes], CHU Pontchaillou [Rennes], Service gastro-entérologie et hépatologie, Centre Hospitalier Compiègne-Noyon, Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Centre Hospitalier Universitaire de Reims (CHU Reims), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Universitaire [Rennes], and Université Lille Nord de France (COMUE)-UNICANCER
Subjects: Oncology, medicine.medical_specialty, business.industry, Colorectal cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematology, Stage ii, medicine.disease, Gastrointestinal tumours, 3. Good health, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Clinical trial, 03 medical and health sciences, 0302 clinical medicine, Pulmonary imaging, Internal medicine, Radiological weapon, Baseline characteristics, medicine, 030212 general & internal medicine, business, 030217 neurology & neurosurgery, Colorectal
Abstract: International audience; Background: PRODIGE 13 is a cooperative prospective multicentre controlled phase III trial evaluating by double randomisation the impact of intensive radiological monitoring versus a standard one and CEA monitoring versus no monitoring in Stage II or III colorectal cancer. This abstract describes patient's baseline characteristics.Methods: Recommendations for colorectal cancer, according to various scientific societies have been based on heterogeneous clinical trials, and indeed mainly on expert opinions. Differences still exist particularly concerning the imaging techniques used. The CEA dosage is also poorly evaluated. Despite their limits, recent trials suggest that survival is increased thanks to clinical monitoring combined with hepatic and pulmonary imaging and possibly CEA assay. PRODIGE 13 is a large randomised trial of monitoring strategy and will evaluate the strategies to...
Published: 2016
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48. Circulating tumor DNA and circulating tumor cells as predictor of outcome in the PRODIGE14-ACCORD21-METHEP2 phase II trial

Author: Trevor Stanbury, Thibault Mazard, Charlotte Proudhon, Rosine Guimbaud, Pascale Mariani, L. Mineur, Marc Ychou, F-C Bidard, M-H Stern, Michel Rivoire, Simon Thezenas, E. Francois, Wulfran Cacheux, J-Y Pierga, F. Khemissa-Akouz, Adrien Saliou, François Ghiringhelli, Jordan Madic, O. Bouche, D. Moussata, Institut Curie, UNICANCER - Institut régional du Cancer [Montpellier] (ICM), CRLCC Val d'Aurelle - Paul Lamarque, Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Léon Bérard [Lyon], Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, CHU Toulouse [Toulouse], Centre Hospitalier Saint Jean de Perpignan, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), the European Society for Medical Oncology, UNICANCER - Institut régional du Cancer [Montpellier] ( ICM ), Centre Hospitalier Universitaire de Reims ( CHU Reims ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Unité de génétique et biologie des cancers ( U830 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Curie [Paris], UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), and Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)
Subjects: 0301 basic medicine, PRODIGE14-ACCORD21-METHEP2, business.industry, Tumor DNA, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematology, 3. Good health, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Circulating tumor cell, Oncology, Circulating tumor DNA, 030220 oncology & carcinogenesis, Cancer research, Medicine, business
Abstract: IF 9.269; International audience; Background: We prospectively detected circulating tumor DNA (ctDNA) and circulating tumor cells (CTC) levels in patients (pts) included in the PRODIGE14-ACCORD21-METHEP2 randomized phase II trial.Methods: The trial enrolled colorectal cancer pts with potentially resectable liver metastases & no prior treatment; the primary endpoint was the rate of R0/R1 liver metastases resection achieved by 1st line regimen (targeted therapies & bi- vs tri-chemotherapy; Ychou, ASCO 2016). Blood samples were collected at inclusion, after 1 month of therapy and before any liver metastases surgery. CTCs (CellSearch) & ctDNA (ddPCR, BioRad) were detected in an experienced laboratory (Inst. Curie).Results: 153 pts had at least one blood analysis. High CTC count (≥3 CTC/7.5ml) was detected in 25/132 pts (19%) at baseline and associated with synchronous...
Published: 2016
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49. Safety and efficacy of FOLFIRINOX in elderly patients with metastatic or locally advanced pancreatic adenocarcinoma: A retrospective analysis

Author: Anne Ploquin, Capucine Baldini, Julien Volet, Mohamed Hebbar, V. Bourgeois, F. El Hajbi, Alexandre Escande, T. Renaut Vantroys, O. Bouche, and C. Desauw
Subjects: Male, medicine.medical_specialty, Organoplatinum Compounds, FOLFIRINOX, Endocrinology, Diabetes and Metabolism, Leucovorin, Antineoplastic Agents, Adenocarcinoma, Irinotecan, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Pancreatic cancer, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Neoplasm Metastasis, Survival analysis, Aged, Neoplasm Staging, Retrospective Studies, Hepatology, Performance status, business.industry, Gastroenterology, Age Factors, Retrospective cohort study, medicine.disease, Survival Analysis, Surgery, Oxaliplatin, Pancreatic Neoplasms, Regimen, Treatment Outcome, Fluorouracil, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Camptothecin, Female, business, medicine.drug, Follow-Up Studies
Abstract: Background FOLFIRINOX is a polychemotherapy regimen currently used to treat inoperable pancreatic cancer in patients with a good performance status (PS). FOLFIRINOX lengthens overall survival time (OS), but no specific data are available in elderly patients. Methods All cases of inoperable pancreatic adenocarcinoma in patients over 70 years old treated with FOLFIRINOX were retrospectively reviewed between 2008 and 2015 in five institutions in France. The primary objective was to evaluate the safety and efficacy of FOLFIRINOX in the elderly. Results Forty-two patients with a median age of 73 years (range: 70–79) and a median PS of 1 (range: 0–2) were included. 88% of patients treated with FOLFIRINOX were enrolled between 2012 and 2015. 24 patients (57%) needed a primary dose reduction but this did not impact OS (median OS 11.7 months (6.9–16.4) compared to 16.6 months (0.37–32.8) without dose reduction, p = 0.69). Twelve patients (29%) experienced grade 3 toxicity. Sensory neuropathy occurred most often (56%). Primary prophylaxis with granulocyte colony stimulating factor (GCSF) was administered to 14 patients (33%). One treatment-related death occurred (septic shock), although this patient had not had primary prophylaxis with GCSF. Median follow-up was 86 months. Median OS was 11.6 months (95%CI: 8.9–14.3). Conclusion Median OS observed in the elderly was similar to OS previously reported in younger patients in the ACCORD 11 trial. FOLFIRINOX is effective in selected, fit elderly patients but with greater grade 3 neurotoxicity. Primary dose reduction and primary GCSF prophylaxis may control tolerance.
Published: 2016

50. Randomized phase III trial in elderly patients comparing LV5FU2 with or without irinotecan for first-line treatment of metastatic colorectal cancer (FFCD 2001–02)

Author: Gilles Breysacher, F. Masskouri, C. Choine, François Morvan, Pascal Hammel, Jean-François Seitz, P. Amoyal, J. Cretin, G. Gatineau-Sailliant, Christophe Locher, Thomas Aparicio, G. Bordes, O. Boulat, David Tougeron, I. Cumin, O. Berthelet, Anne Thirot Bidault, M. Pauwels, X. Moncoucy, Faiza Khemissa, F. Petit-Laurent, X. Adhoute, P. Prost, J.P. Lagasse, Jean-Louis Legoux, J. Ezenfis, N. Le Provost, Pierre Michel, A. Gueye, P. Pouderoux, G. Le Pessec, Julien Taieb, B. Landi, H. Fattouh, A. Azzedine, Mohamed Ramdani, Matthieu Schnee, Laurent Bedenne, Jean-Louis Jouve, C. Rebischung, J. Thaury, Ph. Rougier, C. Lobry, F. Guiliani, Jean-Baptiste Bachet, F. Ricard, L. Stefani, R. Mackiewicz, Dominique Genet, E. Cuillerier, C. Bineau, A.M. Queuniet, P. Couzigou, Jean-Marc Phelip, Eveline Boucher, B. Garcia, D. Cleau, M. Schneider, Iradj Sobhani, M. Mozer, Roger Faroux, Mohamed Gasmi, J. Charneau, Côme Lepage, Thierry Lecomte, Céline Lepère, D. Auby, Eric Terrebonne, R. Benoit, Emmanuel Mitry, D. Gargot, J. Martin, M. Baconnier, V. Derias, Achim Weber, Nadia Bouarioua, L. Chone, Catherine Lombard-Bohas, Patrick Texereau, B. Denis, May Mabro, Emilie Maillard, Sandrine Lavau-Denes, F. Di Fiore, C. Girault, J. Provençal, O. Bouche, F. Bonnetain, A. Gagnaire, Service de Gastro-entérologie [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Oncologie médicale [CHU Limoges], CHU Limoges, Service de gastroentérologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Fédération Francophone de la Cancérologie Digestive, FFCD, Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier de Blois (CHB), Hôpital Nord [CHU - APHM], Centre Hospitalier de Meaux, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de hépato-gastro-entérologie - cancérologie digestive [CH de Perpignan], Centre Hospitalier Saint Jean de Perpignan, Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Métropole Savoie [Chambéry], Hôpital pasteur [Colmar], Centre Hospitalier Régional d'Orléans (CHRO), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service d'oncologie médicale [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital Duchenne, CH Boulogne sur Mer, Clinique Bonnefon, Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Henri Duffaut (Avignon), Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'hépato-gastro-entérologie [APHP Henri Mondor], Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Hôpital Henri Mondor-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Curie [Paris], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP]
Subjects: Oncology, Male, medicine.medical_specialty, Leucovorin, colorectal cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, Adenocarcinoma, Irinotecan, chemotherapy, Gastroenterology, elderly, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Clinical endpoint, Humans, Progression-free survival, geriatric oncology, Aged, Proportional Hazards Models, Aged, 80 and over, business.industry, Hazard ratio, Hematology, Chemotherapy regimen, 3. Good health, Treatment Outcome, Fluorouracil, 030220 oncology & carcinogenesis, Multivariate Analysis, FOLFIRI, 030211 gastroenterology & hepatology, Camptothecin, Female, business, Colorectal Neoplasms, medicine.drug
Abstract: 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.
Published: 2016
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