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1. Phase II randomized trial of capecitabine with bevacizumab and external beam radiation therapy as preoperative treatment for patients with resectable locally advanced rectal adenocarcinoma: long term results

Author: Ramón Salazar, Jaume Capdevila, Jose Luis Manzano, Carles Pericay, Mercedes Martínez-Villacampa, Carlos López, Ferrán Losa, María José Safont, Auxiliadora Gómez-España, Vicente Alonso-Orduña, Pilar Escudero, Javier Gallego, Beatriz García-Paredes, Amalia Palacios, Sebastiano Biondo, Cristina Grávalos, Enrique Aranda, and on behalf of the Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD)
Subjects: Locally-advanced rectal cancer, Bevacizumab, Neoadjuvant, Chemoradiotherapy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Background Preoperative chemoradiotherapy with capecitabine is considered as a standard of care for locally advanced rectal cancer. The “Tratamiento de Tumores Digestivos” group (TTD) previously reported in a randomized Ph II study that the addition of Bevacizumab to capecitabine-RT conferred no differences in the pre-defined efficacy endpoint (pathological complete response). We present the follow-up results of progression-free survival, distant relapse-free survival, and overall survival data at 3 and 5 years. Methods Patients (pts) were randomized to receive 5 weeks of radiotherapy (45 Gy/25 fractions) with concurrent Capecitabine 825 mg/m2 twice daily, 5 days per week with (arm A) or without (arm b) bevacizumab (5 mg/kg once every 2 weeks). Results In our study, the addition of bevacizumab to capecitabine and radiotherapy in the neoadjuvant setting shows no differences in pathological complete response (15.9% vs 10.9%), distant relapse-free survival (81.0 vs 80.4 and 76.2% vs 78.2% at 3 and 5 years respectively), disease-free survival (75% vs 71.7 and 68.1% vs 69.57% at 3 and 5 years respectively) nor overall survival at 5-years of follow-up (81.8% vs 86.9%). Conclusions the addition of bevacizumab to capecitabine plus radiotherapy does not confer statistically significant advantages neither in distant relapse-free survival nor in disease-free survival nor in Overall Survival in the short or long term. Trial registration EudraCT number: 2009–010192-24 . Clinicaltrials.gov number: NCT01043484 .
Published: 2020
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2. Association of miR-21 and miR-335 to microsatellite instability and prognosis in stage III colorectal cancer

Author: Tania Calvo-López, Mateo Paz-Cabezas, Patricia Llovet, Maria Dolores Ibañez, Javier Sastre, Vicente Alonso-Orduña, J.Ma. Viéitez, Alfonso Yubero, Ruth Vera, Elena Asensio-Martínez, Pilar Garcia-Alfonso, Enrique Aranda, Eduardo Diaz-Rubio, and Beatriz Perez-Villamil
Subjects: Proto-Oncogene Proteins B-raf, MicroRNAs, Cancer Research, Oncology, Mutation, Genetics, Humans, Microsatellite Instability, General Medicine, Colorectal Neoplasms, Prognosis
Abstract: BACKGROUND: MicroRNAs (miRs) are frequently altered in colorectal cancer (CRC) and can be used as prognostic factors. OBJECTIVE: To confirm in stage III CRC patients a reported miR signature that was associated to the presence of metastatic disease. To correlate miR expression with microsatellite instability (MSI) and mutations in RAS and BRAF. METHODS: miR-21, miR-135a, miR-206, miR-335 and miR-Let-7a expression was analyzed by RT-qPCR in 150 patients out of the 329 patients used to analyze MSI and RAS and BRAF mutations. Association with disease free survival (DFS) and overall survival (OS) was analyzed. Data was confirmed by a multivariate analysis. RESULTS: MiR-21 high expression (p= 0.034) and miR-335 low expression (p= 0.0061) were significantly associated with MSI-H. A positive trend (p= 0.0624) between miR-135a high expression and RAS mutations was found. Lower miR-21 expression levels are associated with DFS (HR = 2.654, 95% CI: 1.066–6.605, p= 0.036) and a trend with OS (HR = 2.419, 95% CI: 0.749–7.815, p= 0.140). MiR-21 high expression significantly improves DFS of the poor prognosis group (T4 or N2) (p= 0.03). CONCLUSIONS: Association of increased expression of miR-21 and better prognosis in the poor prognostic group may be of interest and could be explored in future prospective clinical trials.
Published: 2022
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3. Upfront primary tumour resection and survival in synchronous metastatic colorectal cancer according to primary tumour location and RAS status: Pooled analysis of the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)

Author: Antonieta Salud, Manuel Valladares-Ayerbes, Javier Sastre, Elena Asensio, Luis Robles, Eduardo Díaz-Rubio, Fernando Rivera, Enrique Aranda, Albert Abad, Auxiliadora Gómez-España, Vicente Alonso-Orduña, Alfredo Carrato, Clara Montagut, Maria Jose Safont, Cristina García González, Manuel Benavides, Encarnación González-Flores, Pilar García-Alfonso, and Jose María Vieitez
Subjects: Oncology, medicine.medical_specialty, Rectal Neoplasms, Colorectal cancer, business.industry, Tumor resection, Antibodies, Monoclonal, Angiogenesis Inhibitors, General Medicine, medicine.disease, Pooled analysis, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Colonic Neoplasms, medicine, Humans, Cooperative group, Surgery, Colorectal Neoplasms, business, Retrospective Studies
Abstract: Retrospective studies and meta-analyses suggest that upfront primary tumour resection (UPTR) confers a survival benefit in patients with asymptomatic unresectable metastatic colorectal cancer (mCRC) undergoing chemotherapy, however a consensus of its role in routine clinical practice in the current era of targeted therapies is lacking. This retrospective study aimed to analyse the survival benefit of UPTR in terms of tumour location and mutational status, in patients with synchronous mCRC receiving chemotherapy and targeted therapy.Survival was analysed in a pooled cohort of synchronous mCRC patients treated with a first-line anti-VEGF or anti-EGFR inhibitor in seven trials of the Spanish TTD group, according to UPTR, tumour-sidedness and mutational profiling.Of 1334 eligible patients, 642 (48%) had undergone UPTR. UPTR was associated with significantly longer overall survival (OS; 25.0 vs 20.3 months; HR 1.30, 95%CI 1.15-1.48; p 0.0001). UPTR was associated with significant OS benefit in both left-sided (HR 1.38, 95%CI 1.13-1.69; p = 0.002) and right-sided (HR 1.39, 95%CI 1.00-1.94; p = 0.049) tumours, RASwt (HR 1.29, 95%CI 1.05-1.60; p = 0.016) and BRAFwt (HR 1.49, 95%CI 1.21-1.84; p = 0.0002) tumours, and treatment with anti-EGFRs (HR 1.47, 95%CI 1.13-1.92; p = 0.004) and anti-VEGFs (HR 1.25, 95%CI 1.08-1.44; p = 0.003). Multivariate analysis identified number of metastatic sites, RAS status, primary tumour location and UPTR as independent prognostic factors for OS.Considering the selection bias inherent to this study, our results support UPTR before first-line anti-EGFR or anti-VEGF targeted therapy in right and left-sided asymptomatic unresectable synchronous mCRC patients. RAS/BRAF mutational status may also influence UPTR function.
Published: 2022
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4. The Frequency of Specific KRAS Mutations, and Their Impact on Treatment Choice and Survival, in Patients With Metastatic Colorectal Cancer

Author: Ana Fernández Montes, Vicente Alonso Orduña, Elena Asensio Martínez, Nuria Rodríguez Salas, Esperanza Torres, Diego Cacho Lavín, Rosa María Rodríguez Alonso, Esther Falcó, Joan Carles Oliva, Lluis Cirera, Jesus García Gómez, and Carles Pericay
Subjects: Cancer Research, Oncology
Abstract: Background Patients with metastatic colorectal cancer (mCRC) and KRAS mutations have a poor prognosis, seemingly dependent on the location of the mutation. This multicenter, retrospective, cohort study assessed the frequency and prognostic value of specific KRAS mutation codon locations in mCRC patients, and survival outcomes in relation to treatment. Materials and Methods Data from mCRC patients treated in 10 Spanish hospitals between January 2011 and December 2015 were analyzed. The main objective was to investigate (1) the impact of KRAS mutation location on overall survival (OS), and (2) the effect of targeted treatment plus metastasectomy and primary tumor location on OS in patients with KRAS mutations. Results The KRAS mutation location was known for 337/2002 patients. Of these, 177 patients received chemotherapy only, 155 received bevacizumab plus chemotherapy, and 5 received anti-epidermal growth factor receptor therapy plus chemotherapy; 94 patients underwent surgery. The most frequent KRAS mutation locations were G12A (33.8%), G12D (21.4%), and G12V (21.4%). Compared with other locations, patients with a G12S mutation had the shortest median OS (10.3 [95% CI, 2.5-18.0] months). OS was longer in patients who underwent surgery versus those who did not, with a trend toward prolonged survival with bevacizumab (median OS 26.7 [95% CI, 21.8-31.7] months) versus chemotherapy alone (median OS 23.2 [95% CI, 19.4-27.0] months). Conclusion These findings confirm that KRAS mutation location may predict survival outcomes in patients with mCRC, and suggest that pre-/post-operative bevacizumab plus metastasectomy provides survival benefits in patients with KRAS mutations.
Published: 2023
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5. A phase 2 multicenter, open-label, randomized, controlled trial in patients with stage II/III colorectal cancer who are ctDNA positive following resection to compare efficacy of autogene cevumeran versus watchful waiting

Author: Scott Kopetz, Van K. Morris, Vicente Alonso-Orduña, Pilar Garcia-Alfonso, Margarita Reboredo, Ana Fernandez Montes, Joan Maurel, David Paez, Anke C. Reinacher-Schick, Thomas Höhler, Javier Carrasco, Barbara Marie Galligan, Luisa Manning, Liane Preußner, Özlem Tureci, and Ugur Sahin
Subjects: Cancer Research, Oncology
Abstract: TPS3641 Background: Colorectal cancer (CRC) is one of the most commonly occurring cancers with high recurrence and mortality rate. Circulating tumor DNA (ctDNA) can be used as a marker of minimal residual disease after completion of surgical resection of stage II/III CRC, where detectable ctDNA levels (positive) post-AdCTx are associated with an increased risk of disease recurrence and novel therapies are needed. Autogene cevumeran is an investigational individualized neoantigen-specific immunotherapy that is designed to harness an immune response against patient-specific, tumor neoantigens. This clinical trial is in progress in patients with Stage II (high risk) / Stage III colorectal cancer who are ctDNA positive following resection. Methods: Autogene cevumeran is being evaluated in an open-label, Phase 2, randomized, controlled trial in patients with Stage II / III CRC patients who are ctDNA positive following resection. Patients are randomized to adjuvant therapy followed by autogene cevumeran compared to adjuvant therapy followed by watchful waiting. The primary endpoint is disease-free survival (DFS). The trial has a Biomarker Cohort of 15 patients who will receive autogene cevumeran irrespective of the ctDNA status to pursue exploratory objectives. The main study of the phase 2 trial consists of a randomized (1:1) design comparing the experimental arm (autogene cevumeran) with the observational arm (watchful waiting) in ctDNA positive CRC patients. A third Exploratory Cohort explores the efficacy and safety of autogene cevumeran in ctDNA positive CRC patients with early recurrence/relapse during or after completion of AdCTx. Patients enrolled onto the experimental group, the biomarker and exploratory cohorts will receive autogene cevumeran 6x q1w, followed by 2x q2w, followed by 7 “booster” doses q6w, to receive a total of 15 doses (dosed at 25μg). AEs are assessed according to CTCAE v5. DFS will be determined by an independent central radiology assessment. Key eligibility criteria include 1) Patients must have stage II/III rectal cancer or stage II (high risk)/III colon cancer that has been surgically resected (R0 confirmed by pathology report); 2) patients must be ctDNA positive following resection; and 3) at least 5 tumor neoantigens must be identified in the provided tumor sample for autogene cevumeran manufacturing (RNA lipoplex, RNA-LPX). ClinicalTrials.gov identifier: NCT04486378.
Published: 2022
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6. 474P Prognostic and predictive role of Consensus Molecular Subtypes (CMS) determined by immunohistochemistry in metastatic colorectal cancer (mCRC)

Author: Isidro Machado, Carlos Fernández-Martos, Vicente Alonso-Orduña, E. Galvez, Carlos Horndler, O. Higuera Gomez, Jorge Aparicio, Louis Vermeulen, R. Leno, V. Heredia Soto, I. Sevilla García, Jaime Feliu, S. ten Hoorn, Ana Ruiz-Casado, Miriam Cuatrecasas, A. Fernández Montes, Marta Mendiola, M. Martin-Richard, M. Méndez, and Juan Maurel
Subjects: Oncology, medicine.medical_specialty, Colorectal cancer, business.industry, Internal medicine, medicine, Immunohistochemistry, Hematology, medicine.disease, business
Published: 2020
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7. VITAL phase 2 study: Upfront 5-fluorouracil, mitomycin-C, panitumumab and radiotherapy treatment in nonmetastatic squamous cell carcinomas of the anal canal (GEMCAD 09-02)

Author: Marta Martin-Richard, Joan Maurel, Jaime Feliu, Teresa Fernandez, Maria Elena Sanchez, Isabel Sevilla, Jaume Capdevila, Ana Leon, Rocio Garcia-Carbonero, Miriam López-Gómez, Ismael Ghanem, Vicente Alonso-Orduña, Laura Cerezo, Carmen Castanon, Pilar García-Alfonso, Monica Caro, Inmaculada Guasch, Begona Quintana-Angel, Carles Conill, Carlos F. Lopez, Amgen, UAM. Departamento de Medicina, Instituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ), Institut Català de la Salut, [Feliu J] Department of Medical Oncology, CIBERONC, Catedra UAM-AMGEN, Hospital Universitario La Paz, Madrid, Spain. [Garcia-Carbonero R] Department of Medical Oncology, Hospital Universitario Virgen del Rocio, Sevilla, Spain. Department of Medical Oncology, imas12, UCM, CNIO, CIBERONC, Hospital Universitario 12 de Octubre, Madrid, Spain. [Capdevila J] Servei d’Oncologia Mèdica, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Guasch I] Department of Medical Oncology, Hospital Althaia-Manresa, Manresa, Spain. [Alonso-Orduna V] Department of Medical Oncology, Instituto de Investigacion Sanitaria de Aragon, Hospital Universitario Miguel Servet, Zaragoza, Spain. [Lopez C] Department of Medical Oncology, Hospital Universitario Marques de Valdecilla, Santander, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Male, 0301 basic medicine, Cancer Research, Colorectal cancer, medicine.medical_treatment, Phases of clinical research, chemotherapy, Severity of Illness Index, Gastroenterology, Target therapy, Recte - Càncer - Quimioteràpia, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias intestinales::neoplasias colorrectales::neoplasias del recto::neoplasias del ano [ENFERMEDADES], neoplasias::neoplasias por tipo histológico::neoplasias glandulares y epiteliales::carcinoma::carcinoma de células escamosas [ENFERMEDADES], Rectal cancer, Original Research, Aged, 80 and over, Proctectomy, Panitumumab, Middle Aged, Anal canal, Anus Neoplasms, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Recte - Càncer - Radioteràpia, Primary tumor, Neoadjuvant Therapy, Survival Rate, medicine.anatomical_structure, Oncology, terapéutica::tratamiento combinado::quimiorradioterapia::quimiorradioterapia complementaria [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], 030220 oncology & carcinogenesis, Female, Fluorouracil, Radiodermatitis, medicine.drug, Adult, medicine.medical_specialty, Neutropenia, Medicina, Mitomycin, lcsh:RC254-282, Disease-Free Survival, 03 medical and health sciences, Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms::Rectal Neoplasms::Anus Neoplasms [DISEASES], Internal medicine, medicine, Humans, Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Carcinoma, Squamous Cell [DISEASES], Chemotherapy, Radiology, Nuclear Medicine and imaging, rectal cancer, radiotherapy, Aged, Radiotherapy, target therapy, business.industry, Therapeutics::Combined Modality Therapy::Chemoradiotherapy::Chemoradiotherapy, Adjuvant [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Clinical Cancer Research, Chemoradiotherapy, Adjuvant, medicine.disease, Radiation therapy, Regimen, 030104 developmental biology, business, Follow-Up Studies
Abstract: Aim VITAL, a phase II single‐arm study, aimed to evaluate efficacy and safety of panitumumab addition to 5‐fluorouracil (5‐FU), mitomycin‐C (MMC) and radiotherapy (RT) in patients with localized squamous cell carcinoma of the anal canal (SCCAC). Methods Adult, treatment‐naïve SCCAC patients (Stage T2‐T4, any N, M0) and ECOG‐PS ≤2, received panitumumab (6 mg/kg, day 1 and Q2W; 8 weeks), 5‐FU (1000 mg/m2/d, days 1‐4 and 29‐32), MMC (10 mg/m2, days 1 and 29) and RT 45 Gy (1.8 Gy/fraction) to the primary tumor and mesorectal, iliac and inguinal lymph nodes, plus 10‐15 Gy boost dose to the primary tumor and affected lymph nodes. The primary objective was disease free survival rate (DFS) at 3‐years (expected 3‐year DFS rate: 73.7 ± 12%). Results Fifty‐eight patients (31 women; median age: 59 years; ECOG‐PS 0‐1:98%; TNM II [29%] (T2 or T3/N0/M0)/IIIA (T1‐T3/N1/M0 or T4/N0/M0) [21%]/IIIB (T4/N1/M0 or any T/N2 or N3/M0) [47%]/nonevaluable [4%]) were included. The median follow‐up was 45 months. The 3‐year DFS rate was 61.1% (95% CI: 47.1, 72.4). The 3‐year overall survival rate was 78.4% (95% CI: 65.1, 87.1). Eighteen patients (31.0%) required a colostomy within 2 years posttreatment. Grade 3‐4 toxicities were experienced by 53 (91%) patients. Most common grade 3‐4 treatment‐related events were radiation skin injury (40%) and neutropenia (24%). No toxic deaths occurred. Improved efficacy in colostomy‐free survival and complete response rate was observed in human papilloma virus positive patients. Conclusions Panitumumab addition to MMC‐5FU regimen in SCCAC patients increases toxicity and does not improve patients’ outcomes. RT plus MMC‐5FU remains the standard of care for localized SCCAC patients., VITAL, a phase II single‐arm study, was aimed to evaluate efficacy and safety of panitumumab addition to 5‐fluorouracil (5‐FU), mitomycin‐C (MMC) and radiotherapy in patients with localized squamous cell carcinoma of the anal canal (SCCAC). The study concluded that panitumumab addition to MMC‐5FU regimen in SCCAC patients increases toxicity and does not improve patients’ outcomes.
Published: 2020

8. 1159MO Survival and prognostic factors analysis of 535 grade 3 gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN): Data from the Spanish Taskforce of Neuroendocrine Tumours Registry (R-GETNE)

Author: Carles Pericay, C. Villabona, Marta Llanos, A Castaño, R. Garcia Centeno, Alexandre Teule, A. Lopez de Sa, M. Sánchez Cánovas, L. Oliva Fernandez, J. Gallego Plazas, Gustavo Crespo, I. Torres, A. La Salvia, P. Jimenez Fonseca, Teresa Alonso, Jaume Capdevila, Ana Custodio, Vicente Alonso-Orduña, M. Benavent, and C. López
Subjects: Oncology, medicine.medical_specialty, business.industry, Internal medicine, Neuroendocrine neoplasm, medicine, Hematology, business
Published: 2020
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9. 471P Identification and validation of a new prognostic score in metastatic colorectal cancer (mCRC): GEMCAD score

Author: Jorge Aparicio, A. Sesma, E. Galvez, Jaime Feliu, H. Manzano, Carlos Fernández-Martos, Jesús Gallego, Faustina Torres, Rosa Gallego, Juan Maurel, H. Oliveres, Vicente Alonso-Orduña, Francis Esposito, M. Martin-Richard, J. Alcaide-Garcia, A. Fernández-Montes, E. Falcó, Ana Ruiz-Casado, Antonieta Salud, and E. Seguí
Subjects: Oncology, medicine.medical_specialty, business.industry, Colorectal cancer, Internal medicine, medicine, Identification (biology), Hematology, business, medicine.disease, Prognostic score
Published: 2020
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10. 1167P SILVELUL SCORE: An original or modified immunohistochemical score (IPS or mIPS) in patients (pts) with pancreatic neuroendocrine tumours (PanNET) treated with everolimus or CAPTEM

Author: J. Hernando, B. García Paredes, L. Lopez Ricarte, Alberto Carmona, I. Sevilla García, Inés González, B. López-San Vicente, M. Benavent, P. Jiménez-Fonseca, Saioa Goñi, J. Pérez Sanz, Maria Luisa Gomez-Dorronsoro, Jose J.G. Marin, Irene Hernandez, A. De Jesus-Acosta, Ana Custodio, Vicente Alonso-Orduña, Gustavo Crespo, A. Viudez, and C. López
Subjects: Oncology, medicine.medical_specialty, Everolimus, business.industry, Hematology, Neuroendocrine tumors, medicine.disease, Internal medicine, medicine, Immunohistochemistry, In patient, business, medicine.drug
Published: 2020
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11. First-line biological agents plus chemotherapy in elderly patients with metastatic colorectal cancer: A retrospective pooled analysis

Author: Pilar García-Alfonso, Jose María Vieitez, Gema Durán, Encarnación González Flores, Albert Abad, Eduardo Díaz-Rubio, Jose Luis Manzano, Reyes Ferreiro Monteagudo, Maria Jose Safont Aguilera, Manuel Valladares-Ayerbes, Beatriz García Paredes, Cristina Gravalos Castro, Vicente Alonso Orduña, Pilar Escudero, Eva Martínez de Castro, Enrique Aranda, Alfredo Carrato, Bartomeu Massuti, Rosa Rodríguez Alonso, and Andres J. Muñoz Martín
Subjects: Oncology, Cancer Research, Chemotherapy, medicine.medical_specialty, business.industry, Colorectal cancer, medicine.medical_treatment, First line, medicine.disease, Pooled analysis, Internal medicine, Medicine, business
Abstract: 4017 Background: Biological agents, in combination with chemotherapy, are recommended as first-line treatment of metastatic colorectal cancer (mCRC); however, evidence guiding appropriate management of elderly patients with mCRC is lacking. This study compared the efficacy and safety outcomes in older versus younger patients with mCRC who received first-line biological therapy. Methods: This retrospective analysis used pooled data from five Spanish TTD collaborative group studies of adults with advanced CRC who received first-line treatment with bevacizumab, cetuximab or panitumumab, stratified by age (≥65 vs < 65 years). Endpoints included progression-free survival (PFS), overall survival (OS), overall response rate (ORR) and safety. Results: In total, 999 patients from five studies were included in the analysis; 480 (48%) were aged ≥65 years and 519 (52%) were aged < 65 years; 733 (73.37%) were treated with bevacizumab, 189 (18.92%) received cetuximab and 77 (7.71%) received panitumumab. Median PFS did not significantly differ between patients aged ≥65 versus < 65 years (9.9 vs 9.4 months; hazard ratio [HR] 1.01; 95% confidence interval [CI] 0.88–1.17). Median OS was significantly shorter in older versus younger patients (21.3 vs 25.0 months; HR 1.21; 95% CI 1.04–1.41; P = 0.0132). There was no significant difference between older versus younger patients in ORR (59% vs 62%). Older patients experienced more treatment-related grade ≥3 adverse events. Conclusions: Biological agents are an effective first-line treatment option for elderly patients with mCRC, with comparable efficacy in PFS and ORR to that observed in younger patients and a manageable safety profile.
Published: 2020
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12. Effect of Aflibercept Plus Modified FOLFOX6 Induction Chemotherapy Before Standard Chemoradiotherapy and Surgery in Patients With High-Risk Rectal Adenocarcinoma The GEMCAD 1402 Randomized Clinical Trial

Author: Joan Maurel, Rakesh K. Jain, Vicente Alonso-Orduña, Antonieta Salud, Miquel Nogué, Laura Layos, Javier Gallego, Rocio Garcia-Carbonero, Ferran Losa, Nuria Rodríguez-Salas, Marta Martin-Richard, Carlos F. Lopez, Jaume Capdevila, R. Vera, Xabier García-Albéniz, Carlos Fernández-Martos, Carles Pericay, Clara Montagut, Ismael Macias, and Inmaculada Guash
Subjects: Cancer Research, medicine.medical_specialty, education.field_of_study, business.industry, Population, Induction chemotherapy, Total mesorectal excision, Surgery, law.invention, 03 medical and health sciences, Regimen, 0302 clinical medicine, Oncology, Randomized controlled trial, law, 030220 oncology & carcinogenesis, Rectal Adenocarcinoma, Medicine, 030212 general & internal medicine, business, education, Chemoradiotherapy, Original Investigation, Aflibercept, medicine.drug
Abstract: IMPORTANCE: Preclinical studies suggest that a vascular endothelial growth factor (VEGF) blockade may play a role in the preoperative treatment of rectal adenocarcinoma; however, how to combine anti-VEGF drugs with neoadjuvant chemotherapy (CT) and/or chemoradiotherapy (CRT) remains controversial. OBJECTIVE: To study the effect of aflibercept plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) induction CT prior to standard CRT and total mesorectal excision (TME) surgery in patients with high-risk rectal adenocarcinoma. DESIGN, SETTING, AND PARTICIPANTS: In the Grupo Español Multidisciplinar En Cancer Digestivo (GEMCAD) 1402 phase 2 randomized clinical trial, 180 patients aged 18 to 75 years, identified by centrally reviewed magnetic resonance imaging to have mrT3c-d/T4/N2 rectal adenocarcinoma, were enrolled from 20 treatment centers in Spain between January 2015 and March 2017. Patients were randomized in a 2:1 treatment to control arm ratio. The primary end point was evaluated at 2 interim and 1 final analyses. The study was designed to perform hypothesis testing at α = .2 and β = .2. A 2-sided P value of
Published: 2019

13. Adenosquamous Cell Carcinoma of the Rectum in a Girl

Author: Carlota Calvo Escribano, Rafael Fernández Atuan, Vicente Alonso Orduña, Jorge Hernando Cubero, Natalia Álvarez García, and Nerea Torrecilla Idoipe
Subjects: Oncology, medicine.medical_specialty, Colorectal cancer, Adenosquamous carcinoma, medicine.medical_treatment, Rectum, Colonoscopy, Gastroenterology, Metastasis, Carcinoma, Adenosquamous, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Biopsy, medicine, Humans, Child, Neoplasm Staging, medicine.diagnostic_test, Rectal Neoplasms, business.industry, Liver Neoplasms, Hematology, Prognosis, medicine.disease, Combined Modality Therapy, Primary tumor, medicine.anatomical_structure, Pediatrics, Perinatology and Child Health, Lymph Node Excision, Female, Lymphadenectomy, Lymph Nodes, business
Abstract: Adenosquamous carcinoma is a rare colorectal tumor with few cases described in the literature; no children have been reported. A 12-year-old-girl presented tenesmus, diarrhea, and iron deficiency anemia. Intestinal bowel disease was suspected, colonoscopy and biopsy were performed and the diagnosis was a squamous cell carcinoma. Chemoradiation therapy based on last colorectal cancer guidelines was started. Complete regression of the primary tumor was observed with lymph node progression. The pathology report of the lymphadenectomy revealed metastasis of adenosquamous carcinoma, although there was not any adenomatous component in the first biopsy. The patient presented progression with liver metastases, despite stable local disease due to response to first-line treatment of the squamous component.
Published: 2015
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14. Prognostic value of KRAS mutations in stage III colon cancer: post hoc analysis of the PETACC8 phase III trial dataset

Author: Josef Thaler, Richard Greil, Johannes Gaenzer, Wolfgang Eisterer, Joerg Tschmelitsch, Hellmut Samonigg, August Zabernigg, Franz Schmid, Günther Steger, Robert Steinacher, Johannes Andel, Alois Lang, Reinhold Függer, Friedrich Hofbauer, Ewald Woell, Dietmar Geissler, Alfred Lenauer, Manfred Prager, Jean-Luc Van Laethem, Eric Van Cutsem, Geert D'Haens, Gauthier Demolin, Joseph Kerger, Guido Deboever, Gilbert Ghillebert, Marc Polus, Hassan RezaieKalantari, Thierry Delaunoit, Jean Charles Goeminne, Marc Peeters, Philippe Vergauwe, Ghislain Houbiers, Yves Humblet, Jos Janssens, Dirk Schrijvers, Erik Vanderstraeten, Jan Vermorken, Daniel Van Daele, Michel Ferrante, Frederic Forget, Alain Hendlisz, Mette Yilmaz, Svend Erik Nielsen, Lene Vestermark, Jim Larsen, Marc Ychou, Ayman Zawadi, Mohamed-Ayman Zawadi, Olivier Bouche, Laurent Mineur, Jaafar Bennouna-Louridi, Louis Marie Dourthe, Eveline Boucher, Julien Taieb, Denis Pezet, Francoise Desseigne, Michel Ducreux, Patrick Texereau, Laurent Miglianico, Philippe Rougier, Serge Fratte, Charles-Briac Levache, Yacine Merrouche, Stephen Ellis, Christophe Locher, Jean-Francois Ramee, Claire Garnier, Frederic Viret, Bruno Chauffert, Isabelle Cojean-Zelek, Pierre Michel, Cedric Lecaille, Christian Borel, Jean-Francois Seitz, Denis Smith, Catherine Lombard-Bohas, Thierry Andre, Jean-Marc Gornet, Francine Fein, Marie-Aude Coulon-Sfairi, Marie-Christine Kaminsky, Jean-Paul Lagasse, Dominique Luet, Pierre-Luc Etienne, Mohamed Gasmi, Andre Vanoli, Suzanne Nguyen, Thomas Aparicio, Hervé Perrier, Noel Stremsdoerfer, Philippe Laplaige, Dominique Arsene, Dominique Auby, Laurent Bedenne, Romain Coriat, Bernard Denis, Patrick Geoffroy, Gilles Piot, Yves Becouarn, Gilbert Bordes, Gael Deplanque, Olivier Dupuis, Frederic Fruge, Rosine Guimbaud, Thierry Lecomte, Gérard Lledo, Iradej Sobhani, Amani Asnacios, Ahmed Azzedine, Christophe Desauw, Marie-Pierre Galais, Dany Gargot, You-Heng Lam, Abakar Abakar-Mahamat, Jean-Francois Berdah, Sylviane Catteau, Marie-Christine Clavero-Fabri, Jean-Francois Codoul, Jean-Louis Legoux, Denis Goldfain, Pierre Guichard, Denis Pere Verge, Jocelyne Provencal, Bruno Vedrenne, Catherine Brezault-Bonnet, Denis Cleau, Jean-Paul Desir, David Fallik, Bruno Garcia, Marie-Hélène Gaspard, Dominique Genet, Johannes Hartwig, Yves Krummel, Tamara MatysiakBudnik, Vanessa Palascak-Juif, Harizo Randrianarivelo, Yves Rinaldi, Albert Aleba, Ariane Darut-Jouve, Aimery de Gramont, Herve Hamon, Frederic Wendehenne, Axel Matzdorff, Michael Konrad Stahl, Wolfgang Schepp, Martin Burk, Lothar Mueller, Gunnar Folprecht, Michael Geissler, Luisa Mantovani-Loeffler, Thomas Hoehler, Walter Asperger, Hendrik Kroening, Ludwig Fischer von Weikersthal, Stefan Fuxius, Matthias Groschek, Johannes Meiler, Tanja Trarbach, Jacqueline Rauh, Nicolas Ziegenhagen, Albrecht Kretzschmar, Ullrich Graeven, Arnd Nusch, Goetz von Wichert, Ralf-Dieter Hofheinz, Gerhard Kleber, Karl-Heinz Schmidt, Ursula Vehling-Kaiser, Claudia Baum, Jochen Schuette, Georg Martin Haag, Wilhelm Holtkamp, Jochen Potenberg, Tobias Reiber, Georg Schliesser, Hans-Joachim Schmoll, Wolfgang Schneider-Kappus, Wolfgang Abenhardt, Claudio Denzlinger, Jan Henning, Bartscht Marxsen, Hans GuenterDerigs, Helmut Lambertz, Ingulf Becker-Boost, Karel Caca, Christian Constantin, Thomas Decker, Henning Eschenburg, Sigrun Gabius, Holger Hebart, Albrecht Hoffmeister, Heinz-August Horst, Stephan Kremers, Malte Leithaeuser, Sebastian Mueller, Siegfried Wagner, Severin Daum, Frank Schlegel, Martina Stauch, Volker Heinemann, Roberto Labianca, Giuseppe Colucci, Dino Amadori, Enrico Mini, Alfredo Falcone, Corrado Boni, Evaristo Maiello, Luciano Latini, Alberto Zaniboni, Giuseppe Aprile, Sandro Barni, Rodolfo Mattioli, Andrea Martoni, Rodolfo Passalacqua, Mario Nicolini, Enzo Pasquini, Carla Rabbi, Enrico Aitini, Alberto Ravaioli, Carlo Barone, Guido Biasco, Stefano Tamberi, Angelo Gambi, Claudio Verusio, Marina Marzola, Giorgio Lelli, Stefano Cascinu, Paolo Bidoli, Massimo Vaghi, Giorgio Cruciani, Francesco Di Costanzo, Alberto Sobrero, Roberto Petrioli, Massimo Aglietta, Oscar Alabiso, Federico Capuzzo, Domenico Cristi Corsi, Stefania Salvagni, Silvana Chiara, Francesco Ferraù, Francesco Giuliani, Sara Lonardi, Nicola Gebbia, Giovanni Mantovani, Evaristo Sanches, Juan Carlos Mellidez, Pedro Santos, Joao Freire, Cristina Sarmento, Luis Costa, Antonio Moreira Pinto, Sergio Barroso, Jorge Espirito Santo, Fátima Guedes, Amélia Monteiro, Anabela Sa, Irene Furtado, Josep Tabernero, Ramon Salazar, Enrique Aranda Aguilar, Fernando Rivera Herrero, Javier Sastre Valera, Manuel ValladaresAyerbes, Jaime FeliuBatlle, Silvia Gil, Carlos Garcia-Giron, Guillermo Lopez Vivanco, Antonia Salud Salvia, Vicente Alonso Orduña, Ruth Vera Garcia, Javier Gallego, Bartomeu Massuti Sureda, Jordi Remon, Maria Jose Safont Aguilera, Luis CireraNogueras, BernadoQueralt Merino, Cristina Gravalos Castro, Purificacion Martinez de Prado, Carlos PijaumePericay, Manuel ConstenlaFigueiras, InmaculadaGuasch Jordan, Maria Jose GomeReina, Amelia Lopez-Ladron Garcia, Antonio Arrivi Garcia-Ramos, Andres Cervantes, Carlos Fernandez Martos, Eugenio MarcuelloGaspar, Ines Cabezas Montero, Pilar Escudero Emperador, Ana Leon Carbonero, Manuel Gallen Castillo, Teresa Garcia Garcia, Jose Garcia Lopez, Encarnacion Gonzalez Flores, Monica GuillotMorales, Marta LlanosMuñoz, Ana López Martín, Joan Maurel, Juan Carlos Camara, Rosario Dueñas Garcia, Mercedes Salgado, Isabel HernandezBusquier, Teresa Checa Ruiz, Adelaida LacastaMuñoa, MiquelNogue Aliguer, Amalia Velasco Ortiz de Taranco, Miguel Mendez Ureña, Ferran Losa Gaspa, Jose Juan Ponce, Carlos Bosch Roig, Pedro Valero Jimenez, Antonio GalanBrotons, Santiago AlbiolRodriguez, Jose Ales Martinez, Liliana Canosa Ruiz, Margarita CentellesRuiz, John Bridgewater, Rob Glynne-Jones, Saad Tahir, Tamas Hickish, Jim Cassidy, and Leslie Samuel
Subjects: Oncology, Hematology
Published: 2015
Full Text: View/download PDF

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

Author: Jean-François Emile, Catherine Julié, Karine Le Malicot, Come Lepage, Josep Tabernero, Enrico Mini, Gunnar Folprecht, Jean-Luc Van Laethem, Stéphanie Dimet, Camille Boulagnon-Rombi, Marc-Antoine Allard, Frédérique Penault-Llorca, Jaafar Bennouna, Pierre Laurent-Puig, Julien Taieb, Josef Thaler, Richard Greil, Johannes Gaenzer, Wolfgang Eisterer, Joerg Tschmelitsch, Felix Keil, Hellmut Samonigg, August Zabernigg, Franz Schmid, Günther Steger, Robert Steinacher, Johannes Andel, Björn Jagdt, Alois Lang, Michael Fridrik, Reinhold Függer, Friedrich Hofbauer, Ewald Woell, Dietmar Geissler, Alfred Lenauer, Manfred Prager, Geert D'Haens, Gauthier Demolin, Joseph Kerger, Guido Deboever, Gilbert Ghillebert, Marc Polus, Eric Van Cutsem, Hassan Rezaie Kalantari, Thierry Delaunoit, Jean Charles Goeminne, Marc Peeters, Philippe Vergauwe, Ghislain Houbiers, Yves Humblet, Jos Janssens, Dirk Schrijvers, Erik Vanderstraeten, Jan Vermorken, Daniel Van Daele, Michel Ferrante, Frederic Forget, Alain Hendlisz, Mette Yilmaz, Svend Erik Nielsen, Lene Vestermark, Jim Larsen, Mohamed-Ayman Zawadi, Olivier Bouche, Laurent Mineur, Jaafar Bennouna-Louridi, Louis Marie Dourthe, Marc Ychou, Eveline Boucher, Denis Pezet, Francoise Desseigne, Michel Ducreux, Patrick Texereau, Laurent Miglianico, Philippe Rougier, Serge Fratte, Charles-Briac Levache, Yacine Merrouche, Stephen Ellis, Christophe Locher, Jean-Francois Ramee, Claire Garnier, Frederic Viret, Bruno Chauffert, Isabelle Cojean-Zelek, Pierre Michel, Cedric Lecaille, Christian Borel, Jean-Francois Seitz, Denis Smith, Catherine Lombard-Bohas, Thierry Andre, Jean-Marc Gornet, Francine Fein, Marie-Aude Coulon-Sfairi, Marie-Christine Kaminsky, Jean-Paul Lagasse, Dominique Luet, Pierre-Luc Etienne, Mohamed Gasmi, Andre Vanoli, Suzanne Nguyen, Thomas Aparicio, Hervé Perrier, Noel Stremsdoerfer, Philippe Laplaige, Dominique Arsene, Dominique Auby, Laurent Bedenne, Romain Coriat, Bernard Denis, Patrick Geoffroy, Gilles Piot, Yves Becouarn, Gilbert Bordes, Gael Deplanque, Olivier Dupuis, Frederic Fruge, Rosine Guimbaud, Thierry Lecomte, Gérard Lledo, Iradej Sobhani, Amani Asnacios, Ahmed Azzedine, Christophe Desauw, Marie-Pierre Galais, Dany Gargot, You-Heng Lam, Abakar Abakar-Mahamat, Jean-Francois Berdah, Sylviane Catteau, Marie-Christine Clavero-Fabri, Jean-Francois Codoul, Jean-Louis Legoux, Denis Goldfain, Pierre Guichard, Denis Pere Verge, Jocelyne Provencal, Bruno Vedrenne, Catherine Brezault-Bonnet, Denis Cleau, Jean-Paul Desir, David Fallik, Bruno Garcia, Marie-Hélène Gaspard, Dominique Genet, Johannes Hartwig, Yves Krummel, Tamara Matysiak Budnik, Vanessa Palascak-Juif, Harizo Randrianarivelo, Yves Rinaldi, Albert Aleba, Ariane Darut-Jouve, Aimery de Gramont, Herve Hamon, Frederic Wendehenne, Axel Matzdorff, Michael Konrad Stahl, Wolfgang Schepp, Martin Burk, Lothar Mueller, Michael Geissler, Luisa Mantovani-Loeffler, Thomas Hoehler, Walter Asperger, Hendrik Kroening, Ludwig Fischer von Weikersthal, Stefan Fuxius, Matthias Groschek, Johannes Meiler, Tanja Trarbach, Jacqueline Rauh, Nicolas Ziegenhagen, Albrecht Kretzschmar, Ullrich Graeven, Arnd Nusch, Goetz von Wichert, Ralf-Dieter Hofheinz, Gerhard Kleber, Karl-Heinz Schmidt, Ursula Vehling-Kaiser, Claudia Baum, Jochen Schuette, Georg Martin Haag, Wilhelm Holtkamp, Jochen Potenberg, Tobias Reiber, Georg Schliesser, Hans-Joachim Schmoll, Wolfgang Schneider-Kappus, Wolfgang Abenhardt, Claudio Denzlinger, Jan Henning, Bartscht Marxsen, Hans Guenter Derigs, Helmut Lambertz, Ingulf Becker-Boost, Karel Caca, Christian Constantin, Thomas Decker, Henning Eschenburg, Sigrun Gabius, Holger Hebart, Albrecht Hoffmeister, Heinz-August Horst, Stephan Kremers, Malte Leithaeuser, Sebastian Mueller, Siegfried Wagner, Severin Daum, Frank Schlegel, Martina Stauch, Volker Heinemann, Evaristo Maiello, Luciano Latini, Alberto Zaniboni, Dino Amadori, Giuseppe Aprile, Sandro Barni, Rodolfo Mattioli, Andrea Martoni, Rodolfo Passalacqua, Mario Nicolini, Enzo Pasquini, Carla Rabbi, Enrico Aitini, Alberto Ravaioli, Carlo Barone, Guido Biasco, Stefano Tamberi, Angelo Gambi, Claudio Verusio, Marina Marzola, Giorgio Lelli, Corrado Boni, Stefano Cascinu, Paolo Bidoli, Massimo Vaghi, Giorgio Cruciani, Francesco Di Costanzo, Alberto Sobrero, Roberto Petrioli, Massimo Aglietta, Oscar Alabiso, Federico Capuzzo, Alfredo Falcone, Domenico Cristi Corsi, Roberto Labianca, Stefania Salvagni, Silvana Chiara, Libero Ciuffreda, Francesco Ferraù, Francesco Giuliani, Sara Lonardi, Nicola Gebbia, Giovanni Mantovani, Evaristo Sanches, Juan Carlos Mellidez, Pedro Santos, Joao Freire, Cristina Sarmento, Luis Costa, Antonio Moreira Pinto, Sergio Barroso, Jorge Espirito Santo, Fátima Guedes, Amélia Monteiro, Anabela Sa, Irene Furtado, Ramon Salazar, Enrique Aranda Aguilar, Fernando Rivera Herrero, Javier Sastre Valera, Manuel Valladares Ayerbes, Jaime Feliu Batlle, Silvia Gil, Albert Abad Esteve, Carlos Garcia-Giron, Guillermo Lopez Vivanco, Antonia Salud Salvia, Vicente Alonso Orduña, Ruth Vera Garcia, Javier Gallego, Bartomeu Massuti Sureda, Jordi Remon, Maria Jose Safont Aguilera, Luis Cirera Nogueras, Bernado Queralt Merino, Cristina Gravalos Castro, Purificacion Martinez de Prado, Carlos Pijaume Pericay, Manuel Constenla Figueiras, Inmaculada Guasch Jordan, Maria Jose Gome Reina, Amelia Lopez-Ladron Garcia, Antonio Arrivi Garcia-Ramos, Andres Cervantes, Carlos Fernandez Martos, Eugenio Marcuello Gaspar, Ines Cabezas Montero, Pilar Escudero Emperador, Ana Leon Carbonero, Manuel Gallen Castillo, Teresa Garcia Garcia, Jose Garcia Lopez, Encarnacion Gonzalez Flores, Monica Guillot Morales, Marta Llanos Muñoz, Ana López Martín, Joan Maurel, Juan Carlos Camara, Rosario Dueñas Garcia, Mercedes Salgado, Isabel Hernandez Busquier, Teresa Checa Ruiz, Adelaida Lacasta Muñoa, Miquel Nogue Aliguer, Amalia Velasco Ortiz de Taranco, Miguel Mendez Ureña, Ferran Losa Gaspa, Jose Juan Ponce, Carlos Bosch Roig, Pedro Valero Jimenez, Antonio Galan Brotons, Santiago Albiol Rodriguez, Jose Ales Martinez, Liliana Canosa Ruiz, Margarita Centelles Ruiz, John Bridgewater, Rob Glynne-Jones, Saad Tahir, Tamas Hickish, Jim Cassidy, Leslie Samuel, UE 1373 Fourrages Environnement Ruminants Lusignan, Institut National de la Recherche Agronomique ( INRA ) -Physiologie Animale et Systèmes d'Elevage ( PHASE ) -Environnement et Agronomie ( E.A. ) -Biologie et Amélioration des Plantes ( BAP ) -Fourrages Environnement Ruminants Lusignan ( FERLUS ), Service de pathologie [CHU Ambroise Paré], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré, Service de Biostatistique, Fédération Francophone de la Cancérologie Digestive, FFCD, 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 d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Vall d'Hebron University Hospital [Barcelona], Dpt of Internal Medicine, Section of Immunoallergology and Respiratory [Florence] Diseases, University of Florence, Carl Gustav Carus University Hospital, Erasme Hospital, Brussels, Centre Hepato-Biliaire, AP-HP Hôpital Paul Brousse, Modèles de Cellules Souches Malignes et Thérapeutiques, Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne ( IMoST ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Clermont Auvergne ( UCA ), Institut de cancérologie de l'Ouest - Nantes ( ICO Nantes ), CRLCC Paul Papin-CRLCC René Gauducheau, Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers ( CRCINA ), Université d'Angers ( UA ) -Université de Nantes ( UN ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche en Santé de l'Université de Nantes ( IRS-UN ) -Centre hospitalier universitaire de Nantes ( CHU Nantes ), Université de Nantes ( UN ), Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique ( MEPPOT - U1147 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Klinikum Wels Grieskirchen, Oncology department [Salzburg], Salzburger Landesklinikum - Uniklinikum Salzburg ( SALK ), Institute of Chemical Reaction Engineering, Hamburg University of Technology, Alfred-Wegener-Institut, Helmholtz-Zentrum für Polar- und Meeresforschung ( AWI ), Department of Medical Oncology, Medical University Vienna, Department of Internal Medicine, Hospital of Steyr, Department Internal Medicine 3, Centre for Hematology and Medical Oncology, General Hospital Linz, Department Medicine LKH, Institut für Festköperfirschung, Institut des Sciences Moléculaires de Marseille ( ISM2 ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Centrale de Marseille ( ECM ) -Aix Marseille Université ( AMU ), University Hospitals Leuven [Leuven], Katholieke Universiteit Leuven ( KU Leuven ), Pharmacology and Toxicology, Ahvaz Jundishapur University of Medical Sciences, Institut de Biologie Computationnelle ( IBC ), Centre de Coopération Internationale en Recherche Agronomique pour le Développement ( CIRAD ) -Institut National de la Recherche Agronomique ( INRA ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut des Sciences Moléculaires ( ISM ), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Centre National de la Recherche Scientifique ( CNRS ), Faculty of Veterinary Medicine, Ghent University [Belgium] ( UGENT ), Medical Oncology, Antwerp University Hospital [Edegem], Recombinaison et Expression Génétique, Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier de L'Ardenne (Libramont), Department of Cardiology [Sivas, Turkey], Cumhuriyet University [Sivas, Turkey], Department of Earth Sciences, Durham University, Department of Oncology, Rigshospitalet [Copenhagen], Odense Hospital, CP Kelco ApS, Centre Hospitalier Universitaire de Reims ( CHU Reims ), 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 ), Université du Québec à Montréal ( UQAM ), Université Panthéon-Sorbonne ( UP1 ), École nationale supérieure d'architecture de Nantes ( ENSA Nantes ), Department of Hepatogastroenterology and Oncology, Hopital Ambroise Pare, 9, Avenue Charles de Gaulle, 92104, Boulogne Cedex, France., Hôpital Ambroise Paré, CH Belfort-Montbéliard, Polyclinique Francheville, Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne ( CHU de Saint-Etienne ), Centre Hospitalier de Meaux, Service d'hématologie, Clinique Catherine de Sienne, Unité de recherche sur les Biopolymères, Interactions Assemblages ( BIA ), Institut National de la Recherche Agronomique ( INRA ), Université de la Méditerranée - Aix-Marseille 2, Centre hospitalier universitaire d'Amiens ( CHU Amiens-Picardie ), CHU Amiens-Picardie, Pôle oncologie médicale, Hôpital des Diaconesses, Génétique du cancer et des maladies neuropsychiatriques ( GMFC ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Bretagne Occidentale - École de sages-femmes ( UBO UFR MSS ESF ), Université de Brest ( UBO ) -Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), 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 [Centre hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Service d'Oncologie Médicale [CHU Saint -Antoine], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ), Service Gastro-Entérologie, CHU Besançon, Université de Franche-Comté ( UFC ) -Université de Franche-Comté ( UFC ), Centre Alexis Vautrin ( CAV ), Ecophysiologie Végétale, Agronomie et Nutritions ( EVA ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Recherche Agronomique ( INRA ), Image et ville ( IV ), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique ( CNRS ), Département informatique ( INFO ), Université européenne de Bretagne ( UEB ) -Télécom Bretagne-Institut Mines-Télécom [Paris], Service de Gastro-entérologie [Avicenne], Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Agence de l'Environnement et de la Maîtrise de l'Energie - ADEME, Service d'hépato-gastroentérologie, CHU Caen-Hôpital côte de nacre, Département de Médecine, Centre hospitalier de Libourne, Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Fondation FondaMental, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor, Variabilité de réponse aux psychotropes ( VariaPsy - U1144 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Diderot - Paris 7 ( UPD7 ), Département d'oncologie digestive, Institut Bergonié - CRLCC Bordeaux, Hôpital St Joseph, Service de Gynécologie et d'Obstétrique ( CHU Lyon ), Hospices Civils de Lyon ( HCL ), Gastro - Entérologie et Nutrition, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Génétique, Immunothérapie, Chimie et Cancer ( GICC ), Université de Tours-Centre National de la Recherche Scientifique ( CNRS ), Université Montpellier 1 ( UM1 ), Service de gastro-entérologie - Hôpital Henri Mondor, Laboratoire Matière et Systèmes Complexes ( Laboratoire MSC ), Université Paris Diderot - Paris 7 ( UPD7 ) -UFR de Physique, France, Amériques, Espagne – Sociétés, pouvoirs, acteurs ( FRAMESPA ), Université Toulouse - Jean Jaurès ( UT2J ) -Centre National de la Recherche Scientifique ( CNRS ), Regional Hospital of Orleans, Histoire, Archéologie et littératures des Mondes chrétiens et musulmans médiévaux ( CIHAM ), École normale supérieure - Lyon ( ENS Lyon ) -Université Lumière - Lyon 2 ( UL2 ) -École des hautes études en sciences sociales ( EHESS ) -Université Jean Moulin - Lyon III ( UJML ) -Université d'Avignon et des Pays de Vaucluse ( UAPV ) -Centre National de la Recherche Scientifique ( CNRS ), Neurobiologie des signaux intercellulaires ( NSI ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Dept Med Genet, Hôpital Erasme (Bruxelles), Polyclinique de Limoges - site François Chénieux [Limoges], Clinique Médicale B, CHU Strasbourg, Service de gastro-entérologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Hôpital Européen [Fondation Ambroise Paré - Marseille], Asklepios Klinikum Uckermark GmbH, DESY, Notkestr 85, D-22607 Hamburg, Germany, NASA Ames Research Center ( ARC ), Department of Chemistry, Center for Structural Biology, Vanderbilt University [Nashville], Biostatistique et Processus Spatiaux ( BIOSP ), Institute of Ecology [Jena], Friedrich-Schiller-Universität Jena, University of Rostock [Germany], Universität Stuttgart [Stuttgart], Oneonta, Zentrum für Innere Medizin, Klinikum Schwäbisch Gmünd/Stauferklinik, Physiopathologie du stress pancréatique, Institut Armand Frappier ( INRS-IAF ), Institut National de la Recherche Scientifique [Québec] ( INRS ) -Réseau International des Instituts Pasteur ( RIIP ) -Institut Armand Frappier, Institut de Mathématiques de Marseille ( I2M ), Aix Marseille Université ( AMU ) -Ecole Centrale de Marseille ( ECM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Department of Computer Science [Freiburg], University of Freiburg [Freiburg], Institut für Mathematik [Berlin], Technische Universität Berlin ( TUB ), Department of Information Engineering, Computer Science and Mathematics, Università degli Studi dell'Aquila [L'Aquila] ( UNIVAQ.IT ), Department of Animal Sciences, North Carolina Agricultural and Technical State University, FEEM, Romagna Cancer Registry, IRST, Luigi Pierantoni Hospital, Observatoire sociologique du changement ( OSC ), Sciences Po-Centre National de la Recherche Scientifique ( CNRS ), Dipartimento di Chimica, Fisica e Ambiente, Università degli Studi di Udine - University of Udine [Italie], Department of Nuclear Medicine, PET/CT Centre, Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Clinica di Oncologia Medica, AO Ospedali Riuniti, Università Politecnica delle Marche [Ancona] ( UNIVPM ), Universidade Nova de Lisboa ( UNINOVA ), Ottawa Hospital Research Institute [Ottawa] ( OHRI ), Oncologia Medica, Ospedali Riuniti, Ospedale 'San Vincenzo', NIPE, CIPES, European Synchrotron Radiation Facility ( ESRF ), Departamento de Engenharia Informática, Faculdade de Engenharia [Porto] ( FEUP ), Universidade do Porto [Porto]-Universidade do Porto [Porto], 3Decide, Unité de recherche Amélioration, Génétique et Physiologie Forestières ( UAGPF ), Universidade Federal de Campina Grande [Campina Grande] ( UFCG ), Instituto de Engenharia de Sistemas e Computadores ( INESC ), Departamento de Ciências Biológicas, Universidade Regional do Cariri ( URCA Brasil ), Department of Biochemistry and Molecular Biology [Barcelona, Spain], Universitat de Barcelona ( UB ), Associated Unit to Consejo Superior de Investigaciones Científicas - CSIC [Barcelona, Spain], University of Barcelona-Institute of Biomedicine - IBUB [Barcelona, Spain], IRCELYON-Caractérisation et remédiation des polluants dans l'air et l'eau ( CARE ), Institut de recherches sur la catalyse et l'environnement de Lyon ( IRCELYON ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire d'analyse et d'architecture des systèmes [Toulouse] ( LAAS ), Centre National de la Recherche Scientifique ( CNRS ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse ( INSA Toulouse ), Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Institut National Polytechnique [Toulouse] ( INP ), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier ( ICGM ICMMM ), Université Montpellier 1 ( UM1 ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Ecole Nationale Supérieure de Chimie de Montpellier ( ENSCM ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Instituto de Ciencia de Materiales de Madrid [Madrid] ( ICMM ), Interactions, Corpus, Apprentissages, Représentations ( ICAR ), École normale supérieure - Lyon ( ENS Lyon ) -Université Lumière - Lyon 2 ( UL2 ) -INRP-Ecole Normale Supérieure Lettres et Sciences Humaines-Centre National de la Recherche Scientifique ( CNRS ), Institut d'Investigacions Biomèdiques August Pi i Sunyer ( IDIBAPS ), North Region Cancer Registry of Portugal, UMR 5805 Environnements et Paléoenvironnements Océaniques et Continentaux ( EPOC ), Observatoire aquitain des sciences de l'univers ( OASU ), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -École pratique des hautes études ( EPHE ) -Centre National de la Recherche Scientifique ( CNRS ), Department of Paediatrics and Intensive Care, Hospital Universitari Sant Joan de Deu, Laboratoire de Psychologie Sociale ( LPS ), Aix Marseille Université ( AMU ), Universitat de València ( UV ), Instituto de Cienca de Materiales de Madrid [Madrid] ( ICMM ), Biology, New Mexico State University, New Mexico State University, Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ), Centre de recherche sur les Ions, les MAtériaux et la Photonique ( CIMAP - UMR 6252 ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Supérieure d'Ingénieurs de Caen ( ENSICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ), Institut d'Electronique et de Télécommunications de Rennes ( IETR ), Université de Nantes ( UN ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National des Sciences Appliquées - Rennes ( INSA Rennes ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ), Computer Science Department - Carnegie Mellon University, University of Pittsburgh, Laboratoire de Sciences Actuarielle et Financière ( SAF ), Université de Lyon-Université de Lyon, Instituto de Oncologia Corachan ( IDOC ), Laboratoire d'informatique de l'école normale supérieure ( LIENS ), École normale supérieure - Paris ( ENS Paris ) -Centre National de la Recherche Scientifique ( CNRS ), Experimental Quantum Optics and Photonics Group, University of Strathclyde, Institut de recherches Asiatiques ( IrAsia ), Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Européen de Réalité Virtuelle ( CERV ), École Nationale d'Ingénieurs de Brest ( ENIB ), Sol Agro et hydrosystème Spatialisation ( SAS ), Institut National de la Recherche Agronomique ( INRA ) -AGROCAMPUS OUEST, Grenoble Institut des Neurosciences ( GIN ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Grenoble-Université Joseph Fourier - Grenoble 1 ( UJF ), Centre de recherche cerveau et cognition ( CERCO ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Laboratoire Géomatériaux et Environnement ( LGE ), Université Paris-Est Marne-la-Vallée ( UPEM ), Hôpital Ambroise Paré [AP-HP], Université Paris-Saclay, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], 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), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Centre hépato-biliaire (CHB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Université de Nantes (UN), Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Salzburger Landesklinikum - Uniklinikum Salzburg (SALK), Alfred-Wegener-Institut, Helmholtz-Zentrum für Polar- und Meeresforschung (AWI), Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Institut de Biologie Computationnelle (IBC), Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Moléculaires (ISM), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Universiteit Gent = Ghent University [Belgium] (UGENT), Antwerp University Hospital [Edegem] (UZA), Hillerød Hospital, Copenhagen University Hospital-Copenhagen University Hospital, Centre Hospitalier Universitaire de Reims (CHU Reims), 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), Université du Québec à Montréal = University of Québec in Montréal (UQAM), Université Paris 1 Panthéon-Sorbonne (UP1), École nationale supérieure d'architecture de Nantes (ENSA Nantes), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de la Recherche Agronomique (INRA), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bretagne Occidentale - École de sages-femmes (UBO UFR MSS ESF), Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Alexis Vautrin (CAV), Ecophysiologie Végétale, Agronomie et Nutritions (EVA), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Recherche Agronomique (INRA), Image et ville (IV), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Département informatique (INFO), Université européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT), 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), Agence de l'Environnement et de la Maîtrise de l'Energie (ADEME), Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Libourne, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fondation FondaMental [Créteil], Variabilité de réponse aux Psychotropes (VariaPsy - U1144), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Service de Gynécologie et d'Obstétrique (CHU Lyon), Hospices Civils de Lyon (HCL), Génétique, immunothérapie, chimie et cancer (GICC), UMR 7292 CNRS [2012-2017] (GICC UMR 7292 CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1), Service de gastro-entérologie [Henri Mondor AP-HP, Créteil], Hôpital Henri Mondor-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Matière et Systèmes Complexes (MSC (UMR_7057)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Hôpital privé Toulon Hyères : Sainte Marguerite, Clinique des Quatre Pavillons, Lormont, France, Neurobiologie des signaux intercellulaires (NSI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), NASA Ames Research Center (ARC), Biostatistique et Processus Spatiaux (BioSP), Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], University of Rostock, State University of New York at Oneonta (SUNY Oneonta), State University of New York (SUNY), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Armand Frappier (INRS-IAF), Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS), Institut de Mathématiques de Marseille (I2M), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Klinikum Deggendorf, Technische Universität Berlin (TU), Università degli Studi dell'Aquila (UNIVAQ), North Carolina A&T State University, University of North Carolina System (UNC)-University of North Carolina System (UNC), Observatoire sociologique du changement (OSC), Sciences Po (Sciences Po)-Centre National de la Recherche Scientifique (CNRS), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Università Politecnica delle Marche [Ancona] (UNIVPM), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Ottawa Hospital Research Institute [Ottawa] (OHRI), European Synchrotron Radiation Facility (ESRF), Departamento de Engenharia Informática [Porto], Faculdade de Engenharia da Universidade do Porto (FEUP), Universidade do Porto-Universidade do Porto, Universidade Federal de Campina Grande [Campina Grande] (UFCG), Instituto de Engenharia de Sistemas e Computadores (INESC), Universidade Regional do Cariri (URCA Brasil), Universitat de Barcelona (UB), IRCELYON-Catalytic and Atmospheric Reactivity for the Environment (CARE), Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Laboratoire d'analyse et d'architecture des systèmes (LAAS), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC), Instituto de Ciencia de Materiales de Madrid (ICMM), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Interactions, Corpus, Apprentissages, Représentations (ICAR), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-INRP-Ecole Normale Supérieure Lettres et Sciences Humaines (ENS LSH)-Centre National de la Recherche Scientifique (CNRS), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), UMR 5805 Environnements et Paléoenvironnements Océaniques et Continentaux (EPOC), Observatoire aquitain des sciences de l'univers (OASU), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Hospital Universitario de Valme, Anenida de Bellavista s/n, Sevilla 41014, Spain, Hospital Son Llatzer, Universitat de València (UV), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hospital Universitari Son Espases, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Instituto de Oncologia Corachan (IDOC), Laboratoire d'informatique de l'école normale supérieure (LIENS), École normale supérieure - Paris (ENS Paris), Institut de recherches Asiatiques (IrAsia), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre Européen de Réalité Virtuelle (CERV), École Nationale d'Ingénieurs de Brest (ENIB), Sol Agro et hydrosystème Spatialisation (SAS), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, 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), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Géomatériaux et Environnement (LGE), Université Paris-Est Marne-la-Vallée (UPEM), Fédération Francophone de Cancérologie Digestive (FFCD), 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), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service d'Oncologie Médicale [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Recherche Agronomique (INRA)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Department of Information Engineering, Computer Science and Mathematics = Dipartimento di Ingegneria e Scienze dell'Informazione e Matematica [L'Aquila] (DISIM), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Département d'informatique - ENS Paris (DI-ENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU), Institute of Biomedicine - IBUB [Barcelona, Spain]-University of Barcelona, Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), AGROCAMPUS OUEST, 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Université Sciences et Technologies - Bordeaux 1-Université Montesquieu - Bordeaux 4-Institut de Chimie du CNRS (INC), AGROCAMPUS OUEST-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Physiologie Animale et Systèmes d'Elevage (PHASE), Institut National de la Recherche Agronomique (INRA)-Environnement et Agronomie (E.A.)-Biologie et Amélioration des Plantes (BAP)-Fourrages Environnement Ruminants Lusignan (FERLUS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Ambroise Paré, University of Florence (UNIFI), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Institut de cancérologie de l'Ouest - Nantes (ICO Nantes), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Centre National de la Recherche Scientifique (CNRS), Ghent University [Belgium] (UGENT), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université du Québec à Montréal (UQAM), Université Panthéon-Sorbonne (UP1), Centre hospitalier universitaire d'Amiens (CHU Amiens-Picardie), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université de Franche-Comté (UFC)-Université de Franche-Comté (UFC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13)-Hôpital Avicenne, Optimisation Thérapeutique en Neuropsychopharmacologie (VariaPsy - U1144), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Biostatistique et Processus Spatiaux (BIOSP), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Technische Universität Berlin (TUB), Università degli Studi dell'Aquila [L'Aquila] (UNIVAQ.IT), Universidade Nova de Lisboa (NOVA), Faculdade de Engenharia [Porto] (FEUP), Unité de recherche Amélioration, Génétique et Physiologie Forestières (UAGPF), IRCELYON-Caractérisation et remédiation des polluants dans l'air et l'eau (CARE), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Consejo Superior de Investigaciones Científicas [Spain] (CSIC), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-INRP-Ecole Normale Supérieure Lettres et Sciences Humaines-Centre National de la Recherche Scientifique (CNRS), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut des sciences du cerveau de Toulouse. (ISCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM), Emile, J, Julie, C, Le Malicot, K, Lepage, C, Tabernero, J, Mini, E, Folprecht, G, Van Laethem, J, Dimet, S, Boulagnon-Rombi, C, Allard, M, Penault-Llorca, F, Bennouna, J, Laurent-Puig, P, Taieb, J, Bidoli, P, Emile, J. -F., Julie, C., Le Malicot, K., Lepage, C., Tabernero, J., Mini, E., Folprecht, G., Van Laethem, J. -L., Dimet, S., Boulagnon-Rombi, C., Allard, M. -A., Penault-Llorca, F., Bennouna, J., Laurent-Puig, P., Taieb, J., Thaler, J., Greil, R., Gaenzer, J., Eisterer, W., Tschmelitsch, J., Keil, F., Samonigg, H., Zabernigg, A., Schmid, F., Steger, G., Steinacher, R., Andel, J., Jagdt, B., Lang, A., Fridrik, M., Fugger, R., Hofbauer, F., Woell, E., Geissler, D., Lenauer, A., Prager, M., D'Haens, G., Demolin, G., Kerger, J., Deboever, G., Ghillebert, G., Polus, M., Van Cutsem, E., Kalantari, H. R., Delaunoit, T., Goeminne, J. C., Peeters, M., Vergauwe, P., Houbiers, G., Humblet, Y., Janssens, J., Schrijvers, D., Vanderstraeten, E., Vermorken, J., Van Daele, D., Ferrante, M., Forget, F., Hendlisz, A., Yilmaz, M., Nielsen, S. E., Vestermark, L., Larsen, J., Zawadi, M. -A., Bouche, O., Mineur, L., Bennouna-Louridi, J., Dourthe, L. M., Ychou, M., Boucher, E., Pezet, D., Desseigne, F., Ducreux, M., Texereau, P., Miglianico, L., Rougier, P., Fratte, S., Levache, C. -B., Merrouche, Y., Ellis, S., Locher, C., Ramee, J. -F., Garnier, C., Viret, F., Chauffert, B., Cojean-Zelek, I., Michel, P., Lecaille, C., Borel, C., Seitz, J. -F., Smith, D., Lombard-Bohas, C., Andre, T., Gornet, J. -M., Fein, F., Coulon-Sfairi, M. -A., Kaminsky, M. -C., Lagasse, J. -P., Luet, D., Etienne, P. -L., Gasmi, M., Vanoli, A., Nguyen, S., Aparicio, T., Perrier, H., Stremsdoerfer, N., Laplaige, P., Arsene, D., Auby, D., Bedenne, L., Coriat, R., Denis, B., Geoffroy, P., Piot, G., Becouarn, Y., Bordes, G., Deplanque, G., Dupuis, O., Fruge, F., Guimbaud, R., Lecomte, T., Lledo, G., Sobhani, I., Asnacios, A., Azzedine, A., Desauw, C., Galais, M. -P., Gargot, D., Lam, Y. -H., Abakar-Mahamat, A., Berdah, J. -F., Catteau, S., Clavero-Fabri, M. -C., Codoul, J. -F., Legoux, J. -L., Goldfain, D., Guichard, P., Verge, D. P., Provencal, J., Vedrenne, B., Brezault-Bonnet, C., Cleau, D., Desir, J. -P., Fallik, D., Garcia, B., Gaspard, M. -H., Genet, D., Hartwig, J., Krummel, Y., Budnik, T. M., Palascak-Juif, V., Randrianarivelo, H., Rinaldi, Y., Aleba, A., Darut-Jouve, A., de Gramont, A., Hamon, H., Wendehenne, F., Matzdorff, A., Stahl, M. K., Schepp, W., Burk, M., Mueller, L., Geissler, M., Mantovani-Loeffler, L., Hoehler, T., Asperger, W., Kroening, H., von Weikersthal, L. F., Fuxius, S., Groschek, M., Meiler, J., Trarbach, T., Rauh, J., Ziegenhagen, N., Kretzschmar, A., Graeven, U., Nusch, A., von Wichert, G., Hofheinz, R. -D., Kleber, G., Schmidt, K. -H., Vehling-Kaiser, U., Baum, C., Schuette, J., Haag, G. M., Holtkamp, W., Potenberg, J., Reiber, T., Schliesser, G., Schmoll, H. -J., Schneider-Kappus, W., Abenhardt, W., Denzlinger, C., Henning, J., Marxsen, B., Derigs, H. G., Lambertz, H., Becker-Boost, I., Caca, K., Constantin, C., Decker, T., Eschenburg, H., Gabius, S., Hebart, H., Hoffmeister, A., Horst, H. -A., Kremers, S., Leithaeuser, M., Mueller, S., Wagner, S., Daum, S., Schlegel, F., Stauch, M., Heinemann, V., Maiello, E., Latini, L., Zaniboni, A., Amadori, D., Aprile, G., Barni, S., Mattioli, R., Martoni, A., Passalacqua, R., Nicolini, M., Pasquini, E., Rabbi, C., Aitini, E., Ravaioli, A., Barone, C., Biasco, G., Tamberi, S., Gambi, A., Verusio, C., Marzola, M., Lelli, G., Boni, C., Cascinu, S., Bidoli, P., Vaghi, M., Cruciani, G., Di Costanzo, F., Sobrero, A., Petrioli, R., Aglietta, M., Alabiso, O., Capuzzo, F., Falcone, A., Corsi, D. C., Labianca, R., Salvagni, S., Chiara, S., Ciuffreda, L., Ferrau, F., Giuliani, F., Lonardi, S., Gebbia, N., Mantovani, G., Sanches, E., Mellidez, J. C., Santos, P., Freire, J., Sarmento, C., Costa, L., Pinto, A. M., Barroso, S., Santo, J. E., Guedes, F., Monteiro, A., Sa, A., Furtado, I., Salazar, R., Aguilar, E. A., Herrero, F. R., Valera, J. S., Ayerbes, M. V., Batlle, J. F., Gil, S., Esteve, A. A., Garcia-Giron, C., Vivanco, G. L., Salvia, A. S., Orduna, V. A., Garcia, R. V., Gallego, J., Sureda, B. M., Remon, J., Safont Aguilera, M. J., Nogueras, L. C., Merino, B. Q., Castro, C. G., de Prado, P. M., Pericay, C. P., Figueiras, M. C., Jordan, I. G., Gome Reina, M. J., Garcia, A. L. -L., Garcia-Ramos, A. A., Cervantes, A., Martos, C. F., Gaspar, E. M., Montero, I. C., Emperador, P. E., Carbonero, A. L., Castillo, M. G., Garcia, T. G., Lopez, J. G., Flores, E. G., Morales, M. G., Munoz, M. L., Martin, A. L., Maurel, J., Camara, J. C., Garcia, R. D., Salgado, M., Busquier, I. H., Ruiz, T. C., Munoa, A. L., Aliguer, M. N., de Taranco, A. V. O., Urena, M. M., Gaspa, F. L., Ponce, J. J., Roig, C. B., Jimenez, P. V., Brotons, A. G., Rodriguez, S. A., Martinez, J. A., Ruiz, L. C., Ruiz, M. C., Bridgewater, J., Glynne-Jones, R., Tahir, S., Hickish, T., Cassidy, J., and Samuel, L.
Subjects: 0301 basic medicine, Oncology, Male, Cancer Research, Organoplatinum Compounds, Colorectal cancer, medicine.medical_treatment, Medizin, Leucovorin, Prospective cohort study, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, FOLFOX, Organoplatinum Compounds/therapeutic use, Antineoplastic Combined Chemotherapy Protocols, tudy, Lymphocytes, Prospective Studies, Leucovorin/therapeutic use, Middle Aged, Prognosis, 3. Good health, Colorectal carcinoma, Fluorouracil, 030220 oncology & carcinogenesis, Predictive value of tests, Colonic Neoplasms, Biomarker (medicine), Lymphocytes/pathology, Female, Adjuvant, medicine.drug, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Fluorouracil/therapeutic use, Biomarkers, Tumor/analysis, 03 medical and health sciences, Lymphocytes, Tumor-Infiltrating, Predictive Value of Tests, Biomarker, Immune response, Internal medicine, medicine, Biomarkers, Tumor, Humans, Survival analysis, Aged, business.industry, medicine.disease, Survival Analysis, Surgery, 030104 developmental biology, Prospective cohort&nbsp, Multivariate Analysis, Colonic Neoplasms/diagnosis, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, business
Abstract: IF 6.029; International audience; BackgroundThe prognostic value of lymphocyte infiltration (LI) of colorectal carcinoma (CC) has been demonstrated by several groups. However, no validated test is currently available for clinical practice. We previously described an automated and reproducible method for testing LI and aimed to validate it for clinical use.Patients and methodsAccording to National Institutes of Health criteria, we designed a prospective validation of this biomarker in patients included in the PETACC8 phase III study. Primary objective was to compare percentage of patients alive and without recurrence at 2 years in patients with high versus low LI (#NCT02364024). Associations of LI with patient recurrence and survival were analysed, and multivariable models were adjusted for treatment and relevant factors. Automated testing of LI was performed on virtual slides without access to clinical data.ResultsAmong the 1220 CC patients enrolled, LI was high, low and not evaluable in 241 (19.8%), 790 (64.8%) and 189 (15.5%), respectively. Primary objective was met with a 2-year recurrence rate of 14.4% versus 21.1% in patients with high and low LI, respectively (p = 0.02). Patients with high LI also had better disease free survival (DFS) and overall survival (OS). Tumour stage, grade, RAS status and BRAF status were with LI the only prognostic markers in multivariable analysis for OS. Subgroup analyses revealed that high LI had better DFS and OS in mismatch repair (MMR) proficient patients, and in patients without RAS mutation, but not in MMR deficient and RAS mutated patients.ConclusionAlthough this is the first validation with high level of evidence (IIB) of the prognostic value of a LI test in colon cancers, it still needs to be confirmed in independent series of colon cancer patients.
Published: 2017
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16. The Role of Fluoropirimidines in Gastrointestinal Tumours: from the Bench to the Bed

Author: Ignacio Matos-García, Jorge Hernando-Cubero, Vicente Alonso-Orduña, and Jaume Capdevila
Subjects: 0301 basic medicine, Drug, Oncology, medicine.medical_specialty, Antimetabolites, Antineoplastic, Pyrrolidines, medicine.medical_treatment, media_common.quotation_subject, Poly (ADP-Ribose) Polymerase-1, Administration, Oral, Poly(ADP-ribose) Polymerase Inhibitors, Tegafur, Trifluridine, Capecitabine, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Biomarkers, Tumor, Humans, Gastrointestinal cancer, Molecular Targeted Therapy, Uracil, Dihydrouracil Dehydrogenase (NADP), media_common, Gastrointestinal Neoplasms, Chemotherapy, Clinical Trials as Topic, Thymidine Phosphorylase, business.industry, Gastroenterology, Cancer, Drug Synergism, Thymidylate Synthase, medicine.disease, Radiation therapy, Clinical trial, Drug Combinations, 030104 developmental biology, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Folic Acid Antagonists, Fluorouracil, business, Thymine, medicine.drug
Abstract: Gastrointestinal tumours are one of the most common types of cancer. Therapeutic options include surgery, radiotherapy, local ablation techniques, targeted agents, and chemotherapy. Fluoroprimidines are one of the most active drug families in digestive tumours and remains the cornerstone of the most commonly used chemotherapy schemes. We review the molecular basis of thymidylate synthase inhibition and the mechanisms of action of 5-fluorouracil, next generation oral fluoropyrimidines (capecitabine, tegafur and the latest S-1 and TAS-102) and antifolates. In addition, mechanisms and biomarkers of resistance and toxicity are explored. Finally, new fluoropyrimidines development and clinical trials ongoing in digestive tumours are reviewed. Further research is necessary to avoid resistance mechanisms, improve clinical outcomes and continue reducing toxicities. Until new drugs become available, the optimization of current therapies should be a priority.
Published: 2017

17. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial

Author: Jaafar, Bennouna, Javier, Sastre, Dirk, Arnold, Pia, Österlund, Richard, Greil, Eric, Van Cutsem, Roger, von Moos, Jose Maria, Viéitez, Olivier, Bouché, Christophe, Borg, Claus-Christoph, Steffens, Vicente, Alonso-Orduña, Christoph, Schlichting, Irmarie, Reyes-Rivera, Belguendouz, Bendahmane, Thierry, André, Stefan, Kubicka, R, Winterhalder, and Meiler, Johannes (Beitragende*r)
Subjects: Adult, Male, Vascular Endothelial Growth Factor A, Oncology, medicine.medical_specialty, Bevacizumab, Colorectal cancer, medicine.medical_treatment, Medizin, Phases of clinical research, Antibodies, Monoclonal, Humanized, Disease-Free Survival, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Humans, Medicine, Neoplasm Metastasis, Aged, Aged, 80 and over, Chemotherapy, business.industry, Standard treatment, Middle Aged, medicine.disease, Oxaliplatin, Irinotecan, Regimen, Female, Colorectal Neoplasms, business, Follow-Up Studies, medicine.drug
Abstract: Bevacizumab plus fluoropyrimidine-based chemotherapy is standard treatment for first-line and bevacizumab-naive second-line metastatic colorectal cancer. We assessed continued use of bevacizumab plus standard second-line chemotherapy in patients with metastatic colorectal cancer progressing after standard first-line bevacizumab-based treatment.In an open-label, phase 3 study in 220 centres in Austria, Belgium, Czech Republic, Denmark, Estonia, Finland, France, Germany, the Netherlands, Norway, Portugal, Saudi Arabia, Spain, Sweden, and Switzerland, patients (aged ≥18 years) with unresectable, histologically confirmed metastatic colorectal cancer progressing up to 3 months after discontinuing first-line bevacizumab plus chemotherapy were randomly assigned in a 1:1 ratio to second-line chemotherapy with or without bevacizumab 2·5 mg/kg per week equivalent (either 5 mg/kg every 2 weeks or 7·5 mg/kg every 3 weeks, intravenously). The choice between oxaliplatin-based or irinotecan-based second-line chemotherapy depended on the first-line regimen (switch of chemotherapy). A combination of a permuted block design and the Pocock and Simon minimisation algorithm was used for the randomisation. The primary endpoint was overall survival, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00700102.Between Feb 1, 2006, and June 9, 2010, 409 (50%) patients were assigned to bevacizumab plus chemotherapy and 411 (50%) to chemotherapy alone. Median follow-up was 11·1 months (IQR 6·4-15·6) in the bevacizumab plus chemotherapy group and 9·6 months (5·4-13·9) in the chemotherapy alone group. Median overall survival was 11·2 months (95% CI 10·4-12·2) for bevacizumab plus chemotherapy and 9·8 months (8·9-10·7) for chemotherapy alone (hazard ratio 0·81, 95% CI 0·69-0·94; unstratified log-rank test p=0·0062). Grade 3-5 bleeding or haemorrhage (eight [2%] vs one [1%]), gastrointestinal perforation (seven [2%] vs three [1%]), and venous thromboembolisms (19 [5%] vs 12 [3%]) were more common in the bevacizumab plus chemotherapy group than in the chemotherapy alone group. The most frequently reported grade 3-5 adverse events were neutropenia (65 [16%] in the bevacizumab and chemotherapy group vs 52 [13%] in the chemotherapy alone group), diarrhoea (40 [10%] vs 34 [8%], respectively), and asthenia (23 [6%] vs 17 [4%], respectively). Treatment-related deaths were reported for four patients in the bevacizumab plus chemotherapy group and three in the chemotherapy alone group.Maintenance of VEGF inhibition with bevacizumab plus standard second-line chemotherapy beyond disease progression has clinical benefits in patients with metastatic colorectal cancer. This approach is also being investigated in other tumour types, including metastatic breast and non-small cell lung cancers.F Hoffmann-La Roche.
Published: 2013
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18. SEOM clinical guidelines for the treatment of advanced colorectal cancer

Author: María Lomas Garrido, Javier Gallego Plazas, Andrés Cervantes Ruipérez, Enrique Casado Sáenz, Rocio Garcia-Carbonero, M. Auxiliadora Gómez España, Dolores Isla Casado, Encarnación González Flores, Pilar Alfonso, Ignacio Juez Martel, and Vicente Alonso Orduña
Subjects: Cancer Research, medicine.medical_specialty, Colorectal cancer, medicine.medical_treatment, MEDLINE, Medical Oncology, Advanced colorectal cancer, medicine, Advanced disease, Humans, Intensive care medicine, Societies, Medical, Therapeutic strategy, Chemotherapy, business.industry, Carcinoma, Cancer, General Medicine, medicine.disease, Surgery, Oncology, Spain, Practice Guidelines as Topic, Disease Progression, Colorectal Neoplasms, business, Algorithms, Kras mutation
Abstract: Colorectal cancer is the first cause of cancer diagnosis in Spain. Over half of the patients are diagnosed with or will eventually develop distant metastasis. The current manuscript aims to provide synthetic practical guidelines for the therapeutic approaches in advanced disease. Available systemic therapeutic options, and integration and sequencing of chemotherapy with surgical procedures are discussed. Extent of disease, treatment objective, tumor kras mutation status, as well as patient's functional and comorbid conditions shall be considered to properly design the most adequate therapeutic strategy.
Published: 2010
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19. Phase II trial of induction irinotecan-cisplatin followed by concurrent irinotecan-cisplatin and radiotherapy for unresectable, locally advanced gastric and oesophageal-gastric junction adenocarcinoma

Author: Bartomeu Massuti, Javier Gallego, Maica Galán, Ana Lucia Yuste, Pilar Escudero, Alfredo Carrato, Adelaida Cardenal, Berta Laquente, Jordi Giralt, A. Sáenz, Maria Eugenia Vega-Villegas, Fernando Rivera, Enrique Aranda, Antonio Antón, Andrés Cervantes, Josep Tabernero, Edith Rodríguez, and Vicente Alonso-Orduña
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Esophageal Neoplasms, medicine.medical_treatment, Adenocarcinoma, Irinotecan, Toxicology, Gastroenterology, Stomach Neoplasms, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Clinical endpoint, Humans, Pharmacology (medical), Stage (cooking), Survival rate, Pharmacology, Cisplatin, business.industry, Cancer, medicine.disease, Combined Modality Therapy, Survival Rate, Radiation therapy, Camptothecin, Esophagogastric Junction, business, Follow-Up Studies, medicine.drug
Abstract: The prognosis of patients with unresectable M0 gastric cancer remains very poor. We performed a phase II trial to explore the efficacy and toxicity of induction irinotecan-cisplatin (IC) followed by concurrent irinotecan-cisplatin and radiotherapy (IC/RT) in this setting.Patients with unresectable M0 gastric (GC) or oesophageal-gastric junction (EGJC) adenocarcinomas were treated with two courses of IC (irinotecan, 65 mg/m(2); cisplatin, 30 mg/m(2) on days 1 and 8 every 21 days) followed by IC/RT (daily radiotherapy-45 Gy-with concurrent IC: irinotecan, 65 mg/m(2), and cisplatin, 30 mg/m(2), on days 1, 8, 15, and 22). Resectability was reassessed after this treatment, and surgical resection was performed if feasible. The primary endpoint was the R0 resection rate after induction treatment.Seventeen patients were included in the study (EGJC: 6; GC: 11). An R0 resection was achieved in only 5 patients (29%), and according to the design of the trial (Simon's optimal two-stage) accrual of patients was terminated after the first stage. No patient died during IC, whereas 3 patients (24%) died during IC/RT and one of 5 resected patients (20%) died during the first 30 days after resection. The median survival was 10.5 months, and the actuarial 2-year survival rate was 27%.Induction IC followed by IC/RT showed poor efficacy and significant toxicity in patients with unresectable GC/EGJC.
Published: 2010
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20. Phase II Trial of Preoperative Irinotecan–Cisplatin Followed by Concurrent Irinotecan–Cisplatin and Radiotherapy for Resectable Locally Advanced Gastric and Esophagogastric Junction Adenocarcinoma

Author: Bartomeu Massuti, Pilar Escudero, Andrés Cervantes, Jordi Giralt, Josep Tabernero, M. Eugenia Vega-Villegas, Adelaida Cardenal, Enrique Aranda, Ana Lucia Yuste, Antonio Antón, Javier Gallego, Alfredo Carrato, Edith Rodríguez, Berta Laquente, A. Sáenz, Vicente Alonso-Orduña, Maica Galán, and Fernando Rivera
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Esophageal Neoplasms, medicine.medical_treatment, Adenocarcinoma, Neutropenia, Irinotecan, Gastroenterology, Drug Administration Schedule, Stomach Neoplasms, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Humans, Medicine, Radiology, Nuclear Medicine and imaging, Prospective Studies, Prospective cohort study, Survival rate, Cisplatin, Chemotherapy, Radiation, business.industry, Remission Induction, medicine.disease, Combined Modality Therapy, Survival Rate, Radiation therapy, Spain, Preoperative Period, Camptothecin, Esophagogastric Junction, business, Algorithms, medicine.drug
Abstract: Purpose To determine in a Phase II trial whether preoperative irinotecan–cisplatin (IC) followed by concurrent IC therapy and radiotherapy (IC/RT) improved outcome in patients with resectable, locally advanced gastric adenocarcinoma (GC) or esophagogastric junction cancer (EGJC). Patients and Methods Patients with resectable Stage II–IV, M0 GC or EGJC made up the study population. The primary endpoint was pathologic complete response (pCR). Two courses of IC (irinotecan, 65mg/m 2 ; cisplatin, 30mg/m 2 on Days 1 and 8 every 21 days) were given. Patients without progression then received IC/RT, consisting of daily radiotherapy (45Gy) with concurrent IC (irinotecan, 65mg/m 2 ; cisplatin, 30mg/m 2 on Days 1, 8, 15, and 22). Surgical resection was performed, if feasible, 5–8 weeks after the end of radiotherapy. Results Twenty-three patients were included in the study: 10 with EGJC and 13 with GC. Two patients (9%) achieved pCR. The incidences of Grade 3–4 toxicities were as follows: IC: neutropenia 35% (febrile 13%), anemia 22%, diarrhea 22%, emesis 8%; IC/RT: neutropenia 52% (febrile 5%), asthenia 19%, anemia 9%, emesis 9%, diarrhea 5%, cardiotoxicity 5%. No patients died during IC or IC/RT. R0 resection was achieved in 15 patients (65%). Median survival was 14.5 months, and the actuarial 2-year survival rate was 35%. Conclusions Preoperative IC followed by IC/RT resulted in moderate response and resection rates with mild toxicity in patients with GC and EGJC.
Published: 2009
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21. Influence of hemoglobin levels on survival after radical treatment of esophageal carcinoma with radiotherapy

Author: Agustina Méndez Villamón, Vicente Alonso Orduña, Javier Valencia Julve, Miriam López-Mata, and Ricardo Escó Barón
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, Esophageal Neoplasms, medicine.medical_treatment, Adenocarcinoma, Gastroenterology, Radiotherapy, High-Energy, Hemoglobins, Postoperative Complications, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Life Tables, Radical surgery, Neoadjuvant therapy, Aged, Retrospective Studies, Univariate analysis, Performance status, business.industry, General Medicine, Middle Aged, Esophageal cancer, Prognosis, medicine.disease, Combined Modality Therapy, Survival Analysis, Neoadjuvant Therapy, Surgery, Esophagectomy, Treatment Outcome, Oncology, Carcinoma, Squamous Cell, Female, Fluorouracil, Cisplatin, business, Biomarkers, Chemoradiotherapy, Follow-Up Studies
Abstract: The objetive was to investigate the possible progn ostic value of blood hemoglobin concentration in the outcome of radical treatment for locally advanced esophageal carcinoma. This was a retrospective analysis of data for 85 patients treated for locally advanced esophageal carcinoma between January 1991 and January 1997 with chemoradiotherapy alone or as neoadjuvant therapy. All patients received chemotherapy (4 cycles of cisplatin 100 mg/m2 on day 1, and continuous infusion 5-fluorouracil 1 g/m2 per day on days 1–5) with concomitant radiotherapy (40 Gy at 2 Gy/session to the esophageal tumor and mediastinum). The response was evaluated after 4 weeks. 69 patients continued toreceive chemoradiotherapy only to a total dose of 60–64 Gy to the esophageal tumor with a 2-cm margin. Sixteen patietns underwent radical surgery. Hemoglobin levels were measured before combined treatment in all patients. The prognostic value of hemoglobin concentration was analyzed statistically, along with other patient-, tumor- and treatment-related factors. Mean follow-up time: 82 months (range 60–99 months). Chemoradiotherapy was followed by an overall clinical response of 69.4%, with complete clinical response in 24.7% of the patients. Mean survival time was 12 months, and overall likelihood of survival after 3 years was 13%. Mean time to progression: 5 months. Median survival time was 12 months in the 69 patients who underwent chemoradiotherapy alone, and 26 months in patients who underwent radical surgery. Univariate analysis showed a hemoglobin value of >13 g/dl to be a prognostic factor for better survival, along with performance status according to the ECOG classification, weight loss
Published: 2006
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22. Adjuvant radiochemotherapy in rectal cancer: analysis of acute and late-onset toxicity

Author: Pilar Escudero Emperador, Javier Valencia Julve, Carmen Velilla Millán, Ricardo Escó Barón, Vicente Alonso Orduña, and Sonia Polo Jaime
Subjects: Oncology, Cancer Research, medicine.medical_specialty, business.industry, Colorectal cancer, medicine.medical_treatment, Incidence (epidemiology), Late onset, macromolecular substances, General Medicine, medicine.disease, Internal medicine, Toxicity, medicine, business, Adjuvant
Abstract: Objective To analyse the factors related to the appearance, incidence and severity of toxicity associated with post-operative radiochemotherapy in rectal cancer.
Published: 2004
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23. Brain metastasis in basaloid undifferentiated anal carcinoma: A case report

Author: Antonio Anton-Torres, Ana Cebollero de Miguel, Natalia Alvarez-Garcia, Alba Hernandez-Garcia, Vicente Alonso-Orduña, and Jorge Hernando-Cubero
Subjects: Cancer Research, Chemotherapy, Pathology, medicine.medical_specialty, business.industry, Anal Carcinoma, anal cancer, medicine.medical_treatment, Cancer, Bone metastasis, Articles, Anal canal, medicine.disease, Radiation therapy, medicine.anatomical_structure, Oncology, basaloid carcinoma, medicine, Anal cancer, brain metastasis, business, cloacogenic carcinoma, Brain metastasis
Abstract: Anal cancer is a rare tumor that accounts for 2% of all colorectal neoplasms. The brain is a rarely affected organ. The aim of the present study was to the review the only four cases of anal cancer brain metastases previously published in the literature. In addition, the current study presents the case of a 69-year-old male diagnosed with basaloid undifferentiated carcinoma of the anal canal (stage IV with liver, lung and bone metastasis). Despite the patient’s good response to chemotherapy and the achievement of a partial response that was maintained for 14 months, brain metastases developed. Although radiotherapy was administered, the patient succumbed to the condition 12 weeks after the diagnosis of brain metastasis.
Published: 2013

24. Diabetes insípida central como primera manifestación clínica de un carcinoma colorrectal metastásico

Author: Teresa Puértolas Hernández, Rosana Grández Ladrón de Guevara, Vicente Alonso Orduña, Abigail Ruiz de Lobera Martínez, Mónica Corral Subías, and Antonio Antón Torres
Subjects: Cancer Research, Pathology, medicine.medical_specialty, business.industry, Colorectal cancer, Usually asymptomatic, Autopsy, General Medicine, medicine.disease, Oncology, Diabetes insipidus, medicine, Clinical case, business, Lung cancer, Infiltration (medical)
Abstract: Metastases of systemic tumours in the hypothalamus-pituitary region are reported to be around 1% to 4% of all intra-cranial metastases. Most of them are diagnosed when the primary tumour is operated-upon, or when widespread metastases occur. The metastasic infiltration of this region is usually asymptomatic and rarely recognised ante-mortem. The metastases rarely clinically manifest, but diabetes insipidus is the most frequent. Autopsy studies have shown breast and lung cancer are the mostfrequent cause of the metastases in this region. We present a clinical case of a patient presenting diabetes insipidus as the first manifestation of a metastasic colorectal cancer.
Published: 2004
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25. Prognostic factors and long-term outcome of pancreatic neuroendocrine neoplasms: Ki-67 index shows a greater impact on survival than disease stage. The large experience of the Spanish National Tumor Registry (RGETNE)

Author: Vicente Alonso-Orduña, Isabel Sevilla, Jose Angel Diaz‐Perez, Vanessa Pachon, Purificacion Martinez Del Prado, Elena Martín-Pérez, Jaume Capdevila, Rocio Garcia-Carbonero, Adolfo Beguiristain-Gomez, Paula Jiménez-Fonseca, Daniel Castellano, Antonio Monleon, A Castaño, Mónica Marazuela, Carles Villabona-Artero, Javier Sastre-Valera, and Ramon Salazar
Subjects: Oncology, Adult, Male, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, Disease, Neuroendocrine tumors, Cellular and Molecular Neuroscience, Young Adult, Endocrinology, Internal medicine, medicine, Biomarkers, Tumor, Health Status Indicators, Humans, Registries, Stage (cooking), Young adult, Aged, Neoplasm Staging, Retrospective Studies, Aged, 80 and over, biology, Endocrine and Autonomic Systems, business.industry, Retrospective cohort study, Middle Aged, medicine.disease, Prognosis, Tumor registry, Pancreatic Neoplasms, stomatognathic diseases, Neuroendocrine Tumors, Ki-67 Antigen, Spain, Ki-67, biology.protein, Female, business
Abstract: Introduction: Pancreatic neuroendocrine neoplasms (PNENs) are uncommon neoplasms with a wide spectrum of clinical behavior. The objective of this study was to assess in a large cohort of patients the relative impact of prognostic factors on survival. Methods: From June 2001 through October 2010, 1,271 patients were prospectively registered online (www.getne.org) at the Spanish National Cancer Registry for Gastroenteropancreatic Neuroendocrine Tumors (RGETNE) by participating centers. Clinical and histopathological features were assessed as potential prognostic factors by uni- and multivariate analyses. Results: Of 483 PNENs, 171 (35%) were functional (F) and 312 (65%) non-functional (NF). NF-PNENs were associated with a higher incidence of histological features denoting more aggressive disease, such as poor tumor differentiation, Ki-67 >20%, or vascular invasion (NF- vs. F-PNENs, respectively, p < 0.05). Nevertheless, functionality was not a significant predictor of survival (p = 0.19). Stage at diagnosis, Ki-67 index, tumor differentiation and surgical resection of the primary tumor were all significant prognostic factors in univariate analysis. However, Ki-67 (>20 vs. ≤2%) (hazard ratio (HR) 2.21, p = 0.01) and surgical resection (yes vs. no) (HR 0.92, p = 0.001) were the only independent predictors of survival in multivariate analysis. Among patients who underwent surgery, high Ki-67 index (HR 10.37, p = 0.02) and poor differentiation (HR 8.16, p = 0.03) were the only independent predictors of clinical outcome. Conclusion: Ki-67 index and tumor differentiation are key prognostic factors influencing survival of patients with PNENs and, in contrast to what it is observed for other solid malignancies, they seem to have a greater impact on survival than the extent of disease. This should be borne in mind by physicians in order to appropriately tailor therapeutic strategies and surveillance of these patients.
Published: 2013

26. Clinical Significance of Tumour Regression Grade in Locally-Advanced Rectal Cancer Treated with Preoperative Chemoradiotherapy

Author: Alba, Hernandez, primary, Eduardo, Polo, additional, Miguel, Ponce Jose, additional, Carlos, Hörndler, additional, Andres, Monzon, additional, Luis, Sarria, additional, Jorge, Hernando, additional, Antonio, Anton, additional, Rosero-Cuesta David, S., additional, and Vicente, Alonso-Orduña, additional
Published: 2014
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27. Everolimus (Eve) Treatment for Advanced G1-G2 Neuroendocrine Tumours (Nets) in the Community Setting: Clinical Benefit Irrespective of Grade or Primary Tumour Site

Author: P. Reguera, Cristina Álvarez-Escolá, Monserrat Mangas, S. Ayuela, M.P. Solis Hernandez, T. Alonso Gordoa, R.G. Herrera Gomez, Emilio Burgos, C. López, Vicente Alonso-Orduña, Jaime Feliu, Rosario Madero, Enrique Grande, Jorge Barriuso, E. Polo, R. Jimeno, Gustavo Crespo, Custodio, Alberto Carmona-Bayonas, and P. Jimenez Fonseca
Subjects: medicine.medical_specialty, Pathology, business.industry, Sunitinib, Hematology, Neuroendocrine tumors, medicine.disease, Gastroenterology, Chemotherapy regimen, Primary tumor, Oncology, Tolerability, Response Evaluation Criteria in Solid Tumors, Internal medicine, Medicine, Progression-free survival, business, Progressive disease, medicine.drug
Abstract: Aim: Randomized studies have demonstrated that EVE has antitumour activity in advanced G1-G2 NETs. However, data in the “real-world” setting outside regulatory trials are limited. We aim to assess EVE efficacy and tolerability in patients (pts) with advanced NETs from daily clinical practice. Methods: A retrospective analysis was carried out on pts with advanced G1-G2 NETs of gastroenteropancreatic and lung origin treated with EVE in six Spanish University hospitals between June-2009 and December-2013. Results: 71 pts (61.9% males) were evaluated with a median age of 56.7 years (20-84). Primary tumor locations were pancreas (pNETs) (50.7%), small intestine (22.5%), colon (7.1%), lung (15.5%) and unknown (1.4%). 32 (45.1%) and 39 (54.9%) pts had G1 and G2 tumours, respectively. Previous systemic therapies included somatostatin analogs (SSAs) (76.1%), chemotherapy (25.3%), sunitinib (23.9%), interferon (7.04%) and other agents (12.7%). Most pts (80.3%) received EVE in combination with SSAs. At the time of the data cut-off (April-2014), 24 (33.8%) pts were still on treatment. Partial response as the best outcome according to RECIST 1.1 criteria was recorded in 7 (9.9%) pts (13.9% pNET, 5.7% non-pNET), stable disease in 59 (83.1%) pts (75% pNET, 83.1% non-pNET) and progressive disease in 5 (7.05%) pts (11.1% pNET, 2.9% non-pNET). With a median follow-up of 18.6 months (ms) (range 6-51), the estimated median progression-free survival (PFS) was 14.4 ms (95% CI, 12.2-15.8) and the median overall survival was not reached. No significant differences in PFS were observed in terms of primary site (pNET: 13.7 ms; 95% CI, 11.3-16.7; non-pNET: 15.2 ms; 95% CI, 12.2-17.8; p = 0.31) or tumour grade (G1: 14.6 ms; 95 CI, 12.8-16.9; G2: 13.2 ms; 95% CI, 11.2-15.8; p = 0.39). EVE-related adverse events (AEs) were mostly grade 1-2 and 15 (21.2%) pts experienced grade 3-4 toxicity. The most common AEs of any grade included stomatitis (67.6%), asthenia (56.3%), diarrhea (54.9%), hyperglycemia (54.9%) and pneumonitis (21.1%). Conclusions: EVE has shown to be an active and well tolerated therapeutic option for unselected patients with both pancreatic and non-pancreatic G1-G2 NETs in routine clinical practice. Disclosure: All authors have declared no conflicts of interest.
Published: 2014
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28. A Validation of Current Prognostic Scores in Metastatic Colorectal Cancer (Mcrc) and a New Prognostic Score (A Gemcad Study)

Author: J.C. Méndez, Antonieta Salud, Pilar Escudero, Carlos Fernández-Martos, J. Feliu, M. Marmol, Marta Martin, Vicente Alonso-Orduña, Juan Maurel, C. García Girón, M.J. Safont, and X. García de Albéniz
Subjects: Oncology, medicine.medical_specialty, Performance status, Karnofsky Performance Status, business.industry, Colorectal cancer, Hematology, medicine.disease, Oxaliplatin, Prognostic score, Internal medicine, medicine, Overall survival, Progression-free survival, Stage (cooking), business, medicine.drug
Abstract: Aim: Background: The two main prognostic scores for mCRC (Kohne and GERCOR) do not account for resectability of liver-only metastasis (LiM) and thus are limited as treatment guidance. We propose a classification of patients based on LiM resectability, performance status (PS) and lactate dehydrogenase (LDH) levels and compare its discrimination capacity against Kohne and GERCOR scores. Methods: We analyzed 395 patients treated with first-line oxaliplatin-based regimes with or without monoclonal antibodies. Patients were classified as stage 1 if LiM were considered resectable ( 4 and 5 cm diameter), PS 0-1 and LDH 1.5 ULN. This score, Kohne, and GERCOR scores were tested for discrimination using Harrel's C index (HCI, higher is better) and calibration using Akaike information criterion (AIC, smaller is better) of progression-free survival (PFS) and overall survival (OS). Results: Group 1 Group 2 Group 3 GEMCAD N 78 206 111 PFS HR (95% CI) 1 (Reference) 2.07 (1.54-2.78) 2.98 (2.15-4.13) PFS HCI (95% CI) 0.66 (0.60-0.73) PFS AIC 3496.2 OS HR (95% CI) 1 (Reference) 2.14 (1.52-3.00) 3.68 (2.55-5.32) OS HCI (95% CI) 0.68 (0.62-0.73) OS AIC 2903.7 Kohne N 159 205 31 PFS HR (95% CI) 1 (Reference) 1.55 (1.23-1.93) 2.86 (1.89-4.31) PFS HCI (95% CI) 0.62 (0.56-0.68) PFS AIC 3515.7 OS HR (95% CI) 1 (Reference) 1.63 (1.27-2.10) 4.57 (2.93-7.13) OS HCI (95% CI) 0.65 (0.60-0.71) OS AIC 2915.4 GERCOR N 116 153 126 PFS HR (95% CI) 1 (Reference) 1.40 (1.08-1.82) 2.04 (1.55-2.68) PFS HCI (95% CI) 0.60 (0.54-0.66) AIC 3517.7 OS HR (95% CI) 1 (Reference) 2.19 (1.62-2.96) 3.21 (2.34-4.40) OS HCI (95% CI) 0.66 (0.62-0.71) OS AIC 2898.4 Conclusions: Conclusions. GEMCAD score performs as well, if not better, than Kohne and GERCOR scores and allows treatment guidance. Disclosure: All authors have declared no conflicts of interest.
Published: 2014
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29. Preoperative Bevacizumab, Capecitabine and Oxaliplatin (CAPOX-B) in Intermediate Risk Rectal Adenocarcinoma, Selected by High Resolution MRI. Gemcad 0801 Study

Author: Jaime Feliu, Jorge Aparicio, Gina Brown, Fernandez-Martos Carlos, Marta Martin, Antonieta Salud, M. Gallen, Rafael Estevan, Javier Gallego, Carles Pericay, Ruth Vera, Maria Jose Safont, Vicente Alonso-Orduña, and Joan Maurel
Subjects: Oncology, medicine.medical_specialty, Bevacizumab, medicine.diagnostic_test, business.industry, Magnetic resonance imaging, Hematology, CAPOX-Bevacizumab Regimen, Preoperative care, Oxaliplatin, Capecitabine, Internal medicine, Rectal Adenocarcinoma, medicine, Bevacizumab/capecitabine, Radiology, business, medicine.drug
Published: 2013
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30. Disease Progression Patterns/Outcome by Disease Extent Following Bevacizumab + Chemotherapy Beyond First Disease Progression in Previously Treated MCRC (ML18147 Study)

Author: Olivier Bouché, Vicente Alonso-Orduña, Richard Greil, Thierry André, Christophe Borg, Stefan Kubicka, Martina Makrutzki, Pia Österlund, Jaafar Bennouna, Claus-Christoph Steffens, Dirk Arnold, Roger von Moos, Daniel Waterkamp, Christoph Schlichting, Jose Maria Vieitez de Prado, Javier Sastre, Eric Van Cutsem, and S. Osborne
Subjects: Oncology, medicine.medical_specialty, Chemotherapy, Bevacizumab, business.industry, medicine.medical_treatment, Disease progression, Hematology, Disease, Chemotherapy regimen, Outcome (game theory), Internal medicine, medicine, business, Previously treated, medicine.drug
Published: 2013
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31. VITAL phase 2 study: Upfront 5‐fluorouracil, mitomycin‐C, panitumumab and radiotherapy treatment in nonmetastatic squamous cell carcinomas of the anal canal (GEMCAD 09‐02)

Author: Jaime Feliu, Rocio Garcia‐Carbonero, Jaume Capdevila, Inmaculada Guasch, Vicente Alonso‐Orduna, Carlos Lopez, Pilar Garcia‐Alfonso, Carmen Castanon, Isabel Sevilla, Laura Cerezo, Carles Conill, Begona Quintana‐Angel, Maria E. Sanchez, Ismael Ghanem, Marta Martin‐Richard, Miriam Lopez‐Gomez, Ana Leon, Monica Caro, Teresa Fernandez, and Joan Maurel
Subjects: chemotherapy, radiotherapy, rectal cancer, target therapy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Aim VITAL, a phase II single‐arm study, aimed to evaluate efficacy and safety of panitumumab addition to 5‐fluorouracil (5‐FU), mitomycin‐C (MMC) and radiotherapy (RT) in patients with localized squamous cell carcinoma of the anal canal (SCCAC). Methods Adult, treatment‐naïve SCCAC patients (Stage T2‐T4, any N, M0) and ECOG‐PS ≤2, received panitumumab (6 mg/kg, day 1 and Q2W; 8 weeks), 5‐FU (1000 mg/m2/d, days 1‐4 and 29‐32), MMC (10 mg/m2, days 1 and 29) and RT 45 Gy (1.8 Gy/fraction) to the primary tumor and mesorectal, iliac and inguinal lymph nodes, plus 10‐15 Gy boost dose to the primary tumor and affected lymph nodes. The primary objective was disease free survival rate (DFS) at 3‐years (expected 3‐year DFS rate: 73.7 ± 12%). Results Fifty‐eight patients (31 women; median age: 59 years; ECOG‐PS 0‐1:98%; TNM II [29%] (T2 or T3/N0/M0)/IIIA (T1‐T3/N1/M0 or T4/N0/M0) [21%]/IIIB (T4/N1/M0 or any T/N2 or N3/M0) [47%]/nonevaluable [4%]) were included. The median follow‐up was 45 months. The 3‐year DFS rate was 61.1% (95% CI: 47.1, 72.4). The 3‐year overall survival rate was 78.4% (95% CI: 65.1, 87.1). Eighteen patients (31.0%) required a colostomy within 2 years posttreatment. Grade 3‐4 toxicities were experienced by 53 (91%) patients. Most common grade 3‐4 treatment‐related events were radiation skin injury (40%) and neutropenia (24%). No toxic deaths occurred. Improved efficacy in colostomy‐free survival and complete response rate was observed in human papilloma virus positive patients. Conclusions Panitumumab addition to MMC‐5FU regimen in SCCAC patients increases toxicity and does not improve patients’ outcomes. RT plus MMC‐5FU remains the standard of care for localized SCCAC patients.
Published: 2020
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32. P-0275 - Clinical Significance of Tumour Regression Grade in Locally-Advanced Rectal Cancer Treated with Preoperative Chemoradiotherapy

Author: Alba, Hernandez, Eduardo, Polo, Miguel, Ponce Jose, Carlos, Hörndler, Andres, Monzon, Luis, Sarria, Jorge, Hernando, Antonio, Anton, Rosero-Cuesta David, S., and Vicente, Alonso-Orduña
Published: 2014
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32 results on '"Vicente Alonso-Orduña"'

1. Phase II randomized trial of capecitabine with bevacizumab and external beam radiation therapy as preoperative treatment for patients with resectable locally advanced rectal adenocarcinoma: long term results

2. Association of miR-21 and miR-335 to microsatellite instability and prognosis in stage III colorectal cancer

3. Upfront primary tumour resection and survival in synchronous metastatic colorectal cancer according to primary tumour location and RAS status: Pooled analysis of the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)

4. The Frequency of Specific KRAS Mutations, and Their Impact on Treatment Choice and Survival, in Patients With Metastatic Colorectal Cancer

5. A phase 2 multicenter, open-label, randomized, controlled trial in patients with stage II/III colorectal cancer who are ctDNA positive following resection to compare efficacy of autogene cevumeran versus watchful waiting

6. 474P Prognostic and predictive role of Consensus Molecular Subtypes (CMS) determined by immunohistochemistry in metastatic colorectal cancer (mCRC)

7. VITAL phase 2 study: Upfront 5-fluorouracil, mitomycin-C, panitumumab and radiotherapy treatment in nonmetastatic squamous cell carcinomas of the anal canal (GEMCAD 09-02)

8. 1159MO Survival and prognostic factors analysis of 535 grade 3 gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN): Data from the Spanish Taskforce of Neuroendocrine Tumours Registry (R-GETNE)

9. 471P Identification and validation of a new prognostic score in metastatic colorectal cancer (mCRC): GEMCAD score

10. 1167P SILVELUL SCORE: An original or modified immunohistochemical score (IPS or mIPS) in patients (pts) with pancreatic neuroendocrine tumours (PanNET) treated with everolimus or CAPTEM

11. First-line biological agents plus chemotherapy in elderly patients with metastatic colorectal cancer: A retrospective pooled analysis

12. Effect of Aflibercept Plus Modified FOLFOX6 Induction Chemotherapy Before Standard Chemoradiotherapy and Surgery in Patients With High-Risk Rectal Adenocarcinoma The GEMCAD 1402 Randomized Clinical Trial

13. Adenosquamous Cell Carcinoma of the Rectum in a Girl

14. Prognostic value of KRAS mutations in stage III colon cancer: post hoc analysis of the PETACC8 phase III trial dataset

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

16. The Role of Fluoropirimidines in Gastrointestinal Tumours: from the Bench to the Bed

17. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial

18. SEOM clinical guidelines for the treatment of advanced colorectal cancer

19. Phase II trial of induction irinotecan-cisplatin followed by concurrent irinotecan-cisplatin and radiotherapy for unresectable, locally advanced gastric and oesophageal-gastric junction adenocarcinoma

20. Phase II Trial of Preoperative Irinotecan–Cisplatin Followed by Concurrent Irinotecan–Cisplatin and Radiotherapy for Resectable Locally Advanced Gastric and Esophagogastric Junction Adenocarcinoma

21. Influence of hemoglobin levels on survival after radical treatment of esophageal carcinoma with radiotherapy

22. Adjuvant radiochemotherapy in rectal cancer: analysis of acute and late-onset toxicity

23. Brain metastasis in basaloid undifferentiated anal carcinoma: A case report

24. Diabetes insípida central como primera manifestación clínica de un carcinoma colorrectal metastásico

25. Prognostic factors and long-term outcome of pancreatic neuroendocrine neoplasms: Ki-67 index shows a greater impact on survival than disease stage. The large experience of the Spanish National Tumor Registry (RGETNE)

26. Clinical Significance of Tumour Regression Grade in Locally-Advanced Rectal Cancer Treated with Preoperative Chemoradiotherapy

27. Everolimus (Eve) Treatment for Advanced G1-G2 Neuroendocrine Tumours (Nets) in the Community Setting: Clinical Benefit Irrespective of Grade or Primary Tumour Site

28. A Validation of Current Prognostic Scores in Metastatic Colorectal Cancer (Mcrc) and a New Prognostic Score (A Gemcad Study)

29. Preoperative Bevacizumab, Capecitabine and Oxaliplatin (CAPOX-B) in Intermediate Risk Rectal Adenocarcinoma, Selected by High Resolution MRI. Gemcad 0801 Study

30. Disease Progression Patterns/Outcome by Disease Extent Following Bevacizumab + Chemotherapy Beyond First Disease Progression in Previously Treated MCRC (ML18147 Study)

31. VITAL phase 2 study: Upfront 5‐fluorouracil, mitomycin‐C, panitumumab and radiotherapy treatment in nonmetastatic squamous cell carcinomas of the anal canal (GEMCAD 09‐02)

32. P-0275 - Clinical Significance of Tumour Regression Grade in Locally-Advanced Rectal Cancer Treated with Preoperative Chemoradiotherapy

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